gebhart/patrepeval huggingface dataset:
Evolution and Classification of Cystine Knot-Containing Hormones and Related Extracellular Signaling Molecules (2001)

The cystine knot three-dimensional structure is found in many extracellular molecules and is conserved among divergent species. The identification of proteins with a cystine knot structure is difficult by commonly used pairwise alignments because the sequence homology among these proteins is low. Taking advantage of complete genome sequences in diverse organisms, we used a complementary approach of pattern searches and pairwise alignments to screen the predicted protein sequences of five model species (human, fly, worm, slime mold, and yeast) and retrieved proteins with low sequence homology but containing a typical cystine knot signature. Sequence comparison between proteins known to have a cystine knot three-dimensional structure (transforming growth factor-beta, glycoprotein hormone, and platelet-derived growth factor subfamily members) identified new crucial amino acid residues (two hydrophilic amino acid residues flanking cysteine 5 of the cystine knot). In addition to the well known members of the cystine knot superfamily, novel subfamilies of proteins (mucins, norrie disease protein, von Willebrand factor, bone morphogenetic protein antagonists, and slit-like proteins) were identified as putative cystine knot-containing proteins. Phylogenetic analysis revealed the ancient evolution of these proteins and the relationship between hormones [e.g. transforming growth factor-beta (TGFbeta)] and extracellular matrix proteins (e.g. mucins). They are absent in the unicellular yeast genome but present in nematode, fly, and higher species, indicating that the cystine knot structure evolved in extracellular signaling molecules of multicellular organisms. All data retrieved by this study can be viewed at http://hormone.stanford.edu/.
Decay of mRNAs targeted by RISC requires XRN1, the Ski complex, and the exosome (2005)

RNA interference (RNAi) is a conserved RNA silencing pathway that leads to sequence-specific mRNA decay in response to the presence of double-stranded RNA (dsRNA). Long dsRNA molecules are first processed by Dicer into 21-22-nucleotide small interfering RNAs (siRNAs). The siRNAs are incorporated into a multimeric RNA-induced silencing complex (RISC) that cleaves mRNAs at a site determined by complementarity with the siRNAs. Following this initial endonucleolytic cleavage, the mRNA is degraded by a mechanism that is not completely understood. We investigated the decay pathway of mRNAs targeted by RISC in Drosophila cells. We show that 5' mRNA fragments generated by RISC cleavage are rapidly degraded from their 3' ends by the exosome, whereas the 3' fragments are degraded from their 5' ends by XRN1. Exosome-mediated decay of the 5' fragments requires the Drosophila homologs of yeast Ski2p, Ski3p, and Ski8p, suggesting that their role as regulators of exosome activity is conserved. Our findings indicate that mRNAs targeted by siRNAs are degraded from the ends generated by RISC cleavage, without undergoing decapping or deadenylation.
Glioma cancer stem cells secrete Gremlin1 to promote their maintenance within the tumor hierarchy (2014)

Glioblastomas are the most prevalent and lethal primary brain tumor and are comprised of hierarchies with self-renewing cancer stem cells (CSCs) at the apex. Like neural stem cells (NSCs), CSCs reside in functional niches that provide essential cues to maintain the cellular hierarchy. Bone morphogenetic proteins (BMPs) instruct NSCs to adopt an astrocyte fate and are proposed as anti-CSC therapies to induce differentiation, but, paradoxically, tumors express high levels of BMPs. Here we demonstrate that the BMP antagonist Gremlin1 is specifically expressed by CSCs as protection from endogenous BMPs. Gremlin1 colocalizes with CSCs in vitro and in vivo. Furthermore, Gremlin1 blocks prodifferentiation effects of BMPs, and overexpression of Gremlin1 in non-CSCs decreases their endogenous BMP signaling to promote stem-like features. Consequently, Gremlin1-overexpressing cells display increased growth and tumor formation abilities. Targeting Gremlin1 in CSCs results in impaired growth and self-renewal. Transcriptional profiling demonstrated that Gremlin1 effects were associated with inhibition of p21(WAF1/CIP1), a key CSC signaling node. This study establishes CSC-derived Gremlin1 as a driving force in maintaining glioblastoma tumor proliferation and glioblastoma hierarchies through the modulation of endogenous prodifferentiation signals.
High Performance Protein Sequence Database Scanning on the Cell Broadband Engine (2009)

