It is well known that a sequence of two non-collinear Lorentz boosts (pure Lorentz transformations) does not correspond to a Lorentz boost, but involves a spatial rotation, the Wigner or Thomas-Wigner rotation. We visualize the interrelation between this rotation and the relativity of distant simultaneity by moving a Born-rigid object on a closed trajectory in several steps of uniform proper acceleration. Born-rigidity implies that the stern of the boosted object accelerates faster than its bow. It is shown that at least five boost steps are required to return the object's center to its starting position, if in each step the center is assumed to accelerate uniformly and for the same proper time duration. With these assumptions, the Thomas-Wigner rotation angle depends on a single parameter only. Furthermore, it is illustrated that accelerated motion implies the formation of an event horizon. The event horizons associated with the five boosts constitute a natural boundary to the rotated Born-rigid object and ensure its finite size.

Wet anaerobic storage of algal biomass is a promising preservation approach which can ensure continuous supply of these feedstocks to biorefineries year-round. An effective solution to preservation must ensure minimal dry matter loss and change in biochemical composition during storage. Therefore, the objective of this study was to investigate the preservation of Nannochloropsis gaditana biomass through wet anaerobic storage and its impact on biomass quality. Prior to storage, algae sample was inoculated with two different strains of lactic acid bacteria and thereafter stored for 30 and 180 days. Each inoculant limited dry matter loss to <10% (dry basis) after the storage durations. Final pH values (4.3 - 4.8) indicate that the biomass samples were properly ensiled, achieving the acidic conditions necessary for preservation. Compositional analysis of the biomass after storage showed a reduction in carbohydrate content, a relative increase in lipid content, and no significant change to the protein fraction. Glucose and galactose were the prevalent sugar monomers. The low dry matter loss and minimal compositional change indicates that wet anaerobic storage is an effective means of preserving algal biomass, ensuring a constant supply of algal biomass feedstock to a biorefinery.

Magnetosomes of magnetotactic bacteria consist of magnetic nanocrystals with defined morphologies enclosed in vesicles originated from cytoplasmic membrane invaginations. Although many proteins are involved in creating magnetosomes, a single magnetosome protein, Mms6, can direct the crystallization of magnetite nanoparticles in vitro. The in vivo role of Mms6 in magnetosome formation is debated and the observation that Mms6 binds ferric and not ferrous iron raises the question of how Mms6 could promote the crystallization of magnetite, which contains both ferric and ferrous iron. Here we show that Mms6 is a ferric reductase that reduces ferric to ferrous iron using NADH and FAD as electron donor and cofactor, respectively. Reductase activity is elevated when Mms6 is integrated into either liposomes or bicelles. Analysis of Mms6 mutants suggests that the C-terminal domain binds iron and the N-terminal domain contains the catalytic site. Although Mms6 forms multimers that involve C-terminal and N-terminal domain interactions, a fusion protein with Mms6, which remains a monomer, displays reductase activity, which suggests that the catalytic site is fully in the monomer. These results are consistent with a hypothesis that Mms6, a membrane protein, promotes the formation of magnetite by a mechanism that involves reducing iron.

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

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track response to therapy, and parse causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD).

Objective: ISPOR is the leading professional society for health economics and outcomes research (HEOR) globally. Recently, it launched its Women in HEOR Initiative, that aims to serve as a catalyst for women’s leadership in the field. Therefore, we were interested to find out how well ISPOR itself is doing in terms of gender diversity at their biggest conference. Methods: We used the conference programmes of ISPOR Europe conferences in 2016, 2017 and 2018 to assess the gender distribution of speakers that participated in issue panels and plenary sessions in these years. Results: 70% of all speakers (N=346) at 85 issue panels and plenary sessions during 2016, 2017, and 2018 were male. Almost one in three panels was all-male (a ‘manel’) and 64% of all panels had mostly male speakers (>50%). In contrast, only 11% of panels had <50% female speakers. Conclusion: Despite laudable effort to support the growth, development and contribution of women in HEOR through its Women in HEOR Initiative, females appear to be severely underrepresented at ISPOR’s biggest conference. ISPOR should make gender diversity a formal requirement for issue panel abstract submissions if it wants to advance women’s leadership in HEOR.

Background: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults. Methods: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam. Multiple linear regression was used to assess the association of each metabolite (log-transformed) in separate models with MRI measures except lacunar infarcts, for which binary logistic regression was used. Results: Higher concentrations of plasma PC aa C36:5 had adverse associations with MRI features of cerebral SVD (odds ratio of 1.69 [95% confidence interval: 1.01, 2.83] with lacunar infarct, and beta of 0.16 log [cm³] [0.02, 0.30] with log [White Matter Hyperintensities (WMH) volume]) while higher concentrations of 3 plasma SM (OH)s were associated with higher total brain volume (beta of 12.0 cm³ [5.5, 18.6], 11.8 cm³ [5.0, 18.6], and 7.3 cm³ [1.2, 13.5] for SM [OH] C22:1, SM [OH] C22:2, and SM [OH] C24:1, respectively). Conclusions: This study identified associations between certain plasma metabolites and brain MRI measures of SVD and neurodegeneration in older adults, particularly higher SM (OH) concentrations with higher total brain volume.

The COVID-19 pandemic which have affected every part of the world have been deemed a public health concern and classified as a pandemic. The government imposing travel bans and quarantine measures have been found to be effective in preventing and reducing the spread of COVID-19. A reduction in physical activity and increase in the consumption of unhealthy foods have been observed to be some of the major implications of quarantine. Adequate physical activity and increased access to healthy foods would help in improving the psychological wellbeing of individuals thereby preventing the development of cardiovascular diseases.

Diet influences, and is influenced by, a wide range of socioeconomic, cultural, geographic, and genetic variables. Here we survey a matrix of such interactions as well as their connection to a variety of health outcomes, in a cohort of 689 diverse adults employed at Emory University and enrolled in the Center for Health Discovery and Well-Being (CHDWB) study. Principal component analysis (PCA) of the Block Food Frequency Questionnaire revealed seven PC cumulatively explaining 25.8% and each individually at least 2% of the proportional consumption of 110 food items. PC1 is strongly correlated with the Healthy Eating Index-2015 measure, and accordingly healthier scores associate with multiple measures of physical and mental health. It, as well as PC2 (likely a measure of food expense) and PC3 (carbohydrate versus protein consumption) show significant geographic structure across the Atlanta metropolitan area, correlating with race and ethnicity, income level, age and sex. Notably, a polygenic score for body mass index (BMI) consisting of 281 SNPs explains 2.8% of the variance in PC5, which is as strong as its association with BMI itself. PC5 appears to differentiate participants with respect to conscious eating behavior related to the choice of diet or comfort foods. Our analysis adds to the growing literature on factor analysis of socio-demographic influences on nutrition and health.

Purpose: Perceptual learning and production practice are basic mechanisms that children depend on to acquire adult levels of speech accuracy. In this study, we examined perceptual learning and production practice as they contributed to changes in speech accuracy in three- and four-year-old children. Our primary focus was manipulating the order of perceptual learning and baseline production practice to better understand when and how these learning mechanisms interact. Method: Sixty-five typically-developing children between the ages of three and four were included in the study. Children were asked to produce CVCCVC nonwords like /bozjəm/ and /tʌvtʃəp/ that were described as the names of make-believe animals. All children completed two separate experimental blocks: a baseline block in which participants heard each nonword once and repeated it, and a test block in which the perceptual input frequency of each nonword varied between 1 and 10. Half of the participants completed a baseline-test order; half completed a test-baseline order. Results: Greater accuracy was observed for nonwords produced in the second experimental block, reflecting a production practice effect. Perceptual learning resulted in greater accuracy during the test for nonwords that participants heard 3 or more times. However, perceptual learning did not carry over to baseline productions in the test-baseline design, suggesting that it reflects a kind of temporary priming. Finally, a post hoc analysis suggested that the size of the production practice effect depended on the age of acquisition of the consonants that comprised the nonwords. Conclusions: The study provides new details about how perceptual learning and production practice interact with each other and with phonological aspects of the nonwords, resulting in complex effects on speech accuracy and learning of form-referent pairs. These findings may ultimately help speech-language pathologists maximize their clients’ improvement in therapy.

Pharmacy personnel often answer telephones to respond to pharmacy customers (subjects) who received messages from automated systems. This research examines the communication process in terms of how users interact and engage with pharmacies after receiving automated messages. No study has directly addressed automated telephone calls and subjects’ interactions. The purpose of this study is to test the interpersonal communication (IC) process of uncertainty in subjects in receipt of automated telephone calls from pharmacies. Subjects completed a survey of validated scales for Satisfaction (S); Relevance (R); Quality (Q); Need for Cognitive Closure (NFC). Relationships between S, R, Q, NFC, and subject preference to an automated telephone call (ATC) were analyzed to determine whether subjects contacting pharmacies display information seeking behavior. This research demonstrates that seeking information occurs if subjects: are dissatisfied with the content of the ATC; perceive that the Q of the ATC is high; perceive that the Q of ATC is high, and like receiving the ATC or with high NFC, and do not like receiving ATCs. Other interactions presented complexities amongst uncertainty and tolerance of NFC within the IC process.

Introduction: The choice of Cardiac Preservation Solution (CPS) for myocardial protection at the time of heart procurement remains controversial and uncertainties persist regarding its effect on the early and midterm Heart Transplantation (HTx) outcomes. Thus, we retrospectively analyzed our adult HTx performed with two different CPS, during a period of 12 years, in terms of hospital mortality, mid-term survival, inotropic score, primary graft dysfunction and rejection score. Methods: From January 2009 to December 2020, 154 adult HT were performed in our hospital. Patients were divided in two groups according to the CPS used: St. Thomas (n=75, group P 1) and HTK-Custodiol (n=79, group P 2). The choice of CPS was related to an institutional policy; from 2009 to 2015, St. Thomas solution was exclusively used, and after that, HTK-Custodiol alone. Results: There was no significant difference between the two groups in terms of preoperative and intraoperative features. Postoperatively, the Custodiol group showed significantly lower inotropic score (p&lt;0.0001), mean rejection score (p= 0.036) and 30 days mortality (p=0.0068). The use of HTK-Custodiol was the only variable that improved midterm survival (HTK-Custodiol vs St Thomas, HR= 0.20 (95% CI: 0.069 -0.6) p=0.0039). Conclusion: In our single center experience, using HTK-Custodiol as myocardial protection during heart procurement leads to improved outcomes after HTx, including postoperative inotropic score, rejection score, 30-days mortality and midterm survival.

ChatGPT, a freely-accessible AI language model designed to generate human-like text responses to users, has been utilized in several areas, such as healthcare industry, to facilitate interactive dissemination of information. Academic advising has been an important factor in promoting success among university students, particularly those from disadvantaged backgrounds. Unfortunately, however, student advising has been marred with problems, with the availability and accessibility of advisors being among the hurdles. The current study explores how ChatGPT might serve to make academic advising more accessible, efficient, and even effective. Researchers compiled a list of questions frequently asked by current and prospective students in a teacher education Bachelor’s degree program in the United States. Then, the questions were typed into the free version of ChatGPT and the answers generated were evaluated for their content and delivery. ChatGPT generated surprisingly high-quality answers, written in an authoritative yet supportive tone, and it was particularly adept at addressing general career-related questions comprehensively, such as career outlook. We argue that ChatGPT may complement, but not replace, human academic advisors and it may very well promote educational equity through empowering students from a wide range of backgrounds with the means to access effective advising.

Recent years have seen a massive increase in research on mindfulness as both a therapeutic practice as well as a protective health factor. While many associations have been made between mindfulness and clinical outcomes, understanding of the underlying mechanistic processes is still in its infancy. In this review, associations between mindfulness and other established frameworks in cognitive control are explored—in particular the dual modes of control framework in cognitive control theory. Studies in mindfulness providing evidence towards a dual-mode mindfulness model are reviewed and compared with the proactive and reactive modes of cognitive control to identify common underlying principles. Studies involving cognitive testing, advanced neuroimaging, and neurotransmitter levels and their associations with proactive and reactive control are reviewed in the context of the dual modes of mindfulness. While evidence supporting relationships between proactive and reactive modes of mindfulness and cognitive control are preliminary, existing literature on mindfulness already supports the notion of two components of mindfulness and is in line with the hypothesis that cognitive control and mindfulness are closely related. Since preliminary evidence suggests that proactive forms of mindfulness are more associated with improvement in clinical outcomes, mindfulness programs could be modified to target proactive mindfulness practices to maximize outcomes. The implications of proactive and reactive mindfulness on therapy, limitations of the framework, and necessity of studies providing direct evidence are further discussed.

