Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduced Glucose Variability With Glucose-Dependent Versus Glucose-Independent Therapies Despite Similar Glucose Control and Hypoglycemia Rates in a Randomized, Controlled Study of Older Patients With Type 2 Diabetes Mellitus

Background: Few studies have evaluated continuous glucose monitoring (CGM) in older patients with type 2 diabetes mellitus (T2DM) not using injectable therapy. CGM is useful for investigating hypoglycemia and glycemic variability, which is associated with complications in T2DM. Methods: A CGM substudy of Individualized treatMent aPproach for oldER patIents in a randomized trial in type 2 diabetes Mellitus (IMPERIUM)) was conducted. Patients were vulnerable (moderately ill and/or frail) older (≥65 years) individuals with suboptimally controlled T2DM. Strategy A comprised glucose-dependent therapies (n = 26) with a nonsulfonylurea oral antihyperglycemic medication (OAM) and a glucagon-like peptide-1 receptor agonist as the first injectable. Strategy B comprised non-glucose-dependent therapies (n = 21) with sulfonylurea as the preferred OAM and insulin glargine as the first injectable. Primary endpoints were duration and percentage of time spent with blood glucose (BG) ≤70 mg/dL over 24 hours at week 24. Results: Duration and percentage of time spent with hypoglycemia at ≤70 mg/dL were similar for Strategy A and Strategy B; glycemic control improved similarly in both arms (LSM change in HbA1c at week 24; A = −1.2%, B = −1.4%). Duration and percentage time spent with euglycemia and hyperglycemia were also similar in both arms. However, Strategy A was associated with lower within-day (21.1 ± 1.2 vs 25.1 ± 1.4, P = .046) and between-day (5.4 ± 1.0 vs 9.1 ± 1.3, P = .038) BG variability (coefficient of variance [LSM ± SE]) at week 24. Conclusions: This CGM substudy in older patients with T2DM showed lower within- and between-day BG variability with glucose-dependent therapies but similar HbA1c reductions and hypoglycemia duration with glucose-independent strategies.
EPS Current Tracking Method Research Based on Hybrid Sensitivity H∞ Control Algorithm

For electric power steering system (EPS), road interference, noise of the sensor, and the uncertainty of the steering system may make EPS control effect and the driver's road sense worse. EPS system which takes advantage of good current tracking ability, good anti-interference ability, and good operation stability is becoming more and more important in automotive research. The traditional H∞ control algorithm can solve the system uncertainty theoretically, but it cannot solve the contradiction between robustness and performance without considering the performance of the system. Therefore, this paper proposes a EPS current tracking method based on the hybrid sensitivity H∞ control algorithm, which takes the current tracking performance as one of the control objectives, so that the system can maximize the robustness and performance. Firstly, the dynamic model of EPS is established. Then, the two-degree-of-freedom vehicle model and tire model are introduced. The state space equation of the system is constructed on the basis of the system state space with random disturbance signals, the hybrid sensitivity H∞ controller is designed in the sensitivity index design, and the proposed algorithm can use weighting function to minimize the performance of the current tracking error as well as the robustness of the yaw rate error in response to robustness. Simulation analysis and experimental verification of EPS system are also carried out. The results show that the control method of the hybrid sensitivity H∞ can better achieve EPS target current tracking, effectively suppress the effect of external interference and noise, improve the system performance and robustness, ensure the driver get good road sense, and improve the system of steering stability.
Self-Distancing Reduces Probability-Weighting Biases

We have abundant evidence that people exhibit biases in weighting probability information. The current study aims to examine whether self-distancing would reduce these biases. Participants in this study were instructed to use either a self-distancing or a self-immersing strategy to regulate their reasoning when they indicated their valuations of different lotteries. The results show that, compared to the baseline group, participants in the self-distancing group exhibited less distortion in the probability-weighting function, while those in the self-immersing group exhibited more distortion. These results offer evidence for the power of self-distancing in reducing probability-weighting biases.
Multi-scale application of the N3 method for intensity correction of MR images

