gebhart/patrepeval huggingface dataset:
Genome-wide Profiling of Genetic Synthetic Lethality Identifies CDK12 as a Novel Determinant of PARP1/2 Inhibitor Sensitivity (2013)

Small-molecule inhibitors of PARP1/2, such as olaparib, have been proposed to serve as a synthetic lethal therapy for cancers that harbor BRCA1 or BRCA2 mutations. Indeed, in clinical trials, PARP1/2 inhibitors elicit sustained antitumor responses in patients with germline BRCA gene mutations. In hypothesizing that additional genetic determinants might direct use of these drugs, we conducted a genome-wide synthetic lethal screen for candidate olaparib sensitivity genes. In support of this hypothesis, the set of identified genes included known determinants of olaparib sensitivity, such as BRCA1, RAD51, and Fanconi's anemia susceptibility genes. In addition, the set included genes implicated in established networks of DNA repair, DNA cohesion, and chromatin remodeling, none of which were known previously to confer sensitivity to PARP1/2 inhibition. Notably, integration of the list of candidate sensitivity genes with data from tumor DNA sequencing studies identified CDK12 deficiency as a clinically relevant biomarker of PARP1/2 inhibitor sensitivity. In models of high-grade serous ovarian cancer (HGS-OVCa), CDK12 attenuation was sufficient to confer sensitivity to PARP1/2 inhibition, suppression of DNA repair via homologous recombination, and reduced expression of BRCA1. As one of only nine genes known to be significantly mutated in HGS-OVCa, CDK12 has properties that should confirm interest in its use as a biomarker, particularly in ongoing clinical trials of PARP1/2 inhibitors and other agents that trigger replication fork arrest.
Immunophenotype of intraductal carcinoma. (1996)

These observations indicate that there are immunophenotypic correlates to the current structural classification of IDC. The immunophenotype of IDC is helpful in subclassifying an IDC and could prove useful as a prognostic indicator for local control in patients treated by breast-conserving therapy.
Feline immunodeficiency virus infects both CD4+ and CD8+ T lymphocytes (1991)

Monoclonal populations of feline T cells, derived from a specific-pathogen-free cat and expressing either the CD4 or CD8 surface antigen, were infected in vitro with two geographically distinct isolates of feline immunodeficiency virus (FIV). Both infected T-cell subsets exhibited decreased cell viability, expressed FIV-encoded proteins, and generated reverse transcriptase activity. All clones examined retained their original surface phenotype after infection. It appears, therefore, that both CD4+ and CD8+ T cells may be productively infected by FIV in vivo.
Liposomes' From theoretical model to cosmetic tool (1989)

Nature des liposomes (vesicules lipidiques a 2 couches), preparation de cosmetiques encapsules dans des liposomes, techniques de caracterisation des liposomes, effet benefique de ces liposomes dans les cosmetiques (absorption plus importante par la peau)
From repression domains to designer zinc finger proteins: a novel strategy of intracellular immunization against HIV. (1996)

Tissue-specific gene regulation of eukaryotic organisms is to a large extent mediated by transcription factors that interact with genomic DNA sequences in a sequence-specific manner. The purpose of this synopsis is to put forward the potential of designer zinc finger proteins in treating infections of human immunodeficiency virus (HIV). Artificial transcription factors containing designer zinc finger structures fused to activator or repressor domains have been designated Transcription Response Modifiers (TRMs). The principle of engineering TRMs has been derived from the analysis of human Krüppel-type zinc finger genes and their products. Our research efforts encompass two fascinating features that are displayed by the human Krüppel-type zinc finger protein KOX1: 1) the Krüppel-type zinc finger domains display rules of sequence-specific DNA recognition, and 2) the evolutionarily conserved Krüppel-associated box (KRAB) presents one of the strongest transcriptional repressors identified so far in mammalian organisms. The KRAB repressor activity is postulated to be mediated through co-repressor molecules, such as Silencing Mediating Protein-1 (SMP-1). Thus, the structural organization and functional analysis of zinc finger proteins revealed principles of zinc finger transcription factors that are applicable for reducing the viral load in individuals infected with HIV. In this article, a novel concept of generating therapeutic proteins is outlined that might be conceptually promising in modulating gene expressions of any kind.
Partial reverse transcripts in virions from human immunodeficiency and murine leukemia viruses (1992)

