Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigating the free radical trapping ability of NXY-059, S-PBN and PBN

The spin trapping ability of the nitrones 2,4-disulphophenyl-N-tert-butyl nitrone (NXY-059), 2-sulphophenyl-N-tert-butyl nitrone (S-PBN) and α-phenyl-N-tert-butyl nitrone (PBN) for both hydroxyl and methanol radicals was investigated using electron paramagnetic resonance (EPR) spectroscopy. The radicals of interest were generated in situ in the spectrometer under constant flow conditions in the presence of each nitrone. The spin adducts formed were detected by EPR spectroscopy. This approach allowed for quantitative comparison of the EPR spectra of the spin adducts of each nitrone. The results obtained showed that NXY-059 trapped a greater number of hydroxyl and methanol radicals than the other two nitrones, under the conditions studied.
CaM kinase Iα–induced phosphorylation of Drp1 regulates mitochondrial morphology

Mitochondria are dynamic organelles that frequently move, divide, and fuse with one another to maintain their architecture and functions. However, the signaling mechanisms involved in these processes are still not well characterized. In this study, we analyze mitochondrial dynamics and morphology in neurons. Using time-lapse imaging, we find that Ca2+ influx through voltage-dependent Ca2+ channels (VDCCs) causes a rapid halt in mitochondrial movement and induces mitochondrial fission. VDCC-associated Ca2+ signaling stimulates phosphorylation of dynamin-related protein 1 (Drp1) at serine 600 via activation of Ca2+/calmodulin-dependent protein kinase Iα (CaMKIα). In neurons and HeLa cells, phosphorylation of Drp1 at serine 600 is associated with an increase in Drp1 translocation to mitochondria, whereas in vitro, phosphorylation of Drp1 results in an increase in its affinity for Fis1. CaMKIα is a widely expressed protein kinase, suggesting that Ca2+ is likely to be functionally important in the control of mitochondrial dynamics through regulation of Drp1 phosphorylation in neurons and other cell types.
Diagnosis, management, and treatment of hepatitis C

These recommendations provide a data-supported approach. They are based on the following: (1) a formal review and analysis of the recently published world literature on the topic (Medline search); (2) the American College of Physicians’ Manual for Assessing Health Practices and Designing Practice Guidelines1 ; (3) guideline policies, including the American Association for the Study of Liver Diseases’ (AASLD) Policy on the Development and Use of Practice Guidelines and the American Gastroenterological Association’s Policy Statement on the Use of Medical Practice Guidelines2; the guideline procedures of the Infectious Diseases Society of America3; and (4) the experience of the authors in the specified topic. These recommendations are fully endorsed by the AASLD, the Infectious Diseases Society of America, and the American College of Gastroenterology. Intended for use by physicians, these recommendations suggest preferred approaches to the diagnostic, therapeutic and preventive aspects of care. They are intended to be flexible, in contrast to standards of care, which are inflexible policies to be followed in every case. Specific recommendations are based on relevant published information. In an attempt to characterize the quality of evidence supporting recommendations, the Practice Guidelines Committee of the AASLD requires a category to be assigned and reported with each recommendation (Table 1).
Bi-directional signaling strategies for dynamic TDD networks

This paper investigates several bi-directional signaling strategies to facilitate decentralized beamformer design in a dynamic time division duplexing (TDD) system. A small-cell network with multi-antenna base stations and user terminals is considered, where the cells are operating either in uplink or downlink mode depending on the instantaneous traffic demand. Decentralized beamformer design is proposed to maximize the weighted sum rate of the network subjected to individual power constraints at BSs and user terminals. The weighted sum mean-squared error (MSE) minimization framework is used to decouple the optimization problem across the nodes, which enables decentralized iterative solution. Iterative algorithms are proposed with the different bi-directional signaling schemes embedded into the TDD frame structure. A detailed signaling flow of exchanging beamformer and channel information is described for each bi-directional signaling strategy. The proposed strategies are compared with the uncoordinated system while taking into account the signaling overhead.
Oral anticoagulation management in primary care with the use of computerized decision support and near-patient testing: a randomized, controlled trial.

