gebhart/patrepeval huggingface dataset:
Dissecting the role of CD4+ T cells in autoimmune diabetes through the use of TCR transgenic mice (1999)

Insulin-dependent diabetes mellitus (IDDM) is an immunological disorder wherein autoimmune-mediated destruction of islet cells in the pancreas results in persistent hyperglycemia. The non-obese diabetic mouse model of IDDM has revealed the importance of multiple factors that impact upon the disease process; however, understanding of primary immune mechanisms leading to IDDM remains elusive. The emergence of transgenic mouse models for IDDM has made important contributions towards clarifying many of these factors, including the cell types, the various effector molecules and the genetic elements involved in the pathogenesis of IDDM. In this review, we will focus on the primary mechanism and mediators of islet beta-cell death, the impact of T-helper lymphocytes on disease progression and the potential role of major histocompatibility complex class II molecules in conferring susceptibility to IDDM.
D7S448 detects aHindIII polymorphism located in the centromere region of chromosome 7 (1991)

Probe pMC27.7 is a 700 bp EcoRI fira nt isolated from a cosmid (RS27) containing the hLA-G class I gene'. The clone was derived from the MHC heniizygous B cell line, 3.1.02. pMC27.7 is found 17 kb 5' of the HL4A-G' class I gene and approximately 100 kb from the hLA-A locus2. The probe resides within a 2.0 kb nonpolymorphic HinduI fragment (35 unrelated individuals tested).
An Ultra-Low-Power Long Range Battery/Passive RFID Tag for UHF and Microwave Bands With a Current Consumption of 700 nA at 1.5 V (2007)

We present for the first time, a fully integrated battery powered RFID integrated circuit (IC) for operation at ultrahigh frequency (UHF) and microwave bands. The battery powered RFID IC can also work as a passive RFID tag without a battery or when the battery has died (i.e., voltage has dropped below 1.3 V); this novel dual passive and battery operation allays one of the major drawbacks of currently available active tags, namely that the tag cannot be used once the battery has died. When powered by a battery, the current consumption is 700 nA at 1.5 V (400 nA if internal signals are not brought out on test pads). This ultra-low-power consumption permits the use of a very small capacity battery of 100 mA-hr for lifetimes exceeding ten years; as a result a battery tag that is very close to a passive tag both in form factor and cost is made possible. The chip is built on a 1-mum digital CMOS process with dual poly layers, EEPROM and Schottky diodes. The RF threshold power at 2.45 GHz is -19 dBm which is the lowest ever reported threshold power for RFID tags and has a range exceeding 3.5 m under FCC unlicensed operation at the 2.4-GHz microwave band. The low threshold is achieved with architectural choices and low-power circuit design techniques. At 915 MHz, based on the experimentally measured tag impedance (92-j837) and the threshold spec of the tag (200 mV), the theoretical minimum range is 24 m. The tag initially is in a "low-power" mode to conserve power and when issued the appropriate command, it operates in "full-power" mode. The chip has on-chip voltage regulators, clock and data recovery circuits, EEPROM and a digital state machine that implements the ISO 18000-4 B protocol in the "full-power" mode. We provide detailed explanation of the clock recovery circuits and the implementation of the binary sort algorithm, which includes a pseudorandom number generator. Other than the antenna board and a battery, no external components are used.
Eight-channel wavelength-division switching experiment using wide-tuning-range DFB LD filters (1988)

A photonic wavelength-division switching system using phase-shift-controllable DFB LD tunable filters was studied. Uniform eight-channel selectivity, error rate and crosstalk characteristics, measured in a switching experiment, are shown to be sufficient for achieving eight wavelength-division multiplexity with 0.8 AA tuning range.
Cell-penetrating Peptide for Enhanced Delivery of Nucleic Acids and Drugs to Ocular Tissues Including Retina and Cornea (2007)

