This article presents a study on the aerodynamic drag of a generic dual-axle flatbed trailer and explores ways to reduce the drag using appendable drag-reducing devices. The primary sources of drag originated from the van and trailer’s rear, along with the trailer’s wheels. The most effective initial device for reducing drag was a full trailer underside cover which offered a 7% drag reduction. Additionally, ladder racks, dropsides, and rear gates were studied, and it was found that protruding ladder racks significantly increased drag. Rear gates added large amounts of drag and should be removed and stored when not needed. The study also explored novel mid-section devices that increased the van’s base pressure and reduced drag. An axle test revealed that drag for single, dual, and triple axle trailers was very similar in direct flow, but different in yawed flow. A drawbar length test showed a near-linear relationship between drawbar length and drag, manifesting as a 1.7% change in drag per 250mm change in drawbar length. Several novel modifications were made to the trailer, including fitting six unique appendable devices, which offered a total 7.3% drag reduction. A novel rear van device known as the Multi-Stage Converging Cavity was introduced which reduced drag by nearly 18%. When all the devices were used together, a total 25% drag reduction was observed for the van-trailer combination.

Ransomware is continually evolving. The most recent tactic is to combine crypto-ransomware with data exfiltration, mandate fraud, and other such schemes to steal from victims and attempt to blackmail them. This paper examines the new trend, its underlying motives, and proposes practical recommendations to help organizations defend against this menace

This paper builds on previous work introducing the Secure Remote Update Protocol (SRUP)—a secure communications protocol for Command & Control applications in the Internet of Things, built on top of MQTT. This paper builds on the original protocol, and introduces a number of additional message types: adding additional capabilities to the protocol. We also discuss the difficulty of proving that a physical device has an identity corresponding with a logical device on the network, and propose a mechanism to overcome this within the protocol.

This study presents a methodology to reveal traces of viral particles, as aerosol with known chemical and molecular structure, in a sample by means of photon and electron interactions. The method is based on Monte Carlo simulations and on the analysis of photon-electron fluxes-spectra through energy channels counts as a function of different aerosol viral concentrations in the air sample and looking at the peculiar photon/electron interactions with the potential abnormal atomic hydrogen (H), oxygen (O), carbon (C), and phosphorus (P) compositions present in the air sample as a function of living and nonliving matter with PO4 group RNA/DNA strands in a cluster configuration.

There is a need for multimodal strategies to keep research participants informed about study results. Our aim was to characterize preferences of genomic research participants from two institutions along four dimensions of general research result updates: content, timing, mechanism, and frequency. Methods: We conducted a web-based cross-sectional survey that was administered from 6-25-2018 to 12-5-2018. Results: 397 participants completed the survey, most of whom (96%) expressed a desire to receive research updates. Preferences with high endorsement included: update content (brief descriptions of major findings, descriptions of purpose and goals, and educational material); update timing (when the research is completed, when findings are reviewed, when findings are published, and when the study status changes); update mechanism (email with updates, and email newsletter); and update frequency (every three months). Hierarchical cluster analyses based on the four update preferences identified four profiles of participants with similar preference patterns. Very few participants in the largest profile were comfortable with budgeting less money for research activities so that researchers have money to set up services to send research result updates to study participants. Conclusion: This work provides evidence of a need for funders to incentivize researchers to communicate results to participants.

The article concerns a relatively small but important fragment of John Paul II's pastoral activity, namely his pilgrimages to Poland: the nature of these pilgrimages, their historical background and teaching - especially to the extent that went beyond the immediate and Polish context. The text is the result not only of reading papal statements, but also of personal observation of the political and social atmosphere. The first two parts contain a concise description of the Pope's eight pilgrimages to Poland (before and after the political transformation). The third highlights out the main universal themes raised by the Pope: the dignity of the person, truth and freedom. During consecutive pilgrimages to Poland, he deepened and expanded the themes of his teaching. This collection of his sermons and speeches to Poles constitutes a comprehensive (devoid of redundant repetitions and omissions) treatment of important social, philosophical and theological issues. John Paul II, when speaking to Poles and about Poles, did not lose his universal perspective; he appealed both to Christians and to all people of good will. Papal pilgrimages to Poland are a significant part of modern Polish history, and their message is a valuable intellectual and spiritual gift.

Charcot-Marie-Tooth (CMT) syndrome is the most common progressive human motor and sensory peripheral neuropathy. CMT type 1E is a demyelinating neuropathy affecting Schwann cells due to pmp22 mutations, modelized by Trembler-J mice. Curcumin, a natural polyphenol com-pound obtained from turmeric (Curcuma longa), exhibits dose- and time-varying antitumor, antioxidant and neuroprotective properties, however, the neurotherapeutic actions of curcumin still remain elusive. Here, we propose curcumin as a possible natural treatment capable of enhancing cellular detoxification mechanisms, resulting in an improvement of the neurodegenerative Trembler-J phenotype. Using a refined method for obtaining enriched Schwann cell cultures, we evaluated the neurotherapeutic action of low dose curcumin treatment on the PMP22 expression, and on the chaperones (HSF1 and Hsp27) and autophagy/mTOR (HDAC6 and ribosomes) pathways in Trembler-J and wild-type genotypes. In wild-type Schwann cells, the action of cur-cumin resulted in strong stimulation of the chaperone and macroautophagy pathway, whereas the modulation of ribophagy showed a mild effect. However, despite the promising neuroprotective effects for the treatment of neurological diseases, we report (demonstrate?) that the action of cur-cumin in Trembler-J Schwann cells could be impaired due to the irreversible impact of ethanol used as a common curcumin vehicle necessary for administration. These results contribute to expand our still limited understanding of PMP22 biology in neurobiology, and expose the intrinsic lability of the neurodegenerative Trembler-J genotype. Furthermore, they unravel interesting physiological mechanisms of cellular resilience relevant for to the pharmacological treatment of the neurodegenerative Tremble J phenotype with curcumin and ethanol. We conclude that the analysis of the effects of the vehicle itself is an essential and in-escapable step to comprehensibly assess the own effects and full potential of curcumin treatment for therapeutic purposes.

This comprehensive study focused on the standard taxi sign used in Ireland, its impact on drag production, fuel expenses, and CO2 emissions. Experimental analysis revealed that the conventional taxi sign significantly increased drag, especially when mounted on streamlined vehicles such as saloon cars, due to flow separation issues on the rear roof and rear windshield. Longitudinal reorientation of the sign offered a 14-fold reduction in drag increase compared to the traditional placement. It was found that positioning the sign in the middle of the roof offered the greatest fuel efficiency. Furthermore, the study estimated that implementing longitudinal repositioning on all Irish taxi signs could save drivers approximately 832 per year and reduce national CO2 emissions by a substantial 22,464 tonnes annually. Comparative analyses with international taxi signs demonstrated that the Irish sign had significantly larger drag contributions, emphasizing the need for improved aerodynamics. To address the inherent drag issue, the study explored novel appendable devices and proposed alternative taxi sign designs. Among the tested solutions, a magnet-mounted front ramp proved the most effective, reducing total drag by nearly 30%. Additionally, a motorized flip-up taxi sign design demonstrated a remarkable 40% reduction in drag. Finally, a newly proposed taxi sign design, featuring longitudinal positioning and pointed triangular front and rear faces, resulted in a minimal 4.3% increase in vehicle drag compared to the baseline car.

We know that the classical Mittag-Leffler function play an important role as solution of fractional order differential and integral equations. We introduce the j-generalized p - k Mittag-Leffler function. We evaluate the second order differential recurrence relation and four different integral representations and introduce a homogeneous linear differential equation whose one of the solution is the j-generalized p-k Mittag-Leffler function. Also we evaluate the certain relations that exist between j-generalized p - k Mittag-Leffler function and Riemann-Liouville fractional integrals and derivatives. We evaluate Mellin-Barnes integral representation of j-generalized p-k Mittag-Le er Function. The relationship of j-generalized p-k Mittag-Leffler Function with Fox H-Function and Wright hypergeometric function is also establish. we obtained its Euler transform, Laplace Transform and Mellin transform. Finally we derive some particular cases.

Field observations of external wounds associated with two common tree injection methods compared open (plug-less) and sealed (plug) systems in green ash (Fraxinus pennsylvanica Marshall) trees . A wound from any cause within 1.37 meters above the ground was common with 28.8% of all trees. The open system had statistically fewer (p<0.001) trees with at least one wound (11.6% of trees) than the sealed system (47.4% of trees). The open system had fewer (P<0.001) wounds (0.17, 0.04 SE) per tree and a smaller (P<0.001) total wound area (25.5 cm2, 8.7 SE) per tree, compared to the sealed system wounds (1.14, 0.13 SE) per tree and the total wound area (99.7 cm2, 16.2 SE) per tree. The incidence of a tree with a wound(s) within 1.37 m above the ground was 7.2 times more likely with trees treated though the sealed system. Wounds in the sealed system were observed to appear to have a high rate of improper application of plugs, which was associated in 77% of the cases to explain the wounds. Implications of study results are further provided to best protect ash trees, while at the same time reducing the incidence external wounding on ash trees.

This paper examines dynamic identity, as it pertains to the IoT; and explores the practical implementation of a mitigation to some of the key weaknesses of a conventional dynamic identity model. This paper explores human-centric and machine-based observer approaches for confirming device identity, permitting automated identity confirmation for deployed systems. It also assesses the advantages of dynamic identity in the context of identity revocation permitting secure change of ownership for IoT devices. The paper explores use-cases for human and machine-based observation for authentication of device identity when devices join a C2 network, and considers the relative merits for these two approaches for different types of system.

Up to forty percent of dairy cows develop metritis or endometritis when pathogenic bacteria infect the uterus after parturition. However, resilient cows remain healthy even when exposed to the same pathogens. Here, we provide a perspective on the mechanisms that dairy cows use to prevent postpartum uterine disease. We suggest that resilient cows prevent the development of uterine disease using the three complimentary defensive strategies of avoiding, tolerating and resisting infection with pathogenic bacteria. Avoidance maintains health by limiting the exposure to pathogens. Avoidance mechanisms include intrinsic behaviors to reduce the risk of infection by avoiding pathogens or infected animals, perhaps signaled by the fetid odor of uterine disease. Tolerance improves health by limiting the tissue damage caused by the pathogens. Tolerance mechanisms include neutralizing bacterial toxins, protecting cells against damage, enhancing tissue repair, and reprogramming metabolism. Resistance improves health by limiting the pathogen burden. Resistance mechanisms include inflammation driven by innate immunity and adaptive immunity, with the aim of killing and eliminating pathogenic bacteria. Farmers can also help cows prevent the development of postpartum uterine disease by avoiding trauma to the genital tract, reducing stress, and feeding animals appropriately during the transition period. Understanding the mechanisms of avoidance, tolerance and resistance to pathogens will inform strategies to generate resilient animals and prevent uterine disease.

In this review, we address issues that relate to the rapid “Warp Speed” development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of “Warp Speed” immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the “Warp Speed” vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.

In this research paper, design and development of pyramidal horn antenna for J-band application is reported. It is particularly designed for 17 dB gain and half beam width about 25 degrees at 6.93 GHz. Horn aperture, horn axial length and distance from the throat of the antenna to aperture are the main design constraints which are calculated and used for the antenna design and simulation. Beam width in E-plane and H-plane horn is calculated and it is 19.18 dB and 22.86 dB respectively. The reported antenna design shows good performance for J-band in radiometry, satellite, and radar applications.

The purpose of this study was to explore the role of moral distress on physician burnout during COVID-19. Physicians in the US were interviewed between February and March 2021; 479 responded to our survey. Results indicated that moral distress was a key mediator in explaining the relationship between perceived organizational support, medical specialization, emotional labor, and coping on burnout. There was no support for increased burnout among female physicians, and contracting COVID-19 likewise did not play a role in burnout. Our findings suggest that physician burnout can be mitigated by increasing perceived organizational support; likewise, physicians who engaged in deep emotional labor and problem-focused coping tended to fare better when it came to feelings of moral distress and subsequent burnout.

