Microsporidia are fungi-like parasites that have the smallest known eukaryotic genome, and for that reason they are used as a model to study the phenomenon of genome decay in parasitic forms of life. Similar to other intracellular parasites that reproduce asexually in an environment with alleviated natural selection, Microsporidia experience continuous genome decay driven by Muller's ratchet - an evolutionary process of irreversible accumulation of deleterious mutations, which leads to gene loss and miniaturization of cellular components. Particularly, Microsporidia have remarkably small ribosomes in which the rRNA is reduced to the minimal enzymatic core. To better understand the impact of Muller's ratchet on RNA and protein molecules in parasitic organisms, particularly regarding their ribosome structure, we have explored an apparent effect of Muller's ratchet on microsporidian ribosomal proteins. Through mass spectrometry, analysis of microsporidian genome sequences and analysis of ribosome structure from non-parasitic eukaryotes, we found that massive rRNA reduction in microsporidian ribosomes appears to annihilate binding sites for ribosomal proteins eL8, eL27, and eS31, suggesting that these proteins are no longer bound to the ribosome in microsporidian species. We then provided an evidence that protein eS31 is retained in Microsporidia due to its non-ribosomal function in ubiquitin biogenesis. To sum up, our study illustrates that while Microsporidia carry the same set of ribosomal proteins as non-parasitic eukaryotes, some of ribosomal proteins are no longer participating in protein synthesis in Microsporidia and they are preserved from genome decay by having extra-ribosomal functions.

In the literature of Low-Energy Nuclear Reactions (LENR), particle tracks in photographic emulsions (and other materials) associated with certain electrical discharges have been reported. Some Russian and French researchers have considered these particles to be magnetic monopoles. These tracks correspond directly to tracks created with a simple uniform exposure to photons without an electrical discharge source. This simpler method of producing tracks supports a comprehensive exploration of particle track properties. Out of 750 exposures with this method, elliptical particle tracks were detected, 22 of which were compared to Bohr-Sommerfeld electron orbits. Ellipses fitted to the tracks were found to have quantized semi-major axis sizes with ratios of ≈n²/α² to corresponding Bohr-Sommerfeld hydrogen ellipses. This prompts inquiry relevant to magnetic monopoles due to the n²/α² force difference between magnetic charge and electric charge using the Schwinger quantization condition. A model using analogy with the electron indicates that the elliptical tracks could be created by a bound magnetically charged particle with mass m_m = 1.45 × 10^-3 eV/c², yet with superluminal velocities. Using a modified extended relativity model, m_m becomes the relativistic mass of a superluminal electron, with m₀ = 5.11 × 10^-3 eV/c², the fine structure constant becomes a mass ratio and charge quantization is the result of two states of the electron.

Based on detection of elliptic particle tracks, $\simeq 137^2 n^2$ bigger than Bohr-Sommerfeld electron orbits, indicating the possible detection of superluminal electrons masquerading as magnetic monopoles, a new structure emerges leading to: (i) a new set of seven elementary lengths; (ii) replacement of the usual motion (Lorentz) transformations by scale transformations between $v^2<c^2$ and $v^2>c^2$ frames; (iii) equivalence of charge between $v^2<c^2$ and $v^2>c^2$ frames based on the Dirac-Schwinger quantization condition; (iv) a relativistic foundation for the Dirac-Schwinger quantization condition; (v) a possible cause of charge quantization; and (vi) the prospect of symmetry in Maxwell's equations. If the elliptic particle tracks are viewed as a magnification of electron orbits, the effect is suggestive of a spacetime distortion such as those predicted in general relativistic theories.

This research paper investigates the enhancement of strength and performance of self-compacting concrete (SCC) for integration in Department of Public Works and Highways (DPWH) projects using a value engineering approach. The study explores key elements of SCC's strength and performance, including mix design optimization, construction practices, and durability considerations. Strategies to optimize SCC's strength, durability, and workability are discussed, emphasizing the benefits of SCC in improving construction efficiency and quality control within DPW infrastructure. The study also identifies challenges and gaps in SCC utilization, such as standardized performance verification and cost considerations, and proposes future directions for advancing SCC technology in civil infrastructure development.

Three significant changes have occurred in the winter climate in Europe recently: increased UK flooding; Iberian drought; and warmer temperatures north of the Alps. The literature links all three to a persistent, significant increase in sea level pressure over Southern Europe, the Mediterranean, Iberia and the Eastern Atlantic (SEMIEA) which changes the atmospheric circulation system: forcing cold fronts to the north away from Iberia; and creating a south westerly flow around the northern perimeter of the high-pressure region bringing warmer, moist air from the subtropical Atlantic to the UK and Europe which increases precipitation in the UK and raises the temperature in Europe. I use the Last Millennium Ensemble, MERRA-2 and Terra-NCEP data to demonstrate that the extreme, anthropogenic, West African aerosol Plume (WAP) which only exists from December to April perturbs the northern, regional Hadley Circulation creating the high pressure in the SEMIEA. I also show that the anthropogenic WAP has only existed in its extreme form in recent decades as the two major sources of the WAP aerosols: biomass burning; and gas flaring have both increased significantly since 1950 due to: a four-fold increase in population; and gas flaring rising from zero to 7.4 billion m3/annum and note that this time span coincides with the changes in the three elements of the winter climate of Europe. I also suggest that it may be possible to eliminate the WAP and return the winter climate of Europe to its natural state after the crucial first step of recognising the cause of the changes is taken.

The creation of protonated water nanoclusters from amorphous water-ice under laboratory conditions suggests the possible ejection of such nanoclusters from ubiquitous amorphous water-ice-covered cosmic dust to interstellar space. The quantum properties of these quintessential water entities introduce a tantalizing prospect that bridges the origins of dark matter, dark energy, and life in the universe. The quantum-entangled diffuse Rydberg electronic states inherent to cosmic water nanoclusters make them plausible candidates for baryonic dark matter. Moreover, they exhibit the capacity to absorb, through the microscopic dynamical Casimir effect, virtual photons originating from zero-point-energy vacuum fluctuations occurring above the water-nanocluster vibrational frequency cutoff. This selective interaction leaves only vacuum fluctuations below these frequencies with gravitational significance, cancelling the vacuum-energy catastrophe and yielding a shared genesis for dark matter and dark energy. Moreover, this theory extends its implications to the origins of life itself, proposing that RNA protocells on Earth and habitable exoplanets may have emerged from the interactions between cosmic water nanoclusters and prebiotic organic molecules, thus yielding an anthropic narrative. Collectively, these findings coalesce into a cosmological framework depicting a cyclic universe, with cosmic water nanoclusters constituting a quintessence scalar field, instead of adhering to the multiverse concept based on cosmic inflation theory. Recent observations of CMB birefringence support this quintessence.

Approximately 6% of adults worldwide suffer from peripheral artery disease (PAD) primarily caused by atherosclerosis of lower limb arteries. Despite optimal medicine and revascularization, many PAD patients remain symptomatic and progress to critical limb ischemia (CLI) and risk major amputation. Delivery of pro-angiogenic factors as proteins or DNA, stem or progenitor cells confers vascular regeneration and functional recovery in animal models of CLI, but the effects are not well replicated in patients and no pro-angiogenic biopharmacological procedures are approved in the US. The reasons are unclear, but animal models that do not represent clinical PAD/CLI are implicated. Consequently, it is unclear whether the obstacles to clinical success lie in the toxic biochemical milieu of human CLI, or in procedures that were optimized by inappropriate models. The question is significant because the former case requires abandonment of current strategies, while the latter encourages continued optimization. These issues are discussed in the context of relevant preclinical and clinical data, and it is concluded that preclinical mouse models that include age and atherosclerosis as the only comorbidities that are consistently present and active in clinical trial patients are essential to predict clinical success. Of the reviewed materials, no biopharmacological procedure that failed in clinical trials had been tested in animal models that included advanced age and atherosclerosis relevant to PAD/CLI.

This study presents a comprehensive comparative analysis of retrofitting techniques aimed at enhancing the seismic resilience of seismically vulnerable historical buildings. Recognizing the dual objectives of structural safety and architectural preservation, this research evaluates and compares several advanced retrofitting methods, including base isolation, strengthening of masonry, steel bracing systems, Fiber-Reinforced Polymer (FRP) wrapping, and damping devices. Each technique is critically assessed based on its effectiveness in mitigating seismic risks, its compatibility with historical architectural features, and its applicability to various building types. Base isolation is highlighted for its ability to decouple buildings from ground motion, thereby significantly reducing seismic forces and protecting architectural integrity. Strengthening of masonry through the use of fiber-reinforced polymers and steel elements enhances the ductility and strength of masonry walls, making them more resilient to seismic forces. Steel bracing systems are shown to provide essential lateral support, particularly in timber-framed structures, improving overall stability and reducing deformation during earthquakes. FRP wrapping is identified as a versatile technique that strengthens structural elements without compromising aesthetic value, making it suitable for reinforcing concrete and masonry components. Damping devices, including viscous dampers and tuned mass dampers, are discussed for their ability to dissipate seismic energy and control structural vibrations, offering a minimally invasive solution that preserves historical aesthetics. The study also addresses several challenges and research gaps associated with these retrofitting techniques, such as ensuring architectural compatibility, assessing long-term material performance, optimizing cost-effectiveness, and navigating complex regulatory frameworks. By advancing knowledge in these areas, the research aims to foster interdisciplinary collaboration and innovation in the development of retrofitting solutions. Ultimately, this study contributes to the ongoing efforts to safeguard historical buildings against seismic hazards. By leveraging cutting-edge technologies and best practices in structural engineering and architectural conservation, stakeholders can develop sustainable, cost-effective, and culturally sensitive retrofitting strategies that protect valuable cultural heritage for future generations.

Urban form is associated with both socio-economic and urban physical properties. This study explores the differences among urban forms in the Seoul Metropolitan Region with a comparison between census-based socioeconomic variables and landscape metrics computed from remotely sensed data. To accomplish this, factor analysis and multi-dimensional scaling were used with the selected variables and metrics. When all of the measures are considered together, four types of cities and towns emerged: 1) exurban-fragmented high growth, 2) exurban-fragmented low growth, 3) compact-extensive urban core and 4) sub-urban compact-high growth. The results indicate that the fusion of knowledge of the physical urban layout and that of socio-economic characteristics is beneficial for a better understanding of urban spatial patterns. However, there remain challenges in delineating each urbanized area and with indicator selection for comparing urban form across cities and towns.

The emergence of the semiconductor industry in the early 1960s resulted in a significant stage in the evolution of computing when large computational problems, as typified by the application of the discrete Fourier transform (DFT) to the task of spectrum estimation, could suddenly, with the availability of suitable algorithms, be solved in close to real time fashion. This paper provides a brief and meandering account of the history of the DFT’s various solutions, referred to generically as the fast Fourier transform (FFT), the algorithm being chosen for its mathematical elegance, practical significance and ever‑increasing range of applications. We touch upon a few of the most striking personalities, places and events that were encountered along the way and look, in particular, at the recent British contribution to the journey.

Access to health services compromises therapeutic adherence in patients with HTN, which is a risk factor for cardiovascular disease and premature death. The aim of the research is to determine the influence of access to health services on adherence to antihypertensive treatment during the COVID-19 pandemic. We included a cross-sectional analytical study. A survey was applied to 241 hypertensive patients at the Daniel Alcides Carrión Hospital, Callao-Peru. Data were analyzed using SPSS software. Absolute and relative frequencies were reported and the chi-square test was applied with a statistical significance level of p&lt;0.05. In addition, multiple logistic regression analysis was performed using the Stepwise method. An association was found between non-adherence to treatment and health expenses (ORa: 1.9 CI 95% 1.7-2.2), not receiving care due to lack of a doctor (ORa: 2.8 CI 95% 1.5-3.2), having difficulty with schedules (ORa: 3.7 CI 95% 2. 3-5.5), fear of receiving care at the hospital (ORa: 4.5 CI 95 % 2.7-6.8), trust in health personnel (ORa: 7.5 CI 95% 2.3-10.5) and considering that the physician does not have enough knowledge (ORa: 3.1 CI 95% 2.4-7.8). Therapeutic adherence was associated with physician availability for care, difficulty with schedules, fear of being seen in the hospital, trust in health personnel, and waiting time.

In 2018, the author identified a previously unknown/unreported association between dexrazoxane and poly(ADP-ribose) (PAR). Interestingly, PAR is a close structural analogue of the polyadenine nucleotide polymer, polyadenosine monophosphate (poly(A)). In this report, subsequent in silico modelling of the interaction between dexrazoxane and poly(A) reveals some notable differences from the previously reported interaction between dexrazoxane and PAR. Significantly, the supramolecular self-assembly of dexrazoxane and poly(A) is distinguished by vertically-orientated nonelectrostatic forces comparable to the stabilizing interactions between stacked bases within DNA. Notably, the vertical separation of 3.4 Å between each stack is consistent with solvent entropy as a dominant driving force in stabilising the interaction. Additionally, concomitant conformational analysis by the author reveals the existence of low energy planar conformers of dexrazoxane. This analysis enables an explanation for the considerable discrepancies and conflicts that exist within the reported pharmacokinetic data for dexrazoxane. Exploring the significance of the interaction between dexrazoxane and poly(A), the author illustrates that survival, translation and replication of the severe acute respiratory syndrome virus 2 (SARS-CoV-2) is absolutely dependent upon the mature and unhindered poly(A) tail of the SARS-CoV-2 genome. The proposition herein, that dexrazoxane, as a chameleonic agent sequesters the poly(A) tail of the SARS-CoV-2 genome by the catalysis of a supramolecular hybrid assembly establishes SARS-CoV-2 infected cells as deep compartments for the accumulation of dexrazoxane. Taken together, dexrazoxane or its demethylated analogue, represent a novel treatment to kill the SARS-CoV-2 virus by irreversible destabilization of the SARS-CoV-2 poly(A) tail.

