Ion channels contribute fundamental properties to all cell membranes. The ion channels are highly diverse in conductivity, structure, location and function. However, many of them can be regulated by common mechanisms, such as voltage or (de-)phosphorylation. Considering primarily pain-related ion channels, this review covers more novel and less known features of ion channel function, also with the aim to transfer knowledge between fields, which get inevitably more separate due to their size.

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (K_d), can be considered as one of the most important characteristics for any antibody-antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC₅₀ approaches the K_d value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to K_d. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols.

A comprehensive kinetic model of the Fischer-Tropsch synthesis (FTS) is developed in a fixed bed reactor under operating conditions (temperature, 230–235°C, pressure, 20–25 bar, gas hourly space velocity, 4000–5000 cm³(STP)/h/g_catalyst ,H₂/CO feed molar ratio, 2.1) over a Co based catalyst. Reaction rate equations based on Eley-Rideal (ER) type model for initiation step and Langmuir-Hinshelwood-Hougen-Watson (LHHW) type model for propagation and termination steps of the FTS reactions have been considered and the readsorption of olefins were taken into account. The model that was reported in the literature was modified in order to explain many significant deviations from the ASF distribution. Optimum parameters have been obtained by Genetic Algorithms (GA). The calculated activation energies to produce n-paraffins and 1-olefins were in the range of 82.24 to 90.68 kJ/mol and 100.66 to 105.24 kJ/mol, respectively. The hydrocarbon distribution in FTS reactions was satisfactorily predicted particularly for paraffins.

From the formalism of the thermodynamics of irreversible processes and the theory of complex systems, characterization of longevity and aging and its relationship with the emergence and evolution of cancer was carried out. It was found that: 1. The rate of entropy production can be used as an index of robustness, plasticity, the aggressiveness of cancer, and as a measure of biological age; 2. The aging process, as well as the evolution of cancer, goes through what we have called “biological phase transition”; 3. The process of metastasis, which occurs through epithelial-mesenchymal transition (EMT), appears as a phase transition far from thermodynamic equilibrium and exhibits Shilnikov chaos-like dynamic behavior. This dynamic guarantees the robustness of the process and, in turn, its unpredictability; 4. It was shown that as the ferroptosis process is strengthened, the complexity of the dynamics associated with the emergence and evolution of cancer decreases. The theoretical framework developed contributes to a better understanding of the biophysical-chemical phenomena of longevity and aging and their relationship with cancer.

Surface treatments of metals based on laser marking technology is an important application in a wide range of industrial fields. By specific combinations of laser processing parameters, the modified surface leads to different textures with specific roughness and colored appearance. Most of current works are focused on the modification of color tonality of flat surfaces, or the development of specific topography features, but the combination of both processes is not usually evaluated, mainly due to the complexity to control the optical properties on rough surfaces. This research presents an analysis of the influence of the micro-geometrical characteristics of periodic patterned laser tracks on the chromaticity and reflectance of Ti6Al4V substrates. The samples were irradiated with an infrared nanosecond pulsed laser under air atmosphere, taking as control parameter the scan speed of the beam. A roughness evaluation, microscopic inspection, absorption and chromaticity examination were conducted. Although micro-crack growth was detected in isolated case (10 mm/s), the possibility of adjusting the result color were demonstrated by controlling the thermal affected zone thickness of the textures. Results of rough/colored combined textures allow opening new perspectives in industrial design, particularly in aesthetic applications with special properties.

Cellular membranes are essential for compartmentalization, maintenance of membrane permeability and fluidity in all three domains of life. Archaea belong to the third domain of life and have a distinct phospholipid composition. Membrane lipids of archaea are ether-linked molecules, specifically dialkyl glycerol diethers (DGDs) and glycerol dialkyl glycerol tetraethers (GDGTs). Terbinafine has been proposed as an inhibitor of GDGT biosynthesis in Archaea based on radiolabel incorporation studies. Here, we have studied the early cellular responses of the archaeon Sulfolobus acidocaldarius to terbinafine whose membrane is mostly composed of the membrane-spanning GDGTs. Depletion of GDGTs and an accompanying accumulation of DGDs upon treatment with terbinafine was growth phase and dose dependent. Additionally, a major shift in the saturation of caldariellaquinones was observed, resulting in the accumulation of unsaturated molecules. Transcriptomic data indicated that terbinafine primarily targets the respiratory complex along with genes involved in motility, fatty acid metabolism and GDGT cyclization. Combined, these findings suggest that respiratory stress is the preliminary response of S.acidocaldarius to terbinafine while targeting multiple proteins involved in isoprenoid biosynthesis and saturation.

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.

In this paper, we relate Poisson’s summation formula to Heisenberg’s uncertainty principle. They both express Fourier dualities within the space of tempered distributions and these dualities are furthermore the inverses of one another. While Poisson’s summation formula expresses a duality between discretization and periodization, Heisenberg’s uncertainty principle expresses a duality between regularization and localization. We define regularization and localization on generalized functions and show that the Fourier transform of regular functions are local functions and, vice versa, the Fourier transform of local functions are regular functions.

With an increase in energy consumption globally, Fischer-Tropsch (FT) synthesis is a good alternative for producing fuels and chemicals from coal, natural gas or biomass. Among them, coal to liquids has been put into production in countries that have large coal reserves. In this process, Fe-based catalysts are commonly used due to their earth abundance, comparatively wide operation range and ready availability to handle low H2/CO ratio from coal. Despite their extensive applications, the kinetic and mechanistic understandings of Fe carburization and FT reaction on Fe-carbides are relatively limited due to the complexity of phase composition of the applied catalysts. This review summarizes the current state of knowledge of FT synthesis on Fe-carbide with an emphasis on underlying mechanism. Specifically, the employment of model catalyst, such as Raney-Fe, could provide a convenient way to furnish kinetic information regarding Fe carburization and subsequent FT reaction. A major challenge for further understanding catalytic reactions occurring at the Fe-carbide surface is correlating FT activity and selectivity to specific active site. To address this issue, the advancements of both DFT calculations and surface science techniques are highly demanded.

An overview of the link between nonequilibrium thermodynamics and complexity theory is offered. It is shown how the rate of entropy production can be quantified through the spectrum of the Lyapunov exponents. It was shown how the entropy production per unit of time meets the necessary and sufficient conditions to be a Lyapunov function and constitutes per se an extremal principle. The entropy production fractal dimension conjecture was established. It is shown how the rate of entropy production as a non-extremal criterion represents an alternative way of sensitivity analysis of differential equations. Finally, an extension to biophysical-chemical systems, on the one hand, the use of the dissipation function is shown, as a thermodynamic potential out of equilibrium, in the characterization of biological phase transitions. On the other hand, it was evidenced how the rate of entropy production represents a physical quantity to evaluate the complexity and robustness of cancer.

Synthetic fuels play an important role in the defossilization of future aviation transport. To reduce the ecological impact of remote airports due to long range transportation of kerosene, a decentralized on-site-production of synthetic paraffinic kerosene is applicable, preferably as near-drop-in fuel or alternatively as blend. One possible solution for such a production of synthetic kerosene is the Power-to-Liquid process. The basic development of a simplified plant layout addressing the specific challenges of a decentralized kerosene production which differ from most current approaches for infrastructural well-connected regions is described. The decisive influence of the Fischer-Tropsch synthesis on the PtL process is shown by means of a steady-state reactor model which was developed in Python and serves as basis for further development of a modular environment able to represent entire process chains. The reactor model is based on reaction kinetics according current literature. The effects of adjustments of the main operation parameters on the reactor behavior are evaluated and the impacts on up- and downstream processes are described. The results prove the governing influence of the Fischer-Tropsch reactor on the PtL process and show its flexibility regarding the desired product fraction output, which makes it an appropriate solution for a decentralized kerosene production.

One important goal of research on heterogeneous catalysis for Fischer Tropsch synthesis (FTS) is to understand the connection linking catalyst morphology and its activity. Development of these effective catalysts highlights the potential for understanding the effectiveness of promoted supported catalysts and revealing their complex and dynamic effects in FTS. The metal-support interaction (MSI) is influenced by the physicochemical and textural features provided by the modified support and can directly influence the sizes of active metal crystallites, reactants and/or products mass transfer, dispersion, mechanical strength, stability and consequently the adsorption-desorption characteristics of the catalyst. Herein, this article explores the general strategies for modifying silica supports (achieved through doping, coating, or promoting the support or support precursor) and how these strategies can be manipulated to further alter catalyst performance and product selectivity by enhancing the amount of active metal species and improving the intrinsic turnover frequency (TOF). Furthermore, the review emphasises a new strategy (the inverse model of the silica support modification) aiming at overcoming the challenges posed by active metal coating or coverage, as well as pore blockages by promoters that occur during conventional preparation of promoted silica supported FT catalysts.

Background: All Payer Claims Databases (APCD) are a rich source of health information, however, race and ethnicity (R&E) data are largely missing. Bayesian Improved Surname Geocoding (BISG) is a common R&E imputation method, yet, validation of BISG in APCDs is lacking. We used the BISG to impute missing R&E in the Oregon APCD. Methods: BISG imputed R&E for Asian Pacific Islanders (API), Blacks, Hispanics and Whites were contrasted to the gold standard (vital statistics) and sensitivity and specificity improvements were assessed. Logistic regression examined whether missing R&E was random across patient characteristics. Results: Among 85,857 individuals in the study, 32.1% (n=27,594) had missing R&E. Missing R&E was not randomly distributed. There were higher odds of missingness among males, Whites, those age 65 and older, and commercially insured individuals. Differences in the percent missing were also found by co-morbid conditions and mortality causes. Imputing the missing R&E with BISG method improved the sensitivity to identify White, Black, API, and Hispanics. Conclusions: APCDs can benefit from enhancing missing R&E with BISG imputation to perform more robust population-health level analyses and identify inequities according to R&E without losing power or dropping non-random records with missing R&E data.

In humans, finely tuned gamma synchronization (60-90 Hz) rapidly appears at movement onset in a motor control network involving primary motor cortex, the basals ganglia and motor thalamus. Yet the functional consequences of brief movement-related synchronization are still unclear. Distinct synchronization phenomena have also been linked to different forms of motor inhibition, including relaxing antagonist muscles, rapid movement interruption and stabilizing network dynamics for sustained contractions. Here I will introduce detailed hypotheses about how intra- and inter-site synchronization could interact with firing rate changes in different parts of the network to enable flexible action control. The here proposed cause-and-effect relationships shine a spotlight on potential key mechanisms of cortico-basal ganglia-thalamo-cortical communication. Confirming or revising these hypotheses will be critical in understanding the neuronal basis of flexible movement initiation, invigoration and inhibition. Ultimately, the study of more complex cognitive phenomena will also become more tractable once we understand the neuronal mechanisms underlying behavioural readouts.

In previous studies we used Laurent Schwartz’ theory of distributions to rigorously introduce discretizations and periodizations on tempered distributions. These results are now used in this study to derive a validity statement for four interlinking formulas. They are variants of Poisson’s Summation Formula and connect four commonly defined Fourier transforms to one another, the integral Fourier transform, the Discrete-Time Fourier Transform (DTFT), the Discrete Fourier Transform (DFT) and the Integral Fourier transform for periodic functions—used to analyze Fourier series. We prove that under certain conditions, these four Fourier transforms become particular cases of the Fourier transform in the tempered distributions sense. We first derive four interlinking formulas from four definitions of the Fourier transform pure symbolically. Then, using our previous results, we specify three conditions for the validity of these formulas in the tempered distributions sense.

In previous studies we found that generalized functions can be smooth, discrete, periodic or discrete periodic and they can either be local or global and they are regular or generalized functions. We also saw that these properties were related to Poisson’s summation formula on one hand and to Heisenberg’s uncertainty principle on the other. In this paper, we interlink these studies and show that scalars (real or complex numbers) considered as trivial functions are discrete and periodic, local and global as well as regular and generalized, simultaneously. However, this is also a paradox because it means that Dirac’s δ and 1 (its Fourier transform) coincide. They both are unity. We show that δ and 1 coincide in the sense of scalars (real or complex numbers) but they differ in the sense of (generalized) functions. This result can moreover be related to Max Born’s principle of reciprocity. It also answers an open question in present-day quantum mechanics because it means that the Dirac delta squared is simply delta.

