Genetic susceptibility in psoriasis is a topic of interest in the initiative to improve targeted treatment strategies. In this review, we discuss genes linked to psoriasis and the available treatment options in context of targeting respective gene products implicated in the pathogenesis of psoriasis. In order to identify relevant genetic markers and treatments, we developed a literature search utilizing PubMed, Google Scholar, MEDLINE, and Web of Science with keywords, including genetic susceptibility to psoriasis, genetics and psoriasis, psoriasis treatments, biologics treatments in psoriasis. Articles in English from database inception to 1/1/23, were included. Case reports and series were excluded. Gene variant forms commonly implicated in the pathogenesis of psoriasis include those encoding for interleukins, interferons, and other mediators involved in inflammatory pathways, such as JAK/STAT, NFk-B, and others. Most commonly utilized treatments for psoriasis include drugs that target inflammatory markers like IL23, IL12, IL17, and TNF-a. TYK2 inhibition has been discussed as an emerging treatment strategy. Multiple genes are linked to the pathogenesis of psoriasis. This understanding may provide an avenue for further development of pharmacologic strategies targeting underlying genetic pathways. Genetically guided treatment may also allow for greater understanding in the selection of biologics.

Hydroperoxides (ROOH) are known as damaging agents capable of mediating mutation, while a role as signaling agents through oxidation of protein sulfhydryls that can alter cancer-related pathways has gained traction. Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme that reduces ROOH at the expense of glutathione (GSH). GPX2 is noted for a tendency of large in-creases or decreases in expression levels during tumorigenesis that leads to investigators focusing on its role in cancer. However, GPX2 is only one component of multiple enzyme families that metabolize ROOH and GPX2 levels are often very low in the context of these other ROOH reducing activities. Colorectal cancer (CRC) was selected as a case study for examining GPX2 function as colorectal tissues and cancers are sites where GPX2 is highly expressed. A case can be made for a significant impact of changes in expression levels. There is also a link between GPX2 and NADPH oxidase 1 (NOX1) from earlier studies that is seldom addressed and is discussed, presenting data on a unique association in colon and CRC. Tumor-derived cell lines are quite commonly used for pre-clinical studies involving the role of GPX2 in CRC. Generally, selection for this type of work is limited to identifying cell lines based on high and low GPX2 expression with the standard re-search scheme of overexpression in low expressing lines and suppression in high expressing lines to identify impacted pathways. This overlooks CRC subtypes among cell lines involving a wide range of gene expression profiles and a variety of driver mutation differences along with a large difference in GPX2 expression levels. A trend for low and high GPX2 expressing cell lines to segregate into different CRC subclasses, indicated in this report, suggests that choices based solely on GPX2 levels may provide misleading and conflicting results by disregarding other properties of cell lines and failing to factor in differences in potential protein targets of ROOH. CRC and cell line classification schemes are presented here that were intended to assist workers in performing pre-clinical studies but are largely unnoted in work on GPX2 and CRC. Studies are often initiated on the premise that the transition from normal to CRC is associated with up-regulation of GPX2. This is probably correct. However, the source normal cells for CRC could be almost any colon cell type, some with very high GPX2 levels. These factors are addressed in this study.

Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by Streptococcus pneumoniae (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen.

The Burkholderia cepacia complex (Bcc) are a group of increasingly multi-drug resistant opportunistic bacteria that can cause severe pulmonary infections. This resistance is driven through a combination of intrinsic factors and the carriage of a broad range of conjugative plasmids harbouring virulence determinants. Therefore, novel treatments are required to not only treat Bcc infection but also to prevent further spread of these virulence determinants. In the search for phages infective for two clinical Bcc isolates, CSP1 phage, a PRD1-like phage was isolated. CSP1 phage was found to require pilus machinery commonly encoded on conjugative plasmids to facilitate infection of multiple Gram-negative bacteria genera including Escherichia and Pseudomonas. Whole genome sequencing and characterisation of one of the clinical Burkholderia isolates revealed it to be Burkholderia contaminans. B. contaminans 5080 was found to contain a genome of over 8 Mbp encoding multiple intrinsic resistance factors, such as efflux pump systems, but more interestingly, carried three novel plasmids encoding multiple putative virulence factors for increased host fitness, including antimicrobial resistance. Even though PRD1-like phages are broad host range, their use in novel antimicrobial treatments shouldn’t be dismissed, as the dissemination potential of conjugative plasmids is extensive. Continued survey of clinical bacterial strains is

A two-stage pilot plant study has been completed that evaluated the performance of a reverse osmosis (RO) membrane process for the treatment of a feedwater that consisted of a blend of nanofiltration (NF) concentrate and brackish groundwater. Membrane performance was assessed by monitoring the process operation, collecting water quality data, and documenting the blended feedwater’s impact on fouling due to a combination of, or solely caused by, plugging, scaling, microbiological, or organic means. Fluorescence and biological activity reaction tests were used to identify the types of organics and microorganisms present in the blended feedwater. Additionally, scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDS) were used to analyze suspended matter that collected on the surfaces of cartridge filters used in the pilot’s pretreatment system. SEM and EDS were also used to evaluate solids collected on the surfaces of 0.45-µm silver filter pads after filtering known volumes of NF concentrate and RO feedwater blends. Water quality analyses confirmed that the blended feedwater contained little to no dissolved oxygen, and the blended feedwater was absent of a significant amount of particulate matter as defined by silt density index and turbidity measurements. However, water quality results suggested that the presence of sulfate, sulfide, iron, anaerobic bacteria, and humic acid organics likely contributed to the formation of pyrite observed on some of the membrane surfaces autopsied at the conclusion of pilot operations. It was determined that first-stage membrane productivity was impacted by the location of cartridge filter pretreatment; however, second-stage productivity was maintained with no observed flux decline during the entire pilot operation’s timeline. Study results indicated that the operation of an RO process treating a blend of NF concentrate and brackish groundwater could maintain a sustainable and productive operation that provided a practical zero-discharge process operation while the dilution of RO feedwater salinity would lower overall production costs.

Background: Permanent Daylight Savings Time (DST) may improve road safety by providing more daylight in the evening but could merely shift risk to morning commutes or increase risk due to fatigue and circadian misalignment. Methods: To identify how potential daylight exposure and fatigue risk could differ between permanent DST versus permanent Standard Time (ST) or current time arrangements (CTA), generic work and school schedules in five United States cities were modeled in SAFTE-FAST biomathematical modeling software. Commute data were categorized by morning (0700-0900) and evening (1600-1800) rush hours. Results: Percent darkness was greater under DST compared to ST for the total waking day (t=2.59, p=0.03) and sleep periods (t=2.46, p=0.045). Waketimes occurred before sunrise 63%±41% percent of the time under DST compared to CTA (42%±37%) or ST (33%±38%; F(2, 74)=76.37; p<0.001). Percent darkness was greater during morning (16%±31%) and lower during evening rush hour (0%±0%) in DST compare to either CTA (morning:7%±23%; evening:7%±14%) or ST (morning:7%±23%; evening:7%±15%). Discussion: Morning rush hour overlapped with students’ commutes and shift worker reverse commutes, which may increase traffic congestion and risk compared to evening rush hour. Switching to permanent DST may be more disruptive than either switching to ST or keeping CTA without noticeable benefit to fatigue or potential daylight exposure.

Over the last two decades, microfluidics has received significant attention from both academia and industry, and researchers report thousands of new prototype devices each year for use in a broad range of environmental, pharmaceutical, and biomedical engineering applications. While lab-on-a-chip fabrication costs have continued to decrease, the hardware required for monitoring fluid flows within microfluidic devices themselves remains expensive and often cost prohibitive for researchers interested in starting a microfluidics project. As microfluidic devices become capable of handling complex fluidic systems, low-cost, precise and real time pressure and flow rate measurement capabilities has become increasingly important. While many labs use commercial platforms and sensor, these solutions can often cost thousands of dollars and can be too bulky for on-chip use. Here we present a new inexpensive and easy -to-use piezoresistive pressure and flow sensor that can be easily integrated into existing on-chip microfluidic channels. The sensor consists of PDMS-Carbon black conductive membranes and uses an impedance analyzer to measure impedance change due fluid pressure. The sensor costs several orders of magnitude less than existing commercial platforms and can monitor local fluid pressures and calculate flow rates based on pressure gradient.

Deep learning techniques are increasingly being recognized as effective image classifiers. Aside from their successful performance in past studies, the accuracies have varied in complex environments in comparison with the popularly applied machine learning classifiers. This study seeks to explore the feasibility for using a U-Net deep learning architecture to classify bi-temporal high resolution county scale aerial images to determine the spatial extent and changes of land cover classes that directly or indirectly impact tidal marsh. The image set used in the analysis is a collection of a 1-m resolution collection of National Agriculture Imagery Program (NAIP) tiles from 2009 and 2019 covering Beaufort County, South Carolina. The U-net CNN classification results were compared with two machine learning classifiers, the Random Trees (RT) and the Support Vector Machine (SVM). The results revealed a significant accuracy advantage in using the U-Net classifier (92.4%) as opposed to the SVM (81.6%) and RT (75.7%) classifiers for overall accuracy. From the perspective of a GIS analyst or coastal manager, the U-Net classifier is now an easily accessible nad powerful tool for mapping large areas. Change detection analysis indicated little areal change on marsh extent, though increased land development throughout the county has the potential to negatively impact the health of the marshes. Future work should explore applying the constructed U-Net classifier to coastal environments in large geographic areas, while also implementing other data sources (e.g., LIDAR, multispectral data) to enhance classification accuracy.

The $k$-means problem is to compute a set of $k$ centers (points) that minimizes the sum of squared distances to a given set of $n$ points in a metric space. Arguably, the most common algorithm to solve it is $k$-means++ which is easy to implement, and provides a provably small approximation factor in time that is linear in $n$. We generalize $k$-means++ to support: (i) non-metric spaces and any pseudo-distance function. In particular, it supports M-estimators functions that handle outliers, e.g. where the distance $\mathrm{dist}(p,x)$ between a pair of points is replaced by $\min {\mathrm{dist}(p,x),1}$. (ii) $k$-means clustering with $m\geq 1$ outliers, i.e., where the $m$ farthest points from the $k$ centers are excluded from the total sum of distances. This is the first algorithm whose running time is linear in $n$ and polynomial in $k$ and $m$.

Radar transmit signal design is a critical factor for the radar performance. In this paper, we investigate the problem of radar signal waveform design under the small signal power conditions for detecting a doubly spread target, whose impulse response can be modeled as a random process, in a colored noise environment. The doubly spread target spans multiple range bins (range-spread) and its impulse response is time-varying due to fluctuation (hence also Doppler-spread), such that the target impulse response is both time-selective and frequency-selective. Instead of adopting the conventional assumption that the target is wide-sense stationary uncorrelated scattering,we assume that the target impulse response is both wide-sense stationary in range and in time to account for the possible correlation between the impulse responses corresponding to close range intervals. The locally most powerful detector, which is asymptotically optimal for small signal cases, is then derived for detecting such targets. The signal waveform is optimized to maximizing the detection performance of the detector or equivalently maximizing the Kullback-Leibler divergence. Numerical simulations validate the effectiveness of the proposed waveform design for the small signal power conditions and performance of optimum waveform design are shown in comparison to the frequency modulated waveform.

Global demand for sleep-tracking wearables, or consumer sleep technologies (CSTs), is steadily increasing. CST marketing campaigns often feature a scientific component, but the scientific relevancy and monetary value of CST features within the sleep research community remains unquantified. Sleep medicine experts were recruited through social media and nonprobability sampling techniques to complete a survey identifying sleep metrics and device features that are most desirable to the scientific community. A hypothetical purchase task (HPT) estimated economic valuation for devices with different features by price. Forty-six (N=46) respondents with an average of 10±6 years’ experience conducting research in real-world settings completed the online survey. Total sleep time was ranked as the most important measure of sleep followed by objective sleep quality while sleep architecture/depth and diagnostic information were ranked as least important. Experts preferred wrist-worn devices that could reliably determine sleep episodes as short as 20 minutes. Economic value was greater for hypothetical devices with longer battery life. These data set a precedent to determine how scientific relevance of a product impacts the potential market value of a CST device. This is the first known attempt to establish consensus opinion or economic valuation for scientifically-desirable CST features and metrics using expert elicitation.