Spatial inhomogeneity due to the radio-frequency coil in MR imaging can confound segmentation results. In 1994, Sled introduced the N3 technique, using histogram deconvolution, for reducing inhomogeneity. We found some scans whose steep inhomogeneity gradient was not fully eliminated by N3. We created a multi-scale application of N3 that further reduces this gradient, and validated it on MNI BrainWeb and actual MRI data. The algorithm was applied to proton density simulated BrainWeb scans (with known inhomogeneity) and 100 standard MRI scans. Intra-slice and inter-slice inhomogeneity measures were created to compare the technique with standard N3. The slope of the estimated bias versus the known bias of BrainWeb data was 1.0 (r=0.9844) for N3 and 1.04 (r=0.9828) for multi-scale N3. The bias field estimated by multi-scale N3 was within 1% root-mean-square of that of standard N3. Over 100 MS patient scans, the average intra-slice measure (0 meaning bias-free) was 0.0694 (uncorrected), 0.0530 (N3) and 0.0402 (multi-scale). The average inter-slice measure (1 meaning bias-free) was 0.9121 (uncorrected), 0.9367 (N3) and 0.9508 (multi-scale). The multi-scale N3 algorithm showed a greater inhomogeneity reduction than N3 in the small percentage of scans bearing a strong gradient, and results similar to N3 in the remaining scans.
Mapping Tyrosine Kinase Receptor Dimerization to Receptor Expression and Ligand Affinities

Tyrosine kinase receptor (RTK) ligation and dimerization is a key mechanism for translating external cell stimuli into internal signaling events. This process is critical to several key cell and physiological processes, such as in angiogenesis and embryogenesis, among others. While modulating RTK activation is a promising therapeutic target, RTK signaling axes have been shown to involve complicated interactions between ligands and receptors both within and across different protein families. In angiogenesis, for example, several signaling protein families, including vascular endothelial growth factors and platelet-derived growth factors, exhibit significant cross-family interactions that can influence pathway activation. Computational approaches can provide key insight to detangle these signaling pathways but have been limited by the sparse knowledge of these cross-family interactions. Here, we present a framework for studying known and potential non-canonical interactions. We constructed generalized models of RTK ligation and dimerization for systems of two, three and four receptor types and different degrees of cross-family ligation. Across each model, we developed parameter-space maps that fully determine relative pathway activation for any set of ligand-receptor binding constants, ligand concentrations and receptor concentrations. Therefore, our generalized models serve as a powerful reference tool for predicting not only known ligand: Receptor axes but also how unknown interactions could alter signaling dimerization patterns. Accordingly, it will drive the exploration of cross-family interactions and help guide therapeutic developments across processes like cancer and cardiovascular diseases, which depend on RTK-mediated signaling.
Early Life Vitamin C Deficiency Does Not Alter Morphology of Hippocampal CA1 Pyramidal Neurons or Markers of Synaptic Plasticity in a Guinea Pig Model

Approximately 15% of the Western world population, including pregnant women and their children, is characterized as vitamin C (vitC) deficient. In guinea pigs, early life vitC deficiency causes spatial memory deficits, decreased hippocampal volume and neuron numbers, in otherwise clinically healthy animals. We hypothesized that vitC deficiency leads to decreased brain-derived neurotrophic factor and synaptic plasticity markers in selected brain areas (frontal cortex, hippocampus and striatum) and cause morphological changes in cornu ammonis 1 pyramidal neurons of the hippocampus either through a direct effect or indirectly by increased oxidative stress. Fifty-seven female guinea pigs were allocated to three groups receiving either 1390, 100 or 0–50 mg vitC/kg feed for 11 weeks. Dietary vitC levels were reflected in the plasma, cortical and adrenal gland levels, however, redox imbalance was only present in the adrenal glands allowing for the investigation of a direct influence of vitC deficiency on the chosen parameters in the brain. Synaptic plasticity markers were not affected in the investigated brain areas and no differences in isolated pyramidal neuron morphology was recorded. Based on our findings, it appears that vitC deficiency may primarily elicit impaired neuronal function through increased levels of oxidative stress.
Lipid binding attenuates channel closure of the outer membrane protein OmpF