As in other organ systems, gene and drug delivery to ocular tissues such as the retina and cornea is hampered by inefficient penetration of therapeutic molecules across the plasma membrane. We describe the use of a novel peptide for ocular delivery (POD) with protein transduction properties, for delivery of small and large molecules across the plasma membrane. POD enters cells within 5 minutes in a temperature dependent manner. POD can compact and deliver plasmid DNA, achieving transgene expression in >50% of human embryonic retinoblasts. Delivery of small interfering RNA (siRNA) duplexes to cells using POD, allowed for silencing of transgene expression by >50%. POD could also be used to deliver quantum dots in vitro and in vivo. Upon ocular delivery, POD rapidly entered neural retina and localized to retinal pigment epithelium (RPE), photoreceptor, and ganglion cells. Additionally, POD was able to enter corneal epithelium, sclera, choroid, and the dura of the optic nerve via topical application. POD also functions as a bacteriostatic, a useful property for a carrier of molecules to post mitotic neural ocular tissues.
A fixed-frequency quasi-sliding control algorithm: application to power inverters design by means of FPGA implementation (2003)

In this paper, a fixed-frequency quasi-sliding control algorithm based on switching surface zero averaged dynamics (ZAD) is reported. This algorithm is applied to the design of a buck-based inverter, and implemented in a laboratory prototype by means of a field programmable gate array (FPGA), taking into account processing speed versus computational complexity trade-off. Three control laws, namely sliding control (SC), fixed-frequency quasi-sliding ZAD and PWM-based control have been experimentally tested to highlight the features of the proposed algorithm. According to the experimental results presented in the paper, the ZAD algorithm fulfills the requirement of fixed switching frequency and exhibits similar robustness properties in the presence of perturbations to those of sliding control mode.
Original Research:Bacillus coagulansSignificantly Improved Abdominal Pain and Bloating in Patients with IBS (2009)

Preliminary data suggest that the patented B coagulans GBI-30, 6086 probiotic may be a safe and effective option for the relief of abdominal pain and bloating for patients with IBS. Larger, extended trials are needed to verify these results.
Acute Hepatotoxicity of Pseudomonas aeruginosa Exotoxin A in Mice Depends on T Cells and TNF (1998)

The most potent virulence factor of Pseudomonas aeruginosa, its exotoxin A (PEA), inhibits protein synthesis, especially in the liver, and is a weak T cell mitogen. This study was performed to correlate hepatotoxic and possible immunostimulatory features of PEA in vivo. Injection of PEA to mice caused hepatocyte apoptosis, an increase in plasma transaminase activities, and the release of TNF, IFN-gamma, IL-2, and IL-6 into the circulation. Most strikingly, liver damage depended on T cells. Athymic nude mice or mice depleted of T cells by anti-Thy1.2 mAb pretreatment failed to develop acute hepatic failure, and survival was significantly prolonged following T cell depletion. Neutralization of TNF or lack of TNF receptors prevented liver injury. In the liver, TNF was produced by Kupffer cells before hepatocellular death occurred. After T cell depletion, Kupffer cells failed to produce TNF. Transaminase release was significantly reduced in perforin knockout mice, and it was even elevated in lpr/lpr mice. These results demonstrate that PEA induces liver damage not only by protein synthesis inhibition but also by TNF- and perforin-dependent, Fas-independent, apoptotic signals.
Cucurbituril Complexes of Viologens Bound to TiO2 Films (2010)

Methylviologen (1,1'-dimethyl-4,4'-bipyridinium dichloride, MV(2+), 1) and a newly synthesized viologen derivative (1-methyl-1'-p-tolyl-4,4'-bipyridinium dichloride, MTV(2+), 2) were encapsulated in a macrocyclic host, cucur[7]bituril, CB[7]. The complexes MV(2+)@CB[7] and MTV(2+)@CB[7] were physisorbed on the surface of TiO(2) nanoparticles films. Viologens 1 or 2, which do not have anchoring group substituents, did not bind to the films in the absence of CB[7]. The complexation into CB[7] was monitored by (1)H NMR spectra in D(2)O solutions, which showed an upfield shift of the viologen protons upon encapsulation. TiO(2) films functionalized with the complexes were studied by FT-IR-ATR and UV-vis absorption. The electrochemical and spectroelectrochemical properties of MV(2+)@CB[7] and MTV(2+)@CB[7] were studied in solution and in electrochromic windows, where the complexes were bound to TiO(2) films cast on FTO. The windows prepared from MV(2+)@CB[7]/TiO(2)/FTO and MTV(2+)@CB[7]/TiO(2)/FTO electrodes showed reversible, sharp (colorless to purple), and fast color switching upon application of -0.8 V. Electrochromic behavior was not observed in control windows prepared in the absence of CB[7].
BMP signaling is a therapeutic target in ovarian cancer (2020)

