gebhart/patrepeval huggingface dataset:
Recombinatorial biosynthesis of polyketides (2011)

Modular polyketide synthases (PKSs) from Streptomyces and related genera of bacteria produce many important pharmaceuticals. A program called CompGen was developed to carry out in silico homologous recombination between gene clusters encoding PKSs and determine whether recombinants have cluster architectures compatible with the production of polyketides. The chemical structure of recombinant polyketides was also predicted. In silico recombination was carried out for 47 well-characterised clusters. The predicted recombinants would produce 11,796 different polyketide structures. The molecular weights and average degree of reduction of the chemical structures are dispersed around the parental structures indicating that they are likely to include pharmaceutically interesting compounds. The details of the recombinants and the chemical structures were entered in a database called r-CSDB. The virtual compound library is a useful resource for computer-aided drug design and chemoinformatics strategies for finding pharmaceutically relevant chemical entities. A strategy to construct recombinant Streptomyces strains to produce these polyketides is described and the critical steps of mobilizing large biosynthetic clusters and producing new linear cloning vectors are illustrated by experimental data.
Persistence of Tumor Infiltrating Lymphocytes in Adoptive Immunotherapy Correlates With Telomere Length (2006)

Transfer of autologous tumor-specific tumor infiltrating lymphocytes (TILs) in adoptive immunotherapy can mediate the regression of tumor in patients with metastatic melanoma. In this procedure, TILs from resected tumors are expanded in vitro, then administered to patients and further stimulated to proliferate in vivo by the administration of high dose IL-2. After in vitro expansion, TILs are often dominated by a few specific clonotypes, and recently it was reported that the persistence in vivo of one or more of these clonotypes correlated with positive therapeutic response. We and others have previously shown that repeated in vitro stimulation and clonal expansion of normal human T lymphocytes results in progressive decrease in telomerase activity and shortening of telomeres, ultimately resulting in replicative senescence. In the studies reported here, we therefore compared telomerase activity and telomere length in persistent and nonpersistent TIL clonotypes before transfer in vivo, and found a correlation between telomere length and clonal persistence. We also observed that TILs proliferate extensively in vivo in the days after transfer, but fail to induce substantial telomerase activity, and undergo rapid decreases in telomere length within days after transfer. Thus, in vivo loss of telomeres by clonotypes that have the shortest telomeres at the time of administration may drive these clones to replicative senescence, whereas cells with longer telomeres are able to persist and mediate antitumor effects. These findings are relevant both to predicting effectiveness of adoptive immunotherapy and in deriving strategies for improving effectiveness by sustaining telomere length.
Importance of Acid–Base Equilibrium in Electrocatalytic Oxidation of Formic Acid on Platinum (2013)

Electro-oxidation of formic acid on Pt in acid is one of the most fundamental model reactions in electrocatalysis. However, its reaction mechanism is still a matter of strong debate. Two different mechanisms, bridge-bonded adsorbed formate mechanism and direct HCOOH oxidation mechanism, have been proposed by assuming a priori that formic acid is the major reactant. Through systematic examination of the reaction over a wide pH range (0-12) by cyclic voltammetry and surface-enhanced infrared spectroscopy, we show that the formate ion is the major reactant over the whole pH range examined, even in strong acid. The performance of the reaction is maximal at a pH close to the pKa of formic acid. The experimental results are reasonably explained by a new mechanism in which formate ion is directly oxidized via a weakly adsorbed formate precursor. The reaction serves as a generic example illustrating the importance of pH variation in catalytic proton-coupled electron-transfer reactions.
Ueber die Einwirkung von Dioxychinon auf Orthodiamine (1891)

nach dem Abkuhlen theilweise erstarrt,
Fractal error for detecting man-made features in aerial images (1994)

A technique is proposed for aiding photointerpreters in detecting man-made features in aerial reconnaissance images. The technique, which uses a metric called fractal error, is based on the observed propensity of natural image features to fit a fractional Brownian motion model. Man-made features usually do not fit this model well, and consequently the fractal error metric may be used as a discriminant function for detecting man-made scene features.
Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia (1988)

Twenty-four patients with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (45 to 100 mg/m2/day). Of these, eight cases had been either nonresponsive or resistant to previous chemotherapy; the other 16 cases were previously untreated. All patients attained complete remission without developing bone marrow hypoplasia. Bone marrow suspension cultures were studied in 15 of the 24 patients. Fourteen of these patients had morphological maturation in response to the retinoic acid (1 mumol/L). Chloroacetate esterase and alpha-naphthyl acetate esterase staining as well as electronmicroscopic examination confirmed that retinoic acid-induced cells differentiated to granulocytes with increased functional maturation (as measured by nitroblue tetrazolium reduction, NBT). The single nonresponder to retinoic acid in vitro was resistant to treatment with retinoic acid but attained complete remission after addition of low-dose cytosine arabinoside (ara-C). During the course of therapy, none of the patients showed any abnormalities in the coagulation parameters we measured, suggesting an absence of any subclinical disseminated intravascular coagulation. The only side effects consisted of mild dryness of the lips and skin, with occasional headaches and digestive symptoms. Eight patients have relapsed after 2 to 5 months of complete remission. The others remain in complete remission at 1+ to 11+ months and are still being followed up. We conclude that all-trans retinoic acid is an effective inducer for attaining complete remission in APL.
A culture system using human foreskin fibroblasts as feeder cells allows production of human embryonic stem cells (2003)

