gebhart/patrepeval huggingface dataset:
Drug-induced apoptosis in B-cell chronic lymphocytic leukemia: relationship between p53 gene mutation and bcl-2/bax proteins in drug resistance. (1996)

We investigated the relationship among chemosensitivity to drug-induced apoptosis in vitro, the presence of p53 gene mutations, and the expression of bcl-2 and bax proteins in B-cells from B-cell chronic lymphocytic leukemia (B-CLL) patients. Apoptosis was induced with a camptothecin analogue, 9-amino-20(s)-camptothecin, or a purine analogue, fludarabine. Cell death was monitored by propidium iodide staining and FACS analysis. Drug-induced apoptosis in B-CLL cells was p53-independent. Immunoblot analysis of bcl-2 and bax expression revealed a correlation between drug-induced apoptosis and the ratio of endogenous levels of bcl-2 to bax proteins. B-CLL cells with none to low bcl-2/bax ratios were drug-sensitive as compared to cells with intermediate to high ratios that were drug-resistant (P = 0.015). Prior to drug treatment, bax protein migrated as a single species of 21 kDa. Following drug-induced apoptosis, anti-bax specific protein complexes of 36-42 kDa were up-regulated. Using two-dimensional gel electrophoresis, bax complexes were disrupted under reducing conditions to reveal homo- and heterodimers of 18 and 21 kDa suggesting that disulfide interactions were required for complex formation. The de novo appearance of the 18 kDa anti-bax specific protein together with its increased expression in drug-sensitive B-CLL B-cells undergoing cell death suggests a role for this protein in the regulation of apoptosis.
Synthesis of fused 1,2,4-triazines: 6- and 7-azapteridine and 6-azapurine ring systems (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of fused 1,2,4-triazines: 6- and 7-azapteridine and 6-azapurine ring systemsJim J. HuangCite this: J. Org. Chem. 1985, 50, 13, 2293–2298Publication Date (Print):June 1, 1985Publication History Published online1 May 2002Published inissue 1 June 1985https://pubs.acs.org/doi/10.1021/jo00213a019https://doi.org/10.1021/jo00213a019research-articleACS PublicationsRequest reuse permissionsArticle Views615Altmetric-Citations52LEARN 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-Alertsclose Get e-Alerts
Mesenchymal Stern Cells from Adult Human Bone Marrow Differentiate into a Cardiomyocyte Phenotype In Vitro (2004)

A method for isolating adult human bone marrow mesenchymal stem cells (MSCs) was established, and the ability of human MSCs to differentiate into cells with characteristics of cardiomyocytes in vitro was investigated. Selected MSC surface antigens were analyzed by flow cytometry. The MSCs at Passage 2 were treated with 5-azacytidine to investigate their differentiation into cardiomyocytes. Characteristics of the putative myogenic cells were determined by immunohistochemistry and transmission electron and confocal microscopies. The expression of myogenic specific genes was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), real-time quantitative PCR, and DNA sequencing. The MSCs were spindle-shaped with irregular processes and were respectively positive for CD(13), CD(29), CD(44), CD(71) and negative for CD(3), CD(14), CD(15), CD(33), CD(34), CD(38), CD(45), and HLA-DR. The myogenic cells differentiated from MSCs were positive for beta-myosin heavy chain (beta-MHC), desmin, and alpha-cardiac actin. When the myogenic cells were stimulated with low concentration of K(+) (5.0 mM), an increase in intracellular calcium fluorescence was observed. Myofilament-like structures were observed in electron micrographs of the differentiated myogenic cells. The mRNAs of beta-MHC, desmin, alpha-cardiac actin, and cardiac troponin T were highly expressed in the myogenic cells. These results indicate that 5-azacytidine can induce human MSCs to differentiate in vitro into cells with characteristics commonly attributed to cardiomyocytes. Cardiomyocytes cultured from bone marrow sources are potentially valuable for repairing injured myocardium.
Flavopiridol given as a 30-min intravenous (IV) bolus followed by 4-hr continuous IV infusion (CIVI) results in clinical activity and tumor lysis in refractory chronic lymphocytic leukemia (CLL) (2004)

