gebhart/patrepeval huggingface dataset:
Treatment of bone metastasis induced by MDA-MB-231 breast cancer cells with an antibody against bone sialoprotein (2006)

The extracellular bone matrix protein bone sialoprotein (BSP) is considered to play an important role in the pathogenesis of lytic skeletal lesions which are associated with severe morbidity in breast, prostate or lung cancer patients. In addition to in vitro studies, nude rats were implanted with 10(5) MDA-MB-231 cells transfected with GFP into a small branch of the femoral artery. Osteolytic lesions of the respective hind leg were detected by X-ray and CT analysis as well as by immunohistochemistry. Exposure of MDA-MB-231GFP cells in vitro to an antibody against BSP (0-400 microg/ml) decreased proliferation, colony formation and migration of these cells by up to 95, 83 and 89 T/C%, respectively. In nude rats, pre-incubation of MDA-MB-231GFP cells prior to inoculation (25-100 microg/ml) reduced the mean osteolytic lesion size to 22 T/C% after 90 days of observation (p<0.05). Treatment of overt lytic metastasis with the anti-BSP antibody (10 mg/kg) resulted in a significantly smaller mean lesion size of 57 T/C% at the end of the observation period (p<0.05) as well as in new bone formation. Immunohistochemical analysis revealed the presence of BSP in MDA-MB-231GFP cells and in vessel endothelium cells during processes such as migration and invasion. In conclusion, an anti-BSP antibody decreased proliferation, colony formation and migration of MDA-MB-231GFP cells in vitro and reduced osteolysis besides inducing bone formation in a nude rat model.
A High-Sensitivity Method for Detection and Measurement of HMGB1 Protein Concentration by High-Affinity Binding to DNA Hemicatenanes (2008)

The new technique, which illustrates the potential of DNA nanoobjects and aptamers to form high-affinity complexes with selected proteins, should provide a valuable tool to further investigate the extracellular functions of HMGB1 and its involvement in inflammatory pathologies.
Expression and Polarized Localization of the Hemochromatosis Gene Product HFE in Retinal Pigment Epithelium (2006)

This is the first report on the expression of HFE in the retina. The specific localization of HFE and its interacting proteins, TfR1 and TfR2, at the basolateral membrane of RPE is relevant to the regulation of iron homeostasis in this cell. Patients with hemochromatosis may have impairment of iron homeostasis in RPE, potentially contributing to age-related RPE dysfunction and retinal degeneration.
Culture and Communication in Israel: The Transformation of Tradition (1973)

This paper is an introduction to a study of what 4,000 Israelis had to say about their leisure, culture, and communication. In a national survey conducted during the spring of 1970, we gathered data on a large variety of cultural activities. With respect to each of them, an effort was made to measure both supply and demand. Thus, we know for cultural events taking place outside the home which events were advertised where, and we know who attends which activities. Likewise, we studied the cultural activities that take place inside the home, paying particular attention to the effect of the introduction of television, and to the fate of the book the newest and oldest media in Israel. We try to do this within two broader contexts. One is behavioural: using the method of time-budget analysis, we have reconstructed the way in which Israelis invest time, that most scarce of human resources, over the 24-hour period of a weekday, a Friday, and a Saturday. The other context is that of attitudes and values: we discuss the functions of cultural activities and communications within the framework of attitudes towards work, leisure, the Sabbath, and holidays, and more generally, in terms of the social and psychological 'needs' that are experienced as salient by Israeli Jews, in their several social roles.
Site-Directed Alteration of Genomic DNA by Small-Fragment Homologous Replacement (2003)

The site-directed alteration of genomic sequences by homologous replacement (1,2), psoralen mutation (3), or site-directed repair-mediated correction (4)is a technology that can be used to achieve a number of different ends, including:the introduction of specific mutations into vectors, development of transgenic animals, and gene therapy.Homologous replacement is versatile, in that sequences can be directly targeted and altered, inserted, or deleted.As such, it shows great potential for gene therapy to treat inherited genetic disorders for which the sequence information is known.Treatment involves direct conversion of mutant sequences to a wild-type genotype, thereby restoring the normal phenotype.Small-fragment homologous replacement (SFHR)is a technique that has shown promise in this application (5). SFHR has been used to correct the most common mutation associated with cystic fibrosis (CF), a 3-bp deletion in the CF transmembrane conductance regulator (CFTR)gene, resulting in the loss of a phenylalanine at amino acid position 508 (Δ508) (6–8).
Asp129 of low molecular weight protein tyrosine phosphatase is involved in leaving group protonation (1994)