This paper puts forward an alteration for Tensor Calculus utliized in a coordinate system which is under a dynamic distortion drawing inspiration from similar fields such as the Calculus of Moving Surfaces (CMS). The paper establishes transformation laws for Tensors within these regions and establishes Operators such as the Tensorial Field Derivative which enforce a Tensorial Transformation on Tensors defined within a Dynamically Moving coordinate system. This variation of Tensor Calculus can be utilized to observe how disciplines such as QFT and Continuum Mechanics would change to accomodate for a distorting coordinate system and can be utliized to develop new theoretical models which account for this temporal distortion particularly within Biological Settings.

This paper presents an extension for principles of Differential Geometry on Surfaces (re-hashed through the budding field of CMS, the Calculus of Moving Surfaces). It analyzes mostly 2D Hypersurfaces with Riemannian Geometry and proposes the construction of a 3D Static Frame combining the Surface Basis Vectors with the Orthogonal Normal Field as a 3D Orthogonal Vector Frame. The paper introduces conventions for manipulating Tensors defined using this 3D Orthogonal Vector Frame as well as Curvature Connections associated with this Vector Frame. It then finally introduces Symbols and Tensors to describe Inner Products and Variance within the 3D Vector Frame and then extends all the above concepts to a surface which is Dynamic utilizing principles from CMS. This formulation has potential to extend identities and concepts from CMS and from Differential Geometry in a compact Tensorial Framework, which agrees with the new Framework proposed by CMS.

The paper describes schemes for the resource-efficient generation of twiddle factors for the fixed-radix version of the ubiquitous fast Fourier transform (FFT) algorithm. The schemes, which are targeted at a parallel implementation of the FFT, provide one with the facility for trading off arithmetic complexity, as expressed in terms of the required numbers of multiplications and additions (or subtractions), against the memory requirement, as expressed in terms of the amount of random access memory (RAM) required for constructing the look-up tables (LUTs) needed for the storage of the two twiddle factor components – one component being derived from the sine function and the other from the cosine function. Examples are provided which illustrate the advantages and disadvantages of each scheme – which are very much dependent upon the length of the FFT to be computed – for both the single-level and multi-level LUTs, highlighting those situations where their adoption might be most appropriate. More specifically, it is seen that the adoption of a multi‑level LUT scheme may be used to facilitate significant reductions in memory – namely, from an O(N) to an memory requirement, for the case of an N‑point FFT, where β ≥ 2 corresponds to the number of distinct angular resolutions used – at a relatively small cost in terms of increased FFT latency and arithmetic complexity.

In this systematic review of the literature on using Machine Learning (ML) for credit risk prediction, we raise the need for financial institutions to use AI and ML to assess credit risk, analyzing large volumes of information. We posed research questions about algorithms, metrics, results, data sets, variables, and related limitations in predicting credit risk. We searched renowned databases to answer them and identified 52 relevant studies with the credit industry microfinance. Challenges and approaches in credit risk prediction using ML models we identified, difficulties with the implemented models such as the black box model, the need for explanatory artificial intelligence, the importance of selecting relevant features, addressing multicollinearity, and the problem of the imbalance in the input data. By answering the questions, we identified that the Boosted Category is the most researched family of ML models; the most commonly used metrics for evaluation are Area Under Curve (AUC), Accuracy (ACC), Recall, precision measure F1 (F1), and Precision; Research mainly uses public data sets to compare models, and private ones to generate new knowledge when applied to the real world. The most significant limitation identified is the representativeness of reality, and the variables primarily used in the microcredit industry are related data to the demographic, the operation, and payment behavior. This study aims to guide the developers of credit risk management tools and software towards the existing offer of ML methods, metrics, and techniques used to forecast it, thereby minimizing possible losses due to default and guiding risk appetite.

The actions of many drugs involve enzyme inhibition. This is exemplified by the inhibitors of monoamine oxidases (MAO) and the cholinsterases (ChE) that have been used for several pharmacological purposes. This review describes key principles and approaches for the reliable determination of enzyme activities and inhibition as well as some of the methods that are in current use for such studies with these two enzymes. Their applicability and potential pitfalls arising from their inappropriate use are discussed. Since inhibitor potency is frequently assessed in terms of the quantity necessary to give 50% inhibition (the IC50 value), the relationships between this and the mode of inhibition is also considered, in terms of the misleading information that it may provide. Incorporation of more than one functionality into the same molecule to give a multi-target-directed ligands (MTDLs) requires careful assessment to ensure that the specific target effects are not significantly altered and that the kinetic behaviour remains as favourable with the MTDL as it does with the individual components. Such factors will be considered in terms of recently developed MTDLs that combine MAO and ChE inhibitory functions.

Circular Economy (CE) is a growing topic among scholars, industry and government aiming at decoupling economic growth and development from the consumption of finite resources. CE incorporates different meanings, from reduce, reuse and recycle activities to environmental degradation or resource scarcity, and supported by specific indicators to attain sustainable development. However, so far, there has been no agreement to measure how effective an industry/product is in making the transition from linear to circular approaches, particularly those affected the society. This research work aims to perform a systematic literature review (n=60) to analyze and discuss how social aspects have been considered and integrated in the CE research so far. Moreover, this review provides and overview of the literature on social impact within CE, that resulted in three main outputs: a knowledge map of the CE, an analysis of social aspects within CE, and the theories/frameworks used to evaluate social impact of CE. Finally, this study brings to light how CE implementation can affect society and highlights the importance of social dimension in the domains of CE and policy-making community, which could help moving CE towards a sustainable development.

Many people with enduring mental health difficulties (EMHD) have reduced social connections and subsequent experiences of isolation and loneliness. This paper outlines the development and trial of a manualised social-identity-based group therapy intervention to increase social connection and develop social skills to build connections outside of healthcare settings. This intervention was developed in line with the quality intervention development (6SQuID) methodology. The paper describes initial data from a feasibility study (which was ceased prematurely due to COVID-19 restrictions). Semi-structured outcome interviews were conducted with the participants and analysed using thematic analysis. Uptake, retention and acceptability of participants was high. Four primary themes were identified across the dataset: Therapeutic Process, Social Identity, Generic Components of Group Therapy and Impact of COVID-19. Participants experienced positive changes in their social behaviour, mood and avoidance. Some were unsure of the concept of social identity while reporting positive changes. A theoretically coherent manualised treatment was developed and tested on a small scale. This study supports social identity-based CBT groups as a potentially effective way of increasing social connection in those with EMHD. Social identity theory supported participants to positively integrate an area of potential social threat into their self-concept and may offer a positive addition to current psychological interventions

To study and monitor the adverse health consequences from using electronic cigarettes, a user’s puff topography, which are quantification parameters of the user’s vaping habits, plays a central role. In this work, we introduce a topography sensor to measure the mass of total particulate matter generated in every puff and to estimate the nicotine yield. The sensor is compact and low-cost, and is integrated into the electronic cigarette device to promptly and conveniently monitor the user’s daily puff topography. The topography sensor is comprised of a photometric sensor and a pressure sensor. The photometric sensor measures the mass concentration of the aerosol, based on scattering of near-infrared light from airborne particles, while the pressure sensor measures the flow rate. The topography sensor was experimented under various conditions with a wide range of atomizer power, puff duration, and inhalation pressure. The sensor’s accuracy was validated by comparing the sensor’s readings with reference measurements, and the results matched closely with the trends reported by existing studies on electronic cigarettes. An example application of tracking a user’s puff topography was also demonstrated. Our topography sensor holds great promise in mitigating health risks of vaping, and in promoting quality control of electronic cigarette products.

In Data Science we are concerned with the integration of relevant sciences in observed and empirical contexts. This results in the unification of analytical methodologies, and of observed and empirical data contexts. Given the dynamic nature of convergence, described are the origins and many evolutions of the Data Science theme. The following are covered in this article: the rapidly growing post-graduate university course provisioning for Data Science; a preliminary study of employability requirements, and how past eminent work in the social sciences and other areas, certainly mathematics, can be of immediate and direct relevance and benefit for innovative methodology, and for facing and addressing the ethical aspect of Big Data analytics, relating to data aggregation and scale effects. Associated also with Data Science is how direct and indirect outcomes and consequences of Data Science include decision support and policy making, and both qualitative as well as quantitative outcomes. For such reasons, the importance is noted of how Data Science builds collaboratively on other domains, potentially with innovative methodologies and practice. Further sections point towards some of the most major current research issues.

We developed a temporal population receptive field model to differentiate the functional and hemodynamic responses in the human LGN. The hemodynamic response of the human LGN is dominated by the richly vascularized hilum, a structure that serves as a point of entry for blood vessels entering the LGN and supplying the substrates of central vision. The location of the hilum along the ventral surface of the LGN and the resulting gradient in the amplitude of the hemodynamic response across the extent of the LGN has made it difficult to segment the human LGN into its more interesting magnocellular and parvocellular regions that represent two distinct visual processing streams. Here, we show that an intrinsic clustering of the LGN responses to a variety of visual input reveals the hilum, and further that this clustering is dominated by the amplitude of the hemodynamic response. We introduce a temporal population receptive field model that includes both a sustained and transient temporal impulse response. When we account for the hemodynamic amplitude, we demonstrate that this temporal response model is able to functionally segregate the residual responses according to their temporal properties.

This paper attempts to address the phenomenon of normal vibrations, (referred to as dynamic vibrations) occurring on a surface which is already in vibrational motion due to other kinematic phenomena. Such a surface will have a metric tensor, normal, and ambient velocity which diverges from the surface’s original various dynamic tensorial descriptors. This paper formulates the wave equation defined in a coordinate space, and extends the equation to observe vibrations on a surface with the use of the Laplace-Beltrami operator in a tensorial fashion drawing on conventions from the newly established Calculus of Moving Surfaces (CMS). The Paper then identifies the way which these normal vibrations will manifest within ambient space. Finally, a counter-intuitive relation between the magnitude of such dynamic vibrations and dynamic surface’s time-dependent mean curvature presents itself, for which dynamic vibrations superimposed on original dynamic motion will eliminate the other, and the surface remains static under an arbitrary initial motion. From this condition, resubstitution within the wave equation yields a novel coupled PDE system which within contains the time-evolution of the surface’s mean curvature and its dynamic vibrations. This analysis can have application for algorithms designed for mechanical stabilization during seismic activity, as well as analyzing stabilization algorithms for other various applications and can also have application with respect to biotechnological innovations for analyzing properties defined on the surface of cell-Like biological entities such as metabolism, lipid content, and actin dynamics.

Classical antibacterial drugs were designed to target specific bacterial properties distinct from host human cells to maximize potency and selectivity. These designs were quite effective as they could be easily derivatized to bear next generation drugs. However, the rapid mutation of bacteria and their associated acquired drug resistance have led to the rise of highly pathogenic superbug bacterial strains for which treatment with first line drugs is no match. More than ever, there is a dire need for antibacterial drug design that goes beyond conventional standards. Taking inspiration by the body’s innate immune response to employ its own supply of labile copper ions in a toxic attack against pathogenic bacteria, which have a very low Cu tolerance, this review article examines the feasibility of Cu-centric strategies for antibacterial preventative and therapeutic applications. Promising results are shown for the use of Cu-containing materials in the hospital setting to minimize patient bacterial infections. Studies directed at disrupting bacterial Cu regulatory pathways elucidate new drug targets that can enable toxic increase of Cu levels and perturb bacterial dependence on iron. Likewise, Cu intracellular chelation/prochelation strategies effectively induce bacterial Cu toxicity. Cu-based small molecules and nanoparticles demonstrate the importance of the Cu ions in their mechanism and display potential synergism with classical drugs.

Groupers (Epinephelidae) are ecologically important mesopredators that support valuable fisheries across the globe. Many groupers display slow growth and maturity, high longevity, ontogenetic habitat shifts, spawning-related migrations and aggregations, and protogynous hermaphroditism, which make them susceptible to overexploitation. In this review, I synthesize available information related to the management of grouper fisheries across the southeastern and Caribbean U.S. I highlight current management challenges, such as managing multispecies reef fish fisheries with growing recreational fishing effort. I discuss management interventions with limited success, such as establishing marine protected areas to improve the populations of groupers that display protogynous hermaphroditism. I also highlight management successes, such as recovering historically depleted grouper stocks, and ecosystem-based considerations in grouper stock assessments. I discuss how climate change and anthropogenic effects are expected to affect groupers. Lastly, I provide examples of stakeholders involved in monitoring and management efforts directed at grouper stocks. The purposes of this review are to demonstrate the complexities of managing grouper fisheries and provide a road map for future research and conservation efforts into these economically and ecologically relevant fishes within and beyond the region.

Betadine (Providone-Iodine) solution is a topically applied antiseptic, which has been used for wound care and surgery for decades for the prevention and treatment of skin and wound infections. However, several studies have documented the ineffectiveness of Betadine solution. Other topical antimicrobial dressings, including those that contain silver, have been used in the management of infected wounds. The present study was undertaken to determine if the combination of 5% Betadine solutions and silver colloidal gel (Ag-gel), is more effective than the individual materials in inhibiting the growth of both Gram negative and Gram positive bacteria. These determinations were carried out by both the colony forming unit (CFU) assay, and confocal laser scanning microscopy (CLSM). Ag-gel showed complete inhibition on all the bacteria, except Klebsiella pneumoniae CI strain while 5% Betadine concentrations did not completely kill any of the tested bacteria. However, K. pneumoniae was completely eliminated in the presence of the combination of 5% Betadine solution plus Ag-gel. Confocal laser microscopy confirmed the CFU results. Thus this study demonstrated that while the individual treatments are not effective in killing all the bacteria tested, the combination of 5% Betadine solution and Ag-gel completely kill all bacteria tested, including K. penumoniae CI.

