Miracle-dz/UniFAR-FTUs huggingface dataset:
Controlling for Intra-Subject and Inter-Subject Variability in Individual-Specific Cortical Network Parcellations

Resting-state functional magnetic resonance imaging (rs-fMRI) offers the opportunity to noninvasively study brain networks within individuals. Previous individual-specific network mappings do not account for intra-subject (within-subject) variability. Therefore, intrasubject variability might be mistaken for inter-subject (between-subject) differences. Here we propose a multi-session hierarchical Bayesian model (MS-HBM) that explicitly differentiates between intra-subject and inter-subject functional connectivity variability, as well as intersubject network spatial variability. Across three datasets, sensory-motor networks exhibited lower inter-subject, but higher intra-subject variability than association networks. Compared with other approaches, MS-HBM parcellations generalized better to new rs-fMRI and taskfMRI data. MS-HBM parcellations from a single rs-fMRI session were comparable to a recent template-matching algorithm using five sessions. Individual-specific MS-HBM cortical parcellations were highly reproducible, while capturing inter-subject network differences. Inter-subject differences in the spatial arrangement of cortical networks could predict individuals’ cognition, personality and emotion, thus highlighting the importance of examining individual-specific network spatial configuration in rs-fMRI studies. CC-BY 4.0 International license not peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was . http://dx.doi. org/10.1101/213041 doi: bioRxiv preprint first posted online Nov. 2, 2017;
GAD65 Autoantibody Responses in Japanese Latent Autoimmune Diabetes in Adult Patients

OBJECTIVE—To determine whether development of insulin requirement in patients with latent autoimmune diabetes in adults (LADA) is accompanied with the emergence of a type 1 diabetes–like autoimmune response. RESEARCH DESIGN AND METHODS—We correlated β-cell–specific autoimmunity reflected in autoantibodies to the 65-kDa isoform of GAD (GAD65) with insulin requirement. We determined GAD65Ab epitope specificities in type 1 diabetic patients, LADA patients without insulin requirement (nonprogressed), and LADA patients that had developed insulin requirement (progressed). RESULTS—Recognition of a type 1 diabetes–specific GAD65Ab epitope was more pronounced in type 1 diabetic patients than in nonprogressed (P < 0.001) or progressed (P < 0.01) LADA patients, with no significant differences between the two LADA cohorts. These differences were particularly pronounced in samples with GAD65Ab titers <1,000 units/ml, with no differences in epitope specificities in samples with higher GAD65Ab titers. Disease duration (initial diabetes diagnosis until sample collection or development of insulin requirement) in nonprogressed and progressed LADA patients, respectively, was not correlated with epitope specificity, suggesting lack of epitope maturation. This was supported by epitope analyses of longitudinal samples from LADA patients during progression to insulin requirement. CONCLUSIONS—First, the GAD65Ab-specific autoimmune reaction in type 1 diabetic patients with low and moderate GAD65Ab titers differs from that in LADA patients, irrespective of insulin requirement. Second, the GAD65Ab-specific autoimmune response in LADA patients does not change after their initial diabetes diagnosis. Finally, LADA patients with high GAD65Ab titers resemble type 1 diabetic patients in their GAD65Ab epitope specificity.
Australian Nurse Practitioner Practice: Value Adding through Clinical Reflexivity

The role of the Australian Nurse Practitioner (NP) is in its infancy and at a crossroads where extensive research demonstrates effective quality care and yet the role remains underrecognised and underutilised. The translation of practice into “value” is critical for the sustainability of NP roles and requires the practitioner to adopt a systematic method of inquiry. Kim's (1999) “Critical Reflective Inquiry” (CRI) method was adapted by two Australian NPs who specialise in diabetes and chronic disease management. Kim highlights the intent of CRI as understanding the meaning of practice, delivering improvements to practice through self-reflection, and the critique of practice that can lead to practice changes and development of new models of care translated to “products” of value. Based on the thematically analysis of 3 years of CRI application, the authors formed 5 headings that represented the NP's practice as Specialised Care Access, Complications and Diagnostics Interventions, Pharmaceutical Treatment, Vulnerable Populations, and Leadership. The utility of CRI demonstrates how NP practice is integral to a continuous cycle of addressing health care services gaps, and the conversion of “products” into “value” and positions the NP to assimilate the role of the practitioner-researcher.
Predataxis behavior in Myxococcus xanthus

