gebhart/patrepeval huggingface dataset:
Selection of Metalloenzymes by Catalytic Activity Using Phage Display and Catalytic Elution (2001)

The metallo-β-lactamase βLII from Bacillus cereus 569/H/9 was displayed on the filamentous phage fd. The phage-bound enzyme fd-βLII was shown to be active on benzylpenicillin as substrate; it could be inactivated by complexation of the essential zinc(II) ion with EDTA and reactivated by addition of a zinc(II) salt. A selection process was designed to extract active phage-bound enzymes from libraries of mutants in three steps: 1. inactivation of active phage-bound enzymes by metal ion complexation, 2. binding to substrate-coated magnetic beads, 3. release of phages capable of transforming the substrate into product upon zinc salt addition. The selection process was first successfully tested on model mixtures containing fd-βLII plus either a dummy phage, a phage displaying an inactive mutant of the serine β-lactamase TEM-1, or inactive and low-activity mutants of βLII. The selection was then applied to extract active phage-bound enzymes from a library of mutants generated by mutagenic polymerase chain reaction (PCR). The activity of the library was shown to increase 60-fold after two rounds of selection. Eleven clones from the second round were randomly picked for sequencing and to characterize their activity and stability.
Online Action Detection in Untrimmed, Streaming Videos - Modeling and Evaluation. (2018)

The goal of Online Action Detection (OAD) is to detect action in a timely manner and to recognize its action category. Early works focused on early action detection, which is effectively formulated as a classification problem instead of online detection in streaming videos, because these works used partially seen short video clip that begins at the start of action. Recently, researchers started to tackle the OAD problem in the challenging setting of untrimmed, streaming videos that contain substantial background shots. However, they evaluate OAD in terms of per-frame labeling, which does not require detection at the instance-level and does not evaluate the timeliness of the online detection process. In this paper, we design new protocols and metrics. Further, to specifically address challenges of OAD in untrimmed, streaming videos, we propose three novel methods: (1) we design a hard negative samples generation module based on Generative Adversarial Network (GAN) framework to better distinguish ambiguous background shots that share similar scenes but lack true characteristics of action start; (2) during training we impose a temporal consistency constraint between data around action start and data succeeding action start to model their similarity; (3) we introduce an adaptive sampling strategy to handle the scarcity of the important training data around action start. We conduct extensive experiments using THUMOS'14 and ActivityNet. We show that our proposed strategies lead to significant performance gains and improve state-of-the-art results. A systematic ablation study also confirms the effectiveness of each proposed method.
A Wavelength Tunable Q-Switched Erbium-Doped Fiber Laser with Fiber Bragg Grating Mirrors (1996)

Q-switched operation of an erbium-doped fiber laser with fiber grating mirrors is demonstrated for the first time. The resonator was formed by splicing two fiber gratings to erbium-doped fiber ends. One of the fiber gratings was periodically stretched by a piezoelectric transducer for the Q-switching operation. An output pulse with a pulse width of 2.46 µ s and a peak power of 2.1 mW was obtained for a 1.48 µ m pump power of 26 mW. The oscillation wavelength was 1.552 µ m and the repetition rate was 1 kHz. The laser oscillation wavelength was tuned from 1.552 µ m to 1.556 µ m by applying lateral stress to one of the fiber grating mirrors.
Bone Mineral Density in Girls with Classical Congenital Adrenal Hyperplasia due to CYP21 Deficiency (2008)

The dose of glucocorticoid used in the treatment of girls with CAH-CYP21 correlated negatively with BMD, and dexamethasone was not selectively harmful.
Manipulating PEPC levels in plants (2002)

