gebhart/patrepeval huggingface dataset:
Introducing technology into the Linux kernel (2008)

There can be no doubt that a great many technologies have been added to Linux™ over the past ten years. What is less well-known is that it is often necessary to introduce a large amount of Linux into a given technology in order to successfully introduce that technology into Linux. This paper illustrates such an introduction of Linux into technology with Read-Copy Update (RCU). The RCU API's evolution over time clearly shows that Linux's extremely diverse set of workloads and platforms has changed RCU to a far greater degree than RCU has changed Linux---and it is reasonable to expect that other technologies that might be proposed for inclusion into Linux would face similar challenges. In addition, this paper presents a summary of lessons learned and an attempt to foresee what additional challenges Linux might present to RCU.
Chromosomal integration of phage lambda by means of a DNA insertion element. (1978)

Phage lambdacam112, which contains the chloramphenicol resistance transposon Tn9 and has a deletion of attP and the int gene, will lysogenize Escherichia coli K-12. Prophage integration occurs at different chromosomal sites, including lacY and malB, but not at attB. All lambdacam112 prophages are excised from the chromosome after induction but with various efficiencies for different locations. Heteroduplex analysis of lambdaplacZ transducing phages isolated from a lacY::lambdacam112 prophage reveals an insertion sequence 1 (IS1) element at the joint of viral and chromosomal DNA. Two lines of evidence indicate that lambdacam112 encodes an excision activity that recognizes the IS1 element: (i) prophage derepression increases the frequency of excision from lacY to yield lac+ revertants, and (ii) lambdacam112 infection increases reversion of a galT::IS1 mutation about 50-fold. Our results indicate that the IS1 termini of TN9 can replace attP as a site for lambda insertion in the bacterial chromosome and that excision events are catalyzed by an IS1-encoded protein under lambda repressor and N gene control.
A Quantitative Study of the Interactions of Bacillus anthracis Edema Factor and Lethal Factor with Activated Protective Antigen (2000)

Bacillus anthracis secretes three proteins, which associate in binary combinations to form toxic complexes at the surface of mammalian cells. Receptor-bound protective antigen (PA) is proteolytically activated, yielding a 63 kDa fragment (PA(63)). PA(63) oligomerizes into heptamers, which bind edema factor (EF) or lethal factor (LF) to form the toxic complexes. We undertook a quantitative analysis of the interactions of EF with PA(63) by means of surface plasmon resonance (SPR) measurements. Heptameric PA(63) was covalently bound by amine coupling to an SPR chip, or noncovalently bound via a C-terminal hexahistidine tag on the protein to Ni(2+)nitrilotriacetate groups on the chip. Values of k(on) and k(off) for EF at 23 degrees C were approximately 3 x 10(5) M(-)(1) s(-)(1) and (3-5) x 10(-)(4) s(-)(1), respectively, giving a calculated K(d) of (1-2) x 10(-)(9) M. A similar value of K(d) (7 x 10(-)(10) M) was obtained when we measured the binding of radiolabeled EF to receptor-bound PA(63) on the surface of L6 cells (at 4 degrees C). Each of these analyses was also performed with LF and LF(N) (the N-terminal 255 residues of LF), and values obtained were comparable to those for EF. The similarity in the dissociation constants determined by SPR and by measurements on the cell surface suggests that the presence of the receptor does not play a large role in the interaction between PA(63) and EF/LF.
Specificity of Leptin Action on Elevated Blood Glucose Levels and Hypothalamic Neuropeptide Y Gene Expression in ob/ob Mice (1996)

