gebhart/patrepeval huggingface dataset:
Targeting of Liposomes to Human Keratinocytes Through Adhesive Peptides from Immunoglobulin Domains in the Presence of IFNM-γ (2002)

T-cell adhesion is often dictated by the presence of intercellular adhesion molecule-1 (ICAM-1) on the target cell surface. Reconstitution of P(0) protein into liposomes increases adhesion to melanoma cells expressing ICAM-1. In our study, the effect of peptides derived from P(0) protein and leukocyte function associated-antigen 1 (LFA-1) on IFN-gamma-stimulated human keratinocytes was investigated. Covalently linked P(0)-peptide-1, from the Ig-like domain, increased specific liposome binding to IFN-gamma-stimulated keratinocytes in a dose-dependent manner. C-terminal-derived P(0)-peptide-3 increased liposome binding nonspecifically. LFA-1 and RGD peptides had no apparent effect. P(0)-peptide-1 is thus a potential targeting ligand for liposomal drug delivery to ICAM-1 expressing keratinocytes in inflammatory dermatoses.
Breast cancer stem cells, cytokine networks, and the tumor microenvironment (2011)

Many tumors, including breast cancer, are maintained by a subpopulation of cells that display stem cell properties, mediate metastasis, and contribute to treatment resistance. These cancer stem cells (CSCs) are regulated by complex interactions with the components of the tumor microenvironment - including mesenchymal stem cells, adipocytes, tumor associated fibroblasts, endothelial cells, and immune cells - through networks of cytokines and growth factors. Since these components have a direct influence on CSC properties, they represent attractive targets for therapeutic development.
Coverage estimation for symbolic model checking (1999)

Although model checking is an exhaustive formal verification method, a bug can still escape detection if the erroneous behavior does not violate any verified property. We propose a coverage metric to estimate the "completeness" of a set of properties verified by model checking. A symbolic algorithm is presented to compute this metric for a subset of the CTL property specification language. It has the same order of computational complexity as a model checking algorithm. Our coverage estimator has been applied in the course of some real-world model checking projects. We uncovered several coverage holes including one that eventually led to the discovery of a bug that escaped the initial model checking effort.
Vesicle−Biopolymer Gels:  Networks of Surfactant Vesicles Connected by Associating Biopolymers (2004)

The effect of adding an associating biopolymer to surfactant vesicles and micelles is studied using rheology and small-angle neutron scattering (SANS). The associating polymer is obtained by randomly tethering hydrophobic alkyl chains to the backbone of the polysaccharide, chitosan. Adding this polymer to surfactant vesicles results in a gel; that is, the sample transforms from a Newtonian liquid to an elastic solid having frequency-independent dynamic shear moduli. SANS shows that the vesicles remain intact within the gel. The results suggest a gel structure in which the vesicles are connected by polymer chains into a three-dimensional network. Vesicle-polymer binding is expected to occur via the insertion of polymer hydrophobes into the vesicle bilayer. Each vesicle thus acts as a multifunctional junction in the network structure. Significantly, gel formation does not occur with the native chitosan that has no hydrophobes. Moreover, adding the hydrophobically modified chitosan to a viscous sample containing wormlike micelles increases the viscosity further but does not give rise to a gel-like response. Thus, the formation of a robust gel network requires both the presence of hydrophobes on the polymer and vesicles in solution.
THE ROLE OF p53 AND CASPASE IN REGULATION APOPTOSIS ACTIVITY (2017)

Apoptosis, or programmed cell death, is a common property of all multicellular organism. Apoptosis occurs normally during development and aging and as a homeostatic mechanism to maintain cell populations in tissue. Apoptosis also accurs as a defense mechanism such as in immune reactions or when cells are damaged by disease or noxious agents. Dysregulation of apoptosis leads to a variety of human pathologies including cancer, autoimmune disease, and neurodegenerative disorders.
Rapid assay--possible application in the diagnosis of premature rupture of the membranes. (1983)

