gebhart/patrepeval huggingface dataset:
Effects of Vasoactive Intestinal Peptide and Pancreatic Polypeptide on Small Bowel Propulsion in the Rat (1977)

Vasoactive intestinal peptide (VIP) and the newly discovered pancreatic polypeptide (PP), both having been proposed as pathogenetic factors in the watery diarrhea syndrome (WDRA), were intravenously infused into rats in order to study the effect on small bowel propulsion. Simultaneously with the infusion of hormone, radioactive test substance was continuously infused into the duodenum of the conscious animal through a permanent catheter. By recording the distribution of radioactivity along the excised gastrointestinal tract, analyses of small bowel propulsion were possible. After infusion of VIP small bowel transit time was significantly prolonged, and the local propagation velocity was retarded both in the proximal and the distal part of the small bowel. PP did not alter small bowel populations. The heavily retarded transport rate after VIP is a propulsive dysfunction and not inconsistent with the clinical sign of diarrhea.
An improved model of association for VH–VL immunoglobulin domains: Asymmetries between VH and VL in the packing of some interface residues (2003)

The antibody-binding site is formed as a result of the association between VH and VL domains. Several studies have shown that this association plays an important role in the mechanism of antigen-antibody interaction (Stanfield et al. Structure 1: 83-93, 1993). Considering this, we propose that variations in the VH-VL association are part of the diversification strategy of the antibody repertoires. Previously, a model of association for VH-VL domains based on geometrical characteristics of the packing at the interface was developed by Chothia et al. (J. Mol. Biol. 186: 61-663, 1985). This model includes a common association form for antibodies and a three-layer structure for the interface. In the present work, a complementary model is introduced to account for the general geometrical restrictions of the VH-VL interface, and particular arrangements related to the chemical properties or the side-chain orientations of participating residues. Groups of residues assume common side-chain orientations, which are apparently related to particular functions of different interface zones. Analyses of amino acid usage and network are in agreement with the side-chain orientation patterns. Based on these observations, a three-zone model has evolved to illuminate geometrical and functional restrictions acting over the VH-VL interface. Additionally, this study has revealed the asymmetrical relationships between VH and VL residues important for the association of the two domains.
From shale oil to biogenic shale gas: retracing organic-inorganic interactions in the Alum Shale (Furongian-Lower Ordovician) in southern Sweden (2015)

Methane-rich gas occurs in the total organic carbon–rich Alum Shale (Furongian to Lower Ordovician) in southern Sweden. The lower part of the thermally immature Alum Shale was impregnated by bitumen locally generated by heating from magmatic intrusions from the Carboniferous to the Permian. Organic geochemical data indicate that the migrated bitumen is slightly degraded. In the upper Alum Shale, where methane is the main hydrocarbon in thermovaporization experiments, centimeter-size calcite crystals occur that contain fluid inclusions filled with oil, gas, or water. The Alum Shale is thus considered a mixed shale oil–biogenic shale gas play. The presented working hypothesis to explain the biogenic methane occurrence considers that water-soluble bitumen components of the Alum Shale were converted to methane. A hydrogeochemical modeling approach allows the quantitative retracing of inorganic reactions triggered by oil degradation. The modeling results reproduce the present-day gas and mineralogical composition. The conceptual model applied to explain the methane occurrence in the Alum Shale in southern Sweden resembles the formation of biogenic methane in the Antrim Shale (Michigan Basin, United States). In both models, melting water after the Pleistocene glaciation and modern meteoric water may have diluted the contents of total dissolved solids (TDS) in basinal brines. Such pore waters with low TDS contents create a subsurface aqueous environment favorable for microbes that have the potential to form biogenic methane. Today, biogenic methane production rates, with shale as the substrate using different hydrocarbon-degrading microbial enrichment cultures in incubation experiments, range from 10 to 620 nmol per gram and per day.
An Essential Role for Histone Deacetylase 4 in Synaptic Plasticity and Memory Formation (2012)

