gebhart/patrepeval huggingface dataset:
Analysis of variable region genes encoding a human anti-DNA antibody of normal origin. Implications for the molecular basis of human autoimmune responses. (1989)

In order to investigate the genetic basis for natural anti-DNA immune responses, we isolated and sequenced the variable gene elements (VH and VL) encoding an anti-DNA antibody expressed by a human hybridoma of normal origin (Kim4.6) and compared these sequences with those reported for four other human anti-DNA antibodies. The Kim4.6 antibody leader and VH segments were identical in nucleotide sequence with the VH1.9III germ-line VH3 gene, and the Kim4.6VL segment showed 98% nucleotide sequence identity with a V lambda I subgroup gene expressed in a Burkitt's lymphoma. Comparative analysis of Kim4.6 and other human hybridoma anti-DNA antibodies indicated that anti-DNA immune responses are diverse in terms of VH and VL gene utilization but may exhibit a bias toward rearrangement of VH genes that are over-represented in the fetal pre-B cell repertoire. Moreover, Kim4.6 and three of four other sequenced human anti-DNA antibodies appear to use a germ-line diversity gene, DXP'1, which may represent a counterpart of the DFL16.1 segment utilized in murine responses to the hapten nitrophenyl. Taken together, our findings indicate that anti-DNA immune responses can be encoded by nonmutated VH genes and that the elements and molecular mechanisms which engender this response are essentially the same among natural and lupus-associated anti-DNA antibodies. Our data also suggest that natural autoimmune responses originate early in B cell ontogeny as is consistent with the hypothesis that autoreactivity plays a major role in shaping the normal immune repertoire.
Hybrid Insulin Peptides Are Autoantigens in Type 1 Diabetes (2019)

We recently established that hybrid insulin peptides (HIPs) are present in human islets and that T cells reactive to HIPs are found in the residual islets of organ donors with type 1 diabetes (T1D). Here, we investigate whether HIP-reactive T cells are indicative of ongoing autoimmunity in patients with T1D. We used interferon-γ enzyme-linked immune absorbent spot analyses on peripheral blood mononuclear cells (PBMCs) to determine whether patients with new-onset T1D or control subjects displayed T-cell reactivity to a panel of 16 HIPs. We observed that nearly one-half of the patients responded to one or more HIPs. Responses to four HIPs were significantly elevated in patients with T1D but not in control subjects. To characterize the T cells reactive to HIPs, we used a carboxyfluorescein succinimidyl ester-based assay to clone T cells from PBMCs. We isolated six nonredundant, antigen-specific T-cell clones, most of which reacting to their target HIPs in the low nanomolar range. One T-cell clone was isolated from the same patient on two different blood draws, indicating persistence of this T-cell clone in the peripheral blood. This work suggests that HIPs are important target antigens in human subjects with T1D and may play a critical role in disease.
FLUOROMETRIC ASSAY FOR CELL PROLIFERATION IN HUMAN TUMOR CELL LINES APPLICATION (2010)

Assessment of in vitro cytotoxicity as a model to explore biological activity of compounds isolated from different sources is the first approached to search molecules with potential anticancer activity. This paper is about how to implement resazurin reduction method as an indirect indicator of cell survival. Indeed both optimal resazurin concentration and incubation time were selected on MCF-7, MKN-45, SiHa, HEp-2, HT-29 and HeLa. Next, we compared survival results by using reduction method MTT and staining method SRB defined as end-point tests, and resazurin method described as slightly toxic to cells. The comparison of the methods was done in terms of survival rate to evaluate the sensitivity of the lines to doxorubicin HCl, a medicine used in cancer. The methods were compared in terms of percentage survival by evaluating cell line sensitivity to doxorubicin HCl (a drug used in cancer treatment). The results show that resazurin reduction method used in 4.4 μM is applicable to detect significant changes in cell population exposed to cytotoxic molecules in routine testing.
Automatic clustering of software systems using a genetic algorithm (2003)

Large software systems tend to have a rich and complex structure. Designers typically depict the structure of software systems as one or more directed graphs. For example, a directed graph can be used to describe the modules (or classes) of a system and their static interrelationships using nodes and directed edges, respectively. We call such graphs "module dependency graphs" (MDGs). MDGs can be large and complex graphs. One way of making them more accessible is to partition them, separating their nodes (i.e. modules) into clusters (i.e. subsystems). In this paper, we describe a technique for finding "good" MDG partitions. Good partitions feature relatively independent subsystems that contain modules which are highly interdependent. Our technique treats finding a good partition as an optimization problem, and uses a genetic algorithm (GA) to search the extraordinarily large solution space of all possible MDG partitions. The effectiveness of our technique is demonstrated by applying it to a medium-sized software system.
3D LSI technology and reliability issues (2011)