Very heavy stratiform precipitation (> 200 mm/per day) occurred in the Hokitika region on the west coast of the South Island of New Zealand on 18 June 2015, under north-westerlies with small CAPE (< 25 J/kg). Analyses of model simulations and observations showed that this heavy rainfall was due to cold front lifting enhanced by orographic lifting over the Southern Alps. At 1.5 km grid-length, the model terrain underestimated the average height of the 103 tallest mountains over the South Island by ~ 800 m. This leads to weaker orographic lifting and mountain blocking, and a faster-moving and stronger cold front in the Hokitika region. As a result, large errors in the heavy rainfall prediction occur. By increasing either the resolved or the sub-grid mountain heights, the simulated rainfall errors were largely reduced through stronger orographic lifting and mountain blocking, and a better simulation of the cold front movement and strength. All the experiments have the same “flow-over” regime with mountain waves and/or wave breaking (Fm ranges 0.61 – 1.21). However, the rainfall amount and distribution on the windward side of mountains altered significantly. Our new findings were that the Southern Alps can have significant indirect effects on heavy rainfall by altering the speed and strength of the cold front, in addition to the well-known direct dynamical effects (i.e., orographic lifting and mountain blocking). A combination of these direct and indirect effects makes the heavy rainfall simulation sensitive to mountain heights even under the same “flow-over” regime.

The present study evaluates the psychometric properties of the Conflicts in Romantic Relationships Over Facebook Use Scale with a sample of Puerto Rican adults. A total of 577 Puerto Ricans participated on this confirmatory and psychometric study. The results confirmed that the scale has a multidimensional structure. These dimensions are: Partner Facebook intrusion, Conflict over Facebook use, and Jealousy over Facebook use. A total of 18 items complied with the criteria of discrimination and presented appropriate factorial loads (6 items per dimension). The Cronbach’s Alpha indexes of the dimensions ranged between .87 and .95 and the omega coefficients ranged between .88 and .95. In summary, the instrument has the appropriate psychometric properties to continue with validation studies, as well as to be implemented in various work areas, both theoretical and applied.

Plant growth-promoting rhizobacteria (PGPR) are members of the plant rhizomicrobiome that enhance plant growth and stress resistance by increasing nutrient availability to the plant, producing phytohormones or other secondary metabolites, stimulating plant defense responses against abiotic stresses and pathogens, or fixing nitrogen. The use of PGPR to increase crop yield with minimal environmental impact is a sustainable and readily applicable replacement for a portion of chemical fertilizer and pesticides required for the growth of high-yielding varieties. Increased plant health and productivity have long been gained by applying PGPR as commercial inoculants to crops, although with uneven results. The establishment of plant-PGPR relationships requires the exchange of chemical signals and nutrients between the partners, and polyamines (PAs) are an important class of compounds that act as physiological effectors and signal molecules in plant-microbe interactions. In this review we focus on the role of PAs in interactions between PGPR and plants. We describe the basic ecology of PGPR and production and function of PAs in them and in the plants with which they interact. We examine the metabolism and the roles of PAs in PGPR and plants individually and during their interaction with one another. Lastly, we describe some directions for future research.

A model that predicts levels of coronavirus (CoV) respiratory/fecal-oral transmission potentials based on the outer shell hardness has been built using neural network (artificial intelligence, AI) analysis of the percentage of disorder (PID) in the nucleocapsid, N, and membrane, M, proteins of the inner and outer viral shells, respectively. Based mainly on the PID of N, SARS-CoV-2 is categorized as having intermediate levels of both respiratory and fecal oral transmission potential. Related to this, other studies have found strong positive correlations between virulence and inner shell disorder among numerous viruses, including Nipah, Ebola, and Dengue viruses. There is some evidence that this is also true for SARS-CoV-2 and SARS-CoV, which have N PIDs of 48% and 50%, and are characterized by case-fatality rates of 7.1% and 10.9%, respectively. The link between levels of respiratory transmission and virulence lies in viral load of body fluids and organ respectively. A virus can be infectious via respiratory modes only if the viral loads in saliva and mucus exceed certain minima. Likewise, a person may die, if the viral load is too high especially in viral organs. Inner shell proteins of viruses play important roles in the replication of viruses, and structural disorder enhances these roles by providing greater efficiency in protein-protein/DNA/RNA/lipid binding. This paper outlines a novel strategy in attenuating viruses involving comparison of disorder patterns of inner shells of related viruses to identify residues and regions that could be ideal for mutation. The M protein of SARS-CoV-2 has one of the lowest M PID values (6%) in its family, and therefore this virus has one of the hardest outer shells, which makes it resistant to antimicrobial enzymes in body fluid. While this is likely responsible for its contagiousness, the risks of creating an attenuated virus with a more disordered M are discussed.

Using insights from cybernetics and an information-based understanding of biological systems, a precise, scientifically inspired, definition of free-will is offered and the essential requirements for an agent to possess it in principle are set out. These are: a) there must be a self to self-determine; b) there must be a non-zero probability of more than one option being enacted; c) there must be an internal means of choosing among options (which is not merely random, since randomness is not a choice). For (a) to be fulfilled, the agent of self-determination must be organisationally closed (a `Kantian whole'). For (c) to be fulfilled: d) options must be generated from an internal model of the self which can calculate future states contingent on possible responses; e) choosing among these options requires their evaluation using an internally generated goal defined on an objective function representing the overall `master function' of the agent and f) for `deep free-will', at least two nested levels of choice and goal (d-e) must be enacted by the agent. The agent must also be able to enact its choice in physical reality. The only systems known to meet all these criteria are living organisms, not just humans, but a wide range of organisms. The main impediment to free-will in present-day artificial robots, is their lack of being a Kantian whole. Consciousness does not seem to be a requirement and the minimum complexity for a free-will system may be quite low and include relatively simple life-forms that are at least able to learn.

We report the development of in vitro propagation protocols through adventitious shoot induction pathway for a rare and medicinal Scutellaria havanensis. In vitro propagation studies using nodal explants showed MS medium supplemented with 10µM 6-Benzylaminopurine induced highest number of adventitious shoots in a time dependent manner. A ten - day incubation was optimum for shoot bud induction as longer exposures resulted in hyperhydricity of the explants and shoots induced. We also report preliminary evidence of Agrobacterium tumefaciens EHA105 - mediated gene transfer transiently expressing of green fluorescent protein in this species. Transformation studies exhibited amenability of various explant tissues, internode being the most receptive. As the plant has medicinal value, research was carried out to evaluate its potential antioxidant capacity and the efficacy of methanolic leaf extracts in curbing the viability of human colorectal cancer cell line HCT116. Comparative total polyphenol, and flavonoid content measurement of fresh and air dried leaf extract revealed that the fresh leaf extracts contain higher total polyphenol and flavonoid content. The HCT 116 cell viability assessed by colorimetric assay using a 3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyltetrazolium bromide, showed a steady growth inhibition after 24 hours of incubation. Scanning Electron Microscopy of leaf surface revealed high density of glandular and non-glandular trichomes. This research provides basis for the conservation of this rare plant and future phytochemical screening and clinical research.

Access to medicines is one of the essential problems in Public Health of low- and middle-income countries (LMICs). The World Health Organization (WHO) defines access to medicines as the possibility of "having continuously accessible and affordable medicines in public or private health facilities that are within a kilometer of the place of residence." Access to medicines, as defined by the WHO, is not fully guaranteed in many LMICs and even in many regions of high-resource countries. The WHO identifies several factors as determinants of limitations in the access to medicines: rational selection, affordable prices, sustainable financing, and reliable health services. The action on these factors makes it possible to improve universal access to medicines with consequent improvement in Public Health. Adequate access to antibiotics and vaccination will avoid a large part of the deaths caused by infectious diseases in the LMICs. However, the emergence of resistance and the difficulties in vaccination campaigns due to socio-political or cultural problems make it challenging to fight many easily treatable infectious diseases. The use and abuse of antibiotics are inevitably associated with the appearance of resistances that make them ineffective. Thus, whereas limited access to antibiotics raises mortality rates from infectious diseases, generalized open access to them ends up eliminating their clinical value. Moreover, the contraction of research in this field for many years has reduced the success in discovering new drugs. Additionally, local market regulations, inadequate selection, inaccessible prices, especially for those of second and third-generation, inefficient health systems, and difficulties of administration and control of prescription compliance, especially in the case of combined therapies, are additional obstacles to universal access to antibiotics. In order to simultaneously improve access to antibiotics and keep resistances under control, it is necessary to develop training and education activities at different social levels (from patients to various Health Care Providers) to complement the national or supranational strategic plans.

The last few decades have witnessed a surge of interest in adventure sports, and an emerging research focus on these activities. However, recent conceptual analyses and scientific reviews have highlighted a major, fundamental question that remains unresolved: what constitutes an adventure sport (and are they ‘sports’ at all)? Despite several proposals for definitions, the field still seems to lack a shared conceptualization. This deficit may be a serious limitation for research and practice, restricting the development of a more nuanced theoretical explanation of participation and prac-tical implications within and across adventure sports. In this article we address another crucial question, how can adventure sports be better understood for research and practice? We briefly summarize previous definitions to address evident confusion and lack of conceptual clarity in the discourse. Alternatively, we propose how an ecological perspective on human behaviors, as in-teractions with the environment, may provide an appropriate conceptualization to guide and enhance future research and practice, using examples from activities such as freeride skiing / snowboarding, white-water kayaking, climbing, mountaineering and the fields of sport science, psychology and avalanche research and education. We draw on ecological dynamics as a trans-disciplinary approach to discuss how this holistic framework presents a more detailed, nuanced, and precise understanding of adventure sports.

SARS-CoV-2 was empirically and computationally found to be of a specific but peculiar evolution. Shell disorder models found that the outer shell (M protein) of SARS-CoV-2 to be among the hardest in its CoV family. The hard outer shell (low M percentage of disorder (PID)) is likely to be related to the SARS-CoV-2 resistance to the antimicrobial enzymes in saliva and mucus, and be responsible for the high-level of viral shedding which has been observed clinically. Experimental studies have also shown that SARS-CoV-2 is more resilient in the environment than many other CoVs, including SARS-CoV-1. Another aspect of the shell disorder models predicts that SARS-CoV-1 is more virulent than SARS-CoV-2 because of higher inner shell disorder (N PID) that helps SARS-CoV-1 replicate faster in vital organs despite being of lesser viral loads in the saliva and mucus, unlike SARS-CoV-2. This has been reaffirmed experimentally, where higher levels (50 folds) of infectious particles were detected in the SARS-CoV-1 samples in comparison with those of SARS-CoV-2. The hard outer shell of SARS-CoV-2 has been found to be associated with burrowing animals, particularly pangolins, which are often in contact with buried feces. For these reasons, the M protein is highly conserved among close relatives of SARS-CoV-2. The phylogenetic tree using M, unlike the genome-wide one, shows that pangolin-CoVs are more closely related to SARS-CoV-2 than bat-RaTG13. Previous phylogenetic studies may have been confused by recombinations that are usually poorly handled. According to the shell disorder models based on the N PID, an attenuated COVID-19 strain is likely to have entered humans via pangolins in 2017 or before, which provides the virus enough time to adapt to humans. This could explain why the SARS-CoV-2 S protein is highly adapted to the human ACE-2. The specific but peculiar evolution has a wide range of clinical, immunological, and epidemiological implications.

A commercially reared domesticated turkey (Meleagris gallopavo) was purchased from a local market and sections of tissue representing leg, thigh, and breast were harvested and processed for analysis of the lipids and proteins present. Leg and thigh tissue was enriched in mitochondrial proteins whereas the breast tissue was enriched in glycolytic enzymes as well as the cytosolic and mitochondrial forms of glycerol-3-phosphate dehydrogenase. A potential marker for breast tissue muscle formation and/or function was also identified. The tissues could clearly be separated based upon their lipid profiles with little differences in cardiolipin levels suggesting that mitochondrial surface areas may be similar across the tissues. The most significant differences in the lipids were found to be higher levels of oxidized lipids in thigh meat. This work provides the first untargeted proteome and lipidome datasets for the domesticated turkey. The proteome dataset is accessible from ProteomeXchange Consortium via the PRIDE partner repository with the identifier PXD008207.

This work investigates centered polygonal lacunary functions restricted from the unit disk onto symmetry angle space which is defined by the symmetry angles of a given centered polygonal lacunary function. This restriction allows for one to consider only the p-sequences of the centered polygonal lacunary functions which are bounded, but not convergent, at the natural boundary. The periodicity of the $p$-sequences naturally gives rise to a convergent subsequence, which can be used as a grounds for decomposition of the restricted centered polygonal lacunary functions. A mapping of the unit disk to the sphere allows for the study of the line integrals of restricted centered polygonal that includes analytic progress towards closed form representations. Obvious closures of the domain obtained from the spherical map lead to four distinct topological spaces of the "broom topology'' type.

Streptococcus mutans is well known for having virulence factors associated with its cariogenic role, such as glucosyltransferases, which have been used as targets for the virtual screening of molecules with inhibitory capacity. The Antigen I/II of S. mutans is involved in the adhesion to the surface of the tooth and the bacterial co-aggregation in the biofilm formation, despite that, this protein has not been used as a target in a virtual strategy search for inhibitors. In this study we identified in silico and evaluated in vitro molecules with adhesion inhibitory potential on S. mutans Ag I/II. A virtual screening of 883,551 molecules was conducted, cytotoxicity analysis on fibroblast cells, S. mutans adhesion studies, scanning electron microscopy analysis for bacterial integrity, and molecular dynamics simulation were also performed. We have found three molecules (ZI-187, ZI-939, ZI-906) that were not cytotoxic and inhibited the adhesion of S. mutans to polystyrene microplates. Molecular dynamic simulation by 300 nanoseconds showed stability of the interaction between ZI-187 and Ag I/II (PDB: 3IPK). This work provides three new molecules that targets Ag I/II and have the capacity to inhibit in vitro the S. mutans adhesion on polystyrene microplates and provides a new computational line for the search and selection of safe inhibitory molecules against different pathogens.

