Miracle-dz/UniFAR-FTUs huggingface dataset:
Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis.

OBJECTIVES To determine whether patients with myasthenia gravis (MG) have serum antibodies to lipoprotein-related protein 4 (LRP4), a newly identified receptor for agrin that is essential for neuromuscular junction formation, and to establish whether such antibodies contribute to MG pathogenesis. DESIGN Serum samples from patients with MG with known status of serum antibodies to the acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) and serum samples from control subjects (healthy individuals and individuals with other diseases) were tested for antibodies to LRP4. Serum samples with such antibodies were tested to determine whether they had the ability to inhibit 2 different functions of LRP4 at the neuromuscular junction. SETTING Serum samples were collected at the Hellenic Pasteur Institute and Wayne State University. Samples were tested for LRP4 autoantibodies at Georgia Health Sciences University. Other immunoreactivities of the samples were tested at the Hellenic Pasteur Institute, Athens, Greece, or processed through University Laboratories of the Detroit Medical Center, Michigan. Patients The study included 217 patients with MG, 76 patients with other neurologic or psychiatric diseases, and 45 healthy control subjects. RESULTS Anti-LRP4 antibodies were detected in 11 of 120 patients with MG without detectable anti-AChR or anti-MuSK antibodies (double seronegative) and in 1 of 36 patients without anti-AChR antibodies but with anti-MuSK antibodies, but they were not detected in any of the 61 patients with anti-AChR antibodies. No healthy control subjects and only 2 of the 76 control patients with neurologic disease had anti-LRP4 antibodies. Serum samples from patients with MG with anti-LRP4 antibodies were able to inhibit the LRP4-agrin interaction and/or alter AChR clustering in muscle cells. CONCLUSIONS Anti-LRP4 antibodies were detected in the serum of approximately 9.2% of patients with double-seronegative MG. This frequency is intermediate compared with 2 recent studies showing anti-LRP4 antibodies in 2% and 50% of patients with double-seronegative MG from different geographic locations. Together, these observations indicate that LRP4 is another autoantigen in patients with MG, and anti-LRP4 autoantibodies may be pathogenic through different immunopathogenic processes.
The Moderating Role of Severity of Service Failure in the Relationship among Regret/Disappointment, Dissatisfaction, and Behavioral Intention

ABSTRACT This study examines the moderating role of severity of service failure between emotions and dissatisfaction, as well as between dissatisfaction and behavioral intention. Results showed that when customers’ regret and disappointment are low, service failure severity has an amplifying impact on their dissatisfaction. It also demonstrates that when customers’ dissatisfaction levels are low, service failure severity plays an important role in their negative word of mouth and switching intention. Therefore, if a restaurant can reduce its number and frequency of critical service failures, then restaurant operators can dramatically enhance customers’ word of mouth testimonials and customer retention.
African American Women Making Race Work in Science, Technology, Engineering, and Math (STEM)

Dr. Geneva is an assistant professor of chemistry at an HBCU located in the Southern United States, where she was also born. Dr. Geneva’s narrative highlights how she interpreted any obstacle during her academic and professional pursuits as opportunities for growth. She also relied upon her spiritual beliefs as a source of strength and empowerment. The significant message I gleaned from Dr. Geneva’s narrative was the relevance of gender, as opposed to race, as the focal point of most of the obstacles she has overcome. Orientation. What are the highlights of your academic/career experiences? I am a fourth-generation teacher, so education is very important in my family. I have always liked math and science. It was not until my junior year in high school where I took advanced placement chemistry and met my teacher, Mrs. Pearl, who was African American and held a master’s degree [that I really started thinking of pursuing a career in chemistry]. Mrs. Pearl described to us her ability to kind of move in and out of different aspects of the chemistry field. She worked in the industry, and now she was able to teach. What intrigued me the most was that she talked about her ability to travel. It was
Low socioeconomic status as a risk factor for gestational diabetes.

