Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipophilicity of the Cystic Fibrosis Drug, Ivacaftor (VX-770), and Its Destabilizing Effect on the Major CF-causing Mutation: F508del

Deletion of phenylalanine at position 508 (F508del) in cystic fibrosis transmembrane conductance regulator (CFTR) is the most common cystic fibrosis (CF)-causing mutation. Recently, ORKAMBI, a combination therapy that includes a corrector of the processing defect of F508del-CFTR (lumacaftor or VX-809) and a potentiator of channel activity (ivacaftor or VX-770), was approved for CF patients homozygous for this mutation. However, clinical studies revealed that the effect of ORKAMBI on lung function is modest and it was proposed that this modest effect relates to a negative impact of VX-770 on the stability of F508del-CFTR. In the current studies, we showed that this negative effect of VX-770 at 10 μM correlated with its inhibitory effect on VX-809-mediated correction of the interface between the second membrane spanning domain and the first nucleotide binding domain bearing F508del. Interestingly, we found that VX-770 exerted a similar negative effect on the stability of other membrane localized solute carriers (SLC26A3, SLC26A9, and SLC6A14), suggesting that this negative effect is not specific for F508del-CFTR. We determined that the relative destabilizing effect of a panel of VX-770 derivatives on F508del-CFTR correlated with their predicted lipophilicity. Polarized total internal reflection fluorescence microscopy on a supported lipid bilayer model shows that VX-770, and not its less lipophilic derivative, increased the fluidity of and reorganized the membrane. In summary, our findings show that there is a potential for nonspecific effects of VX-770 on the lipid bilayer and suggest that this effect may account for its destabilizing effect on VX-809- rescued F508del-CFTR.
Atherosclerotic Index and Traditional Anthropometry for Predicting Carotid Intima Media Thickness in Perimenopausal/Menopausal Women.

Background Atherosclerosis is an important pathologic cause of cardiovascular disease (CVD) and a leading cause of morbidity and mortality worldwide. Menopause involves changes in hormonal status that are associated with an increased risk of developing CVD. The atherogenic index of plasma (AIP) has been used as a predictor of atherosclerosis. Atherosclerosis might also be assessed using a surrogate marker, the carotid artery wall intima media thickness (CIMT). Objective To assess the usefulness of AIP compared with traditional anthropometrics for predicting CIMT in perimenopausal and menopausal women. Material and Method This is a cross-sectional study involving perimenopausal and menopausal women voluntarily recruited. Lipid profiles, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were assessed and AIP was calculated [log (TG/HDL-C)]. The anthropometric parameters of body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR) were assessed. Pearson Chi-square for AIP and anthropometric parameters relationship to CIMT in perimenopausal and menopausal women. Results One hundred fourteen perimenopausal and menopausal women were included in this study. The novel atherosclerotic index of AIP and the anthropometric parameter of BMI were correlated with CIMT in both groups (p<0.01). There was no difference in AIP between perimenopausal and menopausal women. Neither WC nor WHR were different between the two groups. CIMT was significantly thicker in the menopausal compared with the perimenopausal group [0.78±0.16 vs. 0.64±0.09, respectively (p<0.01)]. Conclusion AIP can add significant value when assessing the risk of developing the atherosclerosis marker of thickened CIMT in perimenopausal and menopausal women. A high AIP in menopause may indicate a higher risk of cardiovascular events in spite of no difference in common CVD risk factors such as lipid profile parameters.
Human Anti-Als3p Antibodies Are Surrogate Markers of NDV-3A Vaccine Efficacy Against Recurrent Vulvovaginal Candidiasis

