gebhart/patrepeval huggingface dataset:
Structure of the protease from simian immunodeficiency virus: Complex with an irreversible nonpeptide inhibitor (1993)

A variant of the simian immunodeficiency virus protease (SIV PR), covalently bound to the inhibitor 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP), was crystallized. The structure of the inhibited complex was determined by X-ray crystallography to a resolution of 2.4 A and refined to an R factor of 19%. The variant, SIV PR S4H, was shown to diminish the rate of autolysis by at least 4-fold without affecting enzymatic parameters. The overall root mean square (rms) deviation of the alpha-carbons from the structure of HIV-1PR complexed with a peptidomimetic inhibitor (7HVP) was 1.16 A. The major differences are concentrated in three surface loops with rms differences between 1.2 and 2.1 A. For 60% of the molecule the rms deviation was only 0.6 A. The structure reveals one molecule of EPNP bound per protease dimer, a stoichiometry confirmed by mass spectral analysis. The epoxide moiety forms a covalent bond with either of the active site aspartic acids of the dimer, and the phenyl moiety occupies the P1 binding site. The EPNP nitro group interacts with Arg 8. This structure suggests a starting template for the design of nonpeptide-based irreversible inhibitors of the SIV and related HIV-1 and HIV-2 PRs.
AON-Mediated Exon Skipping for Duchenne Muscular Dystrophy (2012)

Duchenne muscular dystrophy (DMD) is a genetic, X-chromosome recessive, severe and progressive muscle wasting disorder, affecting around 1 in 3500 newborn boys. The onset of the disease is in early childhood and, nowadays, most children are diagnosed before the age of 5. The first signs of muscular weakness become apparent around the age of 2 or 3 years. In most patients the age at which the child starts to walk is delayed (retarded motor development). The children have less endurance and difficulties with running and climbing stairs (Moser, 1984). Gower’s sign is a reflection of the weakness of the muscles of the lower extremities (knee and hip extensors): the child helps himself to get upright from sitting position by using his upper extremities: first by rising to stand on his arms and knees, and then “walking” his hands up his legs to stand upright (Gowers, 1895). Muscle wasting is often symmetrical, however not all muscles are affected to the same extent. A prominent feature of the disease is enlargement of the calve muscle, caused by replacement of muscle fibres by connective and adipose tissue. Furthermore, the pelvic girdle, trunk and abdomen are severely affected and to a lesser extent the shoulder girdle and proximal muscles of the upper extremities. Progressive weakness and contractures of the leg muscles lead to wheelchair-dependency around the age of 10. Thereafter the muscle contractions increase rapidly leading to spinal deformities and scoliosis, often with an asymmetric distribution pattern. Involvement of the intercostal muscles and distortion of the thorax lead to respiratory failure and patients often require assisted ventilation in the mid to late teens. Thereafter dilated cardiomyopathy becomes apparent and most patients die before the age of 30. Another common feature is mental retardation (IQ less than 70) in around 20-30% of the patients (Emery, 2002).
Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics (2002)

HIV entry inhibitors include coreceptor antagonists and the fusion inhibitor T-20. T-20 binds the first helical region (HR1) in the gp41 subunit of the viral envelope (Env) protein and prevents conformational changes required for membrane fusion. HR1 appears to become accessible to T-20 after Env binds CD4, whereas coreceptor binding is thought to induce the final conformational changes that lead to membrane fusion. Thus, T-20 binds to a structural intermediate of the fusion process. Primary viruses exhibit considerable variability in T-20 sensitivity, and determinants outside of HR1 can affect sensitivity by unknown mechanisms. We studied chimeric Env proteins containing different V3 loop sequences and found that gp120coreceptor affinity correlated with T-20 and coreceptor antagonist sensitivity, with greater affinity resulting in increased resistance to both classes of entry inhibitors. Enhanced affinity resulted in more rapid fusion kinetics, reducing the time during which Env is sensitive to T-20. Reduced coreceptor expression levels also delayed fusion kinetics and enhanced virus sensitivity to T-20, whereas increased coreceptor levels had the opposite effect. A single amino acid change (K421D) in the bridging sheet region of the primary virus strain YU2 reduced affinity for CCR5 and increased T-20 sensitivity by about 30-fold. Thus, mutations in Env that affect receptor engagement and membrane fusion rates can alter entry inhibitor sensitivity. Because coreceptor expression levels are typically limiting in vivo, individuals who express lower coreceptor levels may respond more favorably to entry inhibitors such as T-20, whose effectiveness we show depends in part on fusion kinetics.
Antibody Elution Method for Multiple Immunohistochemistry on Primary Antibodies Raised in the Same Species and of the Same Subtype (2009)