Spatial organization of cells is important for both multicellular development and tactic responses to a changing environment. We find that the social bacterium, Myxococcus xanthus utilizes a chemotaxis (Che)-like pathway to regulate multicellular rippling during predation of other microbial species. Tracking of GFP-labeled cells indicates directed movement of M. xanthus cells during the formation of rippling wave structures. Quantitative analysis of rippling indicates that ripple wavelength is adaptable and dependent on prey cell availability. Methylation of the receptor, FrzCD is required for this adaptation: a frzF methyltransferase mutant is unable to construct ripples, whereas a frzG methylesterase mutant forms numerous, tightly packed ripples. Both the frzF and frzG mutant strains are defective in directing cell movement through prey colonies. These data indicate that the transition to an organized multicellular state during predation in M. xanthus relies on the tactic behavior of individual cells, mediated by a Che-like signal transduction pathway.
Identification of Novel SNP in Promoter Sequence of TaGW2-6A Associated with Grain Weight and Other Agronomic Traits in Wheat (Triticum aestivum L.)

TaGW2 is an orthologue of rice gene OsGW2, which encodes E3 RING ubiquitin ligase and controls the grain size in rice. In wheat, three copies of TaGW2 have been identified and mapped on wheat homoeologous group 6 viz. TaGW2-6A, TaGW2-6B and TaGW2-6D. In the present study, using as many as 207 Indian wheat genotypes, we identified four SNPs including two novel SNPs (SNP-988 and SNP-494) in the promoter sequence of TaGW2-6A. All the four SNPs were G/A or A/G substitutions (transitions). Out of the four SNPs, SNP-494 was causal, since it was found associated with grain weight. The mean TGW (41.1 g) of genotypes with the allele SNP-494_A was significantly higher than mean TGW (38.6 g) of genotypes with the allele SNP-494_G. SNP-494 also regulates the expression of TaGW2-6A so that the wheat genotypes with SNP-494_G have higher expression and lower TGW and the genotypes with SNP-494_A have lower expression but higher TGW. Besides, SNP-494 was also found associated with grain length-width ratio, awn length, spike length, grain protein content, peduncle length and plant height. This suggested that gene TaGW2-6A not only controls grain size, but also controls other agronomic traits. In the promoter region, SNP-494 was present in ‘CGCG’ motif that plays an important role in Ca2+/calmodulin mediated regulation of genes. A user-friendly CAPS marker was also developed to identify the desirable allele of causal SNP (SNP-494) for use in marker-assisted selection for improvement of grain weight in wheat. Using four SNPs, five haplotypes were identified; of these, Hap_5 (G_A_G_A) was found to be a desirable haplotype having significantly higher grain weight (41.13g) relative to other four haplotypes (36.33-39.16 g).
The Impact of Caching on BitTorrent-Like Peer-to-Peer Systems

Peer-to-peer file-sharing systems are responsible for a significant share of the traffic between Internet service providers (ISPs) in the Internet. In order to decrease their peer-to-peer related transit traffic costs, many ISPs have deployed caches for peer-to-peer traffic in recent years. We consider how the different types of peer-to-peer caches - caches already available on the market and caches expected to become available in the future - can possibly affect the amount of inter-ISP traffic. We develop a fluid model that captures the effects of the caches on the system dynamics of peer-to-peer networks, and show that caches can have adverse effects on the system dynamics depending on the system parameters. We combine the fluid model with a simple model of inter-ISP traffic and show that the impact of caches cannot be accurately assessed without considering the effects of the caches on the system dynamics. We identify scenarios when caching actually leads to increased transit traffic. Our analytical results are supported by extensive simulations and experiments with real BitTorrent clients.
Concomitant Targeting of TumorCells and Induction of T-cell Response Synergizes to Effectively Inhibit Trastuzumab- Resistant Breast Cancer