This review examines the current understanding of the structural, functional and regulatory properties of C4 and C3 forms of higher plant phosphoenolpyruvate carboxylase. The emphasis is on the interactive metabolic and post-translational controls acting on the enzyme in the physiological context of C4 photosynthesis and the anaplerotic pathway. A brief overview is given concerning the recent developments of PEPC-based genetic engineering of C3 plants with the aim of improving photosynthetic performance in normal and limiting environmental conditions. So far, in spite of achieving a considerable increase in PEPC levels, more work needs to be done with respect to the correct dosage and location before that goal is reached. Some unpublished results on the transformation of maize with a sorghum C4 PEPC cDNA are also presented. They show that it is possible to increase photosynthetic PEPC levels in this C4 plant and that the modification in enzyme content has a pleiotropic physiological impact and, notably, an improved water use efficiency when water is limited.
Differential Biodistribution of Adenoviral Vector In Vivo as Monitored by Bioluminescence Imaging and Quantitative Polymerase Chain Reaction (2006)

A better understanding of the in vivo biodistribution of adenoviral vectors would enable the researcher to anticipate potential side effects due to off-targeted site of transduction, and aid in the strategic design of gene therapy. We combined real-time polymerase chain reaction with in vivo optical imaging to examine viral transduction in liver, lung, spleen, kidney, prostate, and lymph nodes. A replication-deficient serotype 5 adenoviral vector expressing the firefly luciferase gene under the control of a constitutive cytomegalovirus promoter was administered in vivo via different routes. Intravenous and intraperitoneal injections resulted in greatest gene expression and viral DNA in the liver, whereas intraperitoneal injections led to a greater extent of gene delivery to the prostate. Although prostate-directed injection resulted in dominant gene expression in the targeted site, leakage of the vector to other organs was also observed. Vector injection into the lymphatic-rich paw tissue or the subcutaneous tissue of shoulder or chest followed the expected lymphatic drainage pattern, resulting in the accumulation of viral vector in ipsilateral brachial and axillary lymph nodes. Collectively, this study demonstrates that each tissue retains various amounts of adenoviral vector, depending on the route of administration. This knowledge is useful in the strategic design and implementation of adenovirus-mediated gene therapies.
Azido-Containing Diketo Acid Derivatives Inhibit Human Immunodeficiency Virus Type 1 Integrase In Vivo and Influence the Frequency of Deletions at Two-Long-Terminal-Repeat-Circle Junctions (2004)

We previously found that azido-containing beta-diketo acid derivatives (DKAs) are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase (IN) (X. Zhang et al., Bioorg. Med. Chem. Lett., 13:1215-1219, 2003). To characterize the intracellular mechanisms of action of DKAs, we analyzed the antiviral activities of two potent azido-containing DKAs with either a monosubstitution or a disubstitution of azido groups, using single- and multiple-replication-cycle assays. Both azido-containing DKAs significantly inhibited HIV-1 infection in 293T, CEM-SS, and H9 cells (50% inhibitory concentration = 2 to 13 micro M) and exhibited low cytotoxicity (50% cytotoxic concentration = 60 to 600 micro M). Inhibition of HIV-1 IN in vivo was demonstrated by the observation that previously described L-708,906 resistance mutations in HIV-1 IN (T66I and T66I/S153Y) also conferred resistance to the azido-group-containing DKAs. In vitro assays and in vivo analysis indicated that the DKAs did not significantly inhibit the 3' processing and selectively inhibited the strand transfer reaction. In addition, quantitative PCR indicated that two-long-terminal-repeat (2-LTR) circles were elevated in the presence of the azido-containing DKAs, confirming that HIV-1 IN was the intracellular target of viral inhibition. To gain insight into the mechanism by which the DKAs increased 2-LTR-circle formation of 3'-processed viral DNAs, we performed extensive DNA sequencing analysis of 2-LTR-circle junctions. The results indicated that the frequency of deletions at the circle junctions was elevated from 19% for the untreated controls to 32 to 41% in the presence of monosubstituted (but not disubstituted) DKAs. These results indicate that the structure of the DKAs can influence the extent of degradation of viral DNA ends by host nucleases and the frequency of deletions at the 2-LTR-circle junctions. Thus, sequencing analysis of 2-LTR-circle junctions can elucidate the intracellular mechanisms of action of HIV-1 IN inhibitors.
Amyloid precursor protein truncated at any of the ?-secretase sites is not cleaved to ?-amyloid (1996)

