gebhart/patrepeval huggingface dataset:
How the Bfi I restriction enzyme uses one active site to cut two DNA strands (2003)

Unlike other restriction enzymes, BfiI functions without metal ions. It recognizes an asymmetric DNA sequence, 5'-ACTGGG-3', and cuts top and bottom strands at fixed positions downstream of this sequence. Many restriction enzymes are dimers of identical subunits, with one active site for each DNA strand. Others, like FokI, dimerize transiently during catalysis. BfiI is also a dimer but it has only one active site, at the dimer interface. We show here that BfiI remains a dimer as it makes double-strand breaks in DNA and that its single active site acts sequentially, first on the bottom and then the top strand. Hence, after cutting the bottom strand, a rearrangement of either the protein and/or the DNA in the BfiI-DNA complex must switch the active site to the top strand. Low pH values selectively block top-strand cleavage, converting BfiI into a nicking enzyme that cleaves only the bottom strand. The switch to the top strand may depend on the ionization of the cleaved 5' phosphate in the bottom strand. BfiI thus uses a mechanism for making double-strand breaks that is novel among restriction enzymes.
Human Splicing Finder: an online bioinformatics tool to predict splicing signals (2009)

Thousands of mutations are identified yearly. Although many directly affect protein expression, an increasing proportion of mutations is now believed to influence mRNA splicing. They mostly affect existing splice sites, but synonymous, non-synonymous or nonsense mutations can also create or disrupt splice sites or auxiliary cis-splicing sequences. To facilitate the analysis of the different mutations, we designed Human Splicing Finder (HSF), a tool to predict the effects of mutations on splicing signals or to identify splicing motifs in any human sequence. It contains all available matrices for auxiliary sequence prediction as well as new ones for binding sites of the 9G8 and Tra2-beta Serine-Arginine proteins and the hnRNP A1 ribonucleoprotein. We also developed new Position Weight Matrices to assess the strength of 5' and 3' splice sites and branch points. We evaluated HSF efficiency using a set of 83 intronic and 35 exonic mutations known to result in splicing defects. We showed that the mutation effect was correctly predicted in almost all cases. HSF could thus represent a valuable resource for research, diagnostic and therapeutic (e.g. therapeutic exon skipping) purposes as well as for global studies, such as the GEN2PHEN European Project or the Human Variome Project.
Studies on the mechanism of phagocytosis. II. The interaction of macrophages with anti-immunoglobulin IgG-coated bone marrow-derived lymphocytes. (1976)

We have examined the effect of the distribution of anti-immunoglobulin IgG molecules on the surface of bone marrow-derived lymphocytes upon the interaction of these cells with macrophages. Lymphocytes which were diffusely coated with antibodies to surface immunoglogulin were ingested by macrophages. Lymphocytes which had the same number of anti-immunoglobulin IgG molecules redistributed to one pole of the surface bound to the macrophages' Fc receptors but were not ingested. These results confirm our previous hypothesis that ingestion of an immunologically coated particle requires the sequential, circumferential binding of specific receptors on the plasma membrane of a phagocytic cell to immunologic ligands distributed over the entire particle surface. Macrophages which had bound capped lymphocytes by the macrophages' Fc receptors removed the immune complex caps from the lymphocyte surface without destroying the lymphocytes. These lymphocytes remained attached to the macrophage surface. The finding that macrophages can phagocytize immune complexes from the surface of a cell without destroying the cell to which these complexes are attached may be important in understanding the effects of antigens and antibodies on cells participating in a humoral immune response, in identifying the mechanisms by which chronic viral infections are established, and in defining the roles of blocking antibodies in tumor immunity.
In VitroInhibition of Pancreatic Glucagon Secretion by Diphenylhydantoin (1972)

