gebhart/patrepeval huggingface dataset:
Computer design of obligate heterodimer meganucleases allows efficient cutting of custom DNA sequences (2008)

Meganucleases cut long (>12 bp) unique sequences in genomes and can be used to induce targeted genome engineering by homologous recombination in the vicinity of their cleavage site. However, the use of natural meganucleases is limited by the repertoire of their target sequences, and considerable efforts have been made to engineer redesigned meganucleases cleaving chosen targets. Homodimeric meganucleases such as I-CreI have provided a scaffold, but can only be modified to recognize new quasi-palindromic DNA sequences, limiting their general applicability. Other groups have used dimer-interface redesign and peptide linkage to control heterodimerization between related meganucleases such as I-DmoI and I-CreI, but until now there has been no application of this aimed specifically at the scaffolds from existing combinatorial libraries of I-CreI. Here, we show that engineering meganucleases to form obligate heterodimers results in functional endonucleases that cut non-palindromic sequences. The protein design algorithm (FoldX v2.7) was used to design specific heterodimer interfaces between two meganuclease monomers, which were themselves engineered to recognize different DNA sequences. The new monomers favour functional heterodimer formation and prevent homodimer site recognition. This design massively increases the potential repertoire of DNA sequences that can be specifically targeted by designed I-CreI meganucleases and opens the way to safer targeted genome engineering.
Material content of the Universe: introductory survey (1987)

Matter in the Universe can be detected either by the radiation it emits or by its gravitational influence. There is a strong suggestion that the Universe contains substantial hidden matter, mass without corresponding light. There are also arguments from elementary particle physics that the Universe should have closure density, which would also imply hidden mass. Observations of the chemical composition of the Universe interpreted in terms of the hot Big Bang cosmological theory suggest that this hidden matter cannot all be of baryonic form but must consist of weakly interacting elementary particles. A combination of observations and theoretical ideas about the origin of large-scale structure may demand that these particles are of a type which is not yet definitely known to exist.
Ingested Listeria monocytogenes survive and multiply in protozoa (1990)

Listeria monocytogenes cells are ingested by protozoa such as Acanthamoeba sp. or Tetrahymena pyriformis. However, they are not killed, but survive within the protozoa and may multiply intracellularly. The protozoa are lysed within about 8 days, releasing viable L. monocytogenes. No co-existence was observed between L. monocytogenes and Tetrahymena. A co-culture of L. monocytogenes and Acanthamoeba sp. showed a decay of locomotive forms and release of listeria from vegetative protozoan cells whereas the bacteria were destroyed in cysts. These phenomena provide an insight into the pathogenesis of listeria infection in man and warm-blooded animals because intracellular processes occurring in protozoa after ingestion of L. monocytogenes may be similar to those observed in mammalian cells.
Antiphospholipid Antibodies and the Antiphospholipid Syndrome in Systemic Lupus Erythematosus A Prospective Analysis of 500 Consecutive Patients (1989)

Five hundred consecutive patients with systemic lupus erythematosus (SLE) were entered into a prospective study of anticardiolipin antibodies (ACLA) in their 3 major immunoglobulin isotypes and followed thereafter with repeated testing for a mean period of nearly 8 months. Manifestations of SLE that were strongly associated with ACLA included venous thrombosis (particularly when recurrent), thrombocytopenia, hemolytic anemia, recurrent fetal loss, and leg ulcers. Other manifestations found to be associated with ACLA were arterial occlusions, transverse myelitis, and pulmonary hypertension. Conversely, we found no relationship between ACLA and migraine, convulsions, transient ischemic attacks, psychoses, or avascular necrosis of bone. No relationship was found between the presence of ACLA and that of anti-DNA antibodies studied in the same serum sample. Association with ACLA grew stronger and titers became higher in patients with several of the associated manifestations. Statistical analyses revealed the existence of a syndrome, the antiphospholipid syndrome, comprising 2 or more manifestations in conjunction with ACLA titers 5 standard deviations above the mean of normal control subjects, particularly if ACLA had been positive on at least 2 occasions. We propose that such criteria could be applied to the definition of the antiphospholipid syndrome. The presence and the titers of these antibodies related to disease activity and titer decreased by treatment, particularly when they were of the IgM isotype. Patients in whom a thrombotic episode occurred during the course of the study were observed to have a coincident decrease in ACLA titers, a finding that might indicate consumption of the antibody during the event. Treatment and the resulting inactivation of disease appear to have independent effects on ACLA titers. Physicians should therefore be cautious in prescribing high doses of corticosteroids or immunosuppressants to patients with SLE solely because they have high titers of ACLA.
Protective immunity to lethal challenge of the 1918 pandemic influenza virus by vaccination (2006)