Little is known about fertility preservation within the TGD community. Few receive adequate counseling placing them at risk for decision regret. The goal of this project was to develop, and pilot test the Transgender Fertility Preservation Knowledge Scale (TFPKS) to support the development and evaluation of health education resources. A community engaged; cross sectional retrospective design was used. Participants (n=189) provided information describing demographics, healthcare decision-making preferences, experiences/knowledge of fertility preservation, and treatment decision regret. The sample included 189 TGD adults. Most were white and aged 26-35 (33.3%) and not offered a consultation (73.0%). Many (41.2%) report they would have participated if offered. Knowledge regarding fertility preservation to support this desire was low. Most participants identified a patient-centered (69.4%) decision making preference. Much remains to address the healthcare inequities within the TGD population regarding fertility preservation. Overall participants had low levels of knowledge to support decision making. Further, healthcare system and individual barriers to fertility preservation remain prevalent. A foundational step towards addressing these disparities, is the identification of a valid and reliable instrument to measure TGD knowledge of fertility preservation.

The aim of this study was to estimate the association between fear of COVID-19 and risk perception with preventive behavior in health professionals from three Latin American countries. An analytical cross-sectional study was conducted. Health professionals with on-site care in Colombia, Ecuador, Guatemala, and Peru were surveyed. Information was collected through an online self-report questionnaire. The main variables were preventive behavior as the dependent variable and fear of COVID-19 and risk perception as independent variables. Linear regression was used, and Beta coefficients and p-values were calculated. 435 health professionals were included, the majority were aged 42 years or older (45.29%, 95%CI: 40.65%-50.01%) and female (67.82%, 95%CI: 63.27%-72.05%). It was shown that the greater the fear of COVID-19, the greater the preventive behavior of COVID-19 infection (B=2.21, p=0.002 for total behavior; B=1.12, p=0.037 for additional protection at work; B=1.11, p<0.010 for hand washing). The risk perception of COVID-19 infection had a slight direct relationship with preventive behaviors (B=0.28, p=0.021 for total behavior; B=0.13, p=0.015 for hand washing), with the exception of the preventive behavior of using additional protection at work (p=0.339). We found that fear and risk perception are associated with increased practice of hand washing and use of additional protection at work. Further studies are required on the influence of working conditions, job performance and the occurrence of mental health problems in frontline personnel with regard to COVID-19.

Internet-led labour market has become so competitive forcing many organisations from different sectors to embrace e-recruitment. However, realising the value of the e-recruitment from a Requirements Engineering (RE) analysis perspective is challenging. This research is motivated by the results of a failed e-recruitment project conducted in military domain which is used as a case study in this research. After reviewing the various challenges faced in that project through a number of related research domains, this research focuses on two major problems which are the (1) difficulty of scoping, representing, and systematically transforming recruitment problem knowledge towards e-recruitment solution specification; and (2) the difficulty of documenting e-recruitment best practices for reuse purposes in an enterprise recruitment environment. In this paper, a Problem-Oriented Conceptual Model (POCM) with a complementary Ontology for Recruitment Problem Definition (Onto-RPD) is proposed to contextualise the various recruitment problem viewpoints from an enterprise perspective and to elaborate those problem viewpoints towards a comprehensive recruitment problem definition. The POCM and Onto-RPD are developed incrementally using action-research conducted on three real case studies: (1) Secureland Army Enlistment, (2) British Army Regular Enlistment, and (3) UK Undergraduate Universities and Colleges Admissions Service (UCAS). They are later evaluated in a focus group study against a set of criteria. The study showed that the POCM and Onto-RPD provide a strong foundation for representing and understanding the e-recruitment problems from different perspectives.

In an era of unparalleled technical advancement, the pharmaceutical industry is struggling to transform data into increased research and development efficiency, and as a corollary, new drugs for patients. Here, we briefly review some of the commonly discussed issues around this counterintuitive innovation crisis. Looking at both industry and science related factors, we posit that traditional preclinical research is front-loading the development pipeline with data and drug candidates that are unlikely to succeed in patients. Applying a first principles analysis, we highlight the critical culprits and provide suggestions as to how these issues can be rectified through pursuit of a Human Data-driven Discovery (HD3) paradigm. Consistent with other examples of disruptive innovation, we propose that new levels of success are not dependent on new inventions, but rather the strategic integration of existing data and technology assets. In support of these suggestions, we highlight the power of HD3, through recently published proof-of-concept applications in the areas of drug safety analysis and prediction, drug repositioning, rational design of combination therapies and the global response to the Covid19 pandemic. We conclude that innovators must play a key role in expediting the path to a largely human focused, systems-based approach to drug discovery and research.

BACKGROUND: Retinoblastoma is a malignant tumour that develops from the immature cells of the retina. It is the most frequent type of paediatric intraocular cancer and is curable. Clinical and histological findings after enucleation of the affected eye dictate not only the patient's secondary care but also their prognosis. We assessed the clinical and histopathologic predictors of survival among children with retinoblastoma from two tertiary health facilities in Uganda. METHODS: This retrospective research utilized archived formalin fixed & paraffin embedded blocks of eye specimens enucleated between 2014 to 2016 at Mbarara University, pathology department and Ruharo Eye Centre. The specimens were then processed and stained with haematoxylin and eosin. The confirmation of retinoblastoma was made to include histologic stage and features of the tumor. Biographic data of the patients and the clinical features such as leukocoria, proptosis, phthisis, staphyloma, buphthalmos were retrieved from the records.RESULTS: Males (55.1%) dominated the study population (N=78). The median age was 31 months. The commonest clinical sign was leukocoria (69.2%) and the most abundant histopathological stage was stage 1 (41%). Optic nerve invasion 39.5%, choroidal invasion 29.5%, scleral invasion 7.7% and orbital extension 16.7% were seen. Flexner-Wintersteiner rosettes were seen in 24.6%. Necrosis was a prominent feature (71.2%). The two-year survival was estimated to be 62%. Leukocoria (RR 1.1), female gender (RR 1.4), intralaminar optic nerve invasion (RR 7.6) and a lack of orbital extension (RR- 7) were significant predictors of survival.CONCLUSION: Leukocoria and proptosis are noticeable clinical signs of retinoblastoma. Most patients present while in stage one although stage four presentation is also common. Leukocoria, optic nerve invasion, orbital extension, and gender are significant factors predictive of survival in patients with retinoblastoma.

Serum transferrin (sTf) plays a pivotal role in regulating iron biodistribution and homeostasis within the body. The molecular details of sTf Fe(III) binding, blood transport, and cellular delivery through transferrin receptor-mediated endocytosis are generally well-understood. Emerging interest exists in exploring sTf complexation of nonferric metals as it facilitates the therapeutic potential and toxicity of several of them. This review explores recent X-ray structural and physiologically relevant metal speciation studies to understand how sTf partakes in the bioactivity of key non-redox active hard Lewis acidic metals. It challenges preconceived notions of sTf structure function correlations that were based exclusively on the Fe(III) model by revealing distinct coordination modalities that nonferric metal ions can adopt and different modes of binding to metal-free and Fe(III)-bound sTf that can directly influence how they enter into cells and, ultimately, how they may impact human health. This knowledge informs on biomedical strategies to engineer sTf as a delivery vehicle for metal-based diagnostic and therapeutic agents in the cancer field. It is the intention of this work to open new avenues for characterizing the functionality and medical utility of nonferric-bound sTf and to expand the significance of this protein in the context of bioinorganic chemistry.

Llayta is a dietary supplement used by rural communities in Perú and northern Chile since pre-Columbian days. Llayta is the biomass of colonies of a Nostoc cyanobacterium grown in wetlands of the Andean highlands, harvested, sun-dried and sold as an ingredient for human consumption. The biomass has a substantial content of essential amino acids (58% of total amino acids) and polyunsaturated fatty acids (33% total fatty acids). This ancestral practice is being loss and the causes were investigated by an ethnographic approach to register the social representations of Llayta, to document how this Andean feeding practice is perceived and how much the community knows about Llayta. Only 37% of the participants (mostly adults) have had a direct experience with Llayta; other participants (mostly children) did not have any knowledge about it. These social responses reflect anthropological and cultural tensions associated to lack of knowledge on Andean algae, sites where to find Llayta, where it is commercialized, how it is cooked and on its nutritional benefits. The loss of this ancestral feeding practice, mostly on northern Chile, is probably associated to cultural changes, migration of the rural communities, and a very limited access to the available information. We propose that Llayta consumption can be revitalized by developing appropriate educational strategies and investigating potential new food derivatives based on the biomass from the isolated Llayta cyanobacterium.

Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declined responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing macrophage activation are critically involved in arteriolar CNV formation and anti-VEGF resistance. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.

Introduction: Individuals with gout are at higher risk of developing chronic conditions, such as diabetes, chronic kidney disease (CKD), and cardiovascular diseases. In this study, the association between urate-lowering therapy (ULT) use and the prevalence of these conditions was evaluated. Methods: This observational, cross-sectional pharmacoepidemiologic study used the 2013-2018 biannual cycles of the National Health and Nutrition Examination Survey. The inclusion criteria were adults 30 years of age and older with a diagnosis of gout. The association between ULT treatment status and dyslipidemia, coronary heart disease, heart failure, hypertension, and chronic kidney disease was evaluated, as well as associations with select clinical laboratory biomarkers. Results: Use of ULT was 28.9% (95%CI 24.3%-33.9%). There was no significant association between ULT use and the prevalence of heart failure, coronary heart disease, hypertension, or dyslipidemia (p>0.05). Those on ULT had a lower mean eGFR compared to those not on treatment (68.03 versus 74.74 mL/min/1.73m², p=0.014). LDL- and HDL- and total cholesterol were significantly lower among those receiving ULT treatment (p<0.05). Conclusion: ULT use continues to be low among those with gout. Those on ULT were more likely to be diagnosed with CKD, college graduates and above, older males, and obese. Clinical guidelines conditionally recommend ULTs in co-morbid kidney disease; while our results may reflect guidelines recommendation for ULT use in CKD patients, worsening kidney function while taking ULT is unlikely. Further research is necessary to determine the long-term impact of ULTs on kidney function and cardiovascular biomarkers.

In 1990 the Malaysian Government launched Vision 2020 with the goal of Malaysia becoming a ‘fully developed country’ by the year 2020. In this drive for development the country has been examining many of its key natural assets, exploring how to both preserve them whilst ensuring that they make the maximum possible contribution to national development goals. Endau Rompin is one of these assets, being the second largest National Park in Peninsula Malaysia. The rich tropical rainforest flora and fauna of the Park and its hinterland, however, are threatened by various anthropogenic forces, most notably deforestation and poaching; both of which have taken the Park’s flagship species - the Tiger Panthera tigris jacksoni – towards the brink of local extinction. Malaysia’s statutory East Coast Economic Region Development Council commissioned a study to consider ways of increasing tourism revenues from the Park while at the same time reversing these threats. The key conclusion drawn is that a more holistic, landscape-scale approach should be adopted, with Endau Rompin forming part of a wider strategic economic zone based around sustainable tourism and land management. The proposed expanded zone extends eastwards beyond the confines of the Park, across the coastal plain to the South China Sea, and onwards to the neighbouring Mersing Islands. This expanded zone is referred to as Malaysia’s new ‘Rainforest to Reef Region’.

Millions of people worldwide have an inadequate intake of selenium (Se) and zinc (Zn), and agronomic biofortification may minimise these problems. To evaluate the efficacy of combined foliar Se and Zn fertilisation in bread making wheat (Triticum aestivum L.), foliar Se (as NaSeO4) and soil and foliar Zn applications (as ZnSO4·7H2O) were tested individually and in all combinations. A 2-year field experiment was established in southern Spain under semiarid Mediterranean conditions, by following a split-split-plot design. The study year (2017/2018, 2018/2019) was considered as the main-plot factor, soil Zn application (50 kg Zn ha-1, nil Zn) as a subplot factor, and foliar application (nil, 10 g Se ha-1, 8 kg Zn ha-1, 10 g Se ha-1 + 8 kg Zn ha-1) as a sub-subplot factor. The best treatment to increase both Zn and Se concentration in both straw, 12.3- and 2.7-fold respectively, and grain, 1.2- and 4.1-fold respectively was the combined foliar application of Zn and Se. This combined Zn and Se application also increased on average the yield of grain, main product of this crop, by almost 26%. Therefore, bread-making wheat seems to be a very suitable crop to be used in biofortification programs with Zn and Se to alleviate their deficiency in both, people when using its grain and livestock when using its straw.

The desert locust remains a major threat to global food security. Control operations are a crucial tool to manage crisis; this research investigated the nature of control operations conducted between 2019-2021. Historical data on desert locust and control operations were obtained from the survey reports at the FAO Locust Hub and analysed with respect to survey reports, land cover types, cropland/rangeland extent and crop productivity data. We found that 16.1% of the grid cells with locust presence and 14.9% of the grid cells with control operations had a proportion of rangeland higher than 0.75; while 13.3% of the grid cells with locust presence and 13.2% of the grid cells with control operations had a proportion of croplands higher than 0.75, highlighting that locust presence and control operations were reported in both rangeland and cropland. Control operations continue to be used both to reduce overall locust numbers and to protect crops. Furthermore, through identifying which crops were most at risk, our analyses indicate that wheat production was under the highest strain during periods of increased locust infestations.

Background: The clinical outcomes of antiretroviral drugs may be modified by drug interactions; thus, it is important to update the drug interactions in people living with HIV. Aim: To update clinically relevant drug interactions in people living with HIV on antiretroviral therapy. Methods: A systematic review in Medline/PubMed database from July 2017 to December 2022, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. The clinical relevance of drug interaction was grouped into 5 levels according to gravity and probability of occurrence. Results: 361 articles were identified and 148 were included, which allowed the identification of 894 drug interaction pairs. Among these 894 drug pairs, 355 have not been identified previously; and 89 (25.1%) and 72 (20.2%) were of levels 1 and 2, respectively. In addition, for 197 (55.5%) pairs the mechanism was pharmacokinetic. The non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitors (PIs) with 91 (25.6%) and 76 (21.4%) pairs, respectively were more frequent. Conclusions: In people living with HIV on antiretroviral therapy, we identify 355 new drug interaction pairs, of them 161 (45.3%) are assessed as levels 1 and 2 and thus, clinically relevant; a figure that is lower compared to 2014-2107 update. The pharmacokinetic mechanism is the most frequently identified. The non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitors (PIs) are the antiretroviral groups with the highest number of clinically relevant drug interactions.

