gebhart/patrepeval huggingface dataset:
Identification of Phosphatidylinositol 4-Kinase Type II β as the First HLA Class II Associated Minor Histocompatibility Antigen Involved in Graft Versus Leukemia Reactivity. (2007)

Abstract Patients with hematological malignancies can be successfully treated with HLA-matched T cell-depleted allogeneic stem cell transplantation (alloSCT) and subsequent donor lymphocyte infusions (DLI). The efficacy of DLI is mediated by donor T cells recognizing minor histocompatibility antigens (mHags) on malignant recipient cells. Since HLA class II molecules are predominantly expressed on hematopoietic cells, mHag specific CD4+ T cells may selectively mediate Graft-versus-Leukemia (GvL) reactivity without Graft-versus-Host Disease (GvHD). Clinical studies have shown that adoptive transfer of CD4+ donor lymphocytes after HLA-matched alloSCT may lead to clinical remissions with a reduced incidence of GvHD, emphasizing the relevance of CD4+ T cells and HLA class II associated mHags for development of effective anti-tumor T cell therapies after alloSCT with a low risk for GvHD. The aim of this study was to identify the HLA class II associated mHag that is recognized by CD4+ T cells induced in a patient with relapsed chronic myeloid leukemia (CML) after HLA-matched alloSCT who developed strong GvL reactivity with mild GvHD of the skin after treatment with DLI. We previously developed recombinant bacteria cDNA expression libraries based on delivery of exogenous antigens for identification of HLA class II antigens and used this method for identification of the first autosomal HLA class II (HLA-DQB1*0603) associated mHag LB-PI4K2B-1S. LB-PI4K2B-1S has a population frequency of 40–50% and is encoded by the broadly-expressed phosphatidylinositol 4-kinase type II β gene. In the patient with CML, a polyclonal CD4+ T cell response against LB-PI4K2B-1S and simultaneous mHag specific CD8+ T cells were demonstrated. LB-PI4K2B-1S specific CD4+ T cells were shown to recognize the CD34+ CML cells of the patient as well as other leukemic cells. Recognition and lysis of normal hematopoietic cells by LB-PI4K2B-1S specific CD4+ T cells critically depended on the number of HLA-DQ molecules expressed at the cell surface and was restricted to high HLA-DQ-expressing B cells, mature dendritic cells (DC) and EBV-transformed B cells. HLA-DQ expression on T cells, PHA-stimulated blasts, monocytes and immature DC was absent or low and not sufficient for T cell recognition. We also demonstrated that HLA-DQ expression on normal cells of non-hematopoietic origin after extensive culturing with IFN-γ was moderately upregulated as compared to HLA-DR and -DP and not sufficient for recognition by LB-PI4K2B-1S specific CD4+ T cells. In conclusion, the data suggest that LB-PI4K2B-1S specific CD4+ T cells mediated tumor rejection by directly eliminating the malignant cells of the patient as effector cells and stimulating the induction and maintenance of CD8+ T cell immunity as helper cells, and HLA-DQ associated mHags may be appropriate targets for T cell therapies with the aim to selectively stimulate GvL after HLA-matched alloSCT with a low risk for GvHD.
A Sub-1 μW multiparameter injectable BioMote for continuous alcohol monitoring (2018)

This paper presents a wireless, fully-integrated, miniature “BioMote” sensor node that can be injected through a 16-gauge syringe for continuous, long-term alcohol monitoring. A microelectrode electrochemical sensor array that measures alcohol, background, and pH was implemented to differentially measure ethanol while removing interference and motion artifacts. The low-power multi-technique potentiostat supports both amperometric and potentiometric techniques achieving 2.5 nA sensitivity with 30.1 dB dynamic range and 0.5 mV sensitivity with 43 dB dynamic range, respectively. The measurements are transmitted to a wearable device through backscatter using a self-oscillating current-to-frequency (I-to-F) converter. The system is wirelessly powered via the coupling between an on-chip 4-turn coil and a wearable device at 985 MHz. The self-contained 0.85×1.5 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> chip is implemented in 65 nm CMOS and consumes 970 nW.
An Analysis of the Binding of Repressor Protein ModE to modABCD (Molybdate Transport) Operator/Promoter DNA of Escherichia coli (1999)

