gebhart/patrepeval huggingface dataset:
Screening of kinase inhibitors targeting BRAF for regulating autophagy based on kinase pathways (2013)

The aim of this study was to identify agents that regulate autophagy. A total of 544 differentially expressed genes were screened from the intersection set of GSE2435 and GSE31040, which was obtained from the Gene Expression Omnibus database and 19 differentially expressed kinases were selected according to a 'protein kinase database'. Gene ontology‑biological process (GO-BP) enrichment analysis revealed that the 19 kinases were mainly associated with phosphorylation. The protein-protein interaction network exhibited 30 differentially expressed genes that interacted with BRAF, and GO-BP enrichment analysis showed the function of these genes were mainly involved in cell death and apoptosis. The kinase-kinase inhibitor regulatory network identified16 kinase inhibitors that specifically inhibited BRAF. Previous studies indicated that sorafenib is capable of regulating autophagy and regorafenib has also been reported; however, there have been no studies regarding the regulation of autophagy by afatinib, selumetinib, PD318088, axitinib, TAK-733, GDC-0980, GSK2126458, PLX-4720, AS703026, trametinib, GDC-0941 and PF-04217903. Thus, these kinase inhibitors are potential targets for further study on the regulation of autophagy in the future.
Identification of eosinophil lineage–committed progenitors in the murine bone marrow (2005)

Eosinophil lineage-committed progenitors (EoPs) are phenotypically isolatable in the steady-state murine bone marrow. Purified granulocyte/monocyte progenitors (GMPs) gave rise to eosinophils as well as neutrophils and monocytes at the single cell level. Within the short-term culture of GMPs, the eosinophil potential was found exclusively in cells activating the transgenic reporter for GATA-1, a transcription factor capable of instructing eosinophil lineage commitment. These GATA-1-activating cells possessed an IL-5Ralpha(+)CD34(+)c-Kit(lo) phenotype. Normal bone marrow cells also contained IL-5Ralpha(+)CD34(+)c-Kit(lo) EoPs that gave rise exclusively to eosinophils. EoPs significantly increased in number in response to helminth infection, suggesting that the EoP stage is physiologically involved in eosinophil production in vivo. EoPs expressed eosinophil-related genes, such as the eosinophil peroxidase and the major basic protein, but did not express basophil/mast cell-related mast cell proteases. The enforced retroviral expression of IL-5Ralpha in GMPs did not enhance the frequency of eosinophil lineage read-outs, whereas IL-5Ralpha(+) GMPs displayed normal neutrophil/monocyte differentiation in the presence of IL-5 alone. Thus, IL-5Ralpha might be expressed specifically at the EoP stage as a result of commitment into the eosinophil lineage. The newly identified EoPs could be the cellular target in the treatment of a variety of disorders mediated by eosinophils.
Isolation and Characterization of a Population of Immature Dental Pulp Stem Cells Expressing OCT-4 and Other Embryonic Stem Cell Markers (2006)

We report the isolation of a population of immature dental pulp stem cells (IDPSC), which express embryonic stem cell markers Oct-4, Nanog, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81 as well as several other mesenchymal stem cell markers during at least 25 passages while maintaining the normal karyotype and the rate of expansion characteristic of stem cells. The expression of these markers was maintained in subclones obtained from these cells. Moreover, in vitrothese cells can be induced to undergo uniform differentiation into smooth and skeletal muscles, neurons, cartilage, and bone under chemically defined culture conditions. After in vivo transplantation of these cells into immunocompromised mice, they showed dense engraftment in various tissues. The relative ease of recovery and the expression profiles of various markers justify further exploration of IDPSC for clinical therapy.
Photopatternable Silicon Elastomers with Enhanced Mechanical Properties for High-Fidelity Nanoresolution Soft Lithography (2005)