Temperature-index modeling is used to determine the magnitude of temperature depression on the Blanca Massif, Colorado, required to maintain steady-state mass balances of nine reconstructed glaciers at their extent during the Last Glacial Maximum (LGM). The mean temperature depression thus determined is ~8.6 +0.7/–0.9 °C where the uncertainties account for those inherent in the glacier reconstructions, in model parameters (e.g. melt factors), and possible modest changes in LGM precipitation. Associated equilibrium-line altitudes (ELAs) exhibit a statistically significant directional dependency being lower toward the north and east. Under the assumption that regional temperature change was uniform, required changes in precipitation vary systematically – also exhibiting a directional dependency coinciding with that in ELAs – and indicate increases (over modern) occurred on the eastern side of the massif while decreases occurred on the western side. This disparity represents a strengthening of a precipitation asymmetry, particularly winter precipitation, that exists today. The modern precipitation asymmetry may be a consequence of snow being blown over to the eastern side of the massif (advective transport) by southwesterly flow. Intensification of this flow during the LGM would have enhanced advection, and augmented snow accumulation on glaciers, thus explaining the lower ELAs and increased precipitation on that side of the massif.

Demography and behavior of Teinopodagrion oscillans was studied in a protected area from Andean region. Adult damselflies were individually marked, and using their recapture histories we estimated survival, longevity, sex ratio, and population size using Cormack-Jolly-Seber models. Furthermore, aspects of their behaviour were recorded. Survival, recapture, and lifespan were similar for both sexes and all age groups. Mature males were larger and the distance from the water was similar for all individuals. The most supported model was the time-dependent model for survival and recapture (Phi(t) p(t)). This suggests that weather variations affect in a significant way the demography of this population. Individuals exhibited high fidelity to their site perch, perching with open wings near to water on a variety of perch. Mature males make short flights from the perch to intercept conspecific and interspecific males and to hunt prey. Tandem position was formed on macrophytes and then the pair flight away. Oviposition lasted for 11.23 minutes on average, with the females ovipositing by abdomen submersion. Our results offer insights on demographic characteristics and behaviour of this species, providing crucial information for short and long term conservation decisions of the biodiversity in ecosystems of the Andean region.

Temperature-index modeling is used to determine the magnitude of temperature depression in the northern Sawatch Range required to maintain steady-state mass balances of six reconstructed glaciers at their extent during the local Last Glacial Maximum (LLGM), dated at ~21 ka. Assuming no significant differences in precipitation compared to modern values, mean annual temperatures in the region were on average 8.8 +0.5/–0.8 °C cooler than they are today. Allowing for modest increases or decreases in precipitation, required temperature depressions only differ by ± 0.2 °C. Temperature depression in the northern Sawatch Range are consistent, although slightly greater, with those determined in other ranges in Colorado using similar approaches. The estimates presented here are, however, substantially less than those suggested by several downscaled simulations of global LGM climate, that might be due to the need for improved calibration of such downscalings, or the models from which they are derived. Our estimates of LGM temperature depression are considerably greater than that previously determined in the study area and those in two other ranges in Colorado derived using different methodologies, the latter being most likely responsible for the discrepancies.

Cable-supported façades represent a novel approach in the design and technology of double skin façades (DSF). This type of systems not only offer flexibility in terms of exterior finishes, but also regulates the access of solar radiation, thereby transforming the appearance of the building in response to varying daylight conditions. However, the structural performance of these façades under wind, impact and seismic loads remains an active area of research. The study is a groundbreaking work that experimentally evaluates the wind and seismic behaviour of these type of façades. The methodology used for the evaluation of flexible masonry facades includes laboratory tests analysing the individual capacity of the connections and materials of the system under standardized and non-standardized procedures. A full-scale experimental sub-assembly specimen of a representative module of the façade is also subjected to uniformly distributed pressures of wind load tests as well as hard body and soft body impact tests. The setup considered the border conditions, tension loads, and actual materials. Furthermore, the earthquake assessment includes tests of full-scale specimens subjected to these demands. Research findings allowed the refinement and redesign of the system's components granting the validation of the DSF used as a case study.

In the whole world, including Mexico, the rising prevalence of diabetes poses significant challenges to healthcare systems, with a notable impact on hospital admissions even being an ambulatory care sensitive condition, that means, hospital admissions are avoidable. Traditional healthcare methodologies have been instrumental in managing diabetes and preventing complications, yet they often face limitations such as merging, cleansing, and outlier analysis of health data to identify and address diseases effectively. This paper aims to address this gap by conducting a comprehensive comparison of the methodologies used in healthcare and data science for this purpose. This work uses hospital diabetes discharge records from 2010 to 2023, a total of 36,665,793 records, which belong to medical units of the Ministry of Health of Mexico. In this work, we seek to provide the arguments why as a data scientist it is mandatory to learn the field of knowledge of the problem and its implications if this is not done, and therefore to disclose insights that can help in policy decisions and reduce the burden of avoidable hospitalizations. The approach is mainly based on the standardization or adjust rates by sex and age groups. This study provides the foundations for a new way of data scientist must deal with health data.

The large quantity of information retrieved from communities, public data repositories, web pages, or data mining can be sparsed and poorly classified. This work shows how to employ unsupervised classification algorithms such as K-means proper to classify user reviews into their closest category, forming a balanced data set. Moreover, we found that the text vectorization technique significantly impacts the clustering formation, comparing TF-IDF and Word2Vec. The value for mapping a cluster with movie genre was 81.34% ± 20.48 of the cases when the TF-IDF was applied, whereas Word2Vec only yielded a 53.51% ± 24.1. In addition, we highlight the impact of the removal of stop-words. Thus, we detected that pre-compiled lists are not the best method to remove stop-words before clustering because there is much ambiguity, centroids are poorly separated, and only 57% of clusters could match a movie genre. Thus, our proposed approach achieved a 94% of accuracy. After analyzing the classifiers’ results, we appreciated a similar effect when divided by the stop-words method removal. Statistically significant changes were observed, especially in precision metric and Jaccard scores in both classifiers, using custom-generated stop lists rather than pre-compiled ones. Reclassifying sparse data is strongly recommended as using custom-generated stop lists.

Biofilm formation is important in the free-living and symbiotic lifestyles of Sinorhizobium meliloti. Here we show that the S. meliloti NspS-MbaA system is homologous to the c-di-GMP modulating NspS-MbaA system described in Vibrio cholerae and modulates biofilm formation, exopolysaccharide (EPS) production and motility in S. meliloti in response to exogenous polyamines. Biofilm and EPS production in quorum sensing-deficient wild type strain 1021 decreased in cultures containing putrescine, 1,3-diaminopropane or spermine, but were unaffected in a 1021 nspS mutant (1021 nspS). Decreases in biofilm formation caused by these polyamines paralleled decreases in EPS production and increases in nspS transcription. Cell aggregation did not differ markedly between strain 1021 and 1021 nspS. The S. meliloti quorum sensing-proficient Rm8530 wild type strain and nspS mutant (Rm8530 nspS) produced similar levels of biofilm under control conditions and 3.2- and 2.2-fold more biofilm in cultures with norspermidine, but these changes did not correlate with EPS production. Rm8530 nspS aggregated up to several fold more than the wild type under most conditions. Changes caused by polyamines in swimming and swarming motility were not generally dependent on NspS-MbaA in either 1021 or Rm8530. We speculate that the S. meliloti NspS-MbaA system could modulate biofilm formation in response to environmental polyamines.

Hydraulic relationships are important for water resource management, hazard prediction, and modelling. Since Leopold first identified power law expressions that could relate streamflow to top-width, depth, and velocity, hydrologists have been estimating ‘At-a-station Hydraulic Geometries’ (AHG) to describe average flow hydraulics. As the amount of data, data sources, and application needs increase, the ability to apply, integrate and compare disparate and often noisy data is critical for applications ranging from reach to continental scales. However, even with quality data, the standard practice of solving each AHG relationship independently can lead to solutions that fail to conserve mass. The challenge addressed here is how to extend the physical properties of the AHG relations, while improving the way they are hydrologically addressed and fit. We present a framework for minimizing error while ensuring mass conservation at reach - or hydrologic Feature - scale geometries’(FHG) that complies with current state-of-the-practice conceptual and logical models. Through this framework, FHG relations are fit for the United States Geological Survey’s (USGS) Rating Curve database, the USGS HYDRoacoustic dataset in support of the Surface Water Oceanographic Topography satellite mission (HYDRoSWOT), and the hydraulic property tables produced as part of the NOAA/Oakridge Continental Flood Inundation Mapping framework. The paper describes and demonstrates the accuracy, interoperability, and application of these relationships to flood modelling and presents this framework in an R package.

A model to predict the relative levels of respiratory and fecal-oral transmission potentials of coronaviruses (CoVs) by measuring the percentage of protein intrinsic disorder (PID) of the M (Membrane) and N (nucleoprotein) proteins in their outer and inner shells, respectively, was built before the MERS-CoV outbreak. Application of this model to the 2003 SARS-CoV indicated that this virus with M_PID = 8.6% and N_PID = 50.2% falls into group B, which consists of CoVs with intermediate levels of both fecal-oral and respiratory transmission potentials. Further validation of the model came with MERS-CoV (M_PID = 9%, N_PID = 44%) and SARS-CoV-2 (M_PID = 5.5%, N_PID = 48%) falling into the groups C and B, respectively. Group C contains CoVs with higher fecal-oral but lower respiratory transmission potentials. Unlike SARS-CoV, SARS-CoV-2 with M_PID = 5.5% has one of the hardest outer shells among CoVs. This shell hardness is believed to be responsible for high viral loads in the mucus and saliva making it more contagious than SARS-CoV. The hard shell is able to resist the anti-microbial enzymes in body fluids. Further searches have found that high rigidity of outer shell is characteristic for the CoVs of burrowing animals, such as rabbits (M_PID = 5.6%) and pangolins (M_PID = 5-6%), which are in contact with the buried feces. A closer inspection of pangolin-CoVs from 2017-19 reveals that these animals provided a unique window of opportunity for the entry of an attenuated SARS-CoV-2 precursor into the human population in 2017 or earlier, with the subsequent slow and silent spread as a mild cold that followed by its mutations into the current more virulent form. Evidence of this lies in the similarity of shell disorder and genetic proximity of the pangolin-CoVs to SARS-CoV-2 (~90%). A 2017 pangolin-CoV strain shows evidence of higher levels of attenuation and higher fecal-oral transmission associated with lower human infectivity via having lower N_PID (44.8%). Our shell disorder analysis also revealed that lower inner shell disorder is associated with the lesser virulence in a variety of viruses.

The Leave-One-Out (LOO) Green Fluorescent Protein (GFP) approach to biosensor design com-bines computational protein design with split protein reconstitution. LOO-GFPs reversibly fold and gain fluorescence upon encountering its target peptide, which can be redefined by computa-tional design of the LOO site. Such an approach can be used to create reusable biosensors for the early detection of emerging biological threats. Enlightening biophysical inferences for nine LOO-GFP biosensor libraries are presented, with target sequences from dengue, influenza, or HIV, replacing beta strands 7, 8 or 11. An initially low hit rate was traced to components of the energy function, manifesting in the over-rewarding of over-tight side chain packing. Also, screening by colony picking required a low library complexity, but designing a biosensor against a peptide of at least 12 residues requires a high complexity library. This double-bind was solved using a "piecemeal" iterative design strategy. Also, designed LOO-GFPs fluoresced in the unbound state due to unwanted dimerization, but this was solved by fusing a fully functional prototype LOO-GFP to a fiber-forming protein, Drosophila ultrabithorax, creating a biosensor fiber. One in-fluenza hemagglutinin biosensor is characterized here in detail, showing a shifted excita-tion/emission spectrum, a micromolar affinity for the target peptide, and an unexpected pho-to-switching ability.

Despite concerns about the negative effects of social distancing and prolonged school closures on children’s lifestyle and physical activity (PA) during the COVID-19 pandemic, robust evidence is lacking on the impact of the COVID-19 pandemic on children’s wellbeing and daily life. This study aimed to examine changes in the PA levels, sleep patterns and screen time of school-aged children during the different phases of COVID-19 outbreak in Hong Kong using a repeated cross-sectional design. School students (Grades 1 to 12) were asked to report their daily electronic device usage and to fill in a sleep dairy recording their daily sleep and wake-up time. They were equipped with a PA monitor, Actigraph wGT3X-BT, to obtain objective data on their PA levels and sleep patterns. Students were recruited before the pandemic (Sep 2019 – Jan 2020; n=577), during school closures (Mar 2020 – Apr 2020; n=146), and after schools partially reopened (Oct 2020 – Jul 2021; n=227). Our results indicated lower PA levels, longer sleep duration, and longer screen time among participants recruited during school closures than those recruited before the COVID-19 outbreak. Primary school students were found to sleep on average for an extra hour during school closures. Our findings illustrate the impact of social distancing policies during the COVID-19 pandemic on the sleep pattern, screen time, and PA level in school-aged children in Hong Kong. Professionals should reinforce the importance of maintaining a physically active lifestyle, good sleep hygiene, and healthy use of electronic devices to parents and school-aged children during the COVID-19 Pandemic.

Structural hydroxide groups in layered magnesium-aluminum double hydroxides were partially replaced by fluoride ions. Fluorinated and fluorine-free materials were used as hosts for two dyes, carminic acid and hydroxyl naphthol blue, resulting in a hybrid pigment color palette. Additionally, the pigments were protected with a magnesium hydroxide phase to prevent the color from fading over time. The color properties of the pigments were significantly influenced by the host of dye, since the presence of fluorine directly influences the acid-base properties of the layered double hydroxides. Finally, the pigments were successfully applied to prepare colored creams.

