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Misfolded, potentially toxic proteins in the lumen and membrane of the endoplasmic reticulum (ER) are eliminated by proteasomes in the cytosol through ER-associated degradation (ERAD). The ERAD process involves the recognition of substrates in the lumen and membrane of the ER, their translocation into the cytosol, ubiquitination, and delivery to the proteasome for degradation. These ERAD steps are performed by membrane-embedded ubiquitin-ligase complexes of different specificity that together cover a wide range of substrates. Besides misfolded proteins, ERAD further contributes to quality control by targeting unassembled and mislocalized proteins. ERAD also targets a restricted set of folded proteins to influence critical ER functions such as sterol biosynthesis, calcium homeostasis, or ER contacts with other organelles. This review describes the ubiquitin-ligase complexes and the principles guiding protein degradation by ERAD.

A patient in her late 50s with antiphospholipid syndrome presented to general ophthalmology clinic for annual hydroxychloroquine retinopathy screening. She had taken 400 mg hydroxychloroquine daily for over a decade. She denied any visual changes and visual acuity was 20/20. Her examination and fundus photos were normal, but macular optical coherence tomography of the right eye demonstrated inner retinal atrophy and visual field tests revealed a corresponding paracentral scotoma, consistent with a prior cilioretinal artery occlusion. Prior testing from visits with other ophthalmologists revealed that this occlusion had occurred previously, but she had only been informed of not having hydroxychloroquine retinopathy. The possibility of vision loss prompted her to reconsider her prior decision to discontinue anticoagulation. This case demonstrates how anchoring bias may lead clinicians astray, and how the risk of blindness is a strong motivator for patients regarding anticoagulation.

This review highlights new concepts in vascular patterning in the last 10 years, with emphasis on its beauty and complexity. Endothelial cell signaling pathways that respond to molecular or mechanical signals are described, and examples of vascular patterning that use these pathways in brain, skin, heart, and kidney are highlighted. The pathological consequences of patterning loss are discussed in the context of arteriovenous malformations (AVMs), and prospects for the next 10 years presented.

Nasopharyngeal carcinoma can present with epistaxis, cervical lymphadenopathy, audiological symptoms secondary to eustachian tube dysfunction, pain, or neurological symptoms from tumours directly invading the skull base. It is unusual for patients to present with indirect systemic manifestations. Paraneoplastic neurological syndrome can precede clinically overt malignancy by up to 5 years; therefore, a combination of thorough clinical, laboratory and radiological investigations is required to reach a diagnosis. Intravenous immunoglobulin and steroids might improve neurological symptoms initially and prevent irreversible neuronal damage, but treatment of the underlying cancer is important for long-term resolution. Our case adds to a small but growing body of literature related to anti-Ri antibodies, opsoclonus-myoclonus syndrome presentations, and is the first reported association of this combination with nasopharyngeal carcinoma.

Objectives. To test the effects of countermarketing videos addressing common misperceptions about ingredients and claims on children’s sugary drinks. Methods. We conducted an online randomized controlled experiment in January 2021 with US caregivers (n = 600) of young children (aged 8‒37 months) to assess the effects of watching countermarketing versus control videos on intentions to serve sugary and healthy drinks (6-point scales) and attitudes (10-point scales) about fruit drinks and toddler milks. Results. The countermarketing videos significantly reduced positive attitudes about fruit drinks (mean difference = 0.92) and toddler milks (mean difference = 2.10), reduced intentions to serve both (mean difference = 0.50 and 0.92, respectively), and increased intentions to serve plain milk (mean difference = 0.52) versus control videos (all Ps Conclusions. A countermarketing campaign aimed at diverse caregivers of young children designed to correct misleading children’s drink marketing presents a promising public health approach for reducing sugary drink consumption in the first 1000 days. (Am J Public Health. 2022;112(S8):S807–S816. https://doi.org/10.2105/AJPH.2022.307024 )

Xylazine is a nonopioid veterinary anesthetic and sedative that is increasingly detected in the illicit drug supply in the United States. Data indicate a striking prevalence of xylazine among opioid-involved overdose deaths. The emergence of xylazine in the illicit drug supply poses many unknowns and potential risks for people who use drugs. The public health system needs to respond by increasing testing to determine the prevalence of xylazine, identifying its potential toxicity at various exposure levels, and taking mitigating action to prevent harms. Currently, there is little testing capable of identifying xylazine in drug supplies, which limits the possibility of public health intervention, implementation of harm reduction strategies, or development of novel treatment strategies. (Am J Public Health. 2022;112(8):1212–1216. https://doi.org/10.2105/AJPH.2022.306881 )

In this study, we aim to test the intergroup contact hypothesis in the context of social media (specifically: Twitter) combining survey data and data scraped from participants' Twitter accounts.

