Miracle-dz/UniFAR-FTUs huggingface dataset:
On-line machine learning accelerator on digital RRAM-crossbar

On-line machine learning has become the need for future data analytics. This work will show an ℓ2 norm based hardware solver for on-line machine learning that can significantly reduce training time when compared to the traditional gradient-based solution using backward propagation. We will show that the intensive matrix-vector multiplication in ℓ2 norm solution can be mapped onto a distributed in-memory accelerator using the recent resistive switching random access memory (RRAM) device. A digitized matrix-vector multiplication accelerator will be developed based on the distributed RRAM-crossbar. Such a distributed RRAM-crossbar architecture can utilize the reformulated ℓ2 norm solver with a scalable and energy-efficient solution for real-time training and testing in image recognition. Experiment results have shown that significant speedup can be achieved for matrix-vector multiplication in the ℓ2 norm solver such hat the overall training and testing time can be reduced respectively. In addition, large energy saving can be also achieved when compared to the traditional CMOS-based out-of-memory computing architecture.
From Normative Debates to Comparative Methodology: The Three Waves of Post-Charter Supreme Court Scholarship in Canada

This article surveys the literature on the Supreme Court of Canada following the 1982 introduction of the Canadian Charter of Rights and Freedoms, and argues it has taken place in three distinct “waves. ” The first involved tentative, prospective, and normative arguments about the impact of the Charter on national unity and Canada’s political institutions. The second was characterized by the legitimacy debate, the dialogue debate, and qualitative examination of how other political actors responded to Supreme Court decisions. By contrast, the third wave, initiated by American scholars drawing from American research, has been less normative, more comparative, and methodologically rigorous. While this comparative shift has been beneficial, the retreat from normative questions contributes to a misplaced sense that important debates are now settled. We urge scholars to engage in intellectual cross-fertilization by drawing from third-wave contributions to address normative questions about the Supreme Court’s increasingly important role in Canadian politics.
A Bayesian network meta-analysis for binary outcome: how to do it

This study presents an overview of conceptual and practical issues of a network meta-analysis (NMA), particularly focusing on its application to randomised controlled trials with a binary outcome of interest. We start from general considerations on NMA to specifically appraise how to collect study data, structure the analytical network and specify the requirements for different models and parameter interpretations, with the ultimate goal of providing physicians and clinician-investigators a practical tool to understand pros and cons of NMA. Specifically, we outline the key steps, from the literature search to sensitivity analysis, necessary to perform a valid NMA of binomial data, exploiting Markov Chain Monte Carlo approaches. We also apply this analytical approach to a case study on the beneficial effects of volatile agents compared to total intravenous anaesthetics for surgery to further clarify the statistical details of the models, diagnostics and computations. Finally, datasets and models for the freeware WinBUGS package are presented for the anaesthetic agent example.
A fast and reproducible method for albumin isolation and depletion from serum and cerebrospinal fluid

Analysis of serum and plasma proteomes is a common approach for biomarker discovery, and the removal of high‐abundant proteins, such as albumin and immunoglobins, is usually the first step in the analysis. However, albumin binds peptides and proteins, which raises concerns as to how the removal of albumin could impact the outcome of the biomarker study while ignoring the possibility that this could be a biomarker subproteome itself. The first goal of this study was to test a new commercially available affinity capture reagent from Protea Biosciences and to compare the efficiency and reproducibility to four other commercially available albumin depletion methods. The second goal of this study was to determine if there is a highly efficient albumin depletion/isolation system that minimizes sample handling and would be suitable for large numbers of samples. Two of the methods tested (Sigma and ProteaPrep) showed an albumin depletion efficiency of 97% or greater for both serum and cerebrospinal fluid (CSF). Isolated serum and CSF albuminomes from ProteaPrep spin columns were analyzed directly by LC‐MS/MS, identifying 128 serum (45 not previously reported) and 94 CSF albuminome proteins (17 unique to the CSF albuminome). Serum albuminome was also isolated using Vivapure anti‐HSA columns for comparison, identifying 105 proteins, 81 of which overlapped with the ProteaPrep method.
Human Cytomegalovirus UL97 Kinase Is Required for the Normal Intranuclear Distribution of pp65 and Virion Morphogenesis

ABSTRACT Recombinant human cytomegaloviruses that do not express UL97 kinase activity exhibit a distinctive plaque morphology characterized by the formation of highly refractile bodies late in infection. These structures were also observed in infected cells treated with the UL97 kinase inhibitor maribavir. Nuclear inclusions were purified to near homogeneity, and the constituent proteins were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. This analysis demonstrated that the aggregates were formed principally of the tegument proteins pp65 and ppUL25 but also contained additional virion structural proteins including the major capsid protein. Immunoblotting experiments confirmed these results and identified a number of additional viral proteins present in the purified tegument aggregates. Interestingly, the formation of these structures appeared to be dependent on pp65, since it was not induced in cells infected with a recombinant virus with this open reading frame deleted. Morphologically similar aggregates could be reproduced in nuclei of uninfected cells by overexpressing pp65, and their formation was prevented by coexpressing the UL97 kinase. Inhibition of UL97 kinase activity with maribavir or mutation of an essential amino acid in the kinase abolished its ability to prevent aggregate formation. These data taken together suggest that the UL97 kinase impacts the aggregation of pp65 in the nuclei of infected cells. We propose that the kinase plays an important role in the acquisition of tegument during virion morphogenesis in the nucleus and that this activity represents an important step in the production of mature virus particles.
Childhood adversity and cortical thickness and surface area in a population at familial high risk of schizophrenia

Background There is now a well-established link between childhood adversity (CA) and schizophrenia. Similar structural abnormalities to those found in schizophrenia including alterations in grey-matter volume have also been shown in those who experience CA. Method We examined whether global estimates of cortical thickness or surface area were altered in those familial high-risk subjects who had been referred to a social worker or the Children's Panel compared to those who had not. Results We found that the cortical surface area of those who were referred to the Children's Panel was significantly smaller than those who had not been referred, but cortical thickness was not significantly altered. There was also an effect of social work referral on cortical surface area but not on thickness. Conclusions Cortical surface area increases post-natally more than cortical thickness. Our findings suggest that CA can influence structural changes in the brain and it is likely to have a greater impact on cortical surface area than on cortical thickness.
Enhancing Recovery in Coronary Heart Disease (ENRICHD) Study Intervention: Rationale and Design

Objective Depression and low social support are risk factors for medical morbidity and mortality after acute MI. The ENRICHD study is a multicenter, randomized, controlled clinical trial of a cognitive-behavioral treatment for depression and low social support in post-MI patients. A total of 2481 patients were recruited (26% with low social support, 39% with depression, and 34% with low social support and depression). Our objective is to describe the rationale, design, and delivery of the ENRICHD intervention. Methods Key features of the intervention include the integration of cognitive-behavioral and social learning approaches to the treatment of depression and a diverse set of problems that can contribute to low social support; rapid initiation of treatment after MI; a combination of individual and group modalities; adjunctive pharmacotherapy for severe or intractable depression; training, certification, and supervision of therapists; and quality assurance procedures. Results The trial’s psychosocial and medical outcomes will be presented in future reports. Conclusions The ENRICHD protocol targets two complex psychosocial risk factors with a multifaceted intervention, which is delivered in an individualized manner to accommodate a demographically, medically, and psychiatrically diverse patient population. Additional research will be needed to identify optimal matches between patient characteristics and specific components of the intervention.
Mycobacterium abscessus Complex Identification with Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

ABSTRACT We determined that the Vitek MS Plus matrix-assisted laser desorption ionization–time of flight mass spectrometry using research-use-only (RUO) v.4. 12 and in vitro-diagnostic (IVD) v.3. 0 databases accurately identified 41 Mycobacterium abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense isolates identified by whole-genome sequencing to the species but not the subspecies level, from Middlebrook 7H11 and Burkholderia cepacia selective agars. Peak analysis revealed three peaks potentially able to differentiate between subspecies.
Research Progress in the Modification of Quercetin Leading to Anticancer Agents

The flavonoid quercetin (3,3′,4′,5,7-pentahydroxyflavone) is widely distributed in plants, foods, and beverages. This polyphenol compound exhibits varied biological actions such as antioxidant, radical-scavenging, anti-inflammatory, antibacterial, antiviral, gastroprotective, immune-modulator, and finds also application in the treatment of obesity, cardiovascular diseases and diabetes. Besides, quercetin can prevent neurological disorders and exerts protection against mitochondrial damages. Various in vitro studies have assessed the anticancer effects of quercetin, although there are no conclusive data regarding its mode of action. However, low bioavailability, poor aqueous solubility as well as rapid body clearance, fast metabolism and enzymatic degradation hamper the use of quercetin as therapeutic agent, so intense research efforts have been focused on the modification of the quercetin scaffold to obtain analogs with potentially improved properties for clinical applications. This review gives an overview of the developments in the synthesis and anticancer-related activities of quercetin derivatives reported from 2012 to 2016.
A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial.

BACKGROUND West Nile virus (WNV) is a mosquito-borne flavivirus that can cause severe meningitis and encephalitis in infected individuals. We report the safety and immunogenicity of a WNV DNA vaccine in its first phase 1 human study. METHODS A single-plasmid DNA vaccine encoding the premembrane and the envelope glycoproteins of the NY99 strain of WNV was evaluated in an open-label study in 15 healthy adults. Twelve subjects completed the 3-dose vaccination schedule, and all subjects completed 32 weeks of evaluation for safety and immunogenicity. The development of a vaccine-induced immune response was assessed by enzyme-linked immunosorbant assay, neutralization assays, intracelluar cytokine staining, and enzyme-linked immunospot assay. RESULTS The vaccine was safe and well tolerated, with no significant adverse events. Vaccine-induced T cell and antibody responses were detected in the majority of subjects. Neutralizing antibody to WNV was detected in all subjects who completed the 3-dose vaccination schedule, at levels shown to be protective in studies of horses, an incidental natural host for WNV. CONCLUSIONS Further assessment of this DNA platform for human immunization against WNV is warranted. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00106769 .
White matter tract injury and cognitive impairment in human immunodeficiency virusinfected individuals

Approximately half of those infected with the human immunodeficiency virus (HIV) exhibit cognitive impairment, which has been related to cerebral white matter damage. Despite the effectiveness of antiretroviral treatment, cognitive impairment remains common even in individuals with undetectable viral loads. One explanation for this may be subtherapeutic concentrations of some antiretrovirals in the central nervous system (CNS). We utilized diffusion tensor imaging and a comprehensive neuropsychological evaluation to investigate the relationship of white matter integrity to cognitive impairment and antiretroviral treatment variables. Participants included 39 HIV-infected individuals (49% with acquired immunodeficiency syndrome [AIDS]; mean CD4=529) and 25 seronegative subjects. Diffusion tensor imaging indices were mapped onto a common whole-brain white matter tract skeleton, allowing between-subject voxelwise comparisons. The total HIV-infected group exhibited abnormal white matter in the internal capsule, inferior longitudinal fasciculus, and optic radiation; whereas those with AIDS exhibited more widespread damage, including in the internal capsule and the corpus callosum. Cognitive impairment in the HIV-infected group was related to white matter injury in the internal capsule, corpus callosum, and superior longitudinal fasciculus. White matter injury was not found to be associated with HIV viral load or estimated CNS penetration of antiretrovirals. Diffusion tensor imaging was useful in identifying changes in white matter tracts associated with more advanced HIV infection. Relationships between diffusion alterations in specific white matter tracts and cognitive impairment support the potential utility of diffusion tensor imaging in examining the anatomical underpinnings of HIV-related cognitive impairment. The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment.
Sleep Duration and Risk of Liver Cancer in Postmenopausal Women: The Women's Health Initiative Study.

BACKGROUND Sleep duration has been associated with nonalcoholic fatty liver disease, but its association with liver cancer remains unknown. MATERIAL AND METHODS In the prospective Women's Health Initiative Study, 139,368 postmenopausal women reported sleep habits at baseline (1993-1998). We ascertained 175 incident liver cancer cases during an average 13.8 years of follow-up through August 2014. We used multivariable Cox proportional hazard regression models to estimate a hazard ratio (HR) and its 95% confidence interval (95% CI) for risk of liver cancer in association with nocturnal sleep duration. RESULTS Compared to women reporting 6-8 hours of sleep, the HR for liver cancer was 1.94 (95% CI 1.07-3.53) for women reporting ≥9 hours of sleep. Among the obese women, the HR associated with ≥9 hours of sleep was 3.18 (95% CI 1.84-8.60). The HR was 0.93 (95% CI 0.34-2.53) among nonobese women (p value for interaction = 0.18). Short sleep duration (≤5 hours) was not associated with liver cancer risk. CONCLUSION Long sleep duration was associated with a moderate increase in liver cancer risk in obese postmenopausal women in the United States. Larger study is needed to confirm our observation on effect modification by adiposity status.
Constraining Theories of Working Memory with Biophysical Modeling

A debate about the basic unit of representation in working memory (WM) has recently been prominent in the field. Some argue that WM consists of a limited number of “slots. ” These have been equated with object representations ([Luck and Vogel, 1997][1]), but could also arise if the neural coding
PREPARATIVE ISOLATION AND PURIFICATION OF FIVE FLAVONOIDS FROM POGOSTEMON CABLIN BENTH BY HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY AND PREPARATIVE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY

High-speed countercurrent chromatography (HSCCC) and preparative high-performance liquid chromatography (prep-HPLC) were successively used for the separation of pogostone and four flavonoids from Pogostemon cablin (Blanco) Benth. An efficient HSCCC separation was achieved on a two-phase solvent system composed of n-hexane–ethyl acetate–methanol–water (11:5:11:5, v/v/v/v). Three well-separated peaks were obtained in the HSCCC chromatogram. The first and the second fractions each contained two flavonoids that were further separated by preparative HPLC. Consequently, the separation yielded 11.5 mg of 4′,5-Dihydroxy-3′,7-dimethoxyflavanone at a purity of 99%, 20.3 mg of 5-Hydroxy-7,3′,4′-trimethoxyflavanone at a purity of 98%, 18 mg of 5,4′-Dihydroxy-3,7,3′-trimethoxyflavone at a purity of 96%, and 8 mg of 5-Hydroxy-3,7,4′-tetramethoxyflavone at a purity of 98%. The third HSCCC fraction yielded 18.5 mg of pogostone at a purity of 95%. The chemical structures of these compounds were identified by ESI-MSn, 1H-NMR, and 13C-NMR.
Persistence of recipient human leucocyte antigen (HLA) antibodies and production of donor HLA antibodies following reduced intensity allogeneic haematopoietic stem cell transplantation

The effects of reduced intensity conditioning (RIC) on human leucocyte antigen (HLA)‐alloimmunization and platelet transfusion refractoriness (PTR) following allogeneic haematopoietic stem cell transplantation (Allo‐HSCT) are unknown. We studied HLA‐alloantibodies in a cohort of 16 patients (eight HLA‐alloimmunized with pre‐transplant histories of PTR and eight non‐alloimmunized controls) undergoing Allo‐HSCT using fludarabine/cyclophosphamide‐based RIC. Pre‐ and post‐transplant serum samples were analysed for HLA‐antibodies and compared to myeloid, T‐cell and bone marrow plasma cell chimaerism. Among alloimmunized patients, the duration that HLA‐antibodies persisted post‐transplant correlated strongly with pre‐transplant HLA‐antibody mean fluorescence intensity (MFI) and PRA levels (Spearman's rank correlation = 0·954 (P = 0·0048) and 0·865 (P = 0·0083) respectively). Pre‐transplant MFI >10 000 was associated with post‐transplant HLA antibody persistence >100 d (P = 0·029). HLA‐antibodies persisted ≥100 d in 3/8 patients despite recipient chimaerism being undetectable in all lympho‐haematopoietic lineages including plasma cells. Post‐transplant de‐novo HLA‐antibodies developed in three control patients with two developing PTR; the donors for two of these patients demonstrated pre‐existing HLA‐antibodies of equivalent specificity to those in the patient, confirming donor origin. These data show HLA‐antibodies may persist for prolonged periods following RIC. Further study is needed to determine the incidence of post‐transplant PTR as a consequence of donor–derived HLA alloimmunization before recommendations on donor HLA‐antibody screening can be made.
Expression of the Stem Cell Marker, Nanog, in Human Endometrial Adenocarcinoma

The embryonic stem cell self-renewal gene, Nanog, has been shown to be expressed in several tumor types and to regulate tumor development. The aim of this study was to carry out a detailed analysis of Nanog expression in human endometrial adenocarcinoma (EAC). Immunohistochemical analysis and reverse transcription-polymerase chain reaction were used to characterize Nanog, Sox2, and Oct4 expression in tissue arrays containing EAC, benign endometrium samples, and tumorosphere cells. Tumorosphere formation of EAC-derived cells in the stem cell culture medium was also analyzed. Nanog expression was then analyzed in secondary tumors initiated by the injection of tumorospheres or tumorosphere-derived differentiated cells into 15 female nude mice. Apoptosis and cell proliferation were detected in the fluorescence-activated cell sorter and 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide experiments, respectively. The Nanog protein was expressed in a majority of EAC samples (45 of 55, 81.8%), but not in benign endometrium samples (0 of 26, 0.0%). Oct4 and Sox2 were also commonly expressed in EAC samples (42 of 55, 76.4% and 39 of 55, 70.9%, respectively). Subsets of cancer cells from all EAC samples (15 of 15, 100%) exhibited the capacity to form Nanog-positive tumorospheres. The tumorospheres also expressed Nanog, Oct4, and Sox2 mRNA and showed a higher proliferation potential than differentiated cells. All 15 mice that were injected with tumorosphere cell-formed tumors, whereas only 3 of 15 mice injected with differentiated cells derived from tumorospheres developed tumors. All secondary xenograft tumors still expressed Nanog protein and Nanog, Oct4, and Sox2 mRNA, and had higher proliferation and lower apostosis than did differentiated cells. Overexpression of Nanog in EACs suggests that Nanog may represent a potential therapeutic target for EAC. In addition, Nanog may be useful as a biomarker in an immunohistochemical panel to differentiate between EAC and benign endometrial tissues. The expression of Nanog in tumorospheres may be indicative of the presence of a population of endometrial cancer stem cells, and its expression in xenograft tumors suggests that Nanog may also be associated with tumor metastasis.
A dual role for Integrin α6β4 in modulating hereditary neuropathy with liability to pressure palsies

Peripheral myelin protein 22 (PMP22) is a component of compact myelin in the peripheral nervous system. The amount of PMP22 in myelin is tightly regulated, and PMP22 over or under‐expression cause Charcot‐Marie‐Tooth 1A (CMT1A) and Hereditary Neuropathy with Pressure Palsies (HNPP). Despite the importance of PMP22, its function remains largely unknown. It was reported that PMP22 interacts with the β4 subunit of the laminin receptor α6β4 integrin, suggesting that α6β4 integrin and laminins may contribute to the pathogenesis of CMT1A or HNPP. Here we asked if the lack of α6β4 integrin in Schwann cells influences myelin stability in the HNPP mouse model. Our data indicate that PMP22 and β4 integrin may not interact directly in myelinating Schwann cells, however, ablating β4 integrin delays the formation of tomacula, a characteristic feature of HNPP. In contrast, ablation of integrin β4 worsens nerve conduction velocities and non‐compact myelin organization in HNPP animals. This study demonstrates that indirect interactions between an extracellular matrix receptor and a myelin protein influence the stability and function of myelinated fibers.
Levodopa modulates small‐world architecture of functional brain networks in Parkinson's disease

PD is associated with disrupted connectivity to a large number of distributed brain regions. How the disease alters the functional topological organization of the brain, however, remains poorly understood. Furthermore, how levodopa modulates network topology in PD is largely unknown. The objective of this study was to use resting‐state functional MRI and graph theory to determine how small‐world architecture is altered in PD and affected by levodopa administration.