BMP signaling has been found to have tumor-promoting as well as tumor-suppressing effects in different types of tumors. In this study, we investigated the effects of BMP signaling and of BMP inhibitors on ovarian cancer (OC) cells in vitro and in vivo. High expression of BMP receptor 2 (BMPR2) correlated with poor overall survival of OC patients in the TCGA dataset. Both BMP2 and BMPR2 enhanced OC cell proliferation, whereas BMP receptor kinase inhibitors inhibited OC cell growth in cell culture as well as in a mouse model. BMP2 also augmented sphere formation, migration, and invasion of OC cells, and induced EMT. High BMP2 expression was observed after chemotherapy of OC patients in the GSE109934 dataset. In accordance, carboplatin, used for the treatment of OC patients, increased BMP2 secretion from OC cells, and induced EMT partially via activation of BMP signaling. Our data suggest that BMP signaling has tumor-promoting effects in OC, and that BMP inhibitors might be useful therapeutic agents for OC patients. Considering that carboplatin treatment augmented BMP2 secretion, the possibility to use a combination of BMP inhibitors and carboplatin in the treatment of OC patients, would be worth exploring.
Which Pneumococcal Serogroups Cause the Most Invasive Disease: Implications for Conjugate Vaccine Formulation and Use, Part I (2000)

We analyzed >70 recent data sets to compare the serogroups causing invasive pneumococcal disease (IPD) with those represented in conjugate vaccine formulations. Five to 8 and 10-11 serogroups comprise at least 75% of pneumococcal isolates from young children and older children/adults, respectively, in each geographic region. Serogroups in the 7-valent formulation (4, 6, 9, 14, 18, 19, and 23) cause 70%-88% of IPD in young children in the United States and Canada, Oceania, Africa, and Europe, and <65% in Latin America and Asia. Serogroups in the 9-valent formulation (7-valent+1, 5) cause 80%-90% of IPD in each region except Asia (66%). Serogroup 1 accounts for >6% of IPD in each region, including Europe, except the United States and Canada and Oceania. In contrast, several serogroups not found in 7-, 9-, and 11-valent conjugate formulations are significant causes of disease in older children/adults. Nevertheless, each conjugate formulation could prevent a substantial IPD burden in each region and age group.
Extraction and Characterization of Hemicellulose from the Corn Fiber Produced by Corn Wet-Milling Processes (1998)

The industrial processing of corn by wet-milling converts the hull layer into the byproduct known as corn fiber, which is combined with other materials (e.g., steep and fermentation liquids) to make corn gluten feed. Increased fuel ethanol production from corn will necessitate other uses of corn fiber. More than 30% of the corn fiber is in the form of a xylan (CFX) composed mainly of xylose and arabinose. Various procedures were examined for rapid extraction of CFX from corn fiber to obtain a purified material with good recoveries. Using 2% calcium hydroxide and precipitation with ethanol yielded a relatively pure CFX material but required long extraction times (16−20 h) and produced a hard, insoluble fiber residue. Extractions with 15% ammonium hydroxide yielded a rather impure CFX material and required similar long extraction times. Extraction with potassium hydroxide solutions were attempted using various combinations of time, temperature, and concentrations. Extraction with 2% potassium hydroxide at 70 °C for 4−6 h, coupled with calcium hydroxide treatment of the dissolved CFX, produced a highly pure CFX material composed of about 94% neutral sugars (34% arabinose, 52% xylose, 7% galactose, 8% glucose), 7% hexuronic acids, and 3% protein. The overall CFX yields were good (15%), and the residual fiber material still appeared physically suitable for use as a feed or for other uses. Keywords: Xylan; hemicellulose; corn fiber; corn hull; corn gum; corn xylan; arabinoxylan; pentosan
Phosphorylation of Hrs downstream of the epidermal growth factor receptor (2002)

The hepatocyte growth factor-regulated tyrosine kinase substrate Hrs is an early endosomal protein that is thought to play a regulatory role in the trafficking of growth factor/receptor complexes through early endosomes. Stimulation of cells with epidermal growth factor (EGF) rapidly leads to phosphorylation of Hrs, raising the question whether the receptor tyrosine kinase phosphorylates Hrs directly. Here, we present evidence that a downstream kinase, rather than the active receptor kinase is responsible. We show that the nonreceptor tyrosine kinase Src is able to phosphorylate Hrs in vitro and in vivo, but that Hrs is nevertheless phosphorylated in Src-, Yes- and Fyn-negative cells. Moreover, we show that only 10-20% of Hrs is phosphorylated following EGF stimulation, and that phosphorylation occurs at multiple tyrosines located in different parts of Hrs. These results suggest that Hrs is a substrate for several kinases downstream of the EGF receptor.
Interterminal distance and flexibility of a triantennary glycopeptide as measured by resonance energy transfer (1991)

Three geometric isomers of a single triantennary glycopeptide, each containing two fluorophores attached to terminal positions in the molecule, were used to probe distance and flexibility of the oligosaccharide in solution. A dansyl group (energy acceptor) was attached to the C6 of Gal at either position 6', 6, or 8, and a naphthyl-2-acetyl group (energy donor) was coupled to the N terminus of the Ala-Asn peptide. (formula; see text) Resonance energy-transfer measurements revealed an average distance of approximately 22, 18, and 17 A between the donor and the acceptor attached to either the 6, 8, or 6' Gal residue, respectively. The lifetime of the donor's emission was nearly a single-exponential decay of 27 ns (96%), whereas the decay of the donor with proximally attached acceptor was fit by nonlinear least-squares analysis to a multiexponential for each glycopeptide probe. Fitting with a Lorentzian function revealed spatially distinct donor/acceptor distances presumably arising from glycopeptide branch flexibility. The results suggest that the acceptor located at Gal 8 is the most rigid relative to the donor with a single population of distances centered at 18.4 A. In contrast, the acceptor attached to either Gal 6' or 6 displayed two populations of different distances from the donor. The Gal 6 isomer contained a major population with average donor/acceptor separation distance of 21.7 A and a minor population with average separation distance of 9.7 A. Similarly, the Gal 6' isomer showed a major population with donor/acceptor separation distance of 18.3 A and a minor population with separation distance of 11.7 A. These data support the earlier conclusions that the Man alpha(1----6)Man linkage found in the core pentasaccharide of all branched N-linked oligosaccharides is flexible. In addition, the data suggest that the branch containing Gal 6 is also flexible in the triantennary glycopeptide.
Scalable, secure, and highly available distributed file access (1990)

A summary of and historical perspective on work done to implement easy-to-share distributed file systems based on the Unix model are presented. Andrew and Coda are distributed Unix file systems that embody many of the recent advances in solving the problem of data sharing in large, physically dispersed workstation environments. The Andrew architecture is presented, the scalability and security of the system are discussed. The Coda system is examined, with emphasis on its high availability.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Enhancing Outcomes from Major Depression: Using Antidepressant Combination Therapies with Multifunctional Pharmacologic Mechanisms from the Initiation of Treatment (2010)

Traditional guidelines call for treatment of major depression with a sequence of single antidepressants. Augmentation with a second agent generally only occurs when the first agent is well tolerated and when it also provides at least some symptomatic improvement on its own. Since this standard approach leads to low rates of attaining and sustaining remission by the first agent, with diminishing returns for each subsequent agent, there is growing dissatisfaction with this approach to the treatment of major depression. One new trend is to attempt to enhance the rates of sustained remission from a major depressive episode by combining two therapeutic agents from the very initiation of treatment of a major depressive episode. Traditional treatment of major depression begins with a single “first line” antidepressant, and if it does not work or is not tolerated, trying another and then another. Unfortunately, this strategy results in disappointing remission rates for the first antidepressant (Figure 1), and disappointing rates of maintaining any improvement that is attained by this first agent because of high relapse rates over the next year despite continuing treatment with the first antidepressant (Figure 2A). And that is the good news. The bad news is that with each subsequent antidepressant treatment administered remission rates are progressively reduced (Figure 1). For those patients who do improve, they are progressively less likely to sustain their therapeutic gains despite continuing to take the drug that led to their initial improvement (Figure 2).
Inducible Control of Transgene Expression with Ecdysone Receptor: Gene Switches with High Sensitivity, Robust Expression, and Reduced Size (2005)

