gebhart/patrepeval huggingface dataset:
An assessment of the utility of the yeast GreenScreen assay in pharmaceutical screening (2005)

In this paper we describe an initial reproducibility study of 12 proprietary compounds followed by the assessment of 51 marketed pharmaceuticals and, lastly, a summary of the data so far from 2698 proprietary compounds from the Johnson & Johnson (J&J) compound library, in the yeast GreenScreen assay (GSA). In this assay, a reporter system in the yeast cells employs the DNA damage inducible promoter of the RAD54 gene, fused to the extremely stable green fluorescent protein (GFP). The assay proved to be very robust, the Excel templates provided by Gentronix with the assay interfaced well with in-house J&J systems with little adaptation, the assay was very rapid to perform and used very little compound. The results confirm previous work which suggests that the yeast GSA detects different classes of genotoxic compounds to the Ames assay and as a result can help screen out important genotoxic compounds at the pre-regulatory test phase that are missed by Ames-test-based screens alone. A combination of SAR evaluation of genotoxicity plus an Ames-test-based screen and the GSA provides a powerful pre-regulatory test battery to aid in the selection of successful drug candidates.
Methods for Marking Insects: Current Techniques and Future Prospects (2001)

Tracking the movement of insects in their natural habitat is essential for understanding their basic biology, demography, and ethology. A wide variety of markers have been used to assess insect population dynamics, dispersal, territoriality, feeding behavior, trophic-level interactions, and other ecological interactions. The ideal marker should persist without inhibiting the insect's "normal" biology. Furthermore, the marker should be environmentally safe, cost-effective, and easy to use. In this article, we review the current state of knowledge regarding insect marking, document the advantages and limitations of each marking technique, and discuss advances made in marking insects over the past decade.
ChemInform Abstract: Structure of Sch 68631: A New Hepatitis C Virus Proteinase Inhibitor from Streptomyces sp. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Abstract 2547: Caveolin-1 inhibits survivin and increases sensitivity to paclitaxel in breast cancer cells (2010)

Abstract Breast cancer is the second leading cause of death due to cancer in women and approximately 194,280 new cases of breast cancer were diagnosed in 2009. The chemotherapeutic drugs known as taxanes disrupt the microtubule function and arrest cell cycle. Paclitaxel (Taxol) is a taxane that is commonly used to treat patients with breast cancer as well as other types of cancer. However, resistance to paclitaxel remains a hindrance to successful treatment. Previously, we have shown that signaling associated with caveolin-1 (CAV1), a structural protein, is an essential determinant of paclitaxel sensitivity in MCF-7 breast cancer cells. CAV1 is part of this family of proteins that has multiple functions in different cancers but it has been proposed to function as a tumor suppressor in breast cancer. Here we show that CAV1 may promote cell death in response to paclitaxel by inhibiting the function of a pro-survival protein called survivin. Survivin is encoded by the BIRC5 gene and is part of the inhibitors of apoptosis (IAP) family. This protein has numerous functions including inhibition of apoptosis and regulation of the cell cycle. Evidence shows that survivin inhibits cell apoptosis by preventing the activation of caspases, which are proteases associated with cell-mediated apoptosis. Up-regulation of survivin is associated with cancer and usually indicates a poor prognosis. We show that while over-expression of CAV1 down-regulates survivin, over-expression of survivin down-regulates CAV1 in MCF-7 cells. Moreover, MCF-7 cells that over-express survivin show decreased inhibition of cell proliferation in response to 10 nM paclitaxel compared to MCF-7 cells expressing the empty vector (EV, control). Thus, our work highlights the role of CAV1 expression in breast cancer cells as an essential determinant of paclitaxel sensitivity. Findings from this research can help researchers and clinicians to evaluate whether CAV1 expression in breast tumors can help predict its responsiveness to taxanes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2547.
GLP-1 and Extra-islet Effects (2004)

The main target of action of glucagon-like peptide-1 (GLP-1) is the islet, where the hormone stimulates insulin secretion, promotes beta cell proliferation and neogenesis, and inhibits glucagon secretion. However, GLP-1 receptors are also expressed outside the islets, increasing the likelihood that GLP-1 also plays a role in other organs. These functions are mainly the inhibition of gastric emptying, gastric acid secretion and exocrine pancreatic secretion, indicating that the hormone acts as an enterogastrone--a hormone released from the distal portion of the small intestine that inhibits proximal gastrointestinal events. Another important action of GLP-1 is to induce satiety. Other effects of the hormone include cardioprotection, neuroprotection, induction of learning and memory, stimulation of afferent, sensory nerves, stimulation of surfactant production in the lung, dilatation of pulmonary vessels, induction of diuresis, and also under some conditions, induction of antidiabetic actions unrelated to islet function. Thus, GLP-1 clearly has several manifestations of activity. The physiological relevance of these actions and their contribution to the overall antidiabetic action of GLP-1 when used in treatment of type 2 diabetes remains to be established.
Consensus 3D Model of μ-Opioid Receptor Ligand Efficacy Based on a Quantitative Conformationally Sampled Pharmacophore (2011)