beta A4 secretion occurs upon processing of amyloid protein precursor (APP) by beta-secretase (N-terminus of beta A4) and gamma-secretase (C-terminus). To determine the sequence of these activities and the processing intermediate of beta A4, we expressed several truncated APP molecules in human HEK-293 cells. Immunofluorescence and biotinylation studies indicated that full-length APP or APP lacking the cytosolic domain both were located intracellularly, associated with the cell surface and secreted. APPs truncated after amino acid 40, 42, or 43 of beta A4 were not inserted into cell membranes, were found intracellularly but not on the cell surface, and were efficiently secreted into the culture medium. The secretion of APP truncated at amino acid 40 of beta A4 occurred without proteolytic processing. Neither beta A4 nor P3 (the product of the alpha-secretase) was secreted from any of the APP molecules truncated at the gamma-secretase sites. In sharp contrast to this, when the C-terminal 100 amino acids of APP were expressed (APP truncated at the N-terminus of beta A4), a robust beta A4 secretion was observed. Thus, the C-terminal fragment of APP produced by beta-secretase activity is likely to be the processing intermediate of beta A4.
Lysyl oxidase‐like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal‐like breast carcinomas (2011)

Basal-like breast carcinoma is characterized by the expression of basal/myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and frequent triple negative status (ESR-, PR-, Her2neu-). We have previously shown that epithelial-mesenchymal transition (EMT) occurs in basal-like breast tumours and identified Lysyl-oxidase-like 2 (LOXL2) as an EMT player and poor prognosis marker in squamous cell carcinomas. We now show that LOXL2 mRNA is overexpressed in basal-like human breast carcinomas. Breast carcinoma cell lines with basal-like phenotype show a specific cytoplasmic/perinuclear LOXL2 expression, and this subcellular distribution is significantly associated with distant metastatic incidence in basal-like breast carcinomas. LOXL2 silencing in basal-like carcinoma cells induces a mesenchymal-epithelial transition (MET) associated with a decrease of tumourigenicity and suppression of metastatic potential. Mechanistic studies indicate that LOXL2 maintains the mesenchymal phenotype of basal-like carcinoma cells by a novel mechanism involving transcriptional downregulation of Lgl2 and claudin1 and disorganization of cell polarity and tight junction complexes. Therefore, intracellular LOXL2 is a new candidate marker of basal-like carcinomas and a target to block metastatic dissemination of this aggressive breast tumour subtype.
Gene Silencing in the Development of Personalized Cancer Treatment: The Targets, the Agents and the Delivery Systems (2006)

The advent of sophisticated experimental tools that can probe the molecular pathology of cancer has revealed a number of genes and gene families that could prove attractive targets for cancer therapy. Thus, gene silencing strategies have been envisioned to treat cancer by targeting the cancer cell's capacity to: (I) resist conventional treatment methods (chemotherapy and radiotherapy), (II) promote angiogenesis, and (III) metastasize and/or to survive microenvironments that normally would promote cell apoptosis/necrosis. The realization of such strategies is limited by the lack of pharmaceutically-viable technologies that enable the safe and effective delivery of gene-targeting agents to neoplastic cells following systemic administration. There are many reasons for this, including an incomplete understanding of how cancer cells respond when genes are silenced. Further the pharmacokinetic and pharmacodynamic attributes of gene therapy products are not well understood. This review will discuss gene therapy strategies that have been developed based on gene inhibition by the use of antisense oligonucleotides, ribozymes and RNA interference (RNAi). In this context, several particularly promising targets will be described, with a focus on strategies that have progressed to the stage where clinical trials have been initiated. The review highlights product development strategies that emphasize non-viral systemic formulations and the potential for delivery systems to become an enabling technology for development of effective gene therapy products.
Early Diagnosis ofABCB11Spectrum Liver Disorders by Next Generation Sequencing (2017)