Managing the burden of a high-risk hereditary cancer genetic test result, probands are also often tasked with communicating cancer risk information to their family members. Predictably, this duty to warn is associated with emotional and logistical complications. To improve support and outcomes for these patients and their family members, this study aimed to deepen understanding of the hereditary cancer risk communication process. We conducted semi-structured interviews with ConnectMyVariant users that had a familial pathogenic variant in genes associated with hereditary breast and ovarian cancer. During the interviews, the participant and researcher collaboratively developed a communication timeline to represent the longitudinal experience of the participant. We found clear evidence that hereditary breast and ovarian cancer risk communication occurs through successive, ongoing interactions. Follow-up and ongoing communication events preceded 40.8% of the total familial testing reported, corresponding with a correlation coefficient of 0.44. Additionally, we characterized patterns unique to extended family communication. Lastly, our findings provide insight to how probands assess hereditary risk communication. Further validation of these results will inform probands and genetic health professionals of effective patterns when sharing hereditary cancer risk information.

The study is an initial investigation of the feasibility of applying Bayesian sequential analyses to individual participant single-case data for rapid detection of whether or not the individual is benefitting from a low-intensity computerized cognitive training intervention for depression. Patients waiting for, or in follow-up from, outpatient psychological therapy will complete first a two-week period of daily symptom monitoring, followed by two different two-week cognitive training interventions. Data collected will be used to assess feasibility of a future formal case series using Bayesian sequential analyses to determine switching of interventions, and inform the analysis parameters for such a future study.

The purpose of an eyewitness identification procedure is to determine whether the police suspect is guilty or innocent of the crime in question. Rather than presenting the lone suspect to the witness for an identification attempt, it is generally advised that the police investigator first surround the suspect with known-innocent fillers. The rationale is that if the suspect is guilty, the eyewitness ought to be able to pick this person out of a lineup. If the suspect is innocent, these fillers offer that individual protection from mistaken identification as many witnesses who would have otherwise identified the innocent suspect identify a filler instead (e.g., Smith et al., 2018; Smith et al., 2020). Hence, the idea of surrounding the suspect with known-innocent fillers is that we can strike a better trade-off between correct perpetrator identifications and incorrect innocent-suspect identifications. But producing that improved trade-off requires that fillers be selected so that they are, on average, as similar to the witness’ memory for the perpetrator as is the innocent suspect. Lineups in which fillers prevent the innocent suspect from standing out as a better match to the witness’ memory for the perpetrator are called fair and lineups in which the fillers do not prevent the innocent suspect from standing out as a better match to the witness’ memory for the perpetrator are called biased. More than 40 years of research demonstrates that fair lineups lead to a better trade-off between guilty-suspect identifications and innocent-suspect identifications than do biased lineups and that a suspect identification from a fair lineup is far more reliable than a suspect identification from a biased lineup (e.g., Clark, 2012; Lindsay & Wells, 1980; Smith et al., 2017). In the present line of research, we examine how laypeople perceive the reliability of identifications made from fair versus biased lineups. In Experiment 1, we presented laypeople with (1) a brief description of the crime, (2) the witness’ brief description of the perpetrator, (3) a six-person photographic lineup, and (4) the position of the identified lineup member. Each lay participant viewed one fair lineup, where all lineup members match the witness’ description of the perpetrator, and one biased lineup, where only the lineup member who was identified matches the witness’ description of the perpetrator. On each lineup, participants were asked to the likelihood the witness had made an accurate identification. We posited that, counterintuitively, laypeople would judge identifications from biased lineups to be more reliable than identifications from fair lineups. The rationale was that the non-selected lineup members provide a reference group of alternative outcomes that can be contrasted with the identified lineup member. Compared to when only the identified lineup member fits the witness’ description (biased lineup; high perceptual contrast), when all lineup members fit the witness’ description (fair lineup; low perceptual contrast), laypersons might look to the non-identified alternatives, question why not one of these other persons, and lower their reliability judgment accordingly. As we expected, laypeople rated likely accuracy higher for biased lineup than they did for fair lineups (d = .80). In the follow-up experiments, our goal was to determine what information laypeople needed to know before aligning their perceptions of fair and biased lineups to be equivalent to what the research shows to be the truth. To do this, we incrementally added additional instructions to the lineup task in a series of three separate experiments. In Experiment 2, we added to the instructions that the witness identified the suspect. We expected that this inclusion would key participants into the fact that there is only a single suspect present in the lineup (and that the other five are known-innocent, or not suspected of the current crime). In Experiment 3, we instructed participants to keep in mind that the actual culprit might or might not be present in the lineup, which we expected to help guide them to the conclusion that the “correct” answer might be to reject the lineup (or say that the culprit is not present). In Experiment 4, we informed participants that the police designed the lineup by selecting known-innocent fillers from a database of images. We expected that this instruction would help participants to appreciate the intent with which many biased lineups are constructed—to increase the likelihood that the witness would identify the suspect. However, adding on these additional pieces of information had little impact on participants ratings. Throughout the next several experiments, we were interested in determining how lay participants responded when presented with a lineup fairness question, rather than a question about suspect identification accuracy. In Experiment 5 and Experiment 7, we found that participants rated fair lineups as “fairer” than biased lineups, indicating that they were sensitive to the lineup fairness manupulation. Furthermore, in Experiment 5, we found that priming participants with this fairness question attenuated participants’ preferences for the biased lineup over the fair lineup. In fact, in Experiment 8, we found that providing participants with the full set of instructions (tested in Experiments 2 through 4) and priming them with a lineup fairness question (tested in Experiment 5 and 7), led to laypersons rating fair and biased lineups as almost identical in terms of suspect identification accuracy. Save for priming participants with lineup fairness considerations, none of the subtle instructions we provided to participants had much impact on their accuracy ratings for fair and biased lineups. Hence, in Experiment 9, we take a different approach. We will present laypersons with a short passage describing the purpose of lineups to see whether giving them more of a conceptual explanation leads them to appreciate why suspect identification accuracy is higher for fair than for biased lineups. This passage makes four key points: (1) suspects are generated by using the witness’ description, (2) suspects are sometimes innocent, (3) eyewitnesses frequently make false identifications of innocent persons, (4) the purpose of a lineup is to see if the witness recognizes the suspect as the culprit, and (5) lineups can be a good measure of guilt when all fillers match the witness’ description. The passage reads as follows: When a crime occurs there is sometimes an eyewitness who got a view of the culprit and can give a verbal description of that culprit. Police will generate suspects matching the witness’ description. The suspect might be innocent, of course, and so police sometimes put together a lineup (either live or photographic) that includes that suspect and then show that lineup to the eyewitness. It is not uncommon for the suspect in a lineup to in fact be innocent (not the culprit). Because eyewitnesses often mistakenly identify innocent people, police embed the suspect among known-innocent lineup members. These known-innocent lineup members are called “lineup fillers.” In a typical lineup, there are five of these fillers plus the one suspect, thereby yielding a lineup composed of six people. The goal of the lineup is to make sure that an eyewitness actually recognizes the suspect as being the culprit. But if the fillers do not fit the witness’s description of the culprit, then maybe the witness will pick the suspect only because he best fits the description rather than because the witness actually recognizes the suspect as being the culprit. Therefore, the fillers should fit the verbal description that the eyewitness gave of the culprit. If the fillers all fit the description that the eyewitness gave of the culprit and the eyewitness still manages to pick the suspect, the identification is considered good evidence of guilt. We will also use five manipulation check questions to assess participant comprehension of the short passage. Participants will answer these manipulation check questions at the end of the study, after having rated the likely suspect identification accuracy of both a fair and a biased lineup. If participants do not rate suspect identification accuracy as higher for fair than for biased lineups, these manipulation check questions will help us to determine the extent to which that might have been attributable to comprehension issues rather than to the inefficacy of the passage. The questions are listed below, with the correct answers marked by an asterisk. Which of the following is typically true? • *Police develop suspects using the witness' description of the culprit. • Police do not use witness' description of the culprit when developing suspects. • Police develop suspects who look different from the witness' description of the culprit. • None of the above. Suspects in the lineup are _____ innocent. • Always • Never • *Sometimes • Normally Witnesses... • Are always correct. • Are always false. • Rarely make false identifications • *Frequently make false identifications The purpose of a lineup is: • To see if one of the fillers might be the actual culprit in the case • *To see if the eyewitness actually recognizes the suspect as being the culprit rather than simply being the lineup member who best fits the description • To make the task as easy and obvious as possible so that the witness will pick the person the police want them to pick • None of the above Identifications from a lineup are good evidence of guilt if: • *Fillers match the witness' description of the culprit • Fillers do not match the witness' description of the culprit • Regardless of whether or not fillers match the witness' description of the culprit • The suspect looks very different than the other lineup members