We used successfully human foreskin fibroblasts as feeder cells for derivation and continued undifferentiated growth of hES cells. These feeder cells are convenient for IVF units, because no fetal human tissues or tissue from operations are needed.
The role of platelets in acute vascular events. (1980)

Platelets are postulated to have an important role in acute and chronic cardiovascular events. Clinical events may result during the sequence of platelet activation reactions of adhesion, aggregate formation, release of granular constituents, thromboxane A2 formation, microembolization and platelet vascular occlusion. For example, sudden death may occur in patients with increased platelet sensitivity to catecholamine stimulation, platelet aggregate formation and thromboxane A2 generation resulting in ischemic ventricular arrhythmia induced by small-vessel platelet microembolization and local thromboxane A2 vasoconstriction. Whereas angina might be manifest if the microemboli disaggregated and vasospasm were transient, myocardial infarction would follow extensive permanent occlusion of small vessels or localized narrowing by vasospasm and extension of platelet thrombus formation at the site of intimal thickening. Platelets may also have an important role in atherogenesis through the mediation of the platelet-derived growth factor in the proliferative smooth muscle cell intimal lesion. Direct experimental and indirect clinical studies support the concept that platelets are important in cardiovascular events, but the relationship to spasm and to other possibly even more important mechanisms is not clear. Acute myocardial infarction and mural thrombogenesis appear to have the greatest evidence of being platelet-related.
Condition Numbers of Gaussian Random Matrices (2005)

Let $G_{m \times n}$ be an $m \times n$ real random matrix whose elements are independent and identically distributed standard normal random variables, and let $\kappa_2(G_{m \times n})$ be the 2-norm condition number of $G_{m \times n}$. We prove that, for any $m \geq 2$, $n \geq 2$, and $x \geq |n-m|+1$, $\kappa_2(G_{m \times n})$ satisfies ${\scriptsize \frac{1}{\sqrt{2\pi}}} ( { c }/{x} )^{|n-m|+1} < P{\scriptsize(\frac{\kappa_2(G_{m \times n})} {{n}/{(|n-m|+1)}} > x )} < {\scriptsize \frac{1}{\sqrt{2\pi}}} ( { C }/{x} )^{|n-m|+1},$ where $0.245 \leq c \leq 2.000$ and $5.013$ $\leq C \leq 6.414$ are universal positive constants independent of m, n, and x. Moreover, for any $m \geq 2$ and $n \geq 2$, $E(\log\kappa_2(G_{m \times n})) < \log{\scriptsize \frac{n}{|n-m|+1}} + 2.258.$ A similar pair of results for complex Gaussian random matrices is also established.
Asymmetric Amino Acid Activation by Class II Histidyl-tRNA Synthetase from Escherichia coli (2009)

Aminoacyl-tRNA synthetases (ARSs) join amino acids to their cognate tRNAs to initiate protein synthesis. Class II ARS possess a unique catalytic domain fold, possess active site signature sequences, and are dimers or tetramers. The dimeric class I enzymes, notably TyrRS, exhibit half-of-sites reactivity, but its mechanistic basis is unclear. In class II histidyl-tRNA synthetase (HisRS), amino acid activation occurs at different rates in the two active sites when tRNA is absent, but half-of-sites reactivity has not been observed. To investigate the mechanistic basis of the asymmetry, and explore the relationship between adenylate formation and conformational events in HisRS, a fluorescently labeled version of the enzyme was developed by conjugating 7-diethylamino-3-((((2-maleimidyl)ethyl)amino)carbonyl)coumarin (MDCC) to a cysteine introduced at residue 212, located in the insertion domain. The binding of the substrates histidine, ATP, and 5'-O-[N-(l-histidyl)sulfamoyl]adenosine to MDCC-HisRS produced fluorescence quenches on the order of 6-15%, allowing equilibrium dissociation constants to be measured. The rates of adenylate formation measured by rapid quench and domain closure as measured by stopped-flow fluorescence were similar and asymmetric with respect to the two active sites of the dimer, indicating that conformational change may be rate-limiting for product formation. Fluorescence resonance energy transfer experiments employing differential labeling of the two monomers in the dimer suggested that rigid body rotation of the insertion domain accompanies adenylate formation. The results support an alternating site model for catalysis in HisRS that may prove to be common to other class II aminoacyl-tRNA synthetases.
Modifying the host range properties of retroviral vectors (1999)