The goal of this study was the early diagnosis of ABCB11 spectrum liver disorders, especially those focused on benign recurrent intrahepatic cholestasis and progressive familial intrahepatic cholestasis. Fifty patients presenting neonatal cholestasis were evaluated to identify underlying etiologies. Genetic analysis was performed on patients suspected to have syndromic diseases or ABCB11 spectrum liver disorders. Two families with proven ABCB11 spectrum liver disorders were subjected to genetic analyses to confirm the diagnosis and were provided genetic counseling. Whole exome sequencing and Sanger sequencing were performed on the patients and the family members. Idiopathic or viral hepatitis was diagnosed in 34%, metabolic disease in 20%, total parenteral nutrition induced cholestasis in 16%, extrahepatic biliary atresia in 14%, genetic disease in 10%, neonatal lupus in 2%, congenital syphilis in 2%, and choledochal cyst in 2% of the patients. The patient with progressive familial intrahepatic cholestasis had novel heterozygous mutations of ABCB11 c.11C>G (p.Ser4*) and c.1543A>G (p.Asn515Asp). The patient with benign recurrent intrahepatic cholestasis had homozygous mutations of ABCB11 c.1331T>C (p.Val444Ala) and heterozygous, c.3084A>G (p.Ala1028Ala). Genetic confirmation of ABCB11 spectrum liver disorder led to early liver transplantation in the progressive familial intrahepatic cholestasis patient. In addition, the atypically severe benign recurrent intrahepatic cholestasis patient was able to avoid unnecessary liver transplantation after genetic analysis. ABCB11 spectrum liver disorders can be clinically indistinguishable as they share similar characteristics related to acute episodes. A comprehensive genetic analysis will facilitate optimal diagnosis and treatment.
Synthesis of Tethered Polystyrene-block-Poly(methyl methacrylate) Monolayer on a Silicate Substrate by Sequential Carbocationic Polymerization and Atom Transfer Radical Polymerization (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSynthesis of Tethered Polystyrene-block-Poly(methyl methacrylate) Monolayer on a Silicate Substrate by Sequential Carbocationic Polymerization and Atom Transfer Radical PolymerizationBin Zhao and William J. BrittainView Author Information Department of Polymer Science The University of Akron Akron, Ohio 44325-3909 Cite this: J. Am. Chem. Soc. 1999, 121, 14, 3557–3558Publication Date (Web):March 25, 1999Publication History Received28 December 1998Published online25 March 1999Published inissue 1 April 1999https://pubs.acs.org/doi/10.1021/ja984428yhttps://doi.org/10.1021/ja984428yrapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views2325Altmetric-Citations208LEARN 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 SUBJECTS:Copolymers,Polymerization,Porous materials,Radical polymerization,Silicon Get e-Alerts
Heterocyclensynthesen mit MF/Al2O3-Basensystemen: 2-Arylbenzofurane and 2,3-Diarylisochinolin-1(2H)-one (1995)

Synthesis of Heterocycles with MF/Al 2 O 3 Base-Systems: 2-Arylbenzofuranes and 2,3-Diarylisoquinolin-1(2H)-ones2-Benzyloxybenzaldehydes, -acetophenones and -benzophenones substituted in the benzyl part with electron-withdrawing groups, cyclize easily to 2-arylbenzofuranes by using a standardized KF- or CsF-Al2O3 base system. An efficient one-pot synthesis for 2,3-diarylisoquinolin-1(2H)-ones is possible by reacting a variety of arene carbaldehyde anils with phthalides under the same reaction conditions.
Ingestion of Campylobacter pyloridis causes gastritis and raised fasting gastric pH. (1987)

