gebhart/patrepeval huggingface dataset:
Short-chain fatty acid derivatives induce fetal globin expression and erythropoiesis in vivo (2002)

Orally bioactive compounds that induce gamma globin gene expression at tolerable doses are needed for optimal treatment of the beta-hemoglobinopathies. Short-chain fatty acids (SCFAs) of 2 to 6 carbons in length induce gamma globin expression in animal models, and butyrate, phenylbutyrate, and valproate induce gamma globin in human patients. The usefulness of these compounds, however, is limited by requirements for large doses because of their rapid metabolism and their tendency to inhibit cell proliferation, which limits the pool of erythroid progenitors in which gamma globin can be induced. Selected short-chain fatty acid derivatives (SCFADs) were recently found to induce gamma globin and to stimulate the proliferation of hematopoietic cells in vitro. These SCFADs are now evaluated in vivo in nonanemic transgenic mice containing the human beta globin gene locus and in anemic phlebotomized baboons. In mice treated with a SCFAD once daily for 5 days, gamma globin mRNA increased 2-fold, reticulocytes increased 3- to 7-fold, and hematocrit levels increased by 27%. Administration of 3 SCFADs in anemic baboons increased F-reticulocytes 2- to 15-fold over baseline and increased total hemoglobin levels by 1 to 2 g/dL per week despite ongoing significant daily phlebotomy. Pharmacokinetic studies demonstrated 90% oral bioavailability of 2 SCFADs, and targeted plasma levels were maintained for several hours after single oral doses equivalent to 10% to 20% of doses required for butyrate. These findings identify SCFADs that stimulate gamma globin gene expression and erythropoiesis in vivo, activities that are synergistically beneficial for treatment of the beta hemoglobinopathies and useful for the oral treatment of other anemias.
Region competition: unifying snakes, region growing, and Bayes/MDL for multiband image segmentation (1996)

We present a novel statistical and variational approach to image segmentation based on a new algorithm, named region competition. This algorithm is derived by minimizing a generalized Bayes/minimum description length (MDL) criterion using the variational principle. The algorithm is guaranteed to converge to a local minimum and combines aspects of snakes/balloons and region growing. The classic snakes/balloons and region growing algorithms can be directly derived from our approach. We provide theoretical analysis of region competition including accuracy of boundary location, criteria for initial conditions, and the relationship to edge detection using filters. It is straightforward to generalize the algorithm to multiband segmentation and we demonstrate it on gray level images, color images and texture images. The novel color model allows us to eliminate intensity gradients and shadows, thereby obtaining segmentation based on the albedos of objects. It also helps detect highlight regions.
Comparison of Serum High–Molecular Weight (HMW) Adiponectin With Total Adiponectin Concentrations in Type 2 Diabetic Patients With Coronary Artery Disease Using a Novel Enzyme-Linked Immunosorbent Assay to Detect HMW Adiponectin (2006)

Adiponectin (Acrp30), an adipocyte-derived protein, exists in serum as a trimer, a hexamer, and a high-molecular weight (HMW) form, including 12-18 subunits. Because HMW adiponectin may be biologically active, we measured it in serum using a novel enzyme-linked immunosorbent assay (ELISA) confirmed by gel filtration chromatography that the ELISA detected mainly adiponectin with 12-18 subunits, and we compared HMW with total adiponectin concentration in patients with type 2 diabetes. We next investigated the relationship between serum HMW and coronary artery disease (CAD) in 280 consecutive type 2 diabetic patients, including 59 patients with angiographically confirmed CAD. Total adiponectin was measured in serum by a commercially available ELISA. Like serum total adiponectin, HMW adiponectin correlated positively with HDL cholesterol and negatively with triglyceride, insulin sensitivity, creatinine clearance, and circulating inflammatory markers. Total and HMW adiponectin were significantly higher in women than in men, as was the HMW-to-total adiponectin ratio. Serum HMW and the HMW-to-total adiponectin ratio were significantly lower in men with than without CAD (P < 0.05, respectively). In women, the ratio, but neither total nor HMW adiponectin, tended to be lower when CAD was present. In conclusion, determination of HMW adiponectin, especially relative to total serum adiponectin, is useful for evaluating CAD in type 2 diabetic patients.
T Cell/B Cell Collaboration and Autoimmunity: An Intimate Relationship (2018)

