gebhart/patrepeval huggingface dataset:
Targeting of TGF-β-activated protein kinase 1 inhibits chemokine (C-C motif) receptor 7 expression, tumor growth and metastasis in breast cancer (2014)

TGF-β-activated protein kinase 1 (TAK1) is a critical mediator in inflammation, immune response and cancer development. Our previous study demonstrated that activation of TAK1 increases the expression of chemokine (C-C motif) receptor 7 (CCR7) and promotes lymphatic invasion ability of breast cancer cells. However, the expression and association of activated TAK1 and CCR7 in breast tumor tissues is unknown and the therapeutic effect by targeting TAK1 is also unclear. We showed that activated TAK1 (as indicated by phospho-TAK1) and its binding protein TAB1 are strongly expressed in breast tumor tissues (77% and 74% respectively). In addition, increase of phospho-TAK1 or TAB1 is strongly associated with overexpression of CCR7. TAK1 inhibitor 5Z-7-Oxozeaenol (5Z-O) inhibited TAK1 activity, suppressed downstream signaling pathways including p38, IκB kinase (IKK) and c-Jun N-terminal kinase (JNK) and reduced CCR7 expression in metastatic MDA-MB-231 cells. In addition, 5Z-O repressed NF-κB- and c-JUN-mediated transcription of CCR7 gene. Knockdown of TAB1 attenuated CCR7 expression and tumor growth in an orthotopic animal study. More importantly, lymphatic invasion and lung metastasis were suppressed. Collectively, our results demonstrate that constitutive activation of TAK1 is frequently found in human breast cancer and this kinase is a potential therapeutic target for this cancer.
Unique pulmonary antigen presentation may call for an alternative approach toward lung cancer immunotherapy (2013)

Unlike other tumors, lung cancer appears to be poorly sensitive to immunotherapy. We have recently demonstrated an alternative pathway of lung cancer immunosurveillance. Our data indicate a failure of the adaptive immune system to mediate the immunosurveillance of lung cancer and emphasize the prominent role of natural killer cells in this setting.
Inhibition of osteoclastogenesis by RNA interference targeting RANK (2012)

These findings suggest that retrovirus-mediated shRNA targeting RANK inhibits osteoclast differentiation and osteolysis. It may appear an attractive target for preventing osteolysis in humans with a potential clinical application.
In silico discovery of substituted pyrido[2,3-d]pyrimidines and pentamidine-like compounds with biological activity in myotonic dystrophy models (2017)

Myotonic dystrophy type 1 (DM1) is a rare multisystemic disorder associated with an expansion of CUG repeats in mutant DMPK (dystrophia myotonica protein kinase) transcripts; the main effect of these expansions is the induction of pre-mRNA splicing defects by sequestering muscleblind-like family proteins (e.g. MBNL1). Disruption of the CUG repeats and the MBNL1 protein complex has been established as the best therapeutic approach for DM1, hence two main strategies have been proposed: targeted degradation of mutant DMPK transcripts and the development of CUG-binding molecules that prevent MBNL1 sequestration. Herein, suitable CUG-binding small molecules were selected using in silico approaches such as scaffold analysis, similarity searching, and druggability analysis. We used polarization assays to confirm the CUG repeat binding in vitro for a number of candidate compounds, and went on to evaluate the biological activity of the two with the strongest affinity for CUG repeats (which we refer to as compounds 1-2 and 2-5) in DM1 mutant cells and Drosophila DM1 models with an impaired locomotion phenotype. In particular, 1-2 and 2-5 enhanced the levels of free MBNL1 in patient-derived myoblasts in vitro and greatly improved DM1 fly locomotion in climbing assays. This work provides new computational approaches for rational large-scale virtual screens of molecules that selectively recognize CUG structures. Moreover, it contributes valuable knowledge regarding two compounds with desirable biological activity in DM1 models.
Variable region sequences and idiotypic expression of a protective human immunoglobulin M antibody to capsular polysaccharides of Neisseria meningitidis group B and Escherichia coli K1 (1994)