Gene therapy protocols would be greatly facilitated by the availability of targetable injectable vectors which could deliver genes in vivo to specific target cells or to specific disease sites. Efforts to develop such retroviral vectors are therefore a high priority in gene therapy research. In this review, we describe the current state of our understanding of the structure and function of the retroviral envelope glycoprotein complex. We then discuss the results of the various strategies that have been devised to modify the host range of the retroviral envelope glycoproteins with a view to achieving retroviral vectors capable of delivering their genes in a highly specific manner to selected human target cells. The strengths and limitations of these strategies are examined.
Image-Guided Insertion of Transpedicular Screws (1995)

The presented technique provides a safe, accurate, and flexible basis for transpedicular screw placement in the spine. This approach should be further evaluated in clinical applications.
Design and Synthesis of a Versatile Photocleavable DNA Building Block. Application to Phototriggered Hybridization (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDesign and Synthesis of a Versatile Photocleavable DNA Building Block. Application to Phototriggered HybridizationPhillip Ordoukhanian and John-Stephen TaylorCite this: J. Am. Chem. Soc. 1995, 117, 37, 9570–9571Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://pubs.acs.org/doi/10.1021/ja00142a028https://doi.org/10.1021/ja00142a028research-articleACS PublicationsRequest reuse permissionsArticle Views1083Altmetric-Citations70LEARN 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 (2)»Supporting Information Supporting Information Get e-Alerts
All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results [see comments] (1990)

Twenty-two patients with acute promyelocytic leukemia were treated with all-trans retinoic acid (RA, 45 mg/m2 per day) for 90 days. Of the 22, four patients were previously untreated, two were resistant after conventional chemotherapy, and 16 were in first (n = 11), second (n = 4), or third (n = 1) relapse. We observed 14 complete response, four transient responses, one failure, and three early deaths. Length of hospitalization and number of transfusions were notably reduced in complete responders. Correction of coagulation disorders and an increase of WBCs were the first signs of all-trans RA efficacy. Morphologic analysis performed at days 0, 15, 30, 45, 60, and 90 showed that complete remissions were obtained without bone marrow (BM) hypoplasia. Presence of Auer rods in the maturing cells confirmed the differentiation effect of the treatment. At remission, the t(15;17) initially present in 20 patients was not found. The in vitro studies showed a differentiation in the presence of all-trans RA in 16 of the 18 tested cases. The single nonresponder to all trans RA in vitro did not respond in vivo. Adverse effects of RA therapy--skin and mucosa dryness, hypertriglyceridemia, and increase of hepatic transaminases--were frequently noted. We also observed bone pain in 11 patients and hyperleukocytosis in four patients. Whether maintenance treatment consisted of low-dose chemotherapy or all-trans RA, early relapses were observed. Five patients are still in complete remission (CR) at 4 to 13 months. Our study confirms the major efficacy of all-trans RA in M3, even in relapsing patients. Remissions are obtained by a differentiation process.
Constitutive expression of pathogenesis-related proteins PR-1, GRP, and PR-S in tobacco has no effect on virus infection. (1989)

Samsun NN tobacco cells were transformed with chimeric genes for pathogenesis-related (PR) proteins derived from genomic (PR-1a, GRP) or cDNA (PR-S) clones under the transcriptional control of the cauliflower mosaic virus 35S promoter. Regenerated plants were assayed by RNA and protein gel blotting, and plants showing high specific expression of the inserted genes were selected for self-pollination and seed formation. Inspection of second generation transformants showed that constitutive expression of PR-1a, GRP, and PR-S in tobacco in general does not have an effect on the phenotypic appearance of the plants or the expression of other endogenous PR genes. Furthermore, constitutive expression of the above genes does not affect the susceptibility of the plants to infection with tobacco mosaic virus or alfalfa mosaic virus.
Phosphorylation affects the ability of tau protein to promote microtubule assembly. (1984)

Tau is a family of closely related proteins known for its ability to copolymerize with tubulin, inducing the formation of microtubules. When tau was stripped of phosphate by treatment with alkaline phosphatase it underwent a pronounced change in electrophoretic mobility, probably reflecting a conformational change. The dephosphorylated tau promoted significantly more rapid and more extensive polymerization of microtubules though there was no obvious difference in the microtubules formed. Partially purified microtubule protein contains a kinase that can rephosphorylate tau.
Rationally Designed Base Editors for Precise Editing of the Sickle Cell Disease Mutation (2021)