A Phase 1b/2a clinical trial of NDV-3A vaccine containing a Candida albicans recombinant Als3 protein formulated with alum protected women <40 years old from recurrent vulvovaginal candidiasis (RVVC). We investigated the potential use of anti-Als3p sera as surrogate marker of NDV-3A efficacy. Pre- and post-vaccination sera from subjects who experienced recurrence of vulvovaginal candidiasis (R) vs. those who were recurrence-free [non-recurrent (NR)] were evaluated. Anti-Als3p antisera obtained were evaluated for (1) titer and subclass profile and (2) their ability to influence C. albicans virulence traits including hyphal elongation, adherence to plastic, invasion of vaginal epithelial cells, biofilm formation on plastic and catheter material, and susceptibility to neutrophil killing in vitro. Serum IgG titers in NR patients were consistently higher than in R patients, particularly for anti-Als3 subclass IgG2. Sera from vaccinated NR patients reduced hyphal elongation, adhesion to plastic, invasion of vaginal epithelial cells, and biofilm formation significantly more than pre-immune sera, or sera from R- or placebo-group subjects. Pre-adsorption of sera with C. albicans germ tubes eliminated these effects, while heat inactivation did not. Finally, sera from NR subjects enhanced neutrophil-mediated killing of C. albicans relative to pre-immune sera or sera from R patients. Our results suggest that higher Als3p antibody titers are associated with protection from RVVC, attenuate C. albicans virulence, and augment immune clearance of the fungus in vitro. Thus, Als3p serum IgG antibodies are likely useful markers of efficacy in RVVC patients vaccinated with NDV-3A.
Identifying Sciaenid Critical Spawning Habitats by the Use of Passive Acoustics

Abstract Sounds produced by spawning fishes in Pamlico Sound, North Carolina, have been recorded both under captive conditions and in hydrophone and sonobuoy field surveys. These sounds, produced by males, are species specific, are associated with spawning, and are most likely used for advertisement to attract females. Sounds can be discriminated by use of spectral analysis (oscillograms and spectrograms) of recordings, and the peak frequencies produced by each species can be correlated with species and fish size. Sonobuoys were used for passive acoustic surveys, which were “sound truthed” from recordings of captive fishes to determine the timing and location of spawning sites for four species in the family Sciaenidae: Red drum Sciaenops ocellatus, spotted seatrout Cynoscion nebulosus, weakfish C. regalis, and silver perch Bairdiella chrysoura. During May-September 1998, sounds were first detected in the early evening, increased in loudness after sunset, and ended by sunrise. Weakfish and silver perch wer.
Stochastic Gradient Descent with Exponential Convergence Rates of Expected Classification Errors

We consider stochastic gradient descent and its averaging variant for binary classification problems in a reproducing kernel Hilbert space. In the traditional analysis using a consistency property of loss functions, it is known that the expected classification error converges more slowly than the expected risk even when assuming a low-noise condition on the conditional label probabilities. Consequently, the resulting rate is sublinear. Therefore, it is important to consider whether much faster convergence of the expected classification error can be achieved. In recent research, an exponential convergence rate for stochastic gradient descent was shown under a strong low-noise condition but provided theoretical analysis was limited to the squared loss function, which is somewhat inadequate for binary classification tasks. In this paper, we show an exponential convergence of the expected classification error in the final phase of the stochastic gradient descent for a wide class of differentiable convex loss functions under similar assumptions. As for the averaged stochastic gradient descent, we show that the same convergence rate holds from the early phase of training. In experiments, we verify our analyses on the $L_2$-regularized logistic regression.
Baicalin effects on rats with spinal cord injury by anti‐inflammatory and regulating the serum metabolic disorder