Reverse transcription of the retroviral genome is thought to start after virions enter target cells. Purified preparations of human immunodeficiency virus were found to contain virus-specific DNA, detectable by polymerase chain reaction amplification. This DNA resulted from reverse transcription in newly assembled virus particles and not from contamination by cellular DNA, because virions contained a striking excess of early versus late transcripts and because the accumulation of these products was sensitive to 3'-azido-3'-deoxythymidine (zidovudine) treatment of producer cells. A similar observation was made with murine amphotropic retrovirus particles. It is therefore likely that all retroviruses contain partial reverse transcripts.
CD28/B7 interactions are required for sustaining the graft-versus-leukemia effect of delayed post-bone marrow transplantation splenocyte infusion in murine recipients of myeloid or lymphoid leukemia cells (1997)

Graft-vs-leukemia (GVL) can reduce relapse rates after bone marrow transplantation (BMT). Delayed lymphocyte infusion (DLI) post-BMT can mediate a potent GVL effect with less graft-vs-host disease (GVHD) than would be observed if given early post-BMT. In vivo CD28/B7 blockade can reduce GVHD lethality, and B7 ligand expression can augment an antitumor immune response in mice. To examine the role of CD28/B7 interactions in DLI-mediated GVL, we established murine allogeneic BMT models in C57BL/6 (B6) recipients of C1498 (B6 acute myeloid leukemia) or EL4 (B6 acute T cell leukemia) that closely mimic human GVL. Recipients of C1498 and DLI had a marked reduction in relapse. GVL was blocked by anti-B7 mAb infusion. In contrast, recipients of EL4 cells and B10.BR DLI had a more modest GVL effect. The forced expression of B7-1 on EL4 cells markedly augmented the GVL effect of DLI, in contrast to the forced expression of B7-2 on EL4 cells. Relapse rates observed in recipients of C1498-B7-1 and DLI were significantly lower than in recipients of parental C1498 cells. We conclude that the administration of anti-B7 mAbs may impair the GVL effect of DLI and that the forced expression of B7-1 ligands stimulates a GVL effect without adversely affecting the GVHD lethality effect of DLI.
Enantioselective synthesis of .beta.-amino esters through high pressure-induced addition of amines to .alpha.,.beta.-ethylenic esters (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnantioselective synthesis of .beta.-amino esters through high pressure-induced addition of amines to .alpha.,.beta.-ethylenic estersJean. D'Angelo and Jacques. MaddalunoCite this: J. Am. Chem. Soc. 1986, 108, 25, 8112–8114Publication Date (Print):December 1, 1986Publication History Published online1 May 2002Published inissue 1 December 1986https://pubs.acs.org/doi/10.1021/ja00285a051https://doi.org/10.1021/ja00285a051research-articleACS PublicationsRequest reuse permissionsArticle Views748Altmetric-Citations145LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Cloning of a cDNA for a novel insulin-like peptide of the testicular Leydig cells. (1993)

We have isolated complementary DNA clones coding for a novel member of the insulin-like hormone super-family from a boar testis cDNA library. Northern blot analysis and in situ hybridization revealed that the gene is expressed exclusively in prenatal and postnatal Leydig cells. We have tentatively proposed the name Leydig insulin-like (Ley I-L) for the gene and its encoded protein. The Leydig insulin-like protein is synthesized as a 131-amino acid preproprotein, which contains a 24-amino acid signal peptide. Comparison of the deduced amino acid sequence of pro-Leydig insulin-like protein with members of the insulin-like hormone superfamily predicts that the biologically active protein, after proteolytic processing of the C-peptide, consists of a 32-residue-long B-chain and a 26-residue-long A-chain and has a molecular size of 6.25 kDa.
Inhibition of bone resorption in vitro by selective inhibitors of gelatinase and collagenase (1995)