The enormous growth of biological sequence databases has caused bioinformatics to be rapidly moving towards a data-intensive, computational science. As a result, the computational power needed by bioinformatics applications is growing rapidly as well. The recent emergence of low cost parallel multicore accelerator technologies has made it possible to reduce execution times of many bioinformatics applications. In this paper, we demonstrate how the Cell Broadband Engine can be used as a computational platform to accelerate two approaches for protein sequence database scanning: exhaustive and heuristic. We present efficient parallelization techniques for two representative algorithms: the dynamic programming based Smith–Waterman algorithm and the popular BLASTP heuristic. Their implementation on a Playstation®3 leads to significant runtime savings compared to corresponding sequential implementations.
Cloning and characterization of human recombinant antibody Fab fragments specific for types 1 and 2 herpes simplex virus. (1995)

Twenty-six bacterial clones producing human recombinant Fab fragments specific for Herpes Simplex virus (HSV) antigens were obtained from an IgG1k human antibody combinatorial library displayed on filamentous phage, following panning against an HSV lysate. All the Fabs reacted against the HSV lysate in enzyme-linked immunosorbent assay and were able to recognize both type 1 and type 2 HSV in an indirect immunofluorescence assay (IFA). DNA sequencing of the heavy chain variable regions showed that these Fabs were different from those already described. One of these Fabs (Fab19) was purified and subjected to further characterization. Purified Fab19 was able to specifically recognize several different HSV-1 and HSV-2 strains (including 2 reference strains and 12 clinical isolates) in IFA. It was also able to neutralize the infectivity of both HSV-1 and HSV-2 strains, although the neutralizing activity was somewhat lower against HSV-2. In fact, 100% neutralization of infectivity was observed at a Fab concentration of 2 micrograms/100 TCD50 for the majority of HSV-1 strains, while a concentration of 8 micrograms/100 TCD50 was needed for 100% neutralization of all the HSV-2 strains tested. Owing to the above properties, Fab19 appears to be useful for diagnostic purposes and might also prove useful for in vivo immunoprophylaxis and therapy of HSV infections.
An automatic approach for constructing a knowledge base of symptoms in Chinese (2017)

As a result, the KB has more than 26,000 distinct symptoms in Chinese including 3968 symptoms in traditional Chinese medicine and 1029 synonym pairs for symptoms. The KB also includes concepts such as diseases and medicines as well as relations between symptoms and the above related entities. We also link our KB to the Unified Medical Language System and analyze the differences between symptoms in the two KBs. We released the KB as Linked Open Data and a demo at https://datahub.io/dataset/symptoms-in-chinese .
Diazonium-Derived Aryl Films on Gold Nanoparticles: Evidence for a Carbon–Gold Covalent Bond (2011)

Tailoring the surface chemistry of metallic nanoparticles is generally a key step for their use in a wide range of applications. There are few examples of organic films covalently bound to metal nanoparticles. We demonstrate here that aryl films are formed on gold nanoparticles from the spontaneous reduction of diazonium salts. The structure and the bonding of the film is probed with surface-enhanced Raman scattering (SERS). Extinction spectroscopy and SERS show that a nitrobenzene film forms on gold nanoparticles from the corresponding diazonium salt. Comparison of the SERS spectrum with spectra computed from density functional theory models reveals a band characteristic of a Au-C stretch. The observation of this stretch is direct evidence of a covalent bond. A similar band is observed in high-resolution electron energy loss spectra of nitrobenzene layers on planar gold. The bonding of these types of films through a covalent interaction on gold is consistent with their enhanced stability observed in other studies. These findings provide motivation for the use of diazonium-derived films on gold and other metals in applications where high stability and/or strong adsorbate-substrate coupling are required.
G-Protein and Signalling in Pituitary Tumours (2009)

The genesis of pituitary tumours is still under debate. Although these neoplasias are monoclonal in origin, mutations of GNAS1, the gene encoding the alpha subunit of the stimulatory G-protein, Gs, are the only mutational changes unequivocally associated with growth hormone (GH)-secreting adenomas. However, despite the growth advantage that this oncogene has been demonstrated to confer in vitro, patients carrying this mutation have a similar clinical and biochemical phenotype to those who do not carry it. This discrepancy is due to the occurrence of events able to counteract the biological effect of the mutation. Consistent with a potential role of the cyclic adenosine monophosphate pathway in the proliferation of somatotrophs, germline mutations of the gene encoding the type 1alpha regulatory subunit of protein kinase A (PRKAR1A) have been found in patients with the Carney complex, a syndrome including GH-secreting adenomas, whereas alterations in the expression levels of this subunit are frequently observed in sporadic adenomas.
Divalent metal ion binding to a conserved wobble pair defining the upstream site of cleavage of group I self-splicing introns (1995)

The upstream site of cleavage of all group I self-splicing introns is identified by an absolutely conserved U.G base pair. Although a wobble C.A pair can substitute the U.G pair, all other combinations of nucleotides at this position abolish splicing, suggesting that it is an unusual RNA structure, rather than sequence, that is recognized by the catalytic intron core. RNA enzymes are metalloenzymes, and divalent metal ion binding may be an important requirement for splice site recognition and catalysis. The paramagnetic broadening of NMR resonances upon manganese binding at specific sites was used to probe the interaction between divalent metal ions and an oligonucleotide model of a group I intron ribozyme substrate. Unlike previous studies in which only imino proton resonances were monitored, we have used isotopically labelled RNA and a set of complete spectral assignments to identify the location of the divalent metal binding site with much greater detail than previously possible. Two independent metal binding sites were identified for this oligonucleotide. A first metal binding site is located in the major groove of the three consecutive G.C base pairs at the end of double helical stem. A second site is found in the major groove of the RNA double helix in the vicinity of the U.G base pair. These results suggest that metal ion coordination (or a metal bridge) and tertiary interactions identified biochemically, may be used by group I intron ribozymes for substrate recognition.
Characterization of VP22 in Herpes Simplex Virus-Infected Cells (2005)

We examine biochemical characteristics of the herpes simplex virus (HSV) tegument protein VP22 by gel filtration, glycerol sedimentation, and chemical cross-linking experiments and use time course radiolabeling and immunoprecipitation assays to analyze its synthesis and interaction with other infected-cell proteins. VP22 was expressed as a delayed early protein with optimal synthesis requiring DNA replication. In immunoprecipitation assays, VP22 was found in association with several additional proteins including VP16 and a kinase activity likely to be that of UL13. Furthermore, in sizing chromatography experiments, VP22 was present in several higher-order complexes in infected cells. From gel filtration analysis the major form of VP22 migrated with a molecular mass of approximately 160 kDa, consistent with its presence as a tetramer, or a dimer complexed with other proteins, with a fraction of the protein migrating at larger molecular mass. In vitro-synthesized VP22 sedimented in a size range consistent with a mixture of tetramers and dimers. Short N- or C-terminal deletions resulted in migration almost exclusively as dimers, indicating that VP22, in the absence of additional virus-encoded proteins, could form higher-order assemblies, most likely tetramers, but that both N-and C-terminal determinants were required for stabilizing such assemblies. Consistent with this we found that isolated proteins encompassing either the N-terminal or C-terminal region of VP22 sedimented as dimers, and that the purified C-terminal domain could be cross-linked into dimeric structures. These results are discussed with regard to possible virus and host interactions involved in VP22 recruitment into virus particles.
Synthesis of a Hybrid Protein Containing the Iron-Binding Ligand of Bleomycin and the DNA-Binding Domain of Hin (1994)

