gebhart/patrepeval huggingface dataset:
Mastoparan, a peptide toxin from wasp venom, mimics receptors by activating GTP-binding regulatory proteins (G proteins). (1988)

Mastoparan, a peptide toxin from wasp venom, is a nonspecific secretagogue. We show here that mastoparan increases the GTPase activity and the rate of nucleotide binding of several purified GTP-binding regulatory proteins (G proteins) whose function is to couple cell-surface receptors to intracellular mediators. Mastoparan accelerated guanosine-5'-(3-O-thiotriphosphate binding and consequent G protein activation in part by promoting the dissociation of bound GDP, the mechanism by which receptors regulate G proteins. ADP-ribosylation by pertussis toxin, which uncouples receptors from G proteins, selectively inhibited mastoparan-stimulated activation. Like receptors, mastoparan was more potent if the G protein was reconstituted in phospholipid vesicles and was active at micromolar concentrations of Mg2+. The structure of mastoparan in a lipid bilayer is similar to that predicted for a cationic intracellular loop of G protein-coupled receptors. Mastoparan thus displays a novel mode of toxicity by acting directly on G proteins to mimic the role normally played by agonist-liganded receptors.
The Polycomb group protein EZH2 is upregulated in proliferating, cultured human mantle cell lymphoma (2001)

Polycomb group (PcG) proteins are involved in the stable transmittance of the repressive state of their gene targets throughout the cell cycle. Mis-expression of PcG proteins can lead to proliferative defects and tumorigenesis. There are two separate multimeric PcG protein complexes: an EED-EZH2-containing complex and a BMI1-RING1-containing complex. In the normal human follicle mantle, both PcG complexes have mutually exclusive expression patterns. BMI1-RING1 is expressed, but EZH2-EED is not. Here, we studied the expression of both complexes in six cases of mantle cell lymphoma (MCL), which is derived from the follicle mantle. MCL cells can be cultured in vitro and stimulated to proliferation. We found that resting MCL cells expressed BMI1-RING1, but not EZH2-EED, like normal mantle cells. Proliferating MCL cells, however, showed strongly enhanced expression of EZH2. Also, BMI1 and RING1 continued to be expressed in proliferating MCL. This is the first demonstration that EZH2 expression can be upregulated in fresh lymphoma cells. To test whether the enhanced EZH2 expression was causal for the increased proliferation in MCL, we overexpressed EZH2 in two different cell lines. In the B cell-derived Ramos cell line, EZH2 overexpression caused an increase in the proliferation rate. This suggests a possible causal effect between EZH2 upregulation and increased proliferation in haematopoietic cells.
Comparison of Three Methods for the Derivation of a Biologic Scaffold Composed of Adipose Tissue Extracellular Matrix (2010)

Extracellular matrix (ECM)-based scaffold materials have been used successfully in both preclinical and clinical tissue engineering and regenerative medicine approaches to tissue reconstruction. Results of numerous studies have shown that ECM scaffolds are capable of supporting the growth and differentiation of multiple cell types in vitro and of acting as inductive templates for constructive tissue remodeling after implantation in vivo. Adipose tissue represents a potentially abundant source of ECM and may represent an ideal substrate for the growth and adipogenic differentiation of stem cells harvested from this tissue. Numerous studies have shown that the methods by which ECM scaffold materials are prepared have a dramatic effect upon both the biochemical and structural properties of the resultant ECM scaffold material as well as the ability of the material to support a positive tissue remodeling outcome after implantation. The objective of the present study was to characterize the adipose ECM material resulting from three methods of decellularization to determine the most effective method for the derivation of an adipose tissue ECM scaffold that was largely free of potentially immunogenic cellular content while retaining tissue-specific structural and functional components as well as the ability to support the growth and adipogenic differentiation of adipose-derived stem cells. The results show that each of the decellularization methods produced an adipose ECM scaffold that was distinct from both a structural and biochemical perspective, emphasizing the importance of the decellularization protocol used to produce adipose ECM scaffolds. Further, the results suggest that the adipose ECM scaffolds produced using the methods described herein are capable of supporting the maintenance and adipogenic differentiation of adipose-derived stem cells and may represent effective substrates for use in tissue engineering and regenerative medicine approaches to soft tissue reconstruction.
Musical Sound Modeling with Sinusoids plus Noise (1997)