A Brewer Spent Grain (BSG), the most abundant by-product of the brewing process, is mainly used in animal feed and biogas production. The aim of the present work is BSG valorization by yeast fermentation to produce carotenoids. R. mucilaginosa CBS316 was cultured on BSG syrups, supplemented or not with YE and PEP (s-Fsa and Fsa). The biomass and carotenoid production were optimized in flasks and then scaled-up in bioreactor. In flask tests, the maximum biomass concentration was 5.3 and 6.2 g/L for Fsa and s-Fsa cultures, respectively. The maximum carotenoid production was 833 μg/L in Fsa and 1159 μg/L in s-FSA. Considering that the highest specific productivity value (P 7.16 μg/g*h) was obtained with Fsa syrup, this medium was selected for the process scale-up. In bioreactor tests, the maximum concentrations of biomass (4.29 g/L) and carotenoid (396 ug/L) was reached at 72 hours of fer-mentation, 24 h later than in flask. The total carotenoid produced was 524 and 150 ug in bioreactor and flask cultures, respectively. The carotenoids production by R. mucilaginosa was obtained both in Fsa and s-Fsa syrups. The results confirm the possibility to use the syrup as it is, Fsa, thus limiting the process costs.

Men are more likely to develop cancer than women. In fact, male predominance is one of the most consistent cancer epidemiology findings. Additionally, men have a poorer prognosis and an increased risk of secondary malignancies compared to women. These differences have been investigated in order to better understand cancer and to better treat both men and women. In this review, we discuss factors that may cause this gender difference, focusing on urothelial bladder cancer (UBC) pathogenesis. We consider physiological factors that may cause higher male cancer rates, including differences in X chromosome gene expression. We discuss how androgens may promote bladder cancer development directly by stimulating bladder urothelium and indirectly by suppressing immunity. We are particularly interested in natural killer (NK) cells because they are important, but often overlooked anti-cancer lymphocytes.

In this paper, we have established Hermite-Hadamard inequalities for r-preinvex functions via fractional integrals.

The goal of this report was to examine the behavioral economic demand for consumer sleep technologies with different levels of validation and endorsement. The value or importance consumers place in different validation methods and the organizations conducting the evaluations was also assessed. Survey data were collected from 113 participants on Amazon mTurk. Participants indicated their likelihood of purchasing devices that varied in level of validation across a series of increasing prices. Demand curves were analyzed to determine the relative value of each watch type. Participants also reported how valuable or important different aspects of device validation were to them. Devices that were both evaluated against laboratory measures and endorsed by sleep researchers had the most value, followed by those only evaluated against laboratory measures, and then those not evaluated against any laboratory measures. The unit price at which there was 50% probability of purchase was increased by $25 or $44 for evaluation or endorsement, respectively. Respondents indicated the most valuable features were a measure of sleep duration, that it was most important that devices were validated against measures of sleep from a laboratory or hospital, and that they would put a high value on sleep tracker endorsements from a university or academic institution. Consumer demand is greatest for a device that has been evaluated by an independent laboratory for accuracy in measuring sleep and is endorsed by an academic, medical, or government institution. These results indicate a role for scientific evaluation and endorsement in consumer preference for sleep trackers.

Rates of gestational cannabis use have increased despite limited evidence for its safety in fetal life. Recent animal studies demonstrate that prenatal exposure to 9-tetrahydrocannabinol (9-THC, the psychoactive component of cannabis) promotes intrauterine growth restriction (IUGR), culminating in postnatal metabolic deficits. Given IUGR is associated with impaired hepatic function, we hypothesized that 9-THC offspring would exhibit hepatic dyslipidemia. Pregnant Wistar rat dams received daily injections of vehicular control or 3 mg/kg 9-THC i.p. from embryonic day (E) 6.5 through E22. Exposure to 9-THC decreased the liver to body weight ratio at birth, followed by catch-up growth by three weeks of age. At six months, 9-THC-exposed male offspring exhibited increased visceral adiposity and higher hepatic triglycerides. This was instigated by augmented expression of enzymes involved in triglyceride synthesis (ACC, SCD, FABP1, and DGAT2) at three weeks. Furthermore, the expression of hepatic DGAT1/DGAT2 was sustained at six months, concomitant with mitochondrial dysfunction (i.e., elevated p66shc) and oxidative stress. Interestingly, decreases in miR-203a-3p and miR-29a/b/c, both implicated in dyslipidemia, was also observed in these 9-THC-exposed offspring. Collectively, these findings indicate that prenatal 9-THC exposure results in long-term dyslipidemia associated with enhanced hepatic lipogenesis. This is attributed by mitochondrial dysfunction and epigenetic mechanisms.

Fatigue risk to commercial pilots operating under global pandemic conditions had not been in-vestigated prior to COVID-19. Examining how pilots slept during COVID-19 pandemic-specific flights can provide a precedent for estimating fatigue risk for future public health emergencies. Twenty (n=20) pilots flying across five COVID-19 humanitarian missions between Brazil and China wore a sleep-tracking device (the Zulu watch), which has been validated for the estimation of sleep timing (sleep onset and offset), duration, efficiency, and sleep depth (Wake, Interrupted, Light, or Deep Sleep) throughout the mission period. Pilots also reported sleep timing, duration and subjective quality of their in-flight rest periods using a sleep diary. To our knowledge, this is the first report of commercial pilot sleep behavior during ultra-long-range operations under COVID-19 pandemic conditions. Moreover, these analyses provide an estimate of sleep depth during in-flight sleep, which has not been reported previously in the literature.

Residual stress (RS) is the most challenging problem in metal additive manufacturing (AM) since the build-up of high tensile RS may influence the fatigue life, corrosion resistance, crack initiation, and failure of the additively manufactured components. While tensile RS is inherent in all the AM processes, fast and accurate prediction of stress state within the part is extremely valuable and would result in optimization of the process parameters in achieving a desired RS and control of the build process. This paper proposes a physics-based analytical model to rapidly and accurately predict the RS within the additively manufactured part. In this model, a transient moving point heat source (HS) is utilized to determine the temperature field. Due to the high temperature gradient within the proximity of the melt pool area, material experience high thermal stress. Thermal stress is calculated by combining three sources of stresses known as stresses due to the body forces, normal tension, and hydrostatic stress in a homogeneous semi-infinite medium. The thermal stress determines the RS state within the part. Consequently, by taking the thermal stress history as an input, both the in-plane and out of plane RS distributions are found from incremental plasticity and kinematic hardening behavior of the metal by considering volume conservation in plastic deformation in coupling with the equilibrium and compatibility conditions. In this modeling, material properties are temperature-sensitive since the steep temperature gradient varies the properties significantly. Moreover, the energy needed for the solid-state phase transition is reflected by modifying the specific heat employing the latent heat of fusion. Furthermore, the multi-layer and multi-scan aspects of metal AM are considered by including the temperature history from previous layers and scans. Results from the analytical RS model presented excellent agreement with XRD measurements employed to determine the RS in the Ti-6Al-4V specimens.

Seizure development relies on two factors. One is the existence of an overexcitable neuronal network and the other is a trigger that switches normal activity of that network into a paroxysmal state. While mechanisms of local overexcitation have been the focus of many studies, the process of triggering remains poorly understood. We suggest that, apart from the known exteroceptive sources of reflex epilepsy – visual, auditory or olfactory, there is a range of interoceptive triggers, relevant for seizure development in Temporal Lobe Epilepsy (TLE). The hypothesis proposed here aims to explain the prevalence of epileptic activity in sleep and in drowsiness states and provide a detailed mechanism of seizure triggering by interoceptive signals.

In this paper, we classify the function space of all real-valued functions on R denoted as F(R,R) into 28 distinct blocks. Each block contains elements that share common features in terms of the cardinality of their sets of continuity and differentiability. Alongside this classification, we introduce the concept of the Connection, which reveals a special relationship structure between four well-known real-valued functions in real analysis: the Cantor function, Dirichlet function, the Thomae function, and the Weierstrass function. Despite the significance of this field, several perspectives remain unexplored.

Despite great strides in diagnosis and treatment, cardiac diseases remain the number one cause of mortality in the developed world, with rates catching up at an alarming rate in the developing world. Targeted delivery of therapeutics, specifically to cardiomyocytes, would open up new frontiers. Our prior work using a combinatorial in vitro and in vivo phage display methodology identified a 12-amino acid long peptide that targets cardiomyocytes selectively after an intravenous injection in as little as 5 mins, and hence was termed cardiac targeting peptide (CTP: APHLSSQYSRT). CTP has been used to deliver imaging agents, small drug molecules, photosensitizing nanoparticles, exosomes, and even miRNA to cardiomyocytes. As a natural extension for development of CTP as a clinically viable cardiac vector, we now present toxicity studies performed on the peptide. In vitro viability studies were performed in a human left ventricular myocyte cell line with 10µM of Cyanine-5.5 labeled CTP (CTP-Cy5.5). In vitro ion channel profiles were completed for CTP followed by more extensive studies performed by Eurofins in stably transfected cell lines for an extensive list of GPCR-coupled receptors. Positive data for GPCR-coupled receptors was interrogated further with RT-qPCRs performed on mouse heart tissue. In vivo studies consisted of pre- and post-blood pressure monitoring acutely after a single CTP (10 mg/Kg) injection. Further in vivo toxicity studies consisted of injecting 60, 6-week-old, wild-type CD1, male/female mice (1:1) injected with CTP (150 µg/Kg) intravenously. Mice were weighed immediately before injections and daily thereafter. Cohorts of mice were euthanized on day 0, 1, 2, 7 and 14 with inhalational CO2, followed by opening of the chest cavity, collection of blood via cardiac puncture, complete blood count analysis, metabolic profiling, and finally, liver, renal and thyroid studies. Lastly, mouse cardiac MRI was performed immediately before and after injections of CTP (150 µg/Kg) to assess changes in cardiac size or function. Human left ventricular cardiomyocytes showed no decrease in viability after a 30 min incubation with CTP-Cy5.5. In the Eurofins Cardiac Profiler Qube, no significant activation or inhibition of any of seventy-eight protein channels was observed other than OPRM1 and COX2 at the highest tested concentration, neither of which were expressed in mouse heart tissue as assessed by RT-qPCR. There was no change in blood pressures before and after injections with CTP at 10 mg/Kg. Blood counts and chemistries showed no evidence of significant hematological, hepatic or renal toxicities. Lastly, there was no significant difference in cardiac function, size or mass before and after CTP injections. Our studies with CTP showed no activation or inhibition of GPCR-associated receptors in vitro. We found no signals indicative of toxicity in vivo. Most importantly, cardiac functions remained unchanged acutely in response to CTP uptake. Further studies, in good laboratory practices fashion, are needed with more prolonged, chronic administration of CTP conjugated to a specific cargo of choice before human studies can be contemplated.

The effective Supervisory Control and Data Acquisition (SCADA) system can improve the reliability, safety and economic benefits of microgrid operation. In this research, the lower central controller and upper WEB monitoring system are connected by the SCADA system which is as the hub of microgrid intelligent monitoring platform. This system contains a set of specific functions programmed by Java as a middleware which can provide control and communication between the central controller and the upper monitoring system. The system realizes the real-time data acquisition and storage, the control instructions parsing and transmitting, the microgrid security and stability, the load balancing and resource recovery of the microgrid. All that functions have been tested and verified in the actual operation.

In this note we generalize the regularity concept for semigroups in two ways simultaneously: to higher regularity and to higher arity. We show that the one-relational and multi-relational formulations of higher regularity do not coincide, and each element has several inverses. The higher idempotents are introduced, and their commutation leads to unique inverses in the multi-relational formulation, and then further to the higher inverse semigroups. For polyadic semigroups we introduce several types of higher regularity which satisfy the arity invariance principle as introduced: the expressions should not depend of the numerical arity values, which allows us to provide natural and correct binary limits. In the first definition no idempotents can be defined, analogously to the binary semigroups, and therefore the uniqueness of inverses can be governed by shifts. In the second definition called sandwich higher regularity, we are able to introduce the higher polyadic idempotents, but their commutation does not provide uniqueness of inverses, because of the middle terms in the higher polyadic regularity conditions.