Despite being studied for over 30 years, a consensus structure-activity relationship (SAR) that encompasses the full range peptidic and nonpeptidic μ-opioid receptor ligands is still not available. To achieve a consensus SAR the Conformationally Sampled Pharmacophore (CSP) method was applied to develop a predictive model of the efficacy of μ-opioid receptor ligands. Emphasis was placed on predicting the efficacy of a wide range of agonists, partial agonists, and antagonists as well as understanding their mode of interaction with the receptor. Inclusion of all accessible conformations of each ligand, a central feature of the CSP method, enabled structural features between diverse μ-opioid receptor ligands that dictate efficacy to be identified. The models were validated against a diverse collection of peptidic and nonpeptidic ligands, including benzomorphans, fentanyl (4-anilinopiperidine), methadone (3,3-diphenylpropylamines), etonitazene (benzimidazole derivatives), funaltrexamine (C6-substituted 4,5-epoxymorphinan), and herkinorin. The model predicts (1) that interactions of ligands with the B site, as with the 19-alkyl substituents of oripavines, modulate the extent of agonism; (2) that agonists with long N-substituents, as with fentanyl and N-phenethylnormorphine, can bind in an orientation such that the N substitutent interacts with the B site that also allows the basic N-receptor Asp interaction essential for agonism; and (3) that the μ agonist herkinorin, that lacks a basic nitrogen, binds to the receptor in a manner similar to the traditional opioids via interactions mediated by water or a ion. Importantly, the proposed CSP model can be reconciled with previously published SAR models for the μ receptor.
Agonist‐induced down‐regulation of m1 muscarinic receptors and reduction of their mRNA level in a transfected cell line (1990)

Agonist-induced reduction in both the number of m1 muscarinic receptors and the mRNA coding for the receptor protein was investigated in Chinese hamster ovary (CHO) cells which were transfected with the m1 muscarinic receptor gene. Receptor concentration was measured by the specific binding of the muscarinic ligand, [3H]quinuclidinyl benzilate ([3H]QNB), and Northern blot hybridization analysis was used to evaluate the levels of receptor mRNA. Incubation of cells with 1 mM of the muscarinic agonist, carbamylcholine (CBC), for 24 h decreased receptor density and mRNA levels in cells by 65% and 73%, respectively. These results indicate that agonist-induced down-regulation of m1 muscarinic receptors might be due to, at least in part, a decrease in receptor synthesis resulting from a reduction in the steady-state level of their mRNA.
Temporal Edges: The Detection Of Motion And The Computation Of Optical Flow (2005)

A new method for the detection of motion and the computation of optical flow is presented. In the first step of the calculation the intensity history at each pixel is convolved with the second derivative in time of a temporal Gaussian smoothing function. The zero crossings in a single frame of the resulting function indicate the positions of moving edges. Spatial and temporal derivatives of the function at the zero-crossing locations are then used to compute the component of the flow that is normal to the zero-crossing contours. Both the detection of motion and the computation of the normal velocity are insensitive to slow temporal and spatial changes in the image intensity that are caused by illumination effects rather than motion. A framework in which to relate the present work to a number of gradient based flow measurement techniques is also presented.
Prediction of phenotypes of missense mutations in human proteins from biological assemblies (2012)

Single nucleotide polymorphisms (SNPs) are the most frequent variation in the human genome. Nonsynonymous SNPs that lead to missense mutations can be neutral or deleterious, and several computational methods have been presented that predict the phenotype of human missense mutations. These methods use sequence-based and structure-based features in various combinations, relying on different statistical distributions of these features for deleterious and neutral mutations. One structure-based feature that has not been studied significantly is the accessible surface area within biologically relevant oligomeric assemblies. These assemblies are different from the crystallographic asymmetric unit for more than half of X-ray crystal structures. We find that mutations in the core of proteins or in the interfaces in biological assemblies are significantly more likely to be disease-associated than those on the surface of the biological assemblies. For structures with more than one protein in the biological assembly (whether the same sequence or different), we find the accessible surface area from biological assemblies provides a statistically significant improvement in prediction over the accessible surface area of monomers from protein crystal structures (P = 6e-5). When adding this information to sequence-based features such as the difference between wildtype and mutant position-specific profile scores, the improvement from biological assemblies is statistically significant but much smaller (P = 0.018). Combining this information with sequence-based features in a support vector machine leads to 82% accuracy on a balanced dataset of 50% disease-associated mutations from SwissVar and 50% neutral mutations from human/primate sequence differences in orthologous proteins.
Human X-box-binding protein 1 is required for the transcription of a subset of human class II major histocompatibility genes and forms a heterodimer with c-fos. (1991)