We determined the heavy (H)- and light (L)-chain variable (V) region nucleotide and translated amino acid sequences of the human immunoglobulin M(kappa) monoclonal antibody (MAb) 5E1, which is specific for the polysaccharide capsule of Escherichia coli K1 and Neisseria meningitidis group B (poly[alpha(2-->8)-N-acetylneuraminic acid]) and which is protective in animal models of infection. The 5E1 VH gene is a member of the VHIIIb family and is 97% homologous to the 9.1 germ line gene. The 5E1 VL gene is a member of the kappa I subgroup and is 98% homologous to the germ line gene, 15A, also known as KLO12. The VL and/or VH genes used by 5E1 are highly homologous to the V genes encoding antibodies to the Haemophilus influenzae type b polysaccharide and to antibodies reactive with self-antigens such as erythrocyte "i," DNA, and thyroid peroxidase. We also produced three murine anti-idiotype (Id) MAbs against 5E1. All three anti-Ids recognize a minor subset of antimeningococcal B polysaccharide antibodies present in serum from normal adults. Two of the anti-Ids define distinct Ids associated with antibodies having kappa I-15A V regions. These 15A-associated Ids are expressed by some heterologous human antimeningococcal B polysaccharide MAbs, and they also are independently expressed by two human MAbs that are specific for either the H. influenzae b polysaccharide or the i erythrocyte antigen and that utilize the kappa I-15A V region. Taken together, these data indicate that the 5E1 antibody uses V regions that recur in the human antibody repertoires to this polysaccharide and to structurally dissimilar polysaccharides and autoantigens. Thus, the poor immunogenicity of poly[alpha(2-->8)-N-acetylneuraminic acid] cannot be explained by the unavailability of certain critical VH and VL genes required for generation of antibody response.
Oxygen ligation of macromolecule-porphyrin complexes. (1988)

高分子に結合したポルフィリン錯体は, 広い条件範囲で酸素を可逆的に配位する。固相高分子中に分散して密度高く固定されたコバルトポルフリィリンでは, 濃度勾配にしたがって酸素が配位結合をくり返し移行する結果, いわゆる促進輸送の現象が観測される。鉄ポルフィリンは水相系において直ちに不可逆酸化を受けるが, 高分子に結合し特定環境に取り込ませた状態では安定で, 容易に可逆的な酸素錯体を形成する。リン脂質と構造を類似させたポルフィリンの新しい誘導体 (略称:リピドヘム) は, リン脂質と相溶牲の高い分子集合体を形成,生理条件下 (生理塩水溶液, pH7.4, 温度37～40℃, 大気下) で酸素運搬体として機能する。ポルフィリン錯体への酸素配位の観測は, 高分子が形成する錯体部周辺の分子環境解明の手がかりにもなる。
Expression and activation of cdks (1 and 2) and cyclins in the cell cycle progression during liver regeneration. (1994)

In normal adult liver, hepatocytes are arrested in G0, and they rapidly respond to a mass loss by a definite number of divisions. Thus, taking advantage of the in vivo regenerative capacity of the liver following partial hepatectomy, we have analyzed both expression and activation of p34cdc2 (= cdk1) and p33cdk2 through the cell cycle, particularly during the long lasting G1 phase and in the G1/S transition. While p33cdk2 is constantly expressed during the cell cycle, p34cdc2 is completely absent in resting hepatocytes and remains unexpressed for up to 20 h after partial hepatectomy, a time period corresponding to the G1 phase and G1/S transition, and then accumulates in the S, G2, and M phases. No histone H1 kinase activity is detected during the G1 phase, while two peaks of p34cdc2 kinase activity are observed during the S and M phases and only one peak of p33cdk2 kinase activity in the S phase. p34cdc2 forms complexes with both cyclins A and B while p33cdk2 is associated with cyclin A only. Surprisingly, cyclins E and D1 are present in resting liver and with modest variation throughout the cell cycle. Taken together, our data provide evidence that the pattern of G1-associated proteins in hepatocytes during liver regeneration is distinct from that described in other cell types.
Mobyle: a new full web bioinformatics framework (2009)