Two low-molecular-mass inhibitors of matrix metalloproteinases (MMPs), CT1166, a concentration-dependent selective inhibitor of gelatinases A and B, and Ro 31-7467, a concentration-dependent selective inhibitor of collagenase, were examined for their effects on bone resorption and type-I collagenolysis. The test systems consisted of measuring (1) the release of [3H]proline from prelabelled mouse calvarial explants; (2) the release of 14C from prelabelled type-I collagen films by mouse calvarial osteoblasts; and (3) lacunar resorption by isolated rat osteoclasts cultured on ivory slices. In 24 h cultures, CT1166 and Ro 31-7467 inhibited both interleukin-1 alpha- (IL-1 alpha; 10(-10) M) and 1,25-dihydroxyvitamin D3 (10(-8) M)-stimulated bone resorption in cultured neonatal mouse calvariae at concentration selective for the inhibition of gelatinase (10(-9) M for CT1166) and collagenase (10(-8) M for Ro 31-7467) respectively. For each compound the inhibition was dose-dependent, reversible, and complete at a 10(-7) M concentration. However, CT1166 (10(-9) M) and Ro 31-7467 (10(-8) M) in combination were required to completely abolish IL-1 alpha-stimulated bone resorption in mouse calvariae throughout a 96 h culture period. Neither of the inhibitors affected protein synthesis, DNA synthesis nor the IL-1 alpha-stimulated secretion of the lysosomal enzyme, beta-glucuronidase. Both CT1166 and Ro 31-7467 partially inhibited IL-1 alpha-stimulated lacunar resorption by isolated osteoclasts, but were without effect on unstimulated lacunar resorption. Rodent osteoclasts produced collagenase and gelatinases-A and -B activity. In contrast the substrate used to assess osteoclast lacunar resorption contained no detectable collagenase or gelatinase activity. Both compounds dose-dependently inhibited 1,25-dihydroxyvitamin D3 (10(-8) M)-stimulated degradation of type-I collagen by mouse calvarial osteoblasts; however, complete inhibition of collagenolysis was only achieved at concentrations at which CT1166 and Ro 31-7467 act as general MMP inhibitors. This study demonstrates that collagenase and gelatinases A and/or B participate in bone resorption. While these MMPs may be primarily involved in osteoid removal, we conclude that they may also be released by osteoclasts, where they participate in bone collagen degradation within the resorption lacunae.
Virtual Screening for Aryl Hydrocarbon Receptor Binding Prediction (2006)

The overall goal of this study has been to validate computational models for predicting aryl hydrocarbon receptor (AhR) binding. Due to the unavailability of the AhR X-ray crystal structure we have decided to use QSARs models for the binding prediction virtual screening. We have built up CoMFA, Volsurf, and HQSAR models using as a training set 84 AhR ligands. Additionally, we have built a hybrid model combining two of the final selected models in order to give a single operational system. The results show that CoMFA, VolSurf, HQSAR, and the hybrid models gives good results (R(2) equal to 0.91, 0.79, 0.85, and 0.82 and q(2) 0.62, 0.58, 0.62, and 0.70, respectively). Since the techniques analyzed show a good correlation and good prediction also for an external test set, particularly the HQSAR and the hybrid model, we can conclude that these models can be used for predicting AhR binding in virtual screening.
The surface envelope protein gene region of equine infectious anemia virus is not an important determinant of tropism in vitro (1992)

Virulent, wild-type equine infectious anemia virus (EIAV) is restricted in one or more early steps in replication in equine skin fibroblast cells compared with cell culture-adapted virus, which is fully competent for replication in this cell type. We compared the sequences of wild-type EIAV and a full-length infectious proviral clone of the cell culture-adapted EIAV and found that the genomes were relatively well conserved with the exception of the envelope gene region, which showed extensive sequence differences. We therefore constructed several wild-type and cell culture-adapted virus chimeras to examine the role of the envelope gene in replication in different cell types in vitro. Unlike wild-type virus, which is restricted by an early event(s) for replication in equine dermis cells, the wild-type outer envelope gene chimeras are replication competent in this cell type. We conclude that even though there are extensive sequence differences between wild-type and cell culture-adapted viruses in the surface envelope gene region, this domain is not a determinant of the differing in vitro cell tropisms.
Subtype Specific Regulation of Human Vascular α1-Adrenergic Receptors by Vessel Bed and Age (1999)

Human vascular alpha(1)AR subtype distribution differs from animal models, varies with vessel bed, correlates with contraction in mammary artery, and is modulated by aging. These findings provide potential novel targets for therapeutic intervention in many clinical settings.
Constitutive endocytosis and degradation of CD22 by human B cells. (1995)

The CD22 B lymphocyte-surface Ag is an important component of the B cell-surface IgM (sIgM)/B cell receptor complex and has been shown to regulate B cell activation. In addition, this molecule has been shown to be an effective target for immunotherapy of B cell malignancies using immunotoxins and radioimmunoconjugates. In this report we describe the internalization and metabolic degradation of this molecule under constitutive conditions and after stimulation of B cells with phorbol dibutyrate or mAbs binding to sIgM, CD19, and CD22. Flow cytometry, "neuraminidase protection," and "neuraminidase shift" assays demonstrated that CD22 is internalized constitutively by unstimulated B cell lines and subsequently degraded in an acidic intracellular compartment (presumably lysosomes) without detectable recycling of the molecule back to the cell surface. Ligation of CD22 with anti-CD22 mAbs markedly increased CD22 internalization but did not affect the rate of intracellular degradation of CD22, suggesting that anti-CD22 mAbs perturb the intracellular trafficking of CD22. In contrast, CD22 internalization and degradation was unaffected by stimulation of B cell lines with phorbol dibutyrate or ligation of other components of the B cell receptor complex (e.g. CD19, sIgM) with mAbs. These patterns of internalization and degradation under constitutive and stimulated conditions contrast with those reported for other lymphoid differentiation Ags (e.g., the TCR, CD3, CD4, and the transferrin receptor), and may help explain the utility of this molecule as a target for immunoconjugate therapy.
An Outbreak of Infections Caused by Strains of Staphylococcus aureus Resistant to Methicillin and Aminoglycosides. I. Clinical Studies (1979)

In a 22-month period, strains of Staphylococcus aureus resistant to methicillin and multiple aminoglycosides, (designated MARS) were recovered from 108 inpatients with nosocomial infections at a hospital in the midwestern United States. Sixty-six of these patients were staying in a burn unit, and 42 were on other hospital wards. Among the patients with burns, MARS were recovered from the burn wounds of 64%; 32% of the patients with burns had MARS bacteremia. The patients without burns were age-matched with patients with nosocomial infections caused by antibiotic-susceptible strains of S. aureus. Patients from whom MARS were isolated had a longer mean hospital stay (79.6 days vs. 36.9 days; P less than 0.01), developed infection later (26.5 days vs. 13.5 days after admission; P less than 0.01), and had received antibiotic therapy before infection more often (81% vs. 38% of patients; P less than 0.01) than patients in the comparative population. Types of infection and incidences of death and bacteremia were similar in the two groups. Antibiotic-resistant strains of S. aureus may cause serious infections and significant mortality.
Detection of miRNAs with a nanopore single-molecule counter (2012)

miRNAs are short noncoding RNA molecules that are important in regulating gene expression. Due to the correlation of their expression levels and various diseases, miRNAs are being investigated as potential biomarkers for molecular diagnostics. The fast-growing miRNA exploration demands rapid, accurate, low-cost miRNA detection technologies. This article will focus on two platforms of nanopore single-molecule approach that can quantitatively measure miRNA levels in samples from tissue and cancer patient plasma. Both nanopore methods are sensitive and specific, and do not need labeling, enzymatic reaction or amplification. In the next 5 years, the nanopore-based miRNA techniques will be improved and validated for noninvasive and early diagnosis of diseases.
Systemic lidocaine for neuropathic pain relief (2000)