Correction of the obese state induced by genetic leptin deficiency reduces elevated levels of both blood glucose and hypothalamic neuropeptide Y (NPY) mRNA in ob/ob mice. To determine whether these responses are due to a specific action of leptin or to the reversal of the obese state, we investigated the specificity of the effect of systemic leptin administration to ob/ob mice (n = 8) on levels of plasma glucose and insulin and on hypothalamic expression of NPY mRNA. Saline-treated controls were either fed ad libitum (n = 8) or pair-fed to the intake of the leptin-treated group (n = 8) to control for changes of food intake induced by leptin. The specificity of the effect of leptin was further assessed by 1) measuring NPY gene expression in db/db mice (n = 6) that are resistant to leptin, 2) measuring NPY gene expression in brain areas outside the hypothalamus, and 3) measuring the effect of leptin administration on hypothalamic expression of corticotropin-releasing hormone (CRH) mRNA. Five daily intraperitoneal injections of recombinant mouse leptin (150 micrograms) in ob/ob mice lowered food intake by 56% (P < 0.05), body weight by 4.1% (P < 0.05), and levels of NPY mRNA in the hypothalamic arcuate nucleus by 42.3% (P < 0.05) as compared with saline-treated controls. Pair-feeding of ob/ob mice to the intake of leptin-treated animals produced equivalent weight loss, but did not alter expression of NPY mRNA in the arcuate nucleus. Leptin administration was also without effect on food intake, body weight, or NPY mRNA levels in the arcuate nucleus of db/db mice. In ob/ob mice, leptin did not alter NPY mRNA levels in cerebral cortex or hippocampus or the expression of CRH mRNA in the hypothalamic paraventricular nucleus (PVN). Leptin administration to ob/ob mice also markedly reduced serum glucose (8.3 +/- 1.2 vs. 24.5 +/- 3.8 mmol/l; P < 0.01) and insulin levels (7,263 +/- 1,309 vs. 3,150 +/- 780 pmol/l), but was ineffective in db/db mice. Pair-fed mice experienced reductions of glucose and insulin levels that were < 60% of the reduction induced by leptin. The results suggest that in ob/ob mice, systemic administration of leptin inhibits NPY gene overexpression through a specific action in the arcuate nucleus and exerts a hypoglycemic action that is partly independent of its weight-reducing effects. Furthermore, both effects occur before reversal of the obesity syndrome. Defective leptin signaling due to either leptin deficiency (in ob/ob mice) or leptin resistance (in db/db mice) therefore leads directly to hyperglycemia and the overexpression of hypothalamic NPY that is implicated in the pathogenesis of the obesity syndrome.
Kinetic studies on depurination and detritylation of CPG-bound intermediates during oligonucleotide synthesis (1996)

Fully protected CPG-immobilized monomer, dimer and trimer oligonucleotides were used to study depurination during the chemical synthesis of oligonucleotides. Disappearance of the oligonucleotide during acid exposure time relative to an internal thymidine standard not subject to depurination was monitored by reverse phase HPLC analysis. Depurination half-times obtained for dichloroacetic acid (DCA) and trichloroacetic acid (TCA) in methylene chloride were found to be 3% DCA >> 15% DCA > 3% TCA. In order to understand the implications of depurination during DNA synthesis, the detritylation kinetics of model compounds DMT-dG-pT dimer and DMT-[17mer] mixed-base sequence were also measured. These results improve our ability to properly balance the contradictory goals of obtaining maximum detritylation with minimum depurination in oligonucleotide synthesis.
Efficient Generation of Transgenic Rats Through the Male Germline Using Lentiviral Transduction and Transplantation of Spermatogonial Stem Cells (2007)

Spermatozoa produced from spermatogonial stem cells (SSCs) are the vehicle by which genes of a male are passed to the next generation. A single SSC has the ability to self-renew and produce thousands of spermatozoa; therefore, it is an ideal target for genetic modification to efficiently generate transgenic animals in mammalian species. Rats are an important model organism for biological research; however, gene function studies have been difficult because of a limited ability to generate transgenic animals. Transgenic rat production through SSCs offers a means to overcome this obstacle. Because SSCs divide slowly both in vivo and in vitro, lentiviral vectors may be an ideal method for introducing stable genetic modification. Using a lentiviral vector, an enhanced green fluorescent protein (eGFP) transgene was introduced into the genome of cultured rat SSCs, which were microinjected into testes of immunodeficient mice to assess transduction efficiency. Approximately 40% of rat SSCs exposed to the lentiviral vector overnight carried the eGFP transgene and generated colonies of spermatogenesis. When transduced SSCs were transplanted into recipient rat testes, in which endogenous germ cells had been decreased but not eliminated by busulfan treatment, approximately 6% of offspring were transgenic. The transgene was stably integrated into the donor SSC genome and transmitted to and expressed by progeny in subsequent generations. Thus, lentiviral transduction of SSCs followed by transplantation is an effective means for generating transgenic rats through the male germline, and this approach may be applicable to other species in which existing methods are inadequate or not applicable.
Differential Internalization of Superparamagnetic Iron Oxide Nanoparticles in Different Types of Cells (2010)

Superparamagnetic iron oxide nanoparticles (SPION) have attracted great attention for nanomedical applications, but the mechanisms underlying the transmembrane transport of SPION in variant cells has not been fully defined. The present study investigated the internalization of SPION in three cell models with different phagocytic capacity using transmission electron microscopy (TEM) and energy dispersive spectrometer (EDS) analyses. The EDS study aimed to further confirm if the suspected internalized particles were iron-containing SPION. SPION could be taken up quickly by macrophage-like cell line RAW264.7 (with strong phagocytic capacity) and slowly by the 3T3-L1 cells (with weak phagocytic capacity), but not by red blood cells (with no phagocytic capacity). The internalized SPION were mainly found in the cytoplasmic vesicles, with no localization in the endoplasmic reticulum, mitochondria and nucleus. We conclude that the internalization of SPION in the three types of mammalian cells was mediated by phagocytosis, not by direct membrane penetration.
Regional Shape Control of Strategically Assembled Multishape Memory Vitrimers (2015)

Hot-pressing shape memory vitrimers lead to multishape memory, multifunctionality, easy reconfiguration, and the possibility of mass production of arbitrary smart structures.
Dual Roles for Glucokinase in Glucose Homeostasis as Determined by Liver and Pancreatic β Cell-specific Gene Knock-outs Using Cre Recombinase (1999)

Glucokinase (GK) gene mutations cause diabetes mellitus in both humans and mouse models, but the pathophysiological basis is only partially defined. We have used cre-loxP technology in combination with gene targeting to perform global, beta cell-, and hepatocyte-specific gene knock-outs of this enzyme in mice. Gene targeting was used to create a triple-loxed gk allele, which was converted by partial or total Cre-mediated recombination to a conditional allele lacking neomycin resistance, or to a null allele, respectively. beta cell- and hepatocyte-specific expression of Cre was achieved using transgenes that contain either insulin or albumin promoter/enhancer sequences. By intercrossing the transgenic mice that express Cre in a cell-specific manner with mice containing a conditional gk allele, we obtained animals with either a beta cell or hepatocyte-specific knock-out of GK. Animals either globally deficient in GK, or lacking GK just in beta cells, die within a few days of birth from severe diabetes. Mice that are heterozygous null for GK, either globally or just in the beta cell, survive but are moderately hyperglycemic. Mice that lack GK only in the liver are only mildly hyperglycemic but display pronounced defects in both glycogen synthesis and glucose turnover rates during a hyperglycemic clamp. Interestingly, hepatic GK knock-out mice also have impaired insulin secretion in response to glucose. These studies indicate that deficiencies in both beta cell and hepatic GK contribute to the hyperglycemia of MODY-2.
Exercise increases soluble vascular endothelial growth factor receptor-1 (sFlt-1) in circulation of healthy volunteers. (2006)

We have demonstrated that circulating sFlt-1 is significantly increased by exercise in healthy volunteers, which is functionally associated with a transient decrease in circulating free VEGF. This data may provide new insight into the molecular links between physical inactivity and risk of cancer and atherosclerosis.
T-cell Tolerance and Autoimmune Diabetes (2001)

Herein we describe the major signaling events that occur in T-cells upon T-cell receptor (TCR) engagement, and the mechanisms responsible for the induction of T-cell anergy that may ultimately lead to the development of immunospecific therapies in T-cell mediated autoimmune diseases. A new type of antigen presenting molecule (dimeric MHC class-II/peptide, DEF) endowed with antigen-specific immunomodulatory effects such as induction of Th2 polarization and T-cell anergy is also described as a potential antidiabetogenic agent. According to our preliminary results, the MHC II/peptide-based approach may provide rational grounds for further development of antigen-specific immunotherapeutic agents such as human-like MHC lI/peptide chimeras endowed with efficient down-regulatory effects in CD4 T-cell-mediated autoimmune diseases such as Type 1 diabetes, multiple sclerosis, primary biliary cirrhosis, and rheumatoid arthritis.
Double-ternary complex affinity chromatography: preparation of alcohol dehydrogenases (1976)