Background: A careful work-up before Transcatheter aortic valve replacement (TAVR) consists not only of measuring anatomical conditions but also assessment of frailty. Previous studies have evaluated body composition parameters, primarily fat and muscle mass. Few data are available on other frailty parameters, which, however, can be easily determined by pre-TAVR computed tomography (CT). Objectives: The primary objective was to investigate the impact of total muscle area (TMA) and visceral adipose tissue (VAT), as frailty parameters, on 5-year all-cause mortality in patients undergoing TAVR. Methods: Between 01/2017 and 12/2018, consecutive TAVR patients undergoing CT-angiography scan enabling TMA and VAT measurement were included. A single axial image was acquired at the level of the middle third lumbar vertebra to perform TMA and VAT measurements using dedicated slicing software (Sliceomatic, TomoVision). Results: A total of 500 patients qualified for TMA analysis. Age was not associated with a higher risk of 5-year mortality HR 1.02 (95% CI: 0.998 - 1.049; p=0.069). Body surface area normalized TMA (nTMA) was significantly associated with 5-year all-cause mortality (HR 0.927, 95% CI: 0.927-0.997; p= 0.033), while VAT had no effect (HR 1.002, 95% CI: 0.99-1.015; p= 0.7). The effect of nTMA on 5- year all-cause mortality was gender-dependent: the protective effect of higher nTMA was found in male patients (pinteraction: sex * nTMA = 0.007). The combination of normalized TMA and VAT was not associated with higher mortality rates. Conclusion: Normalized TMA derived from routine CT before TAVR complements frailty assessment in patients undergoing TAVR.

Enforcement of animal welfare statutes are the primary protection given for the maintenance of animal welfare and prevention of cruelty. It is speculated that animal law enforcement in Australia has a number of weakness in the enforcement model. These weaknesses create a gap between the goals of animal law enforcement and the reality of the animal law justice system. This gap is defined as the ‘enforcement gap’. This paper identifies and investigates the causes of this gap. The hypothesized causes discussed are (1) the impact the public can have on reporting animal cruelty, (2) the reliance on charitable organizations as enforcement bodies, (3) the inconsistencies in animal welfare legislation, and (4) the role of the sentencing courts. Thus, the causes of the enforcement gap are multifactorial; derived from all stages of the enforcement process. Further research is needed to investigate the concepts raised in this paper. However, it is likely that a combination of structural change to enforcement agencies, legislative reform and public education is required to reduce the enforcement gap.

For many engineering applications it is sufficient to use the concept of simple materials. However, higher gradients of the kinematic variables are taken into account to model materials with internal length scales as well as to describe localization effects using gradient theories in finite plasticity or fluid mechanics. In many approaches length scale parameter have been introduced that are related to a specific micro structure. An alternative approach is possible, if a thermodynamically consistent framework is used for material modelling as shown in the present contribution. However, even if sophisticated and thermodynamically consistent material models can be established there are still not yet standard experiments to determine higher order material constants. In order to contribute to this ongoing discussion system identification based on the method of self-adaptive filtering is proposed in this paper. To evaluate the effectiveness of this approach it has been applied to second-order gradient materials considering longitudinal vibrations. Based on thermodynamically consistent models that have been solved numerically it has been possible to prove that system identification based on self-adaptive filtering can be used effectively for both narrow-band and broadband signals in the field of second-order gradient materials. It has also been found that the differences identified for simple materials and gradient materials allow for condition monitoring and detection of gradient effects in the material behavior.

Dietary recommendations to decrease the risk of cardiovascular disease (CVD) have focused on reducing intake of saturated fatty acids (SFA) for more than 50 years. While the 2015-2020 Dietary Guidelines for Americans advise substituting both monounsaturated and polyunsaturated fatty acids for SFA, evidence supports other nutrient substitutions that will also reduce CVD risk. For example, replacing SFA with whole grains, but not refined carbohydrates, reduces CVD risk. Replacing SFA with protein, especially plant protein may also reduce CVD risk. While dairy fat (milk, cheese) is associated with a slightly lower CVD risk compared to meat, dairy fat results in a significantly greater CVD risk relative to unsaturated fatty acids. As research continues, we will refine our understanding of dietary patterns associated with lower CVD risk.

Retrospective information about the climate system and plant ecophysiology are key inputs in climate and Earth system modelling. Dendrochronology provides such information with large spatiotemporal coverage, and stable carbon isotope (¹³C/¹²C) analysis across tree-ring series is among the most advanced dendrochronological tools. For the past seventy years, this analysis was performed on whole molecules, and, to this day, ¹³C/¹²C variation is attributed to ¹³C discrimination during CO₂ diffusion into leaves and assimilation by rubisco. By contrast, ¹³C discrimination by post-rubisco processes is presumed constant. Here, recently reported results on the first dataset of intramolecular ¹³C discrimination in tree rings were synthesised by variance component analysis. The emerging picture is not consistent with the classical (DR-discrimination-centred) concepts and practices of carbon-isotope dendrochronology. Specifically, leaf and stem post-rubisco discrimination each account for more variation in the data than diffusion-rubisco discrimination, i.e., post-rubisco discrimination is not constant. Furthermore, diffusion-rubisco discrimination is used widely as proxy of leaf intrinsic water-use efficiency (iWUE), a key determinant in the responses of global biogeochemical cycles to climate change. However, since diffusion-rubisco discrimination is a small component of the total data variance, whole-molecule analysis yields confounded iWUE estimates, yet intramolecular analysis will likely offer solutions. Lastly, all currently observed ¹³C/¹²C-climate relationships are attributed to diffusion-rubisco discrimination. However, here, relationships with temperature and radiation derive from leaf-level post-rubisco discrimination while relationships with precipitation derive from stem-level post-rubisco discrimination. That said, advances in mass spectrometry may soon make intramolecular ¹³C/¹²C analysis broadly available taking carbon-isotope dendrochronology to the next level.

We present an overview over eight brightly luminescent Cu(I) dimers of the type Cu2X2(PN)3 with X = Cl, Br, I and P^N = 2-diphenylphosphino-pyridine (Ph2Ppy), 2-diphenylphosphino-pyrimidine (Ph2Ppym), 1-diphenylphosphino-isoquinoline (Ph2Piqn) including three new crystal structures (Cu2Br2(Ph2Ppy)3, 1-Br, Cu2I2(Ph2Ppym)3, 2-I, and Cu2I2(Ph2Piqn)3, 3-I). However, we mainly focus on their photo-luminescence properties. All compounds exhibit combined thermally activated delayed fluorescence (TADF) and phosphorescence at ambient temperature. Emission color, decay time, and quantum yield varies over large ranges. For deeper characterization, we select Cu2I2(Ph2Ppy)3, 1-I, showing a quantum yield of 81 %. DFT and SOC-TDDFT calculations provide insight into the electronic structures of the singlet S1 and triplet T1 states. Both stem from metal+iodide-to-ligand charge transfer transitions. Evaluation of the emission decay dynamics, measured from 1.2 ≤ T ≤ 300 K, gives ∆E(S1-T1) = 380 cm-1 (47 meV), a transition rate of k(S1→S0) = 2.25×106 s-1 (445 ns), T1 zero-field splittings, transition rates from the triplet substates, and spin-lattice relaxation times. We also discuss the interplay of S1-TADF and T1-phosphorescence. The combined emission paths shorten the overall decay time. For OLED applications, utilization of both singlet and triplet harvesting can be highly favorable for improvement of the device performance.

Consumer food environments have transformed dramatically in the last decade. The number of food outlets has increased, and a large proportion of the UK population now purchase food from a takeaway or restaurant at least once a week. Despite these developments, national spending on food control has reduced and many Local Authorities struggle to meet health inspection targets. This work presents a data driven approach to enhance current inspection processes with a view to reduce consumer risk of foodborne illness whilst eating outside the home. We explore the utility of three machine learning algorithms to predict non-compliant food outlets in England and Wales as defined by Food Hygiene Rating Scheme scores >= 2. Using socio-demographic, business type and urbanness features we experiment with under and over sampling strategies at five ratios to address problems of class imbalance in the dataset prior to analysis. We find that Synthetic Minority Over Sampling Technique alongside a Random Forest algorithm with a 1:1 sampling strategy provides the best predictive power. Our final model retrieves 84% of total non-compliant outlets in a test set of 92,595 (sensitivity=0.843, specificity=0.745, precision=0.274). We discuss the utility of machine learning algorithms to prioritise high risk establishments for inspection by Local Authority officials and make recommendations for weighting outcomes to improve their appropriateness in an applied setting.

Proper identification of oriented knots and 2-component links requires a precise link nomenclature. Motivated by questions arising in DNA topology, this study aims to produce a nomenclature unambiguous with respect to link symmetries. For knots, this involves distinguishing a knot type from its mirror image. In the case of 2-component links, there are up to sixteen possible symmetry types for each topology. The study revisits the methods previously used to disambiguate chiral knots and extends them to oriented 2-component links with up to nine crossings. Monte Carlo simulations are used to report on writhe, a geometric indicator of chirality. There are ninety-two prime 2-component links with up to nine crossings. Guided by geometrical data, linking number and the symmetry groups of 2-component links, a canonical link diagram for each link type is proposed. All diagrams but six were unambiguously chosen ( $8_1^{2}5$ , $9_5^2$ , $9_3^{2}4$ , $9_3^{2}5$ , $9_3^{2}9$ , and $9_4^{2}1$ ). We include complete tables for prime knots with up to ten crossings and prime links with up to nine crossings. We also prove a result on the behavior of the writhe under local lattice moves.

The COVID-19 pandemic has had devastating consequences for health, social, and economic domains, but what has received far less focus is the effect on people’s relationship to vital ecological supports, including access to greenspace. We assessed patterns of greenspace use in relation to individual and environmental factors and their relationship with experiencing psychological symptoms under the pandemic. We conducted an online survey recruiting participants from social media for adults in Korea for September–December 2020. The survey collected data on demographics, patterns of using greenspace during the pandemic, and major depression (MD) and generalized anxiety disorder (GAD) symptoms. The Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder 2-item (GAD-2) were applied to identify probable cases of MD and GAD. A logistic regression model assessed the association decreased visits to greenspace after the outbreak compared to 2019 and probable MD and GAD. Among the 322 survey participants, prevalence of probable MD and GAD were 19.3% and 14.9%, respectively. High rates of probable MD (23.3%) and GAD (19.4%) were found among persons currently having job-related and financial issues. Of the total participants, 64.9% reported decreased visits to greenspace after the COVID-19 outbreak. Persons with decreased visits to greenspace had 2.06 higher odds (95% CI: 0.91, 4.67) of probable MD at the time of the survey than persons whose visits to greenspace increased or did not change. Findings suggest that barriers to greenspace use could deprive people of mental health benefits and affect mental health during pandemic; an alternative explanation is that those experiencing poor mental health may be less likely to visit greenspaces during pandemic. This implies the need of adequate interventions on greenspace uses under an outbreak especially focusing on how low-income populations may be more adversely affected by a pandemic and its policy responses.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

EIMIs face the challenge of adapting to the Paris Agreement and the European Green Deal to achieve carbon neutrality. This change is being driven by consumer interest in low-carbon products, regulatory requirements from climate agreements and investors prioritizing sustainability. This pressure is pushing companies to go beyond short-term financial gains and integrate sustainability into their business. The growing awareness of the environmental impact of business models (BM) has fueled the development of Sustainable Business Models (SBMs). This study aims to link the discussion on the role of SBMs in the drivers of decarbonization, to improve the understanding of how the drivers can be integrated and enable new BMs for EIMIs. Based on a structured literature review, semi-structured interviews were conducted in the EIMIs. The study identifies BM-components that are influenced by these drivers and require sustainable business model innovation (SBMI). The results show that decarbonization drivers have a significant impact on all BM components. Experts emphasize the importance of collaborative approaches and cooperation throughout the value chain. This research elaborates on the importance of systematic analysis to understand how companies can effectively manage decarbonization drivers and suggests in-depth exploration within BM-research to uncover potential SBM design options.