Soft lithography has been widely used in stamping and printing processes for microfabrication as a low cost alternative to photolithography. However, conventional poly(dimethyl)siloxane (PDMS) stamp materials have limitations, especially in the submicrometer range, due to their low physical toughness and requirements for thermocuring. A new version of functional stamp materials with adjustable physical toughness has been developed for advanced soft lithography. We thus demonstrate here its photopatternability and nanoresolution soft lithography, which have proven to be difficult using commercial stamp materials.
Nanomolecular HLA-DR10 Antibody Mimics: A Potent System for Molecular Targeted Therapy and Imaging (2008)

To mimic the molecular specificity and cell selectivity of monoclonal antibody (mAb) binding while decreasing size, nanomolecules (selective high-affinity ligands; SHALs), based on in silico modeling, have been created to bind to human leukocyte antigen-DR (HLA-DR10), a signaling receptor protein upregulated on the malignant B-lymphocytes of non-Hodgkin's lymphoma and chronic lymphocytic leukemia. SHALs were synthesized with a biotin or DOTA chelate (1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid), using a solid-phase lysine-polyethyleneglycol backbone to link sets of ligands shown previously to bind to HLA-DR10. Using cell-binding and death assays and confocal microscopy, SHAL uptake, residualization, and cytocidal activity were evaluated in HLA-DR10 expressing and nonexpressing live, human lymphoma cell lines. All of the SHALs tested were selective for, and accumulated in, expressing cells. Reflecting binding to HLA-DR10 inside the cells, SHALs having the Ct ligand (3-(2-([3-chloro-5-trifluoromethyl)-2-pyridinyl]oxy)-anilino)-3-oxopropanionic acid) residualized in expressing cells greater than 179 times more than accountable by cell-surface membrane HLA-DR10. Confocal microscopy confirmed the intracellular residualization of these SHALs. Importantly, SHALs with a Ct ligand had direct cytocidal activity, similar in potency to that of Lym-1 mAb and rituximab, selectively for HLA-DR10 expressing lymphoma cells and xenografts. The results show that SHALs containing the Ct ligand residualize intracellularly and have cytocidal effects mediated by HLA-DR10. These SHALs have extraordinary potential as novel molecules for the selective targeting of lymphoma and leukemia for molecular therapy and imaging. Further, these SHALs can be used to transport and residualize cytotoxic agents near critical sites inside these malignant cells.
Laminin Isoforms and Epithelial Development (1998)

Several different approaches suggest that basement-membrane assembly is important for epithelial development. Basement membranes contain isoforms of collagen IV, proteoglycans, and noncollagenous glycoproteins such as the laminins and nidogens. The expression and role of laminins for epithelial morphogenesis is reviewed. Laminins are large heterotrimeric proteins composed of alpha, beta, and gamma chains. Many major epithelial laminins and their receptors have been identified recently, and the extracellular protein-protein interactions that drive basement-membrane assembly are beginning to be understood. Three laminin alpha-chains are typically made by epithelial, alpha 1, alpha 3, and alpha 5. Three major epithelial heterotrimers can at present be distinguished--laminin-1 (alpha 1 beta 1 gamma 1), laminin-5 (alpha 3 beta 3 gamma 2), and laminin-10 (alpha 5 beta 1 gamma 1)--but other heterotrimers may exist in epithelia. Laminins containing either alpha 1 or alpha 3 chains are largely limited to epithelia, whereas the alpha 5 is also found in endothelial and muscle basement membranes, particularly in the adult. Some epithelial cell types express several laminin alpha-chains, so it is relevant to test how the different laminins affect epithelial cells. Laminins interact with integrin type of receptors on the cell surface, but binding to other proteins has also recently been demonstrated. Two important recent discoveries are the identification of dystroglycan as a major laminin receptor in muscle and epithelia, and nidogen as a high-affinity laminin-binding protein important for basement-membrane assembly. Antibody perturbation experiments suggest that these protein-protein interactions are important for epithelial morphogenesis.
Injection locking dynamics of vertical cavity semiconductor lasers under conventional and phase conjugate injection (1996)