A complementary DNA encoding a member of the leucine-zipper class of proteins (human X-box-binding protein, hXBP-1) that binds to the 3' end of the conserved X box (X2) of the HLA-DRA major histocompatibility complex gene was recently described. Further gel-retardation analysis has demonstrated that hXBP-1 also binds to HLA-DPB X2 but not to other X2 sequences. Transient transfection of a mammalian expression vector with the hXBP-1 cDNA inserted in the antisense orientation represses the surface expression of HLA-DR and HLA-DP in Raji cells. Cotransfection of the antisense hXBP-1 vector with a HLA-DRA/chloramphenicol acetyltransferase (but not a HLA-DQB/chloramphenicol acetyltransferase) reporter plasmid decreases chloramphenicol acetyltransferase activity in Raji cells and in gamma-interferon-treated HeLa cells relative to cells cotransfected with a control antisense vector. Moreover, hXBP-1 is shown to form a stable heterodimer with the product of the c-fos protooncogene. These data suggest that the hXBP-1 c-fos heterodimer is critical for the transcription of a subset of the human class II major histocompatibility complex genes and that the regulatory mechanisms for the different class II genes are distinct.
Supramolecular Coordination Chemistry and Functional Microporous Molecular Materials (2001)

An enormous number and variety of discrete, isolable, supramolecular-coordination-chemistry-based assemblies featuring well-defined nanoscale cavities have been designed, synthesized, and characterized over the past decade. A small number of these have subsequently been used as building blocks for microporous materials and now comprise an important component of an emerging chemistry of microporous molecular materials. The extant materials typically have displayed large void volumes, high internal surface areas, and the ability to withstand the systematic removal of solvent. These and other properties (chemical tailorability, alignment of cavities to form extended channels, good processability, etc.) suggest a number of potentially very exciting applications involving selective molecular transport, sensing, or chemical transformationwith many of these now supported by proof-of-concept experiments.
Major loss of junctional coupling during mitosis in early mouse embryos. (1986)

Junctional coupling was assessed during the transition from the fourth to the fifth cell cycle of mouse embryogenesis by injection of the dye carboxyfluorescein and by measurement of electrical continuity between cells. Junctional coupling, which arises de novo in early 8-cell mouse embryos, subsequently becomes reduced towards the end of the cell cycle as the blastomeres enter into mitosis. Arrest of the cell cycle in metaphase by nocodazole, an inhibitor of tubulin polymerization, reveals that cell coupling becomes undetectable at mitosis. Junctional coupling then is resumed during interphase of the 16-cell stage. Nocodazole itself has no effect on junctional coupling in interphase cells, regardless of the extent of intercellular flattening, whereas taxol, a microtubule-stabilizing agent, does reduce the extent of coupling in interphase cells.
A user's guide to channelrhodopsin variants: features, limitations and future developments (2010)

Channelrhodopsins (ChRs) are light-activated channels from algae that provide these organisms with fast sensors to visible light for phototaxis. Since its discovery, channelrhodopsin-2 (ChR2) has been used as a research tool to depolarize membranes of excitable cells with light. Subsequent chimeragenesis, mutagenesis and bioinformatic approaches have introduced additional ChR variants, such as channelrhodopsin-2 with H134R mutation (ChR2/H134R), channelrhodopsin-2 with E123T mutation (ChETA), Volvox carteri channelrhodopsin-1 (VChR1), Volvox carteri channelrhodopsin-2 (VChR2), channelrhodopsin-2 with C128 or D156A mutations (ChR2/C128X/D156A), chimera D (ChD), chimera EF (ChEF) and chimera EF with I170V mutation (I170V). Each of these ChR variuants has unique features and limitations, but there are few resources summarizing and comparing these ChRs in a systematic manner. In this review, the seven following key properties of ChRs that have significant influences on their effectiveness as research tools are examined: conductance, selectivity, kinetics, desensitization, light sensitivity, spectral response and membrane trafficking. Using this information, valuable qualities and deficits of each ChR variant are summarized. Optimal uses and potential future improvements of ChRs as optogenetic tools are also discussed.
<title>Thermoacoustic CT: imaging principles</title> (2000)