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

Recombinant laboratory plasmids (RLPs) are common in biological research and freely shared among academic research laboratories (ARLs), a practice required by many research funding agencies. However, the generation of accurate, reproducible results in experiments utilizing RLPs can be hampered by a lack of accompanying sequence information and metadata. This culture of RLP sharing without knowledge of sequence or etiology is accepted by publishers, not regulated by governments, and outside the realm of bio-industry. In addition, no centralized infrastructure currently exists to collate such data, which at the moment is fragmented across companies, non-profits, and governments and thus is not easily accessed or enacted toward threat assessment. The ubiquity, free exchange, and dual-use risk of RLPs exemplifies a biosecurity threat and elevates the need to characterize their composition to facilitate improved biorisk management by the academic community. A number of common sense solutions are available to create a culture that addresses the biosecurity gap posed by RLP sharing. Culture shift in RLP management will require new norms, effective data management for collation of RLP sequences and metadata, and an incentive structure that encourages sequencing by stakeholders. The next generation of researchers must initiate and champion this shift with support from funding agencies and endorsement from governments and international organizations. Coordination of efforts and stakeholders will require international public/private collaboration, a structure that will be critical to ensure widespread utility as well as the ability of lower-resourced partners to participate, contribute, and benefit.

Twice-exceptional learners face a unique set of challenges arising from the intersection of extraordinary talent and disability. Neurobiology research has the capacity to complement pedagogical research and provide support for twice-exceptional learners. Very few studies have attempted to specifically address the neurobiological underpinnings of twice-exceptionality. However, neurobiologists have built a broad base of knowledge in nervous system function spanning from the level of neural circuits to the molecular basis of behavior. It is known that distinct neural circuits mediate different neural functions, which suggests that 2e learning may result from enhancement in one circuit and disruption in another. Neural circuits are known to adapt and change in response to experience, a cellular process known as neuroplasticity. Plasticity is controlled by a bidirectional connection between the synapse, where neural signals are received, and the nucleus, where regulated gene expression can return to alter synaptic function. Complex molecular mechanisms compose this connection in distinct neural circuits, and genetic alterations in these mechanisms are associated with both memory enhancements and psychiatric disorder. Understanding the consequences of these changes at the molecular, cellular, and circuit levels will provide critical insights into the neurobiological bases of twice-exceptional learning.

This article explores the significant parallels between big tobacco companies and major social networking sites regarding their influence on public health and society. While acknowledging the fundamental differences in their products and services, the paper scrutinises both industries through five primary lenses: addiction, misinformation, lack of regulation, harm to public health, and youth targeting. Both industries exhibit addictive characteristics, have faced criticism for the spread of misinformation, operate with limited regulation and transparency, and have raised concerns about targeting young demographics. Moreover, the potential harm to public health is a significant concern, with tobacco leading to well-established physical health issues. At the same time, excessive social media use has been linked to psychological harm, particularly among young users. The comparison underscores the necessity for greater regulation and oversight of social media companies, highlighting the urgent need for more comprehensive policies to mitigate potential harm and safeguard public health in the digital age.

Providing patient-centered care to manage chronic pain and opioid use disorder (OUD) is associated with improved health outcomes. However, adopting a holistic approach to providing care is often challenging in rural communities. This study aims to identify and contrast challenges to providing patient-centered care from the perspective of patients and providers. A participatory design approach was adopted to elicit the perceptions of providers and patients with lived experiences of chronic pain and OUD in Jefferson County, Wisconsin. Two focus groups were conducted with each stakeholder group to identify problems that participants face with respect to chronic pain management and OUD and possible solutions. Four interviews were conducted with providers experienced in chronic pain management. Analysis of focus group sessions and interviews show consensus among patients and providers that lack of behavioral health and recovery resources create barriers to effectively manage OUD and chronic pain. However, there was discordance among the two groups about other barriers such as patient and provider attitudes, tapering approach, and access to medications for OUD. This tension among patients and providers can influence patients’ retention in therapy. More efforts are needed to mitigate stigma among providers in rural communities and support psychosocial needs of patients.

Abstract: Theoretical and non-dimensional investigations have been performed to study the vibration control potential of approaches that can be based on viscoelastic but also on endochronic elements. The latter are known from the endochronic theory of plasticity and provide the possibility to establish rate-independent schemes for vibration control. The main question that has to be answered is: Can rate-independent damping be efficiently used to reduce mechanical vibrations? To answer this question non-dimensional models for dynamical systems are derived and analyzed numerically in time-domain as well as in frequency-domain. The results are used to compare the performance of an optimally tuned endochronic absorber to the performance of an optimally tuned dynamic absorber with viscoelastic damping. Based on a novel closed form representation for non-linear systems with endochronic elements, it has been possible to prove that rate-independent control of vibration results in an overall control profit that is close to the control profit obtained by the application of well-established approaches. It has also been found that the new concept is advantageous if anti-resonances have to be considered in broadband vibration control. Based on these novel findings, a practical realization in the context of active vibration control is proposed in which the rate-independent control law is implemented on an appropriate signal processing hardware.

The structures of a number of dimers of sulphur dioxide and ozone have been optimized by means of a series of ab initio calculations. The dimer species have been classified as either genuine energy minima or transition states of first or higher order, and the most probable structures consistent with the experimental data have been confirmed. The molecular orbitals engaged in the interactions resulting in adduct formation have been identified and relations between the orbitals of the dimers of the valence isoelectronic monomer species examined. The vibrational spectra of the most probable structures have been computed, and compared with those reported in the literature, particularly with spectra observed in cryogenic matrices. The calculations have been extended to predict the properties of a number of possible heterodimers formed between sulphur dioxide and ozone.

We suggest progress regarding the following six physics opportunities. List all elementary particles. Describe dark matter. Explain ratios of dark matter to ordinary matter. Explain eras in the history of the universe. Link properties of objects. Interrelate physics models. We use models based on Diophantine equations.

Peptide mapping is an important tool to confirm the correct sequence expressed for a protein and to evaluate protein post-translational modifications (PTMs) that may arise during production, processing, or storage of protein drugs. Our new orally administered drug (Ab-1), a single-domain antibody, is highly stable and resistant to proteolysis. Analysis by the commonly used tryptic map method did not generate sufficient sequence coverage. Alternative methods were needed to study the Ab-1 drug substance (75 mg/mL) and drug product (3 mg/mL). To meet analytical needs, we developed two new peptide map methods with lysyl endopeptidase (Lys-C) digestion. These newly developed protein digestion protocols do not require desalting/buffer-exchange steps, thereby reducing sample preparation time and improving method robustness. Additionally, the protein digestion was performed under neutral pH with methionine acting as a scavenger to minimize artifacts, such as deamidation and oxidation, which are induced during sample preparation. Further, the method for low concentration samples performs comparably to the method for high concentration samples. Both methods provide 100% sequence coverage for Ab-1, and therefore, enable comprehensive characterization for its product quality attributes (PQA) assessment. Both methods can be used to study other antibody modalities.

Introduction: As the paramedic profession continues to grow and evolve, a shift from reactive to holistic patient care models is required. As the first and often the only point of medical contact for many patients from marginalized and under-served populations, the paramedic role, and its potential future implications in caring for these patients needs to be explored. Aim: The objective of this scoping review was to explore the paramedic's role in caring for people who use illicit drugs. Methods: A scoping review of English language literature published since 2002 was conducted using CINAHL, MEDLINE, EMBASE, and Google Scholar. We used a previously published paramedic search term filter for sensitivity combined with search terms related to drug-related substance use and addiction. Studies were selected based on relevance to the research question. Results: A total of 104 peer-reviewed and 14 grey literature articles were selected for inclusion. The main finding of this scoping review is the notable lack of evidence base surrounding the contemporary paramedic role in the care provision of people who use drugs (PWUD). The results highlight high rates of mortality following a paramedic-attended drug poisoning event, presenting a unique opportunity for paramedics to intervene in meaningful ways that extend past traditional drug poisoning response. Conclusions: The interface between the community of PWUD and the paramedic may be a highly influential encounter during a patient's journey through the healthcare system. The evolving role of the paramedic in this encounter requires focused study and should be viewed as a research priority in response to the ongoing drug poisoning crisis.

We try to solve three decades-old physics challenges. List all elementary particles. Describe dark matter. Describe mechanisms that govern the rate of expansion of the universe. We propose new modeling. The modeling uses extensions to harmonic oscillator mathematics. The modeling points to all known elementary particles. The modeling suggests new particles. Based on those results, we do the following. We explain observed ratios of dark matter amounts to ordinary matter amounts. We suggest details about galaxy formation. We suggest details about inflation. We suggest aspects regarding changes in the rate of expansion of the universe. We interrelate the masses of some elementary particles. We interrelate the strengths of electromagnetism and gravity. Our work seems to offer new insight regarding applications of harmonic oscillator mathematics. Our work seems to offer new insight regarding three branches of physics. The branches are elementary particles, astrophysics, and cosmology.

We develop and apply new physics theory. The theory suggests specific unfound elementary particles. The theory suggests specific constituents of dark matter. We apply those results. We explain ratios of dark matter amounts to ordinary matter amounts. We suggest details about galaxy formation. We suggest details about inflation. We suggest aspects regarding changes in the rate of expansion of the universe. The theory points to relationships between masses of elementary particles. We show a relationship between the strength of electromagnetism and the strength of gravity. The mathematics basis for matching known and suggesting new elementary particles extends mathematics for harmonic oscillators.

Matrix vesicles (MVs) are nano-sized extracellular vesicles that are anchored in the extracellular matrix (ECM). In addition to playing a role in biomineralization, osteoblast-derived MVs were recently suggested to have regulatory duties. The aims of this study were to: establish the characteristics of osteoblast-derived MVs in the context of extracellular vesicles like exosomes, assess their role in modulating osteoblast differentiation, and examine their mechanism of uptake. MVs were isolated from the ECM of MG-63 human osteoblast-like cell cultures and characterized via enzyme activity, transmission electron microscopy, nanoparticle tracking analysis, western blot, and small RNA sequencing. Osteoblasts were treated with MVs from two different culture conditions (growth media [GM]; osteogenic media [OM]) to evaluate their effects on differentiation and production of inflammatory markers and on macrophage polarization. MV endocytosis was assessed using a lipophilic, fluorescent dye and confocal microscopy with the role of caveolae determined using methyl-β-cyclodextrin. MVs exhibited a four-fold enrichment in alkaline phosphatase specific activity compared to plasma membranes, were 50-150nm in diameter, possessed exosomal markers CD63, CD81, and CD9 and endosomal markers ALIX, TSG101, and HSP70, and were selectively enriched in microRNA linked to an anti-osteogenic effect and to M2 macrophage polarization. Treatment with GM or OM MVs decreased osteoblast differentiation. Osteoblasts endocytosed MVs by a mechanism that involves caveolae. These results support the hypothesis that osteoblasts produce MVs that participate in the regulation of osteogenesis.

Duke University was founded in 1930 primarily due to funds generated from James B. Duke’s tobacco business. Duke achieved great financial wealth primarily due to the early application of machine rolled cigarettes, as opposed to hand rolled. This early adoption of technology allowed Duke Tobacco to out-produce other companies still selling hand rolled cigarettes. By making smoking more inexpensive and easier than pipe smoking, the cigarette formed the foundation for nicotine addiction in the 1900s, generating huge profits for the tobacco industry. At the time Duke University was founded, little was known about the connection between nicotine, cigarettes, and respiratory diseases such as emphysema and lung cancer. Through James Duke’s philanthropy, the devastating harm from cigarettes has been mitigated in part through the founding of one of the world’s most prominent medical centers and research universities.

Some physicists surmise that gravity lies outside of quantum mechanics. Thus theories like the standard semiclassical theory of quantum to gravity coupling (that of Rosenfeld and Møller) are possible real models of interaction, rather than a mere approximation of a theory of quantum gravity. Unfortunately, semiclassical gravity creates inconsistencies such as superluminal communication. Alternatives by authors such as Diósi, Martin, Penrose, and Wang often use the term 'stochastic' to set themselves apart from the standard semiclassical theory. These theories couple to fluctuations caused by for instance continuous spontaneous localization, hence the term 'stochastic'. This paper looks at stochastic gravity in the framework of a class of emergent or ontological quantum theories, such as those by Bohm, Cetto, and de Broglie. It is found that much or all of the trouble in connecting gravity with a microscopic system falls away, as Einstein's general relativity is free to react directly with the microscopic beables. The resulting continuous gravitational wave radiation by atomic and nuclear systems does not, in contrast to Einstein's speculation, cause catastrophic problems. The small amount of energy exchanged by gravitational waves may have measurable experimental consequences. A very recent experiment by Vinante et al. performed on a small cantilever at mK temperatures shows a surprising non-thermal noise component, the magnitude of which is consistent with the stochastic gravity coupling explored here.