The Mobyle system is distributed under the terms of the GNU GPLv2 on the project web site (http://bioweb2.pasteur.fr/projects/mobyle/). It is already deployed on three servers: http://mobyle.pasteur.fr, http://mobyle.rpbs.univ-paris-diderot.fr and http://lipm-bioinfo.toulouse.inra.fr/Mobyle. The PlayMOBY companion is distributed under the terms of the CeCILL license, and is available at http://lipm-bioinfo.toulouse.inra.fr/biomoby/PlayMOBY/.
Dietary supplements of phenylalanine and other amino acid precursors of brain neuroamines in the treatment of depressive disorders (1984)

Article Dietary supplements of phenylalanine and other amino acid precursors of brain neuroamines in the treatment of depressive disorders was published on September 1, 1984 in the journal Journal of Osteopathic Medicine (volume 84, issue 9).
Measurement of Glucose Uptake in Cultured Cells (2015)

Facilitative glucose uptake transport systems are ubiquitous in animal cells and are responsible for transporting glucose across cell surface membranes. Evaluation of glucose uptake is crucial in the study of numerous diseases and metabolic disorders such as myocardial ischemia, diabetes mellitus, and cancer. Detailed in this unit are laboratory methods for assessing glucose uptake into mammalian cells. The unit is divided into five sections: (1) a brief overview of glucose uptake assays in cultured cells; (2) a method for measuring glucose uptake using radiolabeled 3-O-methylglucose; (3) a method for measuring glucose uptake using radiolabeled 2-deoxyglucose (2DG); (4) a microplate method for measuring 2DG-uptake using an enzymatic, fluorometric assay; and (5) a microplate-based method using a fluorescent analog of 2DG.
Use of Anti-CD3 × Anti-HER2/neu Bispecific Antibody for Redirecting Cytotoxicity of Activated T Cells Toward HER2/neu + Tumors (2001)

Relapse after adjuvant chemotherapy or high-dose chemotherapy with stem cell transplant for high-risk breast cancer remains high and new strategies that provide additional antitumor effects are needed. This report describes methods to generate highly effective HER2/neu-specific cytotoxic T cells by arming activated T cells with anti-CD3 x anti-HER2/neu bispecific antibody (BsAb). OKT3 and 9184 (anti-HER2) monoclonal antibodies (mAb) were conjugated and used to arm T cells that were subsequently tested in binding, cytotoxicity, and cytokine secretion assays. Armed T cells aggregated and specifically killed HER2/neu(+) breast cancer cells. Cytotoxicity emerged after 6 days of culture, was higher in armed T cells than unarmed T cells at all effector to target ratios (E/T) tested, and increased as the arming dose was increased. At an E/T of 20:1, the mean cytotoxicity of armed activated T cells (ATC) from 10 normal subjects increased by 59 +/- 11% (+/-SD) over that seen in unarmed ATC (p < 0.001) and the mean cytotoxicity of armed ATC from 6 cancer patients increased by 32 +/- 9% above that seen for unarmed ATC (p < 0.0004). After arming, the BsAb persisted on ATC up to 72 h and armed ATC continued to be cytotoxic up to 54 h. The amount of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted was 1699, 922, and 3092 pg/ml/10(6) cells per 24 h, respectively, when armed T cells were exposed to a HER2/neu(+) breast carcinoma cell line. These studies show the feasibility and clinical adaptability of this approach for generating large numbers of anti-HER2-specific, cytotoxic T cells for clinical trials.
Phosphatidylinositol 3′‐kinase and tyrosine‐phosphatase activation positively modulate Convulxin‐induced platelet activation. Comparison with collagen (1999)