Trastuzumab is an iconic rationally designed targeted therapy for HER2-positive breast cancers. However, the low response rate and development of resistance call for novel approaches for the treatment of patients. Here, we report that concurrent targeting of tumor cells and activation of T cells in the tumor microenvironment results in a synergistic inhibitory effect on tumor growth and overcomes resistance in two distinct PTEN loss–mediated trastuzumab-resistant mammary tumor mouse models. In vivo combination treatment with HER2/Neu antibody and Akt inhibitor triciribine effectively inhibited tumor growth in both models via inhibiting PI3K/AKT and mitogen-activated protein kinase signaling accompanied by increased T-cell infiltration in the tumor microenvironment. We showed that both CD8þ and CD4þ T cells were essential to the optimal antitumor effect of this combination treatment in an IFNg–dependent manner. Importantly, the antitumor activities of HER2/Neu antibody and triciribine combination treatment were further improved when coinhibitory receptor cytotoxic T-lymphocyte–associated antigen 4 was blocked to enhance the T-cell response. Our data indicate that multitargeted combinatorial therapies targeting tumor cells and concomitantly enhancing T-cell response in the tumor microenvironment could cooperate to exert maximal therapeutic activity, suggesting a promising clinical strategy for treating trastuzumab-resistant breast cancers and other advanced malignancies. Cancer Res; 72(17); 1–12. 2012 AACR.
Transcriptional AutoRegulation of RUNX 1 P 1 Promoter

RUNX1 a member of the family of runt related transcription factors (RUNX), is essential for hematopoiesis. The expression of RUNX1 gene is controlled by two promoters; the distal P1 promoter and the proximal P2 promoter. Several isoforms of RUNX1 mRNA are generated through the use of both promoters and alternative splicing. These isoforms not only differs in their temporal expression pattern but also exhibit differences in tissue specificity. The RUNX1 isoforms derived from P2 are expressed in a variety of tissues, but expression of P1-derived isoform is restricted to cells of hematopoietic lineage. However, the control of hematopoietic-cell specific expression is poorly understood. Here we report regulation of P1-derived RUNX1 mRNA by RUNX1 protein. In silico analysis of P1 promoter revealed presence of two evolutionary conserved RUNXmotifs, 0.6kb upstream of the transcription start site, and three RUNXmotifs within 170bp of the 5’UTR. Transcriptional contribution of these RUNX motifs was studied in myeloid and T-cells. RUNX1 genomic fragment containing all sites show very low basal activity in both cell types. Mutation or deletion of RUNX motifs in the UTR enhances basal activity of the RUNX1 promoter. Chromatin immunoprecipitation revealed that RUNX1 protein is recruited to these sites. Overexpression of RUNX1 in non-hematopoietic cells results in a dose dependent activation of the RUNX1 P1 promoter. We also demonstrate that RUNX1 protein regulates transcription of endogenous RUNX1 mRNA in T-cell. Finally we show that SCL transcription factor is recruited to regions containing RUNXmotifs in the promoter and the UTR and regulates activity of the RUNX1 P1 promoter in vitro. Thus, multiple lines of evidence show that RUNX1 protein regulates its own gene transcription. PLOS ONE | DOI:10.1371/journal.pone. 0149119 February 22, 2016 1 / 17 a11111
Stress corrosion cracking of high-strength steels

Abstract The mechanisms of stress corrosion cracking (SCC) and hydrogen embrittlement were recently reviewed by Lynch in this journal. The present review, in contrast, focuses on the rate-limiting step of the SCC of low-alloy high-strength steels in water and particularly focuses on the influence of the applied stress rate on the SCC of low-alloy high-strength steels. Linearly increasing stress tests of low-alloy high-strength steels in distilled water indicated that the stress corrosion crack velocity increased with increasing applied stress rate until the maximum crack velocity, corresponding to vII in fracture mechanics tests in distilled water. Moreover, the crack velocity was dependent only on the applied stress rate and was not influenced by the steel composition. The rate-limiting step could be the rupture of a surface film, which would control the rate of metal dissolution and/or the production and transport of hydrogen to the crack tip or to the regions ahead of the crack tip.
Descending Corticospinal Control of Intersegmental Dynamics

