gebhart/patrepeval huggingface dataset:
Efficacy of an Inhibitor of Hepatitis B Virus Expression in Combination With Entecavir and Interferon‐α in Woodchucks Chronically Infected With Woodchuck Hepatitis Virus (2020)

RG7834 is a small-molecule inhibitor of hepatitis B virus (HBV) gene expression that significantly reduces the levels of hepatitis B surface antigen (HBsAg) and HBV DNA in a humanized liver HBV mouse model. In the current study, we evaluated the potency of RG7834 in the woodchuck model of chronic HBV infection, alone and in combination with entecavir (ETV) and/or woodchuck interferon-α (wIFN-α). RG7834 reduced woodchuck hepatitis virus (WHV) surface antigen (WHsAg) by a mean of 2.57 log<sub>10</sub> from baseline and WHV DNA by a mean of 1.71 log<sub>10</sub>. ETV + wIFN-α reduced WHsAg and WHV DNA by means of 2.40 log<sub>10</sub> and 6.70 log<sub>10</sub>, respectively. The combination of RG7834, ETV, and wIFN-α profoundly reduced WHsAg and WHV DNA levels by 5.00 log<sub>10</sub> and 7.46 log<sub>10</sub>, respectively. However, both viral parameters rebounded to baseline after treatment was stopped and no antibody response against WHsAg was observed. Effects on viral RNAs were mainly seen with the triple combination treatment, reducing both pregenomic RNA (pgRNA) and WHsAg RNA, whereas RG7834 mainly reduced WHsAg RNA and ETV mainly affected pgRNA. When WHsAg was reduced by the triple combination, peripheral blood mononuclear cells (PBMCs) proliferated significantly in response to viral antigens, but the cellular response was diminished after WHsAg returned to baseline levels during the off-treatment period. Consistent with this, Pearson correlation revealed a strong negative correlation between WHsAg levels and PBMC proliferation in response to peptides covering the entire WHsAg and WHV nucleocapsid antigen. <i>Conclusion:</i> A fast and robust reduction of WHsAg by combination therapy reduced WHV-specific immune dysfunction in the periphery. However, the magnitude and/or duration of the induced cellular response were not sufficient to achieve a sustained antiviral response.
Distributed signal decorrelation in wireless sensor networks using the sparse matrix transform (2011)

In this paper, we propose the vector SMT, a new decorrelating transform suitable for performing distributed anomaly detection in wireless sensor networks (WSN). Here, we assume that each sensor in the network performs vector measurements, instead of a scalar ones. The proposed transform decorrelates a sequence of pairs of vector sensor measurements, until the vectors from all sensors are completely decorrelated. We perform simulations with a network of cameras, where each camera records an image of the monitored environment from its particular viewpoint. Results show that the proposed transform effectively decorrelates image measurements from the multiple cameras in the network. Because it enables joint processing of the multiple images, our method provides significant improvements to anomaly detection accuracy when compared to the baseline case when we process the images independently.
Combined NIRS and DCS measurements of cerebral hemodynamics during intracranial and blood pressure changes (Conference Presentation) (2018)

Cerebral microvascular changes are influenced by intracranial pressure (ICP) as well as mean arterial blood pressure (MAP). The mechanism maintaining blood flow despite changes in either pressure is called cerebral autoregulation. This mechanism is known to be impaired in many diseases, including traumatic brain injury and stroke. Maintaining adequate cerebral blood flow and autoregulation is known to improve long term patient outcomes. However, the influence on the microvasculature and autoregulation of blood pressure vs. fluid increase, hence intracranial pressure, is not well understood. Furthermore, while blood pressure changes can readily be measured, intracranial pressure sensors are invasive and there is a need to overcome this invasiveness. We have recently shown that changes in cerebral perfusion pressure, which is the difference between blood pressure and intracranial pressure, can be correlated to total hemoglobin concentration, as measured non-invasively with near-infrared spectroscopy (NIRS) in non-human primates. These results showed that non-invasive intracranial pressure monitoring should be possible by means of vascular changes as measured with NIRS. In order to quantify autoregulation and differentiate between blood pressure and fluid increase driven vascular changes, we collected data on non-human primates. The primates’ brains were cannulated to induce rapid changes in ICP. Exsanguination was performed to reduce blood pressure. Data was collected with a combined frequency domain NIRS (OxiplexTS, ISS Inc.) and diffuse correlation spectroscopy (DCS) system for measuring hemoglobin concentration changes as well as blood flow changes, respectively. We will present on the experimental implementation as well as data analysis for quantifying cerebral autoregulation.
Figures S1 - S4 from Mechanism-Based Epigenetic Chemosensitization Therapy of Diffuse Large B-Cell Lymphoma (2023)