In this report we have studied the role of phosphatidylinositol 3'-kinase (PI3-K) and tyrosine phosphatase activation on platelet activation by Convulxin (Cvx). Wortmannin, a specific PI3-K inhibitor, and phenylarsine oxide (PAO), a sulfhydryl reagent that inhibits tyrosine phosphatase (PTPase), block Cvx-induced platelet aggregation, granule secretion, inositol phosphate production, and increase in [Ca2+]i. However, PAO does not inhibit Cvx-induced tyrosine phosphorylation of platelet proteins, including Syk and PLCgamma2, but blocked collagen-induced platelet aggregation as well as tyrosine phosphorylation of PLCgamma2. In contrast, Cvx-induced PLCgamma2 tyrosyl phosphorylation was partially inhibited by wortmannin. We conclude that (i) although Cvx and collagen activate platelets by a similar mechanism, different regulatory processes are specific to each agonist; (ii) mechanisms other than tyrosine phosphorylation regulate PLCgamma2 activity; and (iii) besides protein tyrosine kinases, PI3-K (and PTPase) positively modulate platelet activation by both Cvx and collagen, and this enzyme is required for effective transmission of GPVI-Fc receptor gamma chain signal to result in full activation and tyrosine phosphorylation of PLCgamma2 in Cvx-stimulated platelets.
Cyclin-Dependent Kinase Pathways As Targets for Cancer Treatment (2006)

Cyclin-dependent kinases (cdks) are critical regulators of cell cycle progression and RNA transcription. A variety of genetic and epigenetic events cause universal overactivity of the cell cycle cdks in human cancer, and their inhibition can lead to both cell cycle arrest and apoptosis. However, built-in redundancy may limit the effects of highly selective cdk inhibition. Cdk4/6 inhibition has been shown to induce potent G1 arrest in vitro and tumor regression in vivo; cdk2/1 inhibition has the most potent effects during the S and G2 phases and induces E2F transcription factor-dependent cell death. Modulation of cdk2 and cdk1 activities also affects survival checkpoint responses after exposure to DNA-damaging and microtubule-stabilizing agents. The transcriptional cdks phosphorylate the carboxy-terminal domain of RNA polymerase II, facilitating efficient transcriptional initiation and elongation. Inhibition of these cdks primarily affects the accumulation of transcripts with short half-lives, including those encoding antiapoptosis family members, cell cycle regulators, as well as p53 and nuclear factor-kappa B-responsive gene targets. These effects may account for apoptosis induced by cdk9 inhibitors, especially in malignant hematopoietic cells, and may also potentiate cytotoxicity mediated by disruption of a variety of pathways in many transformed cell types. Current work is focusing on overcoming pharmacokinetic barriers that hindered development of flavopiridol, a pan-cdk inhibitor, as well as assessing novel classes of compounds potently targeting groups of cell cycle cdks (cdk4/6 or cdk2/1) with variable effects on the transcriptional cdks 7 and 9. These efforts will establish whether the strategy of cdk inhibition is able to produce therapeutic benefit in the majority of human tumors.
Signal processing for fault detection in photovoltaic arrays (2012)

Photovoltaics (PV) is an important and rapidly growing area of research. With the advent of power system monitoring and communication technology collectively known as the “smart grid,” an opportunity exists to apply signal processing techniques to monitoring and control of PV arrays. In this paper a monitoring system which provides real-time measurements of each PV module's voltage and current is considered. A fault detection algorithm formulated as a clustering problem and addressed using the robust minimum covariance determinant (MCD) estimator is described; its performance on simulated instances of arc and ground faults is evaluated. The algorithm is found to perform well on many types of faults commonly occurring in PV arrays.
The Second PDZ Domain of INAD Is a Type I Domain Involved in Binding to Eye Protein Kinase C (2001)

INAD is a scaffolding protein containing five PSD95/dlg/zonular occludens-1 (PDZ) domains that tether NORPA (phospholipase Cbeta(4)), the TRP calcium channel, and eye-PKC in Drosophila photoreceptors. We previously showed that eye-PKC interacted with the second PDZ domain (PDZ2) of INAD. Sequence comparison with a prototypical type I PDZ domain predicts that PDZ2 is the best candidate among the five PDZ domains to recognize eye-PKC that contains a type I PDZ ligand, Ile-Thr-Ile-Ile, at its carboxyl terminus. Replacement of Ile(-3) in eye-PKC with charged residues resulted in a drastic reduction of the PDZ2 interaction. Substitution of a conserved His with Arg at the second alpha-helix of PDZ2 led to a reduced binding; however, a Leu replacement resulted in an enhanced eye-PKC association. We isolated and sequenced the InaD gene. The coding sequence of InaD contains nine exons spanning 3 kilobases. Translation of coding sequences from three wild-type alleles revealed three SNPs affecting residues, 282, 319, and 333 of INAD. These polymorphisms are localized in PDZ2. Interestingly, we found two of three PDZ2 variants displayed a greater affinity for eye-PKC. In summary, we evaluated the molecular basis of the eye-PKC and PDZ2 association by mutational analysis and concluded that PDZ2 of INAD is a type I domain important for the eye-PKC interaction.
Practical high-impedance fault detection on distribution feeders (1997)

