gebhart/patrepeval huggingface dataset:
Synthesis of unnatural alkaloid scaffolds by exploiting plant polyketide synthase (2011)

HsPKS1 from Huperzia serrata is a type III polyketide synthase (PKS) with remarkable substrate tolerance and catalytic potential. Here we present the synthesis of unnatural unique polyketide-alkaloid hybrid molecules by exploiting the enzyme reaction using precursor-directed and structure-based approaches. HsPKS1 produced novel pyridoisoindole (or benzopyridoisoindole) with the 6.5.6-fused (or 6.6.5.6-fused) ring system by the condensation of 2-carbamoylbenzoyl-CoA (or 3-carbamoyl-2-naphthoyl-CoA), a synthetic nitrogen-containing nonphysiological starter substrate, with two molecules of malonyl-CoA. The structure-based S348G mutant not only extended the product chain length but also altered the cyclization mechanism to produce a biologically active, ring-expanded 6.7.6-fused dibenzoazepine, by the condensation of 2-carbamoylbenzoyl-CoA with three malonyl-CoAs. Thus, the basic nitrogen atom and the structure-based mutagenesis enabled additional C─C and C─N bond formation to generate the novel polyketide-alkaloid scaffold.
The multidrug resistance gene PDR1 from Saccharomyces cerevisiae. (1987)

The Saccharomyces cerevisiae gene PDR1, responsible for pleiotropic drug resistance, was isolated from a genomic DNA cosmid library by hybridization to the flanking LEU1 gene, followed by subcloning the drug-sensitive phenotype into the transformed pdr1-1, pdr1-2, and pdr1-3 drug-resistant mutants. A RNA molecule of 3.5 kilobases was identified as the PDR1 transcript. The nucleotide sequence of the complementing DNA fragment contained a 3192-nucleotide open reading frame. Disruption of the pdr1 and PDR1 genes restored or increased drug sensitivity. Analysis of the PDR1 deduced amino acid sequence revealed several homologies to four different regulatory proteins involved in the control of gene expression, including a cysteine-rich motif suggested to be a metal-binding domain for DNA recognition. A model is proposed of a general transcriptional control by PDR1 of several target genes encoding proteins from plasma, mitochondria, and possibly other permeability barriers.
Amplification of expression of hepatitis B surface antigen in 3T3 cells cotransfected with a dominant-acting gene and cloned viral DNA. (1982)

3T3 cells containing hepatitis B virus DNA sequences can be efficiently selected by exposure to methotrexate after cotransfection with cloned viral DNA and DNA coding for a methotrexate-resistant dihydrofolate reductase. More than 75% of methotrexate-resistant cells isolated after cotransfection with a head-to-tail tandem of the hepatitis B virus genome synthesized viral surface antigen. The antigen was released into the culture medium in the form of 22-nm particles with buoyant density of 1.20 g/ml. No other virally coded proteins were detected in the cells or the culture medium. Application of selective pressure by increasing the concentration of methotrexate resulted in an amplification of viral DNA sequences and a concomitant increase in the rate of synthesis and release of hepatitis B surface antigen. The ability to produce large amounts of surface antigen appears to be a stable trait and has been maintained in these cultures through more than 30 passages.
Theory of Interacting Neural Networks (2002)

In this contribution we give an overview over recent work on the theory of interacting neural networks. The model is defined in Section 2. The typical teacher/student scenario is considered in Section 3. A static teacher network is presenting training examples for an adaptive student network. In the case of multilayer networks, the student shows a transition from a symmetric state to specialisation. Neural networks can also generate a time series. Training on time series and predicting it are studied in Section 4. When a network is trained on its own output, it is interacting with itself. Such a scenario has implications on the theory of prediction algorithms, as discussed in Section 5. When a system of networks is trained on its minority decisions, it may be considered as a model for competition in closed markets, see Section 6. In Section 7 we consider two mutually interacting networks. A novel phenomenon is observed: synchronisation by mutual learning. In Section 8 it is shown, how this phenomenon can be applied to cryptography: Generation of a secret key over a public channel.
Obesity in Adulthood and Its Consequences for Life Expectancy: A Life-Table Analysis (2003)

Obesity and overweight in adulthood are associated with large decreases in life expectancy and increases in early mortality. These decreases are similar to those seen with smoking. Obesity in adulthood is a powerful predictor of death at older ages. Because of the increasing prevalence of obesity, more efficient prevention and treatment should become high priorities in public health.
Perfect ALKemy: Optimizing the Use of ALK-Directed Therapies in Lung Cancer (2014)