Objectives. To evaluate the focused surveillance of blood lead results of 20 micrograms per deciliter (µg/dL) of venous blood and higher received by the California Occupational Blood Lead Registry (Registry) because of new legislation concerning occupational lead poisoning. Methods. We used occupational blood lead results reported to the Registry from January 1, 2020, to December 31, 2021, to describe the current industries with workers having the highest levels of lead poisoning. Results. The Registry received 239 blood lead levels (BLLs) of 20 µg/dL or higher for 151 adults with occupational lead exposure in 28 industries over the study period. Worker BLLs ranged from 20 µg/dL to 55 µg/dL. The industries with the greatest number of workers were storage battery manufacturing, painting contractors, and shooting ranges. Conclusions. Occupational lead poisoning is a health concern across numerous industries in California. The current outdated state and federal occupational lead standards would not require removal from lead work for any of the workers in this study despite extensive evidence of harm at lower BLLs. Strengthened standards could support public health initiatives for worker protection and reduce take-home lead to family members. (Am J Public Health. 2022;112(S7):S690–S694. https://doi.org/10.2105/AJPH.2022.307002 )

Wound healing requires a complex cascade of highly controlled and conserved cellular and molecular processes. These involve numerous cell types and extracellular matrix molecules regulated by the actin cytoskeleton. This microscopic network of filaments is present within the cytoplasm of all cells and provides the shape and mechanical support required for cell movement and proliferation. Here, an overview of the processes of wound healing are described from the perspective of the cell in relation to the actin cytoskeleton. Key points of discussion include the role of actin, its binding proteins, signaling pathways, and events that play significant roles in the phases of wound healing. The identification of cytoskeletal targets that can be used to manipulate and improve wound healing is included as an emerging area of focus that may inform future therapeutic approaches to improve healing of complex wounds. Refereed/Peer-reviewed