To make an accurate movement, the CNS has to overcome the inherent complexities of the multijoint limb. For example, interaction torques arise when motion of individual arm segments propagates to adjacent segments causing their movement without any muscle contractions. Since these passive joint torques significantly add to the overall torques generated by active muscular contractions, they must be taken into account during planning or execution of goal-directed movements. We investigated the role of the corticospinal tract in compensating for the interaction torques during arm movements in humans. Twelve subjects reached to visual targets with their arm supported by a robotic exoskeleton. Reaching to one target was accompanied by interaction torques that assisted the movement, while reaching to the other target was accompanied by interaction torques that resisted the movement. Corticospinal excitability was assessed at different times during movement using single-pulse transcranial magnetic stimulation (TMS) over the upper-arm region of M1 (primary motor cortex). We found that TMS responses in shoulder monoarticular and elbow–shoulder biarticular muscles changed together with the interaction torques during movements in which the interaction torques were resistive. In contrast, TMS responses did not correlate with assistive interaction torques or with co-contraction. This suggests that the descending motor command includes compensation for passive limb dynamics. Furthermore, our results suggest that compensation for interaction torques involves the biarticular muscles, which span both shoulder and elbow joints and are in a biomechanically advantageous position to provide such compensation.
Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia.

BACKGROUND Eltrombopag is an oral thrombopoietin-receptor agonist. This study evaluated the efficacy of eltrombopag for increasing platelet counts and reducing the need for platelet transfusions in patients with thrombocytopenia and chronic liver disease who are undergoing an elective invasive procedure. METHODS We randomly assigned 292 patients with chronic liver disease of diverse causes and platelet counts of less than 50,000 per cubic millimeter to receive eltrombopag, at a dose of 75 mg daily, or placebo for 14 days before a planned elective invasive procedure that was performed within 5 days after the last dose. The primary end point was the avoidance of a platelet transfusion before, during, and up to 7 days after the procedure. A key secondary end point was the occurrence of bleeding (World Health Organization [WHO] grade 2 or higher) during this period. RESULTS A platelet transfusion was avoided in 104 of 145 patients who received eltrombopag (72%) and in 28 of 147 who received placebo (19%) (P<0.001). No significant difference between the eltrombopag and placebo groups was observed in bleeding episodes of WHO grade 2 or higher, which were reported in 17% and 23% of patients, respectively. Thrombotic events of the portal venous system were observed in 6 patients who received eltrombopag, as compared with 1 who received placebo, resulting in the early termination of the study. The incidence and severity of other adverse events were similar in the eltrombopag and placebo groups. CONCLUSIONS Eltrombopag reduced the need for platelet transfusions in patients with chronic liver disease who were undergoing elective invasive procedures, but it was associated with an increased incidence of portal-vein thrombosis, as compared with placebo. (Funded by GlaxoSmithKline; ELEVATE ClinicalTrials.gov number, NCT00678587.).
Effects of hypoxia‐ischemia on monoamine metabolism in the immature brain

We measured acute changes in monoamine metabolites in corpus striatum of immature rat pups exposed to hypoxiaischemia, hypoxia alone, or total global ischemia. Carotid ligations and two hours of 8% oxygen environment in 7‐day‐old pups led to asymmetrical turning behavior, a 70% decrease in endogenous striatal dopamine levels, and a 125% increase in homovanillic acid (HVA) concentrations on the side of ligation. In contrast, hypoxia alone and total global ischemia alone were not associated with HVA level elevation. Elevation of HVA level with hypoxia‐ischemia showed a threshold effect between 1 and 1.5 hours, and this time course paralleled that for production of gross morphological changes in rats raised to maturity. The data suggest that dopamine release from striatal nerve terminals is associated with events causing brain injury during perinatal hypoxia‐ischemia. Tissue HVA in the animal model appears to be a quantitative marker for the effects of the insult on a population of nerve terminals.
Structural Characterization of the Intermolecular Interactions of Synapse-associated Protein-97 with the NR2B Subunit of N-Methyl-d-aspartate Receptors*