Distribution protection systems must balance dependability with security considerations to be practical. This is quite difficult for high-impedance faults. Only highly sensitive algorithms can achieve absolute dependability in detecting very low current faults. This high sensitivity results in a propensity for false tripping, creating a less secure, system and resulting in the potential for decreased service continuity and lower reliability. Researchers at Texas A&M University have balanced fault detection with fault discrimination, resulting in a practical combination of detection algorithms in a commercially viable system. This device has many "intelligent" features, including the ability to analyze and correlate numerous fault characteristics in real time, so that a correct determination of the status of the feeder can be made with a high probability of accuracy. This paper describes the use of multiple algorithms to detect various types of faults and the use of an expert decision maker to decipher incoming data, to determine the status and health of a distribution feeder. Requirements for a practical, secure high-impedance fault relay are also discussed. Finally, Texas A&M has licensed this technology to a commercial partner, which manufactures a device that detects high-impedance faults, in addition to performing numerous other monitoring and protection functions.
Large‐Area Silver‐Coated Silicon Nanowire Arrays for Molecular Sensing Using Surface‐Enhanced Raman Spectroscopy (2008)

Abstract A new and facile method to prepare large‐area silver‐coated silicon nanowire arrays for surface‐enhanced Raman spectroscopy (SERS)‐based sensing is introduced. High‐quality silicon nanowire arrays are prepared by a chemical etching method and used as a template for the generation of SERS‐active silver‐coated silicon nanowire arrays. The morphologies of the silicon nanowire arrays and the type of silver‐plating solution are two key factors determining the magnitude of SERS signal enhancement and the sensitivity of detection; they are investigated in detail for the purpose of optimization. The optimized silver‐coated silicon nanowire arrays exhibit great potential for ultrasensitive molecular sensing in terms of high SERS signal enhancement ability, good stability, and reproducibility. Their further applications in rapidly detecting molecules relating to human health and safety are discussed. A 10 s data acquisition time is capable of achieving a limit of detection of approximately 4 × 10 −6 M calcium dipicolinate (CaDPA), a biomarker for anthrax. This value is 1/15 the infectious dose of spores (6 × 10 −5 M required), revealing that the optimized silver‐coated silicon nanowire arrays as SERS‐based ultrasensitive sensors are extremely suitable for detecting Bacillus anthracis spores.
The digital set-top box as a virtual channel provider (2003)

This research is based on the realization that the desktop computing paradigm is not appropriate for television, because it is adapted to fundamentally different user aspirations and activities. Instead, the virtual channel is a model that aids the organization and dynamic presentation of digital television programming from a combination of live broadcasts, prerecorded content and Internet resources at each set-top box. The goal is to design the respective framework of user interface patterns that consider the affective nature of television usability and facilitate the diversity of viewing situations.
Thermal Rearrangement of Allyl-type Sulfoxides, Sulfones and Sulfinates1 (1950)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThermal Rearrangement of Allyl-type Sulfoxides, Sulfones and Sulfinates1Arthur C. Cope, Dwight E. Morrison, and Lamar FieldCite this: J. Am. Chem. Soc. 1950, 72, 1, 59–67Publication Date (Print):January 1, 1950Publication History Published online1 May 2002Published inissue 1 January 1950https://doi.org/10.1021/ja01157a018RIGHTS & PERMISSIONSArticle Views501Altmetric-Citations62LEARN 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 (1 MB) Get e-Alerts Get e-Alerts