3D integration is the most promising technology to enhance LSI performance beyond scaling theory. 3D LSIs have lots of advantages such as short wiring length, small chip size, and small pin capacitances, which leads to low power dissipation and high processing speed. However, there are still reliability problems to be solved. This paper describes mechanical stresses caused by Cu TSVs and CuSn microbumps and design guideline to minimize stress effects on 3D LSIs.
LOXL4 is downregulated in hepatocellular carcinoma with a favorable prognosis. (2015)

Lysyl oxidase like 4 (LOXL4), a member of the secreted copper-dependent amine oxidases that contribute to the assemble and maintenance of the extracellular matrix (ECM), was found to be up-regulated or down-regulated in different cancer types, suggesting its paradoxical roles in cancer. The specific role of LOXL4 in hepatocellular carcinoma (HCC), however, is still yet to be defined. Twenty-eight pairs of HCC specimens were used for LOXL4 mRNA expression analysis. The mRNA expression in HCC cell lines was examined, and HepG2 was selected for LOXL4 small interfering RNA (siRNA) interference to investigate the biological function of LOXL4, LOXL4 immunohistochemical staining was performed using a tissue microarray containing 298 HCC patients. The prognostic and diagnostic value of LOXL4 was evaluated using Cox regression and Kaplan-Meier analysis. LOXL4 mRNA or protein expression was significantly lower in HCC tissues than peritumoral tissues (LOXL4 mRNA expression, P = 0.018; LOXL4 protein expression, P < 0.001). Low LOXL4 expression was associated with lower overall survival (OS) rates and higher cumulative recurrence rates. Multivariate analysis indicated that LOXL4 was an independent prognostic indicator for OS and time to recurrence (TTR). Our results revealed that LOXL4 was down-regulated in HCC and correlated with aggressive tumors and a worse clinical outcome. LOXL4 may be a potential biomarker to identify the HCC patients with a higher risk of recurrence.
Measurement of the Systemic Inflammatory Response Predicts Cancer-Specific and Non-Cancer Survival in Patients With Cancer (2001)

The assessment of prognosis in patients with advanced cancer remains problematical. The value of C-reactive protein concentration in this context has not been clearly defined. Patients with a diagnosis of colorectal (n = 182), gastric (n = 87), breast (n = 99), or bronchogenic (n = 404) cancer and who had measurements of C-reactive protein and albumin were identified. Median survival, from the time of sampling, ranged from 478 days in the colorectal cancer patients to 60 days in patients with bronchogenic cancer. On univariate analysis, there was, in each tumor type, a significant relationship between the duration of survival and both log10 C-reactive protein and albumin concentrations (P < or = 0.0002). On multivariate analysis, in each tumor type, log10 C-reactive protein remained a significant independent predictor of survival (P < or = 0.0002). When all four groups of cancer patients were analyzed (n = 772), the hazard ratio for a 10-fold increase in C-reactive protein concentration in cancer-specific survival was 2.21 (95% confidence interval = 1.92-2.56, P < 0.0001) and the corresponding hazard ratio for non-cancer survival was 5.48 (95% confidence interval = 3.55-8.46, P < 0.0001). The results of the present study indicate that in advanced cancer patients the presence of a systemic inflammatory response and the magnitude of that response predict the duration of cancer-specific and non-cancer survival.
Leukoencephalomalacia in a horse induced by fumonisin B1 isolated from Fusarium moniliforme. (1988)

Each of two horses was dosed by stomach tube with culture material on maize of Fusarium moniliforme MRC 826. One horse developed severe hepatosis and mild oedema of the brain after 6 doses of 2.5 g of culture material/kg body mass/day in 7 days. The second horse, in a similar experiment but at a dosage rate of 1.25 g/kg/day, developed mild hepatosis and moderate oedema of the brain. In both animals the brain oedema was particularly noticeable in the medulla oblongata. The mycotoxin fumonisin B1 was extracted and purified from the culture material of F. moniliforme MRC, 826 which contained approximately 1 g/kg of this compound. A horse was injected intravenously 7 times from Day 0-Day 9 with 0.125 mg of fumonisin B1/kg body mass/day. Clinical signs of neurotoxicosis, which appeared on Day 8, included nervousness followed by apathy, a wide-based stance, trembling, ataxia, reluctance to move, paresis of the lower lip and tongue, and an inability to eat or drink. Euthanasia was performed on the horse on Day 10 while the animal was in a tetanic convulsion. The principal lesions were severe oedema of the brain and early, bilaterally symmetrical, focal necrosis in the medulla oblongata. This report provides experimental evidence that fumonisin B1, produced by F. moniliforme, causes equine leukoencephalomalacia.
The Peptide Chains of Human Plasmin (1967)

Abstract Human plasminogen and plasmin were found to be monomers by physical measurements. The cleavage of a single disulfide bond in both the proenzyme and enzyme, at pH 9, by reduction with 2-mercaptoethanol in 8 m urea, resulted in complete loss of proteolytic activity. At pH 3, activity losses paralleled the number of disulfide bonds cleaved with complete loss in activity only after total cleavage of all the disulfide bonds (21 to 22). The cleavage of the single interchain disulfide bond of plasmin at pH 9 resulted in the formation of two major chains (α and β) which were first demonstrated by starch gel electrophoresis in 8 m urea-2-mercaptoethanol systems at pH 3. S-Sulfo and S-carboxymethyl derivatives of plasmin were prepared; they were also found to contain two major chains on electrophoresis in starch gels. Sedimentation velocity measurements of both proenzyme and enzyme and their S-carboxymethyl derivatives, in urea-2-mercaptoethanol systems, confirmed the presence of plasmin chains. The amino-terminal amino acid residue of plasminogen and one plasmin chain was found to be lysine, and the amino-terminal amino acid residue of the second plasmin chain was found to be valine. The carboxyl-terminal amino acid sequence of plasminogen and one plasmin chain was found to be Leu-Asn-COOH, and the carboxyl-terminal amino acid sequence of the second plasmin chain was found to be Lys-Arg-COOH. The activation of human plasminogen monomer to plasmin monomer by urokinase is probably due to the cleavage of a single arginyl-valine bond by the activator, which results in a two-chain molecule held together by a single disulfide bond. The spontaneous proteolytic activity of human plasminogen preparations is probably due to contaminating plasmin. It is suggested that the activation of human plasminogen by other activators, such as streptokinase, trypsin, and pig heart activator, may involve a similar hydrolytic cleavage of an arginyl-valine bond.
Human neuroblastoma in nude mice. (1975)

For establishment of a reproducible model of human neuroblastoma, 2 to 5 million of established neuroblastoma cell lines (SK-N-SH, SK-N-MC) were injected s.c. or i.p. into 20 nu/nu mice of a predominantly Swiss back-ground. Following latency periods of 8 to 21 days, tumors developed at the injection site and grew to 4-ml volumes within 3 weeks. Histologically, the tumors resembled the original metastases from which the tumors were derived; however, the SK-N-SH appeared to have evidence of morphological differentiation. When compared to monolayer culture, the heterotransplanted SK-N-SH tumor had decreased dopamine-beta-hydroxylase activity and elevated cyclic adenosine 3':5'-monophosphate phosphodiesterase activity. Activity of cyclic adenosine 3':5'-monophosphate phosphodiesterase in the transplanted SK-N-MC tumor was not appreciably different from the activity in the cultured cells. Serum dopamine-beta-hydroxylase levels in the mice bearing SK-N-SH tumor increased threefold. The SK-N-MC cultured cells lacked dopamine-beta-hydroxylase and did not alter existing serum levels in the SK-N-MC tumor-bearing mice. 67Ga injected i.v. was found to localize in the tumor after 24 hr. Human neuroblastoma in the nude mouse can be a reproducible and informative model for tumor pharmacology, screening, radionuclides, tumor localization and imaging, and investigating morphological differentiation.
Effect of Chronic Intermittent Administration of Inhaled Tobramycin on Respiratory Microbial Flora in Patients with Cystic Fibrosis (1999)

Pseudomonas aeruginosa endobronchial infection causes significant morbidity and mortality among cystic fibrosis patients. Microbiology results from two multicenter, double-blind, placebo-controlled trials of inhaled tobramycin in cystic fibrosis were monitored for longitudinal changes in sputum microbial flora, antibiotic susceptibility, and selection of P. aeruginosa isolates with decreased tobramycin susceptibility. Clinical response was examined to determine whether current susceptibility standards are applicable to aerosolized administration. Treatment with inhaled tobramycin did not increase isolation of Burkholderia cepacia, Stenotrophomonas maltophilia, or Alcaligenes xylosoxidans; however, isolation of Candida albicans and Aspergillus species did increase. Although P. aeruginosa tobramycin susceptibility decreased in the tobramycin group compared with that in the placebo group, there was no evidence of selection for the most resistant isolates to become most prevalent. The definition of resistance for parenteral administration does not apply to inhaled tobramycin: too few patients had P. aeruginosa with a tobramycin MIC >/=16 microgram/mL to define a new break point on the basis of clinical response.
Long-Term Outcomes of Invasive Ipsilateral Breast Tumor Recurrences After Lumpectomy in NSABP B-17 and B-24 Randomized Clinical Trials for DCIS (2011)

Although I-IBTR increased the risk for breast cancer-related death, radiation therapy and tamoxifen reduced I-IBTR, and long-term prognosis remained excellent after breast-conserving surgery for DCIS.
The Candida albicans Biofilm Matrix: Composition, Structure and Function (2017)

A majority of infections caused by <i>Candida albicans</i>-the most frequent fungal pathogen-are associated with biofilm formation. A salient feature of <i>C. albicans</i> biofilms is the presence of the biofilm matrix. This matrix is composed of exopolymeric materials secreted by sessile cells within the biofilm, in which all classes of macromolecules are represented, and provides protection against environmental challenges. In this review, we summarize the knowledge accumulated during the last two decades on the composition, structure, and function of the <i>C. albicans</i> biofilm matrix. Knowledge of the matrix components, its structure, and function will help pave the way to novel strategies to combat <i>C. albicans</i> biofilm infections.
An MDCT Domain Frame-Loss Concealment Technique for MPEG Advanced Audio Coding (2007)

We propose a frame loss concealment technique for decoders compatible with MPEG advanced audio coding (AAC). The spectral information of the lost frame is estimated in the modified discrete cosine transform (MDCT) domain via efficient techniques that are tailored to individual source signal components: in noise-like spectral bins the MDCT coefficients are obtained by shaped-noise insertion, while coefficients in tone-dominant bins are estimated by frame interpolation followed by a refinement procedure so as to optimize the fit of the concealed frames with neighboring frames. Experimental results demonstrate that the proposed technique offers performance superior to techniques adopted in commercial AAC decoders.
A new solution route to hydrogen-terminated silicon nanoparticles: synthesis, functionalization and water stability (2007)

Hydrogen capped silicon nanoparticles with strong blue photoluminescence were synthesized by the metathesis reaction of sodium silicide, NaSi, with NH<sub>4</sub>Br. The hydrogen capped Si nanoparticles were further terminated with octyl groups and then coated with a polymer to render them water soluble. The nanoparticles were characterized by TEM, FT-IR, UV-VIS absorption, and photoluminescence. The Si nanoparticles were shown to have an average diameter of 3.9 ±1.3 nm and exhibited room-temperature photoluminescence with a peak maximum at 438 nm with a quantum efficiency of 32% in hexane and 18% in water; the emission was stable in ambient air for up to 2 months. These nanoparticles could hold great potential as a non-heavy element containing quantum dot for applications in biology.
Segmental trisomy as a mouse model for Down syndrome. (1993)

Mice trisomic for Chromosome (Chr) 16 have been used extensively as an animal model for human Down Syndrome (Trisomy 21). This system has drawbacks, however: trisomy for all of Chr 16 is incompatible with postnatal survival and produces trisomy for many more genes than those conserved in human Chr 21. We report here the development and preliminary characterization of mice that are trisomic for only the segment of mouse Chr 16 that is conserved in human Chr 21. While these segmentally trisomic mice, Ts(17(16)) 65Dn, do not appear to have all the features characteristic of Down Syndrome, they represent a mouse model that survives to adulthood and may be useful to study features of Down Syndrome that develop later in life, such as susceptibility to infection, increased incidence of leukemia, and Alzheimer-like neuropathology.
Pyruvate enhances recovery of rat hearts after ischemia and reperfusion by preventing free radical generation (1993)

Pyruvate protects myocardium from ischemic and anoxic injury, effects that have been attributed to beneficial metabolic alterations. Pyruvate also reacts with hydrogen peroxide in vitro, and pyruvate prevents free radical injury in other organs. Hearts supplied with 2 mM of pyruvate with glucose during reperfusion recovered significantly more mechanical function (81%) than those provided with 2 mM of acetate (which does not react with free radicals) and glucose (49%) or glucose alone (27%). Pyruvate significantly reduced free radical generation during reperfusion as measured with electron spin resonance using the spin-trap 5,5-dimethyl-1-pyrroline-1-oxide. In a model of direct oxidant stress, hearts were perfused with 0.28 mM of hydrogen peroxide. In this model, loss of function was almost entirely prevented by addition of 2 mM of pyruvate. From these results we conclude an important mechanism of protection when pyruvate is supplied during reperfusion is limitation of oxygen-derived free radical damage.
The State of Charge Estimating Methods for Battery: A Review (2013)

An overview of new and current developments in state of charge (SOC) estimating methods for battery is given where the focus lies upon mathematical principles and practical implementations. As the battery SOC is an important parameter, which reflects the battery performance, so accurate estimation of SOC cannot only protect battery, prevent overcharge or discharge, and improve the battery life, but also let the application make rationally control strategies to achieve the purpose of saving energy. This paper gives a literature survey on the categories and mathematical methods of SOC estimation. Based on the assessment of SOC estimation methods, the future development direction of SOC estimation is proposed.
安德烈·关纳—他的设计思路的回顾及其在今天的应用 (1991)

今年是安德烈·关纳(Andre Coyne)(1891-1960)诞辰一百周年纪念。他是一往著名的工程师，新思路的创造者和推广者，他还是一位领导人，造诣根深的学者和音乐家。他的许多思路和创新为发展铺平了道路，甚至在今天，导致了新的应用。本文讨论他的最重要的六项设计思路，并跟踪这些思路至今在坝工建设中的应用发展情况。
High Level Phosphatase Activity Revealed in Chronic Lymphocytic Leukemia Cells That Use Mutated Immunoglobulin Heavy Chain Variable Region Genes and Lack High-Level Expression of the Zeta-Associated Protein 70 (ZAP-70). (2007)

Abstract Signals propagated through the B cell receptor (BCR) guide the maturation and survival of B cells and might factor in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). BCR signaling in CLL cells was investigated at the single-cell level using multiparametric flow cytometry. Concurrent analysis was performed using fluorochrome-conjugated antibodies specific for B-cell surface antigens and a panel of antibodies recognizing specific phospho-peptide epitopes within a selected group of intracellular signaling proteins. CLL samples from patients (N=6) showed weak or minimal signaling activity at p72SYK/p70ZAP, Erk1/2, B-Cell linker protein (BLNK) and phospholipase-Cγ-2, (PLCγ2) when stimulated only at the BCR with anti-μ crosslinking, whereas a robust signal was observed in a control Ramos B cell line. The low-level signaling in CLL cells could be accounted for by either a defect in activation of a key protein required for signaling, or by enhanced inhibition mediated by phosphatases such as SHIP-1, SHIP-2, SHP-1, or SHP-2. To determine whether phosphatases were preventing or dampening BCR activation in CLL samples, CLL cells were treated with hydrogen peroxide (H2O2), a physiologic phosphatase inhibitor generated during BCR signaling that has been used previously to reveal dysregulated BCR signaling in follicular lymphoma (Sing et al., Cell 2005, Reth., Nat. Immunol. 2002, Irish et al., Blood 2006). H2O2 treatment of CLL cells that had molecular features associated with indolent disease (e.g. use of mutated immunoglobulin heavy chain variable region genes (IgVH) and a low level expression of ZAP70) induced high-levels of phosphorylated p72SYK/p70ZAP, ERK1/2, BLNK, and PLCγ2, independent of surface F(ab)2anti-μ ligation. In contrast, CLL-B cells that had molecular features associated with more aggressive disease (expression of unmutated IgVH and high-level expression of ZAP-70) were significantly less responsive to this treatment, even in the presence of F(ab)2anti-μ. Exposure of blood B cells from healthy donors to H2O2 failed to elicit a substantial increase in phosphorylation of these same intracellular signaling proteins. These studies reveal a previously unrecognized, constitutive high-level phosphatase activity in CLL cells that express mutated IgVH and low levels of ZAP-70, possibly contributing to the attenuated signaling observed in these cells following surface IgM ligation. Because this high level of constitutive phosphatase activity was not observed in CLL cells that express unmutated IgVH with high-level expression of ZAP70, flow cytometric measurement of the increased phosphorylation triggered by H2O2 could provide for a useful means with which to distinguish leukemia cells from patients with indolent versus aggressive CLL. Evaluation of additional samples is ongoing to test this hypothesis.