Two extreme wind-driven wildfire events impacted northern and southern California in late 2017 leading to 46 fatalities and thousands of structures lost. This study describes the meteorological and climatological factors that drove and enabled these wildfire events and quantifies the rarity of such conditions over the observational record. Both extreme wildfire events featured fire-weather metrics that were unprecedented in the observational record in addition to a sequence of climatic conditions that preconditioned fuels. The North Bay fires that affected portions of northern California in early October occurred coincident with strong downslope winds. The vast majority of the fires’ devastating effects and acres burned occurred overnight and within the first twelve hours of ignition. By contrast, the southern California fires of December were characterized by the longest Santa Ana wind event on record and included the largest wildfire in California’s history. Both fire events occurred following an exceptionally wet winter that was preceded by the drought of record in California. Fuels were further preconditioned as the warmest summer and autumn on record occurred in northern and southern California, respectively. Accelerated curing of fuels coupled with the delayed onset of autumn precipitation allowed for critically low dead fuel moisture leading up to the foehn wind events. Fire weather conditions were well forecasted several days prior to the fire. However, the rarity of fire-weather conditions that occurred in the wildland urban interface, along with other societal factors were key contributors to wildfire impacts to communities.

South Africa is a water stressed country experiencing mass urbanisation especially towards coastal cities. The country is already enduring the impacts of global warming and climate change with risk of water scarcity in many areas. The risk was evident with Cape Town near encounter with ‘Day Zero’ i.e., the day when water supplies would have been switched off and residents required to queue for daily water rations. The drought exposed the inadequa-cies of the existing water supply system. Paradoxically, in the same drought period, vast amounts of unutilized stormwater that could have augmented water supply run unabated into the ocean through rivers around the city. The study determined that the problem was not necessarily water shortage but lack of adequate water storage. This study investigated the suitability of coastal reservoirs for stormwater harvesting on the over 3000 km South African coastline. The objective was to identify suitable locations for coastal reservoirs. The study un-dertook a systematic process of selecting several candidate locations and eliminating unsuita-ble sites based on international best practice i.e., coastal topography, climate, hydrology, fluvi-al environment, catchment size and river water quality. Nine candidate sites were identified and ranked based on suitability and associated benefits. The identified locations in order of ranking include Knysna River, Berg River, Buffalo River, Kowie River, Thukela River, Orange River, Port of Richards Bay, Port of Durban, and Lourens River. The Knysna site, with a mean annual precipitation of 600 - 800 mm/annum and mean annual runoff of 100 - 500 Mm3/annum, was determined to be the most optimal location.

Historically, urban development has always been centered on coastal areas – with access to waterbodies – seas, rivers and canals being a significant advantage for movement and trade. With most of the world’s megapolises located on coasts, land reclamation offers a solution for the expansion of city centers which are otherwise restricted by the coastline. The current understanding of urban regeneration and development on reclaimed lands is defined in this study, answering the basic questions of what, why and how. This study aims to assess the urban regeneration on reclaimed coastal land based on the principles of sustainable development defined by existing studies. The literature review establishes a theoretical framework and defines performance-based benchmarks identifying the spatial indicators of urban development. Composite indicators namely open space coverage, land use mix, percentage of coast for people, accessibility to public transportation and amenities, availability of pedestrian paths and cycling tracks and adequate road networks are considered for this framework. The conclusions are drawn based on the results of the analysis of spatial layout using GIS as a tool to map and empirically measure each indicator. The framework is validated using a major land reclamation project, West Bay, in the coastal urban area of ​​the city of Doha. The results determine that West Bay has achieved a good level of sustainability, although there are areas that could be enhanced to further improve the overall sustainability of urban development. These findings can serve as a guide for policymakers and various stakeholders for sustainable urban planning on reclaimed coastal lands.

Missing observation is a common problem in scientific and industrial experiments, particularly in a small-scale experiment. They often present significant challenges when experiment repetition is infeasible. In this research, we propose a multi-objective genetic algorithm as a practical alternative for generating optimal mixture designs that remain robust in the face of missing observation. Our algorithm prioritizes designs that exhibit superior D-efficiency while maintaining a high minimum D-efficiency due to missing observation. The focus on D-efficiency stems from its ability to minimize the impact of missing observations on parameter estimates, ensure reliability across the experimental space, and maximize the utility of available data. We study problems with three mixture components where the experimental region is an irregularly shaped polyhedral within the simplex. Our designs have proven to be D-optimal designs, demonstrating exceptional performance in terms of D-efficiency and robustness against missing observations. We provide a well-distributed set of optimal designs derived from the Pareto front, enabling experimenters to select the most suitable design based on their priorities using the desirability function.

The partial discharge (PD) event in high voltage insulation releases energy, exerts mechanical pressure, and generates elastic waves. Detecting and locating these PD events through short-duration acoustic pulses is well-established, particularly in gas-insulated systems and oil-insulated transformers. However, its full potential remains untapped in solid insulation systems, where the propagation capability of acoustic pulse and the acoustic reflections pose fundamental challenges to the Acoustic Emission (AE) detection technique. This study investigates the influence of reflections and multiple paths on the propagating acoustic pulse in polymeric insulating materials using a finite element method (FEM) in COMSOL. It was observed that the reflections from the boundary influence the propagating pulse's shape, peak magnitude, and arrival time. An analytical MATLAB model further quantifies the impact of multiple propagation paths on the shape, magnitude, and arrival time of the pulse travelling in a cylinder. Additionally, a Perfect Matched Layer (PML) was implemented in the COMSOL model to eliminate reflections from the boundary, and it revealed that the acoustic pulse magnitude decreases with distance following the inverse square law. In essence, the models aid in measuring how reflections contribute to the observed signals, facilitating the precise identification of the source of the PD event in the tested system.

Every biological image contains quantitative data that can be used to test hypotheses about how patterns were formed, what entities are associated with one another, and whether standard mathematical methods inform our understanding of biological phenomena. In particular, spatial point distributions and polygonal tessellations are particularly amendable to analysis with a variety of graph theoretic, computational geometric, and spatial statistical tools such as: Voronoi Polygons; Delaunay Triangulations; Perpendicular Bisectors; Circumcenters; Convex Hulls; Minimal Spanning Trees; Ulam Trees; Pitteway Violations; Circularity; Clark-Evans spatial statistics; Variance to Mean Ratios; Gabriel Graphs; and, Minimal Spanning Trees. Furthermore, biologists have developed a number of empirically related correlations for polygonal tessellations such as: Lewis’s Law (the number of edges of convex polygons are positively correlated with the areas of these polygons): Desch’s Law (the number of edges of convex polygons are positively correlated with the perimeters of these polygons); and Errara’s Law (daughter cell areas should be roughly half that of their parent cells’ areas). We introduce a new Pitteway Law that the number of sides of the convex polygons in a Voronoi tessellation of biological epithelia is proportional to the minimal interior angle of the convex polygons as angles less than 90 degrees result in Pitteway violations of the Delaunay dual of the Voronoi tessellation.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an effective and widely used tool in the treatment of Parkinson’s disease (PD). STN-DBS has varied effects on speech. Clinical speech ratings suggest worsening following STN-DBS, but quantitative intelligibility, perceptual, and acoustic studies have produced mixed and inconsistent results. Improvements in phonation and declines in articulation have frequently been reported during different speech tasks under different stimulation conditions. Questions remain about preferred STN-DBS stimulation settings. Seven right-handed, native speakers of English with PD treated with bilateral STN-DBS were studied off medication at three stimulation conditions: stimulators off, 60 Hz (low frequency stimulation - LFS), and the typical clinical setting of 185 Hz (High frequency - HFS). Spontaneous speech was recorded in each condition and excerpts were prepared for transcription (intelligibility) and difficulty judgements. Separate excerpts were prepared for listeners to rate abnormalities in voice, articulation, fluency, and rate. Intelligibility for spontaneous speech was reduced at both HFS and LFS when compared to STN-DBS off. Speech produced at HFS was more intelligible than that produced at LFS, but HFS made the intelligibility task (transcription) subjectively more difficult. Both voice quality and articulation were judged to be more abnormal with STN-DBS on. STN-DBS reduced the intelligibility of spontaneous speech at both LFS and HFS but lowering the frequency did not improve intelligibility. Voice quality ratings with STN-DBS were correlated with the ratings made without stimulation. This was not true for articulation ratings. STN-DBS exacerbated an existing voice disorder and may have introduced new articulatory abnormalities.

The ability to self-direct a research program determines graduate degree completion. Yet, research on incompletion of graduate physics programs assume students’ present level of self-direction adequate and neglects to recognize a lack of self-directed learning as key. One theoretical mathematical physicist focused on changing this challenge of physics graduate education by promoting self-directed learning through the type research flow that has been found to bring the greatest satisfaction to researchers with respect to their insights. This he provided through his space, time, open mindedness and theoretical contributions with his students and in collaboration with his colleagues. A self-directed learner himself, David J. Rowe developed methods of mentoring for encouraging physics graduate students to recognize symmetry as valuable in identifying solutions to problems quickly—helping these students take the lead in finding insightful resolutions to complex, multidimensional, mathematical physics uncertainties. How Rowe set about supporting self-directed learning in his graduate physics education interactions will be examined with the use of narrative research to interpret the texts and conversations with the author he made available. His techniques will be presented and recommendations made regarding how Rowe’s work in this regard can be modeled to improve self-direction in STEM graduate education.

Background: A comprehensive response to the unprecedented SARS-CoV-2 (COVID-19) chal-lenges for public health and its impact on radiation oncology patients and personnel for resilience and adaptability is presented. Methods: The general recommendations included working remote-ly when feasible, implementation of screening/safety and personal protective equipment (PPE) guidelines, social distancing, regular cleaning of treatment environment, and testing for high-risk patients/procedures. All teaching conferences, tumor boards, and weekly chart rounds were con-ducted using a virtual platform. Additionally, specific recommendations were given to each sec-tion to ensure proper patient treatments. The impact of these measures, especially adaptability and resilience, were evaluated through specific questionnaire surveys. Results: These comprehen-sive COVID-19 related measures resulted in most staff expressing a consistent level of satisfaction in regards to personal safety, maintaining a safe work environment, continuing quality patient care and continuing educational activities during the pandemic. There was a significant reduction in patient treatments and on-site patient visits with an appeciable increase in the number of tele-medicine e-visits. Conclusions: Survey results demonstrated substantial adaptability and resili-ence, including in the rapid recovery of departmental activities during the reactivation phase. In the event of a future public health emergency, the measures implemented may be adopted with good outcomes by radiation oncology departments across the globe.

Background: The incidence of spinal metastatic disease has risen with improved cancer survivorship. Separation surgery, the current standard surgical treatment, does not fully address spinal deformity. Advances in operative management warrant reevaluating maximal tumor resection and anterior column reconstruction with corpectomy. Methods: An IRB-approved retrospective single-center review of 63 patients was performed. Demographics, tumor characteristics, clinical and radiographic data, treatments, and neurological and survival outcomes were analyzed. Results: The mean age at presentation was 63.5 ± 9.6 years (range, 37-84 years) and 28 patients (44.4%) were female. Functional outcomes, measured by KPS, RAND-36 survey scores and Oswestry Disability Index all improved postoperatively (pre- vs postop: 70 to 80 (p=0.0056), 26.5 to 46.4 (p=0.0081), and 28.9 to 16.9 (p=0.0613), respectively). Spinal alignment also improved, with Cobb angle measurements showing a reduction in spinal kyphosis from -5 to 0 (p=0.021). Nine patients (14.5%) had non-fatal postoperative complications. The median OS for this cohort was 14.4 months (range, 0.6-145.0 months) with median follow-up time of 15.5 months. Conclusion: In oligometastatic spinal disease patients with good functional status, corpectomy for decompression of neural elements, deformity correction, and spinal stabilization is associated with improvements in pain and functional outcomes without overwhelming morbidity.