&lt;p&gt;Figures S1, S2, S3 and S4 - PDF file 394K, Combinatorial effect of demethylating agents and chemotherapy in cell lines and primary samples&lt;/p&gt;
A novel direct water and Double-Sided Cooled Power Module for HEV/EV inverter (2014)

Direct Water and Double-Sided Cooled Power Modules (DWDSCPM) are especially attractive due to high thermal performances. The DWDSCPM was able to reduce the thermal resistance by 50% and increase power density of the traction inverter by 70% in comparison with a conventional power module.
IDENTIFICATION OF A MAJOR LOCUS CONTRIBUTING TO ERYTHROCYTE 2,3-DIPHOSPHOGLYCERATE VARIABILITY IN HOODED (LONG-EVANS) RATS (1977)

The erythrocyte glycolytic intermediate 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP) play an important role in oxygen transport and delivery by binding to hemoglobin (Hb) and reducing its affinity for oxygen. Considerable quantitative variability in the levels of DPG and ATP exists in human populations and in a population of hooded (Long-Evans) rats we have studied. This paper presents the results of studies on the genetic component of DPG-level variation in an outbred population of hooded rats. Beginning with about 100 rats, a two-way selection experiment was initiated. Pairs of rats with the highest DPG levels were mated to produce a High-DPG rat strain and animals with the lowest DPG levels were mated to produce a Low-DPG strain. Mean DPG levels responded rapidly to selection and, from generation 3 on, the differences between strain means were highly significant. Ten High-DPG strain rats were intercrossed with 10 Low-DPG strain rats of generation 10 to produce an F1 generation in which the DPG levels were almost as high as those of High-DPG animals. This indicates partial dominance of High-DPG alleles. The F2 DPG-level distribution showed two distinct subpopulations. The high DPG subpopulation contained three times as many animals as the low DPG subpopulation. From these results and the statistical analyses performed, it was concluded that the DPG differences between strains were due to an allelic difference at one major locus, the allele carried by the High-DPG strain showing partial dominance over the allele carried by the Low-DPG strain. It appears that this locus may also effect ATP levels to a large extent and is polymorphic in hooded rat populations. Identification of this locus gives us a useful tool for studies of the physiological effects of DPG variability, as well as providing an example of a major gene effect in a quantitatively varying trait.
Aspartate and glutamate transport in unfertilized pig oocytes and blastocysts (1993)

Amino acid transport is facilitated by specific transporters within the plasma membrane of the cell. Mediated Na(+)-independent transport of L-glutamate can be easily detected in mouse oocytes, but it is nearly undetectable in blastocyst-stage embryos. In contrast, the Na(+)-dependent transport of L-aspartate is not detectable in oocytes, but it is detectable in eight-cell embryos and reaches relatively high levels by the blastocyst stage. It is believed that the amino acid transporters responsible are systems x-c and X-AG, respectively. Here we report the detection of Na(+)-dependent L-aspartate transport, which increased as pig blastocysts developed, although Na(+)-dependent aspartate transport was not detected in pig oocytes. Mediated Na(+)-independent L-glutamate transport was not detected in pig oocytes, in contrast to the mouse, nor in early or hatched pig blastocysts. Thus, while the developmental regulation of system X-AG is similar in both the pig and the mouse, system x-c was not detectable in pig oocytes or blastocysts. Elucidation of the molecular mechanisms controlling amino acid transport and other gene expression in early embryos should contribute to an understanding of whether and even why some aspects of developmental regulation of gene expression may need to differ among species.
Association of Epstein‐Barr virus with nasopharyngeal carcinoma in alaskan native patients: Serum antibodies and tissue EBNA and DNA (1981)