BACKGROUND There is increased pressure on primary care physicians to monitor oral anticoagulation. OBJECTIVE To test the null hypothesis that oral anticoagulation care can be provided at least as well in primary care through a nurse-led clinic, involving near-patient testing and computerized decision support software, compared with routine hospital management based on a variety of clinical outcome measures. METHODS A randomized, controlled trial in 12 primary care practices in Birmingham, England (9 intervention and 3 control). Two control populations were used: patients individually randomly allocated as controls in the intervention practices (intrapractice controls) and all patients in control practices (interpractice controls). Intervention practices' patients were randomized to the intervention (practice-based anticoagulation clinic) or control (hospital clinic) group. The main outcome measure was therapeutic control of the international normalized ratio. RESULTS Three hundred sixty-seven patients were recruited (122 intervention patients, 102 intrapractice control patients, and 143 interpractice control patients). Standard measures of control of the international normalized ratio (point prevalence) showed no significant difference between the intervention and control groups. Data on proportion of time spent in the international normalized ratio range showed significant improvement for patients in the intervention group (paired t test, P =.008). CONCLUSIONS Nurse-led anticoagulation clinics can be implemented in novice primary care settings by means of computerized decision support software and near-patient testing. Care given by this model is at least as good as routine hospital follow-up. The model is generalizable to primary health care centers operating in developed health care systems.
Rice Brittle culm 6 encodes a dominant-negative form of CesA protein that perturbs cellulose synthesis in secondary cell walls

The brittle culm (bc) mutants of Gramineae plants having brittle skeletal structures are valuable materials for studying secondary cell walls. In contrast to other recessive bc mutants, rice Bc6 is a semi-dominant bc mutant with easily breakable plant bodies. In this study, the Bc6 gene was cloned by positional cloning. Bc6 encodes a cellulose synthase catalytic subunit, OsCesA9, and has a missense mutation in its highly conserved region. In culms of the Bc6 mutant, the proportion of cellulose was reduced by 38%, while that of hemicellulose was increased by 34%. Introduction of the semi-dominant Bc6 mutant gene into wild-type rice significantly reduced the percentage of cellulose, causing brittle phenotypes. Transmission electron microscopy analysis revealed that Bc6 mutation reduced the cell wall thickness of sclerenchymal cells in culms. In rice expressing a reporter construct, BC6 promoter activity was detected in the culms, nodes, and flowers, and was localized primarily in xylem tissues. This expression pattern was highly similar to that of BC1, which encodes a COBRA-like protein involved in cellulose synthesis in secondary cell walls in rice. These results indicate that BC6 is a secondary cell wall-specific CesA that plays an important role in proper deposition of cellulose in the secondary cell walls.
Dimensionality of joint torques and muscle patterns for reaching

Muscle activities underlying many motor behaviors can be generated by a small number of basic activation patterns with specific features shared across movement conditions. Such low-dimensionality suggests that the central nervous system (CNS) relies on a modular organization to simplify control. However, the relationship between the dimensionality of muscle patterns and that of joint torques is not fixed, because of redundancy and non-linearity in mapping the former into the latter, and needs to be investigated. We compared the torques acting at four arm joints during fast reaching movements in different directions in the frontal and sagittal planes and the underlying muscle patterns. The dimensionality of the non-gravitational components of torques and muscle patterns in the spatial, temporal, and spatiotemporal domains was estimated by multidimensional decomposition techniques. The spatial organization of torques was captured by two or three generators, indicating that not all the available coordination patterns are employed by the CNS. A single temporal generator with a biphasic profile was identified, generalizing previous observations on a single plane. The number of spatiotemporal generators was equal to the product of the spatial and temporal dimensionalities and their organization was essentially synchronous. Muscle pattern dimensionalities were higher than torques dimensionalities but also higher than the minimum imposed by the inherent non-negativity of muscle activations. The spatiotemporal dimensionality of the muscle patterns was lower than the product of their spatial and temporal dimensionality, indicating the existence of specific asynchronous coordination patterns. Thus, the larger dimensionalities of the muscle patterns may be required for CNS to overcome the non-linearities of the musculoskeletal system and to flexibly generate endpoint trajectories with simple kinematic features using a limited number of building blocks.
A Note on Capacity Computation for the Discrete Multiple Access Channel

This paper deals with computation of the capacity region of the discrete memoryless multiple-access channel (MAC), which is equivalent to solving a difficult nonconvex optimization problem. In the literature, it is claimed that for elementary MACs, i.e., MACs for which the size of output alphabet is greater or equal to the sizes of all input alphabets, the Karush-Kuhn-Tucker conditions provide a necessary and sufficient condition for sum-rate optimality. In this paper, we demonstrate that this claim does not hold, even for two-user channels with binary input and binary output alphabets. Consequently, the capacity computation problem for the discrete MAC remains an interesting and mostly unsolved problem.
Structure, function and tissue forms of the C‐terminal globular domain of collagen XVIII containing the angiogenesis inhibitor endostatin