The synapse-associated protein-97 (SAP97) is important in the proper trafficking and cell surface maintenance of the N-methyl-d-aspartate ionotropic glutamate receptor. The molecular scaffold/receptor interaction is mediated by the association of the C terminus of the NR2B subunit of the N-methyl-d-aspartate receptor with the PDZ domains of SAP97. Here, we characterize the binding of the C terminus of NR2B with the PDZ domains of SAP97 and determine the structure of the PDZ1-NR2B complex employing high-resolution NMR. Based on fluorescence anisotropy, the NR2B subunit binds to the first and second PDZ domains of SAP97, with higher affinity for PDZ2; no appreciable binding to PDZ3 could be measured. The structural features of the NR2B bound to PDZ1 is consistent with the canonical PDZ-binding motif with the glutamic acid at the -3 position of the C terminus (i.e. -E-S-D-V) interacting with the β2/β3 loop. Two sites within the loop of PDZ1 were replaced with the corresponding residue from PDZ2, D243G and P245Q. The former mutation, designed to remove a possible Coulombic repulsion between E-3(NR2B) and Asp-243 (PDZ1) has only a minimal effect on binding. The P245Q mutation leads to a 2-fold increase in binding affinity of NR2B, approaching that observed for wild-type PDZ2. These results indicate that modification of the β2/β3 loop provides an avenue for regulating the ligand specificity of PDZ domains.
A Spiffy tool for the simultaneous placement and global routing for three-dimensional field-programmable gate arrays

FPGAs are a useful and flexible alternative to custom design chips, but can suffer from severe interconnection delay. The 3D-FPGA is an alternative to the two-dimensional architecture that has been proposed to reduce these delay problems. Here we present Spiffy-the first tool specifically designed for the placement and global routing of 3D-FPGAs. Spiffy produces some of the best results in the literature, and using Spiffy we can show that when mapped to the 3D-FPGA architecture, circuits tend to have considerably shorter net-length, making this new chip an improvement over the standard architecture.
Recent Advancements in Toxin and Antitoxin Systems Involved in Bacterial Programmed Cell Death

Programmed cell death (PCD) systems have been extensively studied for their significant role in a variety of biological processes in eukaryotic organisms. Recently, more and more researches have revealed the existence of similar systems employed by bacteria in response to various environmental stresses. This paper summarized the recent researching advancements in toxin/antitoxin systems located on plasmids or chromosomes and their regulatory roles in bacterial PCD. The most studied yet disputed mazEF system was discussed in depth, and possible roles and status of such a special bacterial death and TA systems were also reviewed from the ecological and evolutionary perspectives.
Intrinsic Connectivity Networks, Alpha Oscillations, and Tonic Alertness: A Simultaneous Electroencephalography/Functional Magnetic Resonance Imaging Study

Trial-by-trial variability in perceptual performance on identical stimuli has been related to spontaneous fluctuations in ongoing activity of intrinsic functional connectivity networks (ICNs). In a paradigm requiring sustained vigilance for instance, we previously observed that higher prestimulus activity in a cingulo-insular-thalamic network facilitated subsequent perception. Here, we test our proposed interpretation that this network underpins maintenance of tonic alertness. We used simultaneous acquisition of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) in the absence of any paradigm to test an ensuing hypothesis, namely that spontaneous fluctuations in this ICN′s activity (as measured by fMRI) should show a positive correlation with the electrical signatures of tonic alertness (as recorded by concurrent EEG). We found in human subjects (19 male, 7 female) that activity in a network comprising dorsal anterior cingulate cortex, anterior insula, anterior prefrontal cortex and thalamus is positively correlated with global field power (GFP) of upper alpha band (10–12 Hz) oscillations, the most consistent electrical index of tonic alertness. Conversely, and in line with earlier findings, alpha band power was negatively correlated with activity in another ICN, the so-called dorsal attention network which is most prominently involved in selective spatial attention. We propose that the cingulo-insular-thalamic network serves maintaining tonic alertness through generalized expression of cortical alpha oscillations. Attention is mediated by activity in other systems, e.g., the dorsal attention network for space, selectively disrupts alertness-related suppression and hence manifests as local attenuation of alpha activity.