Miracle-dz/UniFAR-FTUs huggingface dataset:
Physiological and perceptual responses to exercising in restrictive heat loss attire with use of an upper-body sauna suit in temperate and hot conditions

ABSTRACT The aim of this experiment was to quantify physiological and perceptual responses to exercise with and without restrictive heat loss attire in hot and temperate conditions. Ten moderately-trained individuals (mass; 69.44±7.50 kg, body fat; 19.7±7.6%) cycled for 30-mins (15-mins at 2 W.kg−1 then 15-mins at 1 W.kg−1) under four experimental conditions; temperate (TEMP, 22°C/45%), hot (HOT, 45°C/20%) and, temperate (TEMPSUIT, 22°C/45%) and hot (HOTSUIT, 45°C/20%) whilst wearing an upper-body “sauna suit”. Core temperature changes were higher (P<0.05) in TEMPSUIT (+1.7±0.4°C.hr−1), HOT (+1.9±0.5°C.hr−1) and HOTSUIT (+2.3±0.5°C.hr−1) than TEMP (+1.3±0.3°C.hr−1). Skin temperature was higher (P<0.05) in HOT (36.53±0.93°C) and HOTSUIT (37.68±0.68°C) than TEMP (33.50±1.77°C) and TEMPSUIT (33.41±0.70°C). Sweat rate was greater (P<0.05) in TEMPSUIT (0.89±0.24 L.hr−1), HOT (1.14±0.48 L.hr−1) and HOTSUIT (1.51±0.52 L.hr−1) than TEMP (0.56±0.27 L.hr−1). Peak heart rate was higher (P<0.05) in TEMPSUIT (155±23 b.min−1), HOT (163±18 b.min−1) and HOTSUIT (171±18 b.min−1) than TEMP (151±20 b.min−1). Thermal sensation and perceived exertion were greater (P<0.05) in TEMPSUIT (5.8±0.5 and 14±1), HOT (6.4±0.5 and 15±1) and HOTSUIT (7.1±0.5 and 16±1) than TEMP (5.3±0.5 and 14±1). Exercising in an upper-body sauna suit within temperate conditions induces a greater physiological strain and evokes larger sweat losses compared to exercising in the same conditions, without restricting heat loss. In hot conditions, wearing a sauna suit increases physiological and perceptual strain further, which may accelerate the stimuli for heat adaptation and improve HA efficiency.
CSL112, a reconstituted, infusible, plasma-derived apolipoprotein A-I: safety and tolerability profiles and implications for management in patients with myocardial infarction

ABSTRACT Introduction: The risk of major adverse cardiac events (MACE) remains elevated soon after a coronary event. High-density lipoprotein (HDL) cholesterol has been proposed as a target to reduce cardiovascular endpoints, but there is growing recognition that increasing the function of HDL may be more important than merely increasing its concentration. CSL112 is a reconstituted, infusible human plasma-derived apolipoprotein A-I (apoA-I) that increases cholesterol efflux capacity – an ex vivo measure of the ability of HDL to accept cholesterol from macrophages. Areas covered: This article reviews the pharmacology of CSL112 and its current clinical development status. Expert opinion: Clinical trials provide clear evidence that LDL cholesterol is involved in the mechanism of atherogenesis, but data for the protective role of HDL cholesterol remains inconclusive. The AEGIS-I trial suggests that the CSL112 elevates the quantity and the functionality of the apoA-I pool. The number of MACE in the AEGIS-I trial was low, but the study was not powered for efficacy. In aggregate, the favorable safety results of the AEGIS-I study encouraged the initiation of a large-scale phase 3 outcomes trial. Any benefit of CSL112, if proven on a large scale, must be weighed against the costs of the compound.
Thy1 (CD90) expression is regulated by DNA methylation during adipogenesis