The effectiveness of systemic lidocaine in relieving acute and chronic pain has been recognized for over 35 years. In particular, systemic lidocaine has been utilized both as a diagnostic and therapeutic tool for intractable neuropathic pain during the last decade. The introduction of oral lidocaine congeners such as mexiletine has significantly extended the usage of lidocaine therapy in chronic pain settings. However, a number of clinical issues remain to be addressed including (1) an effective, meaningful dose range for the clinical lidocaine test, (2) the predictive value of the lidocaine test for an oral trial of lidocaine congeners, (3) identification of pain symptoms and signs relieved by systemic lidocaine, (4) comparisons of therapeutic effects between systemic lidocaine and its oral congeners, and (5) long-term outcomes of systemic lidocaine and its oral congeners. Mechanisms of neuropathic pain relief from lidocaine therapy are yet to be understood. Both central and peripheral mechanisms have been postulated. Systemic lidocaine is thought to have its suppressive effects on spontaneous ectopic discharges of the injured nerve without blocking normal nerve conduction. However, there remain inconsistencies in the scientific basis underlying the clinical application of lidocaine therapy. Recent demonstration of changes in tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels following nerve injury and their link to certain neuropathic pain symptoms may lead to the development of subtype-specific sodium channel blockers. The thoughtful use of lidocaine therapy and the potential application of subtype-specific sodium channel blockers could provide better management of distinctive neuropathic pain symptoms.
Controlling dynamic simulation with kinematic constraints (1987)

Theoretical and numerical aspects of the implementation of a DYNAmic MOtion system, dubbed DYNAMO, for the dynamic simulation of linked figures is presented. The system introduces three means for achieving, control of the resulting motion which have not been present in previous dynamic simulation systems for computer animation. (1) "Kinematic constraints" permit traditional keyframe animation systems to be embedded within a dynamic analysis. Joint limit constraints are also handled correctly through kinematic constraints. (2) "Behavior functions" relate the momentary state of the dynamic system to desired forces and accelerations within the figure. (3) "Inverse dynamics" provides a means of determining the forces required to perform a specified motion.The combination of kinematic and dynamic specifications allows the animator to think about each part of the animation in the way that is most suitable for the task. Successful experimental results are presented which demonstate the ability to provide control without disrupting the dynamic integrity of the resulting motion.
Nanodiscs as a Modular Platform for Multimodal MR-Optical Imaging (2015)

Nanodiscs are monodisperse, self-assembled discoidal particles that consist of a lipid bilayer encircled by membrane scaffold proteins (MSP). Nanodiscs have been used to solubilize membrane proteins for structural and functional studies and deliver therapeutic phospholipids. Herein, we report on tetramethylrhodamine (TMR) tagged nanodiscs that solubilize lipophilic MR contrast agents for generation of multimodal nanoparticles for cellular imaging. We incorporate both multimeric and monomeric Gd(III)-based contrast agents into nanodiscs and show that particles containing the monomeric agent (ND2) label cells with high efficiency and generate significant image contrast at 7 T compared to nanodiscs containing the multimeric agent (ND1) and Prohance, a clinically approved contrast agent.
Influenza virus naked RNA can be expressed upon transfection into cells co-expressing the three subunits of the polymerase and the nucleoprotein from simian virus 40 recombinant viruses (1993)

The functionality of the influenza virus polymerase subunits and the nucleoprotein expressed from simian virus 40 (SV40) recombinants has been tested by their ability to direct the in vivo expression of influenza virus-like RNAs. These RNAs, which contained either the chloramphenicol acetyltransferase (CAT) or haemagglutinin (HA) genes, were synthesized and reconstituted in vitro into viral ribonucleoproteins with a polymerase/nucleoprotein mixture purified from influenza virus-infected cells. Only the coinfection with SV40 recombinant viruses expressing the three polymerase subunits and the nucleoprotein allowed the expression of the transfecting CAT or HA RNAs, confirming that this set of viral genes is the minimal requirement for viral gene expression. Unexpectedly, transfection of the corresponding naked RNAs into SV40 recombinant-infected cells was as effective in directing the synthesis of CAT or HA proteins as the standard reconstituted ribonucleoprotein transfection. These results may be important for the genetic analysis of trans-acting factors involved in influenza virus transcription and replication and may open the way to rescuing influenza viruses in the absence of a helper virus.