There has been a growing call for reform of the U.S. biomedical community in recent years. As a community, we face a growing list of issues including excessive waste, reproducibility, bias, inadequate training, and the absence of sustainable long-term planning that detract from the overall goal of advancing human health. In response to this debate, biomedical stakeholders have taken positive steps forward to remedy these issues. However, we must continually improve upon these steps to promote the long-term stability of the biomedical enterprise. Given the widespread interest of the scientific community in addressing these issues, there exists a unique opportunity to come together and create a new era of biomedical discovery. The completion of this exciting task requires reflection on our view and management of the system, and what the best route to sustainable change may be. Importantly, a coordinated approach that considers the collective make-up of the biomedical system and how processes and people influence collective output and create value for patients is needed. Here, these three areas and the concepts of systems theory, total quality management, and organizational development and their contribution to the management and effectiveness of biomedical discovery are discussed. Importantly recommendations are made concerning overall management strategy, process efficiency and quality research, administrative tasks, organizational cultural challenges, individual and team development, and funding strategy.

Linear elastic fracture modeling coupled with empirical material tension data result in good quantitative agreement with experimental measurements of fracture failure for both brittle and tough epoxy nanocomposites. The nanocomposites comprise diglycidyl ethers of bisphenol A cured with O,O’ bis (2-aminopropylpropylene glycol) (Jeffamine D230) and doped with rubber nanoparticles of varying concentrations. Toughness, critical load, and critical displacement in quasi-static single edge-notched three-point bending are predicted accurately using both surface-based cohesive zone (CZS) and extended finite element (XFEM) methods implemented in Abaqus software. Fracture initiation within a crack is taken at the yield stress from uniaxial tension data. Prediction of fracture processes using a generalized truncated linear traction-separation law was significantly improved by considering the case of a linear softening function. There are no adjustable parameters in the XFEM model. The CZS model requires only optimization of the element displacement at fracture parameter. Thus, these continuum methods describe these materials in mode I fracture with a minimum number of independent parameters.

Many microbes live in habitats below their optimum temperature. Retention of metabolic heat by aggregation or insulation would boost growth. Generation of excess metabolic heat may also provide benefit. A cell that makes excess metabolic heat pays the cost of production, whereas the benefit may be shared by neighbors within a zone of local heat capture. Metabolic heat as a shareable public good raises interesting questions about conflict and cooperation of heat production and capture. Metabolic heat may also be deployed as a weapon. Species with greater thermotolerance gain by raising local temperature to outcompete less thermotolerant taxa. Metabolic heat may provide defense against bacteriophage attack, by analogy with fever in vertebrates. This article outlines the theory of metabolic heat in microbial conflict and cooperation, presenting several predictions for future study.

In recent years, biomedical research has faced increased scrutiny over issues related to reproducibility and quality in scientific findings(1-3). In response to this scrutiny, funding institutions and journals have implemented top-down policies for grant and manuscript review. While a positive step forward, the long-term merit of these policies is questionable given their emphasis on completing a check-list of items instead of a fundamental re-assessment of how scientific investigation is conducted. Moreover, the top-down style of management used to institute these policies can be argued as being ineffective in engaging the scientific workforce to act upon these issues. To meet current and future biomedical needs, new investigative methods that emphasize collective-thinking, teamwork, shared knowledge and cultivate change from the bottom-up are warranted. Here, a perspective on a new approach to biomedical investigation within the individual laboratory that emphasizes collaboration and quality is discussed.

Some peptide-based drugs including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bonds. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO2@TPEA@Pt(IV)) was synthesized via a four-step procedure and used for formation of intramolecular disulfide bonds in peptides. TEM and chemical mapping results for the Pt(II) intermediates and for SiO2@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly distributed Si, O, C, N, Cl, and Pt. The valence state of Pt on the silica nanospheres was characterized by XPS. The Pt(IV) loaded on SiO2@TPEA@Pt(IV) was 0.15 mmol/g, as determined by UV-vis spectrometry. Formation of intramolecular disulfides in six dithiol-containing peptides of variable lengths by use of SiO2@TPEA@Pt(IV) was investigated and the relative oxidation yields were determined by HPLC. In addition, peptide 1 (Ac-CPFC-NH2) was utilized to study the reusability of SiO2@TPEA@Pt(IV). No significant decrease in the relative oxidation yield was observed after ten reaction cycles. Moreover, the structure of SiO2@TPEA@Pt(IV) after being used ten cycles was determined to be similar to its initial one, demonstrating the cycling stability of the complex.

We developed two human induced pluripotent stem cell (hiPSC)/human embryonic stem cell-specific glycan-recognizing mouse antibodies, R-10G and R-17F, using the Tic (JCRB1331) hiPSC line as an antigen. R-10G recognizes a low-sulfate keratan sulfate, and R-17F recognizes lacto-N-fucopentaose-1. To evaluate the general characteristics of stem cell glycans, we used the hiPSC line 201B7 (HPS0063), a prototype iPSC line. Using an R-10G affinity column, an R-10G-binding protein was isolated. The protein yielded a single but very broad band from 480 to 1,236 kDa by blue native gel electrophoresis. After trypsin digestion, the protein was identified as podocalyxin by liquid chromatography/mass spectrometry. According to Western blotting, the protein reacted with R-10G and R-17F. The R-10G positive band was resistant to digestion with glycan-degrading enzymes, including peptide N-glycanase, but the intensity of the band was decreased significantly by digestion with keratanase, keratanase II, and endo-β-galactosidase, suggesting the R-10G epitope to be a keratan sulfate. These results suggest that keratan sulfate-type epitopes are shared by hiPSCs. However, the keratan sulfate from 201B7 cells contained a polylactosamine disaccharide unit (Galβ1-4GlcNAc) at a significant frequency, whereas that from Tic cells consisted mostly of keratan sulfate disaccharide units (Galβ1-4GlcNAc(6S)). In addition, the abundance of the R-10G epitope was significantly lower in 201B7 cells than in Tic cells.

This paper presents a simple drone survey and image processing approach to identifying St. John's wort (Hypericum perforatum) on grazing land in the Hunter Valley NSW, Australia. St John’s wort is an invasive species (weed) that competes with pasture, poisons livestock, can downgrade wool with ‘vegetable fault’, and decreases property values. Identifying the locations of St John wort from the ground can be difficult due to topography, limited access, and/or larger land areas of mixed vegetation. In this study, a drone was used to survey a 174-ha grazing property in the Hunter Valley NSW (Australia). The images were stitched together using commercially available software. A unique Visual Atmospheric Resistance Index (VARI) attribute was identified and used to highlight the presence of St John’s wort in the survey area. These sub-areas were then digitised onto high resolution maps for future planning use by land managers.

Mass transfer restrictions of scaffolds are currently hindering the development of three-dimensional (3D), clinically viable, and tissue engineered constructs. For this situation, a 3D poly(lactide-co-glycolide)/hydroxyapatite porous scaffold, which was much favorable for transfer of nutrients to and waste products from the cells in the pores, was developed in this study. The 3D scaffold had an innovative structure, including macropores with diameters of 300−450 μm for cell ingrowth and microchannels with diameters of 2−4 μm for nutrition and waste exchange. The mechanical strength in wet state was strong enough to offer the structural support. The typical structure was more beneficial for the attachment, proliferation, and differentiation of rabbit bone marrow mesenchymal stem cells (rBMSCs). The alkaline phosphatase (ALP) activity and calcium (Ca) deposition were evaluated on the differentiation of rBMSCs, and the results indicated that the microchannel structure was very favorable for differentiating rBMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, there was rapid healing in the defects treated with the 3D porous scaffold with microchannels, where the bridging by a large bony callus was observed at 12 weeks post-surgery. Based on the results, the 3D porous scaffold with microchannels was a promising candidate for bone defect repair.

Authentic learning opportunities that simulate full scale design and construction experiences using real materials offer ideal experiential learning environments for construction and civil engineering students by challenging students to apply building concepts in practical settings. However, the excessive cost of real building materials required for this mode of education limits access to the vast majority of students. As a result, educational researchers have explored potential alternatives to provide cost-effective experiential learning through activities using mock-up materials (e.g., plastic straws, popsicle sticks) and simulation of experiences using immersive technologies (e.g., virtual reality or augmented reality). While some of these alternatives approximate the environment and others provide physical interaction with mock-up materials, the lack of authenticity in the building materials used introduces some apparent differences between the “authentic” learning environments and their cost-effective approximations. Therefore, this research aims to identify the learning processes reported by students and faculty who participated in authentic learning experiences to understand the ways in which this mode of education offers unique value to construction education. Their interview responses illustrated characteristics of authentic learning experiences that were believed to be critical to the learning process, some of which included: working in groups; interdisciplinary participants; and use of real construction materials. Although some of these characteristics are intrinsically linked to the use of real materials, others do not explicitly refer to interaction with real materials. This may indicate to aspects of the authentic learning processes that educational researchers can strategically target through more cost-effective learning environments like virtual and augmented reality. The contribution of this paper is in identifying the characteristics of authentic learning experiences that may guide educational investment and research innovations that aim to replicate some of these learning experiences through more accessible learning environments.

Uncovering hidden mixture correlation among variables have been investigating in the literature using mixture R-vine copula models. These models are hierarchical in nature. They provides a huge flexibility for modelling multivariate data. As the dimensions increases, the number of the model parameters that need to be estimated is increased dramatically, which becomes along with huge computational times and efforts. This situation becomes even much more harder and complicated in the mixture Regular vine models. Incorporating truncation method with mixture Regular vine models will reduce the computation difficulty for the mixture based models. In this paper, tree-by-tree estimation mixture model is joined with the truncation method, in order to reduce the computational time and the number of the parameters that need to be estimated in the mixture vine copula models. A simulation study and a real data applications illustrated the performance of the method. In addition, the real data applications show the affect of the mixture components on the truncation level.

Centromeres, the chromosomal loci where spindle fibers attach during cell division to segregate chromosomes, are typically found within satellite arrays in plants and animals. Satellite arrays have been difficult to analyze because they comprise megabases of tandem head-to-tail highly repeated DNA sequences. Much evidence suggests that centromeres are epigenetically defined by the location of nucleosomes containing the centromere-specific histone H3 variant cenH3, independently of the DNA sequences where they are located; however, the reason that cenH3 nucleosomes are generally found on rapidly evolving satellite arrays has remained unclear. Recently, long read sequencing technology has clarified the structures of satellite arrays and sparked rethinking of how they evolve, while new experiments and analyses have helped bring both understanding and further speculation about the role these highly repeated sequences play in centromere identification.

Due to the complexity, high-risk, and conservative character of construction companies, advanced digital technologies do not become widely adopted in the short term, while vendors make determined efforts to overcome this and disseminate their technologies. This paper presents the methods of an investigation addressing the extremely complex issues related to the current practices of digital technology adoption in construction. It discusses how construction companies follow a specific logical process linked to need, project objectives, characteristics of the adopting organization, and the characteristics of the new technology to be adopted. The study aims to demonstrate a novel method of data collection and analysis including data and methodological triangulation techniques including the use of NVivo and AHP to explore how companies make the decision to uptake a new technology (e.g. advanced crane, tunnel boring machine or drones) by focusing on customer and vendor activities, their interactions, contributing factors, and people involved in the process. The major original contribution of this paper is to develop an innovative methodological Cube for investigating the Construction Technology Adoption Process (CTAP) covering technology adoption, acceptance, diffusion and implementation concepts. CTAP is a framework that delineates the phases of the process that customer organizations use when deciding to adopt a new digital technology and the parallel vendor activities. The significance of these contributions is that they enable vendors to understand how to match their strategies with customer expectations in each phase of the CTAP. It also provides a benchmark for new construction companies to use the current best practice of decision making. Future research is warranted to more clearly delineate any differences with developing nations or related industries such as mining and property management.

Retinitis pigmentosa-59 (RP59) is a rare, recessive form of RP, caused by mutations in the gene encoding DHDDS (dehydrodolichyl diphosphate synthase). DHDDS forms a heterotetrameric complex with Nogo-B Receptor (NgBR; gene NUS1) to form a cis-prenyltransferase (CPT) enzyme complex, which is required for synthesis of dolichol, which in turn is required for protein N-glycosylation as well as other glycosylation reactions in eukaryotic cells. Herein, we review the published phenotypic characteristics of RP59 models extant, with an emphasis on their ocular phenotypes, based primarily upon knock-in of known RP59-associated DHDDS mutations as well as cell type- and tissue-specific knockout of DHDDS alleles in mice. We also briefly review findings in RP59 patients with retinal disease and other patients with DHDDS mutations causing epilepsy and other neurologic disease. We discuss these findings in the context of addressing “knowledge gaps” in our current understanding of the underlying pathobiology mechanism of RP59, as well as their potential utility for developing therapeutic interventions to block the onset, or to dampen the severity or progression, of RP59.