All pregnant women presenting at our Department of Obstetrics and Gynecology had a routine screening test (50gr glucose) at 24-28 weeks. A positive result (1-h serum glucose > 7.8 mmol/l) was followed, 1-2 weeks later, by a 3-h OGTT with 100gr glucose, performed in the morning after an overnight fast of 8-14 h and after at least 3 days of unrestricted diet and physical activity, using cut-off values previously proposed [4] for extrapolation of the whole blood glucose values to plasma or serum glucose concentrations [5]. Gestational diabetes and IGT were diagnosed when >2 or 1 serum glucose concentrations exceeded these cut-off levels, respectively. The first consecutive 100 IGT, 150 diabetic and 450 normoglycemic women were selected for the present study. All women gave informed consent and the procedures were in accordance with the Helsinki Declaration of 1975. Socioeconomic status was assessed by education levels (primary school, high school, university) and current employment [6]. As reported in Table I, patients with the lowest level of education (primary school) were significantly younger, heavier and smaller and had more frequently previous pregnancies, parental type 2 diabetes and gestational diabetes (the frequency of IGT was not significantly different among the three groups). Their number of weekly working hours was significantly lower. Among these women 31.3% were housewives, 27.4% workwomen, 37.8% employees and 0.4% managers, whereas the corresponding percentages in graduate women were, respectively, 5.1%, 1%, 56.7% and 36.1%. Gestational diabetes was present in 31.1% of workwomen, 28% of housewives, 18.5% of employees and 10.5% of managers. The highest prevalence of gestational diabetes (38.6%) was found in housewives with primary school level of education. In a multiple logistic regression model, after adjustment for age, BMI, parental diabetes, and previous pregnancies, a higher level of education was associated with a reduced risk of gestational diabetes (OR = 0.61; 95%CI 0.4-0.9, p = 0.014), while being a workwoman (OR = 1.73; 95%CI 1.1-2.9, p = 0.032) or a housewife with primary school (OR = 1.87; 95%CI 1.1-3.2, p = 0.019) was associated with an increased risk of gestational diabetes.
The Utilization of RNA Silencing Technology to Mitigate the Voriconazole Resistance of Aspergillus Flavus; Lipofectamine-Based Delivery

Purpose: Introducing the effect of RNAi in fungi to downregulate essential genes has made it a powerful tool to investigate gene function, with potential strategies for novel disease treatments. Thus, this study is an endeavor to delve into the silencing potentials of siRNA on cyp51A and MDR1 in voriconazole-resistant Aspergillus flavus as the target genes. Methods: In this study, we designed three cyp51A-specific siRNAs and three MDR1-specific siRNAs and after the co-transfection of siRNA into Aspergillus flavus, using lipofectamine, we investigated the effect of different siRNA concentrations (5, 15, 25, 50nM) on cyp51A and MDR1 expressions by qRT-PCR. Finally, the Minimum Inhibitory Concentrations (MICs) of voriconazole for isolates were determined by broth dilution method. Results: Cyp51A siRNA induced 9, 22, 33, 40-fold reductions in cyp51A mRNA expression in a voriconazole-resistant strain following the treatment of the cells with concentrations of 5, 15, 25, 50nM siRNA, respectively. Identically, the same procedure was applied to MDR1, even though it induced 2, 3, 4, 10-fold reductions. The results demonstrated a MIC for voriconazole in the untreated group (4µg per ml), when compared to the group treated with cyp51A-specific siRNA and MDR1-specific siRNA, both at concentrations of 25 and 50nM, yielding 2µg per ml and 1µg per ml when 25 nM was applied and 2µg per ml and 0. 5µg per ml when the concentration doubled to 50 nM. Conclusion: In this study, we suggested that siRNA-mediated specific inhibition of cyp51A and MDR1 genes play roles in voriconazole-resistant A.flavus strain and these could be apt target genes for inactivation. The current study promises a bright prospect for the treatment of invasive aspergillosis through the effective deployment of RNAi and gene therapy.
Anisotropy of small-scale scalar turbulence

The anisotropy of small-scale temperature fluctuations in shear flows is analysed by making measurements in high-Reynolds-number atmospheric surface layers. A spherical harmonics representation of the moments of scalar increments is proposed, such that the isotropic part corresponds to the index j = 0 and increasing degrees of anisotropy correspond to increasing j. The parity and angular dependence of the odd moments of the scalar increments show that the moments cannot contain any isotropic part (j = 0), but can be satisfactorily represented by the lowest-order anisotropic term corresponding to j = 1. Thus, the skewnesses of scalar increments (and derivatives) are inherently anisotropic quantities, and are not suitable indicators of the tendency towards isotropy.
Lamivudine, adefovir and tenofovir exhibit long‐lasting anti‐hepatitis B virus activity in cell culture