The iron-binding and oxygen-activating domain of the natural product bleomycin [pyrimidoblamic acid-beta-hydroxy-L-histidine (PBA-beta-OH-His)] was attached to the NH2 terminus of the DNA binding domain of Hin recombinase (residues 139-190). This hybrid 54-residue protein PBA-beta-OH-His-Hin-(139-190) binds specifically to DNA at four distinct Hin binding sites with affinities comparable to those of the unmodified Hin(139-190). In the presence of dithiothreitol, Fe(II).PBA-beta-OH-His-Hin-(139-190) cleaves DNA with specificity remarkably similar to that of Fe(II).EDTA-Hin(139-190). Analysis of the cleavage patterns suggests that site-specific DNA cleavage is mediated by a localized diffusible species, in contrast with cleavage by bleomycin, which occurs through a nondiffusible oxidant. This has implications for the design of second-generation artificial sequence specific DNA cleaving proteins and defines limitations in current efforts to create atom-specific chemistry on DNA.
IL-21–mediated Foxp3 suppression leads to enhanced generation of antigen-specific CD8+ cytotoxic T lymphocytes (2007)

Efforts to reproducibly isolate tumor antigen-specific T cells from patients would be facilitated by removing immunoregulatory barriers. Using a human model for eliciting T-cell responses to tumor-associated antigens, we develop a novel strategy that eliminates nearly all Foxp3-expressing cells through the combination of CD25 depletion and IL-21 treatment resulting in a more than 150-fold decrease in Foxp3(+) cells to virtually undetectable levels and a more than 200-fold increase in antigen-specific cytotoxic T lymphocytes (CTLs). The extent of Foxp3 elimination and degree of expansion of antigen-specific CTLs shown in this study have not previously been achievable and are unique to IL-21. We demonstrate for the first time a possible mechanism for IL-21-mediated expansion of antigen-specific CTLs that involves suppression of Foxp3-expressing cells and reversal of inhibition to tumor-associated antigen-specific CTL generation in vitro. Taken together, the combination of CD25 depletion and IL-21 exposure, by releasing regulatory constraints, leads to markedly enhanced CTL induction and represents a robust strategy for the ex vivo generation of antigen-specific T cells for adoptive cellular therapy.
Fusion thermonucléaire contrôlée: le point sur la recherche (1988)

CRPP
Impella 2.5 (2009)

Impella 2.5 (Abiomed Inc., Danvers, Ma.) is a percutaneous microaxial circulatory support pump that delivers up to 2.5 l/min of systemic flow augmentation by pumping directly from the left ventricle into the ascending aorta. This article describes the device including the insertion method, fundamental principles of action, and clinical results from the completed Protect I clinical trial as well as general use under FDA clearance.
Experimental HBV and δ infections of chimpanzees: Occurrence and significance of intrahepatic immune complexes of HBcAg and δ antigen (1981)

The occurrence and pathogenetic role of intrahepatic deposits of immunoglobulins in experimental viral infection have been evaluated by determining with immunofluorescence their capacity to fix complement in vitro [in vitro complement fixation (VCF)]. Liver biopsies from chimpanzees chronically or acutely infected with hepatitis B virus or the hepatitis B surface antigen (HBsAg)-associated delta agent were used in the study. VCF was observed in each animal expressing hepatitis B core antigen (HBcAg) or delta antigen in the liver and concurrently circulating the homologous antibody in the blood. In acutely infected animals, VCF appeared at the same time that the homologous serum antibody appeared, and the intensity of VCF staining was proportional to the antibody titer in the serum. In animals expressing sequentially the HBcAg/antibody system and then delta antigen and antibody to delta, VCF was first observed in HBcAg-containing nuclei and then in nuclei expressing delta antigen. There was no relationship between VCF and intrahepatic expression of HBsAg or serologic expression of hepatitis B e antigen (HBeAg). A positive VCF reaction appears related to the formation of intrahepatic immune complexes between HBcAg or delta antigen and the homologous antibody. Although acute hepatitis developed in parallel with the occurrence of VCF in two animals, strong VCF fluorescence was also observed in each of the asymptomatic carriers of HBsAg, and, in one of them, preexisting VCF staining of HBcAg disappeared in parallel with development of acute hepatitis. In experimentally infected chimpanzees, the finding in liver biopsies of immune complexes detectable by VCF appears to be a common epiphenomenon without pathogenic significance.
Impaired Decision Making in Suicide Attempters (2005)