Co-ordinated interaction between distinct cell types is a hallmark of successful immune function. A striking example of this is the carefully orchestrated cooperation between helper T cells and B cells that occurs during the initiation and fine-tuning of T-cell dependent antibody responses. While these processes have evolved to permit rapid immune defense against infection, it is becoming increasingly clear that such interactions can also underpin the development of autoimmunity. Here we discuss a selection of cellular and molecular pathways that mediate T cell/B cell collaboration and highlight how <i>in vivo</i> models and genome wide association studies link them with autoimmune disease. In particular, we emphasize how CTLA-4-mediated regulation of CD28 signaling controls the engagement of secondary costimulatory pathways such as ICOS and OX40, and profoundly influences the capacity of T cells to provide B cell help. While our molecular understanding of the co-operation between T cells and B cells derives from analysis of secondary lymphoid tissues, emerging evidence suggests that subtly different rules may govern the interaction of T and B cells at ectopic sites during autoimmune inflammation. Accordingly, the phenotype of the T cells providing help at these sites includes notable distinctions, despite sharing core features with T cells imparting help in secondary lymphoid tissues. Finally, we highlight the interdependence of T cell and B cell responses and suggest that a significant beneficial impact of B cell depletion in autoimmune settings may be its detrimental effect on T cells engaged in molecular conversation with B cells.
A Consensus Document on Bowel Preparation Before Colonoscopy: Prepared by a Task Force From The American Society of Colon and Rectal Surgeons (ASCRS), The American Society for Gastrointestinal Endoscopy (ASGE), and The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) (2006)

Wexner, Steven D. M.D.1,8,a; Beck, David E. M.D. (ASCRS)2; Baron, Todd H. M.D. (ASGE)3; Fanelli, Robert D. M.D. (SAGES)4; Hyman, Neil M.D. (ASCRS)5; Shen, Bo M.D. (ASGE)6; Wasco, Kevin E. M.D. (SAGES)7 Author Information
A peptide export–import control circuit modulating bacterial development regulates protein phosphatases of the phosphorelay (1997)

The phosphorelay signal transduction system activates developmental transcription in sporulation of Bacillus subtilis by phosphorylation of aspartyl residues of the Spo0F and Spo0A response regulators. The phosphorylation level of these response regulators is determined by the opposing activities of protein kinases and protein aspartate phosphatases that interpret positive and negative signals for development in a signal integration circuit. The RapA protein aspartate phosphatase of the phosphorelay is regulated by a peptide that directly inhibits its activity. This peptide is proteolytically processed from an inactive pre-inhibitor protein encoded in the phrA gene. The pre-inhibitor is cleaved by the protein export apparatus to a putative pro-inhibitor that is further processed to the active inhibitor peptide and internalized by the oligopeptide permease. This export-import circuit is postulated to be a mechanism for timing phosphatase activity where the processing enzymes regulate the rate of formation of the active inhibitor. The processing events may, in turn, be controlled by a regulatory hierarchy. Chromosome sequencing has revealed several other phosphatase-prepeptide gene pairs in B. subtilis, suggesting that the use of this mechanism may be widespread in signal transduction.
SaaS Multi-tenant Application Customization (2013)

Cloud computing often uses the multi-tenancy architecture where tenants share system software. It is one of the key features of Software as a Service (SaaS) that enables higher profit margin by leveraging the economics of scale. Tenants residing on a multi-tenant application appear to be the sole owner of the application and not aware of the existence of others. A multi-tenant SaaS application accommodates each tenant's unique requirements by allowing tenant-level customization. A complex SaaS application that supports hundreds, even thousands of tenants could have hundreds of customization points with each of them providing multiple options, and this could result in a huge number of ways to customize the application. This paper proposes an innovative customization approach that studies similar tenants' customization choices and provides guided semi-automated customization process for the future tenants. A semi-automated customization process could enable tenants to quickly implement the customization that best suits their business needs.
Radical Scavenging Action and Its Mode in Procyanidins B-1 and B-3 from Azuki Beans to Peroxyl Radicals (1990)