When generating musical sound on a digital computer, it is important to have a good model whose parameters provide a rich source of meaningful sound transformations. Three basic model types are in prevalent use today for musical sound generation instrument models, spectrum models, and abstract models. Instrument models attempt to parametrize a sound at its source, such as a violin, clarinet, or vocal tract. Spectrum models attempt to parametrize a sound at the basilar membrane of the ear, discarding whatever information the ear seems to discard in the spectrum. Abstract models, such as FM, attempt to provide musically useful parameters in an abstract formula.&#13;\n&#13;\nThis article addresses the second category of synthesis techniques spectrum modeling. The main advantage of this group of techniques is the existence of analysis procedures that extract the synthesis parameters out of real sounds, thus being able to reproduce and modify actual sounds. Our particular approach is based on modeling sounds as stable sinusoids (partials) plus noise (residual component), therefore analyzing sounds with this model and generating new sounds from the analyzed data. The analysis procedure detects partials by studying the time-varying spectral characteristics of a sound and represents them with time-varying sinusoids. These partials are then subtracted from the original sound and the remaining "residual" is represented as a time-varying filtered white noise component. The synthesis procedure is a combination of additive synthesis for the sinusoidal part, and subtractive synthesis for the noise part.
MUC1 immunotherapy is here to stay (2012)

Most approaches targeting MUC1 have been immunotherapies administered to date to more than 1200 patients in clinical trials. Even though these trials focused on advanced cancer, encouraging results were reported particularly for less immunosuppressed patients. Furthermore, spontaneous anti-MUC1 immune responses are associated with better prognosis or with a reduced lifetime risk of developing MUC1+ cancers. MUC1 is abnormally expressed in over 80% of all cancers. Successfully targeting this molecule could benefit over a million patients diagnosed yearly with MUC1+ tumors just in the USA.
RNA interference as an antiviral approach: targeting HIV-1. (2004)

RNA interference (RNAi) is an evolutionary conserved gene-silencing mechanism in which 21- to 23-mer double-stranded short interfering RNA (siRNA) mediates the sequence-specific degradation of mRNA. The recent discovery that exogenously delivered siRNA can trigger RNAi in mammalian cells raises the possibility of using this technology as a therapeutic tool against pathogenic viruses. This review describes the antiviral RNAi field, which is barely two years-old, with an emphasis on recent studies aimed at suppression of HIV-1.
Alkane activation by a highly electrophilic zirconium hydride complex supported on silica (1991)

The silica-grafted zirconium hydride complex, synthesized by hydrogenolysis of the well-defined SiOZrNp3, activates the C–H bonds of cyclooctane and methane as shown by the formation of the corresponding cyclooctyl-and methyl-zirconium complexes.
Termination-altering amino acid substitutions in the beta' subunit of Escherichia coli RNA polymerase identify regions involved in RNA chain elongation. (1994)

To identify regions of the largest subunit of RNA polymerase that are potentially involved in transcript elongation and termination, we have characterized amino acid substitutions in the beta' subunit of Escherichia coli RNA polymerase that alter expression of reporter genes preceded by terminators in vivo. Termination-altering substitutions occurred in discrete segments of beta', designated 2, 3a, 3b, 4a, 4b, 4c, and 5, many of which are highly conserved in eukaryotic homologs of beta'. Region 2 substitutions (residues 311-386) are tightly clustered around a short sequence that is similar to a portion of the DNA-binding cleft in E. coli DNA polymerase I. Region 3b (residues 718-798) corresponds to the segment of the largest subunit of RNA polymerase II in which amanitin-resistance substitutions occur. Region 4a substitutions (residues 933-936) occur in a segment thought to contact the transcript 3' end. Region 5 substitutions (residues 1308-1356) are tightly clustered in conserved region H near the carboxyl terminus of beta'. A representative set of mutant RNA polymerases were purified and revealed unexpected variation in percent termination at six different rho-independent terminators. Based on the location and properties of these substitutions, we suggest a hypothesis for the relationship of subunits in the transcription complex.
Efficiently solving dynamic Markov random fields using graph cuts (2005)