Histone deacetylases (HDACs), a family of enzymes involved in epigenetic regulation, have been implicated in the control of synaptic plasticity, as well as learning and memory. Previous work has demonstrated administration of pharmacological HDAC inhibitors, primarily those targeted to class I HDACs, enhance learning and memory as well as long-term potentiation. However, a detailed understanding of the role of class II HDACs in these processes remains elusive. Here, we show that selective loss of Hdac4 in brain results in impairments in hippocampal-dependent learning and memory and long-term synaptic plasticity. In contrast, loss of Hdac5 does not impact learning and memory demonstrating unique roles in brain for individual class II HDACs. These findings suggest that HDAC4 is a crucial positive regulator of learning and memory, both behaviorally and at the cellular level, and that inhibition of Hdac4 activity may have unexpected detrimental effects to these processes.
Identification and Characterization of the Gene Cluster Involved in Chitin Degradation in a Marine Bacterium, Alteromonas sp. Strain O-7 (2002)

Alteromonas sp. strain O-7 secretes chitinase A (ChiA), chitinase B (ChiB), and chitinase C (ChiC) in the presence of chitin. A gene cluster involved in the chitinolytic system of the strain was cloned and sequenced upstream of and including the chiA gene. The gene cluster consisted of three different open reading frames organized in the order chiD, cbp1, and chiA. The chiD, cbp1, and chiA genes were closely linked and transcribed in the same direction. Sequence analysis indicated that Cbp1 (475 amino acids) was a chitin-binding protein composed of two discrete functional regions. ChiD (1,037 amino acids) showed sequence similarity to bacterial chitinases classified into family 18 of glycosyl hydrolases. The cbp1 and chiD genes were expressed in Escherichia coli, and the recombinant proteins were purified to homogeneity. The highest binding activities of Cbp1 and ChiD were observed when alpha-chitin was used as a substrate. Cbp1 and ChiD possessed a chitin-binding domain (ChtBD) belonging to ChtBD type 3. ChiD rapidly hydrolyzed chitin oligosaccharides in sizes from trimers to hexamers, but not chitin. However, after prolonged incubation with large amounts of ChiD, the enzyme produced a small amount of (GlcNAc)(2) from chitin. The optimum temperature and pH of ChiD were 50 degrees C and 7.0, respectively.
Effect of the Pre-erythrocytic Candidate Malaria Vaccine RTS,S/AS01E on Blood Stage Immunity in Young Children (2011)

Vaccination with RTS,S/AS01E reduces exposure to blood-stage parasites and, thus, reduces anti-merozoite antigen antibody concentrations. However, in this study, these antibodies were not correlates of clinical immunity to malaria. Instead, heterogeneous exposure led to confounded, positive associations between increasing antibody concentration and increasing risk of clinical malaria.
Minimum dependence distance tiling of nested loops with non-uniform dependences (2002)

We address the problem of partitioning nested loops with non-uniform (irregular) dependence vectors. Although many methods exist for nested loop partitioning, most of these perform poorly when parallelizing nested loops with irregular dependencies. We apply the results of classical convex theory and principles of linear programming to iteration spaces and show the correspondence between minimum dependence distance computation and iteration space tiling. The cross-iteration dependencies are analyzed by forming an Integer Dependence Convex Hull (IDCH). A simple way to compute minimum dependence distances from the dependence distance vectors of the extreme points of the IDCH is presented. Using these minimum dependence distances the iteration space can be tiled. Iterations in a tile can be executed in parallel and the tiles can be executed with proper synchronization. We demonstrate that our technique gives much better speedup and extracts more parallelism than the existing techniques.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Transforming growth factor-?3 protects murine small intestinal crypt stem cells and animal survival after irradiation, possibly by reducing stem-cell cycling (2000)