Site-directed mutagenesis was used to explore the functions of a number of acidic residues of bovine low molecular weight protein tyrosine phosphatase. Residues Asp-129, Asp-56, and Asp-92 were mutated to Ala or Asn. The mutant enzymes D56A, D56N, and D92A showed no significant changes in Vmax values, although they did exhibit significantly altered Km values. In contrast, the D129A mutant enzyme exhibited a greater than 2000-fold reduction in Vmax, using p-nitrophenyl phosphate as a substrate. The Vmax values of D129A also exhibited a leaving group dependence, an altered solvent isotope effect of VmaxH/VmaxD of 0.78, and a lack of dependence on the presence of alternative phosphate acceptor alcohols, all properties that distinguish this mutant from wild type enzyme. The differences are due to a change of the rate-limiting step of the catalytic reaction. Asp-129 is concluded to be the proton donor to the leaving group in the phosphorylation step, and its mutation to alanine results in a reduced Vmax value and a change in the rate-limiting step of the catalysis from dephosphorylation to phosphorylation. Mechanistic considerations suggest that other phosphotyrosyl phosphatases having cysteine at the active site may be expected to have a similar requirement for a proton donor.
Advanced data preprocessing for intersites Web usage mining (2004)

Web usage mining applies data mining procedures to analyze user access of Web sites. As with any KDD (knowledge discovery and data mining) process, WUM contains three main steps: preprocessing, knowledge extraction, and results analysis. We focus on data preprocessing, a fastidious, complex process. Analysts aim to determine the exact list of users who accessed the Web site and to reconstitute user sessions-the sequence of actions each user performed on the Web site. Intersites WUM deals with Web server logs from several Web sites, generally belonging to the same organization. Thus, analysts must reassemble the users' path through all the different Web servers that they visited. Our solution is to join all the log files and reconstitute the visit. Classical data preprocessing involves three steps: data fusion, data cleaning, and data structuration. Our solution for WUM adds what we call advanced data preprocessing. This consists of a data summarization step, which will allow the analyst to select only the information of interest. We've successfully tested our solution in an experiment with log files from INRIA Web sites.
A new SBP‐box gene BpSPL1 in silver birch (Betula pendula) (2004)

The SBP-box gene family represents a group of plant-specific genes encoding putative transcription factors. Thus far, SBP-domain protein binding sites have been found in the promoters of Arabidopsis APETALA1 and Antirrhinum SQUAMOSA. A putative SBP-domain binding element has been observed in the promoter of BpMADS5, a close homologue of Arabidopsis FRUITFULL in silver birch (Betula pendula). A novel SBP-box gene from birch named BpSPL1 has been cloned and characterized. The nucleotide sequence of BpSPL1 is similar to Antirrhinum SBP2 and Arabidopsis SPL3, apart from the unique finding that BpSPL1 does not contain an intron typical to all other known SBP-box genes studied thus far. According to Northern blot analysis, BpSPL1 is expressed in birch inflorescences as well as in shoots and leaves. Studies using electrophoretic mobility shift assay demonstrate that there are nuclear proteins in birch inflorescences which specifically bind to the SBP binding element of the promoter of BpMADS5. BpSPL1 expressed in Escherichia coli also specifically binds to this element. According to Southern blot analysis, there are at least two SBP-box genes in birch. The results suggest that SBP-box genes are involved in the regulation of flower development in birch.
Csk Enhances Insulin-Stimulated Dephosphorylation of Focal Adhesion Proteins (1996)