We present the first observational infrared luminosity function (IRLF) measurement in the Epoch of Reionization (EoR) based on a ultraviolet (UV)-selected galaxy sample with the Atacama Large Millimeter Array (ALMA) spectroscopic observations. Our analysis is based on the ALMA large program Reionization Era Bright Emission Line Survey (REBELS), which targets 42 galaxies at z = 6.4–7.7 with [C ii] 158 $\rm{\mu m}$ line scans. 16 sources exhibit dust detection, 15 of which are also spectroscopically confirmed through the [C ii] line. The infrared (IR) luminosities of the sample range from log LIR/L⊙ = 11.4 to 12.2. Using the UV luminosity function as a proxy to derive the effective volume for each of our target sources, we derive IRLF estimates, both for detections and for the full sample including IR luminosity upper limits. The resulting IRLFs are well reproduced by a Schechter function with the characteristic luminosity of $\log L_{*}/\mathrm{ L}_\odot =11.6^{+0.2}_{-0.1}$ . Our observational results are in broad agreement with the average of predicted IRLFs from simulations at z ∼ 7. Conversely, our IRLFs lie significantly below lower redshift estimates, suggesting a rapid evolution from z ∼ 4 to z ∼ 7, into the reionization epoch. The IR obscured contribution to the cosmic star formation rate density at z ∼ 7 amounts to $\mathrm{log(SFRD/{\rm M}_{\odot }\,yr^{-1}\,Mpc^{-3}) = -2.66^{+0.17}_{-0.14} }$ that is at least ∼10 per cent of UV-based estimates. We conclude that the presence of dust is already abundant in the EoR and discuss the possibility of unveiling larger samples of dusty galaxies with future ALMA and JWST observations.

Reduction of the process cycle time has been a major challenge faced by the ground transportation industry when introducing composite components in their design. As a result, composite material manufacturers developed innovative solutions to tackle this problem. The past decade has seen resin manufacturers produce fast curing thermoset resins that can help composite manufacturers reduce process cycle times. Currently, automotive manufacturers use the liquid composite moulding (LCM) process to produce high quality net shape automotive parts, mostly for high performance low volume luxury automobiles. However, the ground transportation industry is a cost driven industry and mass production can be extremely expensive. Among all the LCM processes available, compression resin transfer moulding (CRTM) is seen as a cost-effective solution to meet industry demands. Yet, fast curing resins pose a major challenge in producing high quality parts. Therefore, researchers have been working on process simulation to optimize CRTM for the last three decades. Even though great progress has been achieved in performing CRTM simulation, there is still a huge gap to be addressed in terms of a fully coupled simulation (heat transfer, flow and mechnical) for a large complex 3D part. Hence, this paper aims at simulating the CRTM process using a new approach introduced into the current solver of PAM RTMTM. The simulations were validated using a 3D complex demonstrator part., FPCM-15: 15th International Conference on Flow Processes in Composite Materials, June 27-29, 2023, West Lafayette, IN, USA

Researchers are increasingly recognizing the importance of studying and addressing intersectional stigma within the field of HIV. Yet, researchers have, arguably, struggled to operationalize intersectional stigma. To ensure that future research and methodological innovation is guided by frameworks from which this area of inquiry has arisen, we propose a series of core elements for future HIV-related intersectional stigma research. These core elements include multidimensional, multilevel, multidirectional, and action-oriented methods that sharpen focus on, and aim to transform, interlocking and reinforcing systems of oppression. We further identify opportunities for advancing HIV-related intersectional stigma research, including reducing barriers to and strengthening investments in resources, building capacity to engage in research and implementation of interventions, and creating meaningful pathways for HIV-related intersectional stigma research to produce structural change. Ultimately, the expected payoff for incorporating these core elements is a body of HIV-related intersectional stigma research that is both better aligned with the transformative potential of intersectionality and better positioned to achieve the goals of Ending the HIV Epidemic in the United States and globally. (Am J Public Health. 2022;112(S4):S413–S419. https://doi.org/10.2105/AJPH.2021.306710 )

Background: In the 2022 mpox (monkeypox) outbreak, 79,000 global cases have been reported. Yet, limited dermatologic data have been published regarding lesion morphology and progression. Objective: The objective of this study was to characterize skin lesion morphology, symptomatology, and outcomes of mpox infection over time. Methods: The American Academy of Dermatology/International League of Dermatological Societies Dermatology COVID-19, Mpox, and Emerging Infections Registry captured deidentified patient cases of mpox entered by health care professionals. Results: From August 4 to November 13, 2022, 101 cases from 13 countries were entered, primarily by dermatologists (92%). Thirty-nine percent had fewer than 5 lesions. In 54% of cases, skin lesions were the first sign of infection. In the first 1-5 days of infection, papules (36%), vesicles (17%), and pustules (20%) predominated. By days 6-10, pustules (36%) were most common, followed by erosions/ulcers (27%) and crusts/scabs (24%). Crusts/scabs were the predominant morphology after day 11. Ten cases of morbilliform rash were reported. Scarring occurred in 13% of the cases. Limitations: Registry-reported data cannot address incidence. There is a potential reporting bias from the predilection to report cases with greater clinical severity. Discussion: These findings highlight differences in skin findings compared to historical outbreaks, notably the presence of skin lesions prior to systemic symptoms and low overall lesion counts. Scarring emerged as a major possible sequela.

Additive manufacturing technologies have several well-known advantages; however, the surface quality of the printed parts is poor, compromising the corrosion and mechanical properties. Thus, surface finishing treatments are necessary. The most post-processing treatments proposed in the literature are mechanical or chemical. The formers are contact techniques and cannot be suitable for complex geometry, while the latter use strong and dangerous reagents. This paper is aimed to investigate the effect of the electropolishing treatment, a contactless technique, using an eco-friendly electrolytic solution in reducing the roughness and improving the fatigue properties of Ti6Al4V specimens produced by electron beam melting technology. Several parameters affecting the effectiveness of the electropolishing treatment have been investigated, as interelectrode distance, stirring rate and duration time. An optimal combination of them allowed a uniform surface treatment and a significant roughness reduction (64% of Sa reduction for cylindrical specimens). Under sinusoidal loading conditions with a maximum stress of 378 MPa and a stress ratio equal to R = 0.1, the mean fatigue life of electropolished dog-bone specimens was 250% longer than that of as-built specimens.

Rising daily temperatures and water shortage are two of the major concerns in agriculture. In this work, we analysed the tolerance traits in a tomato line carrying a small region of the Solanum pennellii wild genome (IL12-4-SL) when grown under prolonged conditions of single and combined high temperature and water stress. When exposed to stress, IL12-4-SL showed higher heat tolerance than the cultivated line M82 at morphological, physiological, and biochemical levels. Moreover, under stress IL12-4-SL produced more flowers than M82, also characterized by higher pollen viability. In both lines, water stress negatively affected photosynthesis more than heat alone, whereas the combined stress did not further exacerbate the negative impacts of drought on this trait. Despite an observed decrease in carbon fixation, the quantum yield of PSII linear electron transport in IL12-4-SL was not affected by stress, thereby indicating that photochemical processes other than CO2 fixation acted to maintain the electron chain in oxidized state and prevent photodamage. The ability of IL12-4-SL to tolerate abiotic stress was also related to the intrinsic ability of this line to accumulate ascorbic acid. The data collected in this study clearly indicate improved tolerance to single and combined abiotic stress for IL12-4-SL, making this line a promising one for cultivation in a climate scenario characterized by frequent and long-lasting heatwaves and low rainfall.

INTRODUCTION: In the 330-patient ADVOCATE trial of avacopan for the treatment of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, in which 81% of patients had renal involvement, estimated glomerular filtration rate (eGFR) increased on average 7.3 ml/min per 1.73 m(2) in the avacopan group and 4.1 ml/min per 1.73 m(2) in the prednisone group (P = 0.029) at week 52. This new analysis examines the results in the patient subgroup with severe renal insufficiency at enrollment into the trial, i.e., eGFR ≤20 ml/min per 1.73 m(2). METHODS: eGFR was determined at baseline and over the course of the trial. Changes in eGFR were compared between the 2 treatment groups. RESULTS: In ADVOCATE, 27 of 166 patients (16%) in the avacopan group and 23 of 164 patients (14%) in the prednisone group had a baseline eGFR ≤20 ml/min per 1.73 m(2). At week 52, eGFR increased on average 16.1 and 7.7 ml/min per 1.73 m(2) in the avacopan and prednisone groups, respectively (P = 0.003). The last eGFR value measured during the 52-week treatment period was ≥2-fold higher than baseline in 41% of patients in the avacopan group compared to 13% in the prednisone group (P = 0.030). More patients in the avacopan group versus prednisone group had increases in eGFR above 20, 30, and 45 ml/min per 1.73 m(2), respectively. Serious adverse events occurred in 13 of 27 patients (48%) in the avacopan group and 16 of 23 patients (70%) in the prednisone group. CONCLUSION: Among patients with baseline eGFR ≤20 ml/min per 1.73 m(2) in the ADVOCATE trial, eGFR improved more in the avacopan group than in the prednisone group.

Hepatic cavernous haemangioma is a benign tumour of vascular origin found within the liver. Often incidentally diagnosed, the management of these vascular masses is frequently determined by the size of the mass and symptoms associated with its compression of adjacent structures. Tumours >10 cm are known as giant haemangiomas and are associated with increased risks of compression symptoms, coagulopathies and haemorrhage. Known to express hormone receptors for oestrogen, intervention for these masses remains controversial in the setting of pregnancy where concerns for tumour growth and life-threatening complications are increased. Here we present the case of a woman in her 30s recently diagnosed with a giant haemangioma who is found to be pregnant, their management and a review of the literature.

The apparent virilization of the female spotted hyena raises questions about sex differences in behavior and morphology. We review these sex differences to find a mosaic of dimorphic traits, some of which conform to mammalian norms. These include space-use, dispersal behavior, sexual behavior, and parental behavior. By contrast, sex differences are reversed from mammalian norms in the hyena's aggressive behavior, social dominance, and territory defense. Androgen exposure early in development appears to enhance aggressiveness in female hyenas. Weapons, hunting behavior, and neonatal body mass do not differ between males and females, but females are slightly larger than males as adults. Sex differences in the hyena's nervous system are relatively subtle. Overall, it appears that the "masculinized" behavioral traits in female spotted hyenas are those, such as aggression, that are essential to ensuring consistent access to food; food critically limits female reproductive success in this species because female spotted hyenas have the highest energetic investment per litter of any mammalian carnivore. Evidently, natural selection has acted to modify traits related to food access, but has left intact those traits that are unrelated to acquiring food, such that they conform to patterns of sexual dimorphism in other mammals.

Our understanding of the still unfolding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic would have been extremely limited without the study of the genetics and evolution of this new human coronavirus. Large-scale genome-sequencing efforts have provided close to real-time tracking of the global spread and diversification of SARS-CoV-2 since its entry into the human population in late 2019. These data have underpinned analysis of its origins, epidemiology, and adaptations to the human population: principally immune evasion and increasing transmissibility. SARS-CoV-2, despite being a new human pathogen, was highly capable of human-to-human transmission. During its rapid spread in humans, SARS-CoV-2 has evolved independent new forms, the so-called "variants of concern," that are better optimized for human-to-human transmission. The most important adaptation of the bat coronavirus progenitor of both SARS-CoV-1 and SARS-CoV-2 for human infection (and other mammals) is the use of the angiotensin-converting enzyme 2 (ACE2) receptor. Relaxed structural constraints provide plasticity to SARS-related coronavirus spike protein permitting it to accommodate significant amino acid replacements of antigenic consequence without compromising the ability to bind to ACE2. Although the bulk of research has justifiably concentrated on the viral spike protein as the main determinant of antigenic evolution and changes in transmissibility, there is accumulating evidence for the contribution of other regions of the viral proteome to virus-host interaction. Whereas levels of community transmission of recombinants compromising genetically distinct variants are at present low, when divergent variants cocirculate, recombination between SARS-CoV-2 clades is being detected, increasing the risk that viruses with new properties emerge. Applying computational and machine learning methods to genome sequence data sets to generate experimentally verifiable predictions will serve as an early warning system for novel variant surveillance and will be important in future vaccine planning. Omicron, the latest SARS-CoV-2 variant of concern, has focused attention on step change antigenic events, "shift," as opposed to incremental "drift" changes in antigenicity. Both an increase in transmissibility and antigenic shift in Omicron led to it readily causing infections in the fully vaccinated and/or previously infected. Omicron's virulence, while reduced relative to the variant of concern it replaced, Delta, is very much premised on the past immune exposure of individuals with a clear signal that boosted vaccination protects from severe disease. Currently, SARS-CoV-2 has proven itself to be a dangerous new human respiratory pathogen with an unpredictable evolutionary capacity, leading to a risk of future variants too great not to ensure all regions of the world are screened by viral genome sequencing, protected through available and affordable vaccines, and have non-punitive strategies in place for detecting and responding to novel variants of concern.

Sex differences are commonly observed in behaviors that are closely linked to adaptive function, but sex differences can also be observed in behavioral "building blocks" such as locomotor activity and reward processing. Modern neuroscientific inquiry, in pursuit of generalizable principles of functioning across sexes, has often ignored these more subtle sex differences in behavioral building blocks that may result from differences in these behavioral building blocks. A frequent assumption is that there is a default (often male) way to perform a behavior. This approach misses fundamental drivers of individual variability within and between sexes. Incomplete behavioral descriptions of both sexes can lead to an overreliance on reduced "single-variable" readouts of complex behaviors, the design of which may be based on male-biased samples. Here, we advocate that the incorporation of new machine-learning tools for collecting and analyzing multimodal "big behavior" data allows for a more holistic and richer approach to the quantification of behavior in both sexes. These new tools make behavioral description more robust and replicable across laboratories and species, and may open up new lines of neuroscientific inquiry by facilitating the discovery of novel behavioral states. Having more accurate measures of behavioral diversity in males and females could serve as a hypothesis generator for where and when we should look in the brain for meaningful neural differences.

Mucus fishing syndrome is a chronic inflammatory ocular surface condition characterised by repetitive self-extraction of mucous strands from the eye.A man in his 30s presented with bilateral ocular redness, itch, irritation, tearing and sticky mucoid discharge for 3 months. Examination disclosed bilateral bulbar and tarsal conjunctival injection. Fluorescein staining disclosed a well-circumscribed area of tarsal conjunctival epithelial defect near the inferior lacrimal punctum in both eyes. The patient admitted to a habit of mechanically removing mucus from his eyes several times a day. Demonstration of the mucus extraction process disclosed direct contact of his fingers with the excoriated tarsal conjunctiva in each eye. He was diagnosed with mucus fishing syndrome and his condition resolved within a month after he stopped fishing mucus from his eyes and had a course of topical antibiotics and steroids.Mucus fishing syndrome is an important diagnostic consideration in patients with chronic conjunctivitis.