Expression of the modABCD operon in Escherichia coli, which codes for a molybdate-specific transporter, is repressed by ModE in vivo in a molybdate-dependent fashion. In vitro DNase I-footprinting experiments identified three distinct regions of protection by ModE-molybdate on the modA operator/promoter DNA, GTTATATT (-15 to -8; region 1), GCCTACAT (-4 to +4; region 2), and GTTACAT (+8 to +14; region 3). Within the three regions of the protected DNA, a pentamer sequence, TAYAT (Y = C or T), can be identified. DNA-electrophoretic mobility experiments showed that the protected regions 1 and 2 are essential for binding of ModE-molybdate to DNA, whereas the protected region 3 increases the affinity of the DNA to the repressor. The stoichiometry of this interaction was found to be two ModE-molybdate per modA operator DNA. ModE-molybdate at 5 nM completely protected the modABCD operator/promoter DNA from DNase I-catalyzed hydrolysis, whereas ModE alone failed to protect the DNA even at 100 nM. The apparent K(d) for the interaction between the modA operator DNA and ModE-molybdate was 0.3 nM, and the K(d) increased to 8 nM in the absence of molybdate. Among the various oxyanions tested, only tungstate replaced molybdate in the repression of modA by ModE, but the affinity of ModE-tungstate for modABCD operator DNA was 6 times lower than with ModE-molybdate. A mutant ModE(T125I) protein, which repressed modA-lac even in the absence of molybdate, protected the same region of modA operator DNA in the absence of molybdate. The apparent K(d) for the interaction between modA operator DNA and ModE(T125I) was 3 nM in the presence of molybdate and 4 nM without molybdate. The binding of molybdate to ModE resulted in a decrease in fluorescence emission, indicating a conformational change of the protein upon molybdate binding. The fluorescence emission spectra of mutant ModE proteins, ModE(T125I) and ModE(Q216*), were unaffected by molybdate. The molybdate-independent mutant ModE proteins apparently mimic in its conformation the native ModE-molybdate complex, which binds to a DNA sequence motif of TATAT-7bp-TAYAT.
Parallel Genotyping of Over 10,000 SNPs Using a One-Primer Assay on a High-Density Oligonucleotide Array (2004)

The analysis of single nucleotide polymorphisms (SNPs) is increasingly utilized to investigate the genetic causes of complex human diseases. Here we present a high-throughput genotyping platform that uses a one-primer assay to genotype over 10,000 SNPs per individual on a single oligonucleotide array. This approach uses restriction digestion to fractionate the genome, followed by amplification of a specific fractionated subset of the genome. The resulting reduction in genome complexity enables allele-specific hybridization to the array. The selection of SNPs was primarily determined by computer-predicted lengths of restriction fragments containing the SNPs, and was further driven by strict empirical measurements of accuracy, reproducibility, and average call rate, which we estimate to be >99.5%, >99.9%, and>95%, respectively [corrected]. With average heterozygosity of 0.38 and genome scan resolution of 0.31 cM, the SNP array is a viable alternative to panels of microsatellites (STRs). As a demonstration of the utility of the genotyping platform in whole-genome scans, we have replicated and refined a linkage region on chromosome 2p for chronic mucocutaneous candidiasis and thyroid disease, previously identified using a panel of microsatellite (STR) markers.
Inhibition of acquired immunodeficiency syndrome virus by oligodeoxynucleoside methylphosphonates. (1988)

Antisense oligodeoxynucleotides containing internucleoside methylphosphonate linkages were examined for their ability to inhibit human immunodeficiency virus (HIV)-induced syncytium formation and virus expression. HIV inhibitory activity was found to be dependent on both chain length and the number of phosphonate residues. Introduction of 18 phosphonate groups in an oligomer of chain length 20 significantly increased HIV inhibitory activity relative to the parent oligonucleotide, whereas 5 such groups showed little or no increase in the HIV inhibition capacity. Methylphosphonate-linked oligomers are more stable to nuclease degradation and hence could be potentially useful in the treatment of acquired immunodeficiency syndrome.
Fast block matching algorithms for motion estimation (2002)