The remarkable infectivity and virulence of the 1918 influenza virus resulted in an unprecedented pandemic, raising the question of whether it is possible to develop protective immunity to this virus and whether immune evasion may have contributed to its spread. Here, we report that the highly lethal 1918 virus is susceptible to immune protection by a preventive vaccine, and we define its mechanism of action. Immunization with plasmid expression vectors encoding hemagglutinin (HA) elicited potent CD4 and CD8 cellular responses as well as neutralizing antibodies. Antibody specificity and titer were defined by a microneutralization and a pseudotype assay that could assess antibody specificity without the need for high-level biocontainment. This pseudotype inhibition assay can define evolving serotypes of influenza viruses and facilitate the development of immune sera and neutralizing monoclonal antibodies that may help contain pandemic influenza. Notably, mice vaccinated with 1918 HA plasmid DNAs showed complete protection to lethal challenge. T cell depletion had no effect on immunity, but passive transfer of purified IgG from anti-H1(1918) immunized mice provided protective immunity for naïve mice challenged with infectious 1918 virus. Thus, humoral immunity directed at the viral HA can protect against the 1918 pandemic virus.
Compact hardware realization for Hough based extraction of line segments in image sequences for vehicle guidance (1993)

Important key symbols used in many image processing applications are straight line segments of edges and contours. The real-time determination of straight line symbols in video sequences requires high computational rates which call for application-specific integrated circuits (ASICs). For a vision-based vehicle guidance system a compact image processing unit has been developed which extracts straight lines as symbols for the street boundaries. This unit consists of two specially designed ASICs for the segmentation of symbols and a general programmable microcontroller for high-level processing. The implemented pipeline of the algorithm comprises gradient operation, edge thinning line verification, and Hough transformation. Although the image processing unit was originally developed for vehicle guidance the hardware can be used for other industrial and robotic applications as well.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Combined Real-Time PCR and rpoB Gene Pyrosequencing for Rapid Identification of Mycobacterium tuberculosis and Determination of Rifampin Resistance Directly in Clinical Specimens (2010)

Our laboratory has developed a rapid, sensitive, and specific molecular approach for detection in clinical specimens, within 48 h of receipt, of both Mycobacterium tuberculosis complex (MTBC) DNA and mutations within the 81-bp core region of the rpoB gene that are associated with rifampin (RIF) resistance. This approach, which combines an initial real-time PCR with internal inhibition assessment and a pyrosequencing assay, was validated for direct use with clinical specimens. To assess the suitability of real-time PCR for use with respiratory, nonrespiratory, acid-fast bacillus (AFB)-positive and AFB-negative specimens, we evaluated specimens received in our laboratory between 11 October 2007 and 30 June 2009. With culture used as the "gold standard," the sensitivity, specificity, and positive and negative predictive values were determined for 1,316 specimens to be as follows: for respiratory specimens, 94.7%, 99.9%, 99.6%, and 98.6%, respectively; for nonrespiratory specimens, 88.5%, 100.0%, 100.0%, and 96.9%, respectively; for AFB-positive specimens, 99.6%, 100.0%, 100.0%, and 97.7%, respectively; and for AFB-negative specimens, 75.4%, 99.9%, 98.0%, and 98.4%, respectively. PCR inhibition was determined to be minimal in this assay, occurring in 0.2% of tests. The rpoB gene pyrosequencing assay was evaluated in a similar prospective study, in which 148 clinical specimens positive for MTBC DNA by real-time PCR were tested. The final results revealed that the results of direct testing of clinical specimens by the pyrosequencing assay were 98.6% concordant with the results of conventional testing for susceptibility to RIF in liquid culture and that our assay displayed adequate sensitivity for 96.6% of the clinical specimens tested. Used together, these assays provide reliable results that aid with the initial management of patients with suspected tuberculosis prior to the availability of the results for cultured material, and they also provide the ability to predict RIF resistance in Mycobacterium tuberculosis-positive specimens in as little as 48 h from the time of clinical specimen receipt.
Preclinical evaluation of Seprafilm bioresorbable membrane. (1997)