The use of natural carotenoids as food colorants is an important trend of innovation in the industry due to their low toxicity, their potential as bio-functional ingredients, and the increasing demand for natural and organic foods. Despite these benefits, their inclusion in food matrices presents multiple challenges related to their low stability and low water solubility. The present review covers the main concepts and background of carotenoid inclusion complex formation in cyclodextrins as a strategy for their stabilization, and subsequent inclusion in food products as color additives. The review includes the key aspects of the molecular and physicochemical properties of cyclodextrins as complexing agents, and a detailed review of the published evidence on complex formation with natural carotenoids from different sources in cyclodextrins, comparing complex formation methodologies, recovery, inclusion efficiency, and instrumental characterization techniques. Moreover, process flow diagrams (PFD), based on the most promising carotenoid-cyclodextrin complex formation methodologies, are proposed, and discussed as a potential tool for their future scale-up. This review shows that the inclusion of carotenoids in complexes with cyclodextrins constitutes a promising technology for the stabilization of these pigments, with possible advantages in terms of their stability in food matrices.

Fifty bull calves of the Continental × British crossbred (147.0 ± 1.67 kg body weight, BW) were used in a completely randomized design to investigate the effect varying levels and duration of calcium propionate (CaPr) supplementation on the growth performance, body fat reserves, serum metabolites, and hemogram of high-risk newly received stocker calves. These calves were individually housed and fed a received-diet for 56 d. The calves received the following treatments: 1) No CaPr (CTL), 2) 20 g CaPr/calf/d, 3) 40 g CaPr/calf/d, 4) 60 g CaPr/calf/d, and 5) 80 g CaPr/calf/d, during 14, 28, 42 and 56 d the after arrival. The supplementation with 20 g CaPr from 28 to 56 d after arrival increases average daily gain (ADG) and BW (p &lt; 0.05), and DMI is not affected (p &gt; 0.05). This is reflected at 28 d with increases (p &lt; 0.05) in ADG:DMI ratio and longissimus muscle area (LMA), and at 56 d in back fat thickness (BFT) y fat thickness at the rump (FTR). Also, with 20 g, blood urea nitrogen decreased (p &lt; 0.05); and increases were observed in the activity of gamma glutamyltransferase, monocytes (quadratic trend, p &lt; 0.07) and granulocytes% (quadratic effect, p &lt; 0.03). However, as the level of CaPr increased during the first 14 d after arrival, daily water intake, creatinine, total cholesterol, mean corpuscular hemoglobin concentration (linear effect, p &lt; 0.05), globulin, calcium and mean corpuscular volume (linear trend, p = 0.08) increased, while alkaline phosphatase (linear trend, p = 0.07) and lymphocytes (linear effect, p = 0.05) decreased. Finally, the different levels of CaPr supplementation did not produce any significant effects or differences (p &gt; 0.05), in the remaining serum metabolites and hemogram (p &gt; 0.05). Ultimately, the inclusion of 20 g CaPr/calf/d in the diet for 28 d in newly received stocker calves increases ADG, ADG:DMI ratio and LMA. If extended to 42 or 56 d, the increases in ADG persist, but there is also a rise in body fat reserves (BFT and FTR) at the expense of a reduction in ADG:DMI ratio. Furthermore, the different supplementation levels did not impact the reference range for most serum metabolites or the health of stocker calves.

Organometallic drug development is still in its early stage, but recent studies show that organometallics having iron as the central atom have the possibility of becoming good drug candidates because iron is an important micro-nutrient, and it is compatible with many biological systems, including the human body. Being an eco-friendly Lewis acid, iron can accept the lone pair of electrons from imino(sp2)-nitrogen, and the resultant iron-imine complexes with iron as a central atom have the possibility of interacting with several proteins and enzymes in humans. Iron-imine complexes have demonstrated significant potential as anticancer, bactericidal, fungicidal, and other medicinal activities in recent years. This article systematically discusses major synthetic methods and pharmacological potentials of iron-imine complexes having in vitro activity to significantly affect clinical performance from 2016 to date. In a nutshell, this manuscript offers a simplistic view of iron complexes in medicinal inorganic chemistry: for instance, iron is presented as an "eco-friendly non-toxic" metal (as opposed to platinum) that will lead to non-toxic pharmaceuticals. The abundant literature on iron chelators shows that many iron complexes, particularly if redox-active in cells, can be quite cytotoxic, which can be beneficial for future targeted therapies. While we made every effort to include all the related papers, any omission is purely unintentional.

The cause and prevention of recurrent aphthous stomatitis (also called aphthous ulcers or canker sores) are still unknown. This may be due in part to ignorance of the risk factors present in susceptible people. In this systematic review (PROSPERO record #CRD42019122214), we show that most of the risk factors for the disease are single nucleotide genetic polymorphisms in genes related to the functioning of immune system (TLR4, MMP9, E-selectin, IL-1 beta and TNF-alpha). Single nucleotide genetic polymorphisms do not constitute a modifiable risk. This indicates that, at least in part, susceptibility to recurrent aphthous stomatitis is hereditary, and that these factors cannot be modified.

Solar radiation corresponds to fundamental parameters for solar photovoltaic (PV) technology. Reliable solar radiation prediction became valuable to design solar PV systems, performance, operatively efficient planning, safety operation, grid dispatch and financial characteristics. However, high quality ground-based solar radiation measurements are scarce, especially for very short-term time horizon. Most of the existent studies trained the machine learning (ML) model used dataset with time horizon of 1-hour or day, very fewer studies have been reported using a dataset with a 1-mitute time horizon. In this study, a comprehensive evaluation of nine ensemble learning algorithms (ELA) is performed to estimate the solar radiation in Santo Domingo with a 1-minute time horizon dataset collected from a local weather station. The ensemble learning evaluated included seven homogeneous ensembles; Random Forest (RF), Extra Tree (ET), Adaptive Gradient Boosting (AGB), Gradient Boosting (GB), Extreme Gradient Boosting (XGB), Light Gradient Boosting (LGBM), Histogram-based Gradient Boosting (HGB) and heterogeneous ensemble named as Voting and Stacking. RF, ET, GB, HGB were combined to develop Voting and Stacking and Linear Regression (LR) was adopted in the second layer of the Stacking. Five technical metrics, Mean Squared Error (MSE), Root Mean Squared Error (RMSE), Mean Absolute Error (MAE), Mean Absolute Percentage Error (MAPE) and Coefficient of Determination (R2) were used as criteria to determine the prediction quality of the developed ensemble algorithms. Comparison of the results indicates that the HGB algorithm offers superior prediction performance among the homogeneous ensemble learning and overall, the Stacking provides the best accuracy with metric values of MSE=3218.27, RMSE= 56.73, MAE=29.87, MAPE=10.60, R2=0.964.

Full waveform (FW) LiDAR holds great potential for retrieving vegetation structure parameters at a high level of detail, but this prospect is constrained by practical factors such as lack of available handy processing tools and technical intricacy of waveform processing. This study introduces a new product, named the Hyper Point Cloud (HPC) derived from FW LiDAR data, and explore its potential applications such as tree crown delineation using the HPC-based intensity and percentile height (PH) surfaces, which show a promising solution to the constraints of using FW LiDAR data. Results of the HPC present a new direction to handle FW LiDAR data and offer prospects for studying the mid-story and understory of vegetation with high point density (~ 182 points/m2). The intensity-derived digital surface model (DSM) generated from the HPC shows that the ground region has larger maximum intensity (MAXI) and mean intensity (MI) than the vegetation region while having smaller total intensity (TI) and number of intensities (NI) at the given grid cell. Our analysis of intensity distribution contours at individual tree level exhibit similar patterns, indicating that the MAXI and MI are decreasing from the tree crown center to tree boundary while a rising trend is observed for TI and NI. These intensity variable contours provide a theoretical justification for using HPC-based intensity surfaces to segment tree crowns and exploit their potential for extracting tree attributes. The HPC-based intensity surfaces and the HPC-based PH Canopy Height Models (CHM) demonstrate promising tree segmentation results comparable to the LiDAR derived CHM for estimating tree attributes such as tree locations, crown widths and tree heights. We envision that products such as the HPC and the HPC-based intensity and height surfaces introduced in this study can open new perspectives to use FW LiDAR data and alleviate the technical barrier of exploring FW LiDAR data for detailed vegetation structure characterization.

This study examines the potential of combining decision support approaches to identify optimal bundles of ecosystem services. A forested landscape, Zona de Intervenção Florestal of Paiva and Entre-Douro and Sousa (Portugal), is used to test and demonstrate this potential. The landscape extends over 14,000 ha, representing 1,976 stands. The property is fragmented into 376 holdings. The overall analysis was performed in three steps. First, we selected six alternative solutions (A to F) in a Pareto frontier generated by a multiple criteria method within a decision support system (SADfLOR) for subsequent analysis. Next, an aspatial strategic multi-criteria decision analysis (MCDA) analysis was performed with the Criterium DecisionPlus (CDP) component of another decision support system (EMDS) to assess the aggregate performance of solutions A to F for the entire forested landscape with respect to their utility for delivery of ecosystem services. For the CDP analysis, SADfLOR data inputs were grouped into two sets of primary criteria: Wood Harvested and Other Ecosystem Services. Finally, a spatial logic-based assessment of solutions A to F for individual stands of the study area was performed with the NetWeaver component of EMDS. The NetWeaver model was structurally and computationally equivalent to the CDP model, but the key NetWeaver metric is a measure of the strength of evidence that solutions for specific land stands were optimal for the unit. Solutions D and B performed best in the aspatial strategic MCDA analysis, and a composite of the maps generated by NetWeaver demonstrated the spatial basis for the performance of solutions D and B in individual land stands. We conclude with a discussion of how the combination of decision support approaches encapsulated in the two systems could be further automated.

Anticancer regimens for Hodgkin lymphoma (HL) patients include highly genotoxic drugs that have been very successful in killing tumor cells and providing a 90% disease-free survival at five years. However, these treatments do not have a specific cell target, damaging both cancerous and normal cells. Thus, HL survivors have a high risk of developing new primary cancers, both hematologic and solid tumors, that have been related to treatment. Several studies have shown that after-treatment, HL patients and survivors present persistent chromosomal instability, including non-clonal chromosomal aberrations. The frequency and type of chromosomal abnormalities appear to depend on the type of therapy and the cell type examined. For example, MOPP chemotherapy affects hematopoietic and germ stem cells leading to long-term genotoxic effects and azoospermia, while ABVD chemotherapy affects transiently sperm cells, with most of the patients showing recovery of spermatogenesis. Both regimens have long-term effects in somatic cells, presenting non-clonal chromosomal aberrations and genomic chaos in a fraction of non-cancerous cells. This is a source of karyotypic heterogeneity that could eventually generate a more stable population acquiring clonal chromosomal aberrations and leading towards the development of a new cancer.

This study aimed to investigate Coll-I, III, IV and elastin in canine normal prostate and PC, using Picrosirius red (PSR) and Immunohistochemical (IHC) analysis. Eight normal prostates and 10 PC from formalin-fixed, paraffin-embedded samples were used. Collagen fibers area was analyzed with ImageJ software. The distribution of Coll-I and Coll-III was approximately 80% around prostatic ducts and acini, 15% among smooth muscle and 5% surrounding blood vessels, in both normal prostate and PC. There was a higher median area of Coll-III in PC, when compared to normal prostatic tissue (p=0.001 for PSR and p= 0.05 for IHC). Immunostaining for Coll-IV was observed in the basal membrane of prostate acini, smooth muscle, blood vessels, and nerve fibers of normal and PC samples. Although there was no difference in Coll-IV area between normal tissue and PC, tumors with Gleason score 10 showed absence of Coll-IV, when compared to scores 6 and 8 (p=0.0095). Elastic fibers were found in the septa dividing the lobules and around the prostatic acini of normal samples, and was statistically higher in PC, compared to normal tissue (p=0.00229). Investigation of ECM components brings new information and should be correlated with prognosis in future studies.

Ionic channels are present in eucaryotic plasmatic and intracellular membranes. They coordinate and control several functions. One of the most diverse ionic channels family are the potassium (K) channels. Within this family are the ATP-dependent potassium channels (KATP), which belong to the potassium rectifier channel family. These channels were initially described in heart muscle, yet they are also present in different types of tissues such as pancreatic, skeletal muscle, brain, and vascular and non-vascular smooth muscle. In ß-pancreatic cells, KATP are primarily responsible for maintaining membrane potential and for the depolarization mediated insulin release. KATP density/activity seems to be determinant in physiological the outcome, in pancreatic cells decrease of this density/activity may be related to Insulin resistance (IR). In extra pancreatic tissues KATP relation with IR is beginning to be explored. It is possible that in skeletal muscle, the KATP are involved in insulin dependent glucose recapture and that KATP activation leads to IR. In adipose tissue, KATP containing Kir6.2, could be related to increase in free fatty acids and insulin resistance, therefore, pathological processes leading to a prolonged adipocyte KATP inhibition might promote obesity related to insulin resistance. In central nervous system KATP activation can regulate peripheric glycemia and lead to brain IR which could be a much earlier manifestation of peripheral alterations that lead to the development of pathologies such as obesity and type 2 diabetes mellitus. In this review we aim to discuss the KATP channel characteristics, its relationship to known clinical disorders and the mechanisms and potential relations with peripheral and central insulin resistance.