Diphenylhydantoin (DPH) has been reported to stabilize poorly controlled insulin-dependent diabetes mellitus. Since this condition is characterized by elevated plasma levels of glucagon, the beneficial effect of DPH may be attributable to modification of glucagon release. To investigate this possibility, the effects of DPH on arginine-induced glucagon secretion were studied in the isolated perfused rat pancreas. At 25 μg/ml, DPH markedly diminished glucagon release and had no effect on insulin responses. Evidence is thus presented that DPH directly inhibits pancreatic glucagon secretion. These results suggest DPH may be of value for stabilization of poorly controlled diabetes mellitus.
Human parainfluenza virus type 3 expressing the respiratory syncytial virus pre-fusion F protein modified for virion packaging yields protective intranasal vaccine candidates (2020)

Human respiratory syncytial virus (RSV) and parainfluenza virus type 3 (HPIV3) are among the most common viral causes of childhood bronchiolitis and pneumonia worldwide, and lack effective antiviral drugs or vaccines. Recombinant (r) HPIV3 was modified to express the RSV fusion (F) glycoprotein, the major RSV neutralization and protective antigen, providing a live intranasal bivalent HPIV3/RSV vaccine candidate. This extends previous studies using a chimeric bovine-human PIV3 vector (rB/HPIV3). One advantage is that rHPIV3 expresses all of the HPIV3 antigens compared to only two for rB/HPIV3. In addition, the use of rHPIV3 as vector should avoid excessive attenuation following addition of the modified RSV F gene, which may occur with rB/HPIV3. To enhance its immunogenicity, RSV F was modified (i) to increase the stability of the prefusion (pre-F) conformation and (ii) by replacement of its transmembrane (TM) and cytoplasmic tail (CT) domains with those of HPIV3 F (H3TMCT) to increase incorporation in the vector virion. RSV F (+/- H3TMCT) was expressed from the first (F/preN) or the second (F/N-P) gene position of rHPIV3. The H3TMCT modification dramatically increased packaging of RSV F into the vector virion and, in hamsters, resulted in significant increases in the titer of high-quality serum RSV-neutralizing antibodies, in addition to the increase conferred by pre-F stabilization. Only F-H3TMCT/preN replication was significantly attenuated in the nasal turbinates by the RSV F insert. F-H3TMCT/preN, F/N-P, and F-H3TMCT/N-P provided complete protection against wt RSV challenge. F-H3TMCT/N-P exhibited the most stable and highest expression of RSV F, providing impetus for its further development.
Healing of elderly patients with diabetic foot ulcers, venous stasis ulcers, and pressure ulcers. (2003)

Although elderly patients have physiologic impairments in wound healing, their wounds should be expected to heal with the same frequency of closure as those in younger populations, albeit at a slower rate. However, compared to the general population, the elderly population has a higher incidence of chronic wounds: diabetic foot ulcers, pressure ulcers, and venous stasis ulcers. Experimental and clinical data indicate physiologically impaired healing is characterized by decreased angiogenesis and synthesis of critical growth factors. Further, compared to younger populations, the elderly have a higher rate of mortality associated with specific morbidities, such as sepsis and acute respiratory distress. As these morbidities may develop directly from the wound, early intervention is mandated. In this report, 40 consecutive elderly patients (65-102 years old) with chronic wounds were analyzed. All patients were provided the same treatment protocol and healing was defined as 100% epithelization and no drainage. Despite the wounds presenting in a nonhealing and/or infected state, 73% of these chronic wounds in elderly patients healed. This suggests that elderly patients with diabetic foot ulcers, pressure ulcers, and venous stasis ulcers close their wounds at a similar frequency as younger patients. Therefore, early intervention and comprehensive treatment that includes safe topical therapies, in addition to growth factors and cellular therapy used for chronic wounds, ensure these patients will be spared the morbidities of pain, amputation, osteomyelitis, and even death. We hypothesize that if all elderly patients with chronic wounds are provided early treatment, morbidities (e.g., amputation, sepsis, pain) and associated costs will decrease.
TnphoA and TnphoA' elements for making and switching fusions for study of transcription, translation, and cell surface localization (1992)