Significance Outer-membrane porins are often considered as passive conduits of small molecules across lipid bilayers. Using native mass spectrometry experiments we identify a pH-sensitive lipid-binding mechanism of outer membrane porin F, which enables increased threading of a colicin-derived peptide through open channels. Supported by molecular dynamics simulations and channel recording experiments, we posit that this mechanism attenuates channel opening in response to changes in environmental conditions, specifically pH. These findings have important consequences for mass spectrometry experiments, wherein the role of charge is often overlooked, and they also could help provide understanding of antibiotics that gain access to Gram-negative bacteria through porin-mediated pathways. Strong interactions between lipids and proteins occur primarily through association of charged headgroups and amino acid side chains, rendering the protonation status of both partners important. Here we use native mass spectrometry to explore lipid binding as a function of charge of the outer membrane porin F (OmpF). We find that binding of anionic phosphatidylglycerol (POPG) or zwitterionic phosphatidylcholine (POPC) to OmpF is sensitive to electrospray polarity while the effects of charge are less pronounced for other proteins in outer or mitochondrial membranes: the ferripyoverdine receptor (FpvA) or the voltage-dependent anion channel (VDAC). Only marginal charge-induced differences were observed for inner membrane proteins: the ammonia channel (AmtB) or the mechanosensitive channel. To understand these different sensitivities, we performed an extensive bioinformatics analysis of membrane protein structures and found that OmpF, and to a lesser extent FpvA and VDAC, have atypically high local densities of basic and acidic residues in their lipid headgroup-binding regions. Coarse-grained molecular dynamics simulations, in mixed lipid bilayers, further implicate changes in charge by demonstrating preferential binding of anionic POPG over zwitterionic POPC to protonated OmpF, an effect not observed to the same extent for AmtB. Moreover, electrophysiology and mass-spectrometry–based ligand-binding experiments, at low pH, show that POPG can maintain OmpF channels in open conformations for extended time periods. Since the outer membrane is composed almost entirely of anionic lipopolysaccharide, with similar headgroup properties to POPG, such anionic lipid binding could prevent closure of OmpF channels, thereby increasing access of antibiotics that use porin-mediated pathways.
microRNA-494 Favors HO-1 Expression in Neuroblastoma Cells Exposed to Oxidative Stress in a Bach1-Independent Way

Heme oxygenase 1 (HO-1) is crucially involved in cell adaptation to oxidative stress and has been demonstrated to play an important role in cancer progression and resistance to therapies. We recently highlighted that undifferentiated neuroblastoma (NB) cells are prone to counteract oxidative stress through the induction of HO-1. Conversely, differentiated NB cells were more sensitive to oxidative stress since HO-1 was scarcely upregulated. In this work, we investigated the role played by miR-494, which has been proved to be involved in cancer biology and in the modulation of oxidative stress, in the upregulation of HO-1. We showed that NB differentiation downregulates miR-494 level. In addition, endogenous miR-494 inhibition in undifferentiated cells impairs HO-1 induction in response to exposure to 500 µM H2O2, reducing the number of viable cells. The analysis of Bach1 expression did not reveal any significant modifications in any experimental conditions tested, proving that the impairment of HO-1 induction observed in cells treated with miR-494 inhibitor and exposed to H2O2 is independent from Bach1. Our results underline the role played by miR-494 in favoring HO-1 induction and cell adaptation to oxidative stress and contribute to the discovery of new potential pharmacological targets to improve anticancer therapies.
iTAP, a novel iRhom interactor, controls TNF secretion by policing the stability of iRhom/TACE

The apical inflammatory cytokine TNF regulates numerous important biological processes including inflammation and cell death, and drives inflammatory diseases. TNF secretion requires ADAM17/TACE, which cleaves TNF from its transmembrane tether, releasing it for signalling. The trafficking of ADAM17/TACE to the cell surface, and stimulation of its proteolytic activity, depends on membrane proteins, called iRhoms. To delineate how the TNF/TACE/iRhom axis is regulated, we performed an immunoprecipitation/mass spectrometry screen to identify iRhom-binding proteins. Here we report a novel protein, that we name iTAP (iRhom tail-associated protein) that binds to iRhoms, enhancing the stability of iRhoms and TACE, preventing their degradation in lysosomes. iTAP-null primary human macrophages, or tissues from iTAP KO mice, are dramatically depleted in the levels of iRhom2 and active TACE, and are, consequently, profoundly impaired in TNF production. Our work illustrates iTAP as a physiological rheostat controlling TNF signalling and a novel target for the control of inflammation.
Inhibitory Projections in the Mouse Auditory Tectothalamic System