Mutations in ALK are a common mechanism of acquired resistance to small molecule ALK inhibitors in ALK-rearranged lung cancer. Different mutants exhibit differential sensitivity to ALK inhibitors. Matching the mutational profile of the tumor with the appropriate ALK inhibitor is likely to be important to maximize benefit for patients.
Teaching Cre to follow directions (2009)

have turned the normally unregulated Cre
Neomycin-Induced Hybrid Triplex Formation (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTNeomycin-Induced Hybrid Triplex FormationDev P. Arya, R. Lane Coffee, and I. CharlesView Author Information Laboratory of Medicinal Chemistry Department of Chemistry, Clemson University Clemson, South Carolina 29634 Cite this: J. Am. Chem. Soc. 2001, 123, 44, 11093–11094Publication Date (Web):October 12, 2001Publication History Received22 June 2001Published online12 October 2001Published inissue 1 November 2001https://pubs.acs.org/doi/10.1021/ja016481jhttps://doi.org/10.1021/ja016481jrapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views526Altmetric-Citations74LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Carbohydrates,Genetics,Melting,Peptides and proteins,Stabilization Get e-Alerts
Initiating DNA synthesis: from recruiting to activating the MCM complex (2001)

The exact duplication of a genome once per cell division is required of every proliferating cell. To achieve this goal, eukaryotes adopt a strategy that limits every replication origin to a single initiation event within a narrow window of the cell cycle by temporally separating the assembly of the pre-replication complex (pre-RC) from the initiation of DNA synthesis. A key component of the pre-RC is the hexameric MCM complex, which is also the presumed helicase of the growing forks. An elaborate mechanism recruits the MCM complex to replication origins, and a regulatory chain reaction converts the poised, but inactive, MCM complex into an enzymatically active helicase. A growing list of proteins, including Mcm10 and Cdt1, are involved in the recruitment process. Two protein kinases, the Cdc7-Dbf4 kinase (DDK) and the cyclin-dependent kinase (CDK), trigger a chain reaction that results in the phosphorylation of the MCM complex and finally in the initiation of DNA synthesis. A composite picture from recent studies suggests that DDK is recruited to the pre-RC during G1 phase but must wait until S phase to phosphorylate the MCM complex. CDK is required for the recruitment of Cdc45 and other downstream components of the elongation machinery.
Phagocytosis in Macrophages Lacking Cbl Reveals an Unsuspected Role for Fcγ Receptor Signaling and Actin Assembly in Target Binding (2009)

Fc gamma receptor (Fc gammaR)-mediated phagocytosis is known to require tyrosine kinases (TKs). We identified c-Cbl and Cbl-b as proteins that undergo tyrosine phosphorylation during phagocytosis. Cbl-deficient macrophages displayed enhanced Fc gammaR-mediated signaling and phagocytosis. Surprisingly, binding of IgG-coated targets (EIgG) was also enhanced. c-Cbl-deficient macrophages expressed less Fc gammaRIIb, the inhibitory Fc gamma receptor; however, this did not account for enhanced target binding. We isolated the function of one Fc receptor isoform, Fc gammaRI, using IgG2a-coated targets (EIgG2a). Cbl-deficient macrophages demonstrated a disproportionate increase in binding EIgG2a, suggesting that signal strength regulates binding efficiency toward opsonized targets. In resting cells, Fc gammaRI colocalized with the Src family TK Hck in F-actin-rich structures, which was enhanced in Cbl-deficient macrophages. Target binding was sensitive to TK inhibitors, profoundly inhibited following depletion of cholesterol, and ablated at 4 degrees C or in the presence of inhibitors of actin polymerization. Sensitivity of EIgG binding to cytoskeletal disruption was inversely proportional to opsonin density. These findings challenge the view that Fc gammaR-mediated binding is a passive event. They suggest that dynamic engagement of TKs and the cytoskeleton enables macrophages to serve as cellular "Venus fly traps", with the capacity to capture phagocytic targets under conditions of limiting opsonin density.
The chemistry of the thiol group. (1974)

The chemistry of the thiol group. , The chemistry of the thiol group. , کتابخانه دیجیتال جندی شاپور اهواز
Docking and scoring protein complexes: CAPRI 3rd Edition (2007)