In this work, we investigated the anti‐hepatitis B virus (HBV) activity of lamivudine, adefovir, tenofovir, penciclovir and lobucavir after short‐term (i.e. 24 or 48 h) or continuous (9 days) exposure of the HBV‐containing cell line, HepG2 2.2. 15, to these drugs. Lamivudine maintained significant anti‐HBV activity when added for only 24 or 48 h to the cell cultures compared to when the drug was present for the whole period (9 days) on the cells, i.e. 50% effective concentration (EC50) values for the inhibition of HBV DNA synthesis were 0.07 ± 0.02 μg ml−1 after 24 h of incubation, 0.02 ± 0.01 μg ml−1 after 48 h of incubation and 0.0016 ± 0.001 μg ml−1 after 9 days of incubation. Similarly, the nucleoside phosphonate analogues, adefovir and tenofovir, retained significant anti‐HBV activity when added for only a short period of time to the cells. The EC50 values were 12 ± 1 μg ml−1 (24 h) and 1.0 ± 0.2 μg ml−1 (48 h) vs 0.003 ± 0.001 μg ml−1 (9 days) for adefovir, and 6.5 ± 1.1 μg ml−1 (24 h) and 0.8 ± 0.1 μg ml−1 (48 h) vs 0.03 ± 0.02 μg ml−1 (9 days) for tenofovir. In contrast, penciclovir and lobucavir lost most of their anti‐viral activity when present on the cells for 48 h or less.
Donor genomics influence graft events: the effect of donor polymorphisms on acute rejection and chronic allograft nephropathy.

BACKGROUND Organs procured from deceased donors emanate from individuals with diverse genetic backgrounds. Donor organs, therefore, may vary in their response to injury and immune stimuli in a genetically determined manner. We assessed polymorphisms from 244 renal allograft donors to better understand the impact of donor polymorphisms on selected transplant outcomes. METHODS Donor genomic DNA restriction fragment length polymorphisms were assayed for evidence of common cytokine [interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, TGF-beta, interferon (IFN)-gamma] and chemokine (CCR2, CCR5) polymorphisms. Associations between donor polymorphisms and graft events were determined using chi-square, linear regression, and Kaplan-Meier analyses. RESULTS Several genotypic polymorphisms demonstrated a modest association with acute rejection, including the transforming growth factor (TGF)-beta T/C codon 10 (P= 0.027) and the CCR5 G/A 59029 (P= 0.039) genes by chi-square analysis. Notably, the presence of the T allele in the IFN-gamma gene (+874) demonstrated a highly significant association with biopsy-proven chronic allograft nephropathy (P < 0.008). This association remained highly significant in a multiple linear regression model that incorporated biopsy-proven acute rejection as a covariate. CONCLUSION These data suggest that many of the donor polymorphisms studied in this analysis may influence a recipient's immune response to a renal allograft. However, their greatest impact may be demonstrated in long-term outcomes.
Genome-wide scan for loci of adolescent obesity and their relationship with blood pressure.