Premature rupture of the membranes frequently presents a diagnostic dilemma to the clinician. The presence of alpha-fetoprotein (AFP) in amniotic fluid suggests a possible solution. A rapid, easy-to-use latex agglutination test for AFP was evaluated on 99 amniotic fluid samples of known AFP concentration. Body fluids (maternal serum, urine, vaginal secretions, and seminal fluid) that commonly interfere with other tests were also studied. The sensitivity for amniotic fluids from gestations less than 39 weeks was 93%, and specificity was 94%. The test is most accurate under 35 weeks, when diagnosis is critical. Equivocal results may be resolved by using radioimmunoassay. The results suggest that a rapid assay for AFP may be useful in the diagnosis of ruptured membranes. It has few interfering factors, is safe, and requires no elaborate equipment or training.
Neu differentiation factor (heregulin) induces expression of intercellular adhesion molecule 1: implications for mammary tumors. (1993)

Neu differentiation factor (NDF, also called heregulin) is a 44-kilodalton glycoprotein that stimulates tyrosine phosphorylation of the Neu/HER-2 receptor and induces phenotypic differentiation of certain mammary cancer cell lines to growth-arrested and milk-producing cells. To determine which molecules participate in the concomitant morphological alterations, we analyzed the expression of several cytoskeletal and surface molecules and found that NDF elevated the expression of the intercellular adhesion molecule 1 (ICAM-1) in cultured AU-565 human adenocarcinoma cells. The levels of both the protein and the mRNA of ICAM-1 were elevated after 3-5 days of treatment with NDF. Elevated expression of ICAM-1 was induced also by gamma-interferon and by the tumor-promoting phorbol ester (PMA), albeit with different kinetics. Down-regulation of protein kinase C or its inhibition by calphostin C partially inhibited the effect of NDF, implying that the induction of ICAM-1 may be mediated by protein kinase C. NDF transcripts were detectable in 3 of 9 human mammary tumors, suggesting that the in vitro effect of the factor may be relevant to breast cancer. By selecting Neu-positive human mammary tumors (n = 39), we found a significant correlation (P < 0.001) between the expression of ICAM-1 and histological features of invasive ductal carcinoma with a prominent carcinoma in situ component. When cultured in vitro the cells of these tumors grew in clusters and formed domelike structures reminiscent of comedo-type carcinoma in situ. In addition, the majority of patients with tumors that coexpressed ICAM-1 and Neu had no lymph node involvement, unlike most Neu-positive but ICAM-1-negative tumors, which metastasized to the lymphatic system. Taken together, our observations suggest that the induction of ICAM-1 by NDF may affect the morphology, differentiation state, and metastasis of Neu-expressing mammary tumor cells.
Molecular Genetic Analysis of V-ATPase Function in Drosophila Melanogaster (1997)

V-ATPases are phylogenetically widespread, highly conserved, multisubunit proton pumps. Originally characterised in endomembranes, they have been found to energise transport across plasma membranes in a range of animal cells and particularly in certain epithelia. While yeast is the model of choice for the rapid generation and identification of V-ATPase mutants, it does not allow their analysis in a plasma membrane context. For such purposes, Drosophila melanogaster is a uniquely suitable model. Accordingly, we have cloned and characterised genes encoding several V-ATPase subunits in D. melanogaster and, using P-element technology, we have succeeded in generating multiple new alleles. Reporter gene constructs reveal ubiquitous expression, but at particularly high levels in those epithelial thought to be energised by V-ATPases, and several of the alleles have lethal recessive phenotypes characterised by epithelial dysfunction. These results, while providing the first gene knockouts of V-ATPases in animals, also illustrate the general utility of D. melanogaster as a model for the genetic analysis of ion transport and its control in epithelia.
A randomized, double‐blind comparison of two dosage levels of recombinant factor VIIa in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B, with and without inhibitors (1998)