Baicalin had neuroprotective effects on inhibiting neuronal cell apoptosis induced by spinal cord ischemic injury. This study aimed to explore the protective effects of Baicalin on rats with spinal cord injury (SCI) and its mechanism of action. The recovery of spinal cord nerve function in rats was evaluated by the Basso, Beattie, and Bresnahan (BBB) score and the combine behavioral score (CBS). The expressions of cytokines tumor necrosis factor α (TNF‐α), interleukin‐1β (IL‐1β), and IL‐6 were detected by the enzyme‐linked immunosorbent assay method. Expressions of inflammation‐related proteins were detected by Western blot. Multivariate statistical analysis was performed for serum metabolites. The BBB and CBS score results showed that Baicalin had a certain improvement on rats with SCI. SCI symptoms were significantly improved in low‐dose and high‐dose groups. The levels of TNF‐α, IL‐1β, and IL‐6 in the SCI group were significantly increased. The expressions of NF‐κB p65, NF‐κB p50, p‐IκBα, and IKKα in the SCI group showed the opposite trend compared with the low‐dose and high‐dose groups. Compared with the sham group, glutamine, levels of 3‐OH‐butyrate, N‐acetylaspartate, and glutathione were significantly reduced, and the levels of glutamate and betaine were significantly increased in the SCI group. When Baicalin was administered, the contents of glutamine synthase (GS) and glutaminase (GLS) were significantly reduced, indicating that Baicalin had the effect of improving GS and GLS. Baicalin has protective effects on improving SCI and lower extremity motor function, has a significant anti‐inflammatory effect, and regulates the serum metabolic disorder caused by SCI in rats.
Diversity of Drought Tolerance in the Genus Vigna

Wild relatives of crop plants are thought as reservoir of prominent genetic resources for abiotic stress tolerance. However, insufficient information on genetic variation and phenotypic traits restricts their use for crop breeding. This study focused on wild species of genus Vigna (family Fabaceae) originated from highly humid to arid regions. To clarify the diversity of drought tolerance during the vegetative stage, 69 accessions, including 15 domesticated, and 54 wild accessions, were evaluated under two drought conditions of non-terminal and terminal stresses. In the non-terminal drought condition, the plants were grown in pipes of different heights where surface soil water content decreased faster in pipes with greater height. Relative shoot biomass was used for tolerance evaluation and we identified 19 drought tolerant accessions. Almost of them were wild accessions showing higher relative shoot biomass than that in the domesticated accessions. Domesticated species were mostly classified as drought susceptible but could be improved using tolerant conspecific wild ancestors with cross-compatibility. The tolerance was related with higher plant water status presumably due to small water consumption. However, the variation of drought tolerance could not be explained by simple tolerance factor alone, and other tolerance mechanisms such as deep rooting and increasing in root biomass were found in the tolerant accessions. In the terminal drought condition, the plants were grown in small pots, and the watering was stopped to expose them extreme and rapid soil water scarcity. The tolerance was evaluated as the number of days until wilting. However, the accessions found to be tolerant in the pot experiment were not the same as those in the pipe experiment. In this condition, plant water status was not related with the length of days to wilting. This indicates that different mechanisms are necessary for adaptation to each of the non-terminal and terminal drought conditions. Many accessions were tolerant to one of the conditions, although we identified that some accessions showed tolerance in both experiments. The great diversity in drought tolerance in the genus Vigna might serve to both improve crop drought tolerance and understand the mechanisms of adaptation in drought-prone environments.
Body mass index and waist circumference in early adulthood are associated with thoracolumbar spine shape at age 60-64: The Medical Research Council National Survey of Health and Development

This study investigated associations between measures of adiposity from age 36 and spine shape at 60–64 years. Thoracolumbar spine shape was characterised using statistical shape modelling on lateral dual-energy x-ray absorptiometry images of the spine from 1529 participants of the MRC National Survey of Health and Development, acquired at age 60–64. Associations of spine shape modes with: 1) contemporaneous measures of total and central adiposity (body mass index (BMI), waist circumference (WC)) and body composition (android:gynoid fat mass ratio and lean and fat mass indices, calculated as whole body (excluding the head) lean or fat mass (kg) divided by height2 (m)2); 2) changes in total and central adiposity between age 36 and 60–64 and 3) age at onset of overweight, were tested using linear regression models. Four modes described 79% of the total variance in spine shape. In men, greater lean mass index was associated with a larger lordosis whereas greater fat mass index was associated with straighter spines. Greater current BMI was associated with a more uneven curvature in men and with larger anterior-posterior (a-p) vertebral diameters in both sexes. Greater WC and fat mass index were also associated with a-p diameter in both sexes. There was no clear evidence that gains in BMI and WC during earlier stages of adulthood were associated with spine shape but younger onset of overweight was associated with a more uneven spine and greater a-p diameter. In conclusion, sagittal spine shapes had different associations with total and central adiposity; earlier onset of overweight and prior measures of WC were particularly important.
PCAS: Pruning Channels with Attention Statistics

To implement deep neural networks on small embedded devices, conventional techniques use channel pruning looking considering manual compression rate per layer to reduce parameters. Besides it is difficult to consider the relationships between layers and it takes a lot of time for deeper models. For addressing these issues, we propose a new channel pruning technique based on attention that can evaluate the importance of channels. We improved the method with the criterion to allow the automatic channel selection using a single compression rate for the entire model. Experimental results showed that a parameter reduction of 90.8% and FLOPs reduction of 79.4% was achieved with an accuracy degradation of around 1% for the compressed ResNet-50 model on the CIFAR-10 benchmark.
Feasibility of transabdominal Doppler sonography for studying uterine blood flow characteristics in cycling gilts

Summary Objective: To test for the feasibility of transabdominal Doppler sonography (color, power, pulse wave) to define uterine perfusion characteristics throughout the estrous cycle in gilts. Materials and methods: A total of 15 gilts were synchronized for estrus and scanned in their following spontaneous cycle while being restrained in a purpose-designed mobile crate. To define uterine perfusion characteristics, vessels in between and within uterine cross-sections were imaged and recorded as video sequences to be analyzed by PixelFlux® software for perfused area (Amix), blood flow velocity (vmix) and intensity (Imix) as well as resistance (RIvmix) and pulsatility index (PIvmix). Results: Color Doppler sonography proved to be the only feasible technique, as it was less affected by animal movements than power and pulse wave sonography. As determined by color Doppler sonography, all five parameters determined showed specific patterns through the estrous cycle, i. e. Amix, vmix, Imix were high in proestrus, decreased in estrus and remained low in midestrus and most parts of diestrus; RIvmix and PIvmix with inversely paralleled patterns. Conclusion and clinical relevance: This study has demonstrated that transabdominal color Doppler but not power and pulse wave Doppler sonography is feasible to be performed in crate-restrained gilts for studying uterine perfusion characteristics during the estrous cycle, and that changes of uterine perfusion over the course of the estrous cycle can be clearly followed by color Doppler sonography. Results encourage the use of color Doppler sonography for studying i. e. uterine capacity or uterus related infertility such as for cases of clinically unapparent endometritis.
Understanding and Resolving Failures in Human-Robot Interaction: Literature Review and Model Development

While substantial effort has been invested in making robots more reliable, experience demonstrates that robots operating in unstructured environments are often challenged by frequent failures. Despite this, robots have not yet reached a level of design that allows effective management of faulty or unexpected behavior by untrained users. To understand why this may be the case, an in-depth literature review was done to explore when people perceive and resolve robot failures, how robots communicate failure, how failures influence people's perceptions and feelings toward robots, and how these effects can be mitigated. Fifty-two studies were identified relating to communicating failures and their causes, the influence of failures on human-robot interaction (HRI), and mitigating failures. Since little research has been done on these topics within the HRI community, insights from the fields of human computer interaction (HCI), human factors engineering, cognitive engineering and experimental psychology are presented and discussed. Based on the literature, we developed a model of information processing for robotic failures (Robot Failure Human Information Processing, RF-HIP), that guides the discussion of our findings. The model describes the way people perceive, process, and act on failures in human robot interaction. The model includes three main parts: (1) communicating failures, (2) perception and comprehension of failures, and (3) solving failures. Each part contains several stages, all influenced by contextual considerations and mitigation strategies. Several gaps in the literature have become evident as a result of this evaluation. More focus has been given to technical failures than interaction failures. Few studies focused on human errors, on communicating failures, or the cognitive, psychological, and social determinants that impact the design of mitigation strategies. By providing the stages of human information processing, RF-HIP can be used as a tool to promote the development of user-centered failure-handling strategies for HRIs.
Reliable Diagnostics of HV Transfromers Insulation for Safety Assurance of Power Transmission System. REDIATOOL - an European Research Project

Interest is increasing in replacing the traditional way for determining moisture content in pressboard and paper in insulation of power transformers, based on chemical analyses of oil, by new methods utilising dielectric response measurements. One of the main reasons driving ahead the development of the new techniques is related to the inferior accuracy of the former methodology, especially at lower temperatures.
Self‐reported chemotherapy‐related cognitive impairment compared with cognitive complaints following menopause

Cancer‐related cognitive impairment (CRCI) is commonly reported following the administration of cancer treatment. Current longitudinal studies, primarily in women with breast cancer, suggest that up to 35% to 60% of patients exhibit persistent CRCI (pCRCI) following completion of chemotherapy. Complaints of subjective cognitive decline (SCD) are also commonly reported by women during and following the menopause transition in noncancer patients. Although the majority of evidence for cognitive difficulties in cancer patients and survivors is attributed to chemotherapy, there is growing evidence to suggest that menopausal status can also influence cognitive function in cancer patients.
Celastrol enhances Atoh1 expression in inner ear stem cells and promotes their differentiation into functional auditory neuronal-like cells

ABSTRACT We aimed to investigate the beneficial effect of Celastrol on inner ear stem cells and potential therapeutic value for hearing loss. The inner ear stem cells were isolated and characterized from utricular sensory epithelium of adult mice. The stemness was evaluated by sphere formation assay. The relative expressions of Atoh1, MAP-2 and Myosin VI were measured by RT-PCR and immunoblotting. The up-regulation of MAP-2 was also analysed with immunofluorescence. The in vitro neuronal excitability was interrogated by calcium oscillation. The electrophysiological property was determined by inward current recorded on patch clamp. Our results demonstrated that Celastrol treatment significantly improved the viability and proliferation of mouse inner ear stem cells, and facilitated sphere formation. Moreover, Celastrol stimulated differentiation of mouse inner ear stem cells to neuronal-like cells and enhanced neural excitability. Celastrol also enhanced neuronal-like cell identity in the inner ear stem cell derived neurons, as well as their electrophysiological function. Most notably, these effects were apparently associated with the upregulation of Atoh1 in response to Celastrol treatment. Celastrol showed beneficial effect on inner ear stem cells and held therapeutic promise against hearing loss.
Metabolic Power in Team Sports - Part 1: An Update

Abstract Team sports are characterised by frequent episodes of accelerated/decelerated running. The corresponding energy cost can be estimated on the basis of the biomechanical equivalence between accelerated/decelerated running on flat terrain and constant speed running uphill/downhill. This approach allows one to: (i) estimate the time course of the instantaneous metabolic power requirement of any given player and (ii) infer therefrom the overall energy expenditure of any given time window of a soccer drill or match. In the original approach, walking and running were aggregated and energetically considered as running, even if in team sports several walking periods are interspersed among running bouts. However, since the transition speed between walking and running is known for any given incline of the terrain, we describe here an approach to identify walking episodes, thus utilising the corresponding energy cost which is smaller than in running. In addition, the new algorithm also takes into account the energy expenditure against the air resistance, for both walking and running. The new approach yields overall energy expenditure values, for a whole match,≈14% smaller than the original algorithm; moreover, it shows that the energy expenditure against the air resistance is≈2% of the total.