Biopsy specimens from Alaskan Native patients with nasopharyngeal carcinoma (NPC) and from other patients seen on the otolaryngology service were tested for Epstein-Barr virus-specific DNA and nuclear antigen (EBNA). Serum samples from both groups were tested for various EBV-related antibodies. EBV DNA and EBNA results were in agreement in 29 of 31 tissue specimens tested by the two methods. Ten of 11 biopsies containing NPC cells were positive for EBV DNA. Two NPC patients had biopsies that showed only atypical epithelium but were also positive for EBV DNA or EBNA. The other tissue specimens were negative except for biopsies from two patients: one with a parotid gland lymphoepithelial lesion; another with undifferentiated carcinoma of salivary gland origin.
PHOTOCOAGULATION AND FLUID-GAS EXCHANGE FOR PERSISTENT MACULAR HOLE (1996)

IKUNO, YASUSHI MD; KAMEI, MOTOHIRO MD; OHNO, TAKAYUKI MD; YUASA, TAKENOSUKE MD; LEWIS, JOHN MICHAEL MD; TANO, YASUO MD Author Information
Immunogenicity and immunopathogenicity of an autoimmune epitope are potentiated by increasing MHC binding through residue substitution (1997)

We have previously shown that in Lewis rats, peptide 273-283 (TWEGSGVLPCV) of rat interphotoreceptor retinoid-binding protein (IRBP) serves as a "surrogate" epitope for pathogenic lymphocytes sensitized against peptide 1181-1191 (SWEGVGVVPDV) of bovine IRBP. Yet, peptide 273-283 itself causes experimental autoimmune uveoretinitis (EAU) only at 200 nmol/rat, whereas peptide 1181-1191 is pathogenic even at 0.2 nmol. This difference was attributed to the higher affinity of 1181-1191 to MHC molecules. Here we demonstrate that substitution of putative MHC binding-residues of peptide 273-283 with the corresponding ones of 1181-1191 results in increased binding to MHC and in remarkably elevated immunologic capacities. Analogs of 273-283 were synthesized, in which residues 277 and 282 were substituted with one or both the corresponding amino acids of peptide 1181-1191, V and D, respectively. The main findings were: 1) substitutions drastically increased MHC affinity, namely, 273-283(V277,D282) >> 273-283(D282) >>> 273-283; 2) the substituted analogs were much more immunogenic than the native peptide, inducing cellular responses at much lower doses; 3) the analogs were more antigenic in vitro than the native peptide; 4) the analogs were exceedingly pathogenic; peptide 273-283(V277,D282) caused disease even at 0.02 nmol/rat; and 5) the analogs were superior to the native peptide in their capacity to stimulate production of IFN-gamma by sensitized lymphocytes. Thus, enhancement of affinity of an autoimmune peptide for MHC molecules increases both immunogenicity and pathogenicity.
Alkyl Monolayers on Silica Surfaces Prepared from Neat, Heated ClSi(CH3)2(CH2)6CH=CH2 Analyzed by XPS (2001)

Silane monolayers on silica, prepared from mono-, di-, and trichlorosilanes, are widely used in industry for surface functionalization and modification. However, unlike di-and trichlorosilanes, monochlorosilanes are particularly easy to work with because they can dimerize, but not polymerize, upon reaction with water. Typically, an organic solvent is used when depositing a silane monolayer. Here we show XPS spectra of monolayers of ClSi(CH3)2(CH2)6CH=CH2 (octenyldimethylchlorosilane, CAS# 17196-12-2) on silicon oxide (silicon wafer) prepared using a rapid, solvent-free approach. Reaction conditions are 120 °C for 10 min using the neat (pure) compound, and no inert atmosphere or special treatment of the compound is required.
Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive abnormalities through RhoA signaling (2018)

Atypical brain connectivity is a major contributor to the pathophysiology of neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASDs). TAOK2 is one of several genes in the 16p11.2 microdeletion region, but whether it contributes to NDDs is unknown. We performed behavioral analysis on Taok2 heterozygous (Het) and knockout (KO) mice and found gene dosage-dependent impairments in cognition, anxiety, and social interaction. Taok2 Het and KO mice also have dosage-dependent abnormalities in brain size and neural connectivity in multiple regions, deficits in cortical layering, dendrite and synapse formation, and reduced excitatory neurotransmission. Whole-genome and -exome sequencing of ASD families identified three de novo mutations in TAOK2 and functional analysis in mice and human cells revealed that all the mutations impair protein stability, but they differentially impact kinase activity, dendrite growth, and spine/synapse development. Mechanistically, loss of Taok2 activity causes a reduction in RhoA activation, and pharmacological enhancement of RhoA activity rescues synaptic phenotypes. Together, these data provide evidence that TAOK2 is a neurodevelopmental disorder risk gene and identify RhoA signaling as a mediator of TAOK2-dependent synaptic development.
Cost of Sparse Mesh Layouts Supporting Throughput Computing (2011)

The purpose of this paper is to estimate the cost of utilizing under populated, or sparse, networks on chip (NOC) for chip multiprocessors (CMP). In under-populated NOCs, only a portion of nodes are sources and sinks whereas the rest are simple intermediate nodes increasing communication bandwidth. Compared to dense NOCs, where all nodes can be sources and sinks of communication, the under populated NOCs can be scaled so that any degree of communication frequency of nodes can be supported. The drawback of under populated NOCs is larger network area and bigger logical diameter. GPGPU-style stream-based or high-throughput CMPs can be used to hide the effect of longer latencies. In this paper, we present layouts for mesh-based under populated networks, calculate their wire length distributions and the overall area. Moreover, we present energy consumption calculations for such networks, and show that while the network part of a CMP system based on under populated NOCs can play a major role when considering the chip area and energy consumption, it can be pushed down by increasing the number of dimensions and using meshes instead of tori. We also compare various multidimensional sparse mesh-layouts and conclude the 3-dimensional and 4-dimensional sparse meshes to be the most attractive ones for throughput computing.
Exposure to Airborne Mould in School Environments and Nasal Patency in Children (2012)

Mould in schools has been associated with increased upper airway obstruction in adults. In this study, we investigated the relationship between school indoor mould spore exposure and nasal patency in children. Airborne mould samples were collected in 32 classrooms from 4 primary schools during both summer and winter using a single-stage Anderson sampler. Nasal patency was measured in 275 children in summer and 200 children in winter using acoustic rhinometry. Various mould species were isolated but the most common species found inside the classrooms were Alternaria, Aspergillus niger, Cladosporium spp. and Penicillium spp. In the univariate analyses, significant negative correlations were found between exposure to various mould species, particularly Alternaria, and rhinometric measures in the children. In multivariate analyses, exposure to Alternaria was associated with both decreased mean nasal cross-sectional area ( p = 0.001) and decreased nasal volume ( p = 0.026). Decreased nasal patency was also associated with exposure to A. niger ( p = 0.034) and Penicillium ( p = 0.043) in the classrooms. The findings of this study suggest that exposure to airborne mould, particularly Alternaria, in school environments may affect the upper airways of children.
Quantification of recombinant immunotoxin delivery to solid tumors allows for direct comparison of in vivo and in vitro results (2015)

Solid tumors present challenges for delivery of protein therapeutics; current methods cannot quantify the functional effects of these agents. RG7787 (anti-mesothelin recombinant immunotoxin) is highly cytotoxic to pancreatic cancer cell lines, but with limited activity in vivo. To investigate this discrepancy, we developed a flow cytometry method to quantify the amount of RG7787 internalized per cell in tumors and used it to analyze tumor responses by determining the number of molecules of RG7787 internalized per cell in vivo and comparing it to that needed to kill cells in vitro. At a maximum tolerated dose of 7.5 mg/kg, tumor cells in vivo internalized a wide range of RG7787 with the average amount equivalent to the amount that induced growth arrest in vitro. However, 20% of cells accumulated 20,300 ITs per cell, sufficient to kill cells in vitro. At 2.5 mg/kg the top 20% of cells internalized enough RG7787 to only induce growth arrest. These data are in agreement with tumor responses; 22% regression following a 7.5 mg/kg dose and growth stabilization following 2.5 mg/kg. Comparing amounts of RIT delivered in vivo and in vitro can explain tumor responses and should facilitate the development of more active immunotoxins and other antibody based agents.
Spatial and temporal diversity of glycome expression in mammalian brain (2020)

Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties. Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development. We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse. Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse. We found that glycan expression profiles were dynamically regulated during postnatal developments. A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified. Interestingly, changes primarily attributed to sialylated and fucosylated glycans were extensively observed during PFC development. Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development. Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
Diffusional creep in damascene Cu lines (2001)

Damascene Cu lines are increasingly being used as electrical interconnects in microelectronic integrated circuits. During the manufacturing process, Cu interconnects are subjected to thermal cycling that leads to complex stress states, which affect their reliability. While a realistic assessment of the impact of thermal stresses on the reliability should take into account the inelastic behavior of the damascene Cu lines, unfortunately, little is known about their mechanical behavior. The goal of this work was to identify the physical mechanisms responsible for the inelastic behavior of damascene Cu lines, and to assess the effects of the varied dimensions and passivation layers. The curvature changes caused by thermal cycling of wafers with damascene Cu lines were measured in the temperature range from −80 to 450 °C. At low temperatures, the deformation in the lines is predominantly elastic, but becomes inelastic above 200 °C. Our experimental results indicate that diffusion-controlled creep is the dominant inelastic mechanism at high temperatures. A TaN capping layer was found to suppress inelastic deformation, presumably by preventing diffusion of Cu between the free surface and the grain boundaries. This effect suggests a simple method for comparison of the effectiveness of different capping layers (e.g., TaN, Ta, Si3N4) in inhibiting Cu interfacial diffusion.
Vagus Nerve Stimulation for Blood Pressure and Heart Rate Regulation (2018)

For more than 27 years, implanted vagus nerve stimulation (VNS) devices, with electric current outputs in the 1 to 3.5 mA range, have been developed for many health care applications, including epilepsy and heart disease [1]. Mechanical compression approaches for VNS were administered under surgical conditions, using forceps, in the 1800’s [2]. Outcomes such as Electrocardiogram (ECG) data, blood pressure (BP), and heart rate (HR) were evaluated. Also, non-invasive (NI) mechanical compression of the vagus nerve for various nervous system disorders using hand, thumb, finger and belt pressure was popular in the 1800’s [3]. Cyberonics (now LivaNova) received the first FDA clearance for a surgically implanted electrical VNS device to treat refractory epilepsy in 1997.
Estimation of Hand Grip Strength Using Foot motion Measured by In-shoe Motion Sensor (2022)

There is a strong need to assess frailty in daily living. Hand grip strength (HGS) has been proven to be a very important factor for identifying frailty, however it is always assessed under the guidance of facility clinicians. Our purpose is to demonstrate the possibility of providing HGS estimation by using foot-motion signals measured by an in-shoe motion sensor (IMS) embedded in an insole to achieve high precision HGS assessment in daily living. The foot-motion signals were collected from 62 elder participants (27 men and 35 women). Their HGSs were assessed by a hand dynamometer. Gait parameters, individual properties, and predictors derived from foot-motion signal features in one gait cycle were selected as candidates. Statistical parametric mapping analyses were used to generate predictors from the foot-motion signals. Prior to estimation construction, least absolute shrinkage and selection operator was applied to reduce redundant predictors from candidates. Linear regression models for HGS estimation of men and women were constructed. As the results, we discovered new effective predictors for HGS estimation from foot motions and successfully constructed HGS estimation models that achieved "excellent" agreement with the reference according to intra-class coefficients, and mean absolute errors of 2.96 and 2.57 kg for men and women in leave-one-subject-out cross-validation, respectively. These results suggest that HGS can be estimated with high precision by IMS-measured foot motion and more effective frailty identification in daily living is possible through wearing an IMS.