gebhart/patrepeval huggingface dataset:
The biosynthetic pathway of the nonsugar, high-intensity sweetener mogroside V from Siraitia grosvenorii (2016)

The consumption of sweeteners, natural as well as synthetic sugars, is implicated in an array of modern-day health problems. Therefore, natural nonsugar sweeteners are of increasing interest. We identify here the biosynthetic pathway of the sweet triterpenoid glycoside mogroside V, which has a sweetening strength of 250 times that of sucrose and is derived from mature fruit of luo-han-guo (Siraitia grosvenorii, monk fruit). A whole-genome sequencing of Siraitia, leading to a preliminary draft of the genome, was combined with an extensive transcriptomic analysis of developing fruit. A functional expression survey of nearly 200 candidate genes identified the members of the five enzyme families responsible for the synthesis of mogroside V: squalene epoxidases, triterpenoid synthases, epoxide hydrolases, cytochrome P450s, and UDP-glucosyltransferases. Protein modeling and docking studies corroborated the experimentally proven functional enzyme activities and indicated the order of the metabolic steps in the pathway. A comparison of the genomic organization and expression patterns of these Siraitia genes with the orthologs of other Cucurbitaceae implicates a strikingly coordinated expression of the pathway in the evolution of this species-specific and valuable metabolic pathway. The genomic organization of the pathway genes, syntenously preserved among the Cucurbitaceae, indicates, on the other hand, that gene clustering cannot account for this novel secondary metabolic pathway.
One-Step Synthesis of K-Selective Methacrylic-Acrylic Copolymers Containing Grafted Ionophore and Requiring No Plasticizer (2000)

A main drawback in the application of ion sensors that are based on plasticized polymeric membranes is the problem of leaching of plasticizer and ionophore. Leaching problems can be critical in solid-state minidevices, e.g., ion-selective electrodes or optodes, where a thin ion sensing polymer film is often empolyed. To resolve such problems, we have designed simple methacrylic-acrylic copolymers that required no plasticizer and which include immobilized polymerizable but hydrophilic ionophores such as 4-acryloylamidobenzo-15-crown-5 (AAB15C5) and 4-acryloylamidobenzo-18-crown-6 (AAB18C6) that would normally be susceptible to leaching from plasticized PVC membranes, were used as model ionophores for the immobilization studies. These crown compounds are attractive since they can be employed as a monomeric unit in the copolymer recipe and thus no additional synthesis or polymer modification is required. Copolymers suitable for ion-selective membrane application were synthesized by introducing more than 80 wt. % of n-butyl acrylate to yield copolymers of Tg's between –20 to –30 °C. The molecular weight distributions of these copolymers were M¯w <50 000 Da and they contained 2 to 6 wt. % of immobilized crown ether ionophores. The ‘self-plasticising’ methacrylic-acrylic membranes formed with these acryloyl crown ethers demonstrated good potentiometric responses to potassium ion. In contrast, AAB15C5 and AAB18C6 entrapped in membranes in a more classical ion selective membrane recipe, even when a plasticizer was included, were still inferior in their response to those with membranes containing immobilized ionophores. The restricted mobility of the immobilized ionophores in these self-plasticizing polymer matrices did not appear to hinder the normal complexation behavior of these ionophores. This was inferred from the possible formation of the usual 2:1 and 1:1 ionophore-cation complexes of AAB15C5 and AAB18C6, respectively, in these new copolymer matrices.
Clonal analysis of thymus-repopulating cells presents direct evidence for self-renewal division of human hematopoietic stem cells (2006)

To elucidate the in vivo kinetics of human hematopoietic stem cells (HSCs), CD34+CD38- cells were infected with lentivirus vector and transplanted into immunodeficient mice. We analyzed the multilineage differentiation and self-renewal abilities of individual thymus-repopulating clones in primary recipients, and their descending clones in paired secondary recipients, by tracing lentivirus gene integration sites in each lymphomyeloid progeny using a linear amplification-mediated polymerase chain reaction (PCR) strategy. Our clonal analysis revealed that a single human thymus-repopulating cell had the ability to produce lymphoid and myeloid lineage cells in the primary recipient and each secondary recipient, indicating that individual human HSCs expand clonally by self-renewal division. Furthermore, we found that the proportion of HSC clones present in the CD34+ cell population decreased as HSCs replicated during extensive repopulation and also as the differentiation capacity of the HSC clones became limited. This indicates the restriction of the ability of individual HSCs despite the expansion of total HSC population. We also demonstrated that the extensive self-renewal potential was confined in the relatively small proportion of HSC clones. We conclude that our clonal tracking studies clearly demonstrated that heterogeneity in the self-renewal capacity of HSC clones underlies the differences in clonal longevity in the CD34+ stem cell pool.
The Pharmacological Basis of Therapeutics. (1941)