Journal Article Radical Scavenging Action and Its Mode in Procyanidins B-1 and B-3 from Azuki Beans to Peroxyl Radicals Get access Toshiaki Ariga, Toshiaki Ariga Research and Development Division, Kikkoman Corporation, Noda-shi, Chiba 278, Japan Search for other works by this author on: Oxford Academic Google Scholar Mitsutoshi Hamano Mitsutoshi Hamano Research and Development Division, Kikkoman Corporation, Noda-shi, Chiba 278, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 54, Issue 10, 1 October 1990, Pages 2499–2504, https://doi.org/10.1080/00021369.1990.10870369 Published: 01 October 1990 Article history Received: 10 January 1990 Published: 01 October 1990
Directed Evolution To Investigate Steric Control of Enzymatic Oxidosqualene Cyclization. An Isoleucine-to-Valine Mutation in Cycloartenol Synthase Allows Lanosterol and Parkeol Biosynthesis (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTDirected Evolution To Investigate Steric Control of Enzymatic Oxidosqualene Cyclization. An Isoleucine-to-Valine Mutation in Cycloartenol Synthase Allows Lanosterol and Parkeol BiosynthesisElizabeth A. Hart, Ling Hua, Lisa B. Darr, William K. Wilson, Jihai Pang, and Seiichi P. T. MatsudaView Author Information Department of Chemistry and Department of Biochemistry and Cell Biology Rice University, Houston, Texas 77005 Cite this: J. Am. Chem. Soc. 1999, 121, 42, 9887–9888Publication Date (Web):October 8, 1999Publication History Received21 July 1999Published online8 October 1999Published inissue 1 October 1999https://pubs.acs.org/doi/10.1021/ja992589bhttps://doi.org/10.1021/ja992589brapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views628Altmetric-Citations86LEARN 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 (1)»Supporting Information Supporting Information SUBJECTS:Deprotonation,Fungi,Genetics,Peptides and proteins,Steroids Get e-Alerts
Core excitons and vibronic coupling in diamond and graphite (1993)

The C 1s exciton in diamond is studied by soft x-ray emission excited with high resolution monochromatic photons. A strong phonon sideband of 5 eV wide is observed in the exciton recombination spectrum. With the phonon contribution, the exciton binding energy is estimated to be 1.5 eV. The excited atoms is suggested to undergo Jahn-Teller relaxation similar to that of the nitrogen impurities in diamond. A similar exciton is observed at the ${\mathrm{\ensuremath{\sigma}}}^{\mathrm{*}}$-band threshold in graphite. These results provide new insights to the understanding of the core exciton and the donor problem in diamond and other systems.
Quantum-confined Stark effect in interdiffused AlGaAs/GaAs quantum well (1993)

The quantum-confined Stark effect is analyzed in an interdiffused Al0.3Ga0.7As/GaAs single quantum well (QW) with an as-grown well width of 100 Å, where the confinement profile is modeled by an error function. Results indicate a twofold enhancement of the Stark shift for the interdiffused quantum well over that of the square quantum well for a 50 kV/cm applied field. The fundamental exciton absorption peak also shows a much larger reduction with increasing applied field in the more extensively interdiffused QW. These characteristics may be used to realize optical modulators with higher on/off ratios and lower drive voltages.
Nonhomologous end joining and V(D)J recombination require an additional factor (2003)