We describe a set of elements based on the transposon TnphoA for making transcriptional fusions to the lacZ gene and for making translational fusions to the phoA or lacZ structural gene. Each element can be switched, one for another, by homologous recombination, thereby allowing testing for transcription, translation, or cell surface localization determinants at the same site within a gene. We describe three kinds of elements for making each fusion type. Two kinds are transposition proficient (Tnp+): one encodes kanamycin resistance, and the other encodes tetracycline resistance. The third kind is transposition defective (Tnp-) and encodes kanamycin resistance. In addition, we describe one Tnp- element that has no reporter gene and encodes chloramphenicol resistance; this element is used primarily as a tool to aid in switching fusions. Switching is efficient because each element has in common 254 bp of DNA at the phoA end and 187 bp (or more) of DNA at the IS50R end of TnphoA, and switching is straightforward because individual elements encode different drug resistances. Thus, switched recombinants can be selected as drug-resistant transductants, and they can be recognized as ones that have lost the parental drug resistance and fusion phenotype. Further, switching Tnp+ elements to Tnp- elements reduces problems due to transposition that can arise in P1 crosses or cloning experiments. Some TnphoA and TnphoA' elements cause polar mutations, while others provide an outward promoter for downstream transcription. This feature is especially useful in the determination of operon structures. Strategies for the use of TnphoA and TnphoA' elements in gene analysis are also described.
Low Availability of Aluminum in Formulations for Parenteral Nutrition Containing Silicate (2009)

The concomitant presence of Al and Si in solutions for PN reduces the amount of Al available attributable to the formation of HAS. In amino acid formulations this effect may be slightly reduced given the affinity of certain amino acids for Al. Therefore, amino acids may behave in the same fashion as silicate.
Protection Against Local Irradiation Injury tothe Skin by Locally and Systemically Applied Drugs (1972)

The radioprotective effects of systemically and topically administered cysteamine and WR-2721 were studied in irradiated mouse skin. Topically applied cysteamine showed significant protection only with moderate doses of irradiation. Topically applied WR-2721 had no protective effect at any dose. Systemically administered cysteamine yielded a dose reduction factor (DRF) of 1.7 for acute skin reactions and WR-2721 yielded a DRF of 2.0. Both agents showed a DRF of 1.5 for late tissue changes when administered systemically. The DRF for late tissue changes following local irradiation may be a more meaningful parameter of protective action than the DRF for acute whole-body lethality.
Versatile and Stereoselective Synthesis of Diamino Diol Dipeptide Isosteres, Core Units of Pseudopeptide HIV Protease Inhibitors (1997)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTVersatile and Stereoselective Synthesis of Diamino Diol Dipeptide Isosteres, Core Units of Pseudopeptide HIV Protease InhibitorsFabio Benedetti, Stanislav Miertus, Stefano Norbedo, Alessandro Tossi, and Pavel ZlatoidzkyView Author Information Department of Chemical Sciences and Department of Biochemistry, Biophysics and Macromolecular Sciences, University of Trieste, via Giorgieri 1, I-34127 Trieste, Italy, and Polytech, Area di Ricerca, Padriciano 99, 34012 Trieste, Italy Cite this: J. Org. Chem. 1997, 62, 26, 9348–9353Publication Date (Web):December 26, 1997Publication History Received1 July 1997Published online26 December 1997Published inissue 1 December 1997https://pubs.acs.org/doi/10.1021/jo971202phttps://doi.org/10.1021/jo971202pbrief-reportACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views574Altmetric-Citations36LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Alcohols,Diols,Organic compounds,Organic reactions,Peptides and proteins Get e-Alerts
Impact of simian immunodeficiency virus (SIV) infection on lymphocyte numbers and T-cell turnover in different organs of rhesus monkeys (2003)