Double or multiple antigen labeling in IHC classically relies on the existence of primary antibodies raised in different species or of different IgG isotypes to ensure the specific labeling with the secondary detection systems. However, suitable pairs of primary antibodies are not always available or the best choice (e.g., as diagnostic tools). During the last few years, several methods have been proposed to overcome this, but none of them offers the flexibility needed for reliable double or multiple enzymatic or fluorescent IHC. We present here a procedure that elutes the antibodies after a first round of immunolabeling, which, in combination with precipitation-based detection systems, allows multiple IHC rounds even for primary antibodies raised in the same species and IgG isotype. Compared with other proposed methods, this procedure ensures a reliable enzymatic or fluorescent staining without cross-reactivity and without loss of tissue antigenicity, thus offering a flexible tool for colocalization studies and pathological diagnosis. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.
The Pib gene for rice blast resistance belongs to the nucleotide binding and leucine‐rich repeat class of plant disease resistance genes (1999)

Rice blast, caused by the fungal pathogen Magnaporthe grisea, is one of the most serious diseases of rice. Here we describe the isolation and characterization of Pib, one of the rice blast resistance genes. The Pib gene was isolated by a map-based cloning strategy. The deduced amino acid sequence of the Pib gene product contains a nucleotide binding site (NBS) and leucine-rich repeats (LRRs); thus, Pib is a member of the NBS-LRR class of plant disease resistance genes. Interestingly, a duplication of the kinase 1a, 2 and 3a motifs of the NBS region was found in the N-terminal half of the Pib protein. In addition, eight cysteine residues are clustered in the middle of the LRRs, a feature which has not been reported for other R genes. Pib gene expression was induced upon altered environmental conditions, such as altered temperatures and darkness.
Table extraction using conditional random fields (2003)

The ability to find tables and extract information from them is a necessary component of data mining, question answering, and other information retrieval tasks. Documents often contain tables in order to communicate densely packed, multi-dimensional information. Tables do this by employing layout patterns to efficiently indicate fields and records in two-dimensional form.Their rich combination of formatting and content present difficulties for traditional language modeling techniques, however. This paper presents the use of conditional random fields (CRFs) for table extraction, and compares them with hidden Markov models (HMMs). Unlike HMMs, CRFs support the use of many rich and overlapping layout and language features, and as a result, they perform significantly better. We show experimental results on plain-text government statistical reports in which tables are located with 92% F1, and their constituent lines are classified into 12 table-related categories with 94% accuracy. We also discuss future work on undirected graphical models for segmenting columns, finding cells, and classifying them as data cells or label cells.
Pore‐forming and haemolytic properties of the Gardnerella vaginalis cytoiysin (1993)