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

Precipitation processes are technologies commonly used in hydrometallurgical plants to recover metals or to treat wastewaters. Moreover, solid-liquid separation technologies, such as thickening or filtering, are relevant unit operations, included in the precipitation technologies. These methods are strongly dependent on the characteristics of the solid precipitates formed during the specific precipitation reaction. One of these characteristics is the particle size distribution (PSD) of the solid precipitates which are fed into a solid-liquid separation process. Therefore, PSD determination is a typical practice for the characterization of the slurries generated in a precipitation plant. Furthermore, the precipitates generated in these processes have a colloidal or aggregation behavior, depending on the operational conditions. Nevertheless, the conventional methods used to estimate PSD (e.g., laser diffraction and/or ciclosizer) have not been designed to measure particles that tend to aggregate or disaggregate, since they include external forces (e.g., centrifugal, agitation, pumping and sonication). These forces affect the true size of the aggregates formed in a unit operation, thereby losing representativity in terms of aggregates particle size. This study presents an alternative method of measuring the size distribution of particles with aggregation behavior, particularly, by using non-invasive microscopy and image processing and analysis. The samples used have been obtained from an experimental precipitation process by applying sulfidization to treat the cyanide-copper complexes contained in a cyanidation solution. This method has been validated with statistical tools and compared with a conventional analysis based on laser diffraction. Our results show significant differences between the methods analyzed, demonstrating that image processing and analysis by microscopy is an excellent and non-invasive alternative to obtaining size distribution of aggregates in precipitation processes.

Physics theory has yet to settle on specific descriptions for new elementary particles, for dark matter, and for dark energy forces. Our work extrapolates from the known elementary particles. The work suggests well-specified candidate descriptions for new elementary particles, dark matter, and dark energy forces. This part of the work does not depend on theories of motion. This work embraces symmetries that correlate with motion-centric conservation laws. The candidate descriptions seem to explain data that prior physics theory seems not to explain. Some of that data pertains to elementary particles. Our theory suggests relationships between masses of elementary particles. Our theory suggests a relationship between the strengths of electromagnetism and gravity. Some of that data pertains to astrophysics. Our theory seems to explain ratios of dark matter effects to ordinary matter effects. Our theory seems to explain aspects of galaxy formation. Some of that data pertains to cosmology. Our theory suggests bases for inflation and for changes in the rate of expansion of the universe. Generally, our work proposes extensions to theory in three fields. The fields are elementary particles, astrophysics, and cosmology. Our work suggests new elementary particles and seems to explain otherwise unexplained data.

DNA Topoisomerase IIa (Top2A) is a nuclear enzyme that is a cancer drug target, and there is interest in identifying novel sites on the enzyme to inhibit cancer cells more selectively and to reduce off-target toxicity. The C-terminal domain (CTD) is one potential target, but it is an intrinsically disordered domain, which prevents structural analysis. Therefore, we set out to analyze the sequence of Top2A from 105 species using bioinformatic analysis including the PSICalc algorithm, entropy analysis, and other approaches. Our results demonstrate that large (10th-order) interdependent clusters are found including non-proximal positions across the major domains of Top2A. Further, CTD-specific clusters of 3rd, 4th, and 5th-order were identified that included positions that had been previously analyzed via mutation and biochemical assays. Some of these clusters coincided with positions that when mutated either increased or decreased relaxation activity. Finally, sites of low entropy (i.e., high information content) were identified and mapped as key positions in the CTD. Included in the low entropy sites are phosphorylation sites and charged positions. Together, these results help to build a clearer picture of the critical positions in the CTD and provide potential sites/regions for further analysis.

Polycystic ovary syndrome (PCOS) is a complex, but relatively common endocrine disorder associated with chronic anovulation, hyperandrogenism, and micro-polycystic ovaries [1]. In addition to reduced fertility, people with PCOS have a higher risk of obesity, insulin resistance, and metabolic disease [1], all comorbidities that are associated with mitochondrial dysfunction. This review summarizes human and animal data that report mitochondrial dysfunction and metabolic dysregulation in PCOS to better understand how mitochondria impact reproductive organ pathophysiology. This in-depth review considers all the elements regulating mitochondrial quantity and quality, from mitochondrial biogenesis under transcriptional regulation of both the nuclear and the mitochondrial genome, to the ultrastructural and functional complexes that regulate cellular metabolism and reactive oxygen species production, to dynamics which regulate subcellular interactions that are key to mitochondrial quality control. When any of these mitochondrial functions are disrupted the energetic equilibrium within the cell changes, cell processes can fail, and cell death can occur. If this process is ongoing, it affects tissue and organ function to cause disease. The objective of this review is to consolidate and classify a broad number of PCOS studies to understand how various mitochondrial processes impact reproductive organs including the ovary (oocyte and granulosa cell), uterus, placenta, and circulation to cause reproductive pathophysiology. A secondary objective is to uncover the potential role of mitochondria in transgenerational transmission of PCOS and metabolic disorders.

Speech signals are degraded in real-life environments, product of background noise or other factors. The processing of such signals for voice recognition and voice analysis systems presents important challenges. One of the conditions that make adverse quality difficult to handle in those systems is reverberation, produced by sound wave reflections that travel from the source to the microphone in multiple directions.To enhance signals in such adverse conditions, several deep learning-based methods have been proposed and proven to be effective. Recently, recurrent neural networks, especially those with long and short-term memory (LSTM), have presented surprising results in tasks related to time-dependent processing of signals, such as speech. One of the most challenging aspects of LSTM networks is the high computational cost of the training procedure, which has limited extended experimentation in several cases. In this work, we present a proposal to evaluate the hybrid models of neural networks to learn different reverberation conditions without any previous information. The results show that some combination of LSTM and perceptron layers produce good results in comparison to those from pure LSTM networks, given a fixed number of layers. The evaluation has been made based on quality measurements of the signal's spectrum, training time of the networks and statistical validation of results. Results help to affirm the fact that hybrid networks represent an important solution for speech signal enhancement, with advantages in efficiency, but without a significan drop in quality.

This study investigated the associations of imageability with fear reactivity. Imageability ratings of four word classes: positive and negative (i) emotional and (ii) propriosensitive, neutral and negative (iii) theoretical and (iv) neutral concrete filler, and fear reactivity scores – degree of fearfulness towards different situations (TF score) and total number of extreme fears and phobias (EF score), were obtained from 171 participants. Correlations between imageability, TF and EF scores were tested to analyze how word categories and their valence were associated with fear reactivity. Imageability ratings were submitted to recursive partitioning. Participants with high TF and EF scores had higher imageability for negative emotional and negative theoretical words. The correlations between imageability of negative emotional words and negative theoretical words for EF score were significant. Males showed stronger correlations for imageability of negative emotional words for EF and TF scores. High imageability for positive emotional words was associated with lower fear reactivity in females. These findings were discussed with regard to negative attentional bias theory of anxiety, influence on emotional systems, and gender-specific coping styles. This study provides insight into cognitive functions involved in mental imagery, semantic competence for mental imagery in relation to fear reactivity, and a potential psycholinguistic instrument assessing fear tendency.

Quantum chaos is presented as a paradigm of information processing by dynamical systems at the bottom of the range of phase-space scales. Starting with a brief review of classical chaos as entropy flow from micro- to macro-scales, I argue that quantum chaos came as an indispensable rectification, removing inconsistencies related to entropy in classical chaos: Bottom-up information currents require an inexhaustible entropy production and a diverging information density in phase space, reminiscent of Gibbs' paradox in Statistical Mechanics. It is shown how a mere discretization of the state space of classical models already entails phenomena similar to hallmarks of quantum chaos, and how the unitary time evolution in a closed system directly implies the “quantum death” of classical chaos. As complementary evidence, I discuss quantum chaos under continuous measurement. Here, the two-way exchange of information with a macroscopic apparatus opens an inexhaustible source of entropy and lifts the limitations implied by unitary quantum dynamics in closed systems. The infiltration of fresh entropy restores permanent chaotic dynamics in observed quantum systems. Could other instances of stochasticity in quantum mechanics be interpreted in a similar guise? Where observed quantum systems generate randomness, that is, produce entropy without discernible source, could it have infiltrated from the macroscopic meter? This speculation is worked out for the case of spin measurement.

In several mammalian species including humans, complex stimulation patterns such as cognitive challenge and physical exercise lead to improvements in organ function, organism health and performance, as well as possibly longer lifespans. The hypothesis is presented here that activity-dependent transcriptional programs, induced by these environmental stimuli, temporarily and lightly de-differentiate somatic cells such as neurons and muscle cells into a state that resembles functionally younger cells to allow cellular remodeling and adaptation of the organism to environmental change. This cellular adaptation program targets several process classes that are heavily implicated in aging, such as mitochondrial metabolism, cell-cell communication, intracellular signaling and epigenetic information processing and leads to functional improvements in these areas. I reverse engineer these activity-dependent gene programs, identify critical molecular nexus points such as CREB, MEF2 and cFos and speculate as to how one might leverage them to prevent and attenuate human aging-related decline of body function, enhance human performance and restore more youthful levels of function and morphology. The findings presented here can serve as a basis for the study and development of effective longevity efforts as the underlying gene programs could be used as markers for treatment success and as targets for therapy development.

The topic of this paper is the airborne evaluation of ICESat-2 Advanced Topographic Laser Altimeter System (ATLAS) measurement capabilities and surface-height-determination over crevassed glacial terrain, with a focus on the geodetical accuracy of geophysical data collected from a helicopter. To obtain surface heights over crevassed and otherwise complex ice surface, ICESat-2 data are analyzed using the density-dimension algorithm for ice surfaces (DDA-ice), which yields surface heights at the nominal 0.7~m along-track spacing of ATLAS data. As the result of an ongoing surge, Negribreen, Svalbard, provided an ideal situation for the validation objectives in 2018 and 2019, because many different crevasse types and morphologically complex ice surfaces existed in close proximity. Airborne geophysical data, including laser altimeter data (profilometer data at 905~nm frequency), differential Global Positioning System (GPS), Inertial Measurement Unit (IMU) data, on-board-time-lapse imagery and photographs, were collected during two campaigns in summers of 2018 and 2019. Airborne experiment setup, geodetical correction and data processing steps are described here. To date, there is relatively little knowledge of the geodetical accuracy that can be obtained from kinematic data collection from a helicopter. Our study finds that (1)~Kinematic GPS data collection with correction in post-processing yields higher accuracies than Real-Time-Kinematic (RTK) data collection. (2)~Processing of only the rover data using the Natural Resources Canada Spatial Reference System Precise Point Positioning (CSRS-PPP) software is sufficiently accurate for the sub-satellite validation purpose. (3)~Distances between ICESat-2 ground tracks and airborne ground tracks were generally better than 25~m, while distance between predicted and actual ICESat-2 ground track was on the order of 9~m, which allows direct comparison of ice-surface heights and spatial statistical characteristics of crevasses from the satellite and airborne measurements. (4)~The Lasertech Universal Laser System (ULS), operated at up to 300~m above ground level, yields full return frequency (400~Hz) and 0.06-0.08~m on-ice along-track spacing of height measurements. (5)~Cross-over differences of airborne laser altimeter data are 0.1918 $\pm$ 2.385~m along straight paths over generally crevassed terrain, which implies a precision of approximately 2.4~m for ICESat-2 validation experiments. (6)~In summary, the comparatively light-weight experiment setup of a suite of small survey equipment mounted on a Eurocopter (Helicopter AS-350) and kinematic GPS data analyzed in post-processing using CSRS-PPP leads to high accuracy repeats of the ICESat-2 tracks. The technical results (1)-(6) indicate that direct comparison of ice-surface heights and crevasse depths from the ICESat-2 and airborne laser altimeter data is warranted. The final result of the validation is that ICESat-2 ATLAS data, analyzed with the DDA-ice, facilitate surface-height determination over crevassed terrain, in good agreement with airborne data, including spatial characteristics, such as surface roughness, crevasse spacing and depth, which are key informants on the deformation and dynamics of a glacier during surge.

Dipeptidyl peptidase 9 (DPP9) is a multifunctional intracellular protease with roles in tumour growth, inflammation and mitochondrial function. We developed a hepatocyte-specific DPP9 knockout mouse (DPP9-KO) to explore DPP9 in a mouse model of hepatocellular carcinoma (HCC). DPP9-KO mice were generated by crossing Albumin-Cre mice (Wt/Wt Cre+/+) with DPP9 floxed mice (Fl/Fl Cre-/-). Mice were treated with Diethylnitrosamine and Thioacetamide then an atherogenic High Fat Diet until 28 weeks of age. DPP9-KO mice had reduced liver and subcuta-neous adipose tissue mass and lower fasting plasma glucose, fewer small macroscopic liver nod-ules compared to DPP9-WT mice. However, there were no differences in the total number of mac-roscopic liver nodules, tumour burden, inflammation score and steatosis score. Consistent with the known ability of DPP9 to suppress NLRP1 activation, activated caspase-1 protein was ele-vated in DPP9-KO mouse liver. Additionally, Nfkbib, Cxcl10 and Ccl5 mRNA and protein levels of autophagy marker beclin1 and tumour suppressor p53 were increased. In conclusion, DPP9 de-pletion in hepatocytes may reduce liver cancer initiation, via mechanisms that may include in-creased autophagy and innate tumour suppression in this experimental model. Finally, the data supports DPP9 having a role in glucose regulation by the liver.

Heat-stressed lactating dairy cattle exhibit unique metabolic symptoms; many of which are undoubtedly involved in heat-induced subfertility. Because of its known systemic effects, we hypothesized that γ-aminobutyric acid (GABA) participates in the regulation of insulin and progesterone during heat stress. Multiparous lactating Holstein cows (n=6) were studied during four experimental periods: 1) thermoneutral (TN; d 1-5), 2) TN + hyperinsulinemic-hypoglycemic clamp (d 6-10), 3) heat stress (HS; d 16-20), and 4) HS + euglycemic clamp (d 21-25). Blood samples were collected once daily via coccygeal venipuncture into heparinized evacuated tubes. Analysis of GABA concentrations from all four treatment periods yielded no differences. In direct comparison to TN concentrations, plasma GABA tended to be decreased during HS (16.57±2.64 vs 13.87±2.28 ng/ml, respectively, P = 0.06). Both milk production and plasma insulin were moderately correlated with plasma GABA (r=0.35, P<0.01; r = -0.32, P<0.01). Plasma progesterone was correlated with plasma GABA concentrations during TN but not HS. These results are the first to indicate that peripheral GABA could be involved in regulating aspects of production and reproduction during heat stress. More research is needed to determine its precise role(s).

Japanese encephalitis virus is a mosquito-borne member of the Flaviviridae family. JEV is the leading cause of viral encephalitis in Asia and is characterized by encephalitis, high lethality and neurological sequelae in survivors. The virus also causes severe disease in swine, which are an amplifying host in the transmission cycle, and in horses. US agricultural authorities have recently recognized the threat to the swine industry and initiated preparedness activities. Other mosquito-borne viruses exotic to the Western Hemisphere have been introduced and established in in recent years, including West Nile, Zika, and chikungunya viruses, and JEV has recently invaded continental Australia for the first time. These events amply illustrate the potential threat of JEV to US health security. Susceptible indigenous mosquito vectors, birds, feral and domestic pigs, and possibly bats, constitute the receptive ecological ingredients for spread of JEV in the US. Fortunately, unlike the other virus invaders mentioned above, an inactivated whole virus JE vaccine (IXIARO®) has been approved by the US Food & Drug Administration for human use in advance of a public health emergency, but there is no veterinary vaccine. This paper describes the risks and potential consequences of introduction of JEV in the US, the need to integrate planning for such an event in public health policy and the requirement for additional countermeasures, including antiviral drugs and an improved single dose vaccine that elicits durable immunity in both humans and livestock.

As the embedded device and internet of things (IoTs) concept prevalent in today's world, there is an increasing demand for the security and performance requirements on deploying these devices to private and public sectors. The crucial part of it is to protect privacy, confidentiality and integrity, meanwhile, maintain an adequate level of performance during transmission, storage and access of critical information. While the conventional cryptography methods, such as the Advanced Encryption Standard (AES), SHA$-$2 hashing method and RSA and Diffie Hellman for message authentication and identification, work well on systems which have reasonable processing power and memory capabilities. These do not scale well into a world with embedded systems and sensor networks, in conjunction with their nature of smaller size and lower cost. Thus, in the context of resource constrained device, lightweight cryptography methods are proposed to overcome many of the problems of conventional cryptography possessed. This includes constraints related to physical size, processing requirement, memory limitation, energy drain and production cost. This paper provides a survey of the architectures that are defined as replacements for conventional ciphers within an IoTs space and discuss some trends in the design of future lightweight algorithms. The performance metrics are carefully chosen to reflect and assess the suitability for embedded devices. The aim of this research is to identify the various performance metrics applied on different types of symmetric block ciphers especially lightweight ciphers and compare the results on versatile platforms with stream ciphers and public key methods. The comparative analysis on efficient LW cipher will be tested against other similar block ciphers on both MacBook Pro with Intel core and resource constrained device Raspberry Pi with ARM processor.

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

Physics lacks a confirmed description of dark matter, has yet to develop an adequate understanding of dark energy, and includes unverified conjectures regarding new elementary particles. This essay features modeling that addresses those problems and explains otherwise unexplained data. Our modeling starts from five bases – multipole expansions for the electromagnetic and gravitational fields associated with an object, the list of known elementary particles, some aspects of mathematics for isotropic harmonic oscillators, concordance cosmology, and a conjecture that the universe includes six isomers of most elementary particles. The multipole expansions – which have use in conjunction with Newtonian kinematics modeling, special relativity, and general relativity – lead to a catalog of kinematics properties such as charge, magnetic moment, mass, and repulsive gravitational pressure. The multipole expansions also point to all known elementary particles, some properties of those particles, and properties of some would-be elementary bosons and elementary fermions. The harmonic-oscillator mathematics points to Gauge symmetries regarding some elementary bosons. The would-be elementary fermions lack charge and would measure as dark matter. The conjecture regarding six isomers of most elementary particles rounds out and dominates our specification for dark matter. Five of the isomers form the basis for most dark matter. Our modeling explains ranges of observed ratios of dark matter effects to ordinary matter effects – for the universe, galaxy clusters, two sets of galaxies observed at high redshifts, three sets of galaxies observed at modest redshifts, and one type of depletion of cosmic microwave background radiation. Our description of repulsive gravitational pressure points toward resolution for tensions – between data and modeling – regarding the recent rate of expansion of the universe, resolution for possible tensions regarding large-scale clumping, and resolution for possible tensions regarding interactions between neighboring galaxies. Our work regarding gravity, dark matter, and elementary particles suggests characterizations for eras that might precede the inflationary epoch, a mechanism that might have produced baryon asymmetry, mechanisms that govern the rate of expansion of the universe, and insight about galaxy formation and evolution.

The gauge field equation for fluid mechanics established in Part 1 is developed into a first-order scattering theory in the simplified case of a two-dimensional incompressible flow over a flat plate. This is used to present a model for the origin of Tollmien-Schlichting (TS) waves based on scattering between fluid particles. As a result, analytical formulae for the maximum amplification factor and the transition point from laminar to turbulent flow in the boundary layer are obtained. The mathematical transformations from the stationary field equations in Part 1 to a scattering theory with time evolution along the flow axis using Wick rotation are elaborated in detail.

Brittle fracture of iron and steel above twinning temperatures are caused by cementite grain boundary wall cracks. These were revealed by an Atomic Force Microscope. At temperatures below the Ductile-Brittle Transition, cracks must propagate longitudinally within the cementite walls until the stress is sufficient high for the cracks to propagate across ferrite grains. Calculations using these concepts correctly predict the stress and temperature at the Ductile-Brittle Transition required for fracture to occur. At temperatures above the Ductile-Brittle Transition for hypoeutectoid ferritic steels, dislocations must fracture these walls transversely for plastic deformation to continue. This is responsible for the upper yield point at the elastic limit in these steels followed by a large drop in stress to the lower yield point. Here the walls surround completely all of the grains. Where the walls are segmented such as in iron, dislocations can pass around the walls resulting in a gradual change from elastic to plastic deformation. The Cottrell atmosphere theory of yielding is not supported experimentally. It was the best available until later experiments including those using the Atomic Force Microscope were obtained. Methods are presented here giving yield strength versus temperature and also the parameters for the Hall-Petch and Griffith equations.

The rapid expansion of social media and instant messaging applications, such as WhatsApp, has transformed how individuals and organizations communicate and engage. This think piece explores the potential of integrating WhatsApp as a customer relationship management (w-CRM) tool within the education sector to foster and sustain long-term relationships among students, teaching staff, and non-teaching staff. By leveraging real-time features and the widespread use of WhatsApp, educational institutions can create a more interactive and dynamic learning environment, benefiting all stakeholders involved. The literature highlights the importance of establishing clear frameworks for mutual engagement and interaction and the potential of w-CRM to improve communication between students' families and educational institutions. There are potential risks associated with the pervasive use of WhatsApp, and call for future research to explore strategies for mitigating these risks while maximizing the benefits of w-CRM in the education sector. Longitudinal studies are recommended to evaluate the long-term impact of w-CRM on stakeholder relationships, student outcomes, and overall institutional performance.

QTc interval measurement is a widely used screening tool to assess the risk of cardiac diseases, arrhythmias, and is a useful biomarker for pharmacovigilance. However, interpretation of QTc is difficult in neonates due to hemodynamic maturational changes and uncertainties on reference values. To describe trends in QTc values throughout infancy (1 year of life), and to explore the impact of (non)-maturational changes and medicines exposure, a structured systematic review (PROSPERO CRD42022302296) was performed. In term neonates, a decrease was observed over the first week of life, whereafter values increased until two months of age, followed by a progressive decrease until six months. A similar pattern, with longer QTc values was observed in preterms. QTc is influenced by cord clamping, hemodynamic changes, therapeutic hypothermia, illnesses and sleep, not by sex. Cisapride, domperidone and doxapram result in QTc prolongation in neo-nates. Further research in this age category is needed to improve primary screening practices, earlier detection of risk factors and precision pharmacovigilance.

Drought events are evident effects of climate change around the globe and yield several socio-economic impacts. Such effects are even more relevant for South America (SA) since different activities essential for the continent, like agriculture and energy generation, depend highly on water resources. Thus, this study aimed to evaluate future changes in precipitation and hydro-logical droughts occurrence in SA through climate projections from eight global climate models (GCMs) of CMIP6. To this end, statistical downscaling was applied to the projections with the Quantile Delta Mapping technique, and the method proved to be efficient in reducing systematic biases and preserving GCMs’ trends. For the following decades, the results show considerable and statistically significant reductions in precipitation over most of SA, especially during the austral spring, with the most intense signal under the SSP5-8.5 forcing scenario. Furthermore, GCMs showed mixed signals about projections of the frequency and intensity of drought events. Still, they indicated agreement regarding the increase in duration and severity of events over all of SA and a substantial proportion of moderate and severe events over most of Brazil during the 21st century. These results can be helpful for better management of water resources by deci-sion-makers and energy planners.

The problem of fluid dynamics can be greatly simplified if, for every point in space, the strain-rate tensor is diagonalized. This tensor is introduced into the Navier-Stokes equations via material law and divergence of the stress tensor. This article shows that local SO(3)xU(1) gauge fields can be used to locally diagonalize the diffusion components of the strain-rate tensor. The gauge fields resulting from the connection can be interpreted as convection components of the flow, they show properties of quasiparticles and can be interpreted as elementary vortices. Thus, the proposed approach not only offers new insights for the solution and situative simplification of the Navier-Stokes equations, it also uncovers hidden symmetries within the flow convection, allowing - depending on boundary conditions - further interpretation.

We present a summary of our protocol for employment of small-molecule circadian rhythm modulators. The abilities of compounds to affect oscillations have received significant attention. We outline assessments of circadian changes using indirubin-3’-oxime (IO), 5-iodo-indirubin-3’-oxime (5I-IO), and 5-sulfonic acid-indirubin-3’-oxime (5SA-IO), analyzing effects on Bmal1 and Per2 oscillations and oncogenic features.

There is a long-standing association between exceptional cognitive abilities, of various sorts, and neuropsychiatric illness, but it has historically largely been investigated in an exploratory and non-systematic way. One group in which this association has been investigated with more rigor is in subjects who have been identified as twice exceptional; an educational term describing subjects who are both gifted and diagnosed with a neuropsychiatric disability. This term covers multiple conditions, but is of specific interest in particular in the study of autism spectrum disorder. Recent findings have led to the development of a hypothesis that a certain degree of the neurobiology associated with autism might even be advantageous for individuals and could lead to high giftedness, while becoming disadvantageous, once a certain threshold is surpassed. In this model, the same neurobiological mechanisms confer an increasing advantage up to a certain threshold, but become pathological past that point. Twice-exceptional individuals would be exactly at the inflection point, being highly gifted, but also symptomatic at the same time. Here, we review how existing neuroimaging literature on autism spectrum disorder can inform research on twice exceptionality specifically. We propose to study key neural networks with a robust implication in ASD to identify the neurobiology underlying twice-exceptionality. A better understanding of the neural mechanisms of twice exceptionality should help to better understand resilience and vulnerability to neurodevelopmental disorders and tofurther support affected individuals.

Background: Gluten and casein-containing foods could aggravate the symptoms of children and adolescents with autism spectrum disorder (ASD), and subsequently impact their quality of life. However, there is a mixed opinion among researchers concerning the impact of alternative diet on reducing ASD symptoms. Objective: This scoping review aimed at examining the impact of the ‘’gluten-free, casein-free’’ (GFCF) diet on health outcomes and the quality of life among autistic children and adolescents. Methods: A scoping review of the literature was performed following the Joanna Briggs Institute (JBI) guidelines. Four databases including EbscoHost, Medline, CINAHL and ProQuest were used to obtain subject-specific studies relevant to the research question and published between July 2013 and March 2024. A comprehensive search using keywords such as “autism spectrum disorder”, “gluten-free diet”, and “casein-free diet” was conducted to obtain articles related to the research focus area. Only full-text, peer-reviewed, written in English articles were selected. Data extraction and data analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses- extension to Scoping Review (PRISMA-ScR) protocol. Results: From the initial 586 studies a total of 27 articles were included in the final analysis of the review. The thematic analysis included ‘GFCF diet and improvement of the core autistic symptoms’’, “the gut-brain link’’, ‘’dietary interventions and autism’’, ‘’possible side effects due to the GCFC diet’’, and ‘’ inconclusive studies and mixed opinions’’. Majority of the studies showed positive effect of the GFCF diet on a variety of autistic symptoms including positive changes in cognitive skills, behaviour, and gastrointestinal symptoms while some showed conflicting evidence. Conclusion: The currently available evidence on the impact of ‘GFCF’’ diet on the quality of life of autistic children and adolescents may warrant potentially effective interventions for alleviating symptoms of autism spectrum disorders. However, this scoping review highlighted the need for more research to provide more reliable evidence on the health outcomes and quality of life of ASD sufferers to guide practice.

To evaluate the impact of a new Substance Use Disorder (SUD) education program on medical students' representations, we selected the Substance Abuse Attitude Survey (SAAS) questionnaire, which we adapted to our curriculum and cultural context. To validate this adapted version, we conducted an exploratory factor analysis following the administration of our 29-items bSAAS questionnaire to 657 medical students in Belgium (response rate: 71,1%). 23 items correlated to 3 factors namely "Stereotypes and moralism", "Treatment optimism" and "Specialised treatment" were retained (70% of total variance explained, Cronbach's alpha= 0.80) and constituted the new questionnaire called beSAAS. The factor "Specialised treatment", stood out from previous studies which could be explained by our target population and the impact of the formal, informal, and hidden curriculum in medical education. This study highlighted certain factors influencing stereotypical representations such as age, gender, origin, and personal or professional experience with substance use. Our study allowed us to retain the beSAAS as a good questionnaire to evaluate SUD stigma and highlighted interesting findings to improve SUD training in medicine. Further studies are needed to complete its validity and reliability.

Currently 7.6% of the U.S. young adults aged 18-24 years old currently use e-cigarettes. This study piloted three methods of ENDS cessation by measuring cessation rates, motivational techniques that contributed to cessation success, and participants’ changes after decreasing vape use. Participants were randomized into three study arms [nicotine replacement therapy (NRT) + behavioral support, vape-taper + behavioral support, self-guided] in a 1:1:1 ratio. All participants were invited to attend 9 in-person or phone appointments over the 6 month study period. At 12 weeks, 3 of 7 (42.9%) participants in the NRT + behavioral support arm, 6 of 8 (75%) vape-taper + behavioral support arm, and 7 of 9 (77.8%) self-guided arm self-reported being vape- and nicotine-free. At 6 months, 3 of 7 (42.9%) participants in the NRT + behavioral support arm, 6 of 8 (75%) vape-taper + behavioral support arm, 4 of 9 (44.4%) self-guided arm self-reported being vape- and nicotine-free. A challenge to quitting and remain quit is social pressures, but participants identified self-control and establishing new habits to be the best methods to overcome the desire to vape. Participants who received behavioral support and a vape-taper plan from pharmacists were more likely to be vape- and nicotine-free at 6 months.

The role of vitamin D in the prevention and treatment of non-skeletal health issues has received significant media and research attention in recent years. Costs associated with clinical management of low vitamin D (LVD) have increased exponentially. However, no clear evidence supports vitamin D screening to improve health outcomes. Authoritative bodies and professional societies recommend against population-wide vitamin D screening in community-dwelling adults who are asymptomatic or at low risk of LVD. In order to assess patterns of physician management of LVD in this conflicting environment, we conducted a scoping review of three electronic databases and gray literature. Thirty-eight records met inclusion criteria and were summarized in an evidence table. Results from seven countries showed a consistent increase in vitamin D lab tests and related costs. Many vitamin D testing patterns reflected screening rather than targeted testing for individuals at high risk of vitamin D deficiency or insufficiency. Interventions aimed at managing inappropriate clinical practices related to LVD were effective in the short term. Variability and controversy were pervasive in many aspects of vitamin D management, shining light on physician practices in the face of uncertainty. Future research is needed is needed to inform better clinical guidelines and to assess implementation practices that encourage evidence-based management of LVD in adult populations.

Ovarian cancer (OC) is the most lethal gynecologic malignancy. Cannabis sativa is being used to treat different medical conditions. We sought to examine the effectiveness of combinations of cannabis compounds against OC. Cytotoxic activity was determined by XTT assay on HTB75 and HTB161 cell lines. Apoptosis and cell cycle were determined by fluorescence-activated cell sorting (FACS). Gene expression was determined by quantitative PCR. The two most active fractions, F5 and F7, from a high Δ9–tetrahydrocannabinol (THC) cannabis strain extract and their standard mix (SM) showed cytotoxic activity against OC cells. The most effective phytocannabinoid combination was THC+cannabichromene (CBC)+cannabigerol (CBG). F5, F7 and SM affected cell cycle, led to cell apoptosis and to a marked reduction in cell migration. Moreover, these fractions act in synergy with niraparib, and were ~50 fold more cytotoxic to OC cells than to normal keratenocytes. Niraparib+F7 treatment was effective on OC patient's cells. F7 and the niraparin+fraction (F5 and F7) treatments reduced Mitogen-Activated Protein Kinase 4 (MAPK4) gene expression; this reduction may act in synergy with the niraparib inhibition of Poly (ADP-ribose) polymerase 1 (PARP1) activity. Combinations of cannabis compounds and niraparib should be examined for efficacy in pre-clinical studies and clinical trials.

Chinese-speaking parents are argued to use less cognitive mental-state-talk than their English-speaking counterparts due to their goals in socializing their children to follow an interdependence script. To extend this research, we investigated bilingual Mandarin-English Singaporean mothers who associate different functions for each language as prescribed by their government: English for school and Mandarin for in-group contexts. English and Mandarin maternal mental-state-talk from bilingual Mandarin-English mothers with their toddlers was examined. Mothers produced more cognitive terms in English than in Mandarin and more desire terms in Mandarin than in English. We show that mental-state-talk differs between bilingual parents’ languages, suggesting that mothers adjust their mental-state-talk to reflect each language’s function.

In this article, we describe a simple procedure for evaluating the sterility of nutrient media using a shear-horizontal surface acoustic wave (SH-SAW) biosensor. We used the SH-SAW biosensor platform to monitor the time-dependent phase responses of the material for the media that binds to a monolayer of 3-mercaptopropanyl-N-hydroxy succinimide on the biosensor surface. Increases in the phase shift less than 50% of the starting phase shift recorded 180 minutes after the sterilization indicate a successful sterility test of the media. Our devices were then applied to sterility testing using a viable Escherichia coli (E. coli) K-12 solution to confirm our hypothesis. Filtered LB Broth was the negative control, and a 24-hour culture of E. coli was the positive control. Before testing, the cell solution was pelleted, the media decanted, and then replaced with a 1x phosphate-buffered saline solution (1x PBS). Since we know that the N-hydroxysuccinimide residues will bind to amine groups, only in cases where microbial species are present will the surface binding increase greater than 50%. We confirmed our hypothesis using SH-SAW biosensors and overnight E. coli cultures. The sensitivity for our 250 MHz quartz SH-SAW sensors was calculated based on the response from the E. coli K-12 solution over the linear dynamic range, which appears to be 2x10^4 – 2x10^7 CFU per ml and has a sensitivity of S = 1.655x10^5 o m2 Kg-1. The limit of detection (LOD) for these sensors was calculated to be approximately 2x10^-9 grams (g), which is estimated to be approximately 2,000 Escherichia coli (E. coli) K-12 cells. However, the sensitivity and insertion loss remained approximately unchanged before and after coating the sensor with 3,3'-Dithiobis(succinimidyl) Propionate (DSP).

This paper introduces a novel graph polynomial approach for differentiating tree structures in dependency grammar. Utilizing this polynomial representation, we develop a metric to assess the similarity in syntax. This approach offers a detailed and inclusive analysis of the dependency structures and relationships in sentence construction. We employ this polynomial method to examine sentence structures across various languages in the Parallel Universal Dependencies treebanks. Our analysis includes comparing the syntax of original sentences and their translated counterparts in diverse languages, alongside a comprehensive study of syntactic typologies within these treebanks. Additionally, we explore the application of our methodology in evaluating the syntactic diversity within language corpora.

Mass hauling operations play central roles in construction projects. They typically use many haulers that consume large amounts of energy and emit significant quantities of CO₂. However, practical methods for estimating the energy consumption and CO₂ emissions of such operations during project planning are lacking. This paper presents a detailed model for estimating the energy consumption and CO₂ emissions of mass haulers that integrates the mass hauling plan with a set of predictive equations. The mass hauling plan is generated using a planning program such as DynaRoad in conjunction with data on the productivity of selected haulers and the amount of material to be hauled during cutting, filling, borrowing, and disposal operations. This plan is then used as input for estimating the energy consumption and CO₂ emissions of the selected hauling fleet. The proposed model will help planners to assess the energy and environmental performance of mass hauling plans, and to select hauler and fleet configurations that will minimize these quantities. The model was applied in a case study, demonstrating that it can reliably predict energy consumption, CO₂ emissions, and hauler productivity as functions of the hauling distance for individual haulers and entire hauling fleets.

myfood24 is a comprehensive self-completed online 24-hour dietary recall tool currently used for nutritional assessments in epidemiological research. However, its clinical application has been unexplored. This mixed methods prospective observational study explores the acceptability and usability of myfood24 in a clinical population, women with gestational diabetes (GDM). Women were recruited at their first diabetes antenatal clinic appointment. To assess acceptability and usability, they were asked to complete five 24-hour dietary recalls using myfood24 over two weeks and a user experience questionnaire; with a subset invited to participate in a one-to-one semi-structured interview. Of the 199 participants, mean maternal age was 33 years, mean booking BMI 29.7kg/m2, 36% primiparous, 57% White, 33% Asian. Of these 121 (61%) completed myfood24 at least once and 73 (37%) completed the user questionnaire; 15 were interviewed. Usability of myfood24 was measured using the System Usability Scale (SUS) and found to be good (mean 70.9, 95%CI 67.1, 74.6). Interviews identified several areas for improvement, including optimising its use for mobile devices. myfood24 appears to be acceptable and have potential to support self-management and behaviour change for women with GDM but requires adaptation to record blood glucose results alongside real-time tracking of diet.

The Great Barrier Reef (GBR) is currently experiencing widespread crown of thorns starfish (CoTS) outbreaks as part of the fourth wave of outbreaks since 1962. It is believed that outbreaks have become more frequent on the GBR and elsewhere in the Indo-Pacific associated with anthropogenic causes. The two widely accepted potential causes are (1) anthropogenic nutrient enrichment leading to increased biomass of phytoplankton, the food of the planktonic stage of larval CoTS; and (2) overfishing of predators on the juvenile to adult stages of CoTS, for example, commercial fished species such as coral trout. In this study, we show the evidence for the nutrient enrichment causation hypothesis is strong based on a large number of recent studies in the GBR. We also hypothesise that secondary outbreaks in the region between Cairns and Townsville can also be enhanced by nutrient enriched conditions associated with the annual nutrient discharge from Wet Tropics rivers.

To advance probiotic research, a comprehensive understanding of bacterial interactions with human physiology at the molecular and cellular levels is fundamental. Lacticaseibacillus rhamnosus LGG® is a bacterial strain that has long been recognized for its beneficial effects on human health. Probiotic effector molecules derived from LGG®, including secreted proteins, surface-anchored proteins, polysaccharides, and lipoteichoic acids, that interact with host physiological processes have been identified. In vitro and animal studies have revealed that specific LGG® effector molecules stimulate epithelial cell survival, preserve intestinal barrier integrity, reduce oxidative stress, mitigate excessive mucosal inflammation, enhance IgA secretion, and provide long-term protection through epigenetic imprinting. Pili on the cell surface of LGG® promote adhesion to the intestinal mucosa and ensure close contact to host cells. Extracellular vesicles produced by LGG® recapitulate many of these effects through their cargo of effector molecules. Collectively, the effector molecules of LGG® exert a significant influence on both the gut mucosa and immune system, that promotes intestinal homeostasis and immune tolerance.

Background: There are anecdotal reports on reversible QTc prolongation during therapeutic hypothermia (TH) for moderate to severe neonatal encephalopathy after asphyxia. As the QTc interval is a relevant biomarker to assess safety during medication development, a structured search and review on published neonatal QTc values to generate reference values is warranted to facilate medication development in this specific population. Methods: A structured search and literature assessment (PubMed, Embase, Google Scholar) with ‘Newborn/Infant, QT and hypothermia’ was conducted (October 2021). Retrieved individual values were converted to QTc (Bazett) over postnatal age (day 1-7). Results: We retrieved 94 QTc intervals [during TH (n=50, until day 3) or subsequent normothermia (n=44, day 4-7)] in 33 neonates from 6 publications. The median (range) of QTc intervals during TH was 508 (430-678), and 410 (317-540) ms afterwards (difference 98 ms, or +28 ms/°C decrease). Four additional cohorts (without individual QTc intervals) confirmed the pattern and magnitude of the effect of body temperature on the QTc interval. Conclusions: We added a relevant non-maturational covariate (TH, °C dependent) and generated reference values for the QTc interval in this specific neonatal subpopulation. This knowledge on QTc during TH should be considered and integrated in neonatal medication development.

Meat loss and waste are estimated at each stage along the food chain, but the methods used are complex and the data needed often fragmented. We, therefore, evaluated the feasibility of estimating meat loss and waste using a simpler method comparing meat availability and consumption, using Swiss meat consumption according to a national nutrition survey and Swiss meat availability according to food balance sheets. As availability is reported at the fresh meat level and consumption as consumed, items of the latter were converted to fresh meat equivalents before comparing consumption with availability. Consumed unprocessed meat was directly converted to fresh meat equivalents and consumed meat products after having identified their meat ingredients. Meat availability, meat consumption as consumed and as fresh meat equivalent were 138.4 g/d, 105.5 g/d, and 112.1 g/d, respectively. The resulting total meat loss and waste was 19% and varied from −36% to 38% for the different meat types. Estimating meat loss and waste based on meat availability and consumption derived from a national nutrition survey yielded results varying to such an extent that the evaluated method to estimate meat loss and waste cannot be recommended.

Ebola virus (EBOV) is a zoonotic pathogen causing severe hemorrhagic fevers in humans and non-human primates with high case fatality rates. In recent years, the number and extent of outbreaks has increased, highlighting the importance of better understanding the molecular aspects of EBOV infection and host cell interactions to control this virus more efficiently. Many viruses, including EBOV, have been shown to recruit host proteins for different viral processes. Based on a genome-wide siRNA screen, we recently identified the cellular host factor carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) to be involved in EBOV RNA synthesis. However, mechanistic details of how this host factor plays a role in the EBOV life cycle remain elusive. In this study, we analyzed the functional and molecular interactions between EBOV and CAD. To this end, we used siRNA knockdowns in combination with various reverse-genetics based lifecycle-modelling systems and additionally performed co-immunoprecipitation and co immunofluorescence assays to investigate the influence of CAD on individual aspects of the EBOV life cycle and to characterize the interactions of CAD with viral proteins. Following this approach, we could demonstrate that CAD directly interacts with the EBOV nucleoprotein NP, and that NP is sufficient to recruit CAD into inclusion bodies dependent on the GLN-domain of CAD. Further, siRNA knockdown experiments indicated that CAD is important for both viral genome replication and transcription, while substrate rescue experiments showed that the function of CAD in pyrimidine synthesis is indeed required for those processes. Together this suggests that NP recruits CAD into inclusion bodies via its GLN domain in order to provide pyrimidines for EBOV genome replication and transcription. These results define a novel mechanism by which EBOV hijacks host cell pathways in order to facilitate genome replication and transcription, and provide further basis for the development of host directed broad spectrum antivirals.

The different waves of the COVID-19 pandemic caused dramatic issues regarding the organiza-tion of care. In this context innovative solutions have to be developed in a timely manner to adapted the organization of the care. The establishment of middle care (MC) units is a bright example of such an adaptation. A multidisciplinary MC team, including expert and non-expert respiratory nurses, physicians, physiotherapists, psychologists, nutritionists and social workers, was built and trained to work in the COVID-19 MC unit. Important educational resources were set up to ensure rapid and effective training of the MC team, limiting the admission or delaying transfers to ICU and ensuring optimal management of palliative care. We conducted a retrospec-tive analysis of patient data in the MC unit during the second COVID-19 wave. Fifty-two COVID-19 ‘step-up’ patients admitted to the MC unit were included in the study. Thirty-four (65%) patients worsened, of which 12 (23%) were not eligible for ICU access. In total, 42% of the ICU-eligible patients were managed in the MC unit to avoid the ICU. Among the 22 patients transferred to the ICU, 15 were intubated. The establishment of an MC unit during a pandemic, mixing expert and non-expert respiratory team members, is feasible and needed. MC units possi-bly relieve the pressure exerted on ICUs. A highly trained multidisciplinary team is key to ensur-ing the success of an MC unit during a pandemic.

In 2010, Parties to the Convention on Biological Diversity (CBD) adopted the Strategic Plan for Biodiversity 2011–2020 to address the loss and degradation of nature. Subsequently, most biodiversity indicators continued to decline. Nevertheless, conservation actions can make a positive difference for biodiversity. The emerging Post-2020 Global Biodiversity Framework has potential to catalyze efforts to ‘bend the curve’ of biodiversity loss. Thus, the inclusion of a goal on species, articulated as Goal B in the Zero Draft of the Post-2020 Framework, is essential. However, as currently formulated, this goal is inadequate for preventing extinctions, and reversing population declines; both of which are required to achieve the CBD’s 2030 mission. We contend it is unacceptable that Goal B could be met while most threatened species deteriorated in status and many avoidable species extinctions occurred. We examine the limitations of the current wording and propose an articulation with robust scientific basis. A goal for species that strives to end extinctions and recover populations of all species that have experienced population declines, and especially those at risk of extinction, would help to align actors towards the transformative actions and interventions needed for humans to live in harmony with nature.

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs repurposed for treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule binding to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and other Arbidol derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest quality SPR binding data to S2 over the conditions explored. A molecular docking approach was used to identify the most favorable binding sites on the S2 segment in the prefusion conformation, highlighting two possible small-molecule binding sites for fusion inhibitors. Results from molecular docking and modeling the structure-activity-relationship (SAR) of a newly reported series of Clofazimine derivatives supports the proposed Clofazimine binding site on the S2 segment. When the proposed Clofazimine binding site is superimposed with other experimentally determined coronavirus structures in structure-sequence alignments, the changes in sequence and structure may rationalize the broad-spectrum antiviral activity of Clofazimine in closely related coronavirus such as (SARS-CoV, MERS, hCoV-229E, hCoV-OC43).

Drones are being used more and more frequently and in various ways to attack people and critical infrastructures, which increases their level of danger and makes early detection and risk assessment even more difficult. There is no ultimate drone sensor. Rather, drones can only be effectively detected, if suitable sensor technologies are integrated within a system. Among the best suited sensorics for this purpose are radar and optical sensors, because the advantage of the radar, given by the long detection range, can be well combined with the additional visual-based information gained from a camera in the mid- and short-range, where usually the radar fails detecting micro drones. In this paper, a modular drone detection and assistance system MODEAS is presented, which can be used to automatically detect and track drones within a range up to some kilometers on the sky, but also in complex urban environments, where buildings and vegetation offer a perfect background for camouflage. The system provides an early detection of flying objects as potential drones, when those are not at all or only as small dots visible for the human eye. Main strengths of the system are the robust AI detection to differentiate such an object against clutter (birds, clouds) and its further classification by model and payload recognition, the latter aspect being considered as an indication of dangerousness. Moreover, once a drone is detected, the system follows it automatically, precisely and smoothly with a high-resolution pan-tilt-camera, measuring the distance to the sensor station with a laser rangefinder, compute the geocoordinates and visualize them live on a map. To improve the precision of the detection, a multisensorial fusion of all sensor detections is performed. Furthermore, alarms may be generated when a drone enters a restricted area.

Products derived from Cannabis sativa have gained increased interest and popularity. As these products become common amongst the public, the heath and potential therapeutic values associated with hemp have become a premier focus of research. While the psychoactive and medicinal properties of Cannabis products have been extensively highlighted in literature, the antibacterial properties of CBD have not been explored in depth. This research serves to examine the antibacterial potential of CBD against Salmonella newington and Salmonella typhimurium. In this study we observed bacterial response to CBD exposure through biological assays, bacterial kinetics, and fluorescence microscopy. Additionally, comparative studies between CBD and ampicillin were conducted against Salmonella typhimurium and Salmonella newington to determine comparative efficacy. Furthermore, we observed potential resistance development of our Salmonella spp. against CBD treatment.

We have previously reported that a single test measuring oVEMP n10 to 4000Hz stimuli (either bone-conducted vibration (BCV) or air-conducted sound (ACS)) provides a definitive diagnosis of semicircular canal dehiscence (SCD) in 22 CT-verified patients with a sensitivity of 1.0 and specificity of 1.0. Such a single short screening test has great advantages of speed, minimizing testing time and the exposure of patients to stimulation. However some studies of the 4000Hz test for SCD have reported sensitivity and sensitivity values somewhat less that what we reported.

Intramedullary fixation with elastic stable intramedullary nailing and stabilization with an external fixator are standard methods for the treatment of diaphyseal femoral shaft fractures in children. A retrospective bi-centre cohort study was carried out, including all patients between the ages of 2 and 16 years with isolated traumatic diaphyseal femur fractures, treated either with intramedullary nailing or an external fixator. In total, 57 patients (17 female and 40 male) with a mean age of 6.5 ± 2.7 years (min. 2; max. 16 years) with a mean follow-up period of 6.1 ± 4.6 months (min. 2; max. 26 months), were included in this retrospective study. 33 patients were treated with elastic stable intramedullary nailing and 24 patients, and external fixation. In total, 18 patients (32%) experienced osteosynthesis-related complications: 8 patients (24%) in the elastic stable intramedullary nailing group and 10 (42%) in the external fixation group, leading to revision surgery in 10 patients (18%). At the latest follow-up, all fractures were radiologically healed with no evidence of malangulation or malrotation (defined as &gt;20°) and full weight-bearing. There was a lower rate of complications in the ESIN group than in the external fixation group. Overall, we were unable to show a significant difference between the two methods.

The Finite size Lyapunov exponent (FSLE) has been used extensively since the late 1990’s to diagnose turbulent regimes from Lagrangian experiments and to detect Lagrangian coherent structures in geophysical flows and two-dimensional turbulence. Historically, the FSLE was defined in terms of its computational method rather than via a mathematical formulation, and the behavior of the FSLE in the turbulent inertial ranges is based primarily on scaling arguments. Here we propose an exact definition of the FSLE based on conditional averaging of the finite amplitude growth rate (FAGR) of the particle pair separation. With this new definition, we show that the FSLE is a close proxy for the inverse structural time, a concept introduced a decade before the FSLE. The (in)dependence of the FSLE on initial conditions is also discussed, as well as the links between the FAGR and other relevant Lagrangian metrics, such as the finite time Lyapunov exponent and the second order velocity structure function.

Climate change may cause organisms to seek thermal refuge from rising temperatures, either by shifting their ranges or seeking microrefugia within their existing ranges. We evaluate the potential for thermal stratification to provide refuge for two fish species in the San Francisco Estuary (SFE): Chinook Salmon (Oncorhynchus tshawytscha) and Delta Smelt (Hypomesus transpacificus). We compiled water temperature data from multiple monitoring programs to evaluate spatial, daily, hourly, intra-annual, and inter-annual trends in stratification using generalized additive models. We used our data and models to predict the locations and periods of time that the bottom of the water column could function as thermal refuge for salmon and smelt. Periods in which the bottom was cooler than surface primarily occurred during the peak of summer and during the afternoons, with more prominent stratification during warmer years. Although the SFE is often exceedingly warm for fish species and well-mixed overall, we identified potential for thermal refugia in a long and deep terminal channel for Delta Smelt, and in the periods bordering summer for Chinook Salmon. Thermal stratification may increase as the climate warms, and pockets of cooler water at depth, though limited, may become more important for at-risk fishes in the future.

The concept of green energy is now at the forefront of development discourse, with the United Nations Sustainable Development Goals (SDGs) 7, 11, and 12 all aimed at promoting green energy consumption to combat the three planetary crises: climate change, biodiversity loss, and pollution. Similarly, issues regarding Africa’s natural resource curse have caused a stir in the growth and development literature for some time now and there is no sign that it will die out. This study, the first of its kind, simultaneously assesses the impact of green energy consumption and Africa’s natural resources rents on economic growth by applying the Feasible Generalized Least Square (FGLS) estimator and the dynamic panel models of the Pooled Mean Group (PMG) and Mean Group (MG) estimators on data from 1990 to 2020 for 24 selected African countries. The results show that green energy consumption has a short-run growth-limiting effect and a long-run growth-enhancing effect in Africa. The study also found evidence of the natural resource curse phenomenon in Africa. The study, therefore, calls for the advancement and usage of green energy for both domestic and industrial production in Africa. The study further calls for a revamp in the global tax policy to curb illicit financial activities and strengthening institutional quality for transparency and accountability in the entire value chain of natural resource management in Africa.

In this work, we derive the spectral efficiency, secrecy outage probability, and bit error rate of a communication system assisted by a large intelligent surface (LIS). We consider a single-antenna user and an array of antennas at the transmitter side and the possibility of a direct link between transmitter and receiver. Additionally, there is a single-antenna eavesdropper with a direct link to the transmitter, which is modeled as a Nakagami-m distributed fading coefficient. The channels from transmitter to the LIS and from the LIS to the user may or may not have the line-of-sight (LoS) and are modeled by the Nakagami- m distribution. Moreover, we assume that the LIS elements perform non-ideal phase cancellation leading to a residual phase error that assumes a Von Mises distribution. We show that the resulting channel can be accurately approximated by a Gamma distribution whose parameters are analytically estimated using the moments of the equivalent signal-to-noise ratio. We also provide an upper bound for the error probability for M-QAM modulations. With the derived formulas, we analyze the effect of the strength of the LoS link by varying the Nakagami parameter, m.

Lean body mass (LBM) is correlated with powerlifting performance in athletes competing in different bodyweight classes. However, it remains unknown whether changes in LBM are correlated with performance changes in powerlifters preparing for a competition. Aim of the study was to investigate the changes in LBM and performance in powerlifters preparing for a competition. Eight male powerlifters (age 31.7±9.8years, height 1.77±0.06m, weight 99.2±14.6kg) and three female powerlifters (age 32.7±16.3years, height 1.54±0.06m, weight 66.6±20.9kg), participated in the study. Athletes followed individualized periodized training programs for 12 weeks aiming to maximize their performance for the national championship. Maximum strength (1-RM) in squat, bench press, and deadlift, body composition, grip strength, anaerobic power, quadriceps’ cross sectional area and vastus lateralis muscle architecture were measured before and after the training period. Significant increases were found after the training period in squat (5.8±7.0%, P

Research investigating the neural substrates underpinning parental behaviour has recently gained momentum. Particularly, the hypothalamic medial preoptic area (MPOA) has been identified as a crucial region for parenting. The current study conducted a scientometric analysis of publications from 01 January 1972 to 19 January 2021 using CiteSpace software to determine trends in the scientific literature exploring the relationship between MPOA and parental behaviour. In total, 677 scientific papers were analysed, producing a network of 1509 nodes and 5498 links. Four major clusters were identified: "C-Fos Expression'', "Lactating Rat'', "Medial Preoptic Area Interaction'' and "Parental Behavior''. Their content suggests an initial trend in which the properties of the MPOA in response to parental behavior were studied, followed by a growing attention towards the presence of a brain network, including the reward circuits, regulating such behavior. Furthermore, while attention was initially directed uniquely to maternal behavior, it has recently been extended to the understanding of paternal behaviors as well. Finally, although the majority of the studies were conducted on rodents, recent publications broaden the implications of previous documents to human parental behavior, giving insight into the mechanisms underlying postpartum depression. Potential directions in future works were also discussed.

Since the beginning of the COVID-19 pandemic, extensive drug repurposing efforts sought to identify small molecule antivirals with various mechanisms of action. Here we aim to review research progress on small molecule viral entry and fusion inhibitors that directly bind to the SARS CoV-2 Spike protein. Early in the pandemic, numerous small molecules were identified in drug repurposing screens and reported to be effective in vitro SARS CoV-2 viral entry or fusion inhibitors. However, given minimal experimental information regarding the exact location of small molecule binding sites on Spike, it was unclear what the specific mechanism of action was, or where the exact binding sites were on Spike for some inhibitor candidates. The work of countless researchers has yielded great progress, with the identification of many viral entry inhibitors that target elements on the S1 receptor binding domain (RBD) or N-terminal domain (NTD) and disrupt S1 receptor binding function. In this review, we will also focus on highlighting fusion inhibitors that target inhibition of the S2 fusion function, either by disrupting the formation of the postfusion S2 conformation or alternatively by stabilizing structural elements of the prefusion S2 conformation to prevent conformational changes associated with S2 function. We highlight experimentally validated binding sites on the S1/S2 interface and on the S2 subunit. While most mutations to the Spike protein to date in variants of concern (VOCs) have been localized to the S1 subunit, the S2 subunit sequence is more conserved with only a few observed mutations in proximity to S2 binding sites. Several recent small molecules targeting S2 have been shown to have robust activity over numerous recent VOC mutant strains and/or greater broad spectrum antiviral activity for other more distantly related coronaviruses.

Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behaviour. Moreover, only a few studies have investigated the effect of CBD in female rodents. Therefore, we aimed to i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and in a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects; and ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect one-hour post-injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at one hour and decreasing it at two hours. Ketamine produced an antidepressant-like effect in male and female FSL rats at different doses. In conclusion, strain, sex, and administration time affect CBD's behavioural response to rodents exposed to tests predictive of antidepressant effects.

Despite the increasing popularity of liquid chromatography-mass spectrometry (LC-MS)-based lipidomics, there is a lack of accepted and validated method for lipid extract quality and quantity assessment prior to LC-MS. Fourier-Transform Infrared Spectroscopy (FTIR) has been reported for quantification of pure lipids, however, the sample complexity and purity complex lipid extract quantification in lipidomics experiments could be impact quantification accuracy. Here, we report comprehensive assessment of the sample matrix on the accuracy of lipid quantification using Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy (ATR-FTIR). Pure lipids are characterized by CH-and C=O-stretching vibrations on FTIR, with quantitative range of 40–3000 ng and a limit of detection of 12 ng. Sample extraction method and local baseline subtraction during FTIR spectral processing significantly impact lipid quantification by CH-stretching. To facilitate sample quality screening, we developed the Lipid Quality (LiQ) score from a spectral library of common contaminants, using a ratio of peak heights between CH-stretching vibrations maxima and the collective vibrations from amide/amine, CH-stretching minima and sugar moieties. We evaluated LiQ score as a rapid sample quality control method by comparing to total LC-MS intensity of targeted lipidomics of 107 human plasma lipid extracts. Exclusion of poor-quality samples based on LiQ score improved the correlation between FTIR and LC-MS quantification. Finally, the uncertainty of absolute quantification by FTIR was estimated using a 795 ng SPLASH LipidoMix standard to be &lt;10%. In summary, this study identified key parameters for accurate FTIR-based quantification of complex lipid mixture, and developed a rapid workflow requiring only 1 µL of MS-ready sample and &lt; 5 minutes for routine lipidomics sample quality and quantity assessment.

The ability to read and quantify nucleic acids such as DNA and RNA using sequencing technologies has revolutionized our understanding of life. With the emergence of synthetic biology, these tools are now being put to work in new ways - enabling de novo biological design. Here, we show how sequencing is supporting the creation of a new wave of biological parts and systems, as well as providing the vast data sets needed for the machine learning of design rules for predictive bioengineering. However, we believe this is only the tip of the iceberg and end by providing an outlook on recent advances that will likely broaden the role of sequencing in synthetic biology and its deployment in real-world environments.

The Lightning Network (LN), a second-layer protocol built on top of the Bitcoin blockchain, is an innovative digital payment solution that offers increased convenience, speed, and cost-effectiveness to consumers and businesses alike. However, there is limited literature available on the characteristics of this nascent technology, the depth and breadth of the various business LN-related applications as well as relevant adoption/implementation challenges. This study aims to contribute to the understanding of the LN’s characteristics, its potential in enhancing business operations and its applicability across different sectors, while taking into account adoption and implementation challenges. We apply a narrative review methodology using a semi-systematic approach to examine new and emerging business models empowered by the LN and its characteristics, topology, performance, privacy, and security. We analyze the data to identify key themes and trends in the literature, offering a critical analysis of the strengths and weaknesses of the existing literature. Based on the findings, we provide several clusters of fruitful areas for future research directions. The findings of this study will help businesses make more informed decisions about adopting and leveraging the LN to improve their operations and enhance customer experience.

Responding to changing value creation processes in the sheet metal working sec-tor, where the complexity and interchangeability of products challenge traditional dif-ferentiation strategies, this empirical analysis explores integrating service-oriented and data-driven business models as new paths to ensure competitiveness, especially for small and medium-sized enterprises (SMEs). This study aims to capture the current state and challenges associated with the implementation of these business models in this sector. The research was conducted through semi-structured interviews with SMEs in the industry. The findings indicate that service-oriented and data-driven business models are not yet widely adopted and that manufacturing companies re-quire support in their implementation. Fields of action were identified for the industry. These are "Creating awareness and understanding", "Recognizing added value", "In-creasing company maturity" and "Understanding the change process". Cooperation between science and industry is essential in tackling these fields of action to ensure the successful integration of such business models in manufacturing companies. This pa-per identifies challenges in the fields of action that companies must address through a structured approach promoting awareness, recognizing value, improving organiza-tional maturity, and understanding the change process to successfully implement ser-vice-oriented and data-driven business models.

The objective of this study was to evaluate the efficacy of fungal treatment (Pleurotus ostreatus) of urea-treated rice stubble on growth performance in slow-growing goats. Eighteen crossbred Thai native x Anglo-Nubian male goats (average body weight: 20.4 ± 2.0 kg) were randomly assigned to three experimental total mixed rations containing 35% rice stubble (RS) that was either untreated (URS), urea treated (UTRS) or treated with urea and fungi (UFTRS). URS and UTRS were cultivated and harvested from aseptically fungal spawn, incubated at 25-30 °C for 25 days. Indicators of growth performance were monitored and faeces were collected quantitatively to assess nutrient digestibility, during a 12-week feeding trial. All goats remained healthy throughout experiment. The goats fed UFTRS had a lower feed conversion ratio (kg feed/kg growth) compared to goats fed URS or UTRS. Compared to URS, dietary UFTRS increased nutrient digestibility of slow-growing goats, such as OM (+8.5%), CP (+5.5%), NDF (+39.2%), and ADF (+27.4%). Likewise, dietary UFTRS tended to increase rumen ammonia concentrations but rumen pH and volatile fatty acids were not affected by UFTRS. In conclusion, the present study indicates that the fungal treatment of RS is an effective tool to improve the growth performance of slow-growing goats.

The digital transformation of healthcare is advancing, leading to an increasing availability of clinical data for research. Perioperative big data initiatives were established to monitor treatment quality and benchmark outcomes. However, big data analyzes have long exceeded the status of pure quality surveillance instruments. Large retrospective studies nowadays often represent the first approach to new questions in clinical research and pave the way for more expensive and resource intensive prospective trials. As a consequence, utilization of big data in acute pain and regional anesthesia research considerably increased over the last decade. Multicentric clinical registries and administrative databases (e.g., healthcare claims databases) have collected millions of cases until today, on which basis several important research questions were approached. In acute pain research, big data was used to assess postoperative pain outcomes, opioid utilization, and the efficiency of multimodal pain management strategies. In regional anesthesia, adverse events and potential benefits of regional anesthesia on postoperative morbidity and mortality were evaluated. This article provides a narrative review on the growing importance of big data for research in acute postoperative pain and regional anesthesia.