Stable phase locking of an electrically pumped vertical cavity surface-emitting semiconductor laser (VCSEL) was demonstrated experimentally by injecting light from an edge-emitting master laser into the slave laser VCSEL cavity within a large detuning range (/spl sim/80 GHz). By varying the injected power and frequency detuning, a variety of interesting nonlinear behavior was observed. A theoretical model based on two-field rate equations is presented and compared with experiment, showing good agreement.
Role of Additional Mutations outside the YMDD Motif of Hepatitis B Virus Polymerase in l(−)SddC (3TC) Resistance (1998)

L(-)SddC (3TC) has been shown to be the most promising nucleoside analogue used for the treatment of hepatitis B virus (HBV) infection. Unfortunately, it has been reported that about 12% of HBV-infected patients experience a recurrence of HBV after a period of treatment with 3TC. Point mutations were detected in the HBV polymerase of those viruses from 3TC-resistant patients. A common mutation occurred at methionine in the YMDD motif. In this report, we present mutants that were generated from the HBV genome (adr subtype) by site-directed mutagenesis based on clinical reports from other investigators. With the transient transfection system, it was found that by changing methionine to valine or isoleucine at the YMDD motif, the viral DNA replication would be more than 100-fold less efficient than that of the wild-type virus. Some additional mutations outside the YMDD motif could enhance the replication of the virus containing a YMDD mutation. Various levels of resistance to 3TC were observed in HBV mutants containing point mutations both inside and outside the YMDD motif. These results suggest that the mutations outside the YMDD motif compensate the YMDD mutation to some extent for the viral replication and may also contribute to clinical viral resistance to 3TC.
Amelioration of Type 2 Diabetes by Antibody-Mediated Activation of Fibroblast Growth Factor Receptor 1 (2011)

Antibody-mediated activation of fibroblast growth factor receptor 1 reverses the diabetic phenotype in mice, likely by affecting brown adipose tissues.
Liver gene expression signature to predict response to pegylated interferon plus ribavirin combination therapy in patients with chronic hepatitis C (2007)

NRs and SVRs have different liver gene expression profiles before treatment. The most notable changes occurred mainly in interferon-stimulated genes. Treatment response could be predicted with a two-gene signature (IFI27 and CXCL9).
Stem-Cell-Based Gene Therapy for HIV Infection (2013)

Despite the enormous success of combined anti-retroviral therapy, HIV infection is still a lifelong disease and continues to spread rapidly worldwide. There is a pressing need to develop a treatment that will cure HIV infection. Recent progress in stem cell manipulation and advancements in humanized mouse models have allowed rapid developments of gene therapy for HIV treatment. In this review, we will discuss two aspects of HIV gene therapy using human hematopoietic stem cells. The first is to generate immune systems resistant to HIV infection while the second strategy involves enhancing anti-HIV immunity to eliminate HIV infected cells.
Fusion of Escherichia coli heat-stable enterotoxin and heat-labile enterotoxin B subunit (1987)

The 3' terminus of the DNA coding for the extracellular Escherichia coli heat-stable enterotoxin (ST) devoid of transcription and translation stop signals was fused to the 5' terminus of the DNA coding for the periplasmic B subunit of the heat-labile enterotoxin (LTB) deleted of ribosomal binding sites and leader peptide. By RNA-DNA hybridization analysis, it was shown that the fused DNA was transcribed in vivo into an RNA species in close agreement with the expected molecular weight inferred from the nucleotide sequence. The translation products of the fused DNA resulted in a hybrid molecule recognized in Western blots (immunoblots) with antibodies directed against the heat-labile moiety. Anti-LTB antibodies coupled to a solid support bound ST and LTB simultaneously when incubated with ST-LTB cellular extracts. By [35S]cysteine pulse-chase experiments, it was shown that the fused ST-LTB polypeptide was converted from a precursor with an equivalent electrophoretic mobility of 20,800 daltons to an approximately 18,500-dalton species, which accumulated within the cell. The data suggest that wild-type ST undergoes at least two processing steps during its export to the culture supernatant. Blocking the natural carboxy terminus of ST inhibited the second proteolytic step and extracellular delivery of the hybrid molecule.
How Helpful Is Pneumatic Otoscopy in Improving Diagnostic Accuracy? (2003)