6564 Background: CLL patients (pts) with del(17p13) [p53 gene] have a poor outcome and do not respond to most conventional therapies. Flavopiridol induces apoptosis in CLL cells in a p53-independent manner, but phase I/II studies using a 24–72-hr CIVI schedule showed no activity. Increased drug binding to human plasma proteins prompted pharmacokinetic modeling indicating an optimal dosing schedule of 30-min IV bolus (IVB) followed by 4-hr CIVI. Methods: We report preliminary results of an ongoing phase I study using this schedule. Results: Nine pts (median age 60, range 44–73) with fludarabine-refractory CLL have been enrolled (median prior therapies 7, range 2–13). Five pts had del(17p13); 6 pts were stage III/IV. Pts received 50% of the dose by 30-min IVB and 50% by 4-hr CIVI weekly for 4 doses on a 6-week cycle. Six pts in cohort 1 received 60 mg/m2/dose; 3 pts in cohort 2 received 80 mg/m2/dose. Grade 3–4 toxicity was seen (neutropenia 6, thrombocytopenia 1, dyspnea 1, edema 1, diarrhea 1), but most toxicity was grade 1–2 (fatigue 7, nausea 6, anorexia 6). Tumor lysis was seen in 3 pts in cohort 2. Two pts had tumor lysis to the first dose. One pt completed cycle 1 without further tumor lysis. The other pt died of overwhelming tumor lysis, with predominant hyperkalemia not responding to forced alkaline hydration and IV insulin, and cardiac arrhythmia. A third pt had tumor lysis to dose 1 of cycle 2 and responded to medical management. This pt also developed hypotension that resolved with steroids, suggesting a cytokine release syndrome. Pts completed a median of 1 cycle (range 0–2). Treatment was stopped due to disease progression (3), infection (1), tumor lysis (2), and study interruption to institute guidelines to prevent further tumor lysis (3). Two pts in cohort 1 experienced an NCI 96 partial response lasting 5+ months; 1 of these pts has del(17p13). Conclusions: Single agent flavopiridol given weekly by 30-min IVB followed by 4-hr CIVI is active in refractory CLL, resulting in clinical responses and tumor lysis. Further study of this pharmacokinetically modeled schedule is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Pharmaceuticals
Filtration und Pelletierung (1979)

Aus Tabelle 3 und 4 sowie Bild 17 sind die chemischen Analysen von LD- und Gichtschlämmen verschiedener deutscher Hütten- und Stahlwerke zu ersehen.
Irinotecan Plus Temozolomide for Relapsed or Refractory Neuroblastoma (2006)

This regimen has anti-NB activity, spares vital organs, is feasible with poor bone marrow reserve, causes limited immunosuppression, and allows good quality of life.
Effects of B doping on hydrogen desorption from Si(001) during gas-source molecular-beam epitaxy from Si2H6 and B2H6 (1996)

Boron doping concentrations ≳6×1019 cm−3 were found to increase Si(001) growth rates RSi at low temperatures while decreasing RSi at higher temperatures during gas-source molecular beam epitaxy (GS-MBE) from Si2H6 and B2H6. In order to probe the mechanisms governing these effects, Si(001) samples with B coverages θB ranging from &amp;lt;0.05 to ≂0.5 ML were prepared by exposing clean Si(001)2×1 wafers to B2H6 doses between 2×1017 and 4×1020 cm−2 at 200–400 °C. The samples were then heated to 700 °C to desorb the hydrogen, cooled to 200 °C, and exposed to atomic deuterium until saturation coverage. D2 temperature programmed desorption spectra exhibit β2 and β1 peaks due to dideuteride and monodeuteride desorption at 405 and 515 °C as well as new B-induced peaks, β2* and β1*, at 330 and 470 °C. Increasing θB increases the area under β2* and β1* at the expense of β2 and β1. Moreover, the total D coverage continuously decreases from ≂1.23 ML in the absence of B to ≂0.74 ML at θB=0.5 ML. We propose that the observed B-induced decrease in the Si*-D bond strength, where Si* represents surface Si atoms bonded to second-layer B atoms, is due to charge transfer and increased Si* dimer strain. The Si* to B charge transfer also deactivates Si surface dangling bonds causing the decrease in θD. These results are used to explain the GS-MBE growth kinetics.
Imp/OstA is required for cell envelope biogenesis in Escherichia coli (2002)