Sustainable manufacturing practices are becoming increasingly necessary due to the growing concerns regarding climate change and resource scarcity. Consequently, material recycling technologies have gradually become preferred over conventional processes. This study aimed to recycle waste polylactic acid (PLA) from household-disposed cups and lids to create 3D-printed parts and promote sustainable manufacturing practices. To achieve this, the current study utilised virgin and post-consumer PLA (sourced from household waste) blends. The PC-PLA wastes were shredded and sorted by size with the aid of a washing step, resulting in a filament with a 1.70 ± 0.5 mm diameter without fragmentation or dissolution. A 50:50 wt.% blend of virgin PLA (vPLA) and PC-PLA was selected as the standard recycling percentage based on previous research and resource conservation goals. The study investigated the impact of three 3D printing parameters (layer height (LH), infill density (I), and nozzle temperature (NT))on the quality of 3D-printed parts using a three-level L9 Taguchi orthogonal array. The findings revealed that blending PC-PLA with vPLA led to significant improvements in the tensile, flexural, and impact strengths by 18.40%, 8%, and 9.15%, respectively, compared to those of recycled PLA. This conclusion was supported by the investigation of the fracture surface area, which revealed fractographic features associated with printing parameters, such as plastic deformation and interfilament debonding. An ANOVA analysis revealed a positive influence of larger layer height and high nozzle temperature on the mechanical properties. Subsequently, the optimal printing parameters (LH: 0.3 mm, I: 100%, and NT: 215 °C) were determined using the S/N ratio, and a confirmation test using the optimum printing parameters exhibited a strong correlation with statistically predicted outcomes. Finally, the study used optimum printing parameters to fabricate 100% post-consumer recycled PLA 3D printed parts, demonstrating their potential for low-strength applications. Based on these findings, it can be concluded that virgin and post-consumer recycled PLA blended filament for fabricating 3D printed components is an effective way to support plastic recycling in the context of a circular economy.

This paper seeks to model the crack propagation in of AAs (aluminum-alloys) 2524-T3 and 7050-T7452 subjected to fatigue loading at low temperature. Fatigue crack growth tests were performed on AAs 2524-T3 and 7050-T7452 subjected to constant-amplitude and actual random-spectra loading histories at room temperature of about 25 °C and at cryogenic temperature of -70 °C, respectively, to determine their crack growth properties and residual lives. The interaction mechanisms between cryogenic temperature and the fatigue load were deduced on the basis of the results of fractographic analysis. Temperature-dependent residual lives under actual random-spectrum load history were modeled based on a modified accumulation damage rule by accounting for the load interaction. Good correlation was achieved between the predictions and actual experiments, demonstrating the practical and effective use of the proposed method.

Polymethyl methacrylate (PMMA) polymer is widely used in various fields today. In order to thoroughly reveal the structural impact performance of PMMA materials, this paper is based on the comprehensive Johnson-Cook constitutive model and damage failure model, and accurately confirm the J-C constitutive and damage failure model parameters of PMMA through material test data, The dynamic process of steel bullet impacting PMMA plate structure is analyzed by finite element software ABAQUS. The calculation results show that the numerical simulation results in this paper are in good agreement with the experimental test data. Therefore, the feasibility and accuracy of the impact analysis of PMMA structures based on J-C constitutive and damage failure models in this paper are studied. Finally, based on the J-C constitutive model and damage failure model, the variation of the residual velocity of the bullet with the PMMA plate thickness is analyzed in depth, that is, the results show that the residual velocity of the bullet has a certain linear relationship with the plate thickness.

Genomic medicine is moving from research to the clinic. There is a lack of evidence about the impact of genomic medicine interventions on health outcomes. This is due in part to a lack of standardized outcome measures that can be used across different programs to evaluate the impact of interventions targeted to specific genetic conditions. The eMERGE Outcomes working group (OWG) developed measures to collect information on outcomes following the return of genomic results to participants for several genetic disorders. These outcomes were compared to outcome intervention pairs for genetic disorders developed independently by the ClinGen Actionability working group (AWG). In general, there was concordance between the defined outcomes between the two groups. The ClinGen outcomes tended to be higher level and the AWG scored outcomes represented a subset of outcomes referenced in the accompanying AWG evidence review. eMERGE OWG outcomes were more detailed and discrete, facilitating collection of relevant information from health records. This paper demonstrates that common outcomes for genomic medicine interventions can be identified. Further work is needed to standardize outcomes across genomic medicine implementation projects and make these publicly available to enhance dissemination and assist in making precision public health a reality.

Introduction: The association of gene variants for interleukin 6(IL-6) (rs1800796), interleukin 10 (IL-10) (rs1800896) and tumor necrosis factorα (TNFα (rs1800629) with the occurrence of spontaneous preterm birth (PTB) was investigated to determine whether these genetic variants are a risk factor. Materials and methods: 199 blood samples from pregnant women who had given birth prematurely and 200 control blood samples were analyzed to determine single nucleotide polymor-phisms (SNPs) of genes for IL-6 (rs1800796), IL-10 (rs1800896) and TNFα (rs1800629). The control samples were samples from pregnant women with term delivery. Isolation of DNA was per-formed on mini-spin columns according to the manufacturer's protocol. The quality and purity of the isolated DNA were tested using a Qubit 3 fluorometer. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. The genotypes obtained were an-alyzed using the 7500 Software v2.3 package. Results: Carriers of the A/A genotype for the rs1800629 of the TNFα gene have 4.81 times greater chance of late-onset PTB compared to carriers of the G/G and A/G genotypes in the recessive inheritance model. The presence of the G/G genotype in the recessive inheritance model compared with the G/A and A/A genotypes for the rs1800896 of the IL-10 gene represents a potentially protective factor, with mothers in the term-birth group having an almost 2-fold lower odds of PTB in general and an almost 10-fold lower odds of early PTB. On the other hand, carriers of the A/G genotype of rs1800896 have a 1.54-fold higher chance of preterm birth in general and a 1.6-fold higher chance of late preterm birth in the super dominant inheritance model compared to the A/A and G/G genotypes in the group of mothers with PTB. In this study, no association was found between PTB and rs1800796 of the IL-6 gene. Conclusion: rs1800629 in mothers was associated with PTB. rs1800896 shows a potentially protective effect for the occurrence of PTB in this study. No association was found between PTB and rs1800796.

Seasonal oscillations in the partial pressure of carbon dioxide (pCO2) in the Earth’s atmosphere stronger in northern latitudes are assumed to show that terrestrial photosynthesis exceeds respiration in summer reducing the pCO2, but increasing in winter when respiration exceeds photosynthesis. We disagree, proposing that variations in the temperature of the surface mixing zone of seawater also regulate the atmospheric pCO2, thermodynamically. We show that carbonate (CO32-) concentrations will therefore increase in summer with CaCO3 (calcite or aragonite) becoming less soluble, so calcium and carbonate ions are predicted to aggregate more while CO2 concentration falls in warmer seawater, thermodynamically favoring lower atmospheric pCO2. In winter, these physical processes are reversed, redissolving suspended calcite thus increasing carbonate alkalinity; carbonate concentration lessens as bicarbonate and soluble CO2 increase, raising the pCO2 in air. Our numerical computation shows that thermal fluctuations in equilibria favor absorption from air of more than one mole of CO2 per square meter in summer, coinciding with calcite formation maximizing in warmer water, potentially augmenting limestone reefs if there is a trend for increasing temperature . Another assumption we challenge is that upwelling from deeper water is the sole cause of increases in dissolved inorganic carbon (DIC) and alkalinity in surface waters, particularly in the southern hemisphere. Instead, calcite dissolution is favored as water temperature falls near the surface. It is well established that the seasonal summer decline in atmospheric CO2 coincides in fertile seawater with higher rates of biotic calcification and acidity, allowing increased CO2 capture by photosynthesis. However, its reversal in winter is proposed to be also a result of the cyclic dissolution of calcite as temperature falls, facilitated by biogenic respiration now exceeding photosynthesis; this can mutually provide the CO2 needed to convert carbonate ion alkalinity from calcite dissolution with bicarbonate increasing. Physical reasons why this oscillation is more obvious in the northern hemisphere include greater seasonal variations in water temperature (ca. 7.1 oC) being almost twice that in the cooler southern hemisphere (ca. 4.7 oC) and the greater depth of the surface mixing zone of seawater in the southern oceans. Evidence from 13CO2 fluxes between surface seawater and air is also assessed to test this hypothesis but questions remain regarding the regional rates of inorganic precipitation and dissolution of CaCO3 in the mixing zone. In summary, rapid biogenic calcification is favored by summer photosynthesis, but slower abiogenic calcification is more likely in warmer water.

In the cold deserts of the McMurdo Dry Valleys (MDV) the suitability of soil for microbial life is determined by both contemporary processes and legacy effects. Climatic changes and accompanying glacial activity have caused local extinctions and geochemical changes to soil ecosystems over several million years, while high elevation refugia may have escaped these disturbances and existed under relatively stable conditions. This study describes the impact of historical glacial and lacustrine disturbance events on microbial communities across the MDV. Soil bacterial communities from 17 sites representing either putative refugia or sites disturbed during the Last Glacial Maximum (LGM) (22-17kya) were characterized using 16S metabarcoding. Regardless of geographic distance, several putative refugia sites at elevations above 600 meter displayed highly similar microbial communities. At a regional scale, community composition was found to be influenced by elevation and geographic proximity more so than soil geochemical properties. These results suggest that despite the extreme conditions, diverse microbial communities exist in these putative refugia that have presumably remained undisturbed at least through the last glacial maximum. We suggest that similarities in microbial communities can be interpreted as evidence for historical climate legacies on an ecosystem-wide scale.

Rapidly and repeatedly ascertaining the health status of coral reefs is an ever more pressing issue as part of activities to understand and monitor the damaging impacts of climate change. A combination of increasing ocean temperatures, acidity and frequency of extreme storm events continues to alter the marine environment beyond what sensitive organisms, such as coral, can cope with. It is therefore vital to establish technologies and validated methods to provide a metric or indication into the health of these organisms. There are currently many surveys and techniques used by coral scientists to uncover insights into the status and assessment of coral reefs, from colour wheels to multispectral satellite surveys. Here we outline an array of current techniques and methods focused specifically on coral monitoring and health diagnosis, ranging across the length scales from simple diver-based surveyance to satellite remote sensing. The technique of using hyperspectral fluorescence imaging is also introduced as a viable novel addition to aid and extend the current toolbox of available technologies.

The transverse momentum distribution of J/ψ mesons produced in pp collisions at the center-of-mass energy 5 TeV, 7 TeV，and 13 TeV is described by the modified Hagedorn function which is based on the Tsallis function and Hagedorn function. The calculated results by the modified Hagedorn function are in accord with experimental data measured by the LHCb Collaboration at LHC. The related parameters are obtained and analyzed.

Considered one of the finest first-generation Nigerian writers, John Pepper Clark-Bekederemo, who passed away on 13th October, 2020, had been categorised as a Eurocentric writer. This work assesses the authenticity or otherwise of this critics’ perception of Clark by critiquing his America, their America. By analysing this autobiography vis-à-vis the notion of self and other which is a theoretical concern in contemporary travel writing, it was established, among other things, that every culture has its dark sides which it must not feel too proud to change as time and situation demand; that Clark vehemently rejects the Americans’ claim of sophistication and superiority of their culture over African culture. The paper concludes that contemporary travel writing should be a rightful site for negotiating cultural, political and diplomatic compromises between the Self and the Other since the gulf may be difficult to close altogether.

The ribonuclease H (RNase H) active site of HIV-1 reverse transcriptase (RT) is the only viral enzyme not targeted by approved antiretroviral drugs. Using a fluorescence-based in vitro assay, we screened 65,239 compounds at a final concentration of 10 µM to identify inhibitors of RT RNase H activity. We identified 41 compounds that exhibited 50% inhibitory concentration (i.e., IC50) values < 1.0 µM. Two of these compounds, 2-(4-methyl-3-(piperidin-1-ylsulfonyl)phenyl)benzo[d]isothiazol-3(2H)-one (1) and ethyl 2-(2-(3-oxobenzo[d]isothiazol-2(3H)-yl)thiazol-4-yl)acetate (2), which both share the same benzisothiazolone pharmacophore, demonstrate robust antiviral activity (50% effective concentrations of 1.68 ± 0.94 µM and 2.68 ± 0.54, respectively) in the absence of cellular toxicity. A limited structure-activity relationship analysis identified two additional benzisothiazolone analogs, 2-methylbenzo[d]isothiazol-3(2H)-one (3) and N,N-diethyl-3-(3-oxobenzo[d]isothiazol-2(3H)-yl)benzenesulfonamide (4), which also resulted in inhibition of RT RNase H activity and virus replication. Compounds 1, 2 and 4, but not 3, inhibited the DNA polymerase activity of RT (IC50 values ~ 1 to 6 µM). In conclusion, benzisothiazolone derivatives represent a new class of multifunctional RT inhibitors that warrants further assessment for the treatment of HIV-1 infection.

The COVID-19 pandemic caused by the virus SARS-CoV-2 has been the greatest global threat to human health in the last three years. The most widely used methodologies for the diagnosis of COVID-19 are quantitative reverse transcription polymerase chain reaction (RT-qPCR), used to detect the viral genome, and rapid antigen tests (RATs), also known as lateral flow tests, that employ specific antibodies to detect the viral spike protein. While PCR is considered the gold standard test in terms of specificity and sensitivity, it is time-consuming and requires specialized instrumentation operated by skilled personnel. In contrast, RATs can be used in-home or at point-of care but are less sensitive leading to a higher rate of false negative results. An alternative methodology for the detection of virus is the use of electrochemical biosensors that employ disposable strip electrodes to which binding of viral components elicits a change in electrical signal. Laser-scribed graphene (LSG) electrodes are attractive candidates for use as biosensors electrodes suitable for SARS-COV-2 detection due to their low-cost, patternability and ease of fabrication. In this work, we describe the development of a biosensor for COVID-19 detection that exploits a split-ester bond ligase system (termed ‘EsterLigase’) for immobilization of a virus-specific nanobody to maintain the out-of-plane orientation of the probe to ensure the efficacy of the probe-target recognition process. An anti-spike VHH E nanobody, genetically fused with the EsterLigase domain, was used as the specific probe for the spike receptor-binding domain (SP-RBD) protein as the target. The recognition between the two was measured by the change in the charge transfer resistance, determined by fitting the electrochemical impedance spectroscopy (EIS) spectra. The developed LSG-based biosensor achieved a linear detection range for the SP-RBD from 15 pM to 150 nM with a sensitivity of 0.0866 [log(M)]-1 and a limit of detection (LOD) of 7.68 pM.

Probiotics in cosmetics is a new and burgeoning area of research attracting attention from cosmetic manufacturers and customers looking for natural or additional alternatives in their skincare regimens. Probiotics not only promote beneficial microbiomes to improve skin health but can also modulate the visual, topographical, and mechanical attributes to improve skin quality. This study was conducted in healthy adults to determine the effect of a topical serum formulation containing the live probiotic Micrococcus luteus Q24 on several key cosmetic skin quality parameters and its beneficial impact on the modulation of the skin microbiome. Quantitative changes in various skin parameters were measured using a skin analyzer device and skin swabs were analysed using whole genome sequencing to monitor microbial diversity and levels of probiotic colonisation. Compared to the baseline, a significant reduction in the pore, spots, wrinkles, and impurities scores; and an increase of 101% in the hydration scores were observed. Additionally, 45-80% of participants showed a decrease in pores, spots, wrinkles, and impurities and 90% of participants showed an increase in hydration after 25 days of probiotic serum application. The WGS analysis of the skin swab samples showed a significant increase in the relative abundance of M. luteus Q24. The results from this study indicated that topical application of serum-containing probiotic M. luteus Q24 offers the benefit of improving skin health quality.

Historically, the evaluation and assessment of the clinical response to treatment for canine back pain is subjective and relies on owner and clinician assessment of pain. This study evaluated the use of sequential infrared thermal images as a measure of the response of canine patients with back pain to a prescribed series of photobiomodulation therapy (PBMT) treatments. Qualifying participants had histories of pain and dysfunction associated with spinal osteoarthritis or intervertebral disk disease, or of non-specific uni- or bilateral back pain along the paravertebral epaxial muscles. Each patient was initially thermally imaged prior to PBMT treatment and then received multiple PBMT treatments delivered to the appropriate spinal area on days 1, 2, 3, and 4. Participants were reimaged on day 7. Thermal images provided an objective measure of superficial temperature changes over the area of PBMT treatment of each patient after the PBMT regimen. The temperature correlated with statistically significant changes in Colorado State University Canine Chronic Pain Scale scoring (CPS) and owner assessment using the Canine Brief Pain Inventory (CBPI), which includes a Pain Severity Score (PSS) and Pain Interference Score (PIS). The correlation of objective thermal imaging data with more subjective outcome measures suggests thermal imaging may be a valuable additional tool in monitoring therapy outcome.

Tumid Lupus Erythematosus has been the subject of heated debate as to its correct nosographic classification. In particular, its definition has changed over time, depending on the different studies performed. In this review we address the initial definition of TLE, the changes that have taken place in the understanding and placement within the classification of Lupus Erythematosus (LE), and focus on clinical, histopathological, immunophenotypical and differential diagnosis aspects.

Background: Despite hearing aids adequately compensate for hearing loss, a substantial proportion of the population leave their hearing difficulties untreated. Even though this is a well-known clinical issue, the optimal approach to address this issue during the hearing rehabilitation process is still unclear. Purpose: The present study aims to characterise behavioural and neurophysiological auditory and cognitive processing skills in experienced hearing aid users versus those with normal hearing, aimed at providing clinicians with the evidence required to adequately manage the expectations of their clients, thus indirectly reinforcing hearing-aid adoption within the adult population with hearing loss. Research design: Behavioural tests included auditory, cognitive, and speech-in-noise tasks; and neurophysiological testing included cortical auditory evoked potentials evoked by a /da/ stimulus presented at 65 dB SPL. The tests were selected based on previous literature supporting specific speech-understanding skills. Study sample: Ten participants (7 female, 21—68 years) with bilateral, mild-moderate to moderately-severe sensorineural hearing loss (HL), and 10 with clinically normal hearing (NH, 8 female, 19—62 years) participated in the study. Data collection and analysis: Behavioural data was analysed using multivariate analysis of variance (MANOVA) and neurophysiological analysis used measurements such as independent t-test, time-frequency analysis and inter-trial phase coherence. Results: The NH and HL groups presented similar scores in all the behavioural tasks. Time-frequency analysis revealed a statistically significantly reduction in alpha (8–12 Hz) synchronisation at the centro-frontal electrodes in the HL group – a brain activity pattern that has been associated with listening effort, inhibition and selective attention. Conclusions and significance: Results support the conclusion that hearing aids are effective in compensating for the audibility of their users, enabling them to perform at similar levels than their normal-hearing peers. However, the reduced alpha synchronisation observed in the HL population indicates that adequate audibility does not extend to improved neural responses. Future studies need to investigate the induced activity in speech understanding paradigms to explore the auditory processing differences at cortical level. The results are only from a small sample size but the findings have the potential to support clinicians in managing adequately the expectations of their clients in regards the benefits of hearing aid technologies.

More than 20 lines of independent evidence from clinical observations, studies in laboratory animal models, pharmacokinetic considerations, and numerous temporal and spatial associations previously indicate that numerous genetic and environmental factors leading to inflammation and oxidative stress confer vulnerability to aberrant metabolism of acetaminophen during early development, leading to autism spectrum disorder (ASD). Contrary to this conclusion, multivariate analyses of cohort data adjusting for inflammation-associated factors have tended to show little to no risk of acetaminophen use for neurodevelopment. To resolve this discrepancy, here we use in-silico methods to create an ideal (virtual) population of 120000 individuals in which 50% of all cases of virtual ASD are induced by oxidative stress-associated cofactors and acetaminophen use. We demonstrate that Cox regression analysis of this ideal data set shows little to no risk of acetaminophen use if cofactors which create aberrant metabolism of acetaminophen are adjusted for in the analysis. Further, under-reporting of acetaminophen use is shown to be a considerable problem for this analysis, leading to large and erroneously low calculated risks of acetaminophen use. In addition, we argue that factors which impart susceptibility to acetaminophen-induced injury, and propensity for acetaminophen use itself, can be shared between the prepartum, peripartum, and postpartum periods, creating additional difficulty in analysis of existing datasets to determine risks of acetaminophen exposure for neurodevelopment during a specific time frame. It is concluded that risks of acetaminophen use for neurodevelopment obtained from multivariate analysis of cohort data depend on underlying assumptions in the analyses, and that other evidence, both abundant and robust, demonstrate the critical role of acetaminophen in the etiology of ASD.

Florida geologic units and soils contain a wide range in concentrations of naturally-occurring arsenic. The average range of bulk rock concentrations is 1 to 13.1 mg/kg with concentrations in accessary minerals being over 1,000 mg/kg. Soils contain natural arsenic concentrations of between 0.18 and 2.06 mg/kg with organic-rich soils having the highest concentrations. Anthropogenic sources of arsenic have added about 610,000 metric tons of arsenic into the Florida environment since 1970, thereby increasing background concentrations in soils. The anthropogenic sources of arsenic in soils include: pesticides (used in Florida beginning in the 1890’s), fertilizers, chromated copper arsenate (CCA)-treated wood, soil amendments, cattle-dipping vats, chicken litter, sludges from water treatment plants, and others. The default Soil Cleanup Target Level (SCTL) in Florida for arsenic in residential soils is 2.1 mg/kg which is below some naturally-occurring background concentrations in soils and anthropogenic concentrations in agricultural soils. A review of risk considerations shows that adverse health impacts associated with exposure to arsenic is dependent on many factors and that the Florida cleanup levels are very conservative. Exposure to arsenic in soils at concentrations that exceed the Florida residential cleanup level in residential environments does not necessarily pose a meaningful public health risk.

Strategies implemented worldwide to contain COVID-19 outbreaks varied in severity across different countries, and established a new normal for work and school life (i.e. from home) for many people, reducing opportunities for physical activity. Positive relationships of physical activity with both mental and physical health are well recognised, therefore the aim was to ascertain how New Zealand’s lockdown restrictions impacted physical activity and mental health and wellbeing. Participants (n=4007; mean±SD: age 46.5±14.7y, 72% female, 80.7% New Zealand European) completed (10–26 April 2020) an online amalgamated survey (Qualtrics): International Physical Activity Questionnaire: Short Form; Depression, Anxiety and Stress Scale-9; World Health Organization-Five Well-being Index; Stages of Change Scale. Positive dose response relationships between physical activity levels and wellbeing scores were demonstrated for estimates that were unadjusted (moderate activity OR 3.79, CI 2.88-4.92; high activity OR 8.04, CI 6.07-10.7) and adjusted (confounding variables: age, gender, socioeconomic status, time sitting, co-morbidities) (moderate activity 1.57, CI 1.11-2.52; high activity 2.85, CI 1.97-4.14). The study results support previous research demonstrating beneficial effects of regular physical activity on mental health and wellbeing. Governments may use such results to promote meeting physical activity guidelines in order to protect mental health and wellbeing during the ongoing COVID-19 and future pandemics.

Electroencephalography (EEG) is a brain imaging technique in which electrodes are placed on the scalp. EEG signals are commonly decomposed into frequency bands called delta, theta, alpha, and beta.While these bands have been shown to be useful for characterizing various brain states, their utility as a one-size-fits-all analysis tool remains unclear. We present a two-part data-driven methodology for objectively determining the best EEG bands for a given dataset in this paper. First, a decision tree is used to estimate the optimal frequency band boundaries for reproducing the signal’s power spectrum for a predetermined number of bands. The optimal number of bands is then determined using an Akaike Information Criterion (AIC)-inspired quality score that balances goodness-of-fit with a small band count. Data-driven EEG band discovery may aid in objectively capturing key signal components and uncovering new indices of brain activity.

We address the process of discounting in random environments which allows to value the far future in economic terms. We review several approaches to the problem regarding different well-established stochastic market dynamics in the continuous-time context and include the Feynman-Kac approach. We also review the relation between bond pricing theory and discount and introduce the market price of risk and the risk neutral measures from an intuitive point of view devoid of excessive formalism. We provide the discount for each economic model and discuss their key results. We finally present a summary of our previous empirical studies on several countries of the long-run discount problem.

The pregnane X receptor (PXR) is the main nuclear receptor regulating the expression of xenobiotic metabolizing enzymes and is highly expressed in the liver and intestine. Recent studies have highlighted its additional role in lipid homeostasis, however, the mechanisms of these regulations are not fully elucidated. We investigated the transcriptomic signature of PXR activation in the liver of adult wild-type vs Pxr-/- C57Bl6/J male mice treated with the rodent specific ligand pregnenolone 16α-carbonitrile (PCN). PXR activation increased liver triglyceride accumulation and significantly regulated the expression of 1215 genes mostly xenobiotic metabolizing enzymes. Among the down-regulated genes, we identified a strong peroxisome proliferator-activated receptor α (PPARα) signature. Comparison of this signature with a list of fasting-induced PPARα target genes confirmed that PXR activation decreased the expression of more than 25 PPARα target genes, among which the hepatokine fibroblast growth factor 21 (Fgf21). PXR activation abolished plasmatic levels of FGF21. We provide a comprehensive signature of PXR activation in the liver and identify new PXR target genes that might be involved in the steatogenic effect of PXR. Moreover, we show that PXR activation down-regulates hepatic PPARα activity and FGF21 circulation, which could participate in the pleiotropic role of PXR in energy homeostasis.