Insulin has pleiotropic effects on the regulation of cell physiology through binding to its receptor. The wide variety of tyrosine phosphorylation motifs of insulin receptor substrate 1 (IRS-1), a substrate for the activated insulin receptor tyrosine kinase, may account for the multiple functions of insulin. Recent studies have shown that activation of the insulin receptor leads to the regulation of focal adhesion proteins, such as a dephosphorylation of focal adhesion kinase (pp125FAK). We show here that C-terminal Src kinase (Csk), which phosphorylates C-terminal tyrosine residues of Src family protein tyrosine kinases and suppresses their kinase activities, is involved in this insulin-stimulated dephosphorylation of focal adhesion proteins. We demonstrated that the overexpression of Csk enhanced and prolonged the insulin-induced dephosphorylation of pp125FAK. Another focal adhesion protein, paxillin, was also dephosphorylated upon insulin stimulation, and a kinase-negative mutant of Csk was able to inhibit the insulin-induced dephosphorylation of pp125FAK and paxillin. Although we have shown that the Csk Src homology 2 domain can bind to several tyrosine-phosphorylated proteins, including pp125FAK and paxillin, a majority of protein which bound to Csk was IRS-1 when cells were stimulated by insulin. Our data also indicated that tyrosine phosphorylation levels of IRS-1 appear to be paralleled by the dephosphorylation of the focal adhesion proteins. We therefore propose that the kinase activity of Csk, through the insulin-induced complex formation of Csk with IRS-1, is involved in insulin's regulation of the phosphorylation levels of the focal adhesion proteins, possibly through inactivation of the kinase activity of c-Src family kinases.
Probabilistic color-by-numbers (2013)

We present a probabilistic factor graph model for automatically coloring 2D patterns. The model is trained on example patterns to statistically capture their stylistic properties. It incorporates terms for enforcing both color compatibility and spatial arrangements of colors that are consistent with the training examples. Using Markov Chain Monte Carlo, the model can be sampled to generate a diverse set of new colorings for a target pattern. This general probabilistic framework allows users to guide the generated suggestions via conditional inference or additional soft constraints. We demonstrate results on a variety of coloring tasks, and we evaluate the model through a perceptual study in which participants judged sampled colorings to be significantly preferable to other automatic baselines.
Poor In Vitro Maturation and Pro‐Inflammatory Cytokine Response of Dendritic Cells in Children at Genetic Risk of Type 1 Diabetes (2004)

Type 1 diabetes (T1D) has been associated with an aberrant maturation of dendritic cells (DC). We studied the maturation of monocyte-derived DC in children with newly diagnosed T1D and in healthy children with genetic risk for T1D. Peripheral blood monocytes from children with newly diagnosed T1D (n = 12; mean age 13.2 years), children with human leukocyte antigen (HLA)-risk genotype of T1D (n = 7; mean age 12.7 years) and healthy children (n = 14; mean age 11.2 years) were in vitro differentiated into DC. Expression of HLA-DR, CD80/86 and CD11c and secretion of interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, IL-6 and IL-10 were measured using flow cytometry. Lower percentage of DC expressed CD11c and HLA-DR, and decreased production of TNF-alpha was found in children with newly diagnosed T1D and in children at genetic risk when compared to healthy children. Children with risk genotype also had decreased IL-12 production by DC. Children with T1D and children at genetic risk of T1D appear to have similar aberrancies in the maturation of DC, which may predispose to beta-cell autoimmunity.
NESbase version 1.0: a database of nuclear export signals (2003)

Protein export from the nucleus is often mediated by a Leucine-rich Nuclear Export Signal (NES). NESbase is a database of experimentally validated Leucine-rich NESs curated from literature. These signals are not annotated in databases such as SWISS-PROT, PIR or PROSITE. Each NESbase entry contains information of whether NES was shown to be necessary and/or sufficient for export, and whether the export was shown to be mediated by the export receptor CRM1. The compiled information was used to make a sequence logo of the Leucine-rich NESs, displaying the conservation of amino acids within a window of 25 residues. Surprisingly, only 36% of the sequences used for the logo fit the widely accepted NES consensus L-x(2,3)-[LIVFM]-x(2,3)-L-x-[LI]. The database is available online at http://www.cbs.dtu.dk/databases/NESbase/.
Inhibition by zinc of rhinovirus protein cleavage: interaction of zinc with capsid polypeptides (1976)