In Gram-negative bacteria, all components of the outer membrane are synthesized in the cytoplasm or the cytoplasmic leaflet of the inner membrane and must thus traverse the inner membrane and the periplasm on the way to their final destination. In this study, we show Imp/OstA to have characteristics typical for proteins involved in envelope biogenesis. Imp is essential and forms a high-molecular-weight disulphide-bonded complex in the outer membrane. Upon depletion of Imp, lipids and outer membrane proteins appear in a novel membrane fraction with higher density than the outer membrane. We propose Imp to be part of a targeting/usher system for components of the outer membrane.
Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses (2011)

Understanding the antibody response to HIV-1 in humans that show broad neutralizing serologic activity is a crucial step in trying to reproduce such responses by vaccination. Investigating antibodies with cross clade reactivity is particularly important as these antibodies may target conserved epitopes on the HIV envelope gp160 protein. To this end we have used a clade B YU-2 gp140 trimeric antigen and single-cell antibody cloning methods to obtain 189 new anti-gp140 antibodies representing 51 independent B cell clones from the IgG memory B cells of 3 patients infected with HIV-1 clade A or B viruses and exhibiting broad neutralizing serologic activity. Our results support previous findings showing a diverse antibody response to HIV gp140 envelope protein, characterized by differentially expanded B-cell clones producing highly hypermutated antibodies with heterogenous gp140-specificity and neutralizing activity. In addition to their high-affinity binding to the HIV spike, the vast majority of the new anti-gp140 antibodies are also polyreactive. Although none of the new antibodies are as broad or potent as VRC01 or PG9, two clonally-related antibodies isolated from a clade A HIV-1 infected donor, directed against the gp120 variable loop 3, rank in the top 5% of the neutralizers identified in our large collection of 185 unique gp140-specific antibodies in terms of breadth and potency.
Single-Cell Transcriptomic Analysis of Human Lung Provides Insights into the Pathobiology of Pulmonary Fibrosis (2018)

<b>Rationale:</b> The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual cell populations during pulmonary fibrosis that are important for disease pathogenesis. <b>Objectives:</b> To determine whether single-cell RNA sequencing can reveal disease-related heterogeneity within alveolar macrophages, epithelial cells, or other cell types in lung tissue from subjects with pulmonary fibrosis compared with control subjects. <b>Methods:</b> We performed single-cell RNA sequencing on lung tissue obtained from eight transplant donors and eight recipients with pulmonary fibrosis and on one bronchoscopic cryobiospy sample from a patient with idiopathic pulmonary fibrosis. We validated these data using <i>in situ</i> RNA hybridization, immunohistochemistry, and bulk RNA-sequencing on flow-sorted cells from 22 additional subjects. <b>Measurements and Main Results:</b> We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to nonoverlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. We developed a web-based tool to explore these data. <b>Conclusions:</b> We generated a single-cell atlas of pulmonary fibrosis. Using this atlas, we demonstrated heterogeneity within alveolar macrophages and epithelial cells from subjects with pulmonary fibrosis. These results support the feasibility of discovery-based approaches using next-generation sequencing technologies to identify signaling pathways for targeting in the development of personalized therapies for patients with pulmonary fibrosis.
Use of Verapamil as a Potential P-Glycoprotein Inhibitor in a Patient with Refractory Epilepsy (2004)

Verapamil may offer pharmacoresistant patients hope of improved seizure control due to its potential P-glycoprotein inhibitory effects.
Automatic procedure for aberration compensation in digital holographic microscopy and applications to specimen shape compensation (2006)