Impaired decision making, possibly due to emotional dysfunction, may be a neuropsychological risk factor for suicidal behavior.
A malaria heat‐shock‐like determinant expressed on the infected hepatocyte surface is the target of antibody‐dependent cell‐mediated cytotoxic mechanisms by nonparenchymal liver cells (1990)

Cultured hepatic stages of Plasmodium falciparum and P. yoelii and with a monoclonal antibody recognizing a C-terminal fragment of the P. falciparum heat-shock-like protein (Pfhsp70) revealed that synthesis of this antigen first occurs during intrahepatic development of the parasite, at the two nuclei stage. Using a variety of techniques, including scanning electron microscopy, we observed that this antigenic determinant was expressed on the infected hepatocyte membrane. Its participation in antibody-dependent cell-mediated cytotoxicity was investigated. While no effect was obtained with peripheral blood cells, we found that 25% of the schizonts were specifically lysed when using spleen cells at a killer/target ratio of 30/1. More interestingly, with nonparenchymal liver cells, up to 50% of the hepatic parasites disappeared with a killer/target ratio of 10/1.
Etanercept in arthritis (2005)

Tumour necrosis factor-alpha (TNF-alpha) is one of the inflammatory cytokines. It is released by activated monocytes, macrophages and T lymphocytes and promotes inflammation. TNF-alpha binds to two receptors; one of these is the type 2 TNF receptor (p75). Etanercept is a soluble TNF-receptor fusion protein. It consists of two linked dimmers, each with a ligand-binding portion of the higher affinity type 2 TNF receptor (p75). This fusion protein binds to TNF-alpha and prevents it from interacting with its receptor. Etanercept is given by subcutaneous administration at a dose of 25 mg twice a week. This dosing reflects its half-life of about 4 days. Clinical trials show etanercept is effective and safe to use in rheumatoid arthritis (RA). It reduces disease activity and limits progressive joint damage in both early and late disease. It can be used as a monotherapy or in combination with methotrexate, and in this, the latter approach appears most effective. It is also effective in psoriatic arthritis and ankylosing spondylitis. Although the biologic appears safe, caution is needed to ensure it does not re-activate tuberculosis. It should not be used in patients with disseminated sclerosis, and there are concerns about a potential relationship to lymphoma. Its high cost means there will be continuing debate about the ideal position of this new biologic within the treatment pathway of RA. At present, it is recommended for use when methotrexate and another disease-modifying drug have failed.
Encapsidation studies of poliovirus subgenomic replicons. (1998)

The inclusion of a foreign marker gene, chloramphenicol acetyltransferase (CAT) gene, into the poliovirus genome allows its replication and encapsidation to be easily monitored using a simple enzyme assay. Such poliovirus replicons require the presence of helper virus for their successful propagation and thus are similar to defective interfering (DI) viruses. In genomes containing the CAT gene, the majority of the P1 virus capsid region of the poliovirus genome could be removed without destroying viability. The smallest replicon was significantly smaller than any naturally occurring DI particle so far reported, yet it retained the ability to replicate and be encapsidated by structural proteins provided by helper virus in trans. The efficiency with which the replicons were encapsidated was investigated using a direct immunostaining technique that allows individual cells infected with either a replicon or helper virus to be quantified. These results were compared to the frequencies of trans-encapsidation of polioviruses and coxsackievirus B4 using a two-stage neutralization assay. Poliovirus types 1, 2 and 3 but not coxsackievirus B4, coxsackievirus A21 or rhinovirus 14 provided efficient trans-encapsidation of poliovirus type 3 or type 3-derived replicons. These results suggest that a specific encapsidation process operates and that it does not involve RNA sequences within the region of the genome encoding the capsid proteins.
MicroRNAs in early vertebrate development (2009)

During embryonic development, a precise and tightly regulated hierarchy of gene expression is necessary to ensure the proper formation of all cell types and organs. In all animals and plants,microRNAs play a prominent role in the control of gene expression at the post-transcriptional level. In the last few years,microRNAs have emerged as important players during embryogenesis.As suggested by recent reports, microRNAs regulate crucial developmental processes, such as organizer induction,cell fate determination and body axis formation. In this review,we will discuss the role of microRNAs in early development of vertebrate model systems and in human embryonic stem cells,as an in vitro paradigm for human development.