The performance of methods for predicting protein-protein interactions at the atomic scale is assessed by evaluating blind predictions performed during 2005-2007 as part of Rounds 6-12 of the community-wide experiment on Critical Assessment of PRedicted Interactions (CAPRI). These Rounds also included a new scoring experiment, where a larger set of models contributed by the predictors was made available to groups developing scoring functions. These groups scored the uploaded set and submitted their own best models for assessment. The structures of nine protein complexes including one homodimer were used as targets. These targets represent biologically relevant interactions involved in gene expression, signal transduction, RNA, or protein processing and membrane maintenance. For all the targets except one, predictions started from the experimentally determined structures of the free (unbound) components or from models derived by homology, making it mandatory for docking methods to model the conformational changes that often accompany association. In total, 63 groups and eight automatic servers, a substantial increase from previous years, submitted docking predictions, of which 1994 were evaluated here. Fifteen groups submitted 305 models for five targets in the scoring experiment. Assessment of the predictions reveals that 31 different groups produced models of acceptable and medium accuracy-but only one high accuracy submission-for all the targets, except the homodimer. In the latter, none of the docking procedures reproduced the large conformational adjustment required for correct assembly, underscoring yet again that handling protein flexibility remains a major challenge. In the scoring experiment, a large fraction of the groups attained the set goal of singling out the correct association modes from incorrect solutions in the limited ensembles of contributed models. But in general they seemed unable to identify the best models, indicating that current scoring methods are probably not sensitive enough. With the increased focus on protein assemblies, in particular by structural genomics efforts, the growing community of CAPRI predictors is engaged more actively than ever in the development of better scoring functions and means of modeling conformational flexibility, which hold promise for much progress in the future.
Low temperature synthesis of plutonium hexafluoride using dioxygen difluoride (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLow temperature synthesis of plutonium hexafluoride using dioxygen difluorideJ. G. Malm, P. G. Eller, and L. B. AspreyCite this: J. Am. Chem. Soc. 1984, 106, 9, 2726–2727Publication Date (Print):May 1, 1984Publication History Published online1 May 2002Published inissue 1 May 1984https://pubs.acs.org/doi/10.1021/ja00321a056https://doi.org/10.1021/ja00321a056research-articleACS PublicationsRequest reuse permissionsArticle Views267Altmetric-Citations56LEARN 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
Covalent Immobilization of P-Selectin Enhances Cell Rolling (2007)

Cell rolling is an important physiological and pathological process that is used to recruit specific cells in the bloodstream to a target tissue. This process may be exploited for biomedical applications to capture and separate specific cell types. One of the most commonly studied proteins that regulate cell rolling is P-selectin. By coating surfaces with this protein, biofunctional surfaces that induce cell rolling can be prepared. Although most immobilization methods have relied on physisorption, chemical immobilization has obvious advantages, including longer functional stability and better control over ligand density and orientation. Here we describe chemical methods to immobilize P-selectin covalently on glass substrates. The chemistry was categorized on the basis of the functional groups on modified glass substrates: amine, aldehyde, and epoxy. The prepared surfaces were first tested in a flow chamber by flowing microspheres functionalized with a cell surface carbohydrate (sialyl Lewis(x)) that binds to P-selectin. Adhesion bonds between P-selectin and sialyl Lewis(x) dissociate readily under shear forces, leading to cell rolling. P-selectin immobilized on the epoxy glass surfaces exhibited enhanced long-term stability of the function and better homogeneity as compared to that for surfaces prepared by other methods and physisorbed controls. The microsphere rolling results were confirmed in vitro with isolated human neutrophils. This work is essential for the future development of devices for isolating specific cell types based on cell rolling, which may be useful for hematologic cancers and certain metastatic cancer cells that are responsive to immobilized selectins.
Dispersion of carbon nanotubes in water and non-aqueous solvents (2013)