No other journal can match Anesthesia & Analgesia for its original and significant contributions to the anesthesiology field. Each monthly issue features peer-reviewed articles reporting on the latest advances in drugs, preoperative preparation, patient monitoring, pain management, pathophysiology, and many other timely topics. Backed by internationally-known authorities who serve on the Editorial Board and as Section Editors, Anesthesia &Analgesia is your gateway to everything that is happening in anesthesia and 14 related subspecialties: Analgesia; Ambulatory Anesthesia; Anesthetic Pharmacology; Cardiovascular Anesthesia; Critical Care and Trauma; Economics, Education, and Policy; Neurosurgical Anesthesia; Obstetric Anesthesia; Pain Mechanisms; Pain Medicine; Pediatric Anesthesia; Regional Anesthesia; Patient Safety; and Technology, Computing and Simulation.
Differential T Cell Costimulatory Requirements in CD28-Deficient Mice (1993)

T cell receptor stimulation without costimulation is insufficient for the induction of an optimal immune response. It is thought that engagement of the CD28 molecule with its ligand B7 provides an essential costimulatory signal without which full activation of T cells cannot occur. A mouse strain with a defective CD28 gene was established. Development of T and B cells in the CD28-deficient mice appeared normal. However, T lymphocytes derived from CD28-/- mutant mice had impaired responses to lectins. Lectin stimulation did not trigger interleukin-2 (IL-2) production, IL-2 receptor alpha expression was significantly decreased, and exogenous IL-2 only partially rescued the CD28 defect. Basal immunoglobulin (Ig) concentrations in CD28-deficient mice were about one-fifth of those found in wild-type controls, with low titers of IgG1 and IgG2b but an increase in IgG2a. In addition, activity of T helper cells in CD28-/- mice was reduced and immunoglobulin class switching was diminished after infection with vesicular stomatitis virus. However, cytotoxic T cells could still be induced and the mice showed delayed-type hypersensitivity after infection with lymphocytic choriomeningitis virus. Thus, CD28 is not required for all T cell responses in vivo, suggesting that alternative costimulatory pathways may exist.
Nontoxigenic Clostridium difficile Protects Hamsters against Challenge with Historic and Epidemic Strains of Toxigenic BI/NAP1/027 C. difficile (2013)

Nontoxigenic Clostridium difficile (NTCD) has been shown to prevent fatal C. difficile infection in the hamster model when hamsters are challenged with standard toxigenic C. difficile strains. The purpose of this study was to determine if NTCD can prevent C. difficile infection in the hamster model when hamsters are challenged with restriction endonuclease analysis group BI C. difficile strains. Groups of 10 hamsters were given oral clindamycin, followed on day 2 by 10(6) CFU of spores of NTCD strain M3 or T7, and were challenged on day 5 with 100 CFU of spores of BI1 or BI6. To conserve animals, results for control hamsters challenged with BI1 or BI6 from the present study and controls from previous identical experiments were combined for statistical comparisons. NTCD strains M3 and T7 achieved 100% colonization and were 100% protective against challenge with BI1 (P ≤ 0.001). M3 colonized 9/10 hamsters and protected against BI6 challenge in the colonized hamsters (P = 0.0003). T7 colonized 10/10 hamsters, but following BI6 challenge, cocolonization occurred in 5 hamsters, 4 of which died, for protection of 6/10 animals (P = 0.02). NTCD colonization provides protection against challenge with toxigenic BI group strains. M3 is more effective than T7 in preventing C. difficile infection caused by the BI6 epidemic strain. Prevention of C. difficile infection caused by the epidemic BI6 strain may be more challenging than that of infections caused by historic BI1 and non-BI C. difficile strains.
Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM (2000)