The C‐terminal domain NC1 of mouse collagen XVIII (38 kDa) and the shorter mouse and human endostatins (22 kDa) were prepared in recombinant form from transfected mammalian cells. The NC1 domain aggregated non‐covalently into a globular trimer which was partially cleaved by endogenous proteolysis into several monomers (25–32 kDa) related to endostatin. Endostatins were obtained in a highly soluble, monomeric form and showed a single N‐terminal sequence which, together with other data, indicated a compact folding. Endostatins and NC1 showed a comparable binding activity for the microfibrillar fibulin‐1 and fibulin‐2, and for heparin. Domain NC1, however, was a distinctly stronger ligand than endostatin for sulfatides and the basement membrane proteins laminin‐1 and perlecan. Immunological assays demonstrated endostatin epitopes on several tissue components (22–38 kDa) and in serum (120–300 ng/ml), the latter representing the smaller variants. The data indicated that the NC1 domain consists of an N‐terminal association region (∼50 residues), a central protease‐sensitive hinge region (∼70 residues) and a C‐terminal stable endostatin domain (∼180 residues). They also demonstrated that proteolytic release of endostatin can occur through several pathways, which may lead to a switch from a matrix‐associated to a more soluble endocrine form.
5-W DBR Tapered Lasers Emitting at 1060 nm With a Narrow Spectral Linewidth and a Nearly Diffraction-Limited Beam Quality

Distributed Bragg reflector tapered lasers emitting at a wavelength of about 1060 nm were realized. The expitaxial layer structure leads to a vertical far-field angle of 15deg (full-width at half-maximum). The devices with a total length of 4 mm consist of 2-mm-long ridge waveguide and tapered sections. The input currents to both sections can be independently controlled. The laser reached 5-W output power with a narrow spectral linewidth below 40 pm (95% power) and a nearly diffraction-limited beam quality.
Altered tRNA characteristics and 3′ maturation in bacterial symbionts with reduced genomes

Translational efficiency is controlled by tRNAs and other genome-encoded mechanisms. In organelles, translational processes are dramatically altered because of genome shrinkage and horizontal acquisition of gene products. The influence of genome reduction on translation in endosymbionts is largely unknown. Here, we investigate whether divergent lineages of Buchnera aphidicola, the reduced-genome bacterial endosymbiont of aphids, possess altered translational features compared with their free-living relative, Escherichia coli. Our RNAseq data support the hypothesis that translation is less optimal in Buchnera than in E. coli. We observed a specific, convergent, pattern of tRNA loss in Buchnera and other endosymbionts that have undergone genome shrinkage. Furthermore, many modified nucleoside pathways that are important for E. coli translation are lost in Buchnera. Additionally, Buchnera’s A + T compositional bias has resulted in reduced tRNA thermostability, and may have altered aminoacyl-tRNA synthetase recognition sites. Buchnera tRNA genes are shorter than those of E. coli, as the majority no longer has a genome-encoded 3' CCA; however, all the expressed, shortened tRNAs undergo 3′ CCA maturation. Moreover, expression of tRNA isoacceptors was not correlated with the usage of corresponding codons. Overall, our data suggest that endosymbiont genome evolution alters tRNA characteristics that are known to influence translational efficiency in their free-living relative.
High ferritin levels have major effects on the morphology of erythrocytes in Alzheimer's disease

Introduction: Unliganded iron both contributes to the pathology of Alzheimer's disease (AD) and also changes the morphology of erythrocytes (RBCs). We tested the hypothesis that these two facts might be linked, i.e., that the RBCs of AD individuals have a variant morphology, that might have diagnostic or prognostic value. Methods: We included a literature survey of AD and its relationships to the vascular system, followed by a laboratory study. Four different microscopy techniques were used and results statistically compared to analyze trends between high and normal serum ferritin (SF) AD individuals. Results: Light and scanning electron microscopies showed little difference between the morphologies of RBCs taken from healthy individuals and from normal SF AD individuals. By contrast, there were substantial changes in the morphology of RBCs taken from high SF AD individuals. These differences were also observed using confocal microscopy and as a significantly greater membrane stiffness (measured using force-distance curves). Conclusion: We argue that high ferritin levels may contribute to an accelerated pathology in AD. Our findings reinforce the importance of (unliganded) iron in AD, and suggest the possibility both of an early diagnosis and some means of treating or slowing down the progress of this disease.
Tankyrase 1 and Tankyrase 2 Are Essential but Redundant for Mouse Embryonic Development

Tankyrases are proteins with poly(ADP-ribose) polymerase activity. Human tankyrases post-translationally modify multiple proteins involved in processes including maintenance of telomere length, sister telomere association, and trafficking of glut4-containing vesicles. To date, however, little is known about in vivo functions for tankyrases. We recently reported that body size was significantly reduced in mice deficient for tankyrase 2, but that these mice otherwise appeared developmentally normal. In the present study, we report generation of tankyrase 1-deficient and tankyrase 1 and 2 double-deficient mice, and use of these mutant strains to systematically assess candidate functions of tankyrase 1 and tankyrase 2 in vivo. No defects were observed in development, telomere length maintenance, or cell cycle regulation in tankyrase 1 or tankyrase 2 knockout mice. In contrast to viability and normal development of mice singly deficient in either tankyrase, deficiency in both tankyrase 1 and tankyrase 2 results in embryonic lethality by day 10, indicating that there is substantial redundancy between tankyrase 1 and tankyrase 2, but that tankyrase function is essential for embryonic development.
A census of very-low-mass stars and brown dwarfs in the sigma Orionis cluster