Using a video otoendoscopic test, we found that accurate identification of both the presence and the absence of MEE improved after pneumatic assessment of TM mobility. Providers who were more accurate at otoscopy, defined by higher video total test scores, benefited more from the pneumatic component than providers with lower scores.
Nanoporous Platforms for Cellular Sensing and Delivery (2002)

In recent years, rapid advancements have been made in the biomedical applications of micro and nanotechnology. While the focus of such technology has primarily been on in vitro analytical and diagnostic tools, more recently, in vivo therapeutic and sensing applications have gained attention. This paper describes the creation of monodisperse nanoporous, biocompatible, silicon membranes as a platform for the delivery of cells. Studies described herein focus on the interaction of silicon based substrates with cells of interest in terms of viability, proliferation, and functionality. Such microfabricated nanoporous membranes can be used both in vitro for cell-based assays and in vivo for immunoisolation and drug delivery applications.
Characterization of a mini‐multileaf collimator in a proton beamline (2009)

A mini-multileaf collimator (MMLC) was mounted as a field shaping collimator in a proton beamline at the Massachusetts General Hospital. The purpose is to evaluate the device's dosimetric and mechanical properties for the use in a proton beamline. For this evaluation, the authors compared MMLC and brass aperture shaped dose distributions with regard to lateral and depth dose properties. The lateral fall off is generally broader with the MMLC, with difference varying with proton range from 0.2 to 1.2 mm. Central axis depth dose curves did not show a difference in peak-to-entrance ratio, peak width, distal fall off, or range. Two-dimensional dose distributions to investigate the conformity of MMLC shaped doses show that the physical leaf width of approximately 2.5 mm does not have a significant impact. All differences seen in dose distribution shaped by the MMLC versus brass apertures were shown to be clinically insignificant. Measured neutron doses of 0.03-0.13 mSv/Gy for a closed brass beam block (depending on range) are very low compared to the previously published data. Irradiation of the tungsten MMLC, however, produced 1.5-1.8 times more neutrons than brass apertures. Exposure of the staff resulting from activation of the device is below regulatory limits. The measurements established an equivalency between aperture and MMLC shaped dose distributions.
Hydroxyapatite Granule Graft Combined With Recombinant Human Bone Morphogenic Protein-2 for Solid Lumbar Fusion (2002)

The purpose of this study was to evaluate the availability of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with hydroxyapatite (HA) and autogenous bone. Posterolateral intertransverse fusion between the fifth and sixth lumbar vertebrae was performed in 27 adult Japanese white rabbits. These 27 rabbits were classified into three groups: the autogenous bone group, the HA group, and the bone morphogenic protein (BMP) group. In the HA group, HA (0.5 g) mixed with iliac bone was grafted. In the BMP group, HA (0.5 g) soaked with rhBMP-2 (100 mg) and iliac bone was grafted. At 6 weeks after the procedure, bone union was evaluated. In the BMP group, all cases showed solid bone union, and fusion masses were stiffer than the masses obtained in the other group. Biomechanically and histologically, grafts of HA soaked with rhBMP-2 and iliac bone was clearly effective in obtaining a solid intertransverse arthrodesis.
In vitro Activity of Sagamicin against Ocular Bacterial Isolates (2002)

The in vitro antibacterial activity of sagamicin, gentamicin, tobramycin and norfloxacin was evaluated against 180 recent clinical isolates obtained from patients with ocular infections. Good activity was demonstrated for the 3 aminoglycosides against methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermidis. All 4 compounds showed a lower activity against methicillin-resistant staphylococci. Sagamicin was highly effective against enterobacteriaceae with a MIC(90) of 2 mg/l and presented good antipseudomonal activity similar to that of gentamicin. Intraocular lenses impregnated with a sagamicin solution showed a good antistaphylococcal activity immediately after preparation. In our strain collection, the ability to produce slime was more frequent among methicillin-resistant S. epidermidis strains than methicillin-sensitive S. epidermidis (85 versus 70%). The attachment of 2 S. epidermidis strains to plastic surfaces was partially prevented by sagamicin subinhibitory concentrations. On the contrary, sub-MIC levels of norfloxacin increased the adhesion of S. epidermidis.
Differentiation of promyelocytic leukemia cells HL-60 induced by daidzein in vitro and in vivo. (1993)