In this paper, we present a fast new fully dynamic algorithm for the st-mincut/max-flow problem. We show how this algorithm can be used to efficiently compute MAP estimates for dynamically changing MRF models of labeling problems in computer vision, such as image segmentation. Specifically, given the solution of the max-flow problem on a graph, we show how to efficiently compute the maximum flow in a modified version of the graph. Our experiments showed that the time taken by our algorithm is roughly proportional to the number of edges whose weights were different in the two graphs. We test the performance of our algorithm on one particular problem: the object-background segmentation problem for video and compare it with the best known st-mincut algorithm. The results show that the dynamic graph cut algorithm is much faster than its static counterpart and enables real time image segmentation. It should be noted that our method is generic and can be used to yield similar improvements in many other cases that involve dynamic change in the graph
Cancer Genetics With an Edge (2012)

Their lab helped reveal how faulty genes cause cancer, but Bert Vogelstein and Kenneth Kinzler sometimes irk colleagues with their “reality check” comments on genomic medicine.
Large-scale synthesis of triple helix forming oligonucleotides using a controlled-pore glass support. (1993)

Triple helix forming oligonucleotides that involve purine:purine:pyrimidine interactions are purine-rich oligonucleotides containing 60%-90% G and are usually 25-40 bases long. Synthesis and purification of G-rich oligonucleotides of this length can be difficult even at small scales. Procedures to synthesize these compounds at 200 to 400 mumol scales with high coupling efficiency have been developed using a controlled-pore glass support.
Role of Angiogenesis in Cardiovascular Disease (2005)

The role of angiogenesis in atherosclerosis and other cardiovascular diseases has emerged as a major unresolved issue. Angiogenesis has attracted interest from opposite perspectives. Angiogenic cytokine therapy has been widely regarded as an attractive approach both for treating ischemic heart disease and for enhancing arterioprotective functions of the endothelium; conversely, a variety of studies suggest that neovascularization contributes to the growth of atherosclerotic lesions and is a key factor in plaque destabilization leading to rupture. Here, we critically review the evidence supporting a role for angiogenesis and angiogenic factors in atherosclerosis and neointima formation, emphasizing the problems raised by some of the landmark studies and the suitability of animal models of atherosclerosis and neointimal thickening for investigating the role of angiogenesis. Because many of the relevant studies have focused on the role of vascular endothelial growth factor (VEGF), we consider this work in the wider context of VEGF biology and in light of recent experience from clinical trials of VEGF and other angiogenic cytokines for ischemic heart disease. Also discussed are recent findings suggesting that, although angiogenesis may contribute to neointimal growth, it is not required for the initiation of intimal thickening. Our assessment of the evidence leads us to conclude that, although microvessels are a feature of advanced human atherosclerotic plaques, it remains unclear whether angiogenesis either plays a central role in the development of atherosclerosis or is responsible for plaque instability. Furthermore, current evidence from clinical trials of both proangiogenic and antiangiogenic therapies does not suggest that inhibition of angiogenesis is likely to be a viable therapeutic strategy for cardiovascular disease.
GAS-1 (1999)

The function of the 49-kDa (IP) subunit of complex I is unknown. The finding that mutations in complex I increase sensitivity of C elegans to volatile anesthetics may implicate this physiologic process in the determination of anesthetic sensitivity. The hypersensitivity of animals with a mutation in the gas-1 gene may be caused by a direct anesthetic effect on a mitochondrial protein or secondary effects at other sites caused by mitochondrial dysfunction.
BFAST: An Alignment Tool for Large Scale Genome Resequencing (2009)

We compare BFAST to a selection of large-scale alignment tools -- BLAT, MAQ, SHRiMP, and SOAP -- in terms of both speed and accuracy, using simulated and real-world datasets. We show BFAST can achieve substantially greater sensitivity of alignment in the context of errors and true variants, especially insertions and deletions, and minimize false mappings, while maintaining adequate speed compared to other current methods. We show BFAST can align the amount of data needed to fully resequence a human genome, one billion reads, with high sensitivity and accuracy, on a modest computer cluster in less than 24 hours. BFAST is available at (http://bfast.sourceforge.net).
A hypothalamic follicle-stimulating hormone-releasing decapeptide in the rat (1997)