Motion compensation is an effective method for reducing temporal redundancy found in video sequence compression. However, the complexity of the full-search block matching algorithm (BMA) is extremely high and a number of fast algorithms have been proposed to reduce the computational complexity of the BMA. We propose three techniques for reducing the arithmetic complexity of the BMA. They are namely: (1) domain decimation, (2) error function subsampling, and (3) multiple candidates search. The domain decimation and error function decimation try to reduce the arithmetic complexity by reducing the number of operations in each comparison, the search range and number of locations searched. The multiple candidates search is a technique used to increase the robust of such algorithms. Combination of these techniques can generate algorithms with different tradeoff between arithmetic complexity and quality of prediction.
Introducing Control Flow into Vectorized Code (2007)

Single instruction multiple data (SIMD) functional units are ubiquitous in modern microprocessors. Effective use of these SIMD functional units is essential in achieving the highest possible performance. Automatic generation of SIMD instructions in the presence of control flow is challenging, however, not only because SIMD code is hard to generate in the presence of arbitrarily complex control flow, but also because the SIMD code executing the instructions in all control paths may slow compared to the scalar original, which may bypass a large portion of the code. One promising technique introduced recently involves inserting branches-on-superword-condition-codes (BOSCCs) to bypass vector instructions. In this paper, we describe two techniques that improve on the previous approach. First, BOSCCs are generated in a nested fashion so that even BOSCCs themselves can be bypassed by other BOSCCs. Second, we generate all vec_any_* instructions to bypass even some predicate-defining instructions. We implemented these techniques in a vectorizing compiler. On 14 kernels, the compiler achieves distinct speedups, including 1.99X over the previous technique that generates single- level BOSCCs and vec_any_ne only.
Immunogenicity of therapeutic monoclonal antibodies. (2003)

There are currently 13 monoclonal antibodies or antibody constructs approved for therapeutic use in the US and at least another 400 products are in clinical testing or undergoing regulatory review. Despite widespread use and development of therapeutic monoclonal antibodies, limited information exists regarding the incidence and consequence of immune antibodies generated against many of these products. In this review, analytical methodology and recent data on the immunogenicity of approved therapeutic monoclonal antibodies will be presented. The implications of these findings in relation to potential concerns for repeated or chronic treatment with these powerful and specific therapeutic agents will be discussed.
Spontaneous human squamous cell carcinomas are killed by a human cytotoxic T lymphocyte clone recognizing a wild-type p53-derived peptide (1996)

A cytotoxic T lymphocyte (CTL) clone generated in vitro from the peripheral blood of a healthy HLA-A2-positive individual against a synthetic p53 protein-derived wild-type peptide (L9V) was shown to kill squamous carcinoma cell lines derived from two head and neck carcinomas, which expressed mutant p53 genes, in a L9V/HLA-A2 specific and restricted fashion. Thus, the normal tolerance against endogenously processed p53 protein-derived self-epitopes can be broken by peptide-specific in vitro priming. p53 protein-derived wild-type peptides might thus represent tumor associated target molecules for immunotherapeutical approaches.
SomaticSF3B1Mutation in Myelodysplasia with Ring Sideroblasts (2011)

Mutations in SF3B1 implicate abnormalities of messenger RNA splicing in the pathogenesis of myelodysplastic syndromes. (Funded by the Wellcome Trust and others.).
Abnormal function of the bone marrow microenvironment in chronic myelogenous leukemia: role of malignant stromal macrophages (1995)