Zinic ions rapidly inhibit virus production in HeLa cells infected with human rhinovirus type 1A and lead to the accumulation of human rhinovirus type 1A precursor polypeptides. The degree to which cleavage of these precursors is inhibited is directly dependent on the quantity of cell-associated zinc. Proteolysis resumes after the removal of zinc-containing medium, and the accumulated viral precursors are cleaved predominantly to stable virus polypeptides. The precursors stabilized at the lowest zinc levels are those that contain capsid protein sequences. Furthermore, added zinc is bound to human rhinovirus type 1A capsids and prevents them from forming crystals. Zinc-resistant mutants display antigenic alterations in coat proteins. These results suggest that zinc complexes with rhinovirus coat proteins and alters them so that they cannot function as substrates for proteases or as reactants in the assembly of the virus particles.
The Role of Hyaluronic Acid Fillers (Restylane) in Facial Cosmetic Surgery: Review and Technical Considerations (2007)

Current techniques in nonsurgical facial rejuvenation and shaping with hyaluronic acid fillers are safe, effective, and long-lasting. Combination regimens that include surgical facial rejuvenation techniques and/or coadministration of botulinum toxin type A further optimize results, leading to greater patient satisfaction.
Bipolar Mode Operation and Scalability of Double-Gate Capacitorless 1T-DRAM Cells (2010)

In this paper, we study the operation mode and the scalability of the second generation (type II) of double-gate capacitorless one transistor dynamic random access memory (1T-DRAM) cells. We find that the memory operates by accumulating charge at the gate interfaces, not in the body of the cell. The type-II configuration allows an infinitely long retention of state “1,” whereas the total retention time is limited by the leakage associated with state “0” due to band-to-band tunneling (BTBT) at the source/drain to bulk junctions. Extensive and careful scaling analysis shows that longitudinal scaling is limited by short-channel effects related to source/drain to bulk barrier lowering, whereas transverse scaling is limited by BTBT. We conclude that type-II 1T-DRAM is somewhat more scalable than type-I 1T-DRAM (i.e., 15 nm versus 25 nm). The better scaling perspective of type-II 1T-DRAM cells is ascribed to the higher READ sensitivity, programming window, and retention time.
The genome sequence of the filamentous fungus Neurospora crassa (2003)

Neurospora crassa is a central organism in the history of twentieth-century genetics, biochemistry and molecular biology. Here, we report a high-quality draft sequence of the N. crassa genome. The approximately 40-megabase genome encodes about 10,000 protein-coding genes--more than twice as many as in the fission yeast Schizosaccharomyces pombe and only about 25% fewer than in the fruitfly Drosophila melanogaster. Analysis of the gene set yields insights into unexpected aspects of Neurospora biology including the identification of genes potentially associated with red light photobiology, genes implicated in secondary metabolism, and important differences in Ca2+ signalling as compared with plants and animals. Neurospora possesses the widest array of genome defence mechanisms known for any eukaryotic organism, including a process unique to fungi called repeat-induced point mutation (RIP). Genome analysis suggests that RIP has had a profound impact on genome evolution, greatly slowing the creation of new genes through genomic duplication and resulting in a genome with an unusually low proportion of closely related genes.
Scalable Multicast Key Distribution (1996)

This memo defines an Experimental Protocol for the Internet community. This memo does not specify an Internet standard of any kind. Discussion
Visualizing the Dynamics of EGFR Activity and Antiglioma Therapies In vivo (2007)

Many altered pathways in cancer cells depend on growth factor receptors. In primary malignant gliomas, the amplification/alteration of the epidermal growth factor receptor (EGFR) has been shown to play a significant role in enhancing glioma burden. In an effort to dissect the role of EGFR expression in glioma progression in vivo and evaluate targeted therapies for gliomas, we have genetically engineered glioma cells to visualize the dynamics of EGFR and targeted therapies in real time in vivo. Using engineered lentiviral vectors bearing fusions between EGFR and its exon 2 to 7 deleted variant (EGFRvIII) with green fluorescent protein (GFP) and Renilla luciferase (Rluc), we show that there is a direct correlation between EGFR expression and glioma cell proliferation in the initial stages of glioma progression. To monitor and evaluate EGFR-targeted therapies, we have engineered (a) short hairpin RNAs (shRNA) and (b) clinically used monoclonal antibody, cetuximab. Using EGFR-GFP-Rluc/firefly luciferase (Fluc)-DsRed2 glioma model, we show that both shRNAs and cetuximab result in a considerable reduction in glioma cell proliferation in culture and glioma burden in vivo that can be monitored in real time at a cellular resolution. This study serves as a template to follow the role of growth factor receptor expression in tumor progression and to image therapeutic efficacy of targeted therapies in cancer.
Effects of Synthetic Androgens on Liver Function Using the Rabbit as a Model (2010)