Previous studies indicated that there is a separate hypothalamic control of follicle-stimulating hormone (FSH) release distinct from that of luteinizing hormone (LH). An FSH-releasing factor (FSHRF) was purified from rat and sheep hypothalami, but has not been isolated. We hypothesized that FSHRF might be an analogue of mammalian luteinizing hormone-releasing hormone (m-LHRH) and evaluated the activity of many analogues of m-LHRH and of the known LHRHs found in lower forms. Here we demonstrate that lamprey (l) LHRH-III has a potent, dose-related FSH- but not LH-releasing action on incubated hemipituitaries of male rats. l-LHRH-I on the other hand, had little activity to release either FSH or LH. m-LHRH was equipotent to l-LHRH-III to release FSH, but also had a high potency to release LH in contrast to l-LHRH-III that selectively released FSH. Chicken LHRH-II had considerable potency to release both LH and FSH, but no selectivity in its action. Salmon LHRH had much less potency than the others tested, except for l-LHRH-I, and no selectivity in its action. Because ovariectomized, estrogen, progesterone-treated rats are a sensitive in vivo assay for FSH- and LH-releasing activity, we evaluated l-LHRH-III in this assay and found that it had a completely selective stimulatory effect on FSH release at the two doses tested (10 and 100 pmols). Therefore, l-LHRH-III is a highly potent and specific FSH-releasing peptide that may enhance fertility in animals and humans. It may be the long sought after m-FSHRF.
Proapoptotic activity of Caenorhabditis elegans CED-4 protein in Drosophila : Implicated mechanisms for caspase activation (1999)

CED-4 protein plays an important role in the induction of programmed cell death in Caenorhabditis elegans through the activation of caspases. However, the precise mechanisms by which it activates caspases remain unknown. To investigate the conservation of CED-4 function in evolution, transgenic Drosophila lines that express CED-4 in the compound eye were generated. Ectopic expression of CED-4 in the eyes induced massive apoptotic cell death through caspase activation. An ATP-binding site (P-loop) mutation in CED-4 (K165R) causes a loss of function in its ability to activate Drosophila caspase, and an ATPase inhibitor blocks the CED-4-dependent caspase activity in Drosophila S2 cells. Immunoprecipitation analysis showed that both CED-4 and CED-4 (K165R) bind directly to Drosophila caspase drICE, and the overexpression of CED-4 (K165R) inhibits CED-4-, ecdysone-, or cycloheximide-dependent caspase activation in S2 cells. Furthermore, CED-4 (K165R) partially prevented cell death induced by CED-4 in Drosophila compound eyes. Thus, CED-4 function is evolutionarily conserved in Drosophila, and the molecular mechanisms by which CED-4 activates caspases might require ATP binding and direct interaction with the caspases.
Valgrind (2007)

Dynamic binary instrumentation (DBI) frameworks make it easy to build dynamic binary analysis (DBA) tools such as checkers and profilers. Much of the focus on DBI frameworks has been on performance; little attention has been paid to their capabilities. As a result, we believe the potential of DBI has not been fully exploited. In this paper we describe Valgrind, a DBI framework designed for building heavyweight DBA tools. We focus on its unique support for shadow values -a powerful but previously little-studied and difficult-to-implement DBA technique, which requires a tool to shadow every register and memory value with another value that describes it. This support accounts for several crucial design features that distinguish Valgrind from other DBI frameworks. Because of these features, lightweight tools built with Valgrind run comparatively slowly, but Valgrind can be used to build more interesting, heavyweight tools that are difficult or impossible to build with other DBI frameworks such as Pin and DynamoRIO.
Functional Analyses of Two Cellular Binding Domains of Bovine Lactadherin (2000)