We present a procedure that compensates for phase aberrations in digital holographic microscopy by computing a polynomial phase mask directly from the hologram. The phase-mask parameters are computed automatically without knowledge of physical values such as wave vectors, focal lengths, or distances. This method enables one to reconstruct correct and accurate phase distributions, even in the presence of strong and high-order aberrations. Examples of applications are shown for microlens imaging and for compensating for the deformations associated with a tilted thick plate. Finally we show that this method allows compensation for the curvature of the specimen, revealing its surface defects and roughness. Examples of applications are shown for microlenses and metallic sphere imaging.
Disposition and metabolism of oligodeoxynucleoside methylphosphonate following a single i.v. injection in mice. (1991)

We describe the plasma apparent half-life, distribution profile, and identification of a metabolite of a sequence-specific oligodeoxynucleoside methylphosphonate, 12-mer (a family of nonionic nucleic acid analogues used as antisense agent with potent antiviral activities), in the mouse.
Single-molecule DNA detection with an engineered MspA protein nanopore (2008)

Nanopores hold great promise as single-molecule analytical devices and biophysical model systems because the ionic current blockades they produce contain information about the identity, concentration, structure, and dynamics of target molecules. The porin MspA of Mycobacterium smegmatis has remarkable stability against environmental stresses and can be rationally modified based on its crystal structure. Further, MspA has a short and narrow channel constriction that is promising for DNA sequencing because it may enable improved characterization of short segments of a ssDNA molecule that is threaded through the pore. By eliminating the negative charge in the channel constriction, we designed and constructed an MspA mutant capable of electronically detecting and characterizing single molecules of ssDNA as they are electrophoretically driven through the pore. A second mutant with additional exchanges of negatively-charged residues for positively-charged residues in the vestibule region exhibited a factor of approximately 20 higher interaction rates, required only half as much voltage to observe interaction, and allowed ssDNA to reside in the vestibule approximately 100 times longer than the first mutant. Our results introduce MspA as a nanopore for nucleic acid analysis and highlight its potential as an engineerable platform for single-molecule detection and characterization applications.
Eicosapentaenoic acid prevents arterial calcification in klotho mutant mice (2017)

EPA prevents arterial calcification together with reduction of NOX gene expression and activity via GPR120 in klotho mutant mice.
Thrombospondin-1 controls vascular platelet recruitment and thrombus adherence in mice by protecting (sub)endothelial VWF from cleavage by ADAMTS13 (2005)

The function of thrombospondin-1 (TSP-1) in hemostasis was investigated in wild-type (WT) and Tsp1-/- mice, via dynamic platelet interaction studies with A23187-stimulated mesenteric endothelium and with photochemically injured cecum subendothelium. Injected calcein-labeled WT platelets tethered or firmly adhered to almost all A23187-stimulated blood vessels of WT mice, but Tsp1-/- platelets tethered to 45% and adhered to 25.8% of stimulated Tsp1-/- vessels only. Stimulation generated temporary endothelium-associated ultralarge von Willebrand factor (VWF) multimers, triggering platelet string formation in 48% of WT versus 20% of Tsp1-/- vessels. Injection of human TSP-1 or thrombotic thrombocytopenic purpura (TTP) patient-derived neutralizing anti-ADAMTS13 antibodies corrected the defective platelet recruitment in Tsp1-/- mice, while having a moderate effect in WT mice. Photochemical injury of intestinal blood vessels induced thrombotic occlusions with longer occlusion times in Tsp1-/- venules (1027 +/- 377 seconds) and arterioles (858 +/- 289 seconds) than in WT vessels (559 +/- 241 seconds, P < .001; 443 +/- 413 seconds, P < .003) due to defective thrombus adherence, resulting in embolization of complete thrombi, a defect restored by both human TSP-1 and anti-ADAMTS13 antibodies. We conclude that in a shear field, soluble or local platelet-released TSP-1 can protect unfolded endothelium-bound and subendothelial VWF from degradation by plasma ADAMTS13, thus securing platelet tethering and thrombus adherence to inflamed and injured endothelium, respectively.
Exploratory analyses of consensus molecular subtype-dependent associations of TP53 mutations with immunomodulation and prognosis in colorectal cancer (2019)