The oral administration of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate, allows inducing a beneficial level of blood ketone bodies without the adverse effects due to the adhesion to a ketogenic diet. Several studies documented the therapeutic effectiveness of the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in treating neurodegenerative diseases as well as its boosting activity of athletic and cognitive performances during prolonged physical exercises. Further studies considering this ketone body ester for therapy of other pathologies are also underway. In the present work, we describe the synthesis of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate through the enantioselective transesterification of racemic ethyl 3-hydroxybutyrate with (R)-1,3-butanediol catalyzed by immobilized Candida antarctica lipase B (CAL-B). The enantiopure (R)-1,3-butanediol was in turn obtained from the kinetic resolution of the racemate by CAL-B catalyzed acetylation with vinyl acetate. The economy of the synthetic procedure has been improved by recycling the unreacted (S) enantiomers of the ethyl 3-hydroxybutyrate and 1,3-buatnediol after stereochemical inversion achieved by tosylation and SN2 with ammonium acetate. The overall procedure allows to incorporate up to 70% of the starting racemic reagents into the final product.

For a number of reasons, a curative treatment for most chronic diseases is still unrealized [2–4] and the incidence of many chronic diseases is rapidly increasing [5–9]. A new model is offered as a solution; that being the individualized diagnosis of homeostasis, leading to the correction of epimutations. Individuals with chronic diseases are increasingly being defined by their epigenetic signatures [10,11]. Modern innovations in toxicogenomic studies are also becoming more accurate in their ability to identify the unique epigenetic signature of each toxin [12–14]. Hormesis studies (over 5,000) [15] suggest a universal principle, that a small dose is always a stimulant [16–18].These three facts present an opportunity; a method to diagnose and reverse chronic disease tendencies. This new model requires a paradigm shift in our understanding of disease origins: that dysfunctions in homeostasis [19,20] are the primary and deepest level of chronic disease causation. This is the level where the diagnosis needs to be made and where the corrections need to take place [21].

A model for cell proliferation in developmental fields is derived from information theory using a few biological postulates. The model provides an explanation for the success of the Gompertz equation in describing the growth of embryonic, neoplastic, and regenerative systems. Although this equation has been applied to many growth phenomena, its use has been entirely empirical. A theoretical justification for the use of the Gompertz equation in characterizing developmental processes is presented. The model also accounts for a reported relationship among the parameters of the Gompertz equation. A method for quantification and comparison of the determination of developmental fields at different levels of organization is suggested.

We report the treatment of a 21-year-old female Covid-19 patient by a novel combination of minocycline and a guanosine-restricted diet. Minocycline is an antibiotic with well documented broad spectrum anti-viral effects, including evidence of activity against SARS-CoV-2. Deprivation of guanosine has been documented as an effective anti-viral modality in vitro and in animal models, and specific in vitro activity against CoV-SARS-2 has been reported. The patient's symptoms resolved rapidly.

The compatibility between the de Sitter Swampland conjecture and Ho\v{r}ava-Lifshitz $F(\bar{R})$ theories with a flat FLRW metric is studied. We first study the standard $f(R)$ theories and show that the only way in which the dS conjecture can be made independent of $R$ is by considering a power law of the form $f(R)\sim R^{\gamma}$. The conjecture and the consistency of the theory puts restrictions on $\gamma$ to be greater but close to $1$. For the $F(\bar{R})$ theories described by its two parameters $\lambda$ and $\mu$ we use the equations of motion to construct the function starting with an ansatz for the scale factor in the Jordan frame of the power law form. By doing a conformal transformation on the three metric to the Einstein frame we can obtain an action of gravity plus a scalar filed by relating the parameters of the theory. The non-projectable and projectable cases are studied and the differences are outlined. The $F(\bar{R})$ function obtained consists of terms of the form $\bar{R}^{\gamma}$ with the possibility of having negative power terms. The dS conjecture leads to inequalities for the $\lambda$ parameter, in both versions it gets restricted to be greater but close to $1/3$. For the general case in which $\mu$ and $\lambda$ are considered as independent, the action contains an extra term but we propose that the conjecture is still applicable. Once again the non-projectable and projectable cases are studied. The $F$ function obtained has the same form as before, the consistency of the theory and the dS conjecture lead to a set of inequalities on both parameters that are studied numerically. In all cases $\lambda$ is restricted by $\mu$ around $1/3$ and we obtain $\lambda\to1/3$ if $\mu\to0$. Finally we consider the $f(R)$ limit $\mu,\lambda\to1$ and we obtain consistent results.

In this work, we explore a the different forms of a new type of modified gravity, namely f(φ) gravity. We construct the Big Rip type for the energy density and the curvature of the universe. We show that dark energy is a result of the transformation of the field φ mass (dark matter) to energy. In addition, we provide that Ω_{m}≈0,050, Ω_{DM}≈0,2, Ω_{DE}≈0,746, is in excellent agreement with observation data. We explore a generalized formalism of braneworld modified gravity. We also construct a new field equations, which generalize the Einstein field equations. We provide a relation between the extra dimension in 3-brane with the vacuum energy density. We show that the energy density of matter depends directly on the number of dimensions. We manage to find the value of the Gauss-Bonnet coupling α=1/4 which is a good agreement with the results in the literature, this correspondence creates a passage between f(R) gravity and Gauss-Bonnet gravity, this comparison leads to a number of bulk dimensions equal to D=10¹²¹+4.

This paper examines certain implications from the literature on Tiebout’s model of local gov-ernment service provision, particularly Hamilton’s extension of the model to include local control of land use and property taxation. Our empirical analysis focuses on the use of fiscal zoning to lower property tax rates, a topic that has not been addressed in the extensive Tiebout literature. Using data for over 100 municipalities in the Miami, Florida, metropolitan area, we specify property tax rates as a function of fiscal zoning measures, other municipal characteristics, and tax mimicking. We conclude that single-family zoning is by far the most important variable ex-plaining municipal property tax rates.

A new kind of quantum gates, higher braiding gates, as matrix solutions of the polyadic braid equations (different from the generalized Yang-Baxter equations) is introduced. Such gates lead to another special multiqubit entanglement which can speed up key distribution and accelerate algorithms. Ternary braiding gates acting on three qubit states are studied in details. We also consider exotic noninvertible gates which can be related with qubit loss, and define partial identities (which can be orthogonal), partial unitarity, and partially bounded operators (which can be noninvertible). We define two classes of matrices, star and circle ones, such that the magic matrices (connected with the Cartan decomposition) belong to the star class. The general algebraic structure of the introduced classes is described in terms of semigroups, ternary and $5$-ary groups and modules. The higher braid group and its representation by the higher braid operators are given. Finally, we show, that for each multiqubit state there exist higher braiding gates which are not entangling, and the concrete conditions to be non-entangling are given for the obtained binary and ternary gates.

The advent of zirconia ceramics with excellent mechanical, biomechanical and optical properties has made it an attractive metal-free substitute for titanium implants. Both animal and human studies have documented shortcomings with titanium implants. A review of the current literature on 3 iterations of zirconia implant designs has been challenging due to heterogeneous success data and limited follow-up. Zirconia implants hold promise for a new generation of dental implants, but technical developments are needed for design and material enhancements that will need to be validated by long-term rigorous studies.

In this note we, first, recall that the sets of all representatives of some special ordinary residue classes become $\left( m,n\right) $-rings. Second, we introduce a possible $p$-adic analog of the residue class modulo a $p$-adic integer. Then, we find the relations which determine, when the representatives form a $\left( m,n\right) $-ring. At the very short spacetime scales such rings could lead to new symmetries of modern particle models.

Simple patterns often arise from complex systems. For example, human perception of similarity decays exponentially with perceptual distance. The ranking of word usage versus the frequency at which the words are used has a log-log slope of minus one. Recent advances in big data provide an opportunity to characterize the commonly observed patterns of nature. Those observed regularities set the challenge of understanding the mechanistic processes that generate common patterns. This article illustrates the problem with the recent big data analysis of collective memory. Collective memory follows a simple biexponential pattern of decay over time. An initial rapid decay is followed by a slower, longer lasting decay. Candia et al. successfully fit a two stage model of mechanistic process to that pattern. Although that fit is useful, this article emphasizes the need, in big data analyses, to consider a broad set of alternative causal explanations. In this case, the method of signal frequency analysis yields several simple alternative models that generate exactly the same observed pattern of collective memory decay. This article concludes that the full potential of big data will require better methods for developing alternative, empirically testable causal models.

Autonomous weapons systems (AWS), sometimes referred to as “killer robots”, are receiving evermore attention, both in public discourse as well as by scholars and policymakers. Much of this interest is connected with emerging ethical and legal problems linked to increasing autonomy in weapons systems, but there is a general underappreciation for the ways in which existing law might impact on these new technologies. In this paper, we argue that as AWS become more sophisticated and increasingly more capable than flesh-and-blood soldiers, it will increasingly be the case that such soldiers are “in the power” of those AWS which fight against them. This implies that such soldiers ought to be considered hors de combat, and not targeted. In arguing for this point, we draw out a broader conclusion regarding hors de combat status, namely that it must be viewed contextually, with close reference to the capabilities of combatants on both sides of any discreet engagement. Given this point, and the fact that AWS may come in many shapes and sizes, and can be made for many different missions, we argue that each particular AWS will likely need its own standard for when enemy soldiers are deemed hors de combat. We conclude by examining how these nuanced views of hors de combat status might impact on meaningful human control of AWS.

Microbial competition within plant tissues affects invading pathogens' fitness. Metabolomics is a great tool for studying their biochemical interactions by identifying accumulated metabolites. Xylella fastidiosa, a Gram-negative bacterium causing Pierce's disease (PD) in grapevines, secretes various virulence factors including cell wall degrading enzymes, adhesion proteins, and quorum sensing molecules. These factors, along with outer membrane vesicles, contribute to its pathogenicity. Previous studies demonstrated that co-inoculating X. fastidiosa with Paraburkholderia phytofirmans strain PsJN suppressed PD symptoms. Here, we further investigated the interaction between the phytopathogen and the endophyte by analyzing the exometabolome of wild-type X. fastidiosa and a diffusible signaling factor (DSF) mutant lacking quorum sensing, cultivated with 20% P. phytofirmans spent media. LC-MS and MAGI were used to detect and map metabolites to genomes revealing a total of 121 metabolites, of which 25 were further investigated. These metabolites potentially relate to host adaptation, virulence, and pathogenicity. Notably, this study presents the first comprehensive profile of X. fastidiosa in the presence of P. phytofirmans spent media. The results highlight that P. phytofirmans and the absence of a functional quorum sensing affect the ratios of glutamine to glutamate (Gln:Glu) in X. fastidiosa. Additionally, two compounds with plant metabolism and growth properties, 2-Aminoisobutyric acid and Gibberellic Acid, were downregulated when X. fastidiosa interacted with P. phytofirmans. These findings suggest that P. phytofirmans-mediated disease suppression involves modulation of the exometabolome of X. fastidiosa, impacting plant immunity.

Free-living terrestrial mites (Acari) have persisted through numerous glacial cycles in Antarctica. Very little is known, however, of their genetic diversity and distribution, particularly within the Ross Sea region. To redress this gap, we sampled for mites throughout the Ross Sea region, East Antarctica, including Victoria Land and the Queen Maud Mountains (QMM), covering a latitudinal range of 72-85oS, as well as from Lauft Island near Mt Siple (73oS) in West Antarctica and Macquarie Island (54oS) in the sub-Antarctic. We assessed genetic diversity using mitochondrial cytochrome c oxidase subunit I gene sequences (COI-5P DNA barcode region), and also morphologically identified voucher specimens. We obtained 130 sequences representing four genera: Nanorchestes (n = 30 sequences), Stereotydeus (n = 46), Coccorhagidia (n = 18) and Eupodes (n = 36). Tree-based analyses (maximum likelihood) revealed 13 genetic clusters, representing as many as 23 putative species indicated by Barcode Index Numbers (BINs) from the Barcode of Life Datasystems (BOLD) database. We found evidence for geographically-isolated cryptic species, e.g. within Stereotydeus belli and S. punctatus, as well as unique genetic groups occurring in sympatry (e.g. Nanorchestes spp. in QMM). Collectively, these data confirm high genetic divergence as a consequence of geographic isolation over evolutionary timescales. From a conservation perspective, additional targeted sampling of understudied areas in the Ross Sea region should be prioritised, as further diversity is likely to be found for these short-range endemic mites.