We have screened more than one thousand synthetic and natural chemicals to explore differentiation inducers and found that daidzein has potent differentiation-inducing activity for human leukemia HL-60 cells, both in vitro and in vivo. In vitro study showed that daidzein at concentrations exceeding 10 micrograms/ml caused inhibition of HL-60 cells; and it induced differentiation of the cells into granulocytic lineage as judged by NBT reduction activity, phagocytic ability and morphological characteristics. Flow cytometry study indicated that daidzein arrested HL-60 cells in the G1 phase. The growth of HL-60 cells in the subrenal capsules of mice and in diffusion chambers implanted into the peritoneal cavities of mice was inhibited by 50 mg/kg daidzein. HL-60 cells treated with daidzein in vivo also exhibited characteristic morphological changes of matured cells. Moreover, the colony forming efficiency of HL-60 cells in diffusion chambers in mice was markedly inhibited by the administration of daidzein.
Efficient method for the preparation of peptoids [oligo(N-substituted glycines)] by submonomer solid-phase synthesis (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEfficient method for the preparation of peptoids [oligo(N-substituted glycines)] by submonomer solid-phase synthesisRonald N. Zuckermann, Janice M. Kerr, Stephen B. H. Kent, and Walter H. MoosCite this: J. Am. Chem. Soc. 1992, 114, 26, 10646–10647Publication Date (Print):December 1, 1992Publication History Published online1 May 2002Published inissue 1 December 1992https://pubs.acs.org/doi/10.1021/ja00052a076https://doi.org/10.1021/ja00052a076research-articleACS PublicationsRequest reuse permissionsArticle Views6193Altmetric-Citations1080LEARN 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
Phosphorylation of β-Catenin by AKT Promotes β-Catenin Transcriptional Activity (2007)

Increased transcriptional activity of beta-catenin resulting from Wnt/Wingless-dependent or -independent signaling has been detected in many types of human cancer, but the underlying mechanism of Wnt-independent regulation is poorly understood. We have demonstrated that AKT, which is activated downstream from epidermal growth factor receptor signaling, phosphorylates beta-catenin at Ser552 in vitro and in vivo. AKT-mediated phosphorylation of beta-catenin causes its disassociation from cell-cell contacts and accumulation in both the cytosol and the nucleus and enhances its interaction with 14-3-3zeta via a binding motif containing Ser552. Phosphorylation of beta-catenin by AKT increases its transcriptional activity and promotes tumor cell invasion, indicating that AKT-dependent regulation of beta-catenin plays a critical role in tumor invasion and development.
High Throughput Screening: Methods and Protocols (2002)

Since its first use in antibiotic research in the 1940s, High Throughput Screening (HTS) has evolved into a major enabling tool and methodology in the discovery of pharmaceutical, chemical, and agricultural compounds. In High Throughput Screening, leading scientists and researchers expert in molecular discovery explain the diverse technologies and key techniques used in HTS and demonstrate how they can be applied generically. Writing to create precisely the introductory guidebook they wished had been available when they started in HTS, these seasoned authors illuminate the HTS process with richly detailed tutorials on the biological techniques involved, the management of compound libraries, and the automation and engineering approaches needed. Extensive discussions provide readers with all those key elements of pharmacology, molecular biology, enzymology, and biochemistry that will ensure the identification of suitable targets and screens, and detail the technology necessary to mine millions of data points for meaningful knowledge. By presenting accounts not only of the basic principles underlying HTS technology, but also real-use cases, High Throughput Screening constitutes a highly practical introduction to HTS, even as it also provides sufficient detail to work more productively in today's lead generation laboratories