Damage to the normal replacing tissues of the body, specifically the gastro-intestinal tract, limits the treatment and hence, cure rate of cancer patients. Here, we investigate the possibility that the sensitivity of the gastro-intestinal tract can be manipulated by transforming growth factor beta3 (TGF-beta3), making it more resistant to radiation in a murine model. The effects of TGF-beta3 were assessed using the crypt microcolony assay, a test of crypt stem-cell functional competence, in animal survival studies examining diarrhoea severity, labelling index and crypt size. Prior treatment with TGF-beta3 can result in a 3- to 4-fold increase (protection factor, PF) in surviving crypts, whilst longer exposure can raise the PF to almost 12. Protection of intestinal clonogenic stem cells results in marked protection of survival with a corresponding reduction in the duration and level of diarrhoea and ultimate restoration of normal histology in surviving mice. Inhibition of proliferation can be demonstrated when sufficient TGF-beta3 exposure is studied. Crypt size is also reduced. In conclusion, TGF-beta3 protects small intestinal clonogenic stem cells from radiation damage, reducing diarrhoea and animal mortality. The mode of action is believed to be specific inhibition of stem-cell proliferation.
How to Own the Internet in Your Spare Time (2002)

The ability of attackers to rapidly gain control of vast numbers of Internet hosts poses an immense risk to the overall security of the Internet. Once subverted, these hosts can not only be used to launch massive denial of service floods, but also to steal or corrupt great quantities of sensitive information, and confuse and disrupt use of the network in more subtle ways. We present an analysis of the magnitude of the threat. We begin with a mathematical model derived from empirical data of the spread of Code Red I in July, 2001. We discuss techniques subsequently employed for achieving greater virulence by Code Red II and Nimda. In this context, we develop and evaluate several new, highly virulent possible techniques: hit-list scanning (which creates a Warhol worm), permutation scanning (which enables self-coordinating scanning), and use of Internet-sized hit-lists (which creates a flash worm).
Molecular characterization of a t(2;6) balanced translocation that is associated with a complex phenotype and leads to truncation of theTCBA1gene (2005)

The molecular characterization of balanced chromosomal rearrangements has often been a powerful tool for the positional identification of genes associated with specific diseases. In some instances, these rearrangements may be associated with a variety of different phenotypes, and thus establishing a genotype-phenotype correlation may be a complex process. However, molecular characterization of the rearrangement remains a useful tool for diagnoses or prognoses, or for identifying new genes and establishing a gene-to-function relationship. In this work we describe the characterization of a de novo balanced translocation t(2;6)(q24.3;q22.31) found in a patient with a complex phenotype. The major clinical finding was a severe neurological involvement. Thanks to the molecular characterization of this translocation we found that the rearrangement led to the truncation of the TCBA1 gene on chromosome 6q. We found that the gene is transcribed in different splice variants and is highly specific for the central nervous system. TCBA1 does not show any similarity with other known genes, and no information is available about its function. However, the gene appears to be well conserved among species, and we were able to infer the sequence of a putative mouse homolog of TCBA1. This allowed us to perform a more detailed expression study in mice, thus confirming its specificity for the nervous system. This finding is of particular interest because it suggests that TCBA1 may be correlated with the neurological phenotype of our patient, and possibly mutated in genetic diseases with a neurological phenotype.
CD8+ lymphocyte phenotype and cytokine production in long-term non-progressor and in progressor patients with HIV-1 infection (1996)