The obesity epidemic is developing into the most costly health problem facing the world. Obesity, characterized by excessive adipogenesis and enlarged adipocytes, promotes morbidities such as diabetes, cardiovascular disease and cancer. Regulation of adipogenesis is critical to our understanding of how fat cell formation causes obesity and associated health problems. Thy1 (also called CD90), a widely used stem cell marker, blocks adipogenesis and reduces lipid accumulation. Thy1 knockout-mice are prone to diet-induced obesity. While the importance of Thy1 in adipogenesis and obesity is now evident, how its expression is regulated is not. We hypothesized that DNA methylation plays a role in promoting adipogenesis and affects Thy1 expression. Using the methylation inhibitor 5-aza-2’-deoxycytidine (5-aza-dC), we investigated whether DNA methylation alters Thy1 expression during adipogenesis in both mouse 3T3-L1 pre-adipocytes and mouse mesenchymal stem cells. Thy1 protein and mRNA levels were decreased dramatically during adipogenesis. However, 5-aza-dC treatment prevented this phenomenon. Pyrosequencing analysis shows that the CpG sites at the Thy1 locus are methylated during adipogenesis. These new findings highlight the potential role of Thy1 and DNA methylation in adipogenesis and obesity.
Constriction of Retinal Venules to Endothelin-1: Obligatory Roles of ETA Receptors, Extracellular Calcium Entry, and Rho Kinase

Purpose Endothelin-1 (ET-1) is a potent vasoconstrictor peptide implicated in retinal venous pathologies such as diabetic retinopathy and retinal vein occlusion. However, underlying mechanisms contributing to venular constriction remain unknown. Thus, we examined the roles of ET-1 receptors, extracellular calcium (Ca2+), L-type voltage-operated calcium channels (L-VOCCs), Rho kinase (ROCK), and protein kinase C (PKC) in ET-1-induced constriction of retinal venules. Methods Porcine retinal venules were isolated and pressurized for vasoreactivity study using videomicroscopic techniques. Protein and mRNA were analyzed using molecular tools. Results Retinal venules developed basal tone and constricted concentration-dependently to ET-1. The ETA receptor (ETAR) antagonist BQ123 abolished venular constriction to ET-1, but ETB receptor (ETBR) antagonist BQ788 had no effect on vasoconstriction. The ETBR agonist sarafotoxin S6c did not elicit vasomotor activity. In the absence of extracellular Ca2+, venules lost basal tone and ET-1–induced constriction was nearly abolished. Although L-VOCC inhibitor nifedipine also reduced basal tone and blocked vasoconstriction to L-VOCC activator Bay K8644, constriction of venules to ET-1 remained. The ROCK inhibitor H-1152 but not PKC inhibitor Gö 6983 prevented ET-1-induced vasoconstriction. Protein and mRNA expressions of ETARs and ETBRs, along with ROCK1 and ROCK2 isoforms, were detected in retinal venules. Conclusions Extracellular Ca2+ entry via L-VOCCs is essential for developing and maintaining basal tone of porcine retinal venules. ET-1 causes significant constriction of retinal venules by activating ETARs and extracellular Ca2+ entry independent of L-VOCCs. Activation of ROCK signaling, without involvement of PKC, appears to mediate venular constriction to ET-1 in the porcine retina.
Multistability of model and real dryland ecosystems through spatial self-organization

Significance Today, vast areas of drylands in semiarid climates face the dangers of desertification. To understand the driving mechanisms behind this effect, many theoretical models have been created. These models provide insight into the resilience of dryland ecosystems. However, until now, comparisons with reality were merely visual. In this article, a systematic comparison is performed using data on wavenumber, biomass, and migration speed of vegetation patterns in Somalia. In agreement with reaction–diffusion models, a wide distribution of regular pattern wavenumbers was found in the data. This highlights the potential for extrapolating predictions of those models to real ecosystems, including those that elucidate how spatial self-organization of vegetation enhances ecosystem resilience. Spatial self-organization of dryland vegetation constitutes one of the most promising indicators for an ecosystem’s proximity to desertification. This insight is based on studies of reaction–diffusion models that reproduce visual characteristics of vegetation patterns observed on aerial photographs. However, until now, the development of reliable early warning systems has been hampered by the lack of more in-depth comparisons between model predictions and real ecosystem patterns. In this paper, we combined topographical data, (remotely sensed) optical data, and in situ biomass measurements from two sites in Somalia to generate a multilevel description of dryland vegetation patterns. We performed an in-depth comparison between these observed vegetation pattern characteristics and predictions made by the extended-Klausmeier model for dryland vegetation patterning. Consistent with model predictions, we found that for a given topography, there is multistability of ecosystem states with different pattern wavenumbers. Furthermore, observations corroborated model predictions regarding the relationships between pattern wavenumber, total biomass, and maximum biomass. In contrast, model predictions regarding the role of slope angles were not corroborated by the empirical data, suggesting that inclusion of small-scale topographical heterogeneity is a promising avenue for future model development. Our findings suggest that patterned dryland ecosystems may be more resilient to environmental change than previously anticipated, but this enhanced resilience crucially depends on the adaptive capacity of vegetation patterns.
Testicular seminoma in the aged rat visualized by phase-contrast X-ray computed tomography

Spontaneously growing testicular seminoma in the aged rat was imaged by one of the most sensitive imaging modalities, namely, phase-contrast X-ray computed tomography (CT) with crystal X-ray interferometry. Phase-contrast X-ray CT clearly depicted the detailed inner structures of the tumor and provided 20× magnified images compared to light-microscopic images. Phase-contrast X-ray CT images are generated based on density variations in the object, whereas pathological images are based on differentiation of cellular structures, such as the cellular nuclei and cytoplasm. The mechanism of image generation differs between the two techniques: phase-contrast X-ray CT detects even minute differences in the density among pathological structures, depending, for example, on the number and sizes of the nuclei, variations of the cytoplasmic components, and presence/absence of fibrous septa, cystic changes, and hemorrhage. Thus, phase-contrast X-ray CT with a spatial resolution of 26 µm might allow prediction of the morphological characteristics of a tumor even before histopathological processing.
Bacterial Survivor: An Interactive Game that Combats Misconceptions about Antibiotic Resistance

The growing threat of antibiotic resistant infections remains a huge public health concern. While many people are aware of “superbugs”, the vast majority of the general public does not understand how antibiotic resistance arises in a population of bacteria, and how exactly over use or misuse of antibiotics contributes to this problem. We developed an active learning exercise called “Bacterial Survivor” in order to combat misconceptions about antibiotic resistance in a large undergraduate non-majors microbiology course. The game models the random nature of genetic change, the impact of environment on survival, and illustrates the basic principles of evolution. This hands-on approach has been effective in counteracting student misconceptions about this important topic.
Chemical pharmacotherapy for the treatment of orthostatic hypotension

ABSTRACT Introduction: Orthostatic hypotension (OH) is a common yet often overlooked condition. Particularly debilitating is neurogenic orthostatic hypotension (nOH) caused by deficient neurotransmission of norepinephrine, which is the primary neurotransmitter released at sympathetic peripheral vascular nerve terminals in response to orthostatic stress. Areas covered: In this review, the author summarizes and critiques established and emerging pharmacologic approaches for the management of nOH. Two drugs are currently approved. Midodrine, an α1-adrenoreceptor agonist, acts on capacitance vessels to increase peripheral vascular tone, thus increases arterial pressure. Droxidopa, an orally administered prodrug of norepinephrine, increases circulating norepinephrine levels, causes peripheral vasoconstriction, and increases standing blood pressure. Preliminary studies support the selective use of several off-label drugs in difficult cases. All of these drugs can potentially unmask or exacerbate neurogenic supine hypertension (nSH), which occurs in about half of patients with nOH. Expert opinion: Chemical pharmacotherapy of nOH is best individualized to the needs and condition of each patient and guided by the underlying pathophysiology, severity of orthostatic incapacity, and minimization of comorbidities such as nSH. The goal of therapy is to maintain cerebral perfusion and increase the patient’s ability to engage in upright daily activities. Advances in pharmacogenetics and ambulatory devices hold promise.
Version 3 of the National Alzheimer’s Coordinating Center’s Uniform Data Set

Introduction: In 2015, the US Alzheimer’s Disease Centers (ADC) implemented Version 3 of the Uniform Data Set (UDS). This paper describes the history of Version 3 development and the UDS data that are freely available to researchers. Methods: UDS Version 3 was developed after years of coordination between the National Institute on Aging-appointed Clinical Task Force (CTF), clinicians from ∼30 ADCs, and the National Alzheimer’s Coordinating Center (NACC). The CTF recognized the need for updates to align with the state of the science in dementia research, while being flexible to the diverse needs and diseases studied at the ADCs. Version 3 also developed a nonproprietary neuropsychological battery. Results: This paper focuses on the substantial Version 3 changes to the UDS forms related to clinical diagnosis and characterization of clinical symptoms to match updated consensus-based diagnostic criteria. Between March 2015 and March 2018, 4820 participants were enrolled using UDS Version 3. Longitudinal data were available for 25,337 of the 37,568 total participants using all UDS versions. Discussion: The results from utilization of the UDS highlight the possibility for numerous research institutions to successfully collaborate, produce, and use standardized data collection instruments for over a decade.
Impaired hematopoiesis and leukemia development in mice with a conditional knock-in allele of a mutant splicing factor gene U2af1

Significance Somatic mutations in some splicing factor genes are frequently found in myelodysplastic syndromes (MDS) and MDS-related acute myeloid leukemia (AML), blood cancers with few effective treatment options. However, the pathophysiological effects of these mutations remain poorly characterized. Here, we report the establishment of mouse models to study a common splicing factor mutation, U2AF1(S34F). Production of the mutant protein in the murine hematopoietic compartment disrupts hematopoiesis in ways resembling human MDS. We further identified deletion of the Runx1 gene and other known oncogenic mutations as changes that might collaborate with U2af1(S34F) to give rise to frank AML in mice. However, the U2af1(S34F) mutation was absent in two of the three AML cases, raising the possibility that this mutant protein plays a dispensable role in tumor maintenance. Mutations affecting the spliceosomal protein U2AF1 are commonly found in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML). We have generated mice that carry Cre-dependent knock-in alleles of U2af1(S34F), the murine version of the most common mutant allele of U2AF1 encountered in human cancers. Cre-mediated recombination in murine hematopoietic lineages caused changes in RNA splicing, as well as multilineage cytopenia, macrocytic anemia, decreased hematopoietic stem and progenitor cells, low-grade dysplasias, and impaired transplantability, but without lifespan shortening or leukemia development. In an attempt to identify U2af1(S34F)-cooperating changes that promote leukemogenesis, we combined U2af1(S34F) with Runx1 deficiency in mice and further treated the mice with a mutagen, N-ethyl-N-nitrosourea (ENU). Overall, 3 of 16 ENU-treated compound transgenic mice developed AML. However, AML did not arise in mice with other genotypes or without ENU treatment. Sequencing DNA from the three AMLs revealed somatic mutations homologous to those considered to be drivers of human AML, including predicted loss- or gain-of-function mutations in Tet2, Gata2, Idh1, and Ikzf1. However, the engineered U2af1(S34F) missense mutation reverted to WT in two of the three AML cases, implying that U2af1(S34F) is dispensable, or even selected against, once leukemia is established.
Gestational age and socioeconomic status as mediators for the impact of prenatal alcohol exposure on development at 6 months

Of the many negative outcomes associated with gestational alcohol use, one that has received relatively little attention is preterm birth and its possible contribution to effects of prenatal alcohol exposure (PAE) on development. To examine the increased risk for premature delivery associated with PAE and the joint influence of preterm birth and alcohol on child outcomes, analysis was carried out in a longitudinal cohort recruited in Western Ukraine.
Automated Machine Learning: From Principles to Practices

Machine learning (ML) methods have been developing rapidly, but configuring and selecting proper methods to achieve a desired performance is increasingly difficult and tedious. To address this challenge, automated machine learning (AutoML) has emerged, which aims to generate satisfactory ML configurations for given tasks in a data-driven way. In this paper, we provide a comprehensive survey on this topic. We begin with the formal definition of AutoML and then introduce its principles, including the bi-level learning objective, the learning strategy, and the theoretical interpretation. Then, we summarize the AutoML practices by setting up the taxonomy of existing works based on three main factors: the search space, the search algorithm, and the evaluation strategy. Each category is also explained with the representative methods. Then, we illustrate the principles and practices with exemplary applications from configuring ML pipeline, one-shot neural architecture search, and integration with foundation models. Finally, we highlight the emerging directions of AutoML and conclude the survey.
A bacterial DNA repair pathway specific to a natural antibiotic

All organisms possess several DNA repair pathways to maintain the integrity of their genetic material. Although there are several DNA repair pathways that are well understood, we recently identified several genes in Bacillus subtilis that are important for surviving treatment with drugs that damage DNA. Here, we report a drug specific DNA repair pathway in B. subtilis. We identified genes coding for a previously uncharacterized helicase and exonuclease, mrfA and mrfB, respectively. Deletion of mrfA and mrfB resulted in sensitivity to the DNA damaging agent mitomycin C, but not other types of DNA damage. We found that MrfAB operate independently of canonical nucleotide excision repair, forming a novel excision repair pathway in bacteria. A phylogenetic analysis demonstrates that MrfAB homologs are present in diverse bacterial phyla, and a cross-complementation assay shows that MrfAB function is conserved in closely related species. Mitomycin C is a natural antibiotic that is produced by the soil dwelling bacterium Streptomyces lavendulae, and B. subtilis is also a soil dwelling organism. The specificity of the ΔmrfAB phenotype suggests that MrfAB have been adapted as a countermeasure to mitomycin producing bacteria. Abbreviated Summary Bacteria possess DNA repair pathways to maintain the integrity of their genetic material. The helicase MrfA and the exonuclease MrfB are part of a mitomycin C specific DNA repair pathway in Bacillus subtilis. Despite being present in many bacterial species, MrfAB activity in repairing MMC damaged DNA appears to be restricted to closely related species, suggesting that these proteins have likely been adapted to the specific needs of each bacterium.
Fast 3D Modeling with Approximated Convolutional Kernels

This paper introduces a novel regression methodology for 3D reconstruction, with applications in robotics tasks such as terrain modeling and implicit surface calculation. The proposed methodology is based on projections into a high-dimensional space, that is able to fit arbitrarily complex data as a continuous function using a series of kernel evaluations within a linear regression model. We avoid direct kernel calculation by employing a novel sparse random Fourier feature vector, that approximates any shift-invariant kernel as a series of dot products relative to a set of inducing points placed throughout the input space. The varying properties of these inducing points produce non-stationarity in the resulting model, and can be jointly learned alongside linear regression weights. Furthermore, we show how convolution with arbitrary kernels can be performed directly in this highdimensional continuous space, by training a neural network to learn the Fourier transform of the convolutional output based on information from the input kernels. Experimental results in terrain modeling and implicit surface calculation show that the proposed framework is able to outperform similar techniques in terms of computational speed without sacrificing accuracy, while enabling efficient convolution with arbitrary kernels for tasks such as global localization and template matching within these applications.
CacheLight: Defeating the CacheKit Attack

To protect software systems from attacks, ARM introduced a hardware security extension known as TrustZone. TrustZone provides an isolated execution environment, which can be used to deploy various memory integrity and malware detection tools. However, a new type of rootkit, namely CacheKit, can exploit cache incoherency and cache locking mechanisms in TrustZone to hide itself from such inspections. Therefore, it is imperative to design a new approach to ensure the correct use of cache locking and prevent malicious code from being hidden in the cache. In this paper, we present CacheLight, which leverages the TrustZone and Virtualization extensions of the ARM architecture to allow the system to continue to securely provide these hardware facilities to users while preventing attackers from exploiting them. CacheLight restricts the ability to lock the cache to the Secure World of the processor such that the Normal World can still request certain memory to be locked into the cache by the secure operating system (OS) through a Secure Monitor Call (SMC). This grants the secure OS the power to verify and validate the information that will be locked in the requested cache way thereby ensuring that any data that remains in the cache will not be inconsistent with what exists in main memory for inspection. Malicious attempts to hide data can be prevented and recovered for analysis while legitimate requests can still generate valid entries in the cache.