Understanding African swine fever virus (ASFV) transmission is essential for strategies to minimize virus spread during an outbreak. ASFV can survive for extended time periods in animal products, carcasses, and the environment. While ASFV genome was found in the environment around infected farms, data on the virus survival in soil are scarce. We investigated different soil matrices spiked with ASFV-positive blood from infected wild boar to see if ASFV can remain infectious in the soil beneath infected carcasses. As expected, ASFV genome detection was possible over the entire sampling period. Soil pH, structure, and ambient temperature played a role for the stability of infectious ASFV. Infectious ASFV was demonstrated in specimens originating from sterile sand for at least three weeks, from beach sand for up to two weeks, from yard soil for one week, and from swamp soil for three days. Virus was not recovered from two acidic forest soils. All risk mitigation experiments with citric acid or calcium hydroxide resulted in complete inactivation. In conclusion, stability of infectious ASFV is very low in acidic forest soils but rather high in sandy soils. However, given the high variability, treatment of carcass collection points with disinfectants should be considered.

Targeted cancer therapy has grown exponentially in the last decade, representing the largest frontier in the modern concept of precision medicine. This renaissance is largely due to our rapidly evolving ability to biochemically harness our immune systems to target cancer-specific antigens. Combined with an increasing armamentarium of surgical and non-invasive techniques for cancer mitigation we have upgraded cancer therapy from a non-specific assault on cell-division to a multi-modal, targeted approach. This renaissance has resulted in an increase in the perioperative footprint of patients with advanced cancer. The scope of the perioperative clinician has evolved from one of passive/reactive management of complications to a proactive approach that starts in the preoperative optimization phase and continues into the postoperative period. The perioperative world should not exist in a silo, and thus involvement of the oncology team is paramount. To provide safe oncologic care, it is essential to be up to date in newer cancer therapies, lest we act on erroneous and/or outdated information. Oncologists should weigh in on immune status, recent chemotherapeutic exposures, and potentially evolving toxicities. These might involve critical changes to perioperative infectious prophylaxis, steroid administration, and coagulopathy management. First, patients living beyond the typical life-expectancy for their cancer will carry a high burden of cancer-related downstream effects. General metabolic issues will include malnutrition, cachexia, and gastric outlet obstruction. Severe protein-calorie malnutrition, as well as hepatic and renal dysfunction can impact the metabolism and clearance of drugs. The cardiovascular, endocrinologic, pulmonary, and central nervous system implications of new cancer therapies will be discussed extensively below. Second, we have to enhance our ability to manage a cancer population who may be experiencing increasing novel chemotherapeutic toxicities. Newer agents differ from historical agents, which were blunt-force tools aimed at nonspecific destruction of cell-division. These drugs are efficacious but physiologically costly. Newer immunogenic therapies have a slightly improved acute safety profile, and a more complex chronic toxicity profile that may be overt or insidious. Chronic toxicities can present overtly or as a smoldering undertone to other active medical conditions such as sepsis, pneumonia, failure to thrive, or renal failure. The new therapies discussed in this review occur in the context of an overall increasingly multi-faceted cancer care machine. An example is screening for esophageal cancer in patients with Barrett's esophagus, or periodic chest CTs for patients with a strong history of tobacco use. These interventions are more likely to detect disease while it is still resectable, and resections will commonly accompany neo-adjuvant therapy. These approaches commonly involve new immunotherapies whose efficacy is higher-yield with a lower disease burden. In a recent example, the immune-checkpoint inhibitors (ICIs) ipilimumab plus nivolumab have significantly increased survival rate for squamous cell esophageal cancer when combined with standard chemotherapy. Surgical resection has evolved to one that often accompanies neoadjuvant chemo and radiation. The increasing efficacy of this approach may de-necessitate many major resections, and increase the number of sub-anatomic resections and minimally invasive procedures. Improved techniques - notably for hepatectomy, whipple procedure, prostatectomy, nephrectomy - have increased the safety profile and decreased the perioperative physiologic burden. This has enabled a broader subset of patients (due to cancer burden or due to medical comorbidities) to qualify for the operation, and increased the involvement of anesthesia and their perioperative services. With an increase in surgical candidacy comes an increase in post-surgical complications, and post-surgical maintenance such as drains, embolizations, imaging studies, etc. In the non-OR anesthesia realm, there have been considerable advancements in cancer “micro-treatments” such as hepatic metastasis embolization, tumor ablation, and peri-tumor vascular embolization. There are an ever-increasing number of IR-guided embolizations for bleeding tumors, aspiration of malignant effusions, and drainage of abscesses. This review serves to provide insight into new categories of chemotherapy and their perioperative implications.

Keywords: keyword 1; keyword 2; keyword 3 (List three to ten pertinent keywords specific to the article yet reasonably common within the subject discipline.)

The recent outbreak of Coronavirus Disease 2019 (COVID-19) is a major threat to human health and the global economy. In addition to the development of vaccines there is an urgent need for preventive and therapeutic strategies towards severe COVID-19. Key to this would be a better understanding of the molecular mechanismsoiuuuu affected by SARS-COV-2. To address this, we performed a systems biology approach by integrating available RNA-seq datasets from post-mortem lung tissue of COVID-19 patients and cell culture models infected with SARS-COV-2, Respiratory Syncytial virus or influenza virus. We identified two gene-expression modules that are commonly regulated by the three viral diseases and one that is specific to COVID-19. All 3 gene-expression modules represent key inflammatory processes. We identified several proteins within these networks that can be targeted by FDA approved drugs. Key examples are TNF, NFkB, INTERLEUKIN-1 and ALOX5 signaling pathways. Our data also suggest that Vitamin D supplementation and a ketogenic diet should be further analyzed as preventive strategies. In conclusion, our data highlights the potential of transcriptomics to unravel the pathological processes related to COVID-19 and guide the initiation of clinical trials.

Objective: CAD/CAM generated ceramic implant abutments have recently attracted interest due to their superior customization possibilities and aesthetic advantages. Despite their widespread clinical use, little information is currently available on their surface topography, however. The transmucosal portion of the abutment shoulder is of particular interest, as it ideally supports soft tissue but minimizes mechanical plaque retention. The aim of this in vitro study was to topographically characterize the trans- and subgingival roughness of CAD/CAM zirconia abutments from different manufacturers and compare them with zirconia stock abutments. Material and Method: The surface topography of eight CAD/CAM zirconia implant abutments (tests) and two prefabricated zirconia stock abutments (controls) was determined using focus variation microscopy. Two points on the abutment shoulder were subjected to profilometric examination. 2D and 3D parameters of roughness were obtained and compared. Results: The surface roughness of all the test abutments exceeded the recommended threshold of Ra = 0.2 µm and therefore exhibited an increased risk of mechanical plaque retention. Obvious differences in surface structure were apparent, allowing conclusions to be drawn about the manufacturing method and subsequent reworking processes. Conclusion: Manually reworking the trans- and submucosal area of the investigated CAD/CAM zirconia abutments appears necessary to fulfil the conditions for optimal surface topography. The Sa value as arithmetic mean, taking the maximum height (Sz value) and surface excess (Sdr) into account, is an essential parameter for assessing the surface topography of implant abutments.

This is a study on fractals existing in music. The application case is the composition DIAPHONIES of Michael Paouris. Sliding-window fractal analysis indicate areas of continuous fractality dipped in non-fractal areas of possibly deterministic and stochastic nature. Diverging cases of pronounced non-fractal areas are addressed and also areas of mixed fractality and non-fractality. Many segments exhibit persistency-P (2

The emergence of cloud computing, big data analytics, and machine learning has catalysed the use of remote sensing technologies to enable more timely land management of sustainability indicators such as ground cover and grassland biomass, given the uncertainty of future climate and drought conditions. Here, we examine the potential of “regenerative agriculture”, as an adaptive grazing management strategy to minimise bare ground exposure while maximising pasture biomass productivity. High-intensity sheep grazing treatments were conducted in small fields (less than 1 hectare) for short durations (typically less than 1 day). Paddocks were subsequently spelled to allow pasture biomass recovery (treatments comprising 3, 6, 9, 12, and 15 months) with each compared with control treatments with lighter stocking rates for longer periods (2,000 DSE). Pastures were composed of wallaby grass (Austrodanthonia species), kangaroo grass (Themeda triandra), Phalaris (Phalaris aquatica, and cocksfoot (Dactylis glomerata) were destructively sampled to estimate total standing dry matter (TSDM), standing green biomass, standing dry biomass and trampled biomass. We then invoked a machine learning model using Sentinel-2 imagery to quantify TSDM, standing green biomass and standing dry biomass. Faced with La Nina conditions, regenerative grazing did not significantly impact pasture productivity, with all treatments showing similar TSDM and green biomass. However, regenerative treatments significantly impacted litter fall and trampled material, with the high intensity grazing treatments causing more dry matter trampling, increasing litter, enhancing decomposition rates and surface organic matter. Pasture digestibility was greatest for treatments with minimal spelling (3 months), whereas both standing senescent and trampled material were significantly greater for the treatment with 15-month spell periods. Estimates of TSDM using machine learning with Sentinel-2 imagery underestimated TSDM in treatment plots but explained spatiotemporal variability associated within and across treatments. The root mean square error between the measured and modelled TSDM was 903 kg DM/ha, which was less than the variability measured in the field. We conclude that regenerative grazing with short recovery periods (3-6 months) are most conducive to increasing pasture production under high rainfall conditions, and we speculate that high intensity grazing is likely to positively impact on soil organic carbon through increased litterfall and trampling. Our study paves the way forward for using machine learning with satellite imagery to quantify pasture biomass at small scales, enabling management of pastures from afar.

Compressive sensing originates in the field of signal processing and has recently become a topic of energy-efficient data gathering in wireless sensor networks. In this paper, we propose an energy efficient distributed compressive sensing solution for sensor networks. Proposed solution utilizes sparsity distribution of signals to group sensor nodes into several coalitions and then implements localized compressive sensing inside coalitions. This solution improves data-gathering performance in terms of both data accuracy and energy consumption. The approach curbs both data-transmission costs and number of measurements. Coalition-based data gathering cuts transmission cost, and the number of measurements is reduced by scheduling sensor nodes and adjusting their sampling frequency. Our simulation showed that our approach enhances network performance by minimizing energy cost and improving data accuracy.

It is estimated that about 50% of geriatric rehabilitation patients suffer from sarcopenia. Thereby, malnutrition is frequently associated with sarcopenia and dietary intake is the main modifiable risk factor. During hospitalization, older adults are recommended to consume more dietary protein than the current recommended dietary allowance of 0.8 g/kg body weight per day to optimize the recovery of muscular strength and physical function. This prospective study examined the effect of a short-term protein supplementation with protein-enriched foods and drinks on hand-grip strength, nutritional status and physical function in older patients at risk of malnutrition during a three week inpatient orthopedic rehabilitation stay. The Mini Nutritional Assessment (MNA) was used to assess malnutrition. Patients with a MNA score ≤ 23.5 points were randomly assigned to an intervention group (goal: to consume 1.2–1.5 g protein/kg body weight per day) or a control group (standard care). Both groups carried out the same rehabilitation program. Physical recovery parameters were determined at admission and discharge. There was a trend for participants in the intervention group to consume more protein than the control group (P = 0.058): 95.3 (SD 13.2) g/day as compared to 77.2 (SD 24.2) g/day, which corresponds to a mean protein intake of 1.6 (SD 0.3) g/kg/day vs. 1.3 (SD 0.5) g/kg/day. Dietary protein supplementation increased body weight by an average of 0.9 (SD 1.1) kg and fat mass by an average of 0.9 (SD 1.2) kg as compared with baseline (P = 0.039 and P = 0.050, respectively). There was no significant change in hand-grip strength, body composition and physical function. In conclusion, a short-term intervention with protein-enriched foods and drinks enabled older patients at risk of malnutrition to increase their protein intake to levels that are higher than their required intake. In these older individuals with appropriate protein intake, dietary protein supplementation did not result in a greater improvement in physical recovery outcomes during short-term inpatient rehabilitation. The intervention improved dietary protein intake, but further research (e.g., a full-scale randomized controlled trial with sufficient power) is required to determine the effects on physical function outcomes.