Individuals with systemic lupus erythematosus and rheumatoid arthritis are characterized by the presence of high levels of circulating IgM and IgG autoantibodies. Although IgG autoantibodies often are pathogenic, the role of IgM autoantibodies in autoimmune disease is not clear. Using mice that are unable to secrete IgM but are able to express surface IgM and IgD and to secrete other classes of immunoglobulins, we examined the effect of the absence of secreted IgM in the development of IgG autoantibodies and autoimmune disease in lupus-prone lymphoproliferative (lpr) mice. Compared with regular lpr mice, lpr mice that lack secreted IgM developed elevated levels of IgG autoantibodies to double-stranded DNA and histones and had more abundant deposits of immune complexes in the glomeruli; they also suffered more severe glomerulonephritis and succumbed to the disease at an earlier age. Similarly, the absence of secreted IgM also resulted in an accelerated development of IgG autoantibodies in normal mice. These findings suggest that secreted IgM, including IgM autoantibodies produced naturally or as part of an autoimmune response, may lessen the severity of autoimmune pathology associated with IgG autoantibodies.
A particle-enhanced turbidimetric immunoassay for quantitative determination of orosomucoid in urine: development, validation and reference values (2004)

Increased urinary orosomucoid excretion rate (UOER) is an independent predictor of cardiovascular and all-cause mortality in patients with type 2 diabetes, as demonstrated by a conventional, immunoturbidimetric method. We wanted to optimize the method by developing a fully automated, particle-enhanced turbidimetric (PET) immunoassay with a lower detection limit, to allow assessment of orosomucoid in urine in healthy individuals and patients. A micro-particle-based immunoreagent was prepared for a PET immunoassay. The calibration was traceable to the certified reference material (CRM 470) for specific human serum proteins. We studied 69 healthy adults (28 men and 41 women) to establish reference values for the new assay. The detection limit of orosomucoid in urine was found to be 0.05 mg/l, about 20 times lower than for the conventional assay. Within-run imprecision [CV%, (level)] was 6.7% (0.23 mg/l), 1.0% (1.08 mg/l) and 1.0% (4.69 mg/l). Total imprecision [CV%, (level)] was 10.4% (0.23 mg/l), 3.9% (1.08 mg/l) and 3.4% (4.69 mg/l). Reference values [median (2.5-97.5 percentiles)] for UOER were 0.36 (0.07-2.04) microg/min and for urinary orosomucoid/creatinine ratio 0.04 (0.009-0.17) mg/mmol. We describe a fully automated, transferable, sufficiently precise, high-sensitivity assay for orosomucoid in urine and present reference values traceable to CRM 470.
Blood-borne human plasma cells in steady state are derived from mucosal immune responses (2008)

Providing humoral immunity, antibody-secreting plasma cells and their immediate precursors, the plasmablasts, are generated in systemic and mucosal immune reactions. Despite their key role in maintaining immunity and immunopathology, little is known about their homeostasis. Here we show that plasmablasts and plasma cells are always detectable in human blood at low frequency in any unimmunized donor. In this steady state, 80% of plasmablasts and plasma cells express immunoglobulin A (IgA). Expression of a functional mucosal chemokine receptor, C-C motif receptor 10 (CCR10) and the adhesion molecule beta(7) integrin suggests that these cells come from mucosal immune reactions and can return to mucosal tissue. These blood-borne, CCR10(+) plasmablasts also are attracted by CXCL12. Approximately 40% of plasma cells in human bone marrow are IgA(+), nonmigratory, and express beta(7) integrin and CCR10, suggesting a substantial contribution of mucosal plasma cells to bone marrow resident, long-lived plasma cells. Six to 8 days after parenteral tetanus/diphtheria vaccination, intracellular IgG(+) cells appear in blood, both CD62L(+), beta(7) integrin(-), dividing, vaccine-specific, migratory plasmablasts and nondividing, nonmigratory, CD62L(-) plasma cells of different specificities. Systemic vaccination does not impact on peripheral IgA(+) plasmablast numbers, indicating that mucosal and systemic humoral immune responses are regulated independent of each other.
Survival adjustment of mature dendritic cells by IL-15 (2005)