A general affinity chromatographic method for alcohol dehydrogenase purification has been developed by employing immobilized 4-substituted pyrazole derivatives that isolate the enzyme through formation of a specific ternary complex. Sepharose 4B is activated with 300 mg of cyanogen bromide/ml of packed gel and coupled to 4-[3-(N-6-aminocaproyl)aminopropyl]pyrazole. From crude liver extracts in 50 mM phosphate-0.37 mM nicotinamide adenine dinucleotide, pH 7.5, alcohol dehydrogenase is optimally bound at a capacity of 4-5 mg of enzyme/ml of gel. Addition of ethanol, propanol, or butanol, 500 mM, results in the formation of a second ternary complex, which allows the elution of bound enzyme in high yield and purity. This double-ternary complex affinity chromatography has been applied successfully to human, horse, rat, and rabbit liver extracts to isolate the respective homogeneous alcohol dehydrogenases.
In Vitro and In Vivo Quantification of Adhesion Between Leukocytes and Vascular Endothelium (2003)

When a leukocyte enters a blood vessel, it may continue to move with flowing blood, collide with the vessel wall, adhere transiently or stably, and finally extravasate (1). These interactions are governed by both local hydrodynamic and adhesive forces. The former are determined by the vessel diameter, fluid velocity, viscosity, and hematocrit, and the latter by the number, strength and kinetics of bond formation between adhesion molecules, and by surface area of contact (1-6). Cellular deformability affects both types of forces (7-9). Two families of cell adhesion molecules (CAMs) are involved in leukocyte rolling and stable adhesion. In general, the selectins (P, L, and E) mediate rolling, while the IgG superfamily members (ICAM-1 and VCAM-1) on endothelial cells, with their cognate receptors (β(2) and β(1) integrin receptors) on the leukocytes, mediate firm adhesion, with some overlap in these functions (10-12). The expression of CAMs on the endothelial cells and leukocytes can be modulated by cytokines secreted by a variety of cells (e.g., cancer cells, fibroblasts, macrophages) (13,14). Cellular deformability can be modulated by altering the cytoskeleton, membrane, or cytoplasm, with the cytoskeleton playing the dominant role (7,15,16). In this chapter, we describe methods to quantitate cellular deformability in vitro, CAM expression in vitro, leukocyte-endothelial interaction (LEI) in vitro, and LEI in vivo.
An Optimal Global Nearest Neighbor Metric (1984)

A quadratic metric dAO (X, Y) =[(X - Y)T AO(X - Y)]¿ is proposed which minimizes the mean-squared error between the nearest neighbor asymptotic risk and the finite sample risk. Under linearity assumptions, a heuristic argument is given which indicates that this metric produces lower mean-squared error than the Euclidean metric. A nonparametric estimate of Ao is developed. If samples appear to come from a Gaussian mixture, an alternative, parametrically directed distance measure is suggested for nearness decisions within a limited region of space. Examples of some two-class Gaussian mixture distributions are included.
Development and Validation of Improved Algorithms for the Assessment of Global Cardiovascular Risk in Women (2007)

We developed, validated, and demonstrated highly improved accuracy of 2 clinical algorithms for global cardiovascular risk prediction that reclassified 40% to 50% of women at intermediate risk into higher- or lower-risk categories.
Prevention of Pain on Injection with Propofol: A Quantitative Systematic Review (2000)

The best intervention to prevent pain on injection with propofol is unknown. We conducted a systematic literature search (Medline, Embase, Cochrane Library, bibliographies, hand searching, any language, up to September 1999) for full reports of randomized comparisons of analgesic interventions with placebo to prevent that pain. We analyzed data from 6264 patients (mostly adults) of 56 reports. On average, 70% of the patients reported pain on injection. Fifteen drugs, 12 physical measurements, and combinations were tested. With IV lidocaine 40 mg, given with a tourniquet 30 to 120 s before the injection of propofol, the number of patients needed to be treated (NNT) to prevent pain in one who would have had pain had they received placebo was 1.6. The closest to this came meperidine 40 mg with tourniquet (NNT 1.9) and metoclopramide 10 mg with tourniquet (NNT 2.2). With lidocaine mixed with propofol, the best NNT was 2.4; with IV alfentanil or fentanyl, it was 3 to 4. IV lidocaine before the injection of propofol was less analgesic. Temperature had no significant effect. There was a lack of data for all other interventions to allow meaningful conclusions. The diameter of venous catheters and speed of injection had no impact on pain. Implications: IV lidocaine (0.5 mg/kg) should be given with a rubber tourniquet on the forearm, 30 to 120 s before the injection of propofol; lidocaine will prevent pain in approximately 60% of the patients treated in this manner.
Co-Expression of Mesothelin and CA125 Correlates With Unfavorable Patient Outcome in Pancreatic Ductal Adenocarcinoma (2011)