The bone marrow microenvironment supports and regulates the proliferation and differentiation of hematopoietic cells. Dysregulated hematopoiesis in chronic myelogenous leukemia (CML) is caused, at least in part, by abnormalities in CML hematopoietic progenitors leading to altered interactions with the marrow microenvironment. The role of the microenvironment itself in CML has not been well characterized. We examined the capacity of CML stroma to support the growth of long-term culture-initiating cells (LTC-IC) obtained from normal and CML marrow. The growth of normal LTC-IC on CML stroma was significantly reduced compared with normal stroma. This did not appear to be related to abnormal production of soluble factors by CML stroma because normal LTC-IC grew equally well in Transwells above CML stroma as in Transwells above normal stroma. In addition, CML and normal stromal supernatants contained similar quantities of both growth-stimulatory (granulocyte colony-stimulating factor (CSF), interleukin-6, stem cell factor, granulocyte-macrophage CSF, and interleukin-1 beta) and growth-inhibitory cytokines (transforming growth factor-beta, macrophage inflammatory protein-1 alpha, and tumor necrosis factor-alpha). The relative proportion of different cell types in CML and normal stroma was similar. However, polymerase chain reaction and fluorescence in situ hybridization studies showed the presence of bcr-abl-positivo cells in CML stroma, which were CD14+ stromal macrophages. To assess the effect of these malignant macrophages on stromal function, CML and normal stromal cells were separated by fluorescence-activated cell sorting into stromal mesenchymal cell (CD14-) and macrophage (CD14+) populations. CML and normal CD14- cells supported the growth of normal LTC-IC equally well. However, the addition of CML macrophages to normal or CML CD14- mesenchymal cells resulted in impaired progenitor support. This finding indicates that the abnormal function of CML bone marrow stroma is related to the presence of malignant macrophages. In contrast to normal LTC-IC, the growth of CML LTC-IC on allogeneic CML stromal layers was not impaired and was significantly better than that of normal LTC-IC cocultured with the same CML stromal layers. These studies demonstrate that, in addition to abnormalities in CML progenitors themselves, abnormalities in the CML marrow microenvironment related to the presence of malignant stromal macrophages may contribute to the selective expansion of leukemic progenitors and suppression of normal hematopoiesis in CML.
On beyond classic RACE (rapid amplification of cDNA ends). (1994)

Most attempts to identify and isolate a novel cDNA result in the acquisition of clones that represent only a part of the mRNA's complete sequence. The missing sequence (cDNA ends) can be cloned by PCR, using a technique variously called rapid amplification of cDNA ends (RACE), (1) anchored PCR,(2) or one-sided PCR. (3) Since the initial reports of this technique, many laboratories have developed significant improvements on the basic approach. (4-16) I will describe here the most recent hybrid version of the relatively simple classic RACE, and a more powerful but technically more challenging new RACE protocol that is adapted from the work of a number of laboratories. ~ 24) Commercial RACE kits that are convenient but not as powerful as the most recent versions of classic and new RACE are available from Bethesda Research Laboratories(~l) and Clontech. 5' UTR Coding 3' UTR mRNA Partial cDNA clone ~ [ ~g ~~~D ~~ ~
High performance MPI design using unreliable datagram for ultra-scale InfiniBand clusters (2007)

High-performance clusters have been growing rapidly in scale. Most of these clusters deploy a high-speed interconnect, such as Infini-Band, to achieve higher performance. Most scientific applications executing on these clusters use the Message Passing Interface (MPI) as the parallel programming model. Thus, the MPI library has a key role in achieving application performance by consuming as few resources as possible and enabling scalable performance. State-of-the-art MPI implementations over InfiniBand primarily use the Reliable Connection (RC) transport due to its good performance and attractive features. However, the RC transport requires a connection between every pair of communicating processes, with each requiring several KB of memory. As clusters continue to scale, memory requirements in RC-based implementations increase. The connection-less Unreliable Datagram (UD) transport is an attractive alternative, which eliminates the need to dedicate memory for each pair of processes.In this paper we present a high-performance UD-based MPI design. We implement our design and compare the performance and resource usage with the RC-based MVAPICH. We evaluate NPB, SMG2000, Sweep3D, and sPPM up to 4K processes on an 9216-core InfiniBand cluster. For SMG2000, our prototype shows a 60% speedup and seven-fold reduction in memory for 4K processes. Additionally, based on our model, our design has an estimated 30 times reduction in memory over MVAPICH at 16K processes when all connections are created. To the best of our knowledge, this is the first research work that presents a high-performance MPI design over InfiniBand that is completely based on UD and can achieve near identical or better application performance than RC.
A Novel Sulindac Derivative Inhibits Lung Adenocarcinoma Cell Growth through Suppression of Akt/mTOR Signaling and Induction of Autophagy (2013)

Nonsteroidal anti-inflammatory drugs such as sulindac sulfide have shown promising antineoplastic activity in multiple tumor types, but toxicities resulting from COX inhibition limit their use in cancer therapy. We recently described a N,N-dimethylethyl amine derivative of sulindac sulfide, sulindac sulfide amide (SSA), that does not inhibit COX-1 or -2, yet displays potent tumor cell growth-inhibitory activity. Here, we studied the basis for the growth-inhibitory effects of SSA on human lung adenocarcinoma cell lines. SSA potently inhibited the growth of lung tumor cells with IC50 values of 2 to 5 μmol/L compared with 44 to 52 μmol/L for sulindac sulfide. SSA also suppressed DNA synthesis and caused a G0-G1 cell-cycle arrest. SSA-induced cell death was associated with characteristics of autophagy, but significant caspase activation or PARP cleavage was not observed after treatment at its IC50 value. siRNA knockdown of Atg7 attenuated SSA-induced autophagy and cell death, whereas pan-caspase inhibitor ZVAD was not able to rescue viability. SSA treatment also inhibited Akt/mTOR signaling and the expression of downstream proteins that are regulated by this pathway. Overexpression of a constitutively active form of Akt was able to reduce autophagy markers and confer resistance to SSA-induced cell death. Our findings provide evidence that SSA inhibits lung tumor cell growth by a mechanism involving autophagy induction through the suppression of Akt/mTOR signaling. This unique mechanism of action, along with its increased potency and lack of COX inhibition, supports the development of SSA or related analogs for the prevention and/or treatment of lung cancer.
The effects of laminarin derived fromLaminaria digitataon measurements of gut health: selected bacterial populations, intestinal fermentation, mucin gene expression and cytokine gene expression in the pig (2011)

The aim of the present study was to establish the optimum inclusion level of laminarin derived from Laminaria digitata on selected microbial populations, intestinal fermentation, cytokine and mucin gene expression in the porcine ileum and colon. A total of twenty-one pigs (mean body weight 17·9 kg) were randomly assigned to one of three dietary treatments: T1 - basal (control) diet, T2 and T3 - basal diets supplemented with laminarin included at 300 and 600 parts per million (ppm), respectively. Selected intestinal bacterial populations and volatile fatty acid (VFA) concentrations were measured in the ileum and colon. Relative gene expression levels for specific cytokine and mucin genes were investigated in ileal and colonic tissue in the absence and presence of a lipopolysaccharide (LPS) challenge. There was an up-regulation of MUC2 gene expression at the 300 ppm inclusion level in the ileum. In the colon, there was a significant reduction in the enterobacteriaceae population at the 300 ppm inclusion level (P = 0·0421). Dietary supplementation of 600 ppm laminarin led to a significant increase in MUC2 (P = 0·0365) and MUC4 (P = 0·0401) expression in the colon, and in the total VFA concentration in the caecum (P = 0·0489). A significant increase was also recorded in IL-6 (P = 0·0289) and IL-8 gene expression (P = 0·0245) in LPS-challenged colonic tissue at both laminarin inclusion levels. In conclusion, dietary inclusion of 300 ppm laminarin appears to be the optimum dose in the present study due to the reduction in the enterobacteriaceae populations and enhanced IL-6 and IL-8 cytokine expression in response to an ex vivo LPS challenge.
Artificial tears potpourri: a literature review (2014)

Numerous brands and types of artificial tears are available on the market for the treatment of dysfunctional tear syndrome. Past literature has focused on comparing the components of these products on patient's clinical improvement. The wide array of products on the market presents challenges to both clinicians and patients when trying to choose between available tear replacement therapies. Different formulations affect patients based on etiology and severity of disease. In order to provide an unbiased comparison between available tear replacement therapies, we conducted a literature review of existing studies and National Institutes of Health clinical trials on commercially available, brand name artificial tears. Outcomes evaluated in each study, as well as the percent of patients showing clinical and symptomatic improvement, were analyzed. Fifty-one studies evaluating different brands of artificial tears, and their efficacy were identified. Out of the 51 studies, 18 were comparison studies testing brand name artificial tears directly against each other. Nearly all formulations of artificial tears provided significant benefit to patients with dysfunctional tear syndrome, but some proved superior to others. From the study data, a recommended treatment flowchart was derived.