Recombinant factor VIIa (rFVIIa) was developed to provide an improved procoagulant component capable of 'by-passing' inhibitor antibodies in the treatment of haemophilic patients. The primary objective of this study was to compare the efficacy of two dosage regimens of rFVIIa (given intravenously at periodic intervals) in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B with and without inhibitors. The study was designed as a randomized, double-blind, parallel group, international multicenter trial. Patients were randomly allocated to treatment A: 35 mu kg-1 or B: 70 mu kg-1, in blocks of 2. Within each block, one patient was assigned to the 35 mu kg-1 dosing regimen and the other to 70 mu kg-1 dose. One hundred and fifty subjects from 20 sites were screened for this study and 116 had baseline assessments. Of these, 84 were treated on the protocol and 32 were not treated in the study, in most cases because they did not return to the clinic with an eligible bleeding episode. One hundred and seventy-nine bleeding episodes were treated, of which 145 (81%) were acute haemarthroses. Both treatments were efficacious, with 71% having an excellent (59% and 60%) or effective (12% and 11%) response. Overall, the mean and median number of doses given per episode of joint bleeding were 3.1 and 2, respectively. The mean number of doses was 3.1 for the 70 mu kg-1 group and 2.7 for the 35 mu kg-1 group (P value = 0.142). The study concluded that rFVIIa in a dosage of 35 mu kg-1 or 70 mu kg-1 is both safe and reasonably effective in the treatment of joint or muscle haemorrhages in haemophilic patients with inhibitor antibodies to factor VIII or factor IX. It is concluded that the appropriate dose for the treatment of joint and peripheral muscle bleeding in haemophilic patients with inhibitors is 35-70 mu kg-1 given at 2-3 h intervals until haemostasis is achieved.
MapReduce online (2010)

MapReduce is a popular framework for data-intensive distributed computing of batch jobs. To simplify fault tolerance, many implementations of MapReduce materialize the entire output of each map and reduce task before it can be consumed. In this paper, we propose a modified MapReduce architecture that allows data to be pipelined between operators. This extends the MapReduce programming model beyond batch processing, and can reduce completion times and improve system utilization for batch jobs as well. We present a modified version of the Hadoop MapReduce framework that supports online aggregation, which allows users to see early returns from a job as it is being computed. Our Hadoop Online Prototype (HOP) also supports continuous queries, which enable MapReduce programs to be written for applications such as event monitoring and stream processing. HOP retains the fault tolerance properties of Hadoop and can run unmodified user-defined MapReduce programs.
Efficacy and Safety of Tositumomab and Iodine-131 Tositumomab (Bexxar) in B-Cell Lymphoma, Progressive After Rituximab (2004)

(131)I tositumomab is effective in CD20-positive lymphoma progressive after rituximab, with a 65% OR rate and median PFS of 24.5 months for responders. Patients with follicular grade 1 or 2 histology and tumors < or = 7 cm achieved very high OR and CR rates, with 48% PFS at 3 years.
PTEN Promoter Methylation in Sporadic Thyroid Carcinomas (2006)

The tumor-suppressor gene PTEN/MMAC1, on chromosome 10q23.3, has been implicated in an important number of human tumors, such as thyroid carcinomas. PTEN somatic mutations occur in sporadic tumors of the endometrium, brain, prostate, or melanomas, while germline mutations predispose to development of the multiple hamartoma syndromes (i.e., Cowden's disease and Bannayan-Zonana syndrome). Activation of the two alleles of PTEN is required for its tumor-suppression role. Because the frequency of PTEN suppression in thyroid tumors exceeds that of PTEN mutations or deletions, it is very likely that epigenetic mechanisms, such as promoter hypermethylation, may account for its inactivation in a subset of tumors. The main aim of this study was to assess the frequency of promoter hypermethylation of PTEN in thyroid tumors. We studied frozen tissue samples from 46 papillary carcinomas, 7 follicular carcinomas, 6 follicular adenomas as well as 39 normal thyroid tissue samples. Methylation-specific polymerase-chain reaction (PCR) with three different sets of primers was used. Two of the primer sets were designed to avoid any interference with PTEN pseudogene promoter. PTEN promoter hypermethylation was detected in 21 of 46 (45.7%) papillary carcinomas, 6 of 7 follicular carcinomas, and 5 of 6 follicular adenomas. It was negative in all normal tissues. Negative immunohistochemical staining for PTEN was significantly associated with the presence of promoter hypermethylation (p < 0.001). These results show a high frequency of PTEN promoter hypermethylation, especially in follicular tumors, suggesting its possible role in thyroid tumorigenesis.
TAK1 Mediates the Ceramide Signaling to Stress-activated Protein Kinase/c-Jun N-terminal Kinase (1997)