Climate change is one of the main issues that humanity is currently facing due to carbon dioxide emissions caused by the use of fossil fuels. Organic Rankine cycles may play an important role in reducing these emissions since they can be operated by using industrial waste heat of renewable energies. The present study presents a comprehensive bibliographic review of organic Rankine cycles. The study not only actualizes previous reviews that mainly focused on basic cycles operating on subcritical or supercritical conditions but also includes the analysis of novel cycles such as two-stage and hybrid cycles and the used fluids. Recuperative and regenerative cycles are more efficient than reheated and basic single-stage cycles. The use of two-stage cycles makes it possible to achieve higher thermal efficiencies and net power outputs of up to 20% and 44%, respectively, compared with those obtained with single-stage cycles. Theoretical studies show that hybrid systems, including Brayton and organic Rankine cycles, are the most efficient; however, they require very high temperatures to operate. Most organic Rankine cycle plants produce net power outputs from 1 kW up to several tens of kW, mainly using microturbines and plate heat exchangers.

The high consumption of firewood in Honduras requires the search for alternatives that reduce its negative effects on health, economy, and the environment. One of these alternatives has been the promotion of improved cooking stoves, which achieve a large reduction in firewood consumption. This paper shows a cost-benefit analysis for an improved cooking stove adoption strategy for Honduras. The methodology uses the Long-range Energy Alternatives Planning System, LEAP, a tool globally used in the analysis and formulation of energy policies and strategies. The energy model considers the demand for firewood as well as the gradual introduction of improved cooking stoves, according to premises of a National Strategy. Hence, it is demonstrated that the costs of implementing this adoption strategy are lower than the costs of not implementing it, taking into consideration various scenarios up to and including the year 2030.

Lactic acid bacteria are traditionally applied in a variety of fermented food products and have the capability to produce a wide range of bioactive ingredients during fermentation including vitamins, bacteriocins, bioactive peptides and bioactive compounds. The bioactivity and health benefits associated with these ingredients have gained interest in applications in the functional dairy market and have relevance both as components produced in situ and as functional additives. This review provides a brief description of the regulations regarding the functional food market in the European Union as well as an overview of some of the functional dairy products currently available in the Irish and European markets. A better understanding of the production of these ingredients excreted by lactic acid bacteria can further drive the development and innovation of the continuously growing functional food market.

Natural carotenoids are secondary metabolites that exhibit antioxidant, anti-inflammatory and anti-cancer properties. These types of compounds are in high demand by pharmaceutical, cosmetic, textile and food industries, leading to the search for new natural sources of carotenoids. In recent years, the production of carotenoids from bacteria has become of great interest for industrial applications. In addition to carotenoids with C40-skeletons, some bacteria have the ability to synthesize characteristic carotenoids with C30-skeletons. In this regard, a great variety of methodologies for the extraction and identification of bacterial carotenoids has been reported and this is the first review that condenses much of this information. To understand the diversity of these carotenoids, we present their biosynthetic origin in order to focus on the methodologies employed in their extraction and characterization. Special emphasis has been made on high-performance liquid chromatography-mass spectrometry (HPLC-MS) for the analysis and identification of bacterial carotenoids. We end up this review showing their potential commercial use of bacterial carotenoids. This review is proposed as a guide for the identification of these metabolites, which are frequently reported in new bacteria strains.

Starch is a biopolymer with wide potential for the generation of new biodegradable packages due to its high availability and low price. However, due to its weak functional properties, it is necessary to limit the interaction of some hydroxyl, and to evaluate blends with other polymers to improve their performance. Glycerol plasticized acetylated corn starch films were developed by the casting method, and the impact of incorporating chitosan (TPS:CH) at various proportions (75:25, 50:50, and 25:75 v/v) was studied. The effect of the chitosan ratios on the films' physical, mechanical, water vapor barrier, and thermal properties was evaluated. Chitosan protonated amino groups promote the formation of intermolecular bonds, improving the tensile strength, the thermal stability, the water adsorption capacity, and the gas barrier of starch films. Where the film composed of TPS25-CH75 was the one that presented the best barrier to water vapor. These composite films are a good option for development of biodegradable packaging.

We report a diode pumped solid state (DPSS) laser used for intracavity pump-enhanced difference frequency generation (DFG) to create a 3.5 micron laser. Using a 50 mm-long periodically poled lithium niobate (PPLN) crystal inside the cavity of an Nd:YVO4 solid state laser at 1064 nm with 4.5 W pump power at 808 nm, and a 310 mW C-band signal at 1529 nm, up to 31 mW of mid-infrared output power at 3499 nm is obtained. The cavity requires no active stabilization and/or locking, and the entire cavity is &lt;8 cm in length. The obtained output power corresponds to a black box efficiency of 2.20 %W-1, which is the highest value reported to date for continuous wave DFG based on a bulk nonlinear optical crystal with no active stabilization. Potential future applications in free space optical communication are discussed as well.

Threats to natural ecosystems are closely linked to human development, and the lack, insufficiency or inefficiency of public policies are some of the most important drivers of negative effects on the environment. The contribution of the IUCN’s Red List of Ecosystems (RLE) to conservation topics has been discussed in previous studies; however, to date its implications for conservation in public policies have not been addressed. This perspective discusses how the RLE may support the improvement and development of these policies, specifically through the implications for public policy of each of the criteria that substantiate the threat status of ecosystems. We aim to provide a plausible baseline to the operationalization of RLE in public and conservation policy, facilitating the work of governments, practitioners and decision makers. Finally, we provide recommendations and examples as to how to proceed in creating and modifying different public policy instruments, such as land-use planning, spatial zoning, tax reduction, compensation schemes, climate change adaptation plans, management of introduced species, development offsets and restoration investment. This perspective contributes to implement RLE into public policy and to improve ecosystem conservation by expanding the current scope of RLE into practical and political dimensions through plausible actions, policies and strategies.

The water and wastewater sectors are energy-intensive, and so a growing number of utility companies are seeking to identify opportunities to reduce energy use. Though England’s water sector is of international interest, in particular due to the early experience with privatisation, for the time being very little published data on energy usage exists. We analyse telemetry data from Thames Water Utilities Ltd. (TWUL), which is the largest water and wastewater company in the UK and serves one of the largest mega-cities in the world, London. In our analysis, we (1) break down sectoral energy use into their components, (2) present a statistical method to analyse the long-term trends in use, as well as the seasonality and irregular effects in the data, (3) derive energy-intensity (kWh m³) figures for the system, and (4) compare the energy-intensity of the network against other regions in the world. Our results show that electricity use grew during the period 2009 to 2014 due to capacity expansions to deal with growing water demand and storm water flooding. The energy-intensity of the system is within the range of reported figures for systems in other OECD countries. Plans to improve the efficiency of the system could yield benefits in lower the energy-intensity, but the overall energy saving would be temporary as external pressures from population and climate change are driving up water and energy use.

This research investigates the exposure of plant species to extreme drought events in the Brazilian Atlantic Forest, employing an extensive dataset collected from 205 automatic weather stations across the region. Meteorological indicators derived from hourly data, encompassing precipitation, maximum and minimum air temperature, were utilized to quantify past, current, and future drought conditions. The dataset, comprising 10,299,236 data points, spans a substantial temporal window and exhibits a modest percentage of missing data. Missing data were excluded from analysis, aligning with the decision to refrain from imputation methods due to potential bias. Drought quantification involved the computation of the Aridity Index, the analysis of consecutive hours without precipitation, and the classification of wet and dry days per month. Mann-Kendall trend analysis was applied to assess trends in evapotranspiration and maximum air temperature, considering their significance. The hazard assessment, incorporating environmental factors influencing tree growth dynamics, facilitated the ranking of meteorological indicators to identify regions most exposed to drought events. The results revealed consistent occurrences of extreme rainfall events, indicated by positive outliers in monthly precipitation values. However, significant trends were observed, including an increase in daily maximum temperature and consecutive hours without precipitation, coupled with a decrease in daily precipitation across the Brazilian Atlantic Forest. No significant correlation between vulnerability ranks and weather station latitudes and elevation were found, suggesting geographical location and elevation does not strongly influence observed dryness trends.

As the global population grows, the demand for food increases and puts a strain on food production systems and agricultural productivity, causing soil degradation. Soil Quality Indexes (SQIs) have been developed to maintain and improve soil quality. However, due to the variety of soils and SQIs, analyzing and comparing results has been historically difficult. Therefore, in this study, we carried out a systematic review with meta-analysis focused on soil quality studies of agricultural soils under intensive agriculture using the unified weighted additive SQI methodology (SQIU). We analyzed 65 quality observations obtained from 22 studies. Chemical indicators were the most prevalent in the SQIUs, followed by physical and biological indicators. Conventional soil management had negative effects on soil quality (–7.55%). From the factors analyzed, the minimum database had a significant effect on the soil quality results, but not the number of indicators that made up the SQIU. The SQIU made up of chemical-biological indicators (CB) presented negatively overestimated measurements of soil quality (–32.53%), exaggerating the damage to the analyzed soils. The indicators that correlated most strongly with the size of the effect on agricultural soil quality were the cation exchange capacity (CEC), carbon to nitrogen ratio (C/N), and microbial biomass carbon (MBC). The SQIU is a feasible tool to interpret the quality of agricultural soils around the world, as it makes it possible to obtain a simple and generalized view of soil conditions.

Apple replant disease (ARD) is a complex issue caused by various fungal, oomycetes pathogens and parasites which can differ in their abundance between sites within a geographic region. Knowledge of the specific etiology of ARD at a particular site is required in order to develop commercially viable soil management strategies to combat specific/individual components of the disease. In this study we analyzed the soil from six ARD sites for the presence of fungal, bacterial and oomycetes communities and plant parasitic nematodes. Five fungal, and 17 bacterial classes were differentially represented in the microbiomes from different locations. Mortierellomycetes was the most abundant fungal taxa represented followed by Sordariomycetes. Mortierella exigua a fungal endophyte was the most abundant fungal amplicon sequence variant (ASV) in the core microbiome. Proteobacteria was the most prevalent phylum identified in orchard soils. Several potential phytopathogenic fungi involved in ARD and endophytes including Fusarium oxysporum, F. solani, Nectria ramulariae, Ilyonectria robusta and Nectriaceae were identfied in the orchard soil. Pythium attrantheridium (Globisporangium attrantheridium), P. monospermum and P. ultimum (Globisporangium ultimum) were the most abundant oomycete taxa identified in these soil samples. Six different groups of plant-parasitic nematodes were found across the six orchards soil. Root-lesion nematodes, Pratylenchus spp., which are commonly associated with ARD, were identified in all orchards soil at population densities ranging from 12 to 33/100 cm3 soil. This research contributes valuable understanding of the ARD complex as the apple industry needs alternative approaches to combat the disease.

Forty-five male Dorper crossbred lambs (40.17 ± 0.35 kg BW) were used in order to investigate the effects of the duration of calcium propionate (CaPr) supplementation in lambs finished with zilpaterol hydrochloride (ZH) on the productive performance, carcass characteristics, and meat quality. Lambs were individually housed and fed a finishing-diet for 42 d before being slaughtered. Lambs received the following treatments: 1) No additives (CTL), 2) ZH supplementation for 28 d (with 3 d ZH withdrawal before slaughter) at a dosage of at 7.2 mg/kg diet (ZH), for treatments 3, 4, and 5, lambs received ZH and 10g CaPr/lamb/d throughout the entire phase (42 d), or during the last 28 or 14 d before slaughter. Compared to CTL, ZH lambs exhibited a similar average daily gain (ADG) but had lower dry matter intake (DMI), leading to increased feed efficiency. Supplementing with ZH alone did not affect carcass traits, visceral mass, whole cuts, or meat quality. Lambs that received both CaPr and ZH exhibited quadratic increases (p &lt; 0.05) in final BW (FBW), ADG, and dressing percentage (D%). These increases were optimal at an estimated inclusion durations of 26 d for FBW, 30 for ADG, and 39 d for D%. The ADG:DMI ratio and the longissimus muscle area (LMA) both exhibited quadratic increases (p &lt; 0.05). The optimal duration of CaPr supplementation for ADG:DMI ratio was found to be 28 d, while for LMA, it was 14 d. As the period of CaPr supplementation increased, there was a linear increase (p &lt;0.05) in hot carcass weight, leg circumference, and whole cuts of breast IMPS209 and shoulder IMPS207. Cook loss percent increased quadratically (p &lt; 0.05), being higher when CaPr was included for an estimated duration of 26 d. As the duration of CaPr supplementation increased, the purge loss percentage (PLR) also increased linearly (p &lt; 0.05). In conclusion, including CaPr in the diet for a duration of 28 d in lambs improved the response to ZH supplementation on the productive performance, carcass weight and some whole cuts. However, it can also have a negative effect on PRL%.

This study investigated the effects of flamenco dance on mood and subjective well-being in older women. In a broader context, the question was raised about how participation in dance activities could influence the emotional well-being of this demographic group. Thirty-four older women, aged between 62 and 79 years, with a mean age of 70.11 years (SD = 5.13), voluntarily participated in the study after providing informed consent. All of them were enrolled in a 12-week flamenco dance workshop conducted by the Autoestima Flamenca Association, with one two-hour session per week. Mood measurements (sadness, anxiety, anger, and joy) were taken biweekly before and after each session, and subjective well-being assessments were conducted before and after the intervention. The results revealed significant improvements in the overall mood of the participants, as well as an increase in their subjective well-being. These improvements were observed at both the individual and group levels. In conclusion, participation in flamenco dance demonstrated a positive impact on the mood and subjective well-being of older women. These findings support the idea that physical and artistic activities, such as flamenco dance, can play an important role in promoting emotional well-being in this age group.

Physical activity (PA) benefits are well-established, yet many US adults fail to meet PA guidelines. This is especially true for minorities facing social inequities. This study explored barriers and facilitators to PA among urban Midwestern minorities using a mixed-methods approach framed on the socio-ecological model. A cross-sectional survey was conducted among community-dwelling minorities. Participants were grouped as completing low (LLPA) or high (HLPA) weekly leisure-time PA for comparison. Quantitative analysis included MANOVA, follow-up ANOVAs, and calculation of effect sizes. Qualitative data were assessed using inductive thematic analysis. Twenty-nine adults (44.83% Black, 41.37% Latino) participated in the study. The HLPA group (n = 18) reported higher leisure-time PA (p = 0.001, d = 2.21) and total PA (p = 0.02, d = 1.00) compared to the LLPA group (n = 11). LLPA participants faced more personal barriers to PA (p = 0.02, d = -0.92). Common barriers identified in the interviews included a lack of time and financial costs. Facilitators included social support and available PA facilities. Both groups achieved USPA guidelines through different PA domains. Increasing social support and lowering PA-related costs could enhance participation. Addressing barriers and leveraging existing facilitators are crucial to increasing PA among minorities.