DNA nonhomologous end-joining (NHEJ) is the major pathway for repairing DNA double-strand breaks in mammalian cells. It also functions to carry out rearrangements at the specialized breaks introduced during V(D)J recombination. Here, we describe a patient with T(-)B(-) severe combined immunodeficiency, whose cells have defects closely resembling those of NHEJ-defective rodent cells. Cells derived from this patient show dramatic radiosensitivity, decreased double-strand break rejoining, and reduced fidelity in signal and coding joint formation during V(D)J recombination. Detailed examination indicates that the patient is defective neither in the known factors involved in NHEJ in mammals (Ku70, Ku80, DNA-dependent protein kinase catalytic subunit, Xrcc4, DNA ligase IV, or Artemis) nor in the Mre11/Rad50/Nbs1 complex, whose homologue in Saccharomyces cerevisiae functions in NHEJ. These results provide strong evidence that additional activities are crucial for NHEJ and V(D)J recombination in mammals.
Human stem cell grafts as therapies for motor neuron disease (2008)

Stem cell transplantation, a widely accepted therapeutic approach to diseases of modular organs such as the heart and the endocrine pancreas, remains a controversial option for the nervous system. However, historical advances in the 1990s on key aspects of neural plasticity and the appreciation of the selective vulnerability of nerve cells and systems in degenerative and traumatic diseases require a re-examination of this scepticism. The successes and failures with prior trophic factor therapies are particularly enlightening; many lessons from this era can be creatively absorbed as the early outcomes with stem cell grafts in animal models of disease are evaluated. Stem cell grafting into spinal cord, traditionally a doomed enterprise because of lack of neurogenicity in this region and multiple early failures, is becoming promising again with recent findings from the authors' laboratory and elsewhere that specific types of cells and methods of culture are associated with much improved biological and functional outcomes.
Targeting Inflammatory Pathways for Prevention and Therapy of Cancer: Short-Term Friend, Long-Term Foe (2009)

Chronic infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and high-calorie diet have been recognized as major risk factors for the most common types of cancer. All these risk factors are linked to cancer through inflammation. Although acute inflammation that persists for short-term mediates host defense against infections, chronic inflammation that lasts for long term can predispose the host to various chronic illnesses, including cancer. Linkage between cancer and inflammation is indicated by numerous lines of evidence; first, transcription factors nuclear factor-kappaB (NF-kappaB) and signal transducers and activators of transcription 3 (STAT3), two major pathways for inflammation, are activated by most cancer risk factors; second, an inflammatory condition precedes most cancers; third, NF-kappaB and STAT3 are constitutively active in most cancers; fourth, hypoxia and acidic conditions found in solid tumors activate NF-kappaB; fifth, chemotherapeutic agents and gamma-irradiation activate NF-kappaB and lead to chemoresistance and radioresistance; sixth, most gene products linked to inflammation, survival, proliferation, invasion, angiogenesis, and metastasis are regulated by NF-kappaB and STAT3; seventh, suppression of NF-kappaB and STAT3 inhibits the proliferation and invasion of tumors; and eighth, most chemopreventive agents mediate their effects through inhibition of NF-kappaB and STAT3 activation pathways. Thus, suppression of these proinflammatory pathways may provide opportunities for both prevention and treatment of cancer.
Regulation of Phagosome Maturation by Signals from Toll-Like Receptors (2004)

In higher metazoans, phagocytosis is essential in host defense against microbial pathogens and in clearance of apoptotic cells. Both microbial and apoptotic cells are delivered on a common route from phagosomes to lysosomes for degradation. Here, we found that activation of the Toll-like receptor (TLR) signaling pathway by bacteria, but not apoptotic cells, regulated phagocytosis at multiple steps including internalization and phagosome maturation. Phagocytosis of bacteria was impaired in the absence of TLR signaling. Two modes of phagosome maturation were observed, constitutive and inducible; their differential engagement depended on the ability of the cargo to trigger TLR signaling.
Analysis of skeletal muscle function in the C57BL6/SV129 syncoilin knockout mouse (2008)