In this work, anchoring of cinchona derivatives to trifunctional cores (hub approach) was demonstrated to obtain size-enlarged organocatalysts. By modifying the cinchona skeleton in different positions, we prepared four C3-symmetric size-enlarged cinchona derivatives (hub-cinchonas), which were tested as organocatalysts and their catalytic activities were compared with the parent cinchona (hydroquinine) catalyst. We showed that in the hydroxyalkylation reaction of indole, hydroquinine provides good enantioselectivities (up to 73% ee), while the four new size-enlarged derivatives gave significantly lower values (up to 29% ee) in this reaction. Anchoring cinchonas to trifunctional cores was found to facilitate nanofiltration-supported catalyst recovery using PolarClean alternative solvent. The C3-symmetric size-enlarged organocatalysts were completely rejected by all the applied membranes, whereas the separation of hydroquinine was found to be insufficient using organic solvent nanofiltration. Furthermore, the asymmetric catalysis was successfully demonstrated in the case of Michael reaction of 1,3-diketones and trans-β-nitrostyrene using Hub3-cinchona (up to 96% ee) as a result of the positive effect of the C3-symmetric structure using a bulkier substrate. This means an increased selectivity of the catalyst in comparison to hydroquinine in the latter Michael reaction.

Globally, increasing rates of obesity are one of the most important health issues. The association between breakfast skipping and body weight is contradictory between cross-sectional and interventional studies. The systematic review and meta-analyses aim to summarize this association based on observational longitudinal studies. We included prospective studies on breakfast skipping and overweight/obesity or weight change in adults. Literature was searched until September 2020 in PubMed and Web of Science. Summary RRs with a 95% CI were estimated in pairwise meta-analyses by applying a random-effects model. In total, 9 studies were included in the systematic review and 6 of them were included in the meta-analyses. The meta-analysis indicated an 13% increased RR for overweight/obesity when breakfast was skipped on ≥ 3 days per week compared to ≤ 2 days per week (95% CI: 1.06, 1.21, n=3 studies). The meta-analysis on weight change displays a 21% increased RR for weight gain for breakfast skippers compared to breakfast eaters (95% CI: 1.05, 1.40, n=2 studies). The meta-analysis on BMI change displayed no difference between breakfast skipping and eating (RR=1.02, 95% CI: 0.99, 1.05, n=2 studies). This study provides low meta-evidence for an increased risk for overweight/obesity and weight gain for breakfast skipping.

The corrosion behavior of Fe-containing directionally solidified (DS) and centrifugally cast (CC) Al-Si-Cu-Zn alloys with either Co or Ni additions has been investigated. Electrochemical and immersion corrosion methods were used to investigate the corrosion behavior in 0.6 M NaCl after short (1-hour) and long (30-day) exposure periods. The employed solidification methods allowed the production of samples with a wide range of secondary dendrite arm spacing (SDAS) while preserving Si and Fe-containing phases. The 0.5 wt.% Ni and Co additions led to the growth of the AlFeSi(Ni) and AlFeSi(Co) phases, but no binary AlNi nor AlCo intermetallic par-ticles have been generated. Potentiodynamic polarization studies at early exposure revealed an increase in the corrosion potential as the Ni was added for either fast or slow solidified samples. The electrochemical impedance spectroscopy at early exposure demonstrated that the Ni-modified alloy, on the other hand, was associated to smaller charge transfer resistances, in-dicating a reduction in corrosion resistance after short elapsed time into the electrolyte. Howev-er, 30-day immersion tests revealed much lower corrosion rate of the Ni-modified alloy than the other alloys, while the corrosion rates of the Co-modified and non-modified alloys were simi-lar. In the Ni-containing alloy, decreased corrosion rate under long-term corrosion process was attributed to the formation of a thick and dense alumina layer, effectively protecting the surface under such conditions. This work contributes to a better knowledge of the corrosion behavior of Ni- and Co-corrected Al industrial scrap compositions.

Legacy risks from infrastructures and industrial installations often reveal themselves when a potential for failure has been discovered much later than at the stage of the design and construction of a structure. In which case, there might already be a problem with the legacy installation, or even a crisis, without having had an accident. When the hazard cannot be taken away, the question arises as to how much effort, if any, should be spent on improving the situation. The usefulness of the three archetypical approaches to this problem: setting a standard, the As Low As Reasonably Practicable approach and a case-by-case discourse approach are discussed for their applicability for these legacy risks. Although it would be desirable to retrofit legacy risks to previously set legal requirements as is the case when acceptability limits are set in law or demonstration of ALARP is demanded, it may be impossible to reduce the residual risk to an otherwise acceptable level without taking away or replacing the infrastructure, which is not acceptable either. Therefor in conclusion the only available solution to persistent legacy risk problems seems to be to have a thorough discussion with all relevant stakeholders until an agreement is in some way found.

Respiratory tract epithelium infection plays a primary role in Nipah virus (NiV) pathogenesis and transmission. Knowledge about infection dynamics and host responses to NiV infection in respir-atory tract epithelia is scarce. Studies in non-differentiated primary respiratory tract cells or cell lines indicate insufficient interferon (IFN) responses. However, studies are lacking to determin-ing complex host response patterns in differentiated respiratory tract epithelia to understand NiV replication and spread in swine. Here we characterized infection and spread of NiV in differenti-ated primary porcine bronchial epithelial cells (PBEC) cultivated at the air-liquid-interface (ALI). After the initial infection of only a few apical cells, lateral spread for 12 days with epithelium disruption was observed without releasing substantial amounts of infectious virus from the api-cal or basal sides. Deep time course proteomics revealed pronounced upregulation of genes re-lated to type I/II- IFN, immunoproteasomal subunits, TAP-mediated peptide transport and MHC I antigen presentation. Spliceosomal factors were downregulated. We propose a model in which NiV replication in PBEC is slowed by a potent and broad type I/II-IFN host response with con-version from 26S proteasomes to immunoproteasomal antigen processing and improved MHC I presentation for adaptive immunity priming. NiV induced cytopathic effects could reflect the focal release of cell-associated NiV, which may contribute to efficient airborne viral spread between pigs.

Objective: Our goal is to develop an online questionnaire to survey the prevalence of suicidal behavior. Methods: We developed a questionnaire with 51 variables and proceeded with validations. Validations were performed using face validity, content validity, and construct validity. Reliability was performed by test-rest. Results: The face validity was 1.0 and the content validity was 0.91. The exploratory factor analysis got KMO = 0.86 and extracted one principal factor. The confirmatory factor analysis demonstrates RMSEA= 0.000 and CFI=1.000. The test-retest had an intraclass correlated coefficient of 0.98. Conclusion: The adequate development questionnaire was validated, and we have an instrument to survey suicide behaviors in the pandemic time.

The reaction of arylidene-α-amino esters with electrophilic alkenes to yield the Michael type addition compounds is optimized using several phosphines as organocatalysts. The transformation is very complicated due to the generation of several final compounds, including those derived from the 1,3-dipolar cycloadditions. For this reason, the selection of the reaction conditions is a very complex task and the slow addition of the acrylic system is very important to complete the reaction. The study of the variation of the structural components of the starting imino ester is performed as well as the expansion of other electron-poor alkenes. The crude products have a purity higher than 90% in most cases without any purification. A plausible mechanism is detailed based on the bibliography and the experimental results. The synthesis of pyroglutamate entities, after reduction of the imino group and cyclization, is performed in high yields. In addition, the hydrolysis of the imino group, under acidic media, represents a direct access to glutamate surrogates.

The development of high complexity geometry parts is one of the main goals of the additive manufacturing technology. However, the failure of printed structures and the joining of different parts to create complex assemblies represents a real challenge in the research of efficient and sustainability techniques for the permanent assembly of polymers. Laser welding processes have been used as a single step method to join metals until years ago. Nowadays, the growing trend in the use of thermoplastics for additive manufacturing has led to the need to adapt this technique to materials with a very specific nature and more sensitive to thermal effects. Also, the possibility of transmitting the laser beam through transparent polymer layers allows to focus the energy supply on internal sections of the assembled components. In this research, an infrared laser marking system was used to join two different samples of polylactic acid manufactured by fused deposited modeling technology. In order to increase the effectiveness of the bonding process, a transparent and a dark sample have been used as assembly material, focusing the laser beam on the interface area of the two parts. By means of tensile tests, dimensional measurement and the use of optical microscopy techniques, a basis was established that links the supplied energy by laser to the joining performance.

The retrieval of sun-induced chlorophyll fluorescence is greatly beneficial to studies of marine phytoplankton biomass, physiology, and composition and is required for user applications and services. Customarily phytoplankton chlorophyll fluorescence is determined from satellite measurements through a fluorescence line-height algorithm using three bands around 680 nm. We propose here a modified retrieval, making use of all available bands in the relevant wavelength range with the goal to improve the effectiveness of the algorithm in optically complex waters. For the Ocean and Land Colour Instrument (OLCI) we quantify a Fluorescence Peak Height from fitting a Gaussian function and related terms into the top-of-atmosphere reflectance bands between 650 and 750 nm. This algorithm retrieves, what we call Fluorescence Peak Height from fitting a Gaussian function upon other terms to top-of-atmosphere reflectance bands between 650 and 750 nm. This approach is applicable to Level-1 and Level-2 data. We find a good correlation of the retrieved fluorescence product to global in-situ chlorophyll measurements, as well as a consistent relation between chlorophyll concentration and fluorescence from radiative transfer modelling and OLCI/in-situ comparison. The algorithm is applicable to complex waters without needing an atmospheric correction and vicarious calibration and features an inherent correction of small spectral shifts, as required for OLCI measurements.

Under optimal conditions, just 3–6 ms of visual stimulation suffices for humans to see motion. Motion perception on this time scale implies that the visual system under these conditions reliably encodes, transmits, and processes neural signals with near-millisecond precision. Motivated by in vitro evidence for high temporal precision of motion signals in the primate retina, we investigated how neuronal and perceptual limits of motion encoding relate. Specifically, we examined the correspondence between the time scale at which cat retinal ganglion cells in vivo represent motion information and temporal thresholds for human motion discrimination. The time scale for motion encoding by ganglion cells ranged from 4.6–91 ms, depended nonlinearly on temporal frequency but not on contrast. Human psychophysics revealed that minimal stimulus durations required for perceiving motion direction were similarly brief, 5.6–65 ms, similarly depended on temporal frequency but, above ~10%, not on contrast. Notably, physiological and psychophysical measurements corresponded closely throughout (r = 0.99), despite more than a 20-fold variation in both human thresholds and optimal time scales for motion encoding in the retina. These results demonstrate that neural circuits for motion vision in cortex can maintain and make use of the high temporal fidelity of the retinal output signals.

The philosophy of testing statistical hypothesis is a natural consequence and functional extension of mathematical analysis of Probability. Along with the concept of recurrence when applied to random sequences and functions, it leads to the analysis of a priori and posterior which implies testing statistical hypothesis. Testing statistical hypothesis also involves algebraic, functional and dimensional considerations, which are found in the works of Laplace. Aspects of mathematical analysis such as universality of solutions, Laws of Large Numbers, Entropy, Information, and various functional dependencies are the main factors explained in the five properties that lead to implication of testing statistical hypothesis. Various interesting examples with modern scientific significance from genetics, astrophysics, and other areas give methodological access to answers of different problems and phenomena which are involved in the logic of testing statistical hypothesis.

Multiple sclerosis (MS) and necrotizing periodontitis (NP) are two diseases whose aetiology and pathophysiology do not seem to have a common link; however, the treatment of MS with monoclonal antibodies and the decrease in humoral immunity that this entails can be a trigger or an aggravation in patients who present NP. We present a clinical case of NP in which its clinical manifestations, treatment and evolution during therapy with ocrelizumab are reflected. During the evolution of the case, a rapid progression of NP was evidenced. During her evolution, the patient suffered bilateral pneumonia due to COVID requiring treatment with corticosteroids and antibiotics, which led to clinical relief of her NP. Given this important clinical finding, we consider of great interest the regulated dental monitoring of those patients with MS before, during and after the administration of monoclonal antibodies to prevent periodontal deterioration.