Mast cells are long-lived, granular, myeloid-derived leukocytes that have significant protective and repair functions in tissues. Mast cells sense disruptions in the local microenvironment and are first responders to physical, chemical and biological insults. When activated, mast cells release growth factors, proteases, chemotactic proteins and cytokines thereby mobilizing and amplifying the innate and adaptive immune system. Mast cells are therefore significant regulators of homeostatic functions and may be essential in microenvironmental changes during pathogen invasion and disease. During infection by helminths, bacteria and viruses, mast cells release antimicrobial factors to facilitate pathogen expulsion and eradication. Mast cell-derived proteases and growth factors protect tissues from insect/snake bites and exposure to ultraviolet radiation. Finally, mast cells release mediators that promote wound healing in the inflammatory, proliferative and remodeling stages. Since mast cells have such a powerful repertoire of functions, targeting mast cells may be an effective new strategy for immunotherapy of disease and design of novel vaccine adjuvants. In this review, we will examine how certain strategies that specifically target and activate mast cells can be used to treat and resolve infections, augment vaccines and heal wounds. Although these strategies may be protective in certain circumstances, mast cells activation may be deleterious if not carefully controlled and any therapeutic strategy using mast cell activators must be carefully explored.

The capacity to externally control transcranial magnetic stimulation (TMS) devices is becoming increasingly important in brain stimulation research. Here we introduce MAGIC (MAGnetic stimulator Interface Controller), an open-source MATLAB toolbox for controlling Magstim and MagVenture stimulators. MAGIC includes a series of MATLAB functions which allow the user to arm/disarm the stimulator, send triggers, change stimulator settings such as amplitude, interpulse intervals, and frequency, and receive stimulator setting information via a serial port connection between a computer and the stimulator. By providing external control capability, MAGIC enables greater flexibility in designing research protocols which require trial-by-trial changes of device settings to realize a priori trial randomization or interactive ad hoc adjustment of parameters during an ongoing experiment. MAGIC thus helps to prevent experimental confounds related to the block-wise variation of parameters and facilitates the integration of TMS with cognitive/sensory tasks, and the development of more adaptive brain state-dependent brain stimulation protocols.

Delayed atomic layer deposition (ALD) of ZnO, i.e., area selective (AS)-ALD, was successfully achieved on silicon wafers (Si/SiO2) terminated with tris(dimethylamino)methylsilane (TDMAMS). This resist molecule was deposited in a home-built, near atmospheric pressure, flow-through , gas-phase reactor. TDMAMS has been shown to react with Si/SiO2 in a single cycle/reaction and to drastically reduce the number of silanols that remain at the surface. ZnO was deposited in a commercial ALD system using dimethylzinc (DMZ) as the zinc precursor and H2O as the coreactant. Deposition of TDMAMS was confirmed by spectroscopic ellipsometry (SE), X-ray photoelectron spectroscopy (XPS), and wetting. ALD of ZnO, including its selectivity on TDMAMS – terminated Si/SiO2 (Si/SiO2/TDMAMS), was confirmed by in situ ellipsometry, ex situ SE, XPS, and/or high sensitivity – low energy ion scattering (HS-LEIS). The thermal stability of the TDMAMS resist layer, which is an important parameter for AS-ALD, was investigated by heating Si/SiO2/TDMAMS in air and nitrogen at 330 ºC. ALD of ZnO takes place more readily on Si/SiO2/TDMAMS heated in the air than in N2, suggesting greater damage to the surface heated in the air. To better understand the in situ ALD of ZnO, the data were also plotted as the normalized growth per cycle and to show the selectivity. Even one, short pulse of TDMAMS effectively passivates Si/SiO2. TDMAMS can be an effective small molecule inhibitor of ALD of ZnO on Si/SiO2 surfaces.

A wealth of Full Waveform (FW) LiDAR data are available to the public from different sources, which is poised to boost the extensive application of FW LiDAR data. However, we lack a handy and open source tool that can be used by potential users for processing and analyzing FW LiDAR data. To this end, we introduce waveformlidar, an R package dedicated to FW LiDAR processing, analysis and visualization as a solution to the constraint. Specifically, this package provides several commonly used waveform processing methods such as Gaussian, adaptive Gaussian and Weibull decompositions, and deconvolution approaches (Gold and Richard-Lucy (RL)) with users’ customized settings. In addition, we also developed functions to derive commonly used waveform metrics for characterizing vegetation structure. Moreover, a new way to directly visualize FW LiDAR data is developed through converting waveforms into points to form the Hyper Point cloud (HPC), which can be easily adopted and subsequently analyzed with existing discrete-return LiDAR processing tools such as LAStools and FUSION. Basic explorations of the HPC such as 3D voxelization of the HPC and conversion from original waveforms to composite waveforms are also available in this package. All of these functions are developed based on small-footprint FW LiDAR data, but they can be easily transplanted to the large footprint FW LiDAR data such as Geoscience Laser Altimeter System (GLAS) and Global Ecosystem Dynamics Investigation (GEDI) data analysis. It is anticipated that these functions will facilitate the widespread use of FW LiDAR and be beneficial for better estimating biomass and characterizing vegetation structure at various scales. The package and code examples can be found at https://github.com/tankwin08/waveformlidar.

Developmental modularity has long been viewed as a hierarchical organization that facilitates evolution over macro-evolutionary time through modification or co-option of preexisting modules. More recently, developmental modularity has been proposed as a micro-evolutionary mechanism capable of driving rapid evolution of novel color pattern phenotypes between closely related taxa. In this scenario, swapping allelic variants of modular cis-regulatory elements (CREs) via recombination generates novel phenotypes by shuffling preexisting color pattern modules into new arrangements. Recent evidence from Drosophila and butterflies, however, provides a series of examples in which pleiotropic CREs function in multiple developmental contexts. The potential prevalence of pleiotropy in CRE function is a major barrier to the proposed evolutionary role of CRE modules and encourages us to reconsider the relative importance of modularity for microevolutionary change. Here we first review the case for the apparent frequent exchange of modular color pattern phenotypes as a mechanism facilitating diversification. We then contrast this with recent evidence of CRE pleiotropy and argue that exchange of CRE modules should not be the default assumption, even when phenotypes look modular. Finally, we review experimental data on Heliconius butterfly wing patterns—which appear modular—and introduce the concept of evolutionary modularity as an alternative to developmental modularity. Evolutionary modularity reconciles the appearance of modularity in comparative genomic studies of Heliconius color patterns with experimental data supporting a non-modular architecture. We propose that evolutionary modularity provides a potentially important pathway for exchange of phenotypic elements between hybridizing taxa independent of the underlying developmental architecture.

Quasi-solid composited electrolytes were produced by LiFSI initiated polymerized poly-(Dioxolane) (PDOL) with garnet-LLZO (Li7La2Zr3O12) nanofibers and used in lithium-metal batteries. Linear sweep voltammetry shows that the initial oxidation voltage of 4.6 V for Gel-10% (G10, 10% wt. LLZO in PDOL) vs Li/Li+. EIS test of stainless steel// stainless steel symmetric cells for Gel-1% (G1), Gel-5% (G5) and Gel-10% (G10) show ion conductivity (5*10-5 S/cm). Li/G10/Li symmetric cells have stable stripping-plating cycling performance over 1300 hours continuously with the current density of 0.1 mA/cm2 at 25 oC, indicating a good interface contact and stable lithium-ion transport pathway through the composite electrolytes. LFP/G10/Li batteries have stable charge-discharge plateau, low polarization voltage of 0.07-volt, energy efficiency of 95% and coulombic efficiency of ~99% at current density of 26.3 mA/g at 25 oC for over 100 cycles.

Identification and segmentation of rock particles is very important in geology, mining, engineering construction, and environmental monitoring. Traditional methods for recognizing the rock particle characteristics are time-consuming, labor-intensive, and limited by the geographical scope of the sampling sites, which makes it more difficult to represent the spatial distribution of the rock particles accurately. Recent advancements in deep learning techniques offer promising solutions to automate this process. This study aims at utilizing state-of-the-art (SOTA) Mask R-CNN deep learning algorithm from the Detectron2 framework, to capture global features of rocks that will enable the recognition of rock particles more efficiently, just from having the rock images. These images are subject to image processing techniques such as a Gaussian filter, to denoise and smoothen the image, and an Illumination Adaptive Transformer (IAT) framework, to adjust the lighting exposure; all of which add to improve the quality of the image dataset. Afterward, the Mask R-CNN and Detectron2 models are utilized in training the images using transfer learning. Experimental results from evaluating the performance of the proposed algorithms showcase the effectiveness of the approach, thereby highlighting its potential to revolutionize rock particle segmentation across various domains.

(R)-(+)-3,5-Dinitro-N-(1-phenylethyl)benzothioamide 1 is a potential chiral solvating agent (CSA) for the spectral resolution of enantiomers by 1H NMR spectroscopy. The single enantiomer of 1 was synthesized from commercially (R)-(+)-a-methylbenzylamine 2 in two-steps with 85% yield.

We study certain function algebras and their operator algebra completions on r-discrete abelian groupoids, the corresponding conditional expectations, maximal abelian subalgebras (masa) and eigen-functionals.

Alfalfa (Medicago sativa L.) is a perennial, outcrossing legume crop predominantly grown for hay, silage, or pasture. Intensive selection has resulted in dramatic improvement in fitness traits, including winter survival and disease resistance. However, there has been minimal improvement in other economically important traits, such as hay yield, which is still comparable to 30 years ago. Intensive phenotyping costs on this type of trait hinder high selection pressure to identify superior outcross individuals. Severe inbreeding depression inhibits the development of inbred lines with accumulated favorable alleles that exhibit heterosis. This review highlights the outcomes of inbreeding depression as well as the causes, including unmasking deleterious alleles and triggering self-incompatibility. We tracked the research efforts that unveil the genetic bases underlying deleterious alleles and self-incompatibility. The magnitudes of inbreeding depression were compared with the rate of heterozygous halved time in diploid and tetraploid organisms. To fill in the gaps between the controversy and existing hypotheses, we theorized a dosage dominant model of inheritance. The dosage dominant model is similar to the Mendelian dominance model, in which a genotype exhibits a dominant phenotype if there is a dominant allele (alphabet dominant). The difference is that in the dosage dominant model, a genotype will result in a dominant phenotype if the number of dominant alleles is equal to or greater than the number of recessive alleles. This review also includes a discussion on the development of pseudo inbreds and a hypothesis to identify deleterious alleles using bulked segregant analysis and consequently to purge deleterious alleles using marker-assisted selection, to progress toward the successful development of pure inbred lines in alfalfa.

The state estimation for lithium-ion battery cells has been the topic of many publications concerning the different states of a battery cell. They often focus on a battery cell’s state of charge (SOC) or state of health (SOH). Therefore this paper introduces a, on one hand, a new lithium-ion battery data set with dynamic validation data over degradation and on the other hand a model-based SOC and SOH estimation based on this dataset as a reference. An unscented Kalman filter-based approach was used for SOC estimation and extended with a holistic ageing model to handle the SOH estimation. The paper describes the dataset, the models, the parameterisation, the implementation of the state estimations, and their validation using parts of the dataset resulting in a SOC and SOH estimation over battery life. The results show that the dataset can be used to extract parameters, design models based on it and validate with dynamically degraded battery cells.

Polymerase I (Pol I) is at the epicenter of ribosomal RNA (rRNA) synthesis. Pol I is a target for treatment of cancer. Given the many cellular commonalities between cancer and neurodegeneration (i.e., different faces of the same coin) it seems rational to consider targeting of Pol I or, more generally, rRNA synthesis for treatment of disorders associated with the death of terminally differentiated neurons. Principally, ribosomes synthesize proteins and, accordingly, Pol I can be considered the starting point for protein synthesis. Given that cellular accumulation of abnormal proteins such as α-synuclein and tau is an essential feature of neurodegenerative disorders such as Parkinson disease and fronto-temporal dementia, reduction of protein production is now considered as a viable target for treatment of these and closely related neurodegenerative disorders. Abnormalities in polymerase I activity and rRNA production may also be associated with nuclear and nucleolar stress, DNA damage, and childhood onset neuronal death as is the case for the UBTF E210K neuroregression syndrome. Moreover, restraining the activity of Pol I may be a viable strategy to slow aging. Before starting down the road of Pol I inhibition for treating non-cancerous disorders of the nervous system, many questions must be answered. First, how much Pol I inhibition can neurons tolerate and for how long? Should inhibition of Pol I be continuous or pulsed? Will cells compensate for Pol I inhibition by upregulating the number of active rDNAs? At present, we have no effective and safe disease modulatory treatments for Alzheimer disease, α-synucleinopathies, or tauopathies, and novel therapeutic targets and approaches must be explored.

Abstract: In Australia adoption of reduced tillage and stubble retention cropping systems to conserve soil moisture by growers has seen an increase in the prevalence of the disease Fusarium crown rot (FCR) caused by the stubble-borne fungal pathogen Fusarium pseudograminearum. Durum wheat is particularly susceptible to FCR expressing significant yield and quality losses in the presence of infection. Increasing rates of nitrogen (N) application at sowing exacerbates FCR. However, to achieve the desired grain protein and quality suited to pasta manufacture, N application is necessary and this creates a dilemma for growers. The purpose of this study was to investigate the effects of FCR infection in the presence of different N fertiliser application rates in durum wheat varieties on yield and technological quality. Two durum varieties were evaluated at the same location over two seasons (2020 and 2021). These seasons were characterised by being wetter than normal and showed different responses to FCR and N application. In general, the 2021 season showed better responses to applied N with no impact of FCR. The FCR inoculation while it resulted in significant infection, it had no impacts on yield or grain quality in 2021 while in 2020 yield was reduced and only gluten index was reduced. Jandaroi was found to hold its kernel vitreosity at all protein levels obtaining the premium grade while DBA Lillaroi did not and would suffer downgrade if N application was insufficient. However, higher N application rates needed to achieve 12% + protein saw a reduction in dough strength with Jandaroi holding its dough strength much better than DBA Lillaroi. This was related to the lower glutenin/gliadin (Gli/Glu) ratio in response to applied N at sowing in Jandaroi which helped retain kernels with high vitreousness. This suggests genetics plays an important role in a genotype response to N fertilisation and should be considered when selecting a variety where higher premium grades are desirable.

Symmetry concepts in parametrized dynamical systems may reduce the number of external parameters by a suitable normalization prescription. If, under the action of a symmetry group G, parameter space A becomes a (locally) trivial principal bundle, A ~ A/G x G, then the normalized dynamics only depends on the quotient A/G. In this way, the dynamics of fractional variables in homogeneous epidemic SI(R)S models, with standard incidence, absence of R-susceptibility and compartment independent birth and death rates, turns out to be isomorphic to (a marginally extended version of) Hethcote's classic endemic model, first presented in 1973. The paper studies a 10-parameter master model with constant and I -linear vaccination rates, vertical transmission and a vaccination rate for susceptible newborns. As recently shown by the author, all demographic parameters are redundant. After adjusting time scale, the remaining 5-parameter model admits a 3-dimensional abelian scaling symmetry. By normalization we end up with Hethcote's extended 2-parameter model. Thus, in view of symmetry concepts, reproving theorems on endemic bifurcation and stability in such models becomes needless.

Previous studies demonstrate the critical importance of non-coding RNAs interfacing with chromatin-modifying machinery resulting in promoter-enhancer-based gene regulation and raise the possibility that many other enhancer-like RNAs may operate via similar mechanisms. Critically, more than 80% of the disease-linked variations identified in genome-wide studies are located in the non-coding regions of genomes, especially non-coding RNA, suggesting non-coding RNAs are relevant to disease. Thus, a critical path forward for understanding non-coding RNAs' role, especially long non-coding RNAs, is to understand the genomic regions' transcriptional regulation, especially non-coding regions. Here, we developed a user-friendly R package called SomaGene for studying and identifying enhancer-like non-coding RNAs with enriched somatic mutations in the cancer genome. SomaGene accepts different genomic variants (whole genome/exome somatic point mutations, structural variations, copy number variations) to identify those RNAs that significantly mutated in diseases (e.g., cancer). It then uses multiple publicly available genomics and epigenetics datasets including ENCODE epigenomics annotations, FANTOM5 tissue-specific expression profiles, disease-associated genome-wide association SNPs, and tissue-specific eQTL pairs to identify those RNAs with potentially enhancer function. SomaGene, as a powerful R package, can provide the opportunity to cancer scientists to study the roles of non-coding RNAs in different cancer genomes.

The authors previously found a model of universal quantum computation by making use of the coset structure of subgroups of a free group $G$ with relations. A valid subgroup $H$ of index $d$ in $G$ leads to a \lq magic' state $\left|\psi\right\rangle$ in $d$-dimensional Hilbert space that encodes a minimal informationally complete quantum measurement (or MIC), possibly carrying a finite \lq contextual' geometry. In the present work, we choose $G$ as the fundamental group $\pi_1(V)$ of an exotic $4$-manifold $V$, more precisely a \lq small exotic' (space-time) $R^4$ (that is homeomorphic and isometric, but not diffeomorphic to the Euclidean $\mathbb{R}^4$). Our selected example, due to to S. Akbulut and R.~E. Gompf, has two remarkable properties: (a) it shows the occurence of standard contextual geometries such as the Fano plane (at index $7$), Mermin's pentagram (at index $10$), the two-qubit commutation picture $GQ(2,2)$ (at index $15$) as well as the combinatorial Grassmannian Gr$(2,8)$ (at index $28$) , (b) it allows the interpretation of MICs measurements as arising from such exotic (space-time) $R^4$'s. Our new picture relating a topological quantum computing and exotic space-time is also intended to become an approach of \lq quantum gravity'.

This study investigates the emergence of ertapenem-resistant, meropenem-susceptible (ErMs) among non-carbapenemase producing (NCP) and carbapenemase producing (CP) Escherichia coli and Klebsiella pneumoniae. As mutations for ertapenem resistance establish the genetic background for non-carbapenemase meropenem resistance, there is a great need for antibiotic stewards and researchers to understand the determinants of a strain’s propensity to become resistant. Whole genome sequencing was conducted on clinical carbapenem-resistant E. coli (CREC) and K. pneumoniae (CRKP) across 5 hospitals in San Antonio, U.S. from 2012-2018. The majority of carbapenem resistant Enterobacterales (CRE) were NCP (54%; 41/76). The blaCTX-M was found to be most prevalent among NCP isolates (p = 0.02). LC-MS/MS analysis of carbapenem hydrolysis revealed that blaCTX-M-mediated carbapenem hydrolysis, indicating the need to reappraise the term, “non-carbapenemase (NCP)” for quantitatively uncharacterized CRE strains harboring blaCTX-M. Antimicrobial susceptibility results showed that 56% of all NCPE isolates had an ErMs phenotype (NCPE vs. CPE, p &lt; 0.001), with E. coli driving the phenotype (E. coli vs. K. pneumoniae, p &lt; 0.001). ErMs strains carrying blaCTX-M, had approximately 4-fold more copies of blaCTX-M than ceftriaxone-resistant but ertapenem and meropenem susceptible (EsMs) isolates (3.7 v. 0.9, p &lt; 0.001). ErMs also carried more mobile genetic elements (MGEs), particularly IS26 composite transposons, than EsMs (37 vs. 0.2, p &lt; 0.0001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage of ompC. Overall, this work provides evidence of a collaborative effort between blaCTX-M and OmpC in NCP strains that confer resistance to ertapenem but not meropenem. To thwart potential mismanagement of CRE infected patients, future efforts should focus on understanding the mechanism(s) underlying OmpC loss, developing rapid methods to detect blaCTX-M copy number variants, and targeted antimicrobials for NCPE and ErMs strains.

In this article, we give a brief review of the origin of the neutrino mass in some interesting non-linear supersymmetric models with R-symmetry. These models are able to address and solve the most important problems of the particle physics and provide mechanisms for neutrino mass generation and their mixing parameters in agreement with the current experimental data. Their prediction could be experimentally tested in the near future by collider experiments.

This paper presents a script that classify spatial patterns of residential urban growth using a morpho-structural approach. The script performs a combination of variography analysis and morphological closings over buildings possessing a residential function in 2002 and 2017 within a region located in southern France named Centre-Var. The different bounding regions then allow classifying new residential buildings into different categories according to their degrees of clustering/scattering and to their locations regarding existing urban areas. Preliminary results show that this protocol is able to provide useful insights regarding the degree of contribution of each new residential building to different patterns of urban growth (clustered infill, scattered infill, clustered edge-expansion, scattered edge-expansion, clustered leapfrog and scattered leapfrog). Open-access to the script and to the test region data is provided.

Considering the dynamic stall effects in engineering calculations is essential for correcting the aerodynamic loads acting on wind turbines, both during power production and stand-still cases, and impacts significantly the turbine aeroelastic stability. The employed dynamic stall model needs to be accurate and robust for a wide range of airfoils and range of angle of attack. The present studies are intended to demonstrate the performance of a recently implemented "IAG dynamic stall" model in a wind turbine design tool Bladed. The model is transformed from the indicial type of formulation into a state-space representation. The new model is validated against measurement data and other dynamic stall models in Bladed for various flow conditions and airfoils. It is demonstrated that the new model is able to reproduce the measured dynamic polar accurately without airfoil specific parameter calibration and has a superior performance compared to other models in Bladed.

Hydrogen used as an energy carrier can provide an important route to the decarbonization of energy supplies. However, realizing this opportunity requires a significant increase in both production and transportation capacity. Part of the increase in transportation capacity could be provided by the shipping of liquid hydrogen, but this introduces an energy-intensive liquefaction step into the supply-chain. The energy required for liquefaction can be reduced by developing improved process designs, but since all low-temperature processes are affected by the available heat-sink temperature, local ambient conditions will also affect the energy penalty. This work studies how the energy consumption associated with liquefaction varies with heat-sink temperature through the optimization of design parameters for a typical next-generation hydrogen liquefaction process. The results show that energy consumption increases by around 20%, across the cooling temperature range 5 to 50 °C. Considering just the range 20 to 30 °C there is a 5% increase, illustrating the significant impact ambient temperature can have on energy consumption.

Scientific progress is increasingly dependent on knowledge in computation-ready forms. In the life sciences, among others, many scientists therefore extract and structure knowledge from the literature. In a process called manual curation, they enter knowledge into spreadsheets, or into databases where it serves their and many others' research. Valuable as these curation efforts are, the range and detail of what can practically be captured and shared remains limited, because of the constraints of current curation tools. Many important contextual aspects of observations described in literature simply do not fit in the form defined by these tools, and thus cannot be captured. Here we present the design of an easy-to-use, general-purpose method and interface, that enables the precise semantic capture of virtually unlimited types of information and details, using only a minimal set of building blocks. Scientists from any discipline can use this to convert any complex knowledge into a form that is easily readable and meaningful for both humans and computers. The method VSM forms a universal and high-level language for encoding ideas, and for interacting with digital knowledge.

In CCS projects, the transportation of CO₂ by ship can be an attractive alternative to transportation using a pipeline, particularly when the distance between source and disposal location is large. However, the energy consumption of the liquefaction process can be significant, making the selection of an energy-efficient design an important factor in the minimization of operating costs. Since the liquefaction process operates at low temperature, its energy consumption will vary with ambient temperature, which could be a factor that influences the trade-off point between pipelines and shipping in different geographic locations. A consistent set of data showing the relationship between energy consumption and cooling temperature is therefore potentially useful to CCS system modelling. This study compares the performance of a wide range of CO₂ liquefaction schemes. It applies a methodical approach to the optimization of process operating parameters and studies performance across a range of operating temperatures. A set of data for the minimum energy consumption cases is presented. The main findings are that open-cycle CO₂ processes often offer minimum energy consumption; NH₃ based schemes often offer better performance at higher ambient temperatures; and that for the cooling temperature range 15 to 50 °C, the energy consumption for the best performing liquefaction process rises by around 40%.