Preclinical studies have shown that Seprafilm is safe and effective in reducing postsurgical adhesions. Seprafilm meets the requirements of an ideal barrier and can be a useful adjuvant in abdominal and pelvic surgery.
Structural and Functional Basis for JAK3-Deficient Severe Combined Immunodeficiency (1997)

Mutations of the Janus family kinase JAK3 have been found to be responsible for autosomal recessive severe combined immunodeficiency (SCID) in humans. We report here the analysis of four new unrelated patients affected by JAK3-deficient SCID. The genetic defects were heterogeneous and included a large intragenic deletion as well as different point mutations, leading to missense substitutions, early stop codons, or splicing defects. We performed a series of studies of the biochemical events induced by cytokines on lymphoblastoid B-cell lines obtained from these patients. Abnormalities in tyrosine phosphorylation of JAK3 in response to interleukin-2 (IL-2) and IL-4 were present in all patients. Accordingly, IL-2-mediated phosphorylation of STAT5 was also absent or barely detectable. On the contrary, in all cases, we could show reduced but clear phosphorylation of STAT6 upon IL-4 stimulation. In one patient carrying a single amino acid change (Glu481Gly) in the JH3 domain of JAK3, we observed partially conserved IL-2 responses resulting in reduced but detectable levels of JAK3 and STAT5 phosphorylation. Interestingly, the patient bearing this mutation developed a substantial number of circulating CD4(+)/CD45RO+ activated T lymphocytes that were functionally impaired. In two cases, patients' cells expressed JAK3 proteins with mutations in the JH2 pseudo-kinase domain. A single cysteine to arginine substitution (Cys759Arg) in this region resulted in high basal levels of constitutive JAK3 tyrosine phosphorylation unresponsive to either downregulation by serum starvation or cytokine-mediated upregulation. The characterization of the genetic defects and biochemical abnormalities in these JAK3-deficient patients will help define the role of JAK3 in the ontogeny of a competent immune system and may lead to a better understanding of the JAK3 functional domains.
Specification of e-business process model for PayPal online payment process using Reo (2005)

E-business process modeling allows business analysts to better understand and analyze the business processes, and eventually to use software systems to automate (parts of) these business processes to achieve higher profit. To support e-business process modeling, many business process modeling languages have been used as tools. However, many existing business process modeling languages lack (a) formal semantics, (b) formal computational model, and (c) an integrated view of the business process being modeled. In this paper, we assess the effectiveness of the Reo coordination language as a business process modeling language. We present a specification of PayPal online payment business process model using Reo and evaluate Reo according to the criteria of e-business process modeling with respect to (a) language expressiveness, (b) visual notation and language semantics, (c) analysis and reasoning, (d) simulation and execution
Regulation of the Cytoskeleton and Cell Adhesion by the Rho Family GTPases in Mammalian Cells (1999)

Members of the Rho family of small Ras-like GTPases--including RhoA, -B, and -C, Rac1 and -2, and Cdc42--exhibit guanine nucleotide-binding activity and function as molecular switches, cycling between an inactive GDP-bound state and an active GTP-bound state. The Rho family GTPases participate in regulation of the actin cytoskeleton and cell adhesion through specific targets. Identification and characterization of these targets have begun to clarify how the Rho family GTPases act to regulate cytoskeletal structure and cell-cell and cell-substratum contacts in mammalian cells. The Rho family GTPases are also involved in regulation of smooth muscle contraction, cell morphology, cell motility, neurite retraction, and cytokinesis. However, the molecular mechanisms by which the Rho family GTPases participate in the regulation of such processes are not well established.
Anti-adhesion molecule therapy in Theiler's murine encephalomyelitis virus-induced demyelinating disease (1997)

We examined the role of leukocyte function-associated antigen (LFA)-1 and its counter-receptor intercellular adhesion molecule (ICAM)-1, one of the most important pairs of adhesion molecules, in the development of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Immunohistochemical study showed hyper-expression of ICAM-1 on vascular endothelial cells and expression of LFA-1 on mononuclear infiltrating cells in the spinal cords of TMEV-infected mice. Treatment with mAb to ICAM-1 and/or LFA-1 molecules resulted in significant suppression of the development of demyelinating disease, both clinically and histologically, with down-regulation in the CNS of the respective adhesion molecules after treatment. In mice treated with these mAb, the specific delayed-type hypersensitivity and T cell proliferative responses for TMEV were decreased. The production of tumor necrosis factor-alpha and IFN-gamma in spleen cells was also decreased, but IL-4 production remained unchanged. These data suggest that ICAM-1/LFA-1 interaction is critically involved in the pathogenesis of TMEV-IDD and that antibodies to these adhesion molecules could be a novel therapeutic approach to the treatment of demyelinating diseases such as human multiple sclerosis.
Regulation of Translational Effectors by Amino Acid and Mammalian Target of Rapamycin Signaling Pathways (1999)

Amino acid deprivation of Chinese hamster ovary cells overexpressing human insulin receptors results in deactivation of p70 S6 kinase (p70) and dephosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), which become unresponsive to insulin; readdition of amino acids restores these responses in a rapamycin-sensitive manner, suggesting that amino acids and mammalian target of rapamycin signal through common effectors. Contrarily, withdrawal of medium amino acids from the hepatoma cell line H4IIE does not abolish the ability of insulin to stimulate p70 and 4E-BP1. The addition of 3-methyladenine (3MA) to H4IIE cells deprived of amino acids inhibited the increment in protein degradation caused by amino acid withdrawal nearly completely at 10 mM and also strongly inhibited the ability of insulin to stimulate p70 and 4E-BP1 at 10 mM. Treatment of H4IIE cells with 3MA did not alter the ability of insulin to activate tyrosine phosphorylation, phosphoinositide 3-kinase, or mitogen-activated protein kinase. In conclusion, the ability of H4IIE cells to maintain the insulin responsiveness of the mammalian target of rapamycin-dependent signaling pathways impinging on p70 and 4E-BP1 without exogenous amino acids reflects the generation of amino acids endogenously through a 3MA-sensitive process, presumably autophagy, a major mechanism of facultative protein degradation in liver.
Application of Artificial Intelligence (Artificial Neural Network) to Assess Credit Risk: A Predictive Model For Credit Card Scoring (2015)