The analysis of main approaches to determining essence of health-improving tourism in works of national scientists and researchers is presented. The conclusions are made that the most widespread classification of health-improving tourism is its division into medical and health-improving tourism. The medical tourism includes such its types as medical and sanatorium-health resort, and health-improving tourism covers balneologic, SPA-tourism, Wellness-tourism. The difference between medical and health-improving tourism is determined in order to regulate received services. The author's structure of medical and health-improving services, types of tourism and specialized organizations is developed. The analysis of supply and demand for health-improving tourism in 2014-2020 is presented. The main trends of development of health-improving segment in context of such its directions as increasing of SPA and Wellness industry, development of medical tourism, increasing of return on health tourism are formulated. The factors constraining development and reducing competitiveness of health-improving tourism in Russia are identified and structured.

The paper is devoted to modern experimental and computational studies analysis on the point of asymmetric destruction of ice on the surfaces of the working blades of gas-turbine engine blades. A schematic diagram of an experimental setup has been developed, which consists of the following main elements: a wind tunnel, a cold chamber, a model fan, an electric motor, and a high-speed video camera. The experimental setup makes it possible to carry out laboratory studies of the ice formation and destruction processes. The choice of the experimental test rig parameters was made to allow assessing the icing of the blades of a rotating fan, which reproduces the processes occurring on gas turbine engines. Based on the results of three-dimensional gas-dynamic and strength calculations, the design and basic geometrical parameters of the flow path and the dummy fan were determined. The dependences of compression ratio Pk and the power consumption of a model fan Wcons on the value of the mass air flow Gair for a different number of rotor blades are presented. The choice of materials for the disk hub and blades of a dummy fan which experience tensile and bending loads at high rotation speeds up to 12.000 rpm was made, that satisfies the conditions of static and dynamic strength, also the allowable safety factors were evaluated, and pressure characteristics were obtained.

In the problems of technological mechanics: the manufacture of structures from composites, packaging and deployment of products from prepreg for space purposes, and others, it becomes necessary to calculate the current mechanical properties of a composite material with an incompletely cured binder. Such properties are determined primarily by the binder state, which may be described by the conversion kinetic equation. The parameters of the kinetic equation depend on many factors: temperature, diffusion, the presence of a catalytic system, modifiers, reagents, the formation of by-products of kinetic reactions, the evaporation of reagents, the effect of radiation, etc. Reliable consideration of the influence of each factor in the kinetic equation turns out to be practically impossible. Therefore, most authors use the phenomenological conversion equation based on experimental data, since these data reflect all the features of the kinetic process. We consider the first order conversion equation, which takes into account auto-acceleration and auto-deceleration. The equation parameters are determined on the basis of isothermal experimental data by the following method. The equation for the conversion rate is integrated, the integral is used to construct a system of equations containing experimental data and the desired approximation parameters, which are determined by standard mathematical methods. The dependence of the kinetic equation parameters on temperature is also constructed by approximation. Examples of constructing conversion equations for a two-component and industrial multicomponent Barnes mixture are given. It is shown that the parameters of the kinetic equation in both cases significantly depend on temperature, and for a multicomponent mixture this dependence is more complicated due to the simultaneous implementation of several reactions. Examples of using the obtained kinetic equation to calculate the curing degree of samples under a given temperature loading are given.

The paper is devoted to the numerical analysis of uniaxial loading of a sample of the mechanical metamaterial. The structure of the mechanical metamaterial is constructed of a ring and four ligaments, which make up a tetrachiral structure. The peculiarity of such a structure consists in torsion of the sample under the force load. Two methods of connecting cells in the metamaterial are considered: "adjoining" and "overlapping". The "adjoining" method of joining cells increases the thickness of the internal structure of the sample, which allows us to consider it as a topological defect of the metamaterial. The "overlapping" method saves the base material from which the tetrachiral structure is constructed. Differences in the structure when constructing a three-dimensional sample result in a significant change in the characteristics of the sample. Numerical solution of the problem is performed in a three-dimensional formulation using the finite element method. The constitutive relation describing the behavior of the model corresponds to Hooke's law. Numerical simulation of uniaxial loading made it possible to obtain the results of mechanical response and to analyze the effective properties of metamaterials. A topological defect in the form of a thickening of the internal structure elements led to a difference in the linear dimensions of the two samples. The increased thickness of the unit cell connection elements resulted in a decrease in the effective density of the metamaterial sample. The same sample showed a triple increase in the value of the elastic modulus. The greater ability to resist deformation resulted in a reduced twist effect compared to the sample whose cells were joined by the "overlapping" method. The results obtained will make it possible to program the mechanical behavior and properties of the metamaterial sample.

The article presents the results of analysis of issue of disability because of ovarian cancer in female population of the Chechen Republic. The object of study was total number of women, for the first time and repeatedly recognized as disabled ones. The analysis was applied to three age groups (the young, the middle aged and the elderly) in 2014-2020. It is established that dynamics of disability was characterized by negative trends of increasing of number of the disabled. The clear-cut age differentiation was revealed:the elderly disabled predominated. The study established that the disabled suffer of persistent malfunction of blood circulation system and of immune system that resulted in such life activity limitations as moving, self-service and work functions. The characteristics of structure of ovarian cancer disability according its severity were established. The disabled with second group of disability prevailed in all age groups. At that, percentage of women with first group of disability was higher in the middle-aged disabled. The results of the study testify actuality of optimization of onco-gynecological screening of female population for the purpose of early detection of risk factors and diagnosis of malignant process at initial stages of development. This is rational way to organ-preserving treatment and medical and social prevention of primary ovarian cancer disability. The results of the study can consider as scientific practical base for both targeted routing of preventive and therapeutic and rehabilitation measures.