Campylobacter pyloridis was ingested by a volunteer who had a histologically normal gastric mucosa and fasting gastric pH recordings of less than 2. Three days later he developed moderate to severe attacks of epigastric pain. On the 5th day after ingestion C. pyloridis was cultured from antral biopsies which showed histological acute gastritis. However, fundal histology and fasting gastric pH were normal. On the 8th day fasting gastric pH rose to 7.6. On day 11 C. pyloridis was cultured from both antral and fundal biopsies which showed histological gastritis. Doxycycline was taken for 28 days but infection and gastritis persisted. Bismuth subsalicylate was taken for 28 days and final biopsies, taken 1 wk after stopping therapy, were culture negative. Histology showed a minimal residual chronic gastritis. C. pyloridis can cause an acute upper gastrointestinal illness associated with histological gastritis and an increase in fasting gastric pH.
Changing the pathogenetic roadmap of liver fibrosis? Where did it start; where will it go? (2008)

The pathophysiology of liver injury has attracted the interest of experimentalists and clinicians over many centuries. With the discovery of liver-specific pericytes - formerly called fat-storing cells, Ito-cells, lipocytes, and currently designated as hepatic stellate cells (HSC) - the insight into the cellular and molecular pathobiology of liver fibrosis has evolved and the pivotal role of HSC as a precursor cell-type for extracellular matrix-producing myofibroblasts has been established. Although activation and transdifferentiation of HSC to myofibroblasts is still regarded as the pathogenetic key mechanism of fibrogenesis, recent studies point to a prominent heterogeneity of the origin of myofibroblasts. Currently, the generation of matrix-synthesizing fibroblasts by epithelial-mesenchymal transition, by influx of bone marrow-derived fibrocytes into damaged liver tissue, and by differentiation of circulating monocytes to fibroblasts after homing in the injured liver are discussed as important complementary mechanisms to enlarge the pool of (myo-)fibroblasts in the fibrosing liver. Among the molecular mediators, transforming growth factor-beta (TGF-beta) plays a central role, which is controlled by the bone-morphogenetic protein (BMP)-7, an important antagonist of TGF-beta action. The newly discovered pathways supplement the linear concept of HSC activation to myofibroblasts, point to fibrosis as a systemic response involving extrahepatic organs and reactions, add further evidence to a more or less uniform concept of organ fibrosis in general (e.g. liver, lung, kidney), and offer innovative approaches for the development of non-invasive biomarkers and antifibrotic trials.
Bioactivity of Visual Pigments with Sterically Modified Retinal Analogs (1999)

Studies of several retinal analogs and the rhodopsin pigments incorporating them, lead to further clarification of the structural requirement of the retinal chromophore in the photoactivation process of rhodopsin. The data with a pigment incorporating an acyclic retinal show that the cyclohexene moiety is not required for formation of a stable pigment, which, however, has a reduced photoactivity. Our data also show that extra methyl groups at 13- and 14-positions of 11-cis retinal reduce the rate of retinal binding, photoactivity, and stability of the pigments. These data, taken together, give rise to a clear picture about the binding environment of the retinal chromophore and how retinal interacts with and activates the protein following its photoisomerization. The opsin/11-cis retinal complex has evolved into an ideal system, which is capable of converting photoenergy into Meta-II formation with high efficiency, critical for visual transduction.
Metallodrugs in Medicinal Inorganic Chemistry (2014)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTMetallodrugs in Medicinal Inorganic ChemistryKatja Dralle Mjos and Chris Orvig*View Author Information Medicinal Inorganic Chemistry Group, Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada*E-mail: [email protected]Cite this: Chem. Rev. 2014, 114, 8, 4540–4563Publication Date (Web):January 23, 2014Publication History Received21 August 2013Published online23 January 2014Published inissue 23 April 2014https://doi.org/10.1021/cr400460sCopyright © 2014 American Chemical SocietyRIGHTS & PERMISSIONSACS AuthorChoiceArticle Views54643Altmetric-Citations837LEARN 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 (3 MB) Get e-AlertsSUBJECTS:Cancer,Cancer therapy,Ions,Metals,Pharmaceuticals Get e-Alerts