The objective of this study was to determine whether the rabbit was a suitable model to test new synthetic androgens for potential liver toxicity within a short dosing interval. Adult male rabbits were dosed orally daily on days 0-13 with 17α-methyltestosterone (MT) as a positive control and testosterone (T) as a negative control to validate this model. Synthetic androgens tested were: 7α-methyl-19-nortestosterone (MENT), dimethandrolone-undecanoate (DMAU), and 11β-methyl-19-nortestosterone-17β-dodecylcarbonate (11β-MNTDC). Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), and sorbitol dehydrogenase (SDH), as well as clearance of intravenous injected bromsulfonphthalein (BSP) from serum on days 0, 7, and 14, were determined. As expected, T (10 mg/kg/d) did not adversely affect BSP retention or serum liver enzymes. MT (10 mg/kg/d) increased BSP retention, and AST, ALT, GGT, and SDH levels, indicating that this model could detect androgens known to be hepatotoxic. DMAU and MENT (10 mg/kg/d) increased BSP retention and all 4 serum liver enzymes as well, but the effects were less than those observed with MT at the same dose. All parameters returned to baseline 2 weeks after cessation of dosing. 11β-MNTDC at 10 mg/kg/d did not have an effect on BSP retention or liver enzymes, but a slight increase in serum GGT levels was observed in rabbits treated with 25 mg/kg/d. For the androgens that exhibited liver toxicity at 10 mg/kg/d (MT, DMAU, and MENT), a no-observed-effect level of 1 mg/kg/d was established. Overall ranking of the synthetic androgens from most to least hepatotoxic on the basis of percent BSP retention was: MT & DMAU > MENT > 11β-MNTDC. Hence, the rabbit appears to be a promising model for detection of potential liver toxicity by synthetic androgens using BSP clearance and serum liver enzyme levels as early indicators of injury.
Imaging and Time-Resolved Spectroscopy of Single Molecules at an Interface (1996)

Far-field microscopy was used to noninvasively measure the room-temperature optical properties of single dye molecules located on a polymer-air interface. Shifts in the fluorescence spectrum, due to perturbation by the locally varying molecular environment, and the orientation of the transition dipole moment were correlated to variation in the excited-state lifetime. The lifetime dependence on spectral shift is argued to result from the frequency dependence of the spontaneous emission rate; the lifetime dependence on dipole orientation was found to be a consequence of the electromagnetic boundary conditions on the fluorescent radiation at the polymer-air interface.
Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer (2007)

Epstein-Barr virus (EBV)-associated tumors developing in immunocompetent individuals present a challenge to immunotherapy, since they lack expression of immunodominant viral antigens. However, the tumors consistently express viral proteins including LMP2, which are immunologically "weak" but may nonetheless be targets for immune T cells. We previously showed that a majority of cytotoxic T lymphocytes (CTLs) reactivated using EBV-transformed B-lymphoblastoid cells lines (LCLs) contained minor populations of LMP2-specific T cells and homed to tumor sites. However, they did not produce remissions in patients with bulky disease. We have now used gene transfer into antigen-presenting cells (APCs) to augment the expression and immunogenicity of LMP2. These modified APCs increased the frequency of LMP2-specific CTLs by up to 100-fold compared with unmodified LCL-APCs. The LMP2-specific population expanded and persisted in vivo without adverse effects. Nine of 10 patients treated in remission of high-risk disease remain in remission, and 5 of 6 patients with active relapsed disease had a tumor response, which was complete in 4 and sustained for more than 9 months. It is therefore possible to generate immune responses to weak tumor antigens by ex vivo genetic modification of APCs and the CTLs so produced can have substantial antitumor activity. This study is registered at http://www.cancer.gov/clinicaltrials (protocol IDs: BCM-H-9936, NCT00062868, NCT00070226).