In most HIV-1-infected patients, clinical and immunological progression develops within a few years. Few infected people, termed long-term non-progressors (LTNP), remain healthy and immunologically stable for a long time. The factors governing the maintenance of this condition are not well known, but it is conceivable that CD8+ lymphocytes, cells that play a central role in controlling in vitro HIV replication, may have a part in vivo in this process. The aim of this study was to characterize the phenotypic profile and the cytokine production of CD8+ cells in a group of LTNP patients who had stable CD4+ cell counts (> 500/mm3) for at least 7 years. Their CD8+ absolute numbers were similar to a control group composed of HIV-1+ patients who have a progressive decline of their CD4+ cell counts. However, our multiparameter immunofluorescence studies show that a clinical and immunologically stable condition is associated with the presence of a CD28+, CD95 strongly positive CD8+ population, while disease progression is marked by the CD28-CD95+CD8+ subset. Purified CD8+ cells from LTNP retain their ability to produce IL-2, interferon-gamma (IFN-gamma) and, to a lesser degree, to produce IL-10 and IL-4. In contrast, CD8+ cells from progressors are unable to secrete IL-2 and IL-10. Although CD8+ cytokine profile does not fit with the proposed T helper (Th)1/Th2 switch in progressive HIV infection, LTNP CD8+ T cells maintain their capacity to produce IL-2 and IL-10 (Th0-like), a pattern very similar to that observed in normal HIV healthy controls. We suggest that CD8+ cells expressing CD28, CD95 and having a Th0-like profile may be considered to be associated with long-term survival.
Total Synthesis of the Antitumor Depsipeptide FR-901,228 (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTTotal Synthesis of the Antitumor Depsipeptide FR-901,228Khan W. Li, Jerry Wu, Wenning Xing, and Julian A. SimonView Author Information Department of Chemistry and Chemical Biology Harvard University Cambridge, Massachusetts 02138 Cite this: J. Am. Chem. Soc. 1996, 118, 30, 7237–7238Publication Date (Web):July 31, 1996Publication History Received26 April 1996Published online31 July 1996Published inissue 1 January 1996https://doi.org/10.1021/ja9613724Copyright © 1996 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views3721Altmetric-Citations117LEARN 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 Read OnlinePDF (192 KB) Get e-AlertsSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Alcohols,Aldol reactions,Disulfides,Organic compounds,Peptides and proteins Get e-Alerts
Perceptions of women on the impact of menorrhagia on their health using multi‐attribute utility assessment (1998)

In planning treatment for menorrhagia clinicians can assess a woman's current perception of their health, using a simple to administer clinical scale.
Novel oligodeoxynucleotide agonists of TLR9 containing N3-Me-dC or N1-Me-dG modifications (2006)

Synthetic oligodeoxynucleotides containing unmethylated CpG motifs activate Toll-Like Receptor 9 (TLR9). Our previous studies have shown the role of hydrogen-bond donor and acceptor groups of cytosine and guanine in the CpG motif and identified synthetic immunostimulatory motifs. In the present study to elucidate the significance of N3-position of cytosine and N1-position of guanine in the CpG motif, we substituted C or G of a CpG dinucleotide with N3-Me-cytosine or N1-Me-guanine, respectively, in immunomodulatory oligodeoxynucleotides (IMOs). IMOs containing N-Me-cytosine or N-Me-guanine in C- or G-position, respectively, of the CpG dinucleotide showed activation of HEK293 cells expressing TLR9, but not TLR3, 7 or 8. IMOs containing N-Me-cytosine or N-Me-guanine modification showed activity in mouse spleen cell cultures, in vivo in mice, and in human cell cultures. In addition, IMOs containing N-Me-substitutions reversed antigen-induced Th2 immune responses towards a Th1-type in OVA-sensitized mouse spleen cell cultures. These studies suggest that TLR9 tolerates a methyl group at N1-position of G and a methyl group at N3-position of C may interfere with TLR9 activation to some extent. These are the first studies elucidating the role of N3-position of cytosine and N1-position of guanine in a CpG motif for TLR9 activation and immune stimulation.
The AcCell Series 2000 as a Support System for Training and Evaluation in Educational and Clinical Settings (1997)

Providing effective training, retraining and evaluation programs, including proficiency testing programs, for cytoprofessionals is a challenge shared by many academic and clinical educators internationally. In cytopathology the quality of training has immediately transferable and critically important impacts on satisfactory performance in the clinical setting. Well-designed interactive computer-assisted instruction and testing programs have been shown to enhance initial learning and to reinforce factual and conceptual knowledge. Computer systems designed not only to promote diagnostic accuracy but to integrate and streamline work flow in clinical service settings are candidates for educational adaptation. The AcCell 2000 system, designed as a diagnostic screening support system, offers technology that is adaptable to educational needs during basic and in-service training as well as testing of screening proficiency in both locator and identification skills. We describe the considerations, approaches and applications of the AcCell 2000 system in education programs for both training and evaluation of gynecologic diagnostic screening proficiency.
Hydrogen Peroxide Synthesis: An Outlook beyond the Anthraquinone Process (2006)