The paper discusses the method of obtaining a digital passport of the material and the development of a digital twin of the product at various stages of its manufacture. The object of research is a conical mesh structure. The subject of research is the processes occurring in the product at the manufacturing stages. The following main stages of creating a mesh structure were considered in the work: 3D printing of a workpiece tooling, laying out a carbon unidirectional material, heating and impregnation of the preform with a binder, polymerization of the binder, and warpage of the product geometry. An algorithm for determining the properties of materials and their calibration using modern software and hardware and universal equipment was described. Modeling of the tooling 3D printing process was carried out in the Ansys software package. Step-by-step technological modeling of the transfer molding process was carried out using the ESI PAM-COMPOSITE software package. The result of the simulation is the optimal technological manufacturing parameters and the geometry of the shaping tooling with anticipation of warping.

To select rational parameters of the process of hybrid additive manufacturing of structures made of structural metal alloys and stainless steels, mechanical characteristics capable of serving as indicators of material quality were determined. The most advanced technologies of additive manufacturing by wire-arc surfacing (plasma, plasma arc with a melting electrode, including cold metal transfer) with layer-by-layer forging with a pneumatic impact tool and subsequent heat treatment were used. Aluminum-magnesium alloy AlMg5, titanium alloy Ti-6Al-4V, austenitic stainless steels 12Cr18Ni10Ti (AISI 321) and AISI 308LSi have been studied. Samples were cut from the blanks created by additive manufacturing – blades for standard tests for static uniaxial tension and cylinders for high-speed compression tests by the Kolsky method on a Hopkinson split bar. According to the registered and processed stress–strain curves for all materials, standard strength and ductility characteristics and the Johnson – Cook law of deformation and speed hardening were determined. For a correct assessment of the mechanical properties of additively produced materials, these tests were also carried out for each of them in the form of annealed rolled products. It is established that to compare the efficiency of various technological parameters of additive manufacturing, it is advisable to use static tensile strength and uniform elongation to rupture, having the smallest statistical variation. It was also found acceptable to approximate the Johnson – Cook law of the deformation curves of each of the studied materials according to averaged data, including various technological modes. Certain mechanical characteristics seem to be necessary for the search for effective modes of hybrid additive manufacturing and numerical calculation of various elastic-plastic problems in a dynamic formulation for the studied materials for design and technological needs.

In the deformable solid mechanics, there are concepts associated with continuum points (displacements, relative elongations, shifts) and a set of continuum points – an elementary volume (mass, energy, stresses). The role of such volume in the mechanics of composite materials is played by the representative volume element (RVE).This concept was first introduced by R. Hill (1963). Modern authors use the W.J. Drugan, J.R. Willis (1996) formulation. Based on the analysis of the RVE concept, we formulated its essential features: RVE is the minimum possible sample for numerical tests to determine the effective material parameters of the composite; under any RVE loading, its macroscopic stress-strain state is uniform. Its significance for the mechanics of composite materials is revealed: the existence of RVE for a composite is a criterion for applying the effective modulus theory to the analysis of its stress-strain state; the dehomogenization of a stressed-state composite material at a point is a solution to the micromechanics problem of the RVE stress-strain state determination; the characteristic size of RVE limits the size of the sampling grid in the numerical study. An iterative algorithm for constructing a representative volume of a periodic structure composite and its effective material thermoelastic characteristics is proposed. It is shown that the geometric shape of such a composition is a rectangular parallelepiped. The RVE construction algorithm for periodic compositions is extended to the composites statistically uniformly reinforced with continuous fibers. A method for modeling such materials with a following regular structure is suggested described: in the section perpendicular to the fibers, fiber centers should be located at the vertices of regular triangles. Examples of constructing RVE and thermoelastic material characteristics of specific compositions are given. The calculation results are compared with the data obtained using certified software products.

Introduction: Brazil has been facing the pandemic of COVID-19 since march 2020. More than 540,000 people have died from this disease in the country. Some estimates indicate that the population exposed to SARS-CoV-2 represents 1 to 20%. However, these data are questionable due to the number of asymptomatic and untested individuals. As a result, vaccination for COVID- 19 has become the main means of achieving herd immunity. Objectives: To demonstrate, through local sampling, that broad and rapid vaccination may decrease the rate of COVID-19 detection in individuals potentially exposed to the SARS-CoV-2 virus. Methods: A total of 1,128 individuals were studied, including students and health professionals from Centro Universitário FMABC, who received the two doses of the vaccine for COVID-19 (Oxford/Astrazeneca ® and CoronaVac®). Results: In the studied period, there was a 41% reduction in the demand for RT-PCR tests after vaccination. And a 78.3% reduction in positive results after vaccination started. Conclusion: The results of this study showed that even vaccinating a population with higher exposure to the risk of contamination significantly reduced test positivity and the demand to perform these tests. This emphasizes that vaccination is the best strategy to achieve herd immunity and reduce the spread of the disease.