The pleomorphic bacterium Gardnerella vaginalis releases in the culture broth a haemolytic exotoxin (Gvh) which is probably a virulence determinant of this unique bacterium, implicated in gynaecological and urological disorders. This 59 kDa cytolysin was purified to homogeneity in just one chromatographic step directly from the culture supernatant, a final specific activity up to 1.9 x 10(6) HU mg-1 being obtained. The toxin-induced lesion on human erythrocytes results from the formation of a pore whose radius is approximately 2.4 nm. The damage is inhibited by osmotic protectants and shows a sigmoidal dose-response profile suggesting an aggregation process of haemolysin molecules on the target membrane to create the functional lesion. The extent and the kinetics of haemolysis are strongly dependent on temperature and an activation energy of 64.0 kJ mol-1 has been derived. Lipid membranes can be very efficient inhibitors of Gvh-haemolysis, being able to bind the toxin quite avidly. The inhibitory effect requires the presence of cholesterol and it is stronger when cholesterol is mixed with negatively charged phospholipids rather than with zwitterionic phospholipids, suggesting that a negative surface potential increases the affinity of the toxin for the lipid bilayer. The functional properties of Gvh have been compared with those of Clostridium perfringens thetatoxin (PFO) and Escherichia coli haemolysin (HlyA), which are representative of widespread haemolysins produced by Gram-positive and Gram-negative bacteria, respectively. The toxin shares several features with the family of the so-called 'sulphydryl-activated' cytolysins produced by Gram-positive bacteria, although Gvh does not truly belong to this family, being deactivated by beta-mercaptoethanol and being antigenically distinct from them. We report here for the first time the detection in the vaginal fluid of infected women of a specific IgA response against the toxin.
Low-Level Laser Irradiation Promotes Proliferation and Differentiation of Human Osteoblasts in Vitro (2005)

We conclude that LLLT promotes proliferation and maturation of human osteoblasts in vitro. These results may have clinical implications.
Lapatinib-Associated Toxicity and Practical Management Recommendations (2007)

Lapatinib is an oral receptor tyrosine kinase inhibitor, inhibiting both the ErbB-1 and ErbB-2 receptors. Lapatinib has been shown to have activity in ErbB-2-overexpressing breast cancer in several phase II and III clinical trials. Specifically, lapatinib is effective in patients with metastatic breast cancer, with inflammatory breast cancer, and possibly, with brain metastases. An ongoing clinical trial and another anticipated clinical trial will investigate lapatinib as adjuvant treatment in early-stage disease. Lapatinib has specific toxicities, the most common being diarrhea and rash. Cardiac toxicity is rarely seen with lapatinib. This paper reviews lapatinib-associated toxicities and provides practical management recommendations based on available data.
Purification and composition of protein antifreezes with high cysteine contents from larvae of the beetle, Tenebrio molitor (1982)

Abstract Two antifreeze proteins with thermal hysteresis activity (they depress the freezing point of aqueous solutions by a noncolligative mechanism well below the melting point) were purified from cold‐acclimated larvae of the beetle, Tenebrio molitor . Both proteins have unusual amino acid compositions consisting of high levels of cysteine (15.4 and 28.0 mol%).
Genetic engineering and production of modified fatty acids by the non-conventional oleaginous yeast Trichosporon oleaginosus ATCC 20509 (2015)

Establishing genetic engineering tools for sustainable production of tailor made fatty acids in the non-conventional, oleaginous yeast<italic>Trichosporon oleaginosus</italic>.
Biomimetic Macrocycle-Forming Diels−Alder Reaction of an Iminium Dienophile:  Synthetic Studies Directed Toward Gymnodimine (2005)

The macrocyclic core of gymnodimine has been constructed via an intramolecular Diels-Alder reaction of an alpha,beta-unsaturated iminium dienophile in water. The cycloaddition furnished a single exo-product, along with two endo-products. Through X-ray analysis of a suitable derivative, the stereochemistry of the exo-product was established, thereby demonstrating that its stereochemistry matches that of gymnodimine. In contrast, macrocyclization of an analogous alpha,beta-unsaturated ketone dienophile gave only undesired endo-products. Interestingly, the imine dienophile shows remarkable stability in water. [reaction: see text]
CRUSH: Controlled, Scalable, Decentralized Placement of Replicated Data (2006)

Emerging large-scale distributed storage systems are faced with the task of distributing petabytes of data among tens or hundreds of thousands of storage devices. Such systems must evenly distribute data and workload to efficiently utilize available resources and maximize system performance, while facilitating system growth and managing hardware failures. We have developed CRUSH, a scalable pseudorandom data distribution function designed for distributed object-based storage systems that efficiently maps data objects to storage devices without relying on a central directory. Because large systems are inherently dynamic, CRUSH is designed to facilitate the addition and removal of storage while minimizing unnecessary data movement. The algorithm accommodates a wide variety of data replication and reliability mechanisms and distributes data in terms of user-defined policies that enforce separation of replicas across failure domains
Structural Basis for Sugar Translocation Through Maltoporin Channels at 3.1 Å Resolution (1995)

Trimeric maltoporin (LamB protein) facilitates the diffusion of maltodextrins across the outer membrane of Gram-negative bacteria. The crystal structure of maltoporin from Escherichia coli, determined to a resolution of 3.1 angstroms, reveals an 18-stranded, antiparallel beta-barrel that forms the framework of the channel. Three inwardly folded loops contribute to a constriction about halfway through the channel. Six contingent aromatic residues line the channel and form a path from the vestibule to the periplasmic outlet. Soaking of a crystal with maltotriose revealed binding of the sugar to this hydrophobic track across the constriction, which suggests that maltose and linear oligosaccharides may be translocated across the membrane by guided diffusion along this path.
[Establishment of a transgenic cell model for preliminary screening of chemopreventive agents]. (2007)

To develop a GFP transgenic cell model under the transcriptional control of TK promoter adjacent to which ARE enhancer was inserted. Synthetic oligonucleotide ARE motif was annealed and purified then inserted into pTK-GFP to construct the vector of pARE-TK-GFP. The TK and ARE-TK fragments were amplified by PCR and cloned into pEGFP-N1 to reconstruct eukaryotic expression vectors of pTK-GFP/Neo and pARE-TK-GFP/Neo. They were transfected into HepG2 cells and clones resistant G418 were isolated. PDTC and Lentinan were used to induce the cell levels of GFP and the fluorescence was measured using a fluorescence plate reader. The results showed that the induced level of GFP is significantly increased and have dose-dependeny in a certain range. This findings indicated that such a cell model offered a potential platform for preliminary screening of all kinds of natural or synthetic chemopreventive agents.
Pen‐on‐Paper Flexible Electronics (2011)

Pen-on-paper flexible electronics are fabricated using a conductive silver ink-filled rollerball pen. This approach provides a low-cost, portable route for fabricating conductive text, electronic art, interconnects for light emitting diode (LED) arrays, and three-dimensional (3D) antennas on paper. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Helper T-cell antigenic site identification in the acquired immunodeficiency syndrome virus gp120 envelope protein and induction of immunity in mice to the native protein using a 16-residue synthetic peptide. (1987)

Much effort has been devoted to the analysis of antibodies to acquired immunodeficiency syndrome virus antigens, but no studies, to our knowledge, have defined antigenic sites of this virus that elicit T-cell immunity, even though such immunity is important in protection against many other viruses. T cells tend to recognize only a limited number of discrete sites on a protein antigen. Analysis of immunodominant helper T-cell sites has suggested that such sites tend to form amphipathic helices. An algorithm based on this model was used to identify two candidate T-cell sites, env T1 and env T2, in the envelope protein of human T-lymphotropic virus type IIIB that were conserved in other human immunodeficiency virus isolates. Corresponding peptides were synthesized and studied in genetically defined inbred and F1 mice for induction of lymph node proliferation. After immunization with a 426-residue recombinant envelope protein fragment, significant responses to native gp 120, as well as to each peptide, were observed in both F1 combinations studied. Conversely, immunization with env T1 peptide induced T-cell immunity to the native gp 120 envelope protein. The genetics of the response to env T1 peptide were further examined and revealed a significant response in three of four independent major histocompatibility haplotypes tested, an indication of high frequency responsiveness in the population. Identification of helper T-cell sites should facilitate development of a highly immunogenic, carrier-free vaccine that induces T-cell and B-cell immunity. The ability to elicit T-cell immunity to the native viral protein by immunization with a 16-residue peptide suggests that such sites represent potentially important components of an effective vaccine for acquired immunodeficiency syndrome.
The Cannabinoid Receptor Agonist WIN 55212-2 Inhibits Neurogenic Inflammations in Airway Tissues (2005)

We examined the effects of a cannabinoid receptor agonist, (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-merpholino)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl)methanone (WIN 55212-2), on various respiratory reactions induced by the activation of capsaicin-sensitive afferent sensory nerves (C-fibers). WIN 55212-2 significantly inhibited capsaicin-induced guinea pig bronchoconstriction, but not the neurokinin A-induced reaction. Intravenous injection of WIN 55212-2 also blocked cigarette smoke-induced rat tracheal plasma extravasation. However, substance P-induced rat tracheal plasma extravasation was not affected by the administration of WIN 55212-2. A cannabinoid CB(2) receptor antagonist, {N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide} (SR 144528) reduced the inhibitory effects of WIN 55212-2, but not a cannabinoid CB(1) antagonist, [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride] (SR 141716A). A Maxi-K(+) channel opener, 1-(2'-hydroxy-5'-trifluoromethylphenyl)-5-trifluoromethyl-2(3H)benzimidazolone (NS 1619), specifically inhibited capsaicin-induced guinea pig bronchoconstriction and cigarette smoke-induced rat tracheal plasma extravasation. These findings suggest that WIN 55212-2 inhibits the activation of C-fibers via cannabinoid CB(2) receptors and Maxi-K(+) channels and reduces airway neurogenic inflammatory reactions in vivo.
Quantitative analyses of biochemical kinetic resolution of enantiomers. 2. Enzyme-catalyzed esterifications in water-organic solvent biphasic systems (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTQuantitative analyses of biochemical kinetic resolution of enantiomers. 2. Enzyme-catalyzed esterifications in water-organic solvent biphasic systemsChing Shih Chen, Shih Hsiung Wu, Gary Girdaukas, and Charles J. SihCite this: J. Am. Chem. Soc. 1987, 109, 9, 2812–2817Publication Date (Print):April 1, 1987Publication History Published online1 May 2002Published inissue 1 April 1987https://doi.org/10.1021/ja00243a040RIGHTS & PERMISSIONSArticle Views1164Altmetric-Citations285LEARN 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 (648 KB) Get e-Alerts Get e-Alerts
In vitro optimization of antisense oligodeoxynucleotide design: an example using the connexin gene family. (2006)

The completion of the human and mouse genomes has identified at least 20 connexin isomers in this family of intercellular channel proteins. However, there are no specific gap junction blockers or channel-blocking mimetic peptides available for the study of specific connexins. We designed antisense oligodeoxynucleotides that functionally reduce targeted connexin protein expression and can be used to reveal the biological function of individual connexins in vivo. Connexin mRNA was firstly exposed in vitro to deoxyribozymes complementing the sense coding sequence. Those that cleaved the target connexin mRNA in defined regions were used as the basis to design oligodeoxynucleotides to the accessible sites, thus taking into account tertiary mRNA configurations rather than relying on computed predictions. Antisense oligodeoxynucleotides designed to bind to accessible mRNA sites selectively reduced connexin26 and -43 mRNA expression in a corneal epithelium ex vivo model. Connexin43 protein levels were reduced correlating with the knockdown in mRNA and the protein's rapid turnover; protein levels of connexin26 did not alter, supporting lower turnover rates reported for that protein. We show, for the first time, an inexpensive and empirical approach to the preparation of specific and functional antisense oligodeoxynucleotides against known gene targets in the post-genomic era.