The eyes serve as a window into underlying physical and cognitive processes. Although factors such as pupil size have been studied extensively, a less explored yet potentially informative aspect is blinking. Given its novelty, blink detection techniques are far less available compared to eye-tracking and pupil size estimation tools. In this work, we present a new unsupervised machine learning blink detection strategy using existing eye-tracking technology. The method is compared to two existing techniques. All three algorithms make use of eye aspect ratio values for blink detection. Accurate and rapid blink detection complements existing eye-tracking research and may provide a new informative index of physical and mental status.

Rice, as a staple crop feeding billions, faces constant threats from various diseases jeopardizing global food security. Precise understanding of disease resistance mechanisms is crucial for developing resilient rice varieties. Traditional genetic mapping methods, such as QTL mapping, provide valuable insights into the genetic basis of diseases. However, the complex nature of rice diseases demands a holistic approach to gain accurate knowledge of it. Omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, enable a comprehensive analysis of biological molecules, uncovering intricate molecular interactions within the rice plant. Integration of various mapping techniques using multi-omics data has revolutionized our understanding of rice disease resistance. By overlaying genetic maps with high-throughput omics datasets, researchers can pinpoint specific genes, proteins, or metabolites associated with disease resistance. This integration enhances the precision of disease-related biomarkers with better understanding of their functional roles in disease resistance. Improvement of rice breeding for disease resistance through this integration represents a significant stride in agricultural science because better understanding of the molecular intricacies and interactions underlying disease resistance architecture leads to more precise and efficient development of resilient and productive rice varieties. In this review, we explore how the integration of mapping and omics data can give a transformative impact on rice breeding for enhancing disease resistance.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (>12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

Lightning is responsible for most annually burned area by wildfires in the extratropical region of the Northern Hemisphere. Hence, predicting the occurrence of wildfires requires reliable forecasting of the chance of cloud-to-ground lightning strikes during storms. Here, we describe the development and verification of a probabilistic lightning-strike algorithm designed to run on a uniform 20-km grid over the Continental USA and Alaska. The algorithm consists of a large set of logistic equations parameterized via logistic regression using long-term data records of observed lightning strikes and meteorological reanalysis fields from NOAA. Principal Component Analysis was employed to extract 13 Principal Components (strong predictors) from a list of 611 potential predictors. Our statistical analysis revealed that the occurrence of cloud-to-ground lightning strikes primarily depends on three factors: horizontal temperature distribution by pressure levels, amount of low-level atmospheric moisture, and wind vectors. These physical variables impact the vertical separation of electric charges in the lower troposphere during storms causing the voltage potential between ground and the cloud deck to increase to a level that triggers electrical discharges. Results from a forecast verification using independent data showed excellent model skill, thus making this algorithm suitable for inclusion into software systems forecasting the chance of wildfire ignitions.

Grain quality, cooking quality and nutritional quality traits are some of the major attributes that enhance uptake and utilisation of improved cowpea varieties. Therefore, there is need for a better understanding of the genetic variation and inter-relationships among these quality traits in cowpea to integrate them in cowpea breeding programs. The study was conducted to determine genetic variability among 306 cowpea genotypes for grain quality, cooking quality and nutritional quality traits and to understand the interrelationships among these traits for exploitation in breeding programs. The results showed highly significant differences (P

In tropical Africa, forests and savannas are the two most widespread biomes and potentially represent alternative stable states with divergent species composition. A classic, but untested, hypothesis posited by White (1983) suggests that the transition zones between forests and savannas contain a floristically impoverished assemblage with few representatives from each biome. Further, the evolutionary dimension of diversity has received limited attention, despite its importance for understanding the biogeographic history of biomes. Here, we quantify species richness and several measures of evolutionary diversity in 1° grid cells, using c. 300K occurrence records of trees and shrubs combined with biome affiliation data for 3,125 species. We find that assemblages in transition zones hold fewer woody species than assemblages in forest and savanna zones, as posited by White. However, transition zones hold more phylogenetic diversity than expected given their species richness, whether one considers forest and savanna assemblages separately or together. We also show that the Congo basin forest has low levels of phylogenetic diversity given the number of species and highlight south-eastern African savannas as a centre of savanna woody species richness and phylogenetic diversity. Regions with high phylogenetic diversity given the number of both forest and savanna species were centred around the Dahomey Gap and Cameroon, mainly in transition zones. Overall, our study shows that even if floristically impoverished, transition zones lead to unexpectedly high evolutionary diversity, suggesting they are important centres of evolutionary innovation and diversification.

Zinc is a highly abundant cation in the brain, where it is essential for cellular function, including transcription, enzymatic activity, and cell signaling. However, zinc can also trigger injurious cascades in neurons, contributing to the pathology of neurodegenerative diseases. Mitochondria, critical for meeting the high energy demands of the central nervous system (CNS), are a principal target of the deleterious actions of zinc. An increasing body of work suggests that intracellular zinc, can, under certain circumstances, contribute to neuronal damage by inhibiting mitochondrial energy processes, including dissipation of the mitochondrial membrane potential, leading to ATP depletion. Additional consequences of zinc-mediated mitochondrial damage include reactive oxygen species (ROS) generation, mitochondrial permeability transition, and calcium deregulation. Zinc can also induce mitochondrial fission, resulting in mitochondrial fragmentation, as well as inhibition of mitochondrial motility. Here, we review the known mechanisms responsible for the deleterious actions of zinc on the organelle, within the context of neuronal injury associated with neurodegenerative processes. Elucidating the critical contributions of zinc-induced mitochondrial defects to neurotoxicity and neurodegeneration may provide insight into novel therapeutic targets in the clinical setting.

Mitochondria are semiautonomous organelles, which are pivotal for the energy metabolism of eukaryotic cells. These organelles contain their own genetic system (mtDNA, mitogenome) that encodes to some structural RNAs and organellar proteins. The biogenesis and function of mitochondria is tightly regulated by nuclear-encoded protein cofactors. The mtDNAs of land plants are characteristically large, with a complex mode of gene organization and expression, in particularly at the post-transcriptional level. To become functional, the primary organellar transcripts undergo extensive maturation steps, which include endo- and exo-nucleolytic cleavage, RNA-base editing, and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. Among these, the RNA helicases serve as key players in organellar (mt-)RNA metabolism. This review summarizes the important roles played by these factors in regulating the highly dynamic processes of transcription, RNA processing, and translation within the mitochondria of land plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the organellar gene expression, respiratory functions, and hence the growth, development and physiology of land plants.

This paper describes and demonstrates an autonomous robotic team that can rapidly learn the characteristics of environments that it has never seen before. The flexible paradigm is easily scalable to multi-robot, multi-sensor autonomous teams, and is relevant to satellite calibration/validation and the creation of new remote sensing data products. A case study is described for the rapid characterisation of the aquatic environment, over a period of just a few minutes we acquired thousands of training data points. This training data allowed our machine learning algorithms to rapidly learn by example and provide wide area maps of the composition of the environment. Along side these larger autonomous robots two smaller robots that can be deployed by a single individual were also deployed (a walking robot and a robotic hover-board), observing significant small scale spatial variability.

Neurology is a quickly evolving specialty that requires clinicians to make precise and prompt diagnoses and clinical decisions based on the latest evidence-based medicine practices. In all Neurology subspecialties, Stroke and Epilepsy in particular, clinical decisions affecting patient outcomes depend on neurologists accurately assessing patient disability. Artificial intelligence (AI) can predict the expected neurological impairment from an AIS (Acute Ischemic Stroke), the possibility of ICH (IntraCranial Hemorrhage) expansion, and the clinical outcomes of comatose patients. This review article informs readers of artificial intelligence principles and methods. The article introduces the basic terminology of artificial intelligence before reviewing current and developing AI applications in neurology practice. AI holds promise as a tool to ease a neurologist’s daily workflow and supply unique diagnostic insights by analyzing data simultaneously from several sources, including neurological history and examination, blood and CSF laboratory testing, CNS electrophysiologic evaluations, and CNS imaging studies. AI-based methods are poised to complement the other tools neurologists use to make prompt and precise decisions that lead to favorable patient outcomes.

Damaged connective tissues between the bone and tendons or ligaments are common among adults regardless of activity level. Achilles tendinosis is one of the most common tissue defects and enthesopathies. The patient in this study is a 54-year-old female with chronic Achilles tendinosis from chronic enthesopathy at the Achilles tendon insertion with a retrocalcaneal exostosis for three years who has failed standard-of-care practices for over two years. The patient received extracorporeal pulsed-activated therapy (EPAT) before applying 2ml of CryoText, a Wharton’s jelly tissue allograft. The patient then received class IV laser therapy treatments twice weekly for three weeks. The patient started with a 10/10 VAS at the initial visit. At five weeks post-application, the patient’s score had improved by 80% at 2/10 VAS. By week 13, the patient rated her pain as 0/10 VAS. The improvement in patient-reported pain and functionality reported in this study after the application of Wharton’s Jelly, EPAT, and class IV laser therapy warrants future research studying the safety and efficacy of these patient care modalities together.

Rheumatoid arthritis (RA); is a chronic systemic autoimmune disease which causes loss of joint function and significantly reduces quality of life. Plasma metabolite concentrations of disease-modifying anti-rheumatic drugs (DMARDs) can influence treatment efficacy and toxicity. This study explored the relationship between DMARD metabolising gene variants and plasma metabolite levels in RA patients. DMARD metabolite concentrations were determined by tandem mass-spectrometry in plasma samples from 100 RA patients with actively flaring disease, collected at two intervals. Taqman-probes were used to discriminate single nucleotide polymorphism (SNP) genotypes in cohort genomic DNA: rs246240 (ABCC1), rs1476413 (MTHFR), rs2231142 (ABCG2), rs3740065 (ABCC2), rs4149081 (SLCO1B1), rs4846051 (MTHFR), rs10280623 (ABCB1), rs16853826 (ATIC), rs17421511 (MTHFR) and rs717620 (ABCC2). Mean plasma concentrations of methotrexate (MTX) and MTX-7-OH metabolites were higher (p<0.05, C.I. 95%) at baseline in rs4149081 GA genotype patients. Patients with rs1476413 SNP TT or CT alleles in the have significantly higher (p<0.001, 95% C.I) plasma poly-glutamate metabolites at both study time points and correspondingly elevated disease activity scores. Patients with the rs17421511 SNP AA allele reported significantly lower pain scores (p<0.05, 95% C.I.) at both study intervals. Genotyping strategies could help prioritise treatments to RA patients most likely to gain clinical benefit, whilst minimizing toxicity.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

The study assessed the trapping efficacy of locally-modified 1) Gravid Aedes Trap(GAT) lined with insecticide-treated net (ITN) as a killing agent, 2) Autocidal Gravid Ovitrap(AGO) with sticky board in the semi-field system (SFS) and field setting. Fully-balanced Latin square experiments were conducted to compare GAT lined with ITN vs AGO, both with either yeast or grass infusion. Biogents-Sentinel (BGS) with BG-Lure and no CO2 was used as standard trap for Aedes mosquitoes. In the SFS, GAT outperformed AGO in collecting both nulliparous (65% vs 49%,OR=2.22,[95%CI:1.89-2.60],p

Monitoring the health of coral reefs is essential to understand the damaging impacts of anthropo-genic climate change. Non-invasive methods to survey coral reefs are the most desirable and op-tics-based surveys, ranging from simple photography to multispectral satellite imaging are well es-tablished. Herein, we review these techniques, focusing on their value for coral monitoring and health diagnosis. A new, low-cost hyperspectral imaging technique using linear variable filters is also described. This system is capable of simultaneously producing hyperspectral and photogrammetric outputs, which provides integrated information of reef structure and physiology.

DNA double-strand breaks (DSBs) trigger the Ataxia telangiectasia mutated (ATM)-dependent DNA damage response (DDR), which consists of histone H2AX, MDC1, RNF168, 53BP1, PTIP, RIF1, Rev7, and Shieldin. Early stages of B and T lymphocyte development are dependent on recombination activating gene (RAG)-induced DSBs that form the basis for further V(D)J recombination. Non-homologous end joining (NHEJ) pathway factors recognize, process, and ligate DSBs. Based on numerous loss-of-function studies, DDR factors were thought to be dispensable for the V(D)J recombination. In particular, mice lacking Mediator of DNA Damage Checkpoint Protein 1(MDC1) possessed nearly wild-type levels of mature B and T lymphocytes in the spleen, thymus, and bone marrow. NHEJ factor XRCC4-like factor (XLF)/Cernunnos is functionally redundant with ATM, histone H2AX, and p53-binding protein 1 (53BP1) during the lymphocyte development in mice. Here, we genetically inactivated MDC1, XLF, or both MDC1 and XLF in murine vAbl pro-B cell lines and, using chromosomally integrated substrates, demonstrated that MDC1 stimulates the V(D)J recombination in cells lacking XLF. Moreover, combined inactivation of MDC1 and XLF in mice resulted in synthetic lethality. Together, these findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular.

Evidence that early life exposure to acetaminophen causes neurodevelopmental injury in susceptible children has mounted for more than a decade. Evidence is diverse, including extensive work with laboratory animals, otherwise unexplained associations, factors associated with the metabolism of acetaminophen, and some limited studies in humans. Although evidence has reached an overwhelming level and has been reviewed in detail recently, some controversy remains. In this narrative review, some of those controversies are evaluated. First, the associations through time between acetaminophen use and the prevalence of neurodevelopmental disorders are considered. A systematic review reveals that the use of acetaminophen in the pediatric population was never tracked carefully, but historical events that affected use of the drug were documented and are sufficient to establish apparent correlations with changes in the prevalence of neurodevelopmental disorders. Second, problems with exclusive reliance on results from meta-analyses of large datasets and from studies involving small time frames of drug exposure are reviewed. Third, the potential bias in a study designed to separate the role of vaccines and acetaminophen in the induction of autism spectrum disorder (Autism 2008;12:293-307) is carefully evaluated. Finally, evidence demonstrating why some children are susceptible to acetaminophen-induced neurodevelopmental injury is examined. It is concluded that, at least among the factors considered, there is no valid rationale for controversy regarding the conclusion that early life exposure to acetaminophen causes neurodevelopmental injury in susceptible babies and small children.

Astronauts are at risk of losing 1.0 to 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs and dietary regimens designed to preserve their musculoskeletal system. This loss is the result of microgravity-related impairment of osteocyte and osteoblast function and the consequent upregulation of osteoclast-mediated bone resorption. This review describes the ontogeny of osteoclast hematopoietic stem cells, the contributions of macrophage colony stimulating factor, activator of NFkB and the calcineurin pathways make in osteoclast differentiation, and provides details of bone formation, the osteoclast cytoskeleton, the immune regulation of osteoclasts, and osteoclast mechanotransduction on Earth, in the microgravity of space, and in conditions of simulated microgravity. The article discusses the need to better understand how osteoclasts are able to function in zero gravity and reviews current and prospective therapies that may be used to treat osteoclast-mediated bone disease.

Our study reviews the significance of archaeological parks in the tourism sector, with a specific focus on how digital presence and visitor feedback impact their cultural and touristic appeal. Utilizing statistical analyses such as regression and cluster analysis on data sourced from both Hungarian and Western European parks, the research scrutinizes TripAdvisor and Google ratings, alongside the volume of photographs and reviews. The findings highlight a modest correlation between digital visibility and overall visitor ratings, underscoring the complex relationship between online engagement and the quality of visitor experience. Notably, the cluster analysis identified two distinct groups, signifying diverse levels of visitor engagement and digital visibility across the parks. The conclusions drawn advocate for a comprehensive strategy to enhance visitor experiences, emphasizing the integration of digital engagement with the promotion of the parks cultural and historical values. By exploring the influence of digital presence on the appeal of archaeological parks, our study sheds light on the evolving interface between urban studies and digital heritage, highlighting how digital tools and online platforms are becoming increasingly integral in shaping the perceptions and experiences of urban cultural sites.

Most empirical work on sources of economic growth for different countries lack country-specific empirical evidence to guide policy choices in individual developing countries and previous studies of factor productivity tend to focus on the entire economy or a single sector. In this study, we use the recently developed growth accounting tools to explicitly determine the sources of economic growth at both national and sectoral levels in Zambia between 1970 and 2013. We use data from World Development Indicators and Zambia’s Central Statistical Office. On average, total factor productivity (TFP) contributes about 5.7% to economic growth. Sectoral analysis shows that agriculture contributes the least to GDP and that within each sector; factors that contribute to growth differ. Structural transformation has been slow and contributed to the observed inefficiency. We outline the implications of the observed growth and provide recommendations.

Unmanned Aerial Vehicles (UAVs) equipped with hyperspectral imagers have emerged as an essential technology for the characterization of inland water bodies. The high spectral and spatial resolutions of these systems enable the retrieval of a plethora of optically-active water quality parameters via band ratio algorithms and machine learning methods. However, fitting and validating these models requires access to sufficient quantities of in situ reference data which are time-consuming and expensive to obtain. In this study, we demonstrate how the Generative Topographic Mapping (GTM), a Bayesian realization of the Self-organizing Map, can be used to visualize high-dimensional hyperspectral imagery and extract spectral signatures corresponding to unique endmembers present in the water. Using data collected across a North Texas pond, we first apply the GTM to visualize the distribution of captured reflectance spectra revealing small-scale spatial variability of water composition. Next, we demonstrate how the nodes of the fitted GTM can be interpreted as unique spectral endmembers. Using extracted endmembers together with the normalized spectral similarity score, we are able to efficiently map the abundance of near shore algae as well as the evolution of a rhodamine tracer dye used to simulate water contamination by a localized source.

Mycobacterium avium ssp paratuberculosis (MAP) is the causative agent of Johne’s disease (JD) in animals and a suspected cause of Crohn’s disease (CD) in humans. Crohn’s Disease is a progressive, detrimental granulomatous enteritis of which common therapies are targeted to suppressing certain components of the immune system. The efficacy of these treatments can be variable and temporary with no clear process of selection for the individual patient. However, diagnosis of MAP has been elusive in patients with Crohn’s Disease. In animals it can be detected by several different techniques, including bacterial cell culture, polymerase chain reaction (PCR), and immunological targets. To move to an understanding of the possible pathogenicity of MAP and the sup-posed cause of CD in humans, it is necessary to demonstrate the presence of cell wall deficient mycobacterial (CWDM) forms of MAP in blood and tissue cultures from patients with CD. From this, more tailored and accurate therapies can be implemented and be developed to eradicate this infectious organism from humans. Current anti-mycobacterial antibiotics have limited efficacy as MAP is subtly different from tuberculosis. Newer methods, such as vaccination and gut microbiome remediation will be essential as part of combination therapies.

The study presented hereafter shows a new methodology to reveal traces of polyethylene (the most common microplastic particles, known as a structure of C2H4) in a sample of ocean water by the irradiation of a 50 keV, 1 µA electron beam. This is performed by analyzing the photon (produced by the electrons in water ) fluxes and spectra (i.e. fluxes as a function of photon energy) at different types of contaminated water with an adequate device and in particular looking at the peculiar interactions of electrons/photons with the potential abnormal atomic hydrogen (H), oxygen (O), carbon (C), phosphorus (P) compositions present in the water, as a function of living and not living organic organisms with a PO4 group RNA/DNA strands in a cluster configuration through a volumetric cells grid.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

J/ψ, a charmonium bound state made of a charm and an anti-charm quark, has been discovered in the 1970s and confirmed the quark model. Because the mass of charms quarks is significantly above the Quantum Chromodynamics (QCD) scale ΛQCD, charmonia are considered as excellent probes to test perturbative Quantum Chromodynamics (pQCD) calculations. Over the past decades, they have been studied extensively at different high energy colliders. However, their production mechanisms, which involves multiple scales, are still not very well understood. Recently, in high multiplicity p+p collisions at RHIC and at the LHC, a significant enhancement of J/ψ production yield has been observed, which suggests a strong contribution from the Multi-Parton Interaction (MPI). This is different from the traditional pQCD picture where charm quark pairs are produced from a single hard scattering between partons in p+p collisions. In this work, we will report the J/ψ normalized production yield as a function of normalized charged particle multiplicity over a board range of rapidity and event multiplicity in the J/ψ→μ+μ− channel with PHENIX Run 15 p+p data at \sqrt{s}=200 GeV. The results are compared with PYTHIA 8 simulations with the MPI option on and off. Finally, the outlooks of J/ψ in p+Au and Au+p collisions along with Color Glass Condensate (CGC) predictions and of multiplicity dependent ψ(2S)/J/ψ ratio in p+p data will be briefly discussed.

1). BACKGROUND: Cell wall deficient mycobacteria (CWDM) have seldom been isolated in bacterial culture from human subjects. particularly in clinical disease, such as Crohn’s disease. Techniques have focused on the use of polymerase chain reaction (PCR) for the detection of CWDM in association with inflammatory bowel disease. (IBD). This paper is a report of the development of methods to demonstrate the presence of CWDM using the Ziehl-Neelsen (ZN) stain. This is in addition to the detection of the growth of CWDM in fluid media. 2). METHODS: The use of the ZN stain is suitable for the demonstration of CWDM in clinical samples and cultures, when the staining methods that were common prior to the 1970’s, are adopted. Specific culture media are developed and tested in parallel. Alterations in the concentration of basic fuchsin, and changes in the decolourising solutions are necessary. Decolourising solutions such as 20% concentrated sulphuric acid in water are preferable for detection of CWDM in cultures. 3). RESULTS: CWDM can be readily demonstrated using the simple methods outlined in this report. The ability to visualise the presence of CWDM opens the door to the development of specific fluid media for the isolation of CWDM in culture. 4). CONCLUSION: The ZN stain methods optimised for the demonstration of Mycobacterium tuberculosis complex (MTBC) are not suitable for research into infectious causes of inflammatory bowel disease (IBD), as well as for the detection of CWDM in latent tuberculosis. Revisiting the techniques for the detection of CWDM may also refocus attention on inflammatory diseases considered to be idiopathic, but having hallmarks of an infectious process.

This study aimed to identify sociodemographic and health indicators of diet quality in pre-frail community-dwelling older adults. Pre-frail older adults are those at risk of progression to clinical manifestations of frailty and are targets for preventative intervention. We previously reported that pre-frail older adults have reasonably good overall diet quality. However, further analyses found low intake of energy, protein and several micronutrients. Methods: We collected detailed dietary intake from pre-frail (FRAIL scale 1-2) older adults using NZ Intake24, an online version of 24-hour multiple pass dietary recall. Diet quality was ascertained with the Diet Quality Index-International (DQI-I). We used regression Generalised Linear Models to determine predictors of diet quality and Classification and Regression Tree (CART) analysis to examine the complex relationships of predictors and identified profiles of sub-groups of older adults that predict diet quality. Results. The median age in this sample (n=468) was 80.0 years (77.0-84.0). Living with others, high deprivation index and a higher BMI were independent predictors of poorer diet quality. With CART analysis, we found that those with a BMI &gt;29 kg/m2, living with others and younger than 80 years were likely to have a lower diet quality. Conclusions: We found BMI, living arrangement and socioeconomic status were independent predictors of diet quality in pre-frail older adults, with BMI being the most important variable in this sample when the interacting relationships of these variables were considered. Future research is needed to determine the similarities and/or differences in the profile of subgroups of older adults with poorer diet quality.

In the mammalian isocortex CD44, a cell surface receptor for extracellular matrix molecules, is present in pial-based and fibrous astrocytes of white matter, but not the protoplasmic astrocytes. In the hominid isocortex, CD44+ astrocytes comprise the subpial “interlaminar” astrocytes, sending long processes into the cortex. The hippocampus also contains similar astrocytes. We have examined all levels of the human CNS and found CD44+ astrocytes in every region. Astrocytes in white matter and astrocytes that interact with large blood vessels, but not capillaries in gray matter, are CD44+, the latter extending long processes into the parenchyma. Motor neurons in the brainstem and spinal cord, such as oculomotor, facial, hypoglossal, and in the anterior horn of the spinal cord, are surrounded by CD44+ processes, contrasting with neurons in the cortex, basal ganglia and thalamus. We found CD44+ processes that intercalate between ependymal cells to reach the ventricle and that show a location-specific presence. We also found a CD44+ astrocyte in the molecular layer of the cerebellar cortex. Protoplasmic astrocytes, which do not normally contain CD44, acquire it in pathologies like hypoxia and seizures.

There is significant need for development of a new environmentally friendly, extraction-free sample collection medium that can effectively preserve and protect genetic material for point-of-care, and/or self-collection, home-collection, and mail-back testing. Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was used to create anti-ribonuclease (RNase) Deoxyribonucleic acid (DNA) aptamers against purified RNase A conjugated to paramagnetic carboxylated beads. Following 8 rounds of SELEX carried out under various stringency conditions, e.g., selection using Xtract-Free™ (XF) specimen collection medium, and elevated ambient temperature of 28 ºC, a panel of 5 aptamers was chosen following bioinformatic analysis using next-generation sequencing. The efficacy of aptamer inactivation of RNase was assessed by monitoring Ribonucleic acid (RNA) integrity by fluorometric and real-time RT-PCR analysis. Inclusion of aptamers in reaction incubations resulted in an 8,800 to 11,200-fold reduction of RNase activity, i.e., digestion of viral RNA compared to control. Thus, anti-RNase aptamers integrated into XF collection medium as well as other commercial reagents and kits have great potential for ensuring quality intact RNA for subsequent genomic analysis.

Milk is a complex liquid, and the concentrations of many of its components are under genetic control. Many genes and pathways are known to regulate milk compositon, and the purpose of this review is to highlight how the discoveries of quantitative trait loci (QTL) for milk phenotypes can elucidate these pathways. The main body of this review focusses primarily on QTL discovered in cattle (Bos taurus) as a model species for lactation biology, with occasional references to other ruminant species, and some comparisons with human milk composition are also presented. The following section describes a range of techniques that can be used to help identify the causative genes underlying QTL when the underlying mechanism involves the regulation of gene expression. As genotype and phenotype data bases continue to grow and diversify, new QTL will continue to be discovered, and, although proving the causality of underlying genes and variants remains difficult, these new data sets will further enhance our understanding of lactation biology.

Abstract: This article provides a brief review of the ontogeny of chondrocytes and the pathophysiology of osteoarthritis (OA), and details how physical exercise improves the health of osteoarthritic joints and enhances the potential of mesenchymal stem cells for successful transplantation therapy. In response to exercise chondrocytes increase their production of glycosaminoglycans, bone morphogenic proteins and antiinflammatory cytokines and decrease their production of proinflammatory cytokines and matrix degrading metalloproteinases. These changes are associated with improvements in cartilage organization and reductions in cartilage degeneration. Studies in humans indicate that exercise increases peripheral blood recruitment of bone marrow-derived mesenchymal stem cells (BM-MSC) and upregulates BM-MSC expression of osteogenic and chondrogenic genes, osteogenic micro-RNAs, and osteogenic growth factors. Rodent experiments are uniform in demonstrating that exercise enhances the osteogenic potential of BM-MSC while diminishing their adipogenic potential, and that exercise done after stem cell implantation may benefit stem cell transplant viability. Physical exercise also exerts a beneficial effect on the skeletal system by decreasing immune cell production of osteoclastogenic cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and interferon (INF)-γ while increasing their production anti-osteoclastogenic cytokines IL-10 and transforming growth factor (TGF)-β. In conclusion, physical exercise done both by stem cell donors and recipients may improve the outcome of mesenchymal stem cell transplantation.

We review and assess the classic SIR and SEIR epidemiological models regarding possible applications to the COVID-19 pandemic. In spite of numerous more complicated models, we show how the qualitative features of the solution to the SIR and SEIR models continue to provide valuable public health insights in some scenarios. Using estimated COVID-19 data as of this date, the SEIR model shows that if it were possible to reduce R₀ from 2.5 to 1.25 through social distancing and other measures, the maximum fraction of the population that would become infected at any particular time would drop from 17% to 4%, provided that all of the model assumptions are satisfied. Finally, we compare the classic SIR model with a recent stochastic model with favorable results. Since this comparison underscores the importance of underlying connectivity assumptions, we conclude with Monte-Carlo simulations with specific connectivity that reproduce the classical SIR model with standard incidence.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

The purpose of this work is to study the mechanism of running-in during the friction and to determine the informative parameters characterizing the degree of its completion. During the friction, contact interaction of rough surfaces causes various wave phenomena covering a wide range of frequencies, the subsequent frequency analysis can provide information about the sizes of wave sources and thereby clarify the mechanism of interaction between surface roughness. The using of the wavelet transform for processing of the signals of audible acoustic emission made it possible to determine the beginning and the end of the change in the frequency ranges of the interaction of roughness. The code developed by the authors was used to analyze the acoustic emission signals by using wavelet energy and entropy criteria. The mother wavelet was chosen by carefully evaluating the effectiveness of 54 preliminary candidates for the mother wavelet from 7 wavelet families, ac-cording to three criteria: 1) maximum wavelet energy; 2) Shannon entropy minimum; 3) maximum energy-to-Shannon entropy ratio.

This study examined the relationship between financial sector liberalization and agricultural sector output in Nigeria using annual data spanning the period 1986-2020. Specifically, the objectives of the study are to examine the relationship between lending rate, exchange rate, commercial bank credit to agriculture, inflation rate and agricultural sector output in Nigeria. Ex-post facto research design was employed and the annual time series data were collated from Central Bank of Nigeria (CBN) Statistical Bulletin. The econometrics methods of unit root, co-integration and error correction mechanism were used for the analyses. The outcome of the ADF unit root test show that the variables were stationary. Also the co-integration result showed that there exist co-integration amongst the variables in the model. The results from Error Correction Model indicates that lending rate and inflation rate have a negative relationship on agricultural sector output while exchange rate and commercial bank credit to agriculture have positive relationship on agricultural sector output. Based on these results, this study recommends that government and policy makers in Nigerian should initial policies that will boost investments in the agricultural sector through direct provision of credits to agriculturist and banks should also lend at a very low and subsidized interest rate to enable farmers’ access agricultural loans that will boost agricultural productivity in the economy.

Transposable elements (TEs) are repetitive elements which make up around 45% of the human genome. A class of TEs known as SINE-VNTR-Alu (SVA) demonstrate the capacity to mobilise throughout the genome, resulting in SVA polymorphisms for presence or absence within the population. Although studies have previously highlighted the involvement of TEs within neurodegenerative diseases, such as Parkinson’s disease and amyotrophic lateral sclerosis (ALS), however the exact mechanism has yet to be identified. In this study we used whole genome sequencing and RNA sequencing data of ALS patients and healthy controls from the New York Genome Center ALS Consortium, to elucidate the influence of reference SVA elements on gene expression genome-wide within central nervous system (CNS) tissues. To investigate this, we applied matrix expression quantitative trait loci analysis and demonstrated that reference SVA insertion polymorphisms can significantly modulate the expression of numerous genes, preferentially in the trans position, and in a tissue-specific manner. We also highlight that SVAs significantly regulate mitochondrial genes as well as genes within the HLA and MAPT loci, previously associated within neurodegenerative disease. In conclusion, this study continues to bring to light the effects of polymorphic SVAs on gene regulation and further highlights the importance of TEs within disease pathology.

The standard of care for nonoperative appendicitis patients involves ongoing antibiotic therapy. Yet, there is variability regarding the decision to continue outpatient parenteral antibiotic treatment (OPAT) or transition to oral (PO) antibiotics. Methods: In our single-center retrospective study, we reviewed 46 pediatric patients who underwent nonoperative management of perforated appendicitis with Interventional Radiology (IR) percutaneous drainage. We reviewed age, ethnicity, hospitalization length, antibiotic choice, route and duration, and culture data. Results. Thirty-eight [83%] patients went home on OPAT, 6[13%] on PO, and 2[4%] completed therapy while inpatient. Based on culture susceptibilities of the 38 OPAT patients, 29[76%] had oral antibiotics as an option. The three most common organisms in those sent home on OPAT included Enterococcus faecalis (38 [100%]), Bacteroides spp (33 [87%]) and Escherichia coli (27 [71%]). All patients who grew Pseudomonas aeruginosa had an oral antibiotic as a treatment option; similarly with 93% (25/27) of E. coli, 81% (13/16) of α-hemolytic Streptococcus spp, and 76% (29/38) of Enterococcus faecalis.  Conclusions:  Nearly 80% of patients sent home on OPAT had PO antibiotic regimens options based on the culture susceptibility profiles. This data indicates that using cultures and susceptibility data can help guide antibiotic management, significantly reducing PICC line placement and likely reduce healthcare costs and complications associated with central lines.

Decision tables have been used for many years in data processing and business applications to simulate complex rule sets. Several computer languages have been developed based on rule systems and they are easily programmed in several current languages. Land management and river-reservoir models simulate complex land management operations and reservoir management in highly regulated river systems. Decision tables are a precise yet compact way to model the rule sets and corresponding actions found in these models. In this study, we discuss the suitability of decision tables to simulate management in the river basin scale Soil and Water Assessment Tool (SWAT+) model. Decision tables are developed to simulate automated irrigation and reservoir releases. A simple auto irrigation application of decision tables was developed using plant water stress as a condition for irrigating corn in Texas. Sensitivity of the water stress trigger and irrigation application amounts were shown on soil moisture and corn yields. In addition, the Grapevine Reservoir near Dallas, Texas was used to illustrate the use of decision tables to simulate reservoir releases. The releases were conditioned on reservoir volumes and flood season. The release rules as implemented by the decision table realistically simulated flood releases as evidenced by a daily NSE (Nash-Sutcliffe Efficiency) of 0.52 and a percent bias of -1.1%. Using decision tables to simulate management in land, river and reservoir models was shown to have several advantages over current approaches including: 1) mature technology with considerable literature and applications, 2) ability to accurately represent complex, real world decision making, 3) code that is efficient, modular and easy to maintain, and 4) tables that are easy to maintain, support, and modify.

A strong correlation between karyotype diversity and species richness in mammals was first reported over forty years ago: in mammalian phylogenetic clades, standard deviation of karyotype diversity (KD) closely corresponds to the standard deviation of species richness (SR). These initial studies, however, did not control for phylogenetic signal, raising the possibility that the correlation was due to phylogenetic relatedness among species in a clade. Accordingly, karyotype diversity trivially reflects species diversity simply as a passive consequence of adaptive radiations. A more recent study in mammals has controlled for phylogenetic signal and established the correlation as phylogenetically independent, suggesting that species diversity cannot, in itself, explain the observed corresponding karyotype diversity. The correlation is therefore remarkable because the mechanisms contributing to karyotype diversity are evolutionarily independent of the mechanisms contributing to species diversity. Recently, it was shown in salamanders that the two processes generating genetic diversity and species diversity are indeed independent and operate in parallel, suggesting a potential non-adaptive and non-causal relationship between the two fundamental variables involved in adaptive radiations. The following will examine the relationship between KD and SR in the context of Motoo Kimura’s theory of non-adaptive radiation.

During the last twenty years around the world there has been a rapid increase in the number of people visiting long established religious shrines as well as the creation of new sites by those operating outside the boundaries of institutional religion. This increase is intimately associated with the revival of traditional routes, the creation of new ones and the invention of new rituals (religious, spiritual and secular). To examine this process I will focus on the European region and two contrasting destinations in particular – the Catholic shrine of Lourdes, France, and the pre-Christian shrine of Avebury, England – drawing on my personal involvement in travelling to both destinations and being involved in ritual activities along the route and at the two destinations. In the discussion section of the paper I will explore the relevance of these two case studies to the analysis of power, agency and performance and the ways in which they expose (a) the role of institutions and entrepreneurs in creating rituals and sacred places and (b) the relationship between people and the domesticated landscape.

Abstract: Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation within hepatocytes, but the relative contributions of different macronutrients is still unclear. We inves-tigated the impact of fatty acids, glucose and fructose on lipid accumulation in primary human hepatocytes (PHH) and three different hepatoma cell lines: HepG2, Huh7 and McA-RH7777 (McA). Cells were treated for 48 hours with fatty acids (0 or 200μM), glucose (5mM or 11mM) and fructose (0mM, 2mM or 8mM). Lipid accumulation was measured via Nile Red staining. All cell types accumulated lipid in response to fatty acids (P<0.001). PHH and McA, but not HepG2 or Huh7 cells, accumulated more lipid with 11mM glucose plus fatty acids (P=0.004, fatty acid x glucose interaction, for both), but only PHH increased lipid accumulation in response to fructose (P<0.001). Considerable variation was observed between PHH cells from different individuals. Lipid accumulation in PHH was increased by insulin (P=0.003) with inter-individual variability. Similarly, insulin increased lipid accumulation in both HepG2 and McA cells, with a bigger response in McA in the presence of fatty acids (P<0.001 for fatty acid x insulin). McA were more insulin sensitive than either HepG2 or Huh7 cells in terms of AKT phosphorylation (P<0.001 insulin x cell type interaction). Hence glucose and fructose can contribute to the accumulation of lipid in PHH with considerable inter-individual variation, but hepatoma cell lines are not good models of PHH.

A half-harmonic oscillator, which gets its name because the coordinate is strictly positive, has been quantized and determined that it was a physically correct quantization. This positive result was found using affine quantization (AQ). The main purpose of this paper is to compare results of this new quantization procedure with those of canonical quantization (CQ). Using Ashtekar-like classical variables and CQ, we quantize the same toy model. While these two quantizations lead to different results, they both would reduce to the same classical Hamiltonian if $\hbar\rightarrow0$. Since these two quantizations have differing results, only one of the quantizations can be physically correct. Two brief sections illustrate how AQ can correctly help quantum gravity and the quantization of most field theory problems.

Dispersion tests based on the second order component of smooth test statistics are related to Fisher’s Index of Dispersion test, used for testing for the Poisson distribution when there are no covariates present. Such tests have been recommended in [1] to test for the Poisson distribution when covariates are present. The modified Borel-Tanner (MBT) distribution seems suited to data with extra zeroes, a monotonic decline in counts and longer tails. Here we recommend a dispersion test for the MBT distribution for both when covariates are absent and when they are present.

Loneliness is becoming prevalent across Japan in spite of its a dense population and communal culture. Surveys show 40% of adults report isolation across demographics. The contradiction emerges due to deteriorating social structure with modernization, economic parity, urbanization, and fading conventional setup. The continually social withdrawals, called “hikikomori." Relief seekers have embraced AI based emotive robots, digital avatars, and immersive VR as low-stakes social surrogates despite limited capacity to cultivate human intimacy. To stabilise government attempts awareness through reforms, scheme and support services. But a concrete transformation can be brough in with work-life balance, gender equality and rewire the metrics for self-esteem. Even a perfectly personalized AI cannot replace the human affection lacking in the society. Lasting solutions demand technological aids be balanced by confronting and reinventing community purpose and bring in structural change. Overall Japan’s endemic isolation reveals the societal fraying when modernization privileges independence over interdependence. The path forward rests on restoring cultural foundations to reverse loneliness and social isolation.

Climate change, biodiversity loss, and other social and environmental problems pose grave risks. Progress so far has been incremental and insufficient, and as a result scientists, global policy experts, and the general public increasingly conclude that bold change is required across all sectors of society. At least two kinds of bold change are conceivable: reform of existing societal systems (e.g., financial, economic, legal, and governance systems), including their institutions, policies, rules, and priorities; and transformation, understood as the de novo development of and migration to new, improved systems. This paper is the second in a series of three that together propose a novel science-driven research and development program aimed at societal transformation. Moreover, the series advances a conceptual framework and formal mechanics by which societal transformation might be approached. Two of the underlying hypotheses are that new societal systems can be developed in a science-driven process to be fit for purpose, and system fitness can be compared across designs. Societies are viewed as superorganisms, and systems are viewed as a societal cognitive architecture. The first paper in the series provides definitions, aims, hypotheses, and a worldview. This paper discusses motivations, the role of science in societal transformation, a theory of change, and fitness metrics. The proposed R&amp;D program and theory of change are sound, viable, and affordable. The local-global-viral strategy invites the global science community to play a unique co-leadership role with local communities in the development, testing, and monitoring of new societal systems. Systems are implemented via a novel civic club model, where participation is voluntary. Clubs grow and replicate based on merit and aided by club networks, whose systems are also viewed as societal cognitive architectures. Benefits of the program and strategy are discussed.

Astronauts at are risk of losing 1.0 – 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs designed to preserve the musculoskeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth facor-1 and its receptor IGFR1 play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, and sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.

There is a long trail of research studies testing the in vitro and in vivo efficacy of chloroquine and its derivatives in treating and preventing infection by various coronavirus species. More recent findings have highlighted the possibility of treating patients infected with the 2019 novel coronavirus, SARS-CoV-2. This review describes the mechanism of coronavirus infection, the mechanism of action of chloroquine, and summarizes the available literature highlighting the efficacy of chloroquine as an anti-coronavirus agent. These findings should encourage the wider scientific community to conduct thorough research on the possible efficacy of chloroquine and its derivatives in treating and preventing SARS-CoV-2 infection.

Conventional monitoring relies on "in vivo" (non-destructive) measurements of aboveground organ traits (such as stems, branches, and leaves) to analyze plantation growth trends and assess the effectiveness of management practices like watering and fertilization. This study reveals the necessity of “ex vivo” (destructive) approaches, post-excavation, to ensure fully reliable monitoring of plantation performance, including belowground organ growth and development trends. We showcase the effectiveness of dendrometric analysis, which measures the annual ring width in the secondary xylem (wood) of the taproot and stem. Monitoring above- and belowground organ growth trends allow for the exploration of similarities and differences in how different tree organs respond to internal and external factors. Such monitoring is especially crucial for assessing plantation performance in challenging climates, such as those found in arid and semi-arid lands.

Climate change and over-exploitation are imposing unprecedented threats to the groundwater resource. Globally, groundwater reserves have depleted to the extent that well yield have decreased, pumping cost have risen, and land have irreversibly subsided. In Malawi, groundwater quantity is a national problem, specifically in Mzimba district due to severe droughts. In this study, the spatial and temporal trends of groundwater depletion was assessed using Gravity Recovery and Climate Experiment (GRACE) data and Land Surface Models (LSM) from Global Land Data Assimilation System (GLDAS) and Global Surface Water Explorer (GSWE). The results show that 1. Groundwater storage is depleting at an average rate of-1.0 ± 0.06 cm yr-1(0.1043 km3yr-1) in the study area with high rate of up to -1.2 cm yr-1(0.12516 km3 yr-1) in the western side and as low as –0.4 cm yr-1(0.04172 km3 yr-1) in the eastern part. 2. Groundwater storage increases from -13 cm in November up to 15 cm between May and April. 3. Drought is the primary cause of such depletion trends with correlation between active evapotranspiration and groundwater depletion, and downward surface shortwave radiation and groundwater depletion, at -0.577 and -0.678 respectively. The results from the study reveals the need for the scientific community and the general public to consider groundwater recharge strategies specifically by mitigating climate change to reduce prolonged droughts. The study suggests the need to establish a stand-alone groundwater assessment and monitoring authority for enhanced conservation efforts of the water resource in the country.

Space-borne Synthetic Aperture Radar (SAR) Interferometry (InSAR) is now a key geophysical tool for surface deformation studies. The European Commission’s Sentinel-1 Constellation began acquiring data systematically in late 2014. The data, which are free and open access, have global coverage at moderate resolution with a 6 or 12-day revisit, enabling researchers to investigate large-scale surface deformation systematically through time. However, full exploitation of the potential of Sentinel-1 requires specific processing approaches as well as the efficient use of modern computing and data storage facilities. Here we present LiCSAR, an operational system built for large-scale interferometric processing of Sentinel-1 data. LiCSAR is designed to automatically produce geocoded wrapped and unwrapped interferograms and coherence estimates, for large regions, at 0.001° resolution (WGS-84 system). The products are continuously updated in a frequency depending on prioritised regions (monthly, weekly or live update strategy). The products are open and freely accessible and downloadable through an online portal. We describe the algorithms, processing, and storage solutions implemented in LiCSAR, and show several case studies that use LiCSAR products to measure tectonic and volcanic deformation. We aim to accelerate the uptake of InSAR data by researchers as well as non-expert users by mass producing interferograms and derived products.

Fermented foods and ingredients, including fermentates derived from lactic acid bacteria (LAB) in dairy products, can modulate the immune system. Here we describe the use of reconstituted skimmed milk powder to generate novel fermentates from Lactobacillus helveticus strains SC232, SC234, SC212, and SC210, and from Lacticaseibacillus casei strains SC209 and SC229, and demonstrate using in vitro assays that these fermentates can differentially modulate cytokine secretion by bone marrow derived dendritic cells (BMDCs) when activated with either the viral ligand, loxoribine, or an inflammatory stimulus, lipopolysaccharide. Specifically, we demonstrate that SC232 and SC234 increase cytokines IL-6, TNF-α, IL-12p40, IL-23, IL-27 and IL-10, and decreased IL-1β in primary bone marrow derived dendritic cell (BMDCs) stimulated with a viral ligand. In contrast exposure of these cells to SC212 and SC210 resulted in increased IL-10, IL-1β, IL-23, and decreased IL-12p40 following activation of the cells with the inflammatory stimulus LPS. Interestingly SC209 and SC229 had little or no effect on cytokine secretion by BMDCs. Overall, our data demonstrates that these novel fermentates have specific effects and can differentially enhance key immune mechanisms that are critical to viral immune responses, or can suppress responses involved in chronic inflammatory conditions, such as Ulcerative Colitis (UC), and Crohn’s disease (CD).

It has been well known for a long time that inert gases, such as xenon (Xe), have significant biological effects. As these atoms are extremely unlikely to partake in direct chemical reactions with bio-molecules, such as proteins, lipids and nucleic acids, there must be some other mode of action to account for the effects reported. It has been shown that the topology of proteins allows for cavities and hydrophobic pockets, and it is through an interaction with such protein structures that inert gases are thought to have their action. Recently, it has been mooted that the relatively inert gas molecular hydrogen (H2), also may have its effects through such a mechanism, and so influencing protein structures and actions. H2 is thought to also act through interaction with redox active compounds, particularly the hydroxyl radical (·OH) and peroxynitrite (ONOO-), but not nitric oxide (NO·), superoxide anions (O2·-) or hydrogen peroxide (H2O2). However, instead of having a direct interaction with H2, is there any evidence that these redox compounds can also interact with Xe pockets and cavities in proteins, so either having an independent effect on proteins or interfering with the action of inert gases. This suggestion with be explored here.

This paper surveys estimates of the transmission features of the novel coronavirus, and then proposes a model to address sample-selection bias in estimated determinants of infection. Containment assumptions of the infection forecasting models depend on assumed effects of policies and self-regulating behavior. In the commons dilemma of the pandemic, the perceived ‘low risks’ of unregulated marginal choices do not reflect the full social cost, implying non-pharmaceutical interventions (NPI) to reduce mortality can enhance social welfare. As more economic activity renews with liftings of restrictive NPI (RNPI), a critical question concerns the ability of milder NPI (MNPI) and voluntary precautions to mitigate the risk of greater infections and deaths while also limiting the pandemic’s economic damage and its social costs. Ineffective NPI could lead to continued COVID-19 waves and new types of crises, worsened expectations and delayed economic recoveries. From the central range of surveyed estimates of transmission and alternative herd-immunity-threshold estimates, a ‘worst-case’ virus guidepost suggests eventual deaths of around 25 to 41 million worldwide and 1.1 to 1.7 million in the U.S. needed to reach herd immunity with no vaccine or treatment. The most optimistic study surveyed (theoretical model from a non-reviewed preprint study) combined with the low end of the range of the estimated mortality rate suggests 6 to 9 million deaths worldwide and 250 to 370 thousand in the U.S. to reach herd immunity. Successes in the mix of NPI, treatments, and vaccine can limit the eventual global death toll of the virus. Improved estimation models for forecasting and decision making may assist in better targeting the local timings and mix of NPI. Diagnostic tests for the virus have been largely limited to symptomatic cases, causing possible sample selection bias. A recursive bivariate probit model of infection and testing is proposed along with several possible applications from cross-section or panel-data estimation. Multiple potential explanatory variables, data sources, and estimation needs are specified and discussed.