Non-vertebrate species represent about ~95% of known metazoan (animal) diversity. They remain to this day relatively unexplored genetically, but understanding their genome structure and function is pivotal for expanding our current knowledge of evolution, ecology and biodiversity. Following the continuous improvements and decreasing costs of sequencing technologies, many genome assembly tools have been released, leading to a significant amount of genome projects being completed in recent years. In this review, we examine the current state of genome projects of non-vertebrate animal species. We present an overview of available sequencing technologies, assembly approaches, as well as pre and post-processing steps, genome assembly evaluation methods, and their application to non-vertebrate animal genomes.

Heterotopic ossification (HO) is most dramatically manifested in the rare and severely debilitating disease, fibrodysplasia ossificans progressiva (FOP), in which heterotopic bone progressively accumulates in skeletal muscles and associated soft tissues. The great majority of FOP cases are caused by a single amino acid substitution in the type 1 bone morphogenetic protein (BMP) receptor ACVR1, a mutation that imparts responsiveness to activin A. Although it is well-established that biological sex is a critical variable in a range of physiological and disease processes, the impact of sex on HO in animal models of FOP has not been explored. We show that female FOP mice exhibit both significantly greater and more variable HO responses after muscle injury. Additionally, the incidence of spontaneous HO was significantly greater in female mice. This sex dimorphism is not dependent on gonadally-derived sex hormones, and reciprocal cell transplantations indicate that apparent differences in osteogenic activity are intrinsic to the sex of the transplanted cells. By circumventing the absolute requirement for activin A using an agonist of mutant ACVR1, we show that the female-specific response to muscle injury or BMP2 implantation is dependent on activin A. These data identify sex as a critical variable in basic and preclinical studies of FOP.

Lithium-ion batteries serve as the primary sources of power for electric vehicles (EVs) and hybrid electric vehicles (HEVs). For vehicle applications, battery management systems (BMSs) are nec-essary to protect lithium-ion batteries from overheating and to ensure optimum vehicle perfor-mance. Our approach to developing a BMS was based on recent advances in the application of phase field models for lithium-ion batteries. In particular, our reduced-order model (ROM) uti-lized a dataset generated from the COMSOL® Multiphysics simulation of the Cahn–Hilliard equation for a single particle of a lithium iron phosphate (LiFePO4) cathode: an example of using a reduced-order model (ROM) based on a single-particle model (SPM). The main innovation of our ROM is that the SPM is fully coupled to a heat transfer model at the battery cell level. We utilized principal component analysis to identify a lower-order model that could reproduce the battery’s voltage and temperature response for ambient temperatures ranging from 253 to 298 K and for discharge rates ranging from 1 C to 20.5 C. The reduced-order dataset was then fitted to the ex-perimental data for an A123 Systems 26650 2.3 Ah cylindrical battery using deep neural network (DNN) regression.

In this study we mimic the unique, transparent protective carapace (shell) of myodocopid ostracods, through which their compound eyes see, to demonstrate that the carapace ultrastructure also provides functions of strength and protection for a relatively thin structure. The bulk ultrastructure of the transparent window in the carapace of the relatively large, pelagic cypridinid (Myodocopida) Macrocypridina castanea was mimicked using thin film deposition of dielectric materials to create a transparent, 15 bi-layer material. This biomimetic material was subjected to the natural forces withstood by the ostracod carapace in situ, including scratching by captured prey and strikes by water-borne particles. The biomimetic material was then tested in terms of its extrinsic (hardness value) and intrinsic (elastic modulus) response to indentation along with its scratch resistance. The performance of the biomimetic material was compared with that of a commonly used, anti-scratch resistant lens and polycarbonate that is typically used in the field of transparent armoury. The biomimetic material showed the best scratch resistant performance, and significantly greater hardness and elastic modulus values. The ability of biomimetic material to revert back to its original form (post loading), along with its scratch resistant qualities, offers potential for a biomimetic eye protection coating that could enhance material currently in use.

The fast pace development of the Internet and the Coronavirus Disease (COVID-19) pandemic have impacted considerably on the educative sector; encouraging the constant transformation of the teaching-learning strategies and more in technological areas as Educational Software Engineering. Web programming, a fundamental topic in Software Engineering and Cloud-based applications, deals with various critical challenges in education, such as learning continuous emerging technological tools, plagiarism detection, generating innovative learning environments, among others. Continual change and more with the current digitization becomes a challenge for teachers and students who cannot depend on traditional educational methods. The article presents a sustainable teaching-learning methodology for web programming courses in Engineering Education using a project-based integrated approach adaptable to the continuous web technological advances. The methodology has been developed and improved for 9 years, 15 groups, and 3 different universities. Our results demonstrate that the methodology is 100% adaptable with new technologies that might arise; it also presents the advantages of avoiding plagiarism in the best case and a personalized induction for every specific student in the learning process.

According to the International Union for Conservation of Nature Red List, the scalloped hammerhead (Sphyrna lewini) is a critically endangered species, primarily due to intense fishing and other anthropogenic effects such as pollution. Nowadays, plastic debris contamination is a subject of concern due to its extensive presence in the sea and the digestive tracts of many fish species. The possible effects of plastic debris as a vector of other pollutants are still unknown. We analyzed the digestive tract of hammerhead sharks to investigate the correlation between plastic and other anthropic debris contamination and feeding habits in the eastern region of the Gulf of California. A total of 58 specimens were analyzed from the coastal area, revealing a plastic occurrence frequency of 79.3%. Of these, 91.4% corresponded to fibers, and 8.6% to fragments. The composition of the polymers was primarily cellulose (64.4%). According to their diet, these organisms exhibit benthopelagic habits, feeding both in the water column and on the seabed. These results indicate a high level of contamination of anthropogenic cellulosic microfibers in the area. This changed according to the year, indicating that the anthropic debris ingestion is related to the discharges of human activities and their seasonality rather than to a selection process by the sharks. Although cellulosic microfibers are recognized as a biomaterial, they can harm marine species, posing an additional threat to this iconic shark.

Recently, the world has experienced severe food insecurity problems with most countries having inadequate access to affordable, nutritious and safe foods. Consequently, many food innovations and technologies have been approved to secure sustainable access to food for millions of people. This study investigated the implementation of two technologies to address food insecurity, namely genetically modified foods (GMOs) and the use of antibiotics in crops and animal production. In particular, the study explored how their implementation can be governed responsibly through approved legislation. Therefore, the knowledge, attitudes and practices as well as the governance of antibiotic resistance risks and GMO foods were assessed. In-depth key interviews were conducted for the qualitative survey with triangulation with quantitative data sources. The findings showed that 46% of the population have little knowledge about GMOs with about 79% indicating that food with GM ingredients were being consumed in the country. The main concerns reported on GM foods by most respondents were impact on environment, human health and adverse effects on traditional farming practices with 36% indicating that it intensifies contamination and 32% indicating that it contributes to loss of biodiversity. Notably, 64%) reported that GMOs are a solution to food security and that they are safe. On the use of antimicrobials mainly meant to prevent diseases and access better markets, respondents perceived their use to be associated with antimicrobial resistance a “large level of risk” (score 2 in a scale of 1-3) (M = 1.85, SD = 1.06). Overall, the study found that efforts towards promoting awareness on antibiotic resistance risks and response in human health is relatively limited as reported by 56% of the respondents. Findings show that most of the respondents have only seen minimal or small-scale awareness campaigns. On governance of the two technologies, 71% and 50% of the respondents reported that scientists and elected officials respectively have the greatest role in governance of GMOs with small scale farmers playing a negligible role. Further, it was noted that all the respondents were knowledgeable in AMR and GMO technologies and these findings are crucial to the advancement of food innovations that are geared towards achieving food security in Kenya. This study highlights the risks associated with the poor governance and implementation of technologies and the need for a framework for technological risk governance that is sensitive to local values and socio-economic circumstances that will benefit the achievement.

Manufacturers of photovoltaic modules do not provide all the information necessary to predict their performance under different climatic conditions. This forces the development of mathematical models of behavior and the application of mathematical methods for the calculation of their associated parameters. A toolbox called PVMSim implemented in MATLAB/GUI is proposed in this paper. PVMSIm provides models allowing the simulation of photovoltaic modules. A two-diode model is used to represent the effect of irradiance and temperature on the V-I and V-P characteristic curves. The accuracy of PVMSim has been vaildated by applying the models to two mono-crystalline and multi-crystalline solar modules of different power ratings and manufacturers. The model PVMSim model accuracy was verified against the manufacturer’s datasheet. This paper shows that this tool is useful for designers and professionals who require an intuitive graphical interface for fast and accurate modeling, simulation and sizing of photovoltaic systems.

Chronic kidney disease (CKD) is a major non-communicable disease associated with high rates of premature morbidity and mortality. The prevalence of hypovitaminosis D (deficiency of 25(OH)D or 25D) is greater in racial/ethnic minorities and in patients with CKD than the general population. Low 25D is associated with bone and mineral disorders as well as immune, cardiometabolic and cardiovascular (CV) diseases. Thus, it has been suggested low 25D contributes to the poor outcomes in patients with CKD. The prevalence of hypovitaminosis D rises progressively with advancing severity of kidney disease with over 30% of patients with CKD stage 3 and 70% patients with CKD stage 5 estimated to have low levels of 25D. This report describes several of the abnormal physiologic and counter-regulatory actions related to low 25D in CKD such as those in oxidative stress and inflammatory systems, and some of the preclinical and clinical evidence or lack of thereof of normalizing serum 25D levels to improve outcomes in patients with CKD, and especially for the high risk subset of racial/ethnic minorities who suffer from higher rates of advanced CKD and hypovitaminosis D.

The human-centric approach is a leading trend for future production processes, and collaborative roboticists are key to its realization. This article addresses the challenge of designing a new cus-tom-made non-conventional machine or robot involving toolpath control (interpolated axes) with collaborative functionalities but by using “general-purpose standard" safety and motion control technologies. This is done on a non-conventional Cable-Driven Parallel Robot (CDPR). Safety is assured by safe commands to individual axes, known as Safe Motion Monitoring Functionalities, which limits the axes speed in the event of human intrusion. At the same time, the robot's Motion Controller applies an override to the toolpath speed to accommodate the robot's path speed to the axis’s limitations. The implementation of a new Pre-Warning Zone, prevent unnecessary stops due to the approach of the human operator. The article also details a real experiment that validates the effectiveness of the proposed strategy.

As the rate of discovery of new antibacterial compounds towards multidrug resistant bacteria is declining, there is an urge for the search of molecules that could revert this tendency. Acinetobacter baumannii has emerged as a highly virulent Gram-negative bacterium that has acquired multiple mechanisms against antibiotics and is considered of critical priority. In this work we developed a quantitative structure-property relationship (QSPR) model with 592 compounds for the identification of structural parameters related to their property as antibacterial agents against A. baumannii. QSPR mathematical validation (R2 = 70.27, RN = -0.008, aR2 = 0.014 and δK = 0.021) and its prediction ability (Q2LMO= 67.89, Q2EXT = 67.75, a(Q2)= -0.068, δQ = 0.0, rm2 = 0.229, and ∆rm2 = 0.522) were obtained with different statistical parameters; additional validation jobs were done using three sets of external molecules (R2 = 72.89, 71.64 and 71.56). We used the QSPR model to perform a virtual screening on the BIOFACQUIM natural product database. From this screening our model showed that molecules 32 to 35 and 54 to 68, isolated from different extracts of plants of the Ipomoea sp., are potential antibacterial against A. baumannii. Furthermore, biological assays showed that molecules 56 and 60 to 64 have a wide antibacterial activity against clinical isolated strains of A. baumannii, as well as other multidrug resistant bacteria including Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. Finally, we propose 60 as a potential lead compound due to its broad-spectrum activity and its structural simplicity. Therefore, our QSPR model can be used as a tool for the investigation and search of new antibacterial compounds against A. baumannii.

In this work, we propose an easy and a low cost method for the synthesis of Nitrogen-Doped Graphene NDG and its silver nanowires NW functionalization NWGN. The synthesis was performed using the improved graphene oxide method, chemical reduction of graphene oxide in the presence of caffeine as green nitrogen source and the subsequently the silver nanowires growth in the surface, by the chemical reductions salts in the presence of NG. Achieving a homogeneous growing (coating) of graphene sheets. The samples were analyzed using conventional characterization techniques: SEM-EDX, XRD, FT-IR, RAMAN, TEM, HRTEM, STEM and XPS.

Postharvest physiological deterioration (PPD) of fresh cassava roots limits its shelf-life to about 48 hours. There is a demand for simple, cheap, and logistically feasible solutions for extending the shelf life of fresh cassava roots at industrial processes. In this study, three different types of bag materials were tested (woven polypropylene, tarpaulin, and jute as a potential storage solution for cassava roots with different levels of mechanical damages. Microclimate (temperature, humidity, CO2) was monitored to understand the storage conditions for up to 12 days. The results showed that fresh cassava roots could be stored for 8 days, with minimal PPD and starch loss (2.4 %). How-ever, roots with significant mechanical damage (cuts, breakages) had a considerably shorter shelf life in the storage bag, compare to whole roots and roots with retained peduncle (stalk where roots are connected to the main plant). Wetting the roots and type of bag material were not significant factors in determining the shelf life and starch loss. Carbon dioxide concentration in the stores significantly correlated with the starch loss in fresh cassava roots and is proposed as a possible method for continuously and remotely monitoring starch loss in large scale commercial operations and reduce postharvest losses.