Credit Decisions are extremely vital for any type of financial institution because it can stimulate huge financial losses generated from defaulters. A number of banks use judgmental decisions, means credit analysts go through every application separately and other banks use credit scoring system or combination of both. Credit scoring system uses many types of statistical models. But recently, professionals started looking for alternative algorithms that can provide better accuracy regarding classification. Neural network can be a suitable alternative. It is apparent from the classification outcomes of this study that neural network gives slightly better results than discriminant analysis and logistic regression. It should be noted that it is not possible to draw a general conclusion that neural network holds better predictive ability than logistic regression and discriminant analysis, because this study covers only one dataset. Moreover, it is comprehensible that a “Bad Accepted” generates much higher costs than a “Good Rejected” and neural network acquires less amount of “Bad Accepted” than discriminant analysis and logistic regression. So, neural network achieves less cost of misclassification for the dataset used in this study. Furthermore, in the final section of this study, an optimization algorithm (Genetic Algorithm) is proposed in order to obtain better classification accuracy through the configurations of the neural network architecture. On the contrary, it is vital to note that the success of any predictive model largely depends on the predictor variables that are selected to use as the model inputs. But it is important to consider some points regarding predictor variables selection, for example, some specific variables are prohibited in some countries, variables all together should provide the highest predictive strength and variables may be judged through statistical analysis etc. This study also covers those concepts about input variables selection standards.
High-Spatioresolved Microarchitectural Surface Prepared by Photograft Copolymerization Using Dithiocarbamate:  Surface Preparation and Cellular Responses (1999)

Self-perpetuating photograft copolymerization based on the photochemistry of an iniferter benzyl N,N-diethyldithiocarbamate was utilized to design two types of microprocessed surfaces using a custom-designed apparatus operated by an X−Y step motor. Cellular adhesion and growth responses were studied on (1) a surface upon which five different water soluble polymer regions were photografted with micron order precision and (2) three different gradient surfaces with unidirectionally varying thicknesses of a water soluble graft polymer layer. A striped micropatterned surface (width of each region 500 μm) was prepared by sequential photoirradiation through a photomask with a stripe window on a selected region of a poly(styrene-co-vinylbenzyl N,N-diethyldithiocarbamate)-coated PET film immersed in an aqueous solution of vinyl monomer. The sample stage was moved in a stepwise manner for each change of monomer solution. The monomers studied were N,N-dimethylacrylamide (DMAAm), 2-hydroxyethyl methacrylate (HEMA), N-[3-(dimethylamino)propyl]acrylamide methiodide (DMAPAAmMeI), methacrylic acid sodium salt (MANa), and 3-sulfopropyl methacrylate potassium salt (SMAK). Surface wettability, X-ray photoelectron spectroscopic analyses, and light microscopic visualization by dye staining revealed that five stripe regions, each of which was grafted with a different polymer, were prepared side by side. Seeding and culture of endothelial cells (ECs) on the micropatterned surfaces yielded markedly reduced adhesion on polyDMAAm and polyHEMA. PolyDMAPAAmMeI and polyMANa regions promoted cell adhesion and growth, whereas enhanced adhesion was initially observed but then became markedly reduced over time on polySMAK. Atomic force microscopic (AFM) observation showed that photoirradiation through a photomask in the presence of a monomer solution (DMAAm, DMAPAAmMeI, and MANa) under continuous sample movement yielded a graft-polymer-layer thickness gradient surface. EC adhesion and proliferation gradually decreased with increasing graft layer thickness on the polyDMAPAAmMeI and polyMANa surfaces. In contrast, cell adhesion on the polyDMAAm-grafted surface ceased abruptly above a certain graft thickness. This study shows that, using this photograft copolymerization method, both regional and chemical specific surface modification on the micron level has been achieved, representing a significant advance in the microprocessing of biomedical devices.
Preparation and alkylation of a new chiral oxazoline from L-serine (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticlePreparation and alkylation of a new chiral oxazoline from L-serineJohn F. Hansen and Curt S. CooperCite this: J. Org. Chem. 1976, 41, 19, 3219–3220Publication Date (Print):September 1, 1976Publication History Published online1 May 2002Published inissue 1 September 1976https://pubs.acs.org/doi/10.1021/jo00881a042https://doi.org/10.1021/jo00881a042research-articleACS PublicationsRequest reuse permissionsArticle Views194Altmetric-Citations11LEARN 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