CONTEXT Hypertension, typically considered a disorder of adulthood, is now emerging in adolescence. This is mainly due to the growing prevalence of obesity and the fact that excess body fat increases blood pressure (BP). OBJECTIVE The objective of the study was to investigate whether genome-wide identified gene loci of obesity are associated with elevated BP in adolescence. DESIGN This was a genotype-phenotype association study. SETTING The study was conducted in a French-Canadian founder population. PARTICIPANTS Participants included 598 adolescents, aged 12-18 yr. INTERVENTION Testing associations between 530,011 single-nucleotide polymorphisms (SNP; Human610W-Quad BeadChip) and obesity measures and between identified SNP and BP. PRIMARY OUTCOME MEASURES Total fat mass (TFM) was assessed with bioelectrical impedance, and body mass index (BMI) was determined with anthropometry. BP was measured beat by beat during an hour-long protocol. RESULTS The genome-wide association studies of TFM and BMI revealed two novel and several previously identified loci of obesity. The former were PAX5 (rs16933812, TFM: P = 9.3 × 10(-9)) and MRPS22 (rs7638110, BMI: P = 4.6 × 10(-8)), and the top ones among the latter (P < 5 × 10(-4)) were MC4R (rs17773430, BMI: P = 5.8 × 10(-6)), FTO (rs9930333, BMI: P = 1.9 × 10(-4)), and MTCH2 (rs7120548, BMI: P = 1.9 × 10(-4)). From these five, only the PAX5, MRPS22, and FTO were also associated with BP; their minor allele homozygotes vs. major allele homozygotes showed greater TFM by 2.9-8.0 kg and higher BP by 3.3-6.7 mm Hg. CONCLUSIONS Genome-wide association studies conducted in an adolescent founder population revealed two new and a number of previously identified loci of obesity and demonstrated that several but not all of these loci are also associated with elevated BP. These results begin to reveal the genetic architecture of obesity-induced hypertension.
Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apramycin

Aminoglycosides are potent antibacterials, but therapy is compromised by substantial toxicity causing, in particular, irreversible hearing loss. Aminoglycoside ototoxicity occurs both in a sporadic dose-dependent and in a genetically predisposed fashion. We recently have developed a mechanistic concept that postulates a key role for the mitochondrial ribosome (mitoribosome) in aminoglycoside ototoxicity. We now report on the surprising finding that apramycin, a structurally unique aminoglycoside licensed for veterinary use, shows little activity toward eukaryotic ribosomes, including hybrid ribosomes which were genetically engineered to carry the mitoribosomal aminoglycoside-susceptibility A1555G allele. In ex vivo cultures of cochlear explants and in the in vivo guinea pig model of chronic ototoxicity, apramycin causes only little hair cell damage and hearing loss but it is a potent antibacterial with good activity against a range of clinical pathogens, including multidrug-resistant Mycobacterium tuberculosis. These data provide proof of concept that antibacterial activity can be dissected from aminoglycoside ototoxicity. Together with 3D structures of apramycin-ribosome complexes at 3.5-Å resolution, our results provide a conceptual framework for further development of less toxic aminoglycosides by hypothesis-driven chemical synthesis.
Stochastic modeling of production risk and technical efficiency of Thai koi (Anabas testudineus) farming in Northern Bangladesh

ABSTRACT Thai koi is one of the high commercially valued farm fishes which have expanded tremendously in the northern part of Bangladesh. However, despite its impressive growth in the initial years, output of the industry is highly volatile across different years and farms. This research, following the Just and Pope framework, has made use of Kumbhakar’s (2002) extended stochastic frontier model (SFM) to estimate production risk and technical efficiency (TE) in Thai koi farming. Results show that feed is the most important input significantly influencing production. Zeolite and pesticide appear to be risk-reducing, while fingerlings, labor, feed and salt turn out to be risk-increasing inputs. The inefficiency model indicates that labor and pond area significantly reduce the technical inefficiency. Feed, fingerling and lime also act as TE-improving factors. Education of farmers improves TE, while experience, training and frequency of water change do not impact the TE. The mean TE scores are 0.73 and 0.96 for the flexible risk estimate and conventional SFM estimates, respectively. TE values appear to become exaggerated when production risk is excluded from the model. SFM recognizes that risk is involved in Thai koi farming that causes lower TE.
Thermal Tolerance in Widespread and Tropical Drosophila Species: Does Phenotypic Plasticity Increase with Latitude?