The survival of CD8+/CD44(hi) memory phenotype T cells depends on an IL-15 activity on nonlymphoid cells. Here, we report that IL-15 and its receptor were induced on dendritic cells (DCs) by a combination of IFN-gamma and NF-kappaB relA inducers. IL-15 conferred in an autocrine loop resistance to apoptosis that accompanied the maturation process in DCs in vitro. As an apparent result in vivo, mice deficient in IL-15 or its receptor harbor few DCs. Injecting DCs into IL-15-/- mice was associated with the appearance of CD8+/CD44(hi) T cells that depended on IL-15 expression but also correlated with the longevity of the DCs. These findings support the hypothesis that DCs mediate the effect of IL-15 on CD8+/CD44(hi) memory phenotype T cells.
Localization of ribosomal and telomeric DNA sequences in intact plant nuclei by in‐situ hybridization and three‐dimensional optical microscopy (1990)

We have combined the use of three-dimensional (3-D) fluorescence microscopy and computer image processing of images with in-situ hybridization to analyse the 3-D organization of interphase nuclei in plants. In sections of root tips of Pisum sativum, using cDNA probes, we have shown that telomeres are arranged around the nuclear periphery and that the ribosomal genes in this species appear to exist in discrete, 3-D domains.
Angiopoietin-like protein 4 is a potent hyperlipidemia-inducing factor in mice and inhibitor of lipoprotein lipase (2002)

Studies with KK/San, obese and diabetic model mice having a unique hypotriglyceridemia phenotype, revealed that angiopoietin-like protein 3 (ANGPTL3) regulates lipid metabolism in mice. To determine the lipid-modulating role of other ANGPTLs, we focused on ANGPTL4, which overall shows a significant similarity to ANGPTL3. Surprisingly, an intravenous injection of the ANGPTL4 protein in KK/San mice rapidly increased the circulating plasma lipid levels at a higher rate than ANGPTL3 protein. Furthermore, the ANGPTL4 protein inhibited the lipoprotein lipase activity in vitro.
Retinal Hemodynamics in Early Diabetic Macular Edema (2006)

The objective of this study was to establish the baseline retinal hemodynamic characteristics of stratified groups of diabetic patients at increasing risk for the development of diabetic macular edema (DME). Group 1 had 50 control subjects, group 2 had 56 diabetic patients without clinically visible retinopathy, group 3 had 54 diabetic patients with microaneurysms and/or hard exudates within two disc diameters of the fovea in the absence of clinically manifest DME, and group 4 had 40 patients with clinically manifest DME. Retinal hemodynamics (diameter, velocity, maximum-to-minimum velocity ratio, and flow) were assessed. Intraocular pressure, blood pressure, and relevant systemic markers of diabetes control and complications were also undertaken. The maximum-to-minimum velocity ratio was elevated with increasing risk of clinically significant DME (P < 0.0001). No significant differences were found between the groups with respect to diameter, velocity, or flow. The maximum-to-minimum velocity ratio was correlated to age, duration of diabetes, blood pressure, pulse rate, intraocular pressure, and serum potassium levels. In conclusion, the maximum-to-minimum velocity ratio was significantly increased with increasing risk of development of DME. Retinal arteriolar hemodynamics were positively correlated to age, duration of diabetes, and blood pressure. These findings suggest a reduction in the compliance (i.e., an increase of vascular rigidity) of the arteriolar circulation with increasing risk of DME.
Diabetes Mellitus: Screening and Diagnosis. (2016)

Diabetes mellitus is one of the most common diagnoses made by family physicians. Uncontrolled diabetes can lead to blindness, limb amputation, kidney failure, and vascular and heart disease. Screening patients before signs and symptoms develop leads to earlier diagnosis and treatment, but may not reduce rates of end-organ damage. Randomized trials show that screening for type 2 diabetes does not reduce mortality after 10 years, although some data suggest mortality benefits after 23 to 30 years. Lifestyle and pharmacologic interventions decrease progression to diabetes in patients with impaired fasting glucose or impaired glucose tolerance. Screening for type 1 diabetes is not recommended. The U.S. Preventive Services Task Force recommends screening for abnormal blood glucose and type 2 diabetes in adults 40 to 70 years of age who are overweight or obese, and repeating testing every three years if results are normal. Individuals at higher risk should be considered for earlier and more frequent screening. The American Diabetes Association recommends screening for type 2 diabetes annually in patients 45 years and older, or in patients younger than 45 years with major risk factors. The diagnosis can be made with a fasting plasma glucose level of 126 mg per dL or greater; an A1C level of 6.5% or greater; a random plasma glucose level of 200 mg per dL or greater; or a 75-g two-hour oral glucose tolerance test with a plasma glucose level of 200 mg per dL or greater. Results should be confirmed with repeat testing on a subsequent day; however, a single random plasma glucose level of 200 mg per dL or greater with typical signs and symptoms of hyperglycemia likely indicates diabetes. Additional testing to determine the etiology of diabetes is not routinely recommended.
The Search for Optimal Visual Stimuli (1997)