This is the first report showing that co-expression of mesothelin and CA125 were in pancreatic ductal adenocarcinoma, and such co-expression is associated with a poor prognosis. Our finding suggests that co-expression of these two factors plays a significant role in the acquisition of aggressive clinical behavior.
Generation and characterization of monoclonal antibodies to prostate secretory protein (1990)

Monoclonal antibodies (MAbs) were produced against a highly purified preparation of prostate secretory protein (PSP) isolated from normal seminal plasma. Fifteen antibodies were selected for further evaluation based on their strong reactivity and specificity for PSP. All the MAbs had a specificity for prostate epithelial cells and none reacted to any of a variety of normal tissues as determined by immunoperoxidase staining. Six of the MAbs were selected for further immunohistochemical evaluation based on their ability to recognize different antigenic determinants. Using competitive binding immunoassays, a variety of overlapping specificities were observed with at least 2 distinct epitopes identified. Although some staining variability was noted, the 6 antibodies, in general, gave the same pattern of tissue reactivity. Both the normal prostate and the benign prostate hyperplastic ductal epithelial cells stained intensely, with 78 to 100% and 50-100% of the cells staining, respectively. The number and often the staining intensity of the tumor cells decreased as the tumor became more undifferentiated. Approximately 40 to 100% and 15 to 70% of the tumor cells stained in the moderately-differentiated and well-differentiated carcinoma tissues, respectively, whereas either no staining was observed or less than 20% of the tumor cells stained in the poorly-differentiated and undifferentiated tumors. Most of the metastatic prostate tumors showed either no staining or scattered staining in a few cells (i.e., less than 20%).
Association ofp53 gene mutation with decreased chemosensitivity in human malignant gliomas (1996)

Loss of p53 function is involved in tumorigenesis of various human cancers, but the relation between mutation of the p53 tumor-suppressor gene and the chemo- and radiosensitivity of tumors remains unclear. Mutated p53 gene in malignant glioma is often associated with progression and recurrence of malignancy, and these events are closely linked with increased resistance to both chemotherapy and radiation. We have examined the status of the p53 gene in malignant gliomas obtained from 34 patients (glioblastoma: 29 cases, anaplastic astrocytomas: 5 cases). The chemosensitivities of these specimens using 28 kinds of anti-cancer agents were determined using an in vitro assay system. Overall, 12 mutated cases of p53 gene were found in malignant glioma samples. The mean numbers of effective agents were 0.58 for the tumor samples with p53 mutations and 5.00 for tumors without mutations. Our data indicate that p53 gene mutation predisposes to decreased cell killing via chemotherapy in malignant gliomas.
GeneMarkS: a self-training method for prediction of gene starts in microbial genomes. Implications for finding sequence motifs in regulatory regions (2001)

Improving the accuracy of prediction of gene starts is one of a few remaining open problems in computer prediction of prokaryotic genes. Its difficulty is caused by the absence of relatively strong sequence patterns identifying true translation initiation sites. In the current paper we show that the accuracy of gene start prediction can be improved by combining models of protein-coding and non-coding regions and models of regulatory sites near gene start within an iterative Hidden Markov model based algorithm. The new gene prediction method, called GeneMarkS, utilizes a non-supervised training procedure and can be used for a newly sequenced prokaryotic genome with no prior knowledge of any protein or rRNA genes. The GeneMarkS implementation uses an improved version of the gene finding program GeneMark.hmm, heuristic Markov models of coding and non-coding regions and the Gibbs sampling multiple alignment program. GeneMarkS predicted precisely 83.2% of the translation starts of GenBank annotated Bacillus subtilis genes and 94.4% of translation starts in an experimentally validated set of Escherichia coli genes. We have also observed that GeneMarkS detects prokaryotic genes, in terms of identifying open reading frames containing real genes, with an accuracy matching the level of the best currently used gene detection methods. Accurate translation start prediction, in addition to the refinement of protein sequence N-terminal data, provides the benefit of precise positioning of the sequence region situated upstream to a gene start. Therefore, sequence motifs related to transcription and translation regulatory sites can be revealed and analyzed with higher precision. These motifs were shown to possess a significant variability, the functional and evolutionary connections of which are discussed.