The distribution of insects can often be related to variation in their response to thermal extremes, which in turn may reflect differences in plastic responses or innate variation in resistance. Species with widespread distributions are expected to have evolved higher levels of plasticity than those from restricted tropical areas. This study compares adult thermal limits across five widespread species and five restricted tropical species of Drosophila from eastern Australia and investigates how these limits are affected by developmental acclimation and hardening after controlling for environmental variation and phylogeny. Irrespective of acclimation, cold resistance was higher in the widespread species. Developmental cold acclimation simulating temperate conditions extended cold limits by 2°–4°C, whereas developmental heat acclimation under simulated tropical conditions increased upper thermal limits by <1°C. The response to adult heat-hardening was weak, whereas widespread species tended to have a larger cold-hardening response that increased cold tolerance by 2°–5°C. These patterns persisted after phylogenetic correction and when flies were reared under high and low constant temperatures. The results do not support the hypothesis that widely distributed species have larger phenotypic plasticity for thermal tolerance limits, and Drosophila species distributions are therefore more closely linked to differences in innate thermal tolerance limits.
Regulators of G Protein Signaling 6 and 7

Regulators of G protein signaling (RGS) proteins that contain DEP (disheveled, EGL-10,pleckstrin) and GGL (G protein γsubunit-like) domains form a subfamily that includes the mammalian RGS proteins RGS6, RGS7, RGS9, and RGS11. We describe the cloning of RGS6 cDNA, the specificity of interaction of RGS6 and RGS7 with G protein β subunits, and certain biochemical properties of RGS6/β5 and RGS7/β5 complexes. After expression in Sf9 cells, complexes of both RGS6 and RGS7 with the Gβ5 subunit (but not Gβs 1–4) are found in the cytosol. When purified, these complexes are similar to RGS11/β5 in that they act as GTPase-activating proteins specifically toward Gαo. Unlike conventional Gβγ complexes, RGS6/β5 and RGS7/β5 do not form heterotrimeric complexes with either Gαo-GDP or Gαq-GDP. Neither RGS6/β5 nor RGS7/β5 altered the activity of adenylyl cyclases types I, II, or V, nor were they able to activate either phospholipase C-β1 or -β2. However, the RGS/β5 complexes inhibited β1γ2-mediated activation of phospholipase C-β2. RGS/β5 complexes may contribute to the selectivity of signal transduction initiated by receptors coupled to Gi and Go by binding to phospholipase C and stimulating the GTPase activity of Gαo.
HF Band Shipboard Antenna Design Using Characteristic Modes

The large wavelength of decameter wave brings a lot of practical difficulties to the design of shipboard antennas in high-frequency (HF) band. How to design conformal or even platform-embedded HF antennas raises us a new challenging topic. This paper proposes an approach to address such challenging problem through the combination of the characteristic mode (CM) theory with the structural antenna concept. 1) The CMs are solved to understand the resonant behavior of the ship platform. 2) We synthesize the radiating currents for designated radiation pattern by making use of the CMs of the ship platform. It allows the dominant radiating currents to locally distribute on the superstructure of the ship. Consequently, the superstructure becomes the main radiator. The modal solutions in CM theory ensure the efficiency of the synthesis procedure. 3) Nonprotruding slits are proposed to excite the synthesized currents. As the resultant HF shipboard antenna has no protruding elements around the ship, this design can be considered as either platform-conformal or platform-embedded. As an example, HF antenna on a realistic ship with broadside radiation pattern is designed. Simulation and experimental results on a 1:400 scale model demonstrate the effectiveness of the proposed approach in HF shipboard antenna designs.
ADAPTIVE SIZE MODIFICATION BY DOMINANT FEMALE MEERKATS

Abstract In species of cooperative insects that live in large groups, selection for increased fecundity has led to the evolution of an increased body size among female reproductives, but whether this is also true of cooperative vertebrates is unknown. Among vertebrates, morphological modification of female breeders has only been documented in a single species; in naked mole rats (Heterocephalus glaber), acquisition of alpha status is associated with a significant increase in body size through an elongation of the lumbar vertebrae. Here we provide evidence of morphological modification among breeding females of a cooperative carnivore, the meerkat (Suricata suricatta), and demonstrate that this modification is likely to be adaptive. The same female meerkats were significantly larger when they were dominant than when they were subordinate. This increased body size was not explained by differences in age, foraging efficiency, or investment in offspring care, but may have arisen, in part, through increased levels of hormone that govern bone growth. Increases in body size are likely to result in fitness benefits, for large females delivered larger litters and had heavier offspring, both of which are known to correlate positively with measures of breeding success in meerkats. Our results suggest that the acquisition of alpha status in female meerkats is associated with an adaptive increase in body size and hence that morphological modification of female vertebrates may be more widespread than has been previously supposed.