We have developed instrumentation for measuring the tissue- absorption properties of radio waves in the human body using thermoacoustic interactions. The imaging principles upon which this instrumentation is based are applicable to other irradiation sources, such as visible and IR. We present the imaging reconstruction methodology that we have developed for mapping radiation absorption pattern sin 3D. Both simulated and experimental data are used to illustrate imaging principles.
Analysis of cell death by flow and laser-scanning cytometry (1999)

Abstract Flow cytometry, by providing the possibility of rapid, accurate, and unbiased measurements of a variety of cell components on a cell by cell basis, has become an indispensable methodology in the analysis of cell death (see reviews in refs 1-6). One area of application of flow cytometry is in studies of the mechanism of cell death.
Biocompatible, Thermoresponsive, and Biodegradable:  Simple Preparation of “All-in-One” Biorelevant Polymers (2007)

S.8540-8543
Genetics of FTLD: overview and what else we can expect from genetic studies (2016)

Frontotemporal lobar degeneration (FTLD) comprises a highly heterogeneous group of disorders clinically associated with behavioral and personality changes, language impairment, and deficits in executive functioning, and pathologically associated with degeneration of frontal and temporal lobes. Some patients present with motor symptoms including amyotrophic lateral sclerosis. Genetic research over the past two decades in FTLD families led to the identification of three common FTLD genes (microtubule-associated protein tau, progranulin, and chromosome 9 open reading frame 72) and a small number of rare FTLD genes, explaining the disease in almost all autosomal dominant FTLD families but only a minority of apparently sporadic patients or patients in whom the family history is less clear. Identification of additional FTLD (risk) genes is therefore highly anticipated, especially with the emerging use of next-generation sequencing. Common variants in the transmembrane protein 106 B were identified as a genetic risk factor of FTLD and disease modifier in patients with known mutations. This review summarizes for each FTLD gene what we know about the type and frequency of mutations, their associated clinical and pathological features, and potential disease mechanisms. We also provide an overview of emerging disease pathways encompassing multiple FTLD genes. We further discuss how FTLD specific issues, such as disease heterogeneity, the presence of an unclear family history and the possible role of an oligogenic basis of FTLD, can pose challenges for future FTLD gene identification and risk assessment of specific variants. Finally, we highlight emerging clinical, genetic, and translational research opportunities that lie ahead. Genetic research led to the identification of three common FTLD genes with rare variants (MAPT, GRN, and C9orf72) and a small number of rare genes. Efforts are now ongoing, which aimed at the identification of rare variants with high risk and/or low frequency variants with intermediate effect. Common risk variants have also been identified, such as TMEM106B. This review discusses the current knowledge on FTLD genes and the emerging disease pathways encompassing multiple FTLD genes.
Blind equalization and multiuser detection in dispersive CDMA channels (1998)

The problem of blind demodulation of multiuser information symbols in a high-rate code-division multiple-access (CDMA) network in the presence of both multiple-access interference (MAI) and intersymbol interference (ISI) is considered. The dispersive CDMA channel is first cast into a multiple-input multiple-output (MIMO) signal model framework. By applying the theory of blind MIMO channel identification and equalization, it is then shown that under certain conditions the multiuser information symbols can be recovered without any prior knowledge of the channel or the users' signature waveforms (including the desired user's signature waveform), although the algorithmic complexity of such an approach is prohibitively high. However, in practice, the signature waveform of the user of interest is always available at the receiver. It is shown that by incorporating this knowledge, the impulse response of each user's dispersive channel can be identified using a subspace method. It is further shown that based on the identified signal subspace parameters and the channel response, two linear detectors that are capable of suppressing both MAI and ISI, i.e., a zero-forcing detector and a minimum-mean-square-error (MMSE) detector, can be constructed in closed form, at almost no extra computational cost. Data detection can then be furnished by applying these linear detectors (obtained blindly) to the received signal. The major contribution of this paper is the development of these subspace-based blind techniques for joint suppression of MAI and ISI in the dispersive CDMA channels.
Translational genomics: The challenge of developing cancer biomarkers (2012)

Early detection and definitive treatment of cancer have been shown to decrease death and suffering in epidemiologic and intervention studies. Application of genomic approaches to many malignancies has produced thousands of candidate biomarkers for detection and prognostication, yet very few have become established in clinical practice. Fundamental issues related to tumor heterogeneity, cancer progression, natural history, and biomarker performance have provided challenges to biomarker development. Technical issues in biomarker assay detection limits, specificity, clinical deployment, and regulation have also slowed progress. The recent emergence of biomarkers and molecular imaging strategies for treatment selection and monitoring demonstrates the promise of cancer biomarkers. Organized efforts by interdisciplinary teams will spur progress in cancer diagnostics.