Hydrogen peroxide (H2O2) is widely used in almost all industrial areas, particularly in the chemical industry and environmental protection. The only degradation product of its use is water, and thus it has played a large role in environmentally friendly methods in the chemical industry. Hydrogen peroxide is produced on an industrial scale by the anthraquinone oxidation (AO) process. However, this process can hardly be considered a green method. It involves the sequential hydrogenation and oxidation of an alkylanthraquinone precursor dissolved in a mixture of organic solvents followed by liquid-liquid extraction to recover H2O2. The AO process is a multistep method that requires significant energy input and generates waste, which has a negative effect on its sustainability and production costs. The transport, storage, and handling of bulk H2O2 involve hazards and escalating expenses. Thus, novel, cleaner methods for the production of H2O2 are being explored. The direct synthesis of H2O2 from O2 and H2 using a variety of catalysts, and the factors influencing the formation and decomposition of H2O2 are examined in detail in this Review.
Crown Plasticity and Competition for Canopy Space: A New Spatially Implicit Model Parameterized for 250 North American Tree Species (2007)

This new model, with parameters for US tree species, opens up new possibilities for understanding and modeling forest dynamics at local and regional scales, and may provide a new way to interpret remote sensing data of forest canopies, including LIDAR and aerial photography.
Microsatellite instability induced mutations in DNA repair genes CtIP and MRE11 confer hypersensitivity to poly (ADP-ribose) polymerase inhibitors in myeloid malignancies (2013)

Inactivation of the DNA mismatch repair pathway manifests as microsatellite instability, an accumulation of mutations that drives carcinogenesis. Here, we determined whether microsatellite instability in acute myeloid leukemia and myelodysplastic syndrome correlated with chromosomal instability and poly (ADP-ribose) polymerase (PARP) inhibitor sensitivity through disruption of DNA repair function. Acute myeloid leukemia cell lines (n=12) and primary cell samples (n=18), and bone marrow mononuclear cells from high-risk myelodysplastic syndrome patients (n=63) were profiled for microsatellite instability using fluorescent fragment polymerase chain reaction. PARP inhibitor sensitivity was performed using cell survival, annexin V staining and cell cycle analysis. Homologous recombination was studied using immunocytochemical analysis. SNP karyotyping was used to study chromosomal instability. RNA silencing, Western blotting and gene expression analysis was used to study the functional consequences of mutations. Acute myeloid leukemia cell lines (4 of 12, 33%) and primary samples (2 of 18, 11%) exhibited microsatellite instability with mono-allelic mutations in CtIP and MRE11. These changes were associated with reduced expression of mismatch repair pathway components, MSH2, MSH6 and MLH1. Both microsatellite instability positive primary acute myeloid leukemia samples and cell lines demonstrated a downregulation of homologous recombination DNA repair conferring marked sensitivity to PARP inhibitors. Similarly, bone marrow mononuclear cells from 11 of 56 (20%) patients with de novo high-risk myelodysplastic syndrome exhibited microsatellite instability. Significantly, all 11 patients with microsatellite instability had cytogenetic abnormalities with 4 of them (36%) possessing a mono-allelic microsatellite mutation in CtIP. Furthermore, 50% reduction in CtIP expression by RNA silencing also down-regulated homologous recombination DNA repair responses conferring PARP inhibitor sensitivity, whilst CtIP differentially regulated the expression of homologous recombination modulating RecQ helicases, WRN and BLM. In conclusion, microsatellite instability dependent mutations in DNA repair genes, CtIP and MRE11 are detected in myeloid malignancies conferring hypersensitivity to PARP inhibitors. Microsatellite instability is significantly correlated with chromosomal instability in myeloid malignancies.