Background: Fiber-reinforced composites (FRCs) have been proposed as an alternative to traditional metal alloys for the realization of frameworks in full-arch implant supported prostheses. The aim of the present in vitro study was to evaluate the deflection under load of seven prostheses endowed with frameworks made of different materials, including different types of fiber reinforced composites (FRCs). Methods: A master cast with four implant analogues in correspondence of the two lateral incisors and the two first molars was used to create full-arch fixed prostheses with the same shape and different materials. Prostheses were made in different materials (framework+veneering material): gold alloy+resin (Au+R), titanium+resin (Ti+R), FRC with multi-directional carbon fibers+resin (ICFRC+R), FRC with unidirectional carbon fibers+composite (UCFRC+C), FRC with glass fibers+resin (GFRC+R), FRC with glass fibers+composite (GFRC+C), resin (R, full-acrylic prosthesis). Flexural tests were conducted using Zwick/Roell Z 0.5 machine and the deflection of the lower surface of the prosthesis was measured in order to obtain load/deflection graphs. Results: Greater rigidity and less deflection were recorded for UCFRC+C, GFRC+C, followed by Ti+R, and Au+R. The greatest deformations were observed for resin alone, ICFRC+R and GFRC+R. The results were slightly different in the incisal region probably due to the greater amount of veneering material in this area. Conclusions: When used to realize full-arch frameworks, Au and Ti allow a predictable mechanical behavior with gradual deformations with increasing load. UCFRC also demonstrated good outcomes and less deflection than ICFRCs when loaded. The GFRC full-arch framework may be a valid alternative, however showed greater deflections. Further studies are needed in order to evaluated how different prosthesis design and material thickness might affect the outcomes.

Filter Media (FM) sourced from recycled organic and mineral material offers a low cost and effective means of treating urban stormwater. Using recycled materials rather than from an increasingly scarce source of virgin materials (typically sandy loam soil) can ensure a sustainable long-term economy and environment. This paper presents results from the laboratory analysis and mathematical modeling to highlight the performance of recycled organic and mineral material in removing nutrients and metals from stormwater. Analysis included physical and chemical characterisation such as particle size distribution, saturated hydraulic conductivity (Ksat), bulk density, effective cation exchange capacity, and pollutant removal performance. Design mixes (DM), comprising a combination of organic and mineral materials, were characterised and used to develop/derive modelling design within the Model for Urban Stormwater Improvement Conceptualisation (MUSIC v6) [1]. Comparison is made to the Adoption Guidelines for Stormwater Biofiltration Systems - Summary Report [2] which were based on the Facility for Advancing Water Biofiltration (FAWB) guidelines to assist in the development of biofiltration systems, including the planning, design, construction and operation of those systems. An observed outcome from over two decades of biofiltration guideline development has been the exclusion of alternative biofilter materials due to claims of excessive leaching. Results from this study indicate that high nutrient and metal removal rates can be achieved over a range of hydraulic conductivities using design mixes of recycled organic and mineral materials that have a demonstrated equivalence to existing guideline specifications.

Telemedicine is the use of Information and Communication Technology (ICT) for clinical health care from a distance. The exchange of radiographic images and electronic patient health information/records (ePHI/R) for diagnostic purposes has the risk of confidentiality, ownership identity, and authenticity. In this paper, a data hiding technique for ePHI/R is proposed. The color information in the cover image is used for key generation, and stego-images are produced with ideal case. As a result, the whole stego-system is perfectly secure. This method includes the features of watermarking and steganography techniques. The method is applied to radiographic images. For the radiographic images, this method resembles watermarking, which is an ePHI/R data system. Experiments show promising results for the application of this method to radiographic images in ePHI/R for both transmission and storage purpose.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

Sterol homeostasis in mammalian cells and tissues involves balancing three fundamental processes: de novo sterol biosynthesis; sterol import (e.g., from blood-borne lipoproteins); and sterol export. In complex tissues, composed of multiple different cell types (such as the retina), import and export also may involve intra-tissue, inter-cellular sterol exchange. Disruption of any of these processes can result in pathologies that impact the normal structure and function of the retina. Here, we provide a brief overview of what is known currently about sterol homeostasis in the vertebrate retina and offer a proposed path for future experimental work to further our understanding of these processes, with relevance to the development of novel therapeutic interventions for human diseases involving defective sterol homeostasis.

We investigate and discuss in detail the structure of the restricted singular value decomposition for a tensor triplet under t-product (T-RSVD). The algorithm is provided with a numerical example illustrating the main result. For applications, we consider color image watermarking processing with T-RSVD.

The purpose of the study was to evaluate the success of procedural conscious sedation, using inhaled equimolar nitrous oxide-oxygen (NOIS – EMONO), in patients undergoing routine dental and oral surgery procedures in a Swiss university hospital setting. Materials and methods: The authors conducted a retrospective cohort study of patients that underwent NOIS-supported procedures between 2018 and 2022 at the oral surgery department of the University Hospital of Geneva (HUG), Switzerland. The primary outcome was the measurement of the procedure success and efficacy as defined by the European Society of Anesthesiology. Secondary objectives included the analysis of the types of treatments performed, their indications, patient behavior, and the patient - clinician satisfaction score. Results: 55 patients were included in the study, 85% underwent surgical procedures, the remaining 15% underwent restorative and preventive procedures. The overall treatment success rate was 98.2%, and 97.9% for surgically treated patients. 62% of patients appeared relaxed, calm, and serene, while 16% expressed pain or fear during the procedure. Infiltrative administration of local anesthesia caused stress in 22% of patients, this was significantly lower in sub cohorts who received local topical anesthetics (0%) or a combination of systemic and local topical analgesics (7%). Patients (75%) and clinicians (91%) were satisfied with the procedure. Conclusion: Inhaled equimolar nitrous oxide-oxygen procedural sedation used during dental procedures and oral surgery results in high treatment success and satisfaction rates. The administration of additional topical anesthetics helps reduce the anxiety and stress related to infiltrative anesthesia. Further dedicated studies and prospective trials are needed to confirm these findings.

High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham=-7.499, LogIC50 Stroke=-7.350, P=0.0132, n= 19, 31 respectively). Vasodilatory responses to SNP were identical in isolated aortas in sham and stroke groups. Phenylephrine induced vasoconstriction was impaired in aortas isolated from stroke animals in comparison to sham counterparts (Sham LogEC50= -6.652 vs Stroke LogEC50=-6.475, P< 0.001). Our study demonstrates that 24 hours post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. Aortas from stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while endothelium-independent vasodilatory responses were preserved. Since both vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.

This paper presents the results of simulations of particle-laden air-solid jet flow in long straight tubes using CFD-DEM, along with an analysis of coarse-graining. Although previous studies have used CFD-DEM for similar flows, these have typically been in a dilute flow regime where uncoupled simulations are accurate. However, fully coupled simulations can introduce issues, necessitating validation studies to ensure that all coupling parameters are effectively used and that the physics is accurately represented. This paper validates the simulations against two different experimental studies, with fluid Reynolds numbers between 10,000 and 40,000 and Stokes numbers between 5.6 and 50. Interestingly, the profiles of mean particle velocity exhibit fewer discrepancies as the Stokes number increases but more discrepancies for the root mean square velocity compared to the experiments. Particle number flux is consistent with the experiments after the nozzle exit. Coarse-graining is also applied to the same simulations, achieving relatively accurate results. However, as expected, scaling of contact collision frequencies, forces, and stresses cannot be achieved, meaning that coarse-graining may be useful for comparing designs or operating parameters on an industrial scale but falls short when measuring the total energy dissipation of one experiment.

This paper presents an analysis of linear viscous stress Favre-Averaged turbulence models for computational fluid dynamics (CFD) of fully turbulent round jets with a long straight tube geometry in the near field. Although similar work has been performed in the past with very relevant solutions, considerations were not given for the issues and limitations involved with coupling between an Eulerian and Lagrangian phase, such as in fully two-way coupled CFD-DEM. These issues include limitations on solution domain, mesh cell size, wall modelling, and momentum coupling between the two phases in relation to the particles size. Therefore, within these considerations, solutions are provided to the Navier-Stokes equations with various turbulence models using a three-dimensional wedge long straight tube geometry for fully developed turbulence flow. Simulations are performed with a Reynolds number of 15000 and 50000 using two different tube diameters. It is found that a modified k−ε turbulence model achieved the most agreeable results for both the velocity and turbulent flow fields between these two flow regimes, while a modified k−ω SST/BSL also provided suitable results.

Selective laser melting (SLM) is one of the widely used techniques in metallic additive manufacturing, in which high-density laser powder is utilized to selectively melting layers of powders to create geometrically complex parts. Temperature distribution and molten pool geometry directly determine the balling effect, and concentrated balling phenomenon significantly deteriorates surface integrity and mechanical properties of the part. Finite element models have been developed to predict temperature distribution and molten pool geometry, but they were computationally expensive. In this paper, the three-dimensional temperature distributions are predicted by analytical models using point moving heat source and semi-ellipsoidal moving source respectively. The molten pool dimensions under various process conditions are obtained from the three-dimensional temperature predictions and experimentally validated. Ti-6Al-4V alloy is chosen for the investigation. Good agreements between the predictions and the measurements are observed. The presented models are also suitable for other metallic materials in the SLM process.

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

Aedes aegypti transmits major arboviruses of public health importance, including dengue, chikungunya, Zika, and yellow fever. The use of insecticides represents the cornerstone of vector control, however insecticide resistance in Ae. aegypti has become widespread. Understanding the molecular basis of insecticide resistance in this species is crucial to design effective resistance management strategies. Here, we applied Illumina RNA-Seq to study the gene expression patterns associated with resistance to three widely used insecticides (malathion, alpha-cypermethrin and lambda-cyhalothrin) in Ae. aegypti populations from 2 sites (Manatí and Isabela) in Puerto Rico (PR). Cytochrome P450s were the most over-expressed detoxification genes across all resistant phenotypes. Some detoxification genes (CYP6Z7, CYP28A5, CYP9J2, CYP6Z6, CYP6BB2, CYP6M9, and two CYP9F2 orthologs) were commonly over-expressed in mosquitoes that survived exposure to all three insecticides (independent of geographical origin) while others including CYP6BY1 (malathion), GSTD1 (alpha-cypermethrin), CYP4H29 and GSTE6 (lambda-cyhalothrin) were uniquely overexpressed in mosquitoes that survived exposure to specific insecticides. The gene ontology (GO) terms associated with monooxygenase, iron binding, and passive transmembrane transporter activities were significantly enriched in 4 out of 6 resistant vs susceptible comparisons while serine protease activity was elevated in all insecticide resistant groups relative to the susceptible strain. Interestingly, cuticular-related protein genes (chinase and chitin) were predominantly downregulated, which was also confirmed in the functional enrichment analysis. This RNA-Seq analysis presents a detailed picture of the candidate detoxification genes and other pathways that are potentially associated with pyrethroid and organophosphate resistance in Ae. aegypti populations from PR. These results could inform development of novel molecular tools for detection of resistance-associated gene expression in this important arbovirus vector and guide the design and implementation of resistance management strategies.

To assess the presence of organochlorine pollutants (OCP) in Alaskan sub-Arctic latitudes, we analyzed ice core and meltwater samples from Jarvis Glacier, a polythermal glacier in Interior Alaska. Jarvis Glacier is receding as atmospheric warming continues throughout the region, increasing opportunity for OCP transport both englacially and into the proglacial watershed. Across all meltwater and ice core samples we identify the pesticides DDT, DDE and DDD, α- HCH and ϒ-HCH. OCP concentrations in ice core samples were highest at the 7-14 m depth (0.51 ng/L of DDT) and decreased gradually approaching the bedrock at 79m. Meltwater concentrations from the proglacial creek slightly exceeded concentrations found in the ice core, potentially indicating aggregate OCP glacial loss, with peak OCP concentration (1.12 ng/L of DDD) taken in July and potentially associated to peak melt. Ongoing use of DDT to fight Malaria in Asia, and the extended atmospheric range of HCH may account for concentrations in near-surface ice, correlating with use and atmospheric transport. The opportunity for biota bioaccumulation of OCPs, or human uptake of OCPs from glacial meltwater, may increase as glacial melt continues.

A Friedmann-Lemaitre-Robertson-Walker space-time model with all curvatures k=0,±1 is explored in f(R,T) gravity. The solutions are obtained via the parametrization of the scale factor that leads to a model transiting from a decelerated universe to an accelerating one. The physical features of the model are discussed and analysed.