Syncoilin is a 64-kDa intermediate filament protein expressed in skeletal muscle and enriched at the perinucleus, sarcolemma, and myotendinous and neuromuscular junctions. Due to its pattern of cellular localization and binding partners, syncoilin is an ideal candidate to be both an important structural component of myocytes and a potential mediator of inherited myopathies. Here we present a report of a knockout mouse model for syncoilin and the results of an investigation into the effect of a syncoilin null state on striated muscle function in 6-8-week-old mice. An analysis of proteins known to associate with syncoilin showed that ablation of syncoilin had no effect on absolute expression or spatial localization of desmin or alpha dystrobrevin. Our syncoilin-null animal exhibited no differences in cardiotoxin-induced muscle regeneration, voluntary wheel running, or enforced treadmill exercise capacity, relative to wild-type controls. Finally, a mechanical investigation of isolated soleus and extensor digitorum longus indicated a potential differential reduction in muscle strength and resilience. We are the first to present data identifying an increased susceptibility to muscle damage in response to an extended forced exercise regime in syncoilin-deficient muscle. This study establishes a second viable syncoilin knockout model and highlights the importance of further investigations to determine the role of syncoilin in skeletal muscle.
The placebo effect in healthy volunteers: Influence of experimental conditions on the adverse events profile during phase I studies (1993)

In contrast to the plethora of publications on placebo effects in patients, very little is known about placebo effects in healthy volunteers during clinical pharmacology studies. We therefore reviewed the adverse events spontaneously reported during placebo administration in 109 double-blind, placebo-controlled studies involving 1228 volunteers. The overall incidence of adverse events in the healthy volunteers during placebo administration was 19%. As expected, complaints were more frequent after repeated dosing (28%) and in elderly subjects (26%). Overall, the most frequent adverse events were headache (7%), drowsiness (5%), and asthenia (4%), with some variation depending on study design and population. In conclusion, these data shed new light on the impact of experimental conditions on the results of safety evaluations in healthy volunteers participating in clinical pharmacology studies.
Recent Advances in Autonomic Function Tests of the Cardiovascular System in Children (1998)

Recent advances in computer technology have made it possible to noninvasively determine fast and dynamic changes in autonomic nervous activity in humans. Power spectral analysis of heart rate variation, beat-to-beat blood pressure analysis, skin blood flow by the laser Doppler technique, sensitive sudorometry and direct measurement of sympathetic nervous discharge have been successfully applied in adults, but there are still only few studies reported in children and adolescents. This article reviews the usefulness of these autonomic function tests in the pediatric field including reliability and methodological limits. Power spectral analysis of heart rate variability seems to be a new potential method, but there have been only few studies in children. Orthostatic maneuvers with noninvasive beat-to-beat measurement of finger arterial pressure, especially during active standing, is useful for the evaluation of orthostatic intolerance in children as well as adults with autonomic failure. A new pharmacological method using multiple autonomic agents might indicate a more precise information including alpha- and beta-adrenoceptor sensitivity. It should be realized that a single test cannot identify impaired autonomic functions, and a combination of several autonomic tests should be employed. Moreover, age-related changes and racial differences in autonomic function should be considered when interpreting obtained results.
Synthesis of new s‐triazolo[4,3‐b] pyridazines (1971)

Abstract A new synthesis of s ‐triazolo[4,3‐ b ]pyridazine derivatives has been achieved starting from 3,6‐dichloropyridazine. The method opens the way to substitutions in the 2‐ or 3‐ positions. A tri‐cycloderivative, a bis‐ s ‐triazolopyridazine, has also been synthesized.
Dependence Speculative Multithreaded Architecture (1997)

Boosting instruction level parallelism in dynamically scheduled processors requires a large instruction window. The approach taken by current superscalar processors to build the instruction window is known to have important limitations, such as the requirement of more powerful instruction fetch mechanisms and the increasing complexity and delay of the issue logic. In this paper we present a novel processor architectures (which is called DeSM) that takes a completely different approach to build a large instruction window. The idea is to identify at run-time sections of code that correspond to loops and execute concurrently several iterations even if they are dependent. Unlike superscalar processors, instructions are not decoded in sequential order and thus, the dependence checking mechanism of superscalar processors would not work for DeSM processors. In a DeSM processor, inter-thread dependences are speculated (i.e. they are predicted and instructions are executing obeying the predicte...