Contemporary methods for dispersion of carbon nanotubes in water and non-aqueous media are discussed. Most attention is paid to ultrasonic and plasma techniques and other physical techniques, as well as to the use of surfactants, functionalizing and debundling agents of distinct nature (elemental substances, metal and organic salts, mineral and organic acids, oxides, inorganic and organic peroxides, organic sulfonates, polymers, dyes, natural products, biomolecules, and coordination compounds). Special studies on CNTs solubilization are examined.
Amino acid sequence of the λ light chain of a human myeloma immunoglobulin (IgG new) (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAmino acid sequence of the λ light chain of a human myeloma immunoglobulin (IgG new)Betty L. Chen and Roberto J. PoljakCite this: Biochemistry 1974, 13, 6, 1295–1302Publication Date (Print):March 1, 1974Publication History Published online1 May 2002Published inissue 1 March 1974https://pubs.acs.org/doi/10.1021/bi00703a037https://doi.org/10.1021/bi00703a037research-articleACS PublicationsRequest reuse permissionsArticle Views70Altmetric-Citations21LEARN 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
Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone. (1989)

Abstract A T cell clone (ACH-2) derived from T cells infected with HIV-1 was found to produce HIV-1 in response to stimulation with a monokine-enriched supernatant prepared by culturing human monocyte/macrophages with bacterial LPS (LPS-MO SN). Monokine induction of ACH-2 cells resulted in augmented virus production reflected by an increase in reverse transcriptase activity and in the synthesis of all major viral proteins. Examination of the cells by indirect immunofluorescence revealed that 10 to 15% of uninduced cells constitutively expressed HIV proteins, whereas 100% showed positive immunofluorescence in response to LPS-MO SN. This induction of virus by LPS-MO SN resulted in approximately a 100-fold increase of infectious virus production over uninduced ACH-2 cells. LPS alone could not induce HIV-1 expression, whereas LPS-MO SN resulted in the greatest virus expression. Cell separation studies confirmed the source of the inducing factor(s) to be cells bearing the mature monocyte/macrophage marker, Leu M3. Biochemical fractionation of the LPS-MO SN suggested that one or more factors, having apparent Mr of approximately 45 kDa, were involved in this induction. Absorption of the LPS-MO SN with immunoaffinity gels specific for human TNF-alpha was shown to completely remove the HIV inducing activity for the ACH-2 cell line.
The Use of Vasopressin Bolus to Treat Refractory Hypotension Secondary to Reperfusion During Orthotopic Liver Transplantation (2006)

To the Editor: Vasopressin infusions have been used to treat hypotension in a variety of situations (1–4). However, without an initial loading dose, there may be a significant delay until the medication has an effect (1,5). There are little data to suggest a safe and effective bolus dose of vasopressin. The following case provides additional support for the safe use of bolus vasopressin. A 53-yr-old, 82 kg, male underwent orthotopic liver transplantation for hepatitis C cirrhosis and hepatocellular carcinoma. Surgery was uneventful up to the time of reperfusion, including systolic blood pressure (≈95–110 mm Hg), pulmonary arterial pressure (30/14 mm Hg), and central venous pressure (≈10 mm Hg). The patient received one gram of calcium chloride 1 min before reperfusion. Within 1–2 min after liver reperfusion, his arterial blood pressure decreased to 55/30 mm Hg, pulmonary arterial pressure increased to 38/19 mm Hg, and central venous pressure increased to 12 mm Hg. An additional gram of calcium and increasing bolus doses of norepinephrine as large as 160 μg plus a norepinephrine infusion of 16 μg/min failed to accomplish more than a transient increase in systolic blood pressure to 81 mm Hg. Two bolus doses of vasopressin, 0.4 U each, increased the systolic blood pressure to 98 mm Hg, which was sustained for 3–5 min. Another vasopressin bolus of 0.4 U vasopressin was administered, and the patient was placed on vasopressin infusion at 4 U/h. The norepinephrine and vasopressin infusions were maintained for the duration of the surgery and into the early postoperative period. Pulmonary arterial pressure and central venous pressure returned to baseline within 15–30 min. The patient did not become acidotic. Urine output was satisfactory during and after the procedure. There were no adverse cardiac, neurologic, hepatic, renal, or pulmonary events. The graft functioned well and the patient was discharged home on the fifth postoperative day. This report provides support for the use of vasopressin bolus and infusion in treating hypotension refractory to catecholamines resulting from the reperfusion syndrome during liver transplantation. The vasopressin dose of 0.4 U is 2 orders of magnitude less than that recommended in advanced cardiac life support protocols (40 U) (6) and may not be the optimal bolus dose. Well-controlled studies need to be conducted to establish the indications, safety, and efficacy of bolus vasopressin for rapid correction of hypotension. Jonathan V. Roth, MD Department of Anesthesiology Albert Einstein Medical Center Philadelphia, PA [email protected]