The glycoprotein bovine lactadherin (formerly known as PAS-6/7) comprises two EGF-like domains and two C-like domains found in blood clotting factors V and VIII. Bovine lactadherin binds to alpha(v)beta(5) integrin in an RGD-dependent manner and also to phospholipids, especially phosphatidyl serine. To define and characterize these bindings the interactions between lactadherin and different mammalian cell types were investigated. Using recombinant forms of bovine lactadherin, the human breast carcinomas MCF-7 cells expressing the alpha(v)beta(5) integrin receptor were shown to bind specifically to RGD containing lactadherin but not to a mutated RGE lactadherin. A monoclonal antibody against the alpha(v)beta(5) integrin receptor and a synthetic RGD-containing peptide inhibited the adhesion of MCF-7 cells to lactadherin. Green monkey kidney MA-104 cells, also expressing the alpha(v)beta(3) together with the alpha(v)beta(5) integrin, showed binding to bovine lactadherin via both integrins. To investigate the interaction of lipid with lactadherin two fragments were expressed corresponding to the C1C2 domains and the C2 domain. Both fragments bound to phosphatidyl serine in a concentration-dependent manner with an affinity similar to native lactadherin (K(d) = 1.8 nM). A peptide corresponding to the C-terminal part of the C2 domain inhibited the binding of lactadherin to phospholipid in a concentration-dependent manner, and finally it was shown that lactadherin mediates binding between artificial phosphatidyl serine membranes and MCF-7 cells. Taken together these results show that lactadherin can act as link between two surfaces by binding to integrin receptors through its N-terminus and to phospholipids through its C-terminus.
Update on theIn VitroActivity of Daptomycin Tested against 17,193 Gram-positive Bacteria Isolated From European Medical Centers (2005-2007) (2009)

The antimicrobial susceptibility patterns of 17,193 Gram-positive isolates consecutively collected from 28 medical centers in 12 countries in europe and israel in 2005-2007 were evaluated by Clinical and laboratory Standards institute (CLSI) broth microdilution methods supplemented with calcium to 50 mg/l for testing daptomycin. Overall, the rate of methicillin-resistant Staphylococcus aureus (MRSA) was 28.3%, varying from 32.3% in 2005 to 27.1% in 2006 and 28.5% in 2007. Vancomycin resistance rates were 0.8% and 21.5% among Enterococcus faecalis and E. faecium, respectively. Among E. faecium, vancomycin resistance increased from 17.9% in 2005 to 26.3% in 2007, and varied from 0.0% in Spain, Sweden and Switzerland to as high as 54.6% in ireland for 2007. All isolates tested, except for seven CoNS (0.2%; 3,234 tested) were considered susceptible to daptomycin using breakpoints established by the United States food and Drug Administration, the CLSI and the EUCAST. Daptomycin was very active against all Gram-positive species with the highest minimum inhibitory concentration (MIC) results being 1, 4, 2 and 4 mg/l for S. aureus, coagulase-negative staphylococci, E. faecalis and E. faecium, respectively. Daptomycin activity was not adversely influenced by resistance to oxacillin among staphylococci or to vancomycin among enterococci.
Capturing Social Networking Privacy Preferences: Can Default Policies Help Alleviate Tradeoffs between Expressiveness and User Burden? (2018)

Social networking sites such as Facebook and MySpace thrive on the exchange of personal content such as pictures and activities. These sites are discovering that people's privacy preferences are very rich and diverse. In theory, providing users with more expressive settings to spec- ify their privacy policies would not only enable them to better articulate their preferences, but could also lead to greater user burden. In this ar- ticle, we evaluate to what extent providing users with default policies can help alleviate some of this burden. Our research is conducted in the context of location-sharing applications, where users are expected to specify conditions under which they are willing to let others see their lo- cations. We de ne canonical policies that attempt to abstract away user- speci c elements such as a user's default schedule, or canonical places, such as "work" and "home." We learn a set of default policies from this data using decision-tree and clustering algorithms. We examine trade- offs between the complexity / understandability of default policies made available to users, and the accuracy with which they capture the ground truth preferences of our user population. Speci cally, we present results obtained using data collected from 30 users of location-enabled phones over a period of one week. They suggest that providing users with a small number of canonical default policies to choose from can help reduce user burden when it comes to customizing the rich privacy settings they seem to require.
Anomaly Detection in Network Traffic Traces Using Latent Dirichlet Allocation (2012)

The detection of anomalies in network traffic can assist network operators in controlling and securing computer networks. Latent Dirichlet Allocation can be applied to com- puter network traffic, where word counts are replaced with packet counts, and documents, with user sessions. I describe the processing of network traces collected at UNC, and the results of running LDA on these traces. The resulting model can be used to detect anomalies in other network traces on the UNC network. Variational inference is run on a second trace, and three anomalies are detected and analyzed. A simulated Denial of Service Attack is also detected by the model.