Integration of <i>TP53</i> mutation status with the CMS framework in primary CRC suggested subtype-dependent immunobiological associations with prognostic and potentially immunotherapeutic implications, warranting independent validation.
Recognition of errors in three‐dimensional structures of proteins (1993)

A major problem in the determination of the three-dimensional structure of proteins concerns the quality of the structural models obtained from the interpretation of experimental data. New developments in X-ray crystallography and nuclear magnetic resonance spectroscopy have accelerated the process of structure determination and the biological community is confronted with a steadily increasing number of experimentally determined protein folds. However, in the recent past several experimentally determined protein structures have been proven to contain major errors, indicating that in some cases the interpretation of experimental data is difficult and may yield incorrect models. Such problems can be avoided when computational methods are employed which complement experimental structure determinations. A prerequisite of such computational tools is that they are independent of the parameters obtained from a particular experiment. In addition such techniques are able to support and accelerate experimental structure determinations. Here we present techniques based on knowledge based mean fields which can be used to judge the quality of protein folds. The methods can be used to identify misfolded structures as well as faulty parts of structural models. The techniques are even applicable in cases where only the C alpha trace of a protein conformation is available. The capabilities of the technique are demonstrated using correct and incorrect protein folds.
Photolabile protecting group for histidine (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotolabile protecting group for histidineSuresh M. Kalbag and Roger W. RoeskeCite this: J. Am. Chem. Soc. 1975, 97, 2, 440–441Publication Date (Print):January 1, 1975Publication History Published online1 May 2002Published inissue 1 January 1975https://doi.org/10.1021/ja00835a046RIGHTS & PERMISSIONSArticle Views571Altmetric-Citations28LEARN 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 InReddit PDF (283 KB) Get e-Alertsclose Get e-Alerts
Diffusion kernels on graphs and other discrete structures (2002)

The application of kernel-based learning algorithms has, so far, largely been confined to realvalued data and a few special data types, such as strings. In this paper we propose a general method of constructing natural families of kernels over discrete structures, based on the matrix exponentiation idea. In particular, we focus on generating kernels on graphs, for which we propose a special class of exponential kernels, based on the heat equation, called diffusion kernels, and show that these can be regarded as the discretisation of the familiar Gaussian kernel of Euclidean space.
Intracellular hydroxyl radical production induced by recombinant human tumor necrosis factor and its implication in the killing of tumor cells in vitro. (1989)

This study investigated the effect of recombinant human tumor necrosis factor (rhTNF) on hydroxyl radical production by established cell lines in vitro, and its implication in the killing of tumor cells by rhTNF. During incubation of TNF sensitive mouse tumorigenic fibroblast L-M cells (2 X 10(7) cells) in the presence of rhTNF (100 U), hydroxyl radical production as detected by the evolution of methane gas from dimethyl sulfoxide increased gradually, at 18 h reaching 1.8 times that in the absence of rhTNF. This increase was dependent on the concentration of rhTNF and was effectively prevented by the simultaneous addition of anti-rhTNF monoclonal antibody III 2F3, which inhibited both the binding of rhTNF to its receptor and the cytotoxic activity of rhTNF. The addition of iron chelator 2,2'-bipyridine, which inhibits iron-catalized Fenton reaction and so inhibits hydroxyl radical generation, suppressed both the increase of hydroxyl radical production and the cytotoxicity induced by rhTNF. A similar increase in hydroxyl radical production in the presence of rhTNF was also detected with TNF-sensitive human myosarcoma-derived KYM cells, but no such increase was detected with TNF insensitive human embryonic lung fibroblast HEL cells. The results show that rhTNF induces increased hydroxyl radical production in TNF-sensitive cells, and suggest that this plays an important role in the mechanism of tumor cell killing by rhTNF.