Ceramide has been proposed as a second messenger molecule implicated in a variety of biological processes. It has recently been reported that ceramide activates stress-activated protein kinase (SAPK, also known as c-Jun NH2-terminal kinase JNK), a subfamily member of mitogen-activated protein kinase superfamily molecules and that the ceramide/SAPK/JNK signaling pathway is required for stress-induced apoptosis. However, the molecular mechanism by which ceramide induces SAPK/JNK activation is unknown. Here we show that TAK1, a member of the mitogen-activated protein kinase kinase kinase family, is activated by treatment of cells with agents and stresses that induce an increase in ceramide. Ceramide itself stimulated the kinase activity of TAK1. Expression of a constitutively active form of TAK1 resulted in activation of SAPK/JNK and SEK1/MKK4, a direct activator of SAPK/JNK. Furthermore, expression of a kinase-negative form of TAK1 interfered with the activation of SAPK/JNK induced by ceramide. These results indicate that TAK1 may function as a mediator of ceramide signaling to SAPK/JNK activation.
Molecular cloning and sequence analysis of cDNA coding for the precursor of the human cysteine proteinase inhibitor cystatin C (1987)

Recombinant cystatin C producing clones were isolated from a human placenta lambda gt11 cDNA library. The cDNA insert of one of the clones, containing 777 base pairs, encodes the complete mature cystatin C (120 amino acids) and a hydrophobic leader sequence of 26 amino acids, indicating an extracellular function of the inhibitor. The deduced protein sequence confirms the protein sequence of cystatin C isolated from human urine, but differs in one position from the sequence of the cystatin C fragment deposited as amyloid in hereditary cerebral hemorrhage with amyloidosis.
In-silico discovery of cancer-specific peptide-HLA complexes for targeted therapy (2016)

Peptide-HLA complexes identified using our novel strategy could enable discovery of cancer-specific targets for engineered T-cells or antibody based therapy with minimal off-target toxicity.
Cutting Edge: Interactions Through the IL-10 Receptor Regulate Autoimmune Diabetes (2001)

BDC2.5/nonobese diabetic (NOD) transgenic mice express a TCR from a diabetogenic T cell clone yet do not spontaneously develop diabetes at high incidence. Evidence exists showing that in the absence of endogenous TCR alpha-chain rearrangements this transgenic mouse spontaneously develops diabetes and that CTLA-4 negatively regulates diabetes onset. This strongly suggests that onset of diabetes in BDC2.5/NOD mice is governed by T cell regulation. We addressed the mechanism of immune regulation in BDC2.5/NOD mice. We find that activated spleen cells from young, but not old, BDC2.5/NOD mice are able to transfer diabetes to NOD-scid recipients. We have used anti-IL-10R to show that the failure of splenocytes from older mice to transfer diabetes is due to dominant regulation. We furthermore found that diabetes developed following anti-IL-10R treatment of 6-wk old BDC2.5/NOD mice indicating that endogenous IL-10 plays a key role in the regulation of diabetes onset in this transgenic mouse.
Immunotherapeutic Approaches to Alzheimer's Disease (2003)

Although neurodegenerative diseases such as Alzheimer's disease are not classically considered mediated by inflammation or the immune system, in some instances the immune system may play an important role in the degenerative process. Furthermore, it has become clear that the immune system itself may have beneficial effects in nervous system diseases considered neurodegenerative. Immunotherapeutic approaches designed to induce a humoral immune response have recently been developed for the treatment of Alzheimer's disease. These studies have led to human trials that resulted in both beneficial and adverse effects. In animal models, it has also been shown that immunotherapy designed to induce a cellular immune response may be of benefit in central nervous system injury, although T cells may have either a beneficial or detrimental effect depending on the type of T cell response induced. These areas provide a new avenue for exploring immune system-based therapy of neurodegenerative diseases and will be discussed here with a primary focus on Alzheimer's disease. We will also discuss how these approaches affect microglia activation, which plays a key role in therapy of such diseases.
[Gene cloning of human dopaminergic D3 receptor and identification of its chromosome]. (1990)

The coding region of the human dopaminergic D3 receptor gene was cloned and sequenced. The deduced amino acid sequence displays a global homology of 78% with rat D3 receptor with a deletion of 46 residues within the third intracytoplasmic loop. Southern analysis assigned the human gene to chromosome 3.
Cloning and characterization of the Bacillus subtilis birA gene encoding a repressor of the biotin operon (1995)