Base editors are fusions of a deaminase and CRISPR-Cas ribonucleoprotein that allow programmable installment of transition mutations without double-strand DNA break intermediates. The breadth of potential base editing targets is frequently limited by the requirement of a suitably positioned Cas9 protospacer adjacent motif. To address this, we used structures of Cas9 and TadA to design a set of inlaid base editors (IBEs), in which deaminase domains are internal to Cas9. Several of these IBEs exhibit shifted editing windows and greater editing efficiency, enabling editing of targets outside the canonical editing window with reduced DNA and RNA off-target editing frequency. Finally, we show that IBEs enable conversion of the pathogenic sickle cell hemoglobin allele to the naturally occurring HbG-Makassar variant in patient-derived hematopoietic stem cells.
Swine influenza virus strains recognize sialylsugar chains containing the molecular species of sialic acid predominantly present in the swine tracheal epithelium (1997)

We determined the ratio of N-glycolylneuraminic acid (Neu5Gc) to N-acetylneuraminic acid (Neu5Ac) in swine respiratory epithelia by fluorometric high-performance liquid chromatography, and examined the binding specificity of swine influenza virus strains for gangliosides containing different molecular species of sialic acid (Neu5Ac and Neu5Gc), and for bovine erythrocyte sialoglycoprotein 2 (GP-2) containing Neu5Gc as its predominate sialic acid (96% of total sialic acids). The presence of Neu5Gc, which had not been detected in human tracheal epithelia, and Neu5Ac in swine tracheal epithelia was observed in a 1:1 ratio. The swine influenza virus H1 and H3 isolates tested, except for A/swine/Iowa/15/30 (H1N1), displayed a marked binding ability for sialylsugar chains containing Neu5Gc compared with that of the human influenza virus strains. These results suggest that swine influenza viruses recognize sialylsugar chains containing the molecular species of sialic acid present predominantly in the swine tracheal epithelium.
Comparison of the healing of open tibial fractures covered with either muscle or fasciocutaneous tissue in a murine model (2008)

The objective of this study was to compare the effects of soft tissue coverage by either muscle or fasciocutaneous tissue on the healing of open tibial fractures in a murine model. An open tibial fracture, stripped of periosteum with intramedullary fixation, was created in mice. Experimental groups were devised to allow exclusive comparison of either muscle alone or skin plus fascia in direct contact with healing bone. To exclusively assess the relative efficacy of muscle and fasciocutaneous tissue to promote healing of a fracture stripped of periosteum, a piece of sterile inert material (polytetrafluoroethylene) was positioned anteriorly, excluding skin and fascia (muscle group) or posteriorly, excluding muscle (fasciocutaneous group). Skeletal repair was assessed histologically and quantified by histomorphometry; quantitative peripheral computed tomography (pQCT) and mechanical testing using a four-point bending technique. This standardized, reproducible model allowed characterization of the morphology of open fracture healing. At 28 days postfracture, there was faster healing in the experimental muscle coverage group compared to skin and fascia alone. Furthermore, there was almost 50% more cortical bone content and a threefold stronger union beneath muscle compared to fasciocutaneous tissue (p < 0.05 by one-way ANOVA). Exclusive comparison of muscle and fasciocutaneous tissue in our novel murine model demonstrates that muscle is superior for the coverage of open tibial fractures for both the rate and quality of fracture healing.
Regulation of Alternative Splicing by Histone Modifications (2010)

Alternative splicing of pre-mRNA is a prominent mechanism to generate protein diversity, yet its regulation is poorly understood. We demonstrated a direct role for histone modifications in alternative splicing. We found distinctive histone modification signatures that correlate with the splicing outcome in a set of human genes, and modulation of histone modifications causes splice site switching. Histone marks affect splicing outcome by influencing the recruitment of splicing regulators via a chromatin-binding protein. These results outline an adaptor system for the reading of histone marks by the pre-mRNA splicing machinery.
VIP: a protocol providing host mobility (1994)

article Free Access Share on VIP: a protocol providing host mobility Authors: Fumio Teraoka Sony Computer Science lab., Inc., Tokyo, Japan Sony Computer Science lab., Inc., Tokyo, JapanView Profile , Keisuke Uehara The Univ. of Electro-Communications, Tokyo, Japan The Univ. of Electro-Communications, Tokyo, JapanView Profile , Hideki Sunahara Advanced Institue of Science and Technology—Nara, Nara, Japan Advanced Institue of Science and Technology—Nara, Nara, JapanView Profile , Jun Murai Keio Univ., Fujisawa, Japan Keio Univ., Fujisawa, JapanView Profile Authors Info & Claims Communications of the ACMVolume 37Issue 8Aug. 1994 pp 67–ff.https://doi.org/10.1145/179606.179657Published:01 August 1994Publication History 41citation448DownloadsMetricsTotal Citations41Total Downloads448Last 12 Months31Last 6 weeks10 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF