gebhart/patrepeval huggingface dataset:
HIV Excision Utilizing CRISPR/Cas9 Technology: Attacking the Proviral Quasispecies in Reservoirs to Achieve a Cure (2014)

Recently several gene-editing technologies developed are being explored for their potential utility in providing new and unique treatments for HIV. One of these technologies is the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)9 system. This system is being explored for its utility against host genes important to HIV infection, namely the HIV coreceptor CCR5, and for excision of the integrated genome from infected cells by targeting selected genes or genomic regions, especially the HIV-1 promoter or long terminal repeat (LTR). One of the major hurdles with the development of this technology for use in patients is defining the LTR sequence spectrum within the viral quasispecies present in the integrated virus and how that effects the number of guide RNAs (gRNAs) required to completely excise all proviral genomes. In this study, the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort was utilized to demonstrate that 1 the predominant sequence of the integrated proviral LTR within the PBMC compartment shows a decrease in the amount of variation per year regardless of the type of therapy; 2 predominant HIV-1 LTR sequence undergoes continued genetic change with respect to the predominant genotype in these cells for at least 6 years while on effective suppressive ART; 3 using next generation sequencing (NGS), to demonstrate that 4 of the 8 patient samples examined could have a complete gRNA regimen designed to target all known quasispecies; and 4 length of HAART therapy may reduce the number of gRNA required to eradicate provirus as shown by NGS and gRNA design for longitudinal samples of patient A0017 in the CARES cohort. Overall, these studies demonstrate the feasibility of addressing at least one of the major technological challenges of CRISPR/Cas9-mediated HIV-1 proviral genome eradication involving the effective targeting of all viral quasispecies in a given patient sample.
Identifying mRNA subsets in messenger ribonucleoprotein complexes by using cDNA arrays (2000)

Genomic array technologies provide a means for profiling global changes in gene expression under a variety of conditions. However, it has been difficult to assess whether transcriptional or posttranscriptional regulation is responsible for these changes. Additionally, fluctuations in gene expression in a single cell type within a complex tissue like a tumor may be masked by overlapping profiles of all cell types in the population. In this paper, we describe the use of cDNA arrays to identify subsets of mRNAs contained in endogenous messenger ribonucleoprotein complexes (mRNPs) that are cell type specific. We identified mRNA subsets from P19 embryonal carcinoma stem cells by using mRNA-binding proteins HuB, eIF-4E, and PABP that are known to play a role in translation. The mRNA profiles associated with each of these mRNPs were unique and represented gene clusters that differed from total cellular RNA. Additionally, the composition of mRNAs detected in HuB-mRNP complexes changed dramatically after induction of neuronal differentiation with retinoic acid. We suggest that the association of structurally related mRNAs into mRNP complexes is dynamic and may help regulate posttranscriptional events such as mRNA turnover and translation. Recovering proteins specifically associated with mRNP complexes to identify and profile endogenously clustered mRNAs should provide insight into structural and functional relationships among gene transcripts and/or their protein products. We have termed this approach to functional genomics ribonomics and suggest that it will provide a useful paradigm for organizing genomic information in a biologically relevant manner.
Design of inhibitors from the three-dimensional structure of alcohol dehydrogenase. Chemical synthesis and enzymic properties (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDesign of inhibitors from the three-dimensional structure of alcohol dehydrogenase. Chemical synthesis and enzymic propertiesCharles Freudenreich, Jean Pierre Samama, and Jean Francois BiellmannCite this: J. Am. Chem. Soc. 1984, 106, 11, 3344–3353Publication Date (Print):May 1, 1984Publication History Published online1 May 2002Published inissue 1 May 1984https://pubs.acs.org/doi/10.1021/ja00323a048https://doi.org/10.1021/ja00323a048research-articleACS PublicationsRequest reuse permissionsArticle Views1222Altmetric-Citations27LEARN 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
Shk1, a homolog of the Saccharomyces cerevisiae Ste20 and mammalian p65PAK protein kinases, is a component of a Ras/Cdc42 signaling module in the fission yeast Schizosaccharomyces pombe. (1995)

We describe a protein kinase, Shk1, from the fission yeast Schizosaccharomyces pombe, which is structurally related to the Saccharomyces cerevisiae Ste20 and mammalian p65PAK protein kinases. We provide genetic evidence for physical and functional interaction between Shk1 and the Cdc42 GTP-binding protein required for normal cell morphology and mating in S. pombe. We further show that expression of the STE20 gene complements the shk1 null mutation and that Shk1 is capable of signaling to the pheromone-responsive mitogen-activated protein kinase cascade in S. cerevisiae. Our results lead us to propose that signaling modules composed of small GTP-binding proteins and protein kinases related to Shk1, Ste20, and p65PAK, are highly conserved in evolution and participate in both cytoskeletal functions and mitogen-activated protein kinase signaling pathways.
Oat–maize chromosome addition lines: A new system for mapping the maize genome (1997)

Novel plants with individual maize chromosomes added to a complete oat genome have been recovered via embryo rescue from oat (Avena sativa L., 2n = 6x = 42) x maize (Zea mays L., 2n = 20) crosses. An oat-maize disomic addition line possessing 21 pairs of oat chromosomes and one maize chromosome 9 pair was used to construct a cosmid library. A multiprobe (mixture of labeled fragments used as a probe) of highly repetitive maize-specific sequences was used to selectively isolate cosmid clones containing maize genomic DNA. Hybridization of individual maize cosmid clones or their subcloned fragments to maize and oat genomic DNA revealed that most high, middle, or low copy number DNA sequences are maize-specific. Such DNA markers allow the identification of maize genomic DNA in an oat genomic background. Chimeric cosmid clones were not found; apparently, significant exchanges of genetic material had not occurred between the maize-addition chromosome and the oat genome in these novel plants or in the cloning process. About 95% of clones selected at random from a maize genomic cosmid library could be detected by the multiprobe. The ability to selectively detect maize sequences in an oat background enables us to consider oat as a host for the cloning of specific maize chromosomes or maize chromosome segments. Introgressing maize chromosome segments into the oat genome via irradiation should allow the construction of a library of overlapping fragments for each maize chromosome to be used for developing a physical map of the maize genome.
Making money by generating power from non-conventional source (2007)

In the hope to make money by generating power from nonconventional sources, IFSL Limited, which works towards executing renewable energy projects, is now set to increase profitability from the sale proceeds accruing from carbon credits, the new buzzword in business. Most of the non polluting industries are going to benefit from this new revenue stream. Sales of these carbon credits will take place under the Clean Development Mechanism (CDM) of the Kyoto Protocol. Carbon credits are a new form of money exchange intended to reduce pollution. Renewable energy projects are eligible for getting benefits from emission trading under the CDM. IFSL is a beneficiary under this programme and is eligible for selling carbon credits in the international market. The paper traces the evolution of IFSL Limited. At the outset we explore the background of IFSL, the motivation for the promoters to set up the organization and how it has grown. As a part of the study, we examine the different projects undertaken and their progress. The paper examines the financial performance and future stock predications. The paper also discusses the possibilities to generate power from municipality waste.
Fluorescent Decay Times of Excitons Bound to Isoelectronic Traps in GaP and ZnTe (1967)

An investigation of the radiative decay times of bound excitons in GaP: N, GaP: Bi, and ZnTe: O is reported. New experimental techniques involving the use of a pulsed Van de Graaff generator for exciting the samples in liquid refrigerants are described. In each material, decay to the ground state of the electronic complex can occur through either an allowed ($A$) or forbidden ($B$) transition. A study of the temperature dependence of the kinetics permits the individual decay components, ${\ensuremath{\tau}}_{A}$ and ${\ensuremath{\tau}}_{B}$, to be separated. For each material, these quantities are used to calculate the oscillator strengths of the transitions, and a value for $\frac{N}{{\ensuremath{\alpha}}_{0}(A)}$, where $N$ is the density of impurities, and ${\ensuremath{\alpha}}_{0}(A)$ the value of the absorption coefficient at the $A$ line. Agreement is found with independent measurements of $\frac{N}{{\ensuremath{\alpha}}_{0}(A)}$ in GaP: N and GaP: Bi. The values of $\frac{{\ensuremath{\tau}}_{B}}{{\ensuremath{\tau}}_{A}}$ substantiate a proposed classification of the impurities into isoelectronic donors and acceptors. In ZnTe: O, a mechanism is proposed to account for the approximately constant fluorescent efficiency and anomalous increase in decay time with increasing temperature in the range 30 to 300\ifmmode^\circ\else\textdegree\fi{}K. In each material, the luminescence quenches at higher temperatures, and the simultaneous decrease in decay time enables activation energies and capture cross sections to be determined.
Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. (1994)

The current modalities for the repair of defects of the articular cartilage have many disadvantages. The transplantation of progenitor cells that will form cartilage and bone offers a possible alternative to these methods. As demonstrated in this report, autologous, bone-marrow-derived, osteochondral progenitor cells can be isolated and grown in vitro without the loss of their capacity to differentiate into cartilage or bone. Sufficient autologous cells can be generated to initiate the repair of articular cartilage and the reformation of subchondral bone. The repair tissues appear to undergo the same developmental transitions that originally led to the formation of articular tissue in the embryo.(ABSTRACT TRUNCATED AT 400 WORDS)
SoK: Eternal War in Memory (2013)

Memory corruption bugs in software written in low-level languages like C or C++ are one of the oldest problems in computer security. The lack of safety in these languages allows attackers to alter the program's behavior or take full control over it by hijacking its control flow. This problem has existed for more than 30 years and a vast number of potential solutions have been proposed, yet memory corruption attacks continue to pose a serious threat. Real world exploits show that all currently deployed protections can be defeated. This paper sheds light on the primary reasons for this by describing attacks that succeed on today's systems. We systematize the current knowledge about various protection techniques by setting up a general model for memory corruption attacks. Using this model we show what policies can stop which attacks. The model identifies weaknesses of currently deployed techniques, as well as other proposed protections enforcing stricter policies. We analyze the reasons why protection mechanisms implementing stricter polices are not deployed. To achieve wide adoption, protection mechanisms must support a multitude of features and must satisfy a host of requirements. Especially important is performance, as experience shows that only solutions whose overhead is in reasonable bounds get deployed. A comparison of different enforceable policies helps designers of new protection mechanisms in finding the balance between effectiveness (security) and efficiency. We identify some open research problems, and provide suggestions on improving the adoption of newer techniques.
Mammalian Hibernation: Cellular and Molecular Responses to Depressed Metabolism and Low Temperature (2003)

Mammalian hibernators undergo a remarkable phenotypic switch that involves profound changes in physiology, morphology, and behavior in response to periods of unfavorable environmental conditions. The ability to hibernate is found throughout the class Mammalia and appears to involve differential expression of genes common to all mammals, rather than the induction of novel gene products unique to the hibernating state. The hibernation season is characterized by extended bouts of torpor, during which minimal body temperature (Tb) can fall as low as -2.9 degrees C and metabolism can be reduced to 1% of euthermic rates. Many global biochemical and physiological processes exploit low temperatures to lower reaction rates but retain the ability to resume full activity upon rewarming. Other critical functions must continue at physiologically relevant levels during torpor and be precisely regulated even at Tb values near 0 degrees C. Research using new tools of molecular and cellular biology is beginning to reveal how hibernators survive repeated cycles of torpor and arousal during the hibernation season. Comprehensive approaches that exploit advances in genomic and proteomic technologies are needed to further define the differentially expressed genes that distinguish the summer euthermic from winter hibernating states. Detailed understanding of hibernation from the molecular to organismal levels should enable the translation of this information to the development of a variety of hypothermic and hypometabolic strategies to improve outcomes for human and animal health.
Tapprints (2012)

This paper shows that the location of screen taps on modern smartphones and tablets can be identified from accelerometer and gyroscope readings. Our findings have serious implications, as we demonstrate that an attacker can launch a background process on commodity smartphones and tablets, and silently monitor the user's inputs, such as keyboard presses and icon taps. While precise tap detection is nontrivial, requiring machine learning algorithms to identify fingerprints of closely spaced keys, sensitive sensors on modern devices aid the process. We present TapPrints, a framework for inferring the location of taps on mobile device touch-screens using motion sensor data combined with machine learning analysis. By running tests on two different off-the-shelf smartphones and a tablet computer we show that identifying tap locations on the screen and inferring English letters could be done with up to 90% and 80% accuracy, respectively. By optimizing the core tap detection capability with additional information, such as contextual priors, we are able to further magnify the core threat.
Monocyte Dependent Regulation of Autoimmune Inflammation (2009)

In chronic inflammation, across a number of quite different pathological conditions, monocytes accumulate. In autoimmune disease, these cells are widely recognised to play an inflammatory and tissue destructive role. But these cells also inhibit T cell proliferation by a range of different mechanisms that are accompanied by the depletion of specific amino acids in the local microenvironment and the downregulation of the T cell receptor zeta chain. This occurs within the pro-inflammatory environment and in the presence of Th1 (IFNgamma) and Th17 (IL-17) cytokines. In tumours, related cells are part of a population called myeloid-derived suppressor cells (MDSC) and they are associated with immunosuppression. Their depletion can lead to clinical improvement. In organ specific autoimmune disease, where such cells can be found in the spleen and in target organs, recent evidence indicates that they may play a role in limiting the T cell response to autoantigens in the target tissue. This occurs by a targeted disruption of T cell division. In this review we discuss evidence for the presence on MDSC in murine and human autoimmune disease and the mechanisms by which such cells inhibit T cell proliferation.
Structure‐Based Design, Synthesis and Biochemical Testing of Novel and Potent Smac Peptido‐Mimetics. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Miniaturization of capillary electrophoresis systems using micromachining techniques (1998)

Capillary electrophoresis in its different modes of operation is demonstrated to be a separation technique suitable to be integrated into a planar microdevice. The use of micromachining techniques allows complex capillary geometries to be formed, providing good sensitivity and high separation efficiency when optical detection such as laser-induced fluorescence is coupled. Several research groups and companies have focused their research aims in the development and improvement of microstructures using different substrates and configurations. Although in the last 5 years an important number of publications have been reported in this area, several devices are still in a perfectioning phase. Great promises are offered for the rapid and efficient processing of various types of samples, with fundamental application in biological and clinical assays. © 1998 John Wiley & Sons, Inc. J Micro Sep 10: 339–355, 1998
Discovery, Structure−Activity Relationships, Pharmacokinetics, and Efficacy of Glucokinase Activator (2R)-3-Cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide (RO0281675) (2010)

Glucokinase (GK) is a glucose sensor that couples glucose metabolism to insulin release. The important role of GK in maintaining glucose homeostasis is illustrated in patients with GK mutations. In this publication, identification of the hit molecule 1 and its SAR development, which led to the discovery of potent allosteric GK activators 9a and 21a, is described. Compound 21a (RO0281675) was used to validate the clinical relevance of targeting GK to treat type 2 diabetes.
Murine monoclonal antibodies to colon-specific antigen p. (1990)

A previous report described the production of monoclonal antibodies Mu-1, -2, -3, and -4 against colon-specific antigen p. We now report the tissue distribution of the reactive epitopes. Each of the monoclonal antibodies was reactive with epitopes shared by the entire length of the intestine, with Mu-2 and Mu-3 determinants being present in the stomach as well. Mu-1 and Mu-4 appeared to have a more restricted distribution than did Mu-2 and Mu-3, which were present in several nongastrointestinal tissues. Unfortunately, these MAbs were not ideal for in vivo use against colorectal carcinoma. Mu-1 was not present in neoplastic colon tissue, Mu-2 and Mu-4 were reactive with granulocytes, and Mu-3 was reactive with kidney tubules and connective tissue. An additional fusion was performed from which Mu-9 was selected for further study. Among normal adult tissues this monoclonal antibody gave reactivity restricted to the intestines. The stomach and all nonintestinal tissues were negative by immunoperoxidase. Among colon tumors 60% were positive for the Mu-9 epitope. The data suggest Mu-9 may be a good candidate for in vivo targeting of diagnostic and therapeutic agents to colon cancer.
Purification and properties of human platelet heparitinase. (1982)

An endoglycosidase which cleaves heparin and heparan sulfate was isolated from outdated human platelets by freeze-thaw solubilization, heparin-Sepharose chromatography, DEAE-cellulose chromatography, hydroxylapatite chromatography, octyl-agarose chromatography, concanavalin A-Sepharose chromatography, and Sephacryl S-200 gel filtration. The overall extent of purification of the platelet heparitinase is about 240,000-fold and the overall yield of the enzyme is about 5.6% as compared to the initial freeze-thaw solubilization preparation. The final product is physically homogeneous as judged by disc gel electrophoresis at acidic pH as well as gel filtration chromatography and exhibits an apparent molecular weight of approximately 134,000. Furthermore, our results indicate that the above enzyme is present within platelet lysosomes. The biologic potency of the endoglycosidase was examined as a function of pH. The data show that the platelet heparitinase is maximally active from pH 5.5 to pH 7.5. However, the enzyme possesses minimal ability to cleave heparin at pH less than 4.0 or greater than 9.0. The substrate specificity of the platelet endoglycosidase was determined by identifying susceptible linkages within the heparin molecule that can be cleaved by the above component. Our studies indicate that this enzyme is only able to hydrolyze glucuronsylglucosamine linkages. Furthermore, investigation of the structure of the disaccharide which lies on the nonreducing end of the cleaved glucuronic acid residue suggests that N-sulfation of the glucosamine moiety or ester sulfation of the adjacent iduronic acid groups are not essential for bond scission.
Comparison of PF4/Heparin ELISA Assay With the14C-Serotonin Release Assay in the Diagnosis of Heparin-induced Thrombocytopenia (1995)

The diagnosis of heparin-induced thrombocytopenia (HIT) may be affirmed by demonstrating heparin-dependent anti-platelet antibodies using the 14C-serotonin release assay (SRA). In this study, results of the SRA was compared with the recently described platelet factor 4 (PF4)/heparin enzyme-linked immunosorbent assay (ELISA). Compared with the SRA, the sensitivity and specificity of a PF4/heparin ELISA was 87% and 92%, respectively, using an assay developed in our laboratory; and 90% and 98%, respectively, using a commercially developed kit (Diagnostica Stago, Asnieres, France). However, antibodies to PF4/heparin were also detected in up to 8% of patients whose plasma was negative by SRA, and 23% of patients receiving heparin who were not thrombocytopenic. These data indicate that results obtained with the PF4/heparin ELISA and the SRA are generally in accord in patients with a clinical diagnosis of HIT. However, discrepant results occur in approximately 20% of cases because of the greater sensitivity of ELISA and the possible involvement of other heparin-binding proteins. The fact that each assay contributes independent information in some cases must be considered in the sequence of test performance and in providing consultation to the practicing hematologist.