The ecdysone receptor (EcR)-based gene regulation system is a tool for controlling gene expression. To improve the sensitivity of this system, we evaluated many two-hybrid format synthetic gene constructs in which the GAL4 DNA binding domain was fused to the ligand binding domain of the Choristoneura fumiferana EcR mutant V390I/Y410E (GEvy), and various activation domains--VP16, p53, p65, or E2F-i--were fused to the EF domains of chimeric human RXR. These gene switches were assayed in NIH3T3 cells, HEK293 cells, and in mouse quadriceps in the presence of the nonsteroidal inducer RG-115819 or GS-E. All of the two-hybrid format constructs had no or very low background in the "off" condition and high luciferase reporter gene expression levels in "on" conditions. Extremely high sensitivity was achieved, with EC50 values in the subnanomolar range and with maximal induction at 10 nM RG-115819. Co-expression of both receptor genes with encephalomyocarditis virus (EMCV) or eIF4G internal ribosome entry site (IRES) sequences gave robust induction levels. To reduce the size of the switch construct, we tested single receptor formats, in which any of 14 different activation domains were fused to GEvy. We identified several switches with acceptable levels of basal and maximal induction levels. The gene switches described here provide receptor configuration options suitable for gene function studies, therapeutic protein production in cell culture, transgenic mouse models, and gene/cell therapy.
Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors (2017)

Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing.
Interim safety analysis from TYTAN: A phase III Asian study of lapatinib in combination with paclitaxel as second-line therapy in gastric cancer. (2010)

4057 Background: The standard care for advanced gastric adenocarcinoma varies between Western and Asian countries. In patients with HER2-positive advanced gastric cancer, the anti-HER2 antibody trastuzumab recently showed a significant survival benefit in the first-line therapy (ASCO 2009). Second-line weekly paclitaxel has shown favorable response rates (14.3-40.0%) in patients with gastric cancer and is now used widely in Japan and well accepted in other Asian countries. Successful data with lapatinib, a dual inhibitor of HER2 and EGFR, in combination with paclitaxel have been reported from several breast cancer trials. In vitro, lapatinib showed an anti-proliferative activity on N87, a HER2-positive gastric cancer cell line. Based on these backgrounds, we planned TYTAN (lapatinib [Tykerb] with paclitaxel [Taxol] in Asian ErbB2+[HER2+] Gastric Cancer Study), an open-label, randomized phase III study of second-line therapy with paclitaxel with or without lapatinib in patients with HER2-positive gastric cancer. Methods: Patients with advanced gastric cancer who showed a progression during the first-line therapy were screened for HER2 status by fluorescence in situ hybridization. Then, HER2-amplified patients were randomized to either weekly paclitaxel (80 mg/m2) alone or with daily lapatinib (1,500 mg/day). The primary endpoint is overall survival with a required sample size of 260 being enrolled from 5 Asian countries. Interim safety assessment to evaluate feasibility of this regimen has been planned after approximately every 50 patients enrolled. Results: At data cut-off, 107 patients were included in the combined safety analysis of both treatment arms. Rash (25 patients), neutropenia (37 patients), and diarrhea (37 patients) were reported, with 2 (8%), 33 (89%) and 6 (16%) patients, respectively, having grade 3 or greater events. No unexpected adverse events have been observed with this drug combination. Conclusions: Interim safety analysis of TYTAN study showed no significant safety issues and the Independent Data Monitoring Committee has recommended that the trial proceed as planned. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline Bristol-Myers Squibb, Chugai Pharma, Daiichi Sankyo, EMD Serono, GlaxoSmithKline, sanofi-aventis, Taiho Pharmaceutical, Yakult Honsha GlaxoSmithKline GlaxoSmithKline