Dietary supplements are more and more often used to increase daily intake of essential vitamins and minerals. These preparations are classified as special category of foods and are subject to food law, not pharmaceutical regulations. As a result the requirements to dietary supplements are much less restrictive than to medications. Also simple and inexpensive procedure of registration causes that the number of dietary supplements is widely spread every year. On every manufacturing phases of dietary supplements, there is a risk of contamination. One of the pollutions might be mercury which is classified as heavy metal. Its inorganic compounds damage kidneys and liver and methylmercury is easily absorbed from gastrointestinal system. Methylmercury is distributed in all tissues, also in nervous system. The aim of study was to determine the level of mercury in multivitamins and multiminerals preparations and to analyze the results. The study included 22 dietary supplements containing vitamins and minerals available on Polish market. Mercury was analyzed with atomic absorption spectrometry using AMA 254. The concentrations of Hg was 0.22–5.85 µg/kg (the average content was 2.40 µg/kg). The highest average mercury content was 4.51 µg/kg, whereas the lowest one was 0.31 µg/kg. The results was also analyzed in individual groups depending on main component and indication for use as well as pharmaceutical formulation. Also according to manufacturer’s recommendation, the dose of mercury taken with a single medicine was estimated for time of a day, a week, a month, 3 months and also a year. The findings were compared to limits defined in regulations of European Union and PTWI set by JECFA to assess the health risk. The results presented in this study proved that the amount of mercury in tested dietary supplements is much lower than the value of valid regulations. Analyzed supplements as long as they are used with the recommendation of manufacturer, do not pose a threat to human health.

In the concept of the process signature, the relationship between a material load and the modification remaining in the workpiece is used to better understand and optimize manufacturing processes. The basic prerequisite for this is to be able to measure the loads occurring during the machining process in the form of mechanical deformations. Speckle photography is suitable for this in-process measurement task and is already used in a variety of ways for in-plane deformation measurements. The shortcoming of this fast and robust measurement technique based on image correlation techniques is that out-of-plane deformations in the direction of the measurement system cannot be detected and increases the measurement error of in-plane deformations. In this paper, we investigate a method that infers local out-of-plane motions of the workpiece surface from the decorrelation of speckle patterns and is thus able to reconstruct three-dimensional deformation fields. The implementation of the evaluation method enables a fast reconstruction of 3D deformation fields, so that the in-process capability remains given. First measurements in a deep rolling process show that dynamic deformations underneath the die can be captured and demonstrate the suitability of the speckle method for manufacturing process analysis.

Advanced ceramics are recognized as key enabling materials possessing combinations of properties not achievable in other material classes. They are characterized by very high thermal, chemical and mechanical resistance and also usually have a lower density than metals. These properties predestine ceramics for many different applications, especially space applications.In the aerospace sector aerospike nozzles promise performance and application advantages compared to classic bell nozzles but are also inherently more complex to manufacture due to their shape. AM methods drastically simplify or even enable the fabrication of those complex structures while minimising the number of individual parts. The applicability of ceramic AM (“CerAMfacturing”) on rocket engines and especially nozzles is consequently investigated in the frame of the “MACARONIS” project, a cooperation of the Institute of Aerospace Engineering at Technische Universität Dresden and the Fraunhofer Institute for Ceramic Technologies and Systems (IKTS) in Dresden. The goal is to develop novel large size aerospike thrust nozzles including areas of highest resolution and fineness. Finding a suitable AM process that enables the realisation of both aspects is extremely challenging. One possibility could be the hybridization of shaping methods, in that case CerAM VPP (ceramic additive manufacturing via vat photopolymerization) and CerAM FFF (ceramic additive manufacturing via fused filament fabrication) in combination with sinter joining. This contribution focuses on the high resolution CerAM VPP process, in particular the development, characterization and testing of a new photoreactive Al₂O₃ suspension validated by AM of novel aerospike nozzles.

Although previous studies have focused on the adverse effects of the COVID-19 pandemic on various professional groups (particularly in the health and nursing care sector), this study aims to close a research gap by assessing perspectives of students and young professionals in epidemiology and public health in Germany in terms of shifts in workload, work content, and related challenges caused by the pandemic. We conducted a cross-sectional survey between mid-February and mid-March 2022. Quantitative data were analyzed via standardized mean differences. Qualitative data based on answers to open-ended questions were analyzed via a qualitative content analysis. Overall, 172 individuals participated in this survey. Results indicate that students felt burdened the most by lack of exchange with other students and lecturers. Study participants employed in public health experienced changes in their employment, because they had changes in their work content- and administration-wise, which was accompanied with a high burden due to the workload. Multiple demands that can have an impact on both acquired skills and mental health during the professional qualification phase were mentioned by the participants. Therefore, more in-depth analyses are needed for investigating the impact the pandemic will have on the (future) public health workforce in the long run.

Amid to the COVID-19 pandemic, digital health literacy (DHL) has become a significant public health concern. This research aims to assess information seeking behavior, as well as the ability to find relevant information and deal with DHL among university students in Pakistan. An online-based cross-sectional survey, using a web-based interviewing technique, was conducted to collect data on DHL. Simple bivariate and multivariate linear regression was performed to assess the association of key characteristics with DHL. The results show a high DHL related to COVID-19 in 54.3% of students. Most of the Pakistani students demonstrated ~50% DHL in all dimensions, except of reliability. Multivariate findings showed that gender, sense of coherence and importance of information were found to be significantly associated with DHL. However, a negative association was observed with students’ satisfaction with information. This led to the conclusion that critical operational and navigations skills are essential to achieve COVID-19 DHL and cope with stress, particularly to promote both personal and community health. Focused interventions and strategies should be designed to enhance DHL amongst university students to combat the pandemic.

As air traffic demand grows, robust, data-driven anomaly detection methods are required to ensure that aviation systems become safer and more efficient. The terminal airspace is identified as the most critical airspace for both individual flight-level and system-level safety and efficiency. As such, developing data-driven anomaly detection methods to analyze terminal airspace operations is paramount. With the expansion of ADS-B technology, open-source flight tracking data has become more readily available to enable larger-scale analyses of aircraft operations. This paper makes a distinction between spatial metrics in ADS-B trajectory data and energy metrics derived from ADS-B trajectory data. Motivated by the limited number of approaches that simultaneously consider both spatial and energy metrics, this paper introduces the concepts of spatial anomalies and energy anomalies. In particular, it proposes a novel, unified framework for detection of spatial and energy anomalies in ADS-B trajectory data (and associated derived metrics). The framework consists of three main parts - a data processing procedure, a spatial anomaly detection method, and an energy anomaly detection method. The framework is demonstrated utilizing four months of ADS-B trajectory data associated with arrivals at San Francisco International Airport, and the relationship between the spatial and energy anomalies in this terminal airspace is explored. The results that stem from the implementation of this framework indicate that if an aircraft is spatially not conforming to an identified set of air traffic flows representing standard spatial operations, then this aircraft is more likely to experience non-conformance to standard operations in its energy metrics. Aviation operators, such as air traffic controllers, may benefit from this observation, as it may factor into decision-making in instances where there is the potential to instruct an aircraft to spatially deviate from standard operations. Additionally, this research revealed underlying differences between trajectories that are spatially nominal yet energy-anomalous and those trajectories that are spatially anomalous and energy-anomalous. Focusing solely on energy anomaly detection does not provide insight into potential spatial-related decisions that may have been made to result in off-nominal energy behavior.

We discuss two methods to detect the presence and location of a person in a small-scale room and compare the performances. The first method is Direct Intersection, which determines a coordinate point based on the intersection of spheroids defined by observed distances of high-intensity reverberations. The second method, Sonogram analysis, overlays all channel’s room impulse responses to generate an intensity map for the observed environment. We demonstrate that the former method has lower computation complexity and higher accuracy for small numbers of channels, while the latter performs more robustly.

An efficient stereoselective three-component reaction for the synthesis of spiro[4H-chromene-3,3’-oxindole] derivatives was realized through an organocatalyzed cascade Knoevenagel/Michael/cyclization reaction using a quinidine-derived squaramide as the catalyst. Under the optimized conditions, the reactions of isatins, malononitrile, and sesamol yield the desired spirooxindoles in good yields (75–87%) and moderate to high ee values (up to 90% ee). Two pairs of selected enantiomers were subjected to evaluate their antiproliferative activities on three types of human cancer cell lines using the MTT assay. The results indicated that stereoselectivity and electrical effect showed significant impact on activity. Enanotiomer R-3f exhibited optimal cytotoxic activity against U2OS cell line, which was close to the inhibitory activity of positive control, Adriamycin.

The up-to-date challenge towards clean road transport are non-exhaust emissions. Important advances regarding measurement systems, including well defined characterisation techniques, as well as regulation, will happen in the next few years. In this work we present detailed results of particle emissions from a test bed for wheel suspension and brakes, consisting of aerosol (size distribution, particle number (PN) and mass (PM)) and electron microscopy measurements (EM) under different load conditions. Standard tyres and brakes from series production were tested with a high-load driving cycle while particle measurements were conducted by gravimetric measurements and with a TSI SMPS, a TSI APS and a GRIMM OPS. Furthermore, samples were analyzed by electron microscopy. A bimodal particle size distribution (PSD) was obtained with the SMPS, with peaks at 20nm and around 400nm. EM analysis of >1400 single particles from the electrostatic sampler matches the PSD results. EM analysis also showed ultrafine particles, mainly from O, Fe, Si, Ba, Mg and S and also fractal particles with high C fractions. Our results suggest, in agreement with previously published literature, that particulate emissions are related to brake disc temperature and occur in significant amounts above a threshold temperature.

Conventional mechanical Fourier Transform Spectrometers (FTS) are able to simultaneously measure absorption and dispersion spectra of gas-phase samples. However, they usually need very long measurement times to achieve time-resolved spectra with a good spectral and temporal resolution. Here, we present a mid-infrared dual-comb-based FTS in an asymmetric configuration, providing broadband absorption and dispersion spectra with a spectral resolution of 5 GHz, a temporal resolution of 20 μs, and a total measurement time of a few minutes. We used the dual-comb spectrometer to monitor the reaction dynamics of methane and ethane in an electrical plasma discharge. We observed ethane/methane formation as a recombination reaction of hydrocarbon radicals in the discharge in various static and dynamic conditions. The results demonstrate a new analytical approach for measuring fast molecular absorption and dispersion changes and monitoring fast dynamics of chemical reactions, which can be interesting for chemical kinetic research and particularly for the combustion and plasma analysis community.

The influence of distant London dispersion forces on the docking preference of alcohols of different size between the two lone electron pairs of the carbonyl group in pinacolone is explored by infrared spectroscopy of the OH stretching fundamental in supersonic jet expansions of 1:1 solvate complexes. Experimentally, no pronounced tendency of the alcohol to switch from the methyl to the bulkier tert-butyl side with increasing size is found. In all cases, methyl docking dominates by at least a factor of two, whereas DFT-optimized structures suggest a very close balance for the larger alcohols, once corrected by CCSD(T) relative electronic energies. Together with inconsistencies when switching from a C4 to a C5 alcohol, this points at deficiencies of the investigated B3LYP and in particular TPSS functionals even after dispersion correction, which cannot be blamed on zero point energy effects. The search for density functionals which describe the harmonic frequency shift, the structural change and the energy difference between the docking isomers of larger alcohols to unsymmetric ketones in a satisfactory way is open.

Dog Assisted Therapy is hypothesized to lower stress in children with Autism Spectrum Disorder (ASD) and children with Down Syndrome (DS), which may be visible on a physiological level. In this study, we measured Heart Rate Variability (HRV) and salivary cortisol of 20 children with DS or ASD at the beginning and end of 6 weekly sessions of Dog-Assisted Therapy. We found a decrease of cortisol levels during single sessions, but no overall effect after 6 sessions (6 weeks). The effect of Dog Assisted Therapy on the increase of HRV could not be confirmed. This study is one of the first to use physiological measurements to test the effects of DAT.

Iterated games, in which the same economic interaction is repeatedly played between the same agents, are an important framework for understanding the effectiveness of strategic choices over time. To date very little work has applied information theory to the information sets used by agents in order to decide what action to take next in such strategic situations. This article looks at the mutual information between previous game states and an agent's next action by introducing two new classes of games: ’invertible games’ and ‘cyclical games'. By explicitly expanding out the mutual information between past states and the next action we show under what circumstances these expressions can be simplified. These information measures are then applied to the Traveler's Dilemma game and the Prisoner's Dilemma game, the Prisoner's Dilemma being invertible, to illustrate their use. In the Prisoner's Dilemma a novel connection is made between the computational principles of logic gates and both the structure of games and the agents' decision strategies. This approach is applied to the cyclical game Matching Pennies to analyse the foundations of a behavioural ambiguity between two well studied strategies: ‘Tit-for-Tat' and ’Win-Stay, Lose-Switch'.

The Total Algae Peak Integration Retrieval TAPIR relates the chlorophyll-a absorption coefficient at 440 nm (a440) to the reflectance peak near 683 nm induced by chlorophyll-a properties. The two-step retrieval provides both the hyperspectral quantification of the phytoplankton fluorescence and scattering and the estimation of a440 from reflectance signals. Integrating the peak, the Total Algae Peak (TAP) accounts for the variance in the peak's magnitude, shape, and central peak wavelength. TAPIR is a solely optical approach estimating a440 and supports the application of retrieval-independent individual regional bio-optical models afterwards to retrieve the chlorophyll-a concentration. Simulations reveal the major sensitivity on the considered model chlorophyll-a absorption spectrum and its single scattering albedo. Additional water and atmosphere constituents have a low impact. An uncertainty assessment reveals uncertainties of less than 30% for TAPIR a440 greater than 0.8 m-1 and less than 38% for lower a440. In optically complex waters, first validation efforts promise the applicability of TAPIR for high chlorophyll-a concentration estimations in the presence of additional water constituents. The technique is generic and considers external conditions (sun zenith angle, number of measurement bands, surface or satellite measurements, and radiometric quantity). TAPIR applies to all kind of waters including optically complex waters, arctic to tropical regions, and inland, coastal, and open ocean waters. Among other hyperspectral satellite sensors, the Environmental Mapping and Analysis Program (EnMAP) provides sufficient sampling bands for the application of TAPIR.

Micronutrient deficiencies (MNDs), also known as hidden hunger, affects more than a quarter of the global population. Agronomic biofortification helps to increase concentration of a target mineral in food crops and improve human mineral dietary intake. It is a means of providing nutrient dense foods to a larger population especially among rural resource poor settings, providing that they have access to mineral fertilizers. However, the feasibility of agronomic biofortification in combating hidden hunger depends on several factors besides fertilizer access, including crop type, genotype, climate, soils, and soil mineral interactions. Consideration of its effectiveness to increasing human mineral intakes to daily requirements and improvement to human health and the cost effectiveness the program is also important. In this paper we reviewed available literature regarding the potential effectiveness and challenges of agronomic biofortification to improve crop micronutrient concentrations and reduce hidden hunger.

Cisplatin is an election chemotherapeutic agent for many cancer treatments. Its cytotoxicity against neoplastic cells is mirrored by that taking place in healthy cells and tissues, resulting in serious adverse events. A very frequent one is ototoxicity, causing hearing loss which may permanently affect quality of life after successful oncologic treatments. Exacerbated oxidative stress is a main cytotoxic mechanism of cisplatin, including ototoxicity. Previous reports have shown antioxidant protection against cisplatin ototoxicity, but there is a lack of comparative studies on the otoprotectant activity and mechanism of antioxidant formulations. In this paper we report that a combination of vitamins A, C, E and Mg++ (ACEMg), previously shown to protect against noise-induced hearing loss, reverses auditory threshold shifts, promotes outer hair cell survival, and attenuates oxidative stress in the cochlea after cisplatin treatment, thus protecting against extreme cisplatin ototoxicity in the rat. The addition of 500 mg N-acetylcysteine (NAC), which administered individually also shows significant attenuation of cisplatin ototoxicity, to the ACEMg formulation, results in degradation of ACEMg otoprotection. Mg++ administered alone, as MgSO4, also prevents cisplatin ototoxicity, but in combination with 500 mg NAC, otoprotection also is greatly degraded. Increasing the dose of NAC to 1000 mg, also results in dramatic loss of otoprotection activity compared with 500 mg NAC. These findings support that single antioxidants or antioxidant combinations, particularly ACEMg in this experimental series, have significant otoprotection efficacy against cisplatin ototoxicity. However, an excess of combined antioxidants and/or elevated doses, above a yet to be defined “antioxidation threshold”, results in unrecoverable redox imbalance with loss of otoprotectant activity.

Background: Metastatic oral squamous cell carcinoma (OSCC) is associated with poor patient prognosis. Metastasis is a complex process involving various proteins, tumor cell alterations including changes caused by the epithelial-to-mesenchymal transition (EMT) process, and interactions with the tumor microenvironment (TME). In this study, we investigate a combined protein marker system consisting of connexin 43 (Cx43), EMMPRIN (CD147), E-cadherin and vimentin during the invasive metastatic process of OSCC and the possibility of using this system for prognosis prediction. Methods: The protein expression profiles of Cx43, EMMPRIN, E-cadherin and vimentin were investigated by immunohistochemistry in tissue samples from 24 OSCC patients. The metastatic process was mapped through different regions of interest (ROI) of adjacent healthy oral mucosa (OM), center of primary OSCC, invasive front (IF), and local cervical lymph node metastases (LNM). Disease-free survival (DFS) and overall survival (OS) were the primary clinical endpoints. Results: Significant changes in the expression profiles of the different marker proteins were detected between the different ROIs (all p values < 0.05). Multivariable Cox regression analysis revealed a significant effect of increased EMMPRIN expression towards IF on DFS (p = 0.019) and OS (p = 0.023). The combined predictive analysis showed a significant predictive value of the marker system for DFS (p = 0.0017) and OS (p = 0.00044). Conclusions: The combined marker system was able to significantly predict patient prognosis. An increase in EMMPRIN expression towards IF showed the strongest effect and could be an interesting new antimetastatic therapy approach.

In this paper we will find that, according to holographic principle {\cite{Holografico}} and thus considering Universe as the ensemble of $\aleph$ information bits or minimum particles of mass $m_{g}$, the contribution to galactic rotation curves can be due the rest of the visible Universe through a non-local collective gravitational interaction of all particles within the Universe's horizon, as a consequence of which all particles are gravitationally entangled and form a unified statistical ensemble. Therefore, we can to describe this global effect in terms of standard local Newtonian gravity within galaxies for the explanation of flatness galactic rotation curves as a possible alternative to the dark matter or MOND hypothesis. We will find a solution for the baryonic Tully-Fischer relation: $M_{b} = A v_{f}^4 \iff A = \left[a_{0}G \right]^{-1}$ with $a_{0} = \frac{cH_{0}}{2\pi}$, where $H_{0}$ is the Hubble constant at present Time $t_{0}$ and $M_{b}$, $G$ and $c$ are the galaxy baryonic mass, gravitational constant and constant speed of light in vacuum respectively. Also we will find the mass discrepancy-acceleration relation, thus obtaining a possible solution for each of the three laws of rotationally supported galaxies proposed in ({\cite{McGaugh}},{\cite{McGaugh1}}).

Smart manufacturing encompasses a category of manufacturing that employs computer-integrated capabilities and technologies to enhance supply chain optimization, production efficiency, and recyclability. Yet limited studies have been conducted to optimize these prospects from the perspective of low resource countries where such innovative studies have not been adequately explored. This paper aims to examine the implications of smart manufacturing practices (Smart Procurement, Smart Supply Chain, Smart Production Planning and Control, Automation and Industrial Robot, and Supply Chain Configuration) on pro-environmental behaviour and develop a baseline moderated mediation model to explain the relationship between smart manufacturing and pro-environmental behaviour with a role of green dynamic capability, and environmental orientation. This study is anchored on quantitative research approach, deductive reasoning, and explanatory design. Cross – sectional survey data have been obtained from 382 manufacturing companies in Ghana. Our hypotheses have been tested using Structural Equation Modelling and SMART-PLS version 3.8.9. The study has revealed that smart manufacturing practices significantly and positively relate to pro-environmental behaviour. Moreover, green dynamic capability and environmental orientation moderate the relationship between smart manufacturing and pro-environmental behaviour. The implications of the study include the emergence of a baseline model to guide policymakers, practitioners, and academicians to explain the relationship between smart manufacturing and sustainable manufacturing in the context of developing countries. Again, the social implication of the study includes the realisation of decent job and economic growth, responsible consumption and production as well as actions taken to combat climate change.

The fatigue life of welded joints under cyclic loading is a complex process that can be roughly divided into fatigue crack initiation, crack propagation and final fracture. Usually, these phases are evaluated separately. Several methods are available to estimate the extent of the different phases in welded components, such as stress-based fatigue concepts for crack initiation or linear elastic fracture mechanics for crack propagation; however, distinguishing these phases in welded components is a complex procedure and often relies on assumptions such as transition crack sizes. The objective of this study is to investigate the relationship between fatigue crack initiation and propagation in welded joints using artificially notched specimens with welded joints characteristics of different notch acuity (different radii and opening angle). The experiments show that the investigated relationship basically depends on the notch acuity, the load level and the stress ratio.

In a recent paper, we calculate spectral energy distributions (SEDs) for 1425 Fermi blazars, classifications of low synchrotron peak sources (LSPs) if log $\nu_{\rm p} (\rm Hz) \leq $ 14.0, intermediate synchrotron peak sources (ISPs) if $14.0 < \,\log\, \nu_{\rm p} (\rm Hz) \leq 15.3 $, and high synchrotron peak sources (HSPs) if $ \log\, \nu_{\rm p} (\rm Hz) > 15.3$ are made based on 999 logarithms of synchrotron peak frequencies with known redshift, and we obtain an empirical relation to estimate the synchrotron peak frequency, $\nu_{\rm p}^{\rm Eq.}$ from effective spectral indexes $\alpha_{ox}\, {\rm and}\, \alpha_{ro}$ as $\log \nu_{\rm p}^{\rm Eq.} = 16+4.238X $ if $X < 0$, and $\log \nu_{\rm p}^{\rm Eq.} = 16+4.005Y $ if $X > 0$, where $X = 1.0 - 1.262 \alpha_{ro} - 0.623 \alpha_{ox}$, and $Y = 1.0 + 0.034 \alpha_{ro} - 0.978 \alpha_{ox}$ \cite{Fan16}. In the present work, we investigate the correlation between the peak frequency and the radio to X-ray spectral index, that between peak luminosity (integrated luminosity) and $\gamma$-ray/optical luminosity, and that between peak luminosity and integrated luminosity. Some discussions are presented.

Global anaesthesia workforce limitations contribute to emigration of skilled anaesthesiologists from lower- to higher-income countries, jeopardizing workforce balance and patient outcomes in Pakistan. This study aims to explore challenges experienced by anaesthesiologists in Punjab, Pakistan’s most populous province, and necessary changes to encourage their retention. We conducted a qualitative study to examine perspectives of anaesthesiologists who chose to serve in Pakistan. We drew data from semi-structured interviews conducted with 25 purposively-sampled consultant anaesthesiologists. We analysed data thematically and distinguished the practice hurdles faced by anaesthesiologists in public and private hospitals of Punjab. The main reasons to work abroad could be broadly categorized under two inductive themes, i.e. practice hurdles in public and private sector. Both had distinct issues which compromised the number and quality of anaesthesia workforce in the country. The key outcomes were workplace security, promotion/incentive issues and gender inequalities in the government sector. The private sector had improper salaries and facilities, anaesthesiologist’s dependency on surgeons for getting work and lack of out-of-theatre practice which minimise the scope and earnings of anaesthesiologist within the country. There is a need to overcome surgeon dependency and hospital manipulation by fixing salary percentages for each surgical case and encouraging direct patient-anaesthesiologist relationships.

This paper offers a comprehensive examination of the process involved in developing and automating supervised end-to-end machine learning workflows for forecasting and classification purposes. It offers a complete overview of the components (i.e. feature engineering, model selection, etc), principles (i.e. bias-variance decomposition, model complexity, overfitting, model sensitivity to feature assumptions and scaling, output interpretability, etc), models (i.e. neural networks, regression models, etc), methods (i.e. Cross-Validation, data augmentation, etc), metrics (i.e. Mean Squared Error, F1-score, etc) and tools that rule most supervised learning applications with numerical and categorical data, as well as their integration, automation, and deployment. The end goal and contribution of this paper is the education and guidance of the non-AI expert academic community over complete and rigorous machine learning pipelines and data science practices, from problem scoping to design and state-of-the-art automation tools, including basic principles and reasoning in the choice of methods. The paper delves into the critical stages of supervised machine learning workflow development, many of which are often omitted by researchers due to brevity, and covers foundational concepts essential for understanding and optimizing a functional machine learning workflow, thereby offering a holistic view of task-specific application development for applied researchers who are not AI experts.

The Energy Performance of Buildings Directive 2010 calls for the Nearly Zero Energy Standard for new buildings from 2021 onwards: Buildings using “almost no energy” are powered by renewable sources or energy produced by the building itself. For residential buildings, this ambitious new standard has already been reached. But for other building types this goal is still far away. The potential of these buildings to meet a Nearly Zero Energy Standard was investigated by analyzing ten case studies representing non-residential buildings with different uses. The analysis shows that the primary characteristics common to critical building types are a dense building context with a very high degree of technical installation (such as hospital, research and laboratory buildings). The large primary energy demand of these types of buildings cannot be compensated by building and property-related energy generation including off-site renewables. If the future Nearly Zero Energy Standard were to be defined with lower requirements because of this, the state related properties of Bavaria suggest that the real potential energy savings available in at least 85% of all new buildings would be insufficiently exploited. Therefore, it would be useful to instead individualize the legal energy verification process for new buildings to distinguish critical building types such as laboratories and hospitals.

Starting from acid chlorides, alkynes, tryptamines, and acroyl chloride, 21 densely substituted tetrahydro-beta-carbolines are prepared in a four-component one-pot reaction. In this study, the aza-Michael addition step to generate intermediate enaminones is optimized in the presence of ytterbium triflate. Moreover, apart from acroyl chloride, all reactants can be deployed in almost equimolar ratios, which increases the atom economy of the sequence. For mechanistic rationali-zation, the concluding aza-anellation was investigated by DFT calculations on potential inter-mediates and corresponding activation energies, revealing that the aza-anellation rather pro-ceeds via ene-reaction than via electrocyclization.

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

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

For our research on droplet deformation and breakup in scaled high-pressure homogenizing units we developed a pressure stable inline droplet generator. It consists of an optically accessible flow channel with a combination of stainless steel and glass capillaries and a 3D printed orifice. The droplet size is determined online by live image analysis. The influence of the orifice diameter, the mass flow of the continuous phase and the mass flow of the disperse phase on the droplet diameter was investigated. Furthermore, the droplet detachment mechanisms were identified. Droplet diameters with small diameter fluctuation between 175 µm and 500 µm could be realized, which allows a precise adjustment of the Ca and We Number in the subsequent scaled high pressure homogenizer disruption unit. The determined influence of geometry and process parameters on the resulting droplet size and droplet detachment mechanism agreed well with literature on microfluidics. Furthermore, droplet trajectories in an exemplary scaled high-pressure homogenizer disruption unit are presented which show that the droplets can be reinjected on a trajectory close to the center axis or close to the wall, which should result in different stresses on the droplets.

The concept of a Social License to Operate (SLO) has become increasingly important in the sustainability literature in recent years. Having its origins in the business discourse of the mining industry with respect to limiting opposition to mining projects, the notion of a social contract above and beyond legal requirements has since become applied across a number of different industries. Despite the concepts adoption confusion exists over the practices and outcomes of SLO, and particularly the nature of engagement. Given this situation it is surprising that not more attention to the role of marketing, and social marketing in particular, in operationalizing the concept. The paper discusses the potential of social marketing to contribute to SLO. Economic, political and social relations are complex in SLO and exchange is intricate in such relational environments. A community-based social marketing orientation is proposed as a means to improve exchange relations and enhance engagement. Seven models of SLO related social marketing models are discussed with community-based social marketing and adaptive co-marketing models being regarded as the most positive for the achievement of an SLO. Potential barriers to adoption of these approaches are noted.

Fourier transform infrared (FTIR) absorption spectroscopy of cold molecules and clusters in supersonic slit jet expansions complements and extends more sensitive action spectroscopy techniques and provides important reference data for the latter. We describe how its major drawback, large substance and carrier gas consumption, can be alleviated by one to two orders of magnitude via direct and continuous recycling of the gas mixture. This is achieved by a combination of dry rotary lobe and screw pump compression. The signal-to-noise ratio is boosted by the established buffered giant gas pulse technique with full interferogram synchronization. The buildup of water impurities typically limits the recycling gain, but is turned into a feature for the study of hydrate complexes of volatile molecules. Continuous operation with a single gas filling over several days becomes practical and useful. Decadic absorbances in the low ppm range are detectable and the mid infrared range can be recorded simultaneously with the near infrared. The less straightforward hydration number assignment of spectral features in direct absorption spectroscopy is supported by a gradual water buildup at a rate of less than 0.5 mg/h. A recent reassignment proposal for the water dimer OH stretching spectrum is refuted and vibrational spectra of vacuum-isolated 18O-water clusters are presented for the first time. Methanol docking on asymmetric ketones is used to illustrate the advantages and limitations of the recycling concept. Previous assignments of the hydrate complex of 1-phenylethanol are confirmed. Additional features of the setup await testing and refinement, but the recycling technique already substantially widens the applicability of direct absorption spectroscopy of neutral molecular clusters. It may be attractive for other high-throughput jet spectrometers.

Preliminary clinical data suggest pain reduction through fasting in different diagnoses. This uncontrolled observational clinical study examined the effects of prolonged modified fasting on pain and functional parameters in hip and knee osteoarthritis. Patients admitted to the inpatient department of Internal Medicine and Nature-based Therapies of the Immanuel Hospital Berlin between February 2018 and March 2020, answered questionnaires at the beginning and end of inpatient treatment, as well as 3, 6 and 12 months after discharge. Additionally, selected blood and anthropometric parameters were routinely assessed during the inpatient stay. Fasting was performed as part of a multimodal integrative treatment program, with daily caloric intake of <600 kcal for 7.7 ± 1.7 days. N=125 consecutive patients were included. Results revealed an amelioration of overall symptomatology (WOMAC Index score: -14.8±13.31; p<0.001; d=0.78), and pain alleviation (NRS Pain: -2.7±1.98, p<0.001, d=1.48). Pain medication was reduced, stopped, or replaced by herbal remedies in 36% of patients. Improvements were also observed in secondary outcome parameters, including increased quality of life (WHO-5: +4.5±4.94, p<0.001, d=0.94), reduced anxiety (HADS-A: -2.1±2.91, p<0001, d=0.55) and depression (HADS-D: -2.3±3.01, p<0.001, d=0.65), decreases in body weight (-3.6 kg ± 1.65, p< 0.001, d=0.21), and blood pressure (systolic: -6.2±15.93, p<0.001, d= 0.43; diastolic: -3.7±10.55, p<0.001, d=0.43). Results suggest that patients with osteoarthritis of the lower extremities may profit from a prolonged fast embedded in a multimodal integrative treatment regarding quality of life, pain, and disease-specific functional parameters. Confirmatory RCTs are warranted to further investigate these hypotheses.

The assessment of seismic risk in urban areas with high seismicity is certainly one of the most important problems that territorial managers have to face. A reliable evaluation of this risk is the basis for the design of both specific seismic improvement interventions and emergency management plans. Unappropriate seismic risk assessments may provide misleading results and induce bad decisions with relevant economic and social impact.The seismic risk in urban areas is mainly linked to three factors, namely, “hazard”, “exposure” and “vulnerability”. Hazard measures the potential of an earthquake to produce harm; exposure evaluates the amount of population exposed to harm; vulnerability represents the proneness of considered buildings to suffer damages in case of an earthquake. Estimates of such factors may not always coincide with the perceived risk of the resident population. The propensity to implement structural seismic improvement interventions aimed at reducing the vulnerability of buildings depends significantly on the perceived risk.This paper investigates on the difference between objective and perceived risk and highlights some critical issues. The aim of this study is to calibrate opportune policies, which allow addressing the most appropriate seismic risk mitigation options with reference to current levels of perceived risk. We propose the introduction of a Seismic Policy Prevention index (SPPi). This methodology is applied to a case-study focused on a densely populated district of the city of Catania (Italy).

Fumaric acid esters (FAEs) are small molecules with anti-oxidative, anti-inflammatory and immune-modulating effects. Dimethyl fumarate (DMF) is the best characterised FAE and is approved and registered for the treatment of psoriasis and Relapsing-Remitting Multiple Sclerosis (RRMS). Psoriasis and RRMS share an immune-mediated aetiology, driven by severe inflammation and oxidative stress. DMF, as well as monomethyl fumarate and diroximel fumarate, are commonly prescribed first-line agents with favourable safety and efficacy profiles. The potential benefits of FAEs against other diseases that appear pathogenically different but share the pathologies of oxidative stress and inflammation are currently investigated.

Today, various questionnaires are available to assess Adverse Childhood Experiences (ACEs) in children; however, it is uncertain if these questionnaires comprehensively address the adversities of vulnerable subgroups, specifically refugee children. This review's objectives are to (1) identify current ACE questionnaires and determine if they are suitable for assessing refugee children’s adversities, and (2) identify those previously used within a refugee population. A systematic literature search was conducted across five databases for articles published since 2010, including studies using an ACE questionnaire that recognized multiple adversities in healthy children and were published in English. A total of 103 ACE questionnaires were identified in 506 studies. Only 14 of the 103 questionnaires addressed a refugee-specific adversity. Their ability to capture refugee children’s experiences was limited: available questionnaires used a maximum of three items to assess refugee-specific adversities, covering only a fraction of forms of adversities relevant to refugee children. Psychometric characteristics were rarely reported. In addition, only two ACE questionnaires were used within a refugee population. With the tools currently available, it is not possible to comprehensively assess the exposure to and severity of the adversities faced by refugee children. The perpetuation of ongoing crises necessitates assessing refugee children's adversities to understand how their well-being is affected and to identify children at risk.

We address the problem of finding a unique graph embedding that best describes a graph's "topology". This issue is of particular interest in the chemistry of materials. Graphs that admit a tiling in 3-dimensional Euclidean space are termed tessellate, those that do not decussate. We give examples of decussate and tessellate graphs that are finite and 3-periodic. We conjecture that a graph has at most one tessellate embedding. We give reasons for considering this the default "topology" of periodic graphs.

Bovine herpesvirus (BoHV)-5 is a worldwide distributed pathogen usually associated with a lethal neurological disease (meningoencephalitis) in dairy and beef cattle resulting in important economic losses due to the cattle industry. Using recombinant glycoprotein D of BoHV-5 (rgD5), we evaluated the long-duration humoral immunity of the recombinant vaccines in a cattle model. Here we report that two doses of intramuscular immunization, particularly with the rgD5ISA vaccine, are superior to iBoHV-5ISA immunization in the induction of long-lasting antibody responses. Recombinant gD5 antigen elicited tightly mRNA transcription of the Bcl6 and the chemokine receptor CXCR5 which mediate memory B cells and long-lived plasma cells in germinal centers (GCs). In addition, using an in-house Enzyme-Linked Immunosorbent Assay (ELISA) we observed higher and earlier responses of rgD5-specific IgG antibody and the upregulation of mRNA transcription of IL2, IL4, IL10, IL15 and IFN-γ cytokines in rgD5 vaccinated cattle, indicating a mixed immune response. We further show that rgD5 immunization provides protection against both BoHV -1 and -5. Our findings indicate that the rgD5-based vaccine represents an effective vaccine strategy to induce an efficient control of alpha-herpesviruses.

The diverse socio-economic and environmental impacts that the set-up of a new photovoltaic installation has must be weighed carefully in order to reach the best possible solution. Among the different photovoltaic systems there are several classification criteria, depending on the technology, application and the size of the modules that define them. The size (installed nominal capacity) stands out as an impartial and critical measure in the decision making process. In this article we use a multi-criteria decision making method to analyse the responses of five experts to a detailed questionnaire in which several different criteria are correlated with various photovoltaic installation sizes. The limitation associated to the low number of experts is addressed with a robustness and sensitivity analysis. With this study we seek first, to apply and demonstrate the feasibility of a methodology which combines technical information with multi-criteria decision making methods, and second, to obtain a clear result oriented that increases the benefits of a forthcoming photovoltaic installation of modules in distributed generation adding up to 1GW total peak power in standard conditions. We observe a consistent result in which smaller photovoltaic modules are the ideal solution that maximises the socio-economic benefits of any installation. If a decision has to be taken about the type of photovoltaic plant to be installed, the conclusion is clear: given a certain size, small, easily scalable installations are the best solution for stake-holders, for the inhabitants, and for the environment.

The article presents the results of cyanide leaching of gold-containing concentrate using the trichlorocyanuric acid (TCCA) oxidizer. Gold-containing concentrate obtained from a gold tailings sample from a gold recovery factory (GRF) in one of the deposits of Kazakhstan that was not previously studied for concentrability. According to X-ray phase analysis and energy dispersive spectrometry (DSM) data, the main compounds in the tailings sample under study are: pyrite FeS2, quartz SiO2, calcite CaCO3, albite NaAlSi3O8, muscovite KAl2Si3AlO10(OH)8, dolomite CaMg(CO3)2, and oxidized iron compounds. Microscopic studies have established the presence of gold grains in free form, ranging in size from 0.9-10.2 mkm Au-ultrafine and fine gold. Obtaining a gold-containg concentrate with a gold content of 15.95 g / t is possible according to the enrichment scheme, which includes centrifugal separation, classification according to the fineness class -0.05 mm, additional grinding of hydrocyclone sands to a fineness of 90.0-95.0% of the class finer than 0.050 mm, and control centrifugal separation. Since pyrite in technogenic raw materials is the main gold-containing mineral, this paper presents studies on the oxidizability of pyrite with the TCCA oxidizer. The results of studies on the oxidation of pyrite using the TCCA oxidizer show that the products of its hydrolysis oxidize pyrite with the formation of various iron compounds on its surface. Pretreatment of gold-containing concentrate with oxidizer TCCA for 3 hours before the cyanidation process (20 hours) allows to increase the recovery of gold in the solution by 5.8 %.

Future, flexible thermal energy conversion systems require new, demand-optimized high-performance materials. The High performance Ferritic (HiperFer) stainless steels, under development at the Institute of Microstructure and Properties of Materials (IEK-2) at Forschungszentrum Jülich GmbH in Germany, provide a balanced combination of fatigue, creep and corrosion resistance at reasonable price. This paper outlines the scientific background of alloy performance development, which resulted in an age-hardening ferritic, stainless steel grade. Furthermore, technological properties are addressed and the potential concerning application is estimated by benchmarking versus conventional state of the art materials.

This work investigated the isothermal holding time dependence of the densification, microstructure, weight loss and tensile properties of Fe-Mn-Si powder compacts. Elemental Fe, Mn and Si powder mixtures with a nominal composition of Fe-28Mn-3Si (in weight percent) were ball milled for 5h and subsequently pressed under a uniaxial pressure of 400 MPa. The compacted Fe-Mn-Si powder mixtures were sintered at 1200 ℃ for 0, 1, 2 and 3 h, respectively. In general, the density, weight loss and tensile properties increased with the increase of isothermal holding time. A significant increase in density, weight loss and tensile properties occurred in the compacts isothermally holding for 1 h, as compared to those with no isothermal holding. However, further extension of isothermal holding time (2 and 3 h) only played a limited role in promoting the density and tensile properties. The weight loss of the sintered compacts was mianly caused by the sublimation of Mn in Mn depletion region on the surface layer of the sintered Fe-Mn-Si compacts. The length of the Mn depletion region increased as isothermal holding time increased. A single α-Fe phase was detected on the surface of all the sintered compacts, and the locations beyond the Mn depletion region were comprised of a dual dominant γ-austenite and minor ε-martensite.

Aluminum, a contentious trace element found in the environment, has been demonstrated to have harmful effects on both humans and animals. In contrast, Sempervivum tectorum, an evergreen plant, has been found to offer numerous beneficial effects for both humans and animals. Therefore, this study aims to assess the protective effect of S. tectorum on certain reproductive biomarkers in male rats exposed to aluminum. Thirty-five Wistar rats were randomly divided into five groups: NTC (no-treatment control) received distilled water; NC (negative control) received drinking water containing 1 mg/L aluminum sulfate (AS); E1 received 1 mg/L AS along with an 8% S. tectorum extract; PC (positive control) received only 8% S. tectorum extract; E2 received 1 mg/L AS for three months followed by 8% extract for one month. The study analyzed testosterone, LH, FSH, body weight, and the histological structure of the testis, epididymis, and prostate, as well as the levels of zinc, manganese, copper, and iron in these organs. Significant decreases in body weight, testis, and epididymis size were observed in the aluminum-exposed groups compared to the control, whereas these decreases were not significant in the S. tectorum-treated groups compared to the control. Aluminum exposure led to significant decreases in testosterone and LH levels, with FSH levels showing a non-significant decrease in males, which were mitigated significantly by the administration of the plant extract. Histological analysis revealed alterations in the testis, epididymis, and prostate of the AS-exposed groups, including necrosis of seminiferous tubule epithelium and Leydig cells in the testis, and basal epithelial necrosis in the epididymis and prostate. Aluminum levels increased in all organs studied, while levels of zinc, copper, iron, and manganese decreased, showing a negative and significant correlation with aluminum levels. The aqueous extract of S. tectorum demonstrated a protective effect on certain studied biomarkers in male rats affected by aluminum exposure.

This paper will discuss Data, Information, Knowledge, and Wisdom, which is commonly referred to as DIKW. The DIKW Pyramid Model that is often referenced in both academics and practitioner circles will be discussed and shown to be faulty on several levels, including. a lack of definitional agreement. A new DIKW framework will be proposed that focuses on what the DIKW elements do in the way humans think, not what they are by definition. Information as a replacement for wasted physical resources in goal-oriented tasks will be a central organizing point. The paper will move the DIKW discussion to the computer-based concept of Digital Twins (DTs) and its augmentation of how we can use DIKW to be more effective and efficient. This will especially be the case as we move to Intelligent Digital Twins (IDT) with Artificial Intelligence (AI).

By using a systems biological perspective and available literature on human social interaction, grouping, and cohesiveness, a new coherent model is proposed that integrates existing social integration and neurobiological research into a theoretical neurobiological framework of personality and social interaction. This model allows for the coherent analysis of complex social systems and interactions within them, and proposes a framework for estimating group cohesiveness and evaluating group structures in order to build and organize optimized social groups. This „Neurobiological-Associative“ model proposes two primary feedback loops, with environmental conditioning (learning) being sorted into an associative model that modulates interaction with the social environment, and which impacts the second feedback loop involving the individuals' neurobiological capacity. In this paper, the concept of neurobiological capacity is developed and based upon contemporary research on intelligence, personality, and social behavior with a focus on the oxytocin, serotonin, and dopamine systems. The basis of social exclusion and group structure is thus, expressed in the very most simple terms, neurobiological compatibility and risk assessment modulated by an internal associative model.

Considering that life on earth evolved about 3.7 billion years ago, vertebrates are young, appearing in the fossil record during the Cambrian explosion about 542 to 515 million years ago. Results from sequence analyses of genomes from bacteria, yeast, plants, invertebrates and vertebrates indicate that receptors for adrenal steroids (aldosterone, cortisol), and sex steroids (estrogen, progesterone, testosterone) also are young, with an estrogen receptor and a 3-ketosteroid receptor first appearing in basal chordates (cephalochordates: amphioxus), which are close ancestors of vertebrates. Through gene duplication and divergence of the 3-ketosteroid receptor, receptors that respond to androgens, glucocorticoids, mineralocorticoids and progestins evolved in vertebrates. Thus, an ancestral progesterone receptor and an ancestral corticoid receptor, the common ancestor of the glucocorticoid and mineralocorticoid receptors, evolved in jawless vertebrates (cyclostomes: lampreys, hagfish). This was followed by evolution of an androgen receptor, distinct glucocorticoid and mineralocorticoid receptors and estrogen receptor-α and -β in cartilaginous fishes (gnathostomes: sharks). Further evolution of mineralocorticoid signaling occurred with the evolution of aldosterone synthase in lungfish, a forerunner of terrestrial vertebrates. Adrenal and sex steroid receptors are not found in echinoderms: and hemichordates, which are ancestors in the lineage of cephalochordates and vertebrates. The evolution of steroid receptors at key nodes in the evolution of vertebrates, in which steroid receptors act as master switches to regulate differentiation, development, reproduction, immune responses, electrolyte homeostasis and stress responses, argues for an important role for steroid receptors in the evolutionary success of vertebrates, considering that the human genome contains about 22,000 genes, which is not much larger than genomes of invertebrates, such as Caenorhabditis elegans (~18,000 genes) and Drosophila (~14,000 genes).

There is much concern about disruption of endocrine physiology regulated by steroid hormones in humans, other terrestrial vertebrates and fish by industrial chemicals, such as bisphenol A, and pesticides, such as DDT. These endocrine-disrupting chemicals influence steroid-mediated physiology in humans and other vertebrates by competing with steroids for receptor binding sites, disrupting diverse responses involved in reproduction, development and differentiation. Here I discuss that due to evolution of the progesterone receptor (PR) and mineralocorticoid receptor (MR) after ray-finned fish and terrestrial vertebrates diverged from a common ancestor, each receptor evolved to respond to different steroids in ray-finned fish and terrestrial vertebrates. In elephant shark, a cartilaginous fish, ancestral to ray-finned fish and terrestrial vertebrates, both progesterone and 17,20-beta-dihydroxy-progesterone activate the PR. During the evolution of ray-finned fish and terrestrial vertebrates, the PR in terrestrial vertebrates continued responding to progesterone and evolved to weakly respond to 17,20-beta-dihydroxy-progesterone. In contrast, the physiological progestin for the PR in zebrafish and other ray-finned fish is 17,20-beta-dihydroxy-progesterone, and ray-finned fish PR responds weakly to progesterone. The MR in fish and terrestrial vertebrates also diverged to have different responses to progesterone. Progesterone is a potent agonist for elephant shark MR, zebrafish MR and other fish MRs, in contrast to progesterone’s opposite activity as an antagonist for aldosterone, the physiological mineralocorticoid for human MR. These different physiological ligands for fish and terrestrial vertebrate PR and MR need to be considered in applying data for their disruption by chemicals in fish and terrestrial vertebrates to each other.

This research investigates the potential application of generative language models, especially ChatGPT, in aviation safety analysis as a means to enhance the efficiency of safety analyses and accelerate the time it takes to process incident reports. In particular, ChatGPT was leveraged to generate incident synopses from narratives, which were subsequently compared with ground truth synopses from the Aviation Safety Reporting System (ASRS) dataset. The comparison was facilitated by using embeddings from Large Language Models (LLMs), with aeroBERT demonstrating the highest similarity due to its aerospace-specific fine-tuning. A positive correlation was observed between synopsis length and their cosine similarity. In a subsequent phase, human factor issues involved in incidents as identified by ChatGPT were compared to human factor issues identified by safety analysts. A concurrence rate of 61% was found, with ChatGPT demonstrating a cautious approach towards attributing human factor issues. Finally, the model was used to attribute incidents to relevant parties. As no dedicated ground truth column existed for this task, a manual evaluation was conducted. ChatGPT attributed the majority of incidents to the Flight Crew, ATC, Ground Personnel, and Maintenance. This study opens new avenues for leveraging AI in aviation safety analysis.

The spillover of the terrorist activities of Boko Haram, a Nigerian jihadi group, into Cameroon’s northern region has resulted in security challenges and humanitarian activity opportunities for Christian churches. The insurgents have attacked and destroyed churches, abducted Christians, worsened Muslim-Christian relations, and caused a humanitarian crisis. Aggregately, these ensuing phenomena have adversely affected Christian churches in this region, triggering an aura of responses: coping strategies, humanitarian work among refugees, and inter-faith dialogue. These responses are predicated on Christianity’s potential as a resource for peace, compassion, and love. In this study we emphasize the role of Christian churches in dealing with the Boko Haram insurgency. It opens up with a contextualization of Boko Haram in Cameroon’s north. This is followed by an examination of the brutality meted out on Christians and church property. The final section is an examination of the spiritual, humanitarian and relief services provided by Christian churches. The paper argues that although Christian churches have suffered at the hands of Boko Haram insurgents, they have engaged in various beneficial responses underpinned by the Christian values of peace and love.

Modern gastroenterology, which occupies the pages of scientific journals without alternative, began as an initiative of manufacturers of diagnostic equipment. For widespread advertising, they selected practical doctors who were not familiar with the methodology of science and superficial knowledge of physiology. This is how a group led by DeMeester arose, which in 1976 published the DeMeester score, i.e., the normal limit for esophageal pH monitoring. pH <4, less than 4% of the time per day was considered normal, i.e., it was unreasonably claimed that such reflux is physiological. This article proves that this study was carried out with numerous methodological errors, which led to an erroneous conclusion. For a long time, pH monitoring was considered the gold standard and with its help hypotheses were proposed that form the basis of modern gastroenterology. The article proves the fallacy of 13 hypotheses, which are presented as theories. Numerous articles using pH monitoring have publicized this method. Practitioners became "great scientists", equipment manufacturers became successful businessmen. Over time, they found other groups of practitioners to promote devices for impedance ph monitoring, high-resolution manometry, and many others. At the same time, a network of reviewers who believe in the infallibility of the luminaries do not allow studies that contradict their faith to be published. Thus, fundamental science was destroyed, which alone could assess the harm of false research both for science and for patients. Conclusion This study provides a list of hypotheses, that were previously considered theories, but since scientific evidence has proven these assumptions to be false, they should be excluded from subsequent use and citation.

Statistical modeling lies at the heart of product design and development throughout numerous engineering disciplines, especially since processing large amounts of data has become increasingly ubiquitous. While mathematical statistics provide elegant guidance pertaining to the question of whether or not some particular underlying modeling assumptions are justified and appropriate, when pursuing a more comprehensive assessment of product design and development other considerations often increase in significance. Therefore, we will examine and analyze the tedious interactions and implications of statistical modeling choices and product liability exposure. To the best of our knowledge, this paper is the first to draw attention to and explore some often overlooked or oversimplified dangers and pitfalls that enter the equation when product design heavily relies on statistical modeling. In particular, through a diligent analysis of both statistical and legal aspects we will explore how statistically optimal procedures may yield far from optimal outcomes in terms of product liability when applied to actual real life problems and why suboptimal nonparametric or robust approaches may constitute better alternatives.

Problem solving is one of the most important components of the human cognition that affects for ages the progress of the human society. Mathematical modelling is a special type of problem solving concerning problems related to science or everyday life situations. The present study is a review of the author’s earlier works on problem solving and mathematical modelling from the scope of Education. Its real goal is that it presents in a systematic way and in a few pages only the results of many years research on the subject. This helps the reader to get a comprehensive idea about a very important topic belonging to the core of Mathematics Education, which is very useful to those wanting to study deeper the subject and get directions for further research in the area.

Recently concluded, large-scale cancer genomics studies involving multiregion sequencing of primary tumors and paired metastases appear to indicate that many or most cancer patients have one or more “clonal" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. Achilles Therapeutics is currently the only company specifically targeting clonal mutations. However, they are doing so with tumor-derived T cells. To address the potential limitations of immunotherapy, I have devised another approach for exploiting clonal mutations, which I call “Oncolytic Vector Efficient Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). The ideal version of OVERCOME would likely employ a bioengineered facultative intracellular bacterium. The bacterium would initially be attenuated, but (transiently) reverse its attenuation upon clonal mutation detection.

Knowledge about laminar-turbulent transition on operating multi-megawatt wind turbine blades needs sophisticated equipment like hot-films or microphone arrays. Contrarily thermographic pictures can easily be taken from the ground and temperature differences indicate different states of the boundary layer. The accuracy however, still is an open question, so that an aerodynamic glove known from experimental research on aero-planes was used to classify the boundary-layer state of a 2 megawatt wind turbine blade operating in the orthern part of Schleswig-Holstein, Germany. State-of-the-art equipment for measurering static surface pressure was used for monitoring the lift distribution. To distinguish laminar and turbulent parts of the boundary layer (suction side only) 48 microphones were applied together with ground-based thermographic cameras from two teams. Additionally, an optical camera mounted on the hub was used to survey vibrations. During start-up (from 0 to 9 rpm) extended, but irregularly shaped regions of a laminar boundary layer were observed which had the same extension measured both with microphones and Thermography. When an approximately constant rotor rotation (9 rpm corresponding to approximately 6 m/s wind-speed) was achieved, a flow transition was visible at the expected position of 40 % chord length on the rotor blade, which was fouled with dense turbulent wedges and an almost complete turbulent state on the glove was detected. In all observations, quantitative determination of the flow transition positions from thermography and microphones agree well within their accuracy.

SETMAR is a protein lysine methyltransferase that is involved in several DNA processes, including DNA repair via the non-homologous end joining (NHEJ) pathway, regulation of gene expression, illegitimate DNA integration, and DNA decatenation. However, SETMAR is an atypical protein lysine methyltransferase since in anthropoid primates, the SET domain is fused to an inactive DNA transposase. The presence of the DNA transposase domain confers to SETMAR a DNA binding activity towards the remnants of its transposable element, which has resulted in the emergence of a gene regulatory function. Both the SET and the DNA transposase domains are involved in the different cellular roles of SETMAR, indicating the presence of novel and specific functions in anthropoid primates. In addition, SETMAR is dysregulated in different types of cancer, indicating a potential pathological role. While some light has been shed on SETMAR functions, more research and new tools are needed to better understand the cellular activities of SETMAR and to investigate the therapeutic potential of SETMAR.

The conventional explanation of delayed-choice experiments seems to violate our causal intuition. This apparent violation is caused by a misinterpretation of the conventional formulation of quantum mechanics. I reanalyze these experiments using advanced and time-symmetric formulations of quantum mechanics. All three formulations give the same experimental predictions, but the advanced and time-symmetric formulations violate our causal intuition that effects only happen after causes. I explore reasons why our causal intuition may be wrong at the quantum level. I also suggest how conventional causation might be recovered in the classical limit, and speculate on cosmological boundary conditions.

Stellar heated gas and dust makes a significant entropic/information energy contribution to the universe. At temperatures ~10⁷ the ~10⁸⁶ bits are equivalent to ~10⁷⁰J, equivalent to the energy equivalence of the universe’s ~10⁵³ kg ordinary baryon matter. A survey of stellar mass density measurements shows this dark energy contribution has a constant energy density that effectively mimics a cosmological constant over the redshift range z<1.35. The measurable difference between this information energy and a true cosmological constant is small, with a maximum difference of <2% in Hubble parameter at z~2. As information energy is significant and co-located with hot baryons it produces gravitational effects that resemble dark matter. Information energy is shown to be consistent with the dark matter effects observed in clusters of colliding galaxies (e.g. Bullet Cluster), with dark matter location specified by baryon location and strongest in regions of highest luminosity / temperature. The dark matter fraction measured in galaxy surveys more closely fits an information energy explanation than the fraction expected in the standard ɅCDM model. Information energy provides a solution to the cosmological coincidence problem and also would allow the cosmological constant to take the preferred zero value.

Adeno-associated viral (AAV) vectors can be used for gene delivery. AAV.CAP-Mac was recently developed; it can cross the blood-brain barrier and transduce cells throughout the CNS. However, some brain regions were not transduced in adult rhesus monkeys. Additionally, AAV vectors can only package 5 kb of DNA. Also, AAV vectors may be genotoxic and cytotoxic, especially at high doses. Finally, AAV vectors are very expensive to produce at sufficiently high titers for treatment. Off-the-shelf cell-based delivery systems wherein the cells can infiltrate the target tissue and be hyper-motile would be ideal. Also, mRNA-based gene editing would be a transient treatment, and thus be much safer.

Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a post-mitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. It may be the case that lipofuscin accumulation is the main issue with regard to current age-related disease. Degradation in situ may be an insurmountable task currently. However, a method of systemic lipofuscin removal is discussed herein.

This review covers some of the central relationships between artificial intelligence, psychology, and economics through the lens of information theory, specifically focusing on formal models of decision-theory. In doing so we look at a particular approach that each field has adopted and how information theory has informed the development of the ideas of each field. A key theme is expected utility theory, its connection to information theory, and the Bayesian approach to decision-making and forms of (bounded) rationality. What emerges from this review is a broadly unified formal perspective derived from three very different starting points that reflect the unique principles of each field. Each of the three approaches reviewed can, in principle at least, be implemented in a computational model in such a way that, with sufficient computational power, they could be compared with human abilities in complex tasks. However, a central critique that can be applied to all three approaches was first put forward by Savage in {\it The Foundations of Statistics} and recently brought to the fore by the economist Binmore: Bayesian approaches to decision-making work in what Savage called `small worlds' but cannot work in `large worlds'. This point, in various different guises, is central to some of the current debates about the power of artificial intelligence and its relationship to human-like learning and decision-making. Recent work on artificial intelligence has gone some way to bridging this gap but significant questions still need to be answered in all three fields in order to make progress on these problems.

Here we present a fast and highly scalable community structure preserving network module detection that recursively integrates graph sparsification and clustering. Our algorithm, called SparseClust, participated in the most recent DREAM community challenge on disease module identification, an open competition to comprehensively assess module identification methods across a wide range of biological networks.

Research into the causes of neurotoxicity in Alzheimer’s Dementia (AD) has focused on neurofibrillary tangles and beta amyloid (Aβ) plaques. This paper proposes the heterodox theory that these hallmarks of AD are the visible effects, not direct causes of neuronal necrosis. Rather AD results from a combination of age-induced, disproportional decline in physiological support for aerobic metabolism, and dysregulation of the sleep cycle processes. The hypothesis is that the decimation of neurons in AD results from a combination of neurotoxicity and increased apoptosis caused by: 1. direct damage from toxic waste products of anaerobic glycolysis due to a progressive decline in the capacity of neurons to perform oxidative phosphorylation (OXPHOS) and an increased reliance on anaerobic glycolysis to meet metabolic needs; 2. impaired cellular repair and effluent release due to dysregulation of non-rapid eye movement (NREM) sleep allowing damage to cell membranes and synaptic junctions to accumulate inducing a chronic inflammatory response; 3. indirect damage from products produced by inflammatory reaction to toxic metabolites; 4. neuronal apoptosis from the AβPP-mediated pathway due to the age-induced decline of growth hormone (GH), GH-releasing hormone (GHRH) and insulin-like growth factor (IGF).

Extensive genome structure variation, such as copy number variations (CNVs) and presence/absence variations, is the basis for the remarkable maize genetic diversity; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene, ZmLOX5, leads to increased resistance of maize to herbivory by fall armyworms (FAW). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5, referred to as Yu796-2×LOX5. To test whether introgression of the Yu796-2×LOX5 locus into the herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either 2, 1 or 0 copies of the Yu796-2×LOX5 locus in the B73 background by six back crosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2×LOX5 inbred line displayed increased resistance against FAW associated with increased expression of ZmLOX5, increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×LOX5, resulting from the increased JA catabolism. Furthermore, B73-2×LOX5 displayed enhanced drought tolerance likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into the productive, but susceptible, crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.

Requirements are predominantly written in Natural Language (NL), which makes them accessible to stakeholders with varying degrees of experience, as compared to a model-based language which requires special training. However, despite its benefits, NL can introduce ambiguities and inconsistencies in requirements, which may eventually result in system quality degradation and system failure altogether. The system complexity that characterizes current systems warrants an integrated and comprehensive approach to system design and development. This need has brought about a paradigm shift towards Model-Based Systems Engineering (MBSE) approaches to system design and a departure from traditional document-centric methods. While, MBSE shows great promise, the ambiguities and inconsistencies present in NL requirements hinder their conversion to models directly. The field of Natural Language Processing (NLP) has demonstrated great potential in facilitating the conversion of NL requirements into a semi-machine-readable format that enables their standardization and use in a model-based environment. A first step towards standardizing requirements consists of classifying them according to the ``type'' (design, functional, performance, etc.) they represent. To that end, a language model capable of classifying requirements needs to be fine-tuned on labeled aerospace requirements. This paper presents the development of an annotated aerospace requirements corpus and its use to fine-tune BERT$_\text{BASE-UNCASED}$ to obtain aeroBERT-Classifier: a new language model for classifying aerospace requirements into design, functional, or performance requirements. A comparison between aeroBERT-Classifier and bart-large-mnli (zero-shot text classification) showcased the superior performance of aeroBERT-Classifier on classifying aerospace requirements despite being fine-tuned on a small labeled dataset.

Through the use of a simplified model of consciousness this paper illustrates the symptoms of schizophrenia linked to neocortical structures and functions. It makes the case that the bewildering and varied presentation of symptoms in schizophrenia can be analyzed and explained using such models. The model is used to illustrate the central thesis of the paper, that schizophrenia is a disorder of neurogenesis which leads to progressive neurochemical, functional and neurophysiological changes that create the characteristic behaviors of the disease.