HIV infection leads to reduced numbers and increased turnover of CD4(+) T cells in blood. However, blood represents only 2% of the total lymphocyte pool, and information about other organs is lacking, leading to controversy about the effects of HIV infection on T-cell homeostasis. Therefore, we have determined phenotype and turnover of lymphocyte subsets in various tissues of macaques. Infection with simian immunodeficiency virus (SIV) resulted in increased proliferation rates of T cells in all organs. Despite reduced CD4 counts in blood, absolute numbers of CD4(+) T cells were increased in spleen and lymph nodes and remained stable in nonlymphoid organs such as liver, lung, bone marrow, and brain during the asymptomatic phase, indicative for an altered tissue distribution. In animals killed with first signs of AIDS, total body CD4 counts and proliferation rates had returned to control levels, whereas thymocytes were almost completely absent. Our data show that a drastically increased turnover in the early stages of HIV infection, driven by a generalized immune activation rather than a homeostatic response to CD4(+) T-cell destruction, is followed by exhaustion of the regenerative capacity of the immune system.
Basic Studies on the Bone Formation Ability by Platelet Rich Plasma in Rabbits (2004)

In both experiments, a prosperous bone formation was observed from the beginning more in the group treated with PRP than in the group untreated. In experiment 2, gradual appearances of the bone formation were observed in the bubble of beta-TCP. In application with artificial bone materials, bone formations by PRP were suitably observed.
On an Axiomatic Approach to Manufacturing and Manufacturing Systems (1978)

A manufacturing system consists of the following processes; design, materials selection and processing, assembly, and quality control. Maximum productivity of a given manufacturing system can be obtained only through optimization of the entire system rather than through optimization of its components individually. A system can be optimized through either a thorough understanding of the entire system and the interactions between its components, i.e., an algorithmic approach; or through the application of axioms to each decision-making step. This paper discusses an axiomatic approach to manufacturing and a methodology for developing axioms. Several hypothetical axioms and some of their corollaries are presented with examples to illustrate the basic concepts.
A robust algorithm for text string separation from mixed text/graphics images (1988)

The development and implementation of an algorithm for automated text string separation that is relatively independent of changes in text font style and size and of string orientation are described. It is intended for use in an automated system for document analysis. The principal parts of the algorithm are the generation of connected components and the application of the Hough transform in order to group components into logical character strings that can then be separated from the graphics. The algorithm outputs two images, one containing text strings and the other graphics. These images can then be processed by suitable character recognition and graphics recognition systems. The performance of the algorithm, both in terms of its effectiveness and computational efficiency, was evaluated using several test images and showed superior performance compared to other techniques.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Sedation and Delirium in the Intensive Care Unit (2014)

atients in intensive care units (ICUs) are treated with many interventions (most notably endotracheal intubation and invasive mechanical ventilation) that are observed or perceived to be distressing. Pain is the most common memory patients have of their ICU stay. 1 Agitation can precipitate accidental removal of endotracheal tubes or of intravascular catheters used for monitoring or administration of life-sustaining medications. Consequently, sedatives and analgesics are among the most commonly administered drugs in ICUs.
Clinical Experience with a Human Thyroid Cell Bioassary for Thyroid-Stimulating Immunoglobin * (1984)

A sensitive, specific, and practical bioassay for thyroid-stimulating immunoglobulin (TSI) is now available for clinical use. Fifty-seven of 61 patients with untreated hyperthyroid Graves' disease were TSI positive (sensitivity, 93%). TSI was undetectable in all normal subjects and in patients with Hashimoto's thyroiditis (without concurrent Graves' ophthalmopathy), nontoxic goiter, and toxic nodular goiter (specificity, 100%). The prevalence of TSI in serum declined after therapy, particularly during methimazole or propylthiouracil treatment. TSI correlated well with relapse or remission after antithyroid drug therapy. All 12 patients who were TSI negative at the time of discontinuing antithyroid drug therapy remained in remission (average follow-up of 10 months). TSI values in Graves' disease correlated better with thyroid dysfunction than with ophthalmopathy. Prenatal TSI activity tended to be higher in mothers of infants who developed neonatal Graves' disease than in at-risk mothers who delivered normal infants. However, there was considerable overlap between the two groups.
Differential effects of interleukin-15 and interleukin-2 on differentiation of bipotential T/natural killer progenitor cells. (1996)