Context. The knowledge of the initial mass function (IMF) in open clusters constitutes one way of constraining the formation of low-mass stars and brown dwarfs, along with the frequency of multiple systems and the properties of disks. Aims. The aim of the project is to determine the shape of the mass function in the low-mass and substellar regimes in the σ Orionis cluster (~3 Myr, ~352 pc, solar metallicity) as accurately as possible and compare it with the results in other clusters. Methods. We have analysed the near-infrared photometric data from the fourth data release (DR4) of the UKIRT Infrared Deep Sky Suvey (UKIDSS) Galactic clusters survey (GCS) to derive the cluster luminosity and mass functions, evaluate the extent of the cluster, and study the distribution and variability of low-mass stars and brown dwarfs down to the deuterium-burning limit. Results. We have recovered most of the previously published members and found a total of 287 candidate members within the central 30 arcmin in the 0.5–0.009 $M_{\odot}$ mass range, including new objects not previously reported in the literature. This new catalogue represents a homogeneous dataset of brown dwarf member candidates over the central 30 arcmin of the cluster. The expected photometric contamination by field objects with similar magnitudes and colours to σ Orionis members is ~15%. We present evidence of variability at the 99.5% confidence level over ~yearly timescales in 10 member candidates that exhibit signs of youth and the presence of disks. The level of variability is low ( ≤ 0.3 mag) and does not impact the derivation of the cluster luminosity and mass functions. Furthermore, we find a possible dearth of brown dwarfs within the central five arcmin of the cluster, which is not caused by a lower level of photometric sensitivity around the massive, O-type multiple star σ Ori in the GCS survey. Using state-of-the-art theoretical models, we derived the luminosity and mass functions within the central 30 arcmin from the cluster centre, with completeness down to $J = 19$ mag, corresponding to masses ranging from 0.5 $M_{\odot}$ down to the deuterium-burning mass boundary (~0.013 $M_{\odot}$). Conclusions. The mass function of σ Orionis in this mass interval shows a power law index α = 0.5 ± 0.2 (when expressed as d N /d M $\propto$ $M^{-\alpha}$), which agrees with the one derived for the 3–5 Myr cluster Upper Sco (based on similar data obtained with the GCS) in the same mass range.
A method to identify and correct problematic software activity data: exploiting capacity constraints and data redundancies

Mining software repositories to understand and improve software development is a common approach in research and practice. The operational data obtained from these repositories often do not faithfully represent the intended aspects of software development and, therefore, may jeopardize the conclusions derived from it. We propose an approach to identify problematic values based on the constraints of software development and to correct such values using data redundancies. We investigate the approach using issue and commit data of Mozilla project. In particular, we identified problematic data in four types of events and found the fraction of problematic values to exceed 10% and rapidly rising. We found the corrected values to be 50% closer to the most accurate estimate of task completion time. Finally, we found that the models of time until fix changed substantially when data were corrected, with the corrected data providing a 20% better fit. We discuss how the approach may be generalized to other types of operational data to increase fidelity of software measurement in practice and in research.
Early Activation of Caspases during T Lymphocyte Stimulation Results in Selective Substrate Cleavage in Nonapoptotic Cells

Apoptosis induced by T cell receptor (TCR) triggering in T lymphocytes involves activation of cysteine proteases of the caspase family through their proteolytic processing. Caspase-3 cleavage was also reported during T cell stimulation in the absence of apoptosis, although the physiological relevance of this response remains unclear. We show here that the caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) blocks proliferation, major histocompatibility complex class II expression, and blastic transformation during stimulation of peripheral blood lymphocytes. Moreover, T cell activation triggers the selective processing and activation of downstream caspases (caspase-3, -6, and -7), but not caspase-1, -2, or -4, as demonstrated even in intact cells using a cell-permeable fluorescent substrate. Caspase-3 processing occurs in different T cell subsets (CD4+, CD8+, CD45RA+, and CD45RO+), and in activated B lymphocytes. The pathway leading to caspase activation involves death receptors and caspase-8, which is also processed after TCR triggering, but not caspase-9, which remains as a proenzyme. Most importantly, caspase activity results in a selective substrate specificity, since poly(ADP-ribose) polymerase (PARP), lamin B, and Wee1 kinase, but not DNA fragmentation factor (DFF45) or replication factor C (RFC140), are processed. Caspase and substrate processing occur in nonapoptotic lymphocytes. Thus, caspase activation is an early and physiological response in viable, stimulated lymphocytes, and appears to be involved in early steps of lymphocyte activation.