The medial geniculate body (MGB) is the target of excitatory and inhibitory inputs from several neural sources. Among these, the inferior colliculus (IC) is an important nucleus in the midbrain that acts as a nexus for auditory projections, ascending and descending, throughout the rest of the central auditory system and provides both excitatory and inhibitory inputs to the MGB. In our study, we assessed the relative contribution from presumed excitatory and inhibitory IC neurons to the MGB in mice. Using retrograde tract tracing with cholera toxin beta subunit (CTβ)-Alexa Fluor 594 injected into the MGB of transgenic, vesicular GABA transporter (VGAT)-Venus mice, we quantitatively analyzed the projections from both the ipsilateral and contralateral IC to the MGB. Our results demonstrate inhibitory projections from both ICs to the MGB that likely play a significant role in shaping auditory processing. These results complement prior studies in other species, which suggest that the inhibitory tectothalamic pathway is important in the regulation of neuronal activity in the auditory forebrain.
Some Remarks on Focus Adverbs

Much of what we have to say in the present paper should be thought of as an attempt to get a better understanding of the intricate complexities surrounding focus adverbs. To this end, we discuss a number of restrictions which govern the occurrence of different classes of focus adverbs in Dutch. German and English We are aware that in doing so we limit ourselves primarily to the descriptive level-a decision which some may well disapprove of. Indeed, when Pullum (1988) speaks of the 'slow agony of empirical endeavor', the characterizes this posiaon in the following way. 'Simply listing facts will do us no good . It it easy. It is boring. Anyone can do it. But ultimately it is useless to serious linguistic research. ' It goes without aying that we, too, completely disagree with this way of presenting the matter. When one tries to characterize focus phonemena, it is immediately clear that there are numerous lexical differences which interact in subtle ways with regular syntactic and semantic patterns. In our opinion, a linguistically interesting theory of focus should be able to account for these differential patterns. The strategy followed explicitly by Altmann (1976. 1978) and Jacobs (1983). and implicitly by many others, which is to concentrate a few common focus particles (often the words for only and even), and to hope that the rest will somehow conform to the patterns exhibited by the selected items, may lead to some initial progress, but must eventually be replaced by a more comprehensive effort. It is dangerous to rely too much on the assumed homogeneity of linguistic classes, especially in the closed-class systems. It is also important to gain a comparative perspective on focus adverbs by comparing items from different languages if a theory is to be constructed with the explanatory depth and broad empirical coverage of current theories of WH-movement or anaphoric dependencies. We give a number of examples where it is useful to compare items taken from English, German and Dutch. To summarize: this paper reviews some of the major problems which a comprehensive theory of focus adverbs needs to address, describes some of the variations to be found among focus adverbs, and places this against the background of some of the available accounts of focus adverbs.
A Thin Film Flexible Supercapacitor Based on Oblique Angle Deposited Ni/NiO Nanowire Arrays

With high power density, fast charging-discharging speed, and a long cycling life, supercapacitors are a kind of highly developed novel energy-storage device that has shown a growing performance and various unconventional shapes such as flexible, linear-type, stretchable, self-healing, etc. Here, we proposed a rational design of thin film, flexible micro-supercapacitors with in-plane interdigital electrodes, where the electrodes were fabricated using the oblique angle deposition technique to grow oblique Ni/NiO nanowire arrays directly on polyimide film. The obtained electrodes have a high specific surface area and good adhesion to the substrate compared with other in-plane micro-supercapacitors. Meanwhile, the as-fabricated micro-supercapacitors have good flexibility and satisfactory energy-storage performance, exhibiting a high specific capacity of 37.1 F/cm3, a high energy density of 5.14 mWh/cm3, a power density of up to 0.5 W/cm3, and good stability during charge-discharge cycles and repeated bending-recovery cycles, respectively. Our micro-supercapacitors can be used as ingenious energy storage devices for future portable and wearable electronic applications.
Wolbachia pipientis grows in Saccharomyces cerevisiae evoking early death of the host and deregulation of mitochondrial metabolism

Wolbachia sp. has colonized over 70% of insect species, successfully manipulating host fertility, protein expression, lifespan, and metabolism. Understanding and engineering the biochemistry and physiology of Wolbachia holds great promise for insect vector‐borne disease eradication. Wolbachia is cultured in cell lines, which have long duplication times and are difficult to manipulate and study. The yeast strain Saccharomyces cerevisiae W303 was used successfully as an artificial host for Wolbachia wAlbB. As compared to controls, infected yeast lost viability early, probably as a result of an abnormally high mitochondrial oxidative phosphorylation activity observed at late stages of growth. No respiratory chain proteins from Wolbachia were detected, while several Wolbachia F1F0‐ATPase subunits were revealed. After 5 days outside the cell, Wolbachia remained fully infective against insect cells.
Predictive polymorphisms for breast cancer in postmenopausal Mexican women

Context: Several factors contribute to the increase in breast cancer (BC) incidence, such as lifetime exposure to estrogen, early menarche and older ages at first birth, menopause, and the increased prevalence of postmenopausal obesity. In fact, there is an association between an increased BC risk and elevated estrogen levels, which may be involved in carcinogenesis via the estrogen receptor alpha (ERα) encoded by the ESR1 gene. Interestingly, there is an antagonistic relationship between ERα and the aryl hydrocarbon receptor (AhR) in BC cells. Aims: Herein, we explore the combined effects of the ESR1 (XbaI, PvuII) and AhR polymorphisms on BC development in Mexican women according to their menopausal status. Settings and Design: Investigation was performed using a cases and controls design. Subjects and Methods: In a group of 96 cases diagnosed with BC and 111 healthy women, the single-nucleotide polymorphisms ESR1 (XbaI, PvuII) and AhR gene were identified by qPCR. Statistical Analysis Used: Chi-square test or Fisher's exact test were used. Statistical analyses were conducted using the STATA statistical package (Version 10.1, STATA Corp., College Station, TX, USA). Results: The G/G XbaI genotype was more prevalent in the cases than in the controls (P = 0.008). Moreover, Mexican women carrying the XbaI (wild type [WT]/G or G/G) ESR1 genotype have higher risk (12.26-fold) for developing postmenopausal BC than individuals carrying the WT/WT genotype. Conclusions: The presence of the G/G genotype of XbaI may be considered a susceptibility allele in Mexican women. Due to increased postmenopausal BC risk, the XbaI (WT/G or G/G) alleles may be used as a postmenopausal predictive factor for BC in Mexican women.
Projected climate and agronomic implications for corn production in the Northeastern United States

Corn has been a pillar of American agriculture for decades and continues to receive much attention from the scientific community for its potential to meet the food, feed and fuel needs of a growing human population in a changing climate. By midcentury, global temperature increase is expected to exceed 2°C where local effects on heat, cold and precipitation extremes will vary. The Northeast United States is a major dairy producer, corn consumer, and is cited as the fastest warming region in the contiguous U.S. It is important to understand how key agronomic climate variables affect corn growth and development so that adaptation strategies can be tailored to local climate changes. We analyzed potential local effects of climate change on corn growth and development at three major dairy locations in the Northeast (Syracuse, New York; State College, Pennsylvania and Landisville, Pennsylvania) using downscaled projected climate data (2000–2100) from nine Global Climate Models under two emission pathways (Representative Concentration Pathways (RCP) 4.5 and 8.5). Our analysis indicates that corn near the end of the 21st century will experience fewer spring and fall freezes, faster rate of growing degree day accumulation with a reduction in time required to reach maturity, greater frequencies of daily high temperature ≥35°C during key growth stages such as silking-anthesis and greater water deficit during reproductive (R1-R6) stages. These agronomic anomalies differ between the three locations, illustrating varying impacts of climate change in the more northern regions vs. the southern regions of the Northeast. Management strategies such as shifting the planting dates based on last spring freeze and irrigation during the greatest water deficit stages (R1-R6) will partially offset the projected increase in heat and drought stress. Future research should focus on understanding the effects of global warming at local levels and determining adaptation strategies that meet local needs.