Bipotential T/natural killer (NK) progenitor cells are destined to differentiate mainly into T cell receptor (TCR) alpha beta and TCR gamma delta cells in a thymic microenvironment, whereas extrathymically they selectively develop into NK cells. The exact environmental conditions that are required for differentiation into these three leukocyte populations are largely unknown. In this report, we have investigated and compared the effect of interleukin (IL)-15 and IL-2 in this process. The IL-15 receptor is composed of the gamma and beta chains of the IL-2 receptor (IL-2R gamma and IL-2R beta) and of a specific alpha chain (IL-15R alpha). Here, it is shown that IL-15 mRNA is mainly expressed in thymic epithelial stromal cells, whereas IL-2 mRNA is exclusively expressed in thymocytes. IL-2R beta-expressing cells were present in the fetal thymus with a CD25-CD44+Fc gamma R+HSA-/low TCR- phenotype, which is characteristic of progenitor cells. These cells also expressed IL-15R alpha messenger RNA. Sorted IL-2R beta + TCR- cells differentiated into TCR alpha beta and TCR gamma delta cells after transfer to alymphoid thymic lobes, whereas culture of the same sorted cells in cell suspension in the presence of IL-15 resulted in the generation of functional NK cells. This shows that IL-2R beta +TCR- cells of the fetal thymus contain bipotential T/NK progenitors. Addition of low concentrations of IL-15 to fetal thymic organ culture (FTOC) resulted in an increase of all T cell subpopulations. The largest expansion occurred in the TCR gamma delta compartment. In contrast, low concentrations of IL-2 did not result in a higher total cell number and did not induce outgrowth of TCR gamma delta cells. High concentrations of IL-15 blocked TCR alpha beta development and shifted differentiation towards NK cells. Differentiation towards TCR gamma delta cells still proceeded. High concentrations of IL-2 similarly induced development into NK cells, but the cell number was fourfold lower than in IL-15 cultures. Importantly, blocking of IL-2R alpha in IL-2-treated FTOC resulted in a drastic increase in cell number, indicating that IL-2R alpha negatively regulates cell expansion. Collectively, these experiments provide direct evidence that IL-15 and IL-2 differentially affect the differentiation of bipotential T/NK progenitors.
Immortalization of human B lymphocytes by a plasmid containing 71 kilobase pairs of Epstein-Barr virus DNA (1995)

We have assembled derivatives of Epstein-Barr Virus (EBV) that include 71 kbp of noncontiguous DNA sequences cloned into a prokaryotic F-factor plasmid. These mini-EBVs, when introduced into an EBV-containing lymphoblastoid cell, can be packaged by the endogenous helper virus. One such mini-EBV was found to have a single C residue deleted from its EBNA3a open reading frame. When packaged, this mini-EBV initiates proliferation of infected primary human B lymphocytes only in conjunction with a complementing helper virus. Proliferation of the infected cells, however, was maintained either alone by the mini-EBV containing the mutated EBNA3a open reading frame or alone by its derivative in which the EBNA3a open reading frame had been healed of its lesion by recombination with the helper virus. The mini-EBV with a wild-type EBNA3a open reading frame when packaged alone can both initiate and maintain proliferation upon infection of primary human B lymphocytes. These findings identify 41% of EBV DNA which is sufficient to immortalize primary human B lymphocytes and provide an assay to distinguish virus contributions to initiation or maintenance of cell proliferation or both. They also identify EBNA3a as a transforming gene, which contributes primarily to the initiation of cell proliferation.
Quantum‐Dot‐Tagged Reduced Graphene Oxide Nanocomposites for Bright Fluorescence Bioimaging and Photothermal Therapy Monitored In Situ (2012)

Quantum-dot-tagged reduced graphene oxide (QD-rGO) nanocomposites (left) internalized into targeted tumor cells display bright fluorescence from the QDs (right); by absorbing NIR radiation incident on the rGO and converting it into heat, they also cause simultaneous cell death and fluorescence reduction (bottom). The nanocomposite is thus capable of tumor imaging, photothermal therapy and in situ monitoring of treatment in progress.
Small Cell Carcinoma of the Esophagus (1994)

Small cell carcinoma of the esophagus should be regarded as a systemic disease, and multimodality treatment, including chemotherapy, should be used. Surgery may be offered in selected patients to manage local disease as part of a chemotherapy-based treatment program.