The Bacillus subtilis birA gene, which regulates biotin biosynthesis, has been cloned and characterized. The birA gene maps at 202 degrees on the B. subtilis chromosome and encodes a 36,200-Da protein that is 27% identical to Escherichia coli BirA protein. Three independent mutations in birA that lead to deregulation of biotin synthesis alter single amino acids in the amino-terminal end of the protein. The amino-terminal region that is affected by these three birA mutations shows sequence similarity to the helix-turn-helix DNA binding motif previously identified in E. coli BirA protein. B. subtilis BirA protein also possesses biotin-protein ligase activity, as judged by its ability to complement a conditional lethal birA mutant of E. coli.
Developmental pattern of ANF gene expression reveals a strict localization of cardiac chamber formation in chicken (2002)

In mouse, atrial natriuretic factor (ANF) gene expression was shown to be a marker for chamber formation within the embryonic heart. To gain insight into the process of chamber formation in the chicken embryonic heart, we analyzed the expression pattern of cANF during development. We found cANF to be specifically expressed in the myocardium of the morphologically distinguishable atrial and ventricular chambers, similar to ANF in mouse. cANF expression was never detected in the myocardium of the atrioventricular canal (AVC), inner curvature, and outflow tract (OFT), which is lined by endocardial cushions. Expression was strictly excluded from the interventricular myocardium and most proximal part of the bundle branches, as identified by the expression of Msx-2, whereas the rest of the bundle branches, trabeculae, and surrounding working myocardium did express cANF. The myocardium that forms de novo within the cushions after looping did not express cANF. At HH9 cANF expression was first observed in a subset of cardiomyocytes, which was localized ventrally in the fused heart tube and laterally in the unfused cardiac sheets. Together, these results show that cANF expression can be used to distinguish differentiated chamber (working) myocardium, including the peripheral ventricular conduction system, from embryonic myocardium. We conclude that differentiation of chamber myocardium takes place already at HH9 at the ventral side of the linear heart tube, possibly preceded by latero-medial signals in the unfused cardiac sheets.
P2‐445: Enhancement of dentate gyrus neurogenesis and associated memory by a neurotrophic peptide (2008)

This study was undertaken to address adult hippocampal neurogenesis as a therapeutic target to improve cognition. A secondary aim was to study whether neurotrophic factors, believed to be responsible for maintaining favorable microenvironment in the brain, can be mimicked by small peptides. Peptides were designed based on biologically active regions of human Ciliary Neurotrophic Factor (CNTF), and were tested in vitro in adult rat hippocampal progenitor cultures and in vivo in 8–10 month old normal adult female mice. We report the development of a novel 11-mer peptide based on human CNTF which increases proliferation and survival of adult hippocampal progenitors both in vitro and in normal adult mice. This peptide, CNTF 6, also induces early neuronal fate commitment and neuronal maturation in newly divide progenitors. Most importantly, it enhances hippocampal dependent spatial learning and memory in normal adult mice. This effect is not only due to increased neurogenesis but also due to recruitment of neurons into memory networks, increase in synaptic activity and elaboration of neuronal processes. The fact that CNTF6 mimics the neurotrophic activity of CNTF and that this small peptide is effective when given peripherally and non-invasively and is free of untoward effect, i.e. weight loss caused by its parent molecule, demonstrates its potential for prevention and treatment of age-associated cognitive decline and learning and memory disorder.
Susceptibilities of human immunodeficiency virus type 1 enzyme and viral variants expressing multiple resistance-engendering amino acid substitutions to reserve transcriptase inhibitors (1994)

To evaluate the potential that multiply resistant human immunodeficiency virus type 1 variants may arise during combination nucleoside and nonnucleoside reverse transcriptase inhibitor therapy, we constructed a series of mutant reverse transcriptase enzymes and viruses that coexpressed various combinations of resistance-associated amino acid substitutions. Substitutions at residues 100 (Leu-->Ile) and 181 (Tyr-->Cys), which mediate resistance to the nonnucleosides, suppressed resistance to 3'-azido-3'-deoxythymidine (AZT) when coexpressed with AZT-specific substitutions. However, a number of viral variants that exhibited significantly reduced susceptibilities to both classes of inhibitors were constructed.