Natural disasters such as hurricanes may contribute to mosquito abundance and, consequently, arbovirus transmission risk. In 2011, flooding from Hurricane Irene in eastern North Carolina (NC) resulted in increased mosquito populations that hindered recovery efforts. Budget shortfalls in NC have reduced the functionality of long-term mosquito surveillance and control programs; hence, many counties rely on the Federal Emergency Management Agency for post-disaster mosquito control. This pilot study examines mosquito abundance pre- and post-aerial insecticide spraying at eight study sites in Washington and Tyrrell Counties in rural eastern NC after Hurricane Irene. Percent change was calculated and compared for traps in areas that received aerial pesticide application and those that did not. Traps in spray zones show decreases in mosquito abundance when compared to control traps (treatment: -52.93%; control: 3.55%), although no significant differences (P = 0.286) were found in mosquito abundance between groups. Implications of reactive rather than proactive mosquito control responses are discussed.
Dental disease and risk of coronary heart disease and mortality. (1993)

Dental disease is associated with an increased risk of coronary heart disease, particularly in young men. Whether this is a causal association is unclear. Dental health may be a more general indicator of personal hygiene and possibly health care practices.
Identification of SSF1, CNS1, and HCH1 as multicopy suppressors of a Saccharomyces cerevisiae Hsp90 loss-of-function mutation (1999)

Hsp90 functions in a multicomponent chaperone system to promote the maturation and maintenance of a diverse, but specific, set of target proteins that play key roles in the regulation of cell growth and development. To identify additional components of the Hsp90 chaperone system and its targets, we searched for multicopy suppressors of various temperature-sensitive mutations in the yeast Hsp90 gene, HSP82. Three suppressors were isolated for one Hsp90 mutant (glutamate --> lysine at amino acid 381). Each exhibited a unique, allele-specific pattern of suppression with other Hsp90 mutants and had unique structural and biological properties. SSF1 is a member of an essential gene family and functions in the response to mating pheromones. CNS1 is an essential gene that encodes a component of the Hsp90 chaperone machinery. The role of HCH1 is unknown; its sequence has no strong homology to any protein of known function. SSF1 and CNS1 were weak suppressors, whereas HCH1 restored wild-type growth rates at all temperatures tested to cells expressing the E381K mutant. Overexpression of CNS1 or HCH1, but not SSF1, enhanced the maturation of a heterologous Hsp90 target protein, p60(v-src). These results suggest that like Cns1p, Hch1p is a general modulator of Hsp90 chaperone functions, whereas Ssf1p likely is either an Hsp90 target protein or functions in the same pathway as an Hsp90 target protein.
Cross‐reactivity of GroEL antibodies with human heat shock protein 60 and quantification of pathogens in atherosclerosis (2005)

These results support the hypothesis that in some patients, cross-reactivity of the immune response to bacterial HSPs including those of periodontal pathogens, with arterial endothelial cells expressing hHSP60 may be a possible mechanism for the association between atherosclerosis and periodontal infection.
Evaluation of parallel copying garbage collection on a shared-memory multiprocessor (1993)

A parallel copying garbage collection algorithm for symbolic languages executing on shared-memory multiprocessors is proposed. The algorithm is an extension of Baker's sequential algorithm with a novel method of heap allocation to prevent fragmentation and facilitate load distribution during garbage collection. An implementation of the algorithm within a concurrent logic programming system, VPIM, has been evaluated and the results, for a wide selection of benchmarks, are analyzed here. The authors show 1) how much the algorithm reduces the contention for critical sections during garbage collection, 2) how well the load-balancing strategy works and its expected overheads, and 3) the expected speedup achieved by the algorithm.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cardiopulmonary Bypass Induces Release of Soluble CD40 Ligand (2002)

The present study demonstrates that CPB causes an increase in the concentration of plasma sCD40L. The corresponding decrease in platelet CD40L suggests that this prothrombotic and proinflammatory protein was derived primarily from platelets and may contribute to the thrombotic and inflammatory complications associated with CPB.