Single image deraining (SID) has shown its importance in many advanced computer vision tasks. Though many CNN based image deraining methods have been proposed, how to effectively remove raindrops while maintaining background structure remains a challenge that needs to be overcome. Most of the deraining work focuses on removing rain streaks, but in heavy rain images, the dense accumulation of rainwater or the rain curtain effect significantly interferes with the effective removal of rain streaks, and often introduces some artifacts that make the scene more blurry. In this paper, we propose a new network structure R-PReNet for single image deraining with good background structure maintaining. This framework fully utilizes the cyclic recursive structure of PReNet. Moreover, we introduce residual channel prior (RCP) and feature fusion modules for better deraining performance by focusing on background feature information. Compared with the previous methods, our method has significantly improvement effect on the rainstorm image with the artifacts removing and good visual detail restoring.

We analyze the behavior of relativistic spherical objects within the context of modified $f(R,T)$ gravity considering Tolman VI spacetime, where gravitational lagrangian is a function of Ricci scalar(R) and trace of energy momentum tensor(T) i.e,$ f(R,T)= R+ 2\beta T$, for some arbitrary constant $\beta$. For developing our model, we have chosen $\pounds_{m} = -p$, where $ \pounds_{m}$ represents matter lagrangian. For this investigation, we have chosen three compact stars namely PSR J1614-2230 [Mass=(1.97$\pm$ 0.4)M$_\odot$; Radius= 9.69$_{-0.02} ^{+0.02}$ Km] ,Vela X-1 [Mass=(1.77$\pm$ 0.08)M$_\odot$; Radius= 9.560$_{-0.08} ^{+0.08}$ Km] and 4U 1538-52 [Mass=(9.69)M$_\odot$; Radius= 1.97 Km]. In this theory the equation of pressure isotropy is identical to standard Einstein's theory. So all known metric potential solving Einstein's equations are also valid here. In this paper, we have investigated the effort of coupling parameter ($\beta$) on the local matter distribution. Sound of speed and adiabatic index are higher with grater values of $\beta$ while on contrary mass function and gravitational redshift are lower with higher values of $\beta$ . For supporting the theoretical results, graphical representation are also employed to analyze the physical viability of the compact stars.

The main contribution of this paper is to develop a graphical tool to evaluate the suitability of a candidate parametric model to fit a data set. The practical motivation is to check the adequacy of the so called SAINT model proposed in Jarner and Kryger (2011). This model has been implemented in practice by an important European pension fund concerned with setting annuity reserves for all current or former employees of Denmark. So, one particular relevant question is whether this mortality model is actually fitting old-age. Our graphical test can be described as follows. First we transform the data by means of the parametric model which is being evaluated. Should the model be correct, the transformed data will be in accordance with an Exponential distribution with rate 1. Then we construct a family of local linear hazard estimates based on the data on the transformed scale. Finally we use the statistical tool SiZer to assess the goodness-of-fit of the Exponential distribution to the data on the transformed scale. If the model is correct the SiZer map should not reveal any significant feature in the family of kernel estimates. Our method allow us to establish a diagnostic regarding the validity of the SAINT model when describing mortality patterns in four different countries.

Tight regulation of gene transcription is essential for normal development, tissue homeostasis and disease-free survival. Enhancers are distal regulatory elements in the genome that provide specificity to gene expression programs and are frequently misregulated in cancer. Recent studies examined various enhancer-driven malignant dependencies and identified different approaches to specifically target these programs. In this review, we describe numerous features that make enhancers good transcriptional targets in cancer therapy and discuss different approaches to overcome enhancer perturbation. Interestingly, a number of approved therapeutic agents such as cyclosporine, steroid hormones, and thiazolidinediones actually function by affecting enhancer landscapes by directly targeting very specific transcription factor programs. More recently, a broader approach to targeting deregulated enhancer programs has been achieved via Bromodomain and Extraterminal (BET) inhibition or perturbation of transcription-related cyclin-dependent kinases (CDK). One challenge to enhancer-targeted therapy is proper patient stratification. We suggest that monitoring of enhancer RNA (eRNA) expression may serve as a unique biomarker of enhancer activity that can help to predict and monitor responsiveness to enhancer-targeted therapies. A more thorough investigation of cancer-specific enhancers and the underlying mechanisms of deregulation will pave the road for an effective utilization of enhancer modulators in a precision oncology approach to cancer treatment.

Pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R) has a higher affinity for pituitary adenylate cyclase- activating polypeptide (PACAP) than for vasoactive intestinal peptide (VIP). PACAP exerts its neuroprotective effects through PAC1-R. PAC1-R has become a target for drug development, and we targeted PAC1-R to screen small positive allosteric modulator 1 (SPAM1). SPAM1 has a neuroprotective effects, and in the D-galactose (D-gal) mouse model, SPAM1 improved the structure of the hippocampal dentate gyrus and restored the number of neurons. Compared with D-gal model mice, SPAM1 treatment upregulated the expression of Sirtuin 6 (SIRT6) and Lamin B1, and downregulated the expression of YinYang 1 (YY1) and p16. Consistent with this, the same results were obtained in senescent RGC-5 cells. Meanwhile, SPAM1 was also found to up-regulate SIRT6 and down-regulate YY1 expression in normal RGC-5 cells. Then, we further explored the mechanism of SPAM1 neuroprotection by whole transcriptome sequencing and proteomic analysis, and found that SPAM is involved in the longevity regulating pathway, and confirmed the up-regulation of neurofilament light polypeptide and neurofilament medium polypeptide by western blot, thus laying a pharmacological foundation for SPAM1 as a therapeutic agent for neurodegenerative diseases. polypeptide and neurofilament medium polypeptide. Thus, it lays a pharmacological foundation for SPAM1 as a therapeutic drug for neurodegenerative diseases.

In this paper, we first define the concepts of r-fuzzy soft α-open (semi-open and δ-open) sets on fuzzy soft topological spaces based on the article Aygunoglu et al. (Hacet. J. Math. Stat., 43 (2014), 193-208), and the relations of these sets with each other are established. In addition, we introduce the concepts of fuzzy soft δ-closure (δ-interior) operators, and study some properties of them. Also, the concept of r-fuzzy soft δ-connected sets is introduced and studied with help of fuzzy soft δ-closure operators. Thereafter, we define the concepts of fuzzy soft α-continuous (β-continuous, semi-continuous, pre-continuous and δ-continuous) functions, which are weaker forms of fuzzy soft continuity, and some properties of these functions along with their mutual relationships are discussed. Moreover, a decomposition of fuzzy soft α-continuity and a decomposition of fuzzy soft semi-continuity is obtained. Finally, as a weaker form of a fuzzy soft continuity, the concepts of fuzzy soft almost (weakly) continuous functions are defined, and some properties are specified. Additionally, we explore the notion of continuity in a very general setting called, fuzzy soft (L, M, N, O)-continuous functions and a historical justification is introduced.

Low-resource languages often face the problem of insufficient data, which leads to poor quality in machine translation. One approach to address this issue is data augmentation. Data augmentation involves creating new data by transforming existing data through methods such as flipping, cropping, rotating, and adding noise. Traditionally, pseudo-parallel corpora are generated by randomly replacing words in low-resource language machine translation. However, this method can introduce ambiguity as the same word may have different meanings in different contexts. This study proposes a new approach for low-resource language machine translation, which involves generating pseudo-parallel corpora by replacing phrases. The performance of this approach is compared with other data augmentation methods, and it is observed that combining it with other data augmentation methods further improves performance. To enhance the robustness of the model, R-Drop regularization is also used. R-Drop is an effective method for improving the quality of machine translation. The proposed method was tested on Chinese-Kazakh (Latin script) translation tasks, resulting in performance improvements of 4.99 and 7.7 for Chinese-to-Kazakh and Kazakh-to-Chinese translations, respectively.

Early detection of wildfires has been limited using the sun-synchronous orbit satellites due to their low temporal resolution and wildfires’ fast spread in the early stage. NOAA’s geostationary weather satellites GOES-R can acquire images every 15 minutes at 2km spatial resolution, and have been used for early fire detection. However, advanced processing algorithms are needed to provide timely and reliable detection of wildfires. In this research, a deep learning framework, based on Gated Recurrent Units (GRU), is proposed to detect wildfires at early stage using GOES-R dense time series data. GRU model maintains good performance on temporal modelling while keep a simple architecture, makes it suitable to efficiently process time-series data. 36 different wildfires in North and South America under the coverage of GOES-R satellites are selected to assess the effectiveness of the GRU method. The detection times based on GOES-R are compared with VIIRS active fire products at 375m resolution in NASA’s Fire Information for Resource Management System (FIRMS). The results show that GRU-based GOES-R detections of the wildfires are earlier than that of the VIIRS active fire products in most of the study areas. Also, results from proposed method offer more precise location on the active fire at early stage than GOES-R Active Fire Product in mid-latitude and low-latitude regions.

We present a methodology to enable users to interact with statistical information owned by an institution and stored in a cloud infrastructure. Mainly based on R, this approach was developed following the open-data philosophy. Also, since we use R, the implementation is mainly based on open-source software. R gives several advantages from the point of view of data management and acquisition, as it becomes a common framework that can be used to structure the processes involved in any statistical operation. This simplifies the access to the data and enable to use all the power of R in the cloud information. This methodology was applied successfully to develop a tool to manage the data of the Centre d’Estudis d’Opinió, but it can be applied to other institutions to enable open access to its data. The infrastructure also was deployed to a cloud infrastructure, to assure the scalability and a 24/7 access.

While the mortality rates of cancer are generally declining, pancreatic cancer persists to be an exception with a 5-year-survival rate of less than 7%. Late diagnosis and resistance to conventional therapies contribute to high mortality rates in spite of the remarkable recent advances in cancer management and research. Consequently, there is an urgent need to find new and unconventional therapeutic targets to improve prognosis and survival of pancreatic cancer patients. In this review, we discuss the transcriptional effects of the most widely used epigenetic inhibitors in pancreatic cancer focusing on Bromodomain and Extraterminal domain (BET) and Histone Deacetylase (HDAC) inhibitors, which are currently highly promising therapeutic options. We suggest that these inhibitors can be better utilized at lower doses which exploit their transcriptional modulatory effects on pancreatic cancer transcriptional programs directed by specific factors such as MYC and FOXA1, rather than simply based on their anti-proliferative effects. This approach can potentially help avoid the intolerable adverse events frequently elicited by the use of these treatments at higher doses. In particular, we underscore the crucial role of distal regulatory elements in mediating the specific effects of these epigenetic inhibitors and propose using them in a more selective and prudent manner.

Despite improved knowledge regarding diagnosis and treatment of osteomyelitis of the jaw (OMJ), it remains a clinical challenge for oral and maxillofacial surgeons. This study aimed to identify risk factors associated with severe forms of OMJ, i.e. related to the occurrence of major complications or the refractory course of the disease. A retrospective study was performed based on the medical records of all patients diagnosed with OMJ from the past 20 years. Collected data included demographic information, medical and dental history, clinical, radiological, and bacterial findings as well as treatment modalities. The main outcome variables were the onset of major complications and treatment results. Fifty-four patients were included. Our results showed that alcohol and smoking habits, as well as malnutrition, were significantly associated with the occurrence of major complications. We also established that dental implant–induced OMJ should be considered as an aggressive subtype of OMJ. Finally, clinical bone exposure was significantly associated with unfavorable outcomes, whereas dental causes or radiological evidence of periosteal reaction were predictive of successful outcomes. Identifying such factors could be useful in preventing serious complication and informing patients about the refractory course of the disease based on the presence of these factors.

The oil and gas industry in Nigeria, a vital contributor to the nation's economy, has long been associated with significant environmental challenges. Pollution, habitat destruction, and greenhouse gas emissions have raised global concerns about sustainability and corporate responsibility. This empirical study explores the relationship between environmental accounting practices and the financial performance of listed oil and gas companies in Nigeria. We investigated eight oil and gas companies that are publicly traded on the Nigerian Stock Exchange Market (NGX) as of January 17, 2022, from 2011 to 2022. The study employs Driscoll-Kraay standard errors and reveals that environmental accounting had significant effects on returns on assets, earnings per share, and liquidity ratio. The study revealed that the implementation of environmental accounting practices had diverse effects on the performance of oil and gas companies in Nigeria. The findings encourage policymakers and stakeholders in the sector to utilise the insights and design more effective regulations and incentives that promote environmental corporate responsibility. Also, valuable insights into the potential benefits and challenges associated with adopting environmental accounting practices, and influencing the decision-making processes of corporate stakeholders were provided to ensure sustainability in terms of improved financial performance of the oil and gas sector in Nigeria.