gebhart/patrepeval huggingface dataset:
Metabolic syndrome, age‐associated neuroendocrine disorders, and dysregulation of tryptophan—kynurenine metabolism (2010)

The neuroendocrine theory of aging identified a cluster of conditions (hypertension, obesity, dyslipidemia, diabetes type 2, menopause, late onset depression, vascular cognitive impairment, impairment of immune defense, and some forms of cancer, e.g., breast and prostate) as age-associated neuroendocrine disorders (AAND). Obesity, dyslipidemia, hypertension, and type 2 diabetes were later described as metabolic syndromes (MetS). Chronic inflammation is currently considered as a common feature of MetS/AAND. One of the mechanisms by which chronic inflammation might trigger and/or maintain the development of MetS/AAND is transcriptional induction of indoleamine 2,3-dioxygenase (IDO), rate-limiting enzyme of tryptophan (TRY)-kynurenine (KYN) pathway, by pro-inflammatory cytokines (PIC). Activation of IDO shifts TRY metabolism from serotonin synthesis to formation of "kynurenines." Diminished serotonin production is associated with mental depression while increased formation of kynurenines might contribute to development of MetS/AAND via their apoptotic, neurotoxic, and pro-oxidative effects, and upregulation of inducible nitric oxide synthase, phospholipase A2, arachidonic acid, prostaglandin, 5-lipoxygenase, and leukotriene cascade. The combined presence of high producers of alleles of polymorphic PIC genes (e.g., interferon-gamma and tumor necrosis factor alpha) might account for the genetic predisposition to high levels of PIC production, leading to "superinduction" of IDO. The other rate-limiting enzyme of the TRY-KYN pathway, TRY 2,3-dioxygenase, is activated by substrate (TRY) and cortisol. Therefore, KYN-TRY metabolism might be the meeting point for gene-environment interaction and a new target for prevention and treatment of MetS/AAND.
Deficiency of Carnitine in Cachectic Cirrhotic Patients (1977)

Carnitine is synthesized from lysine and methionine. In the rat, inadequate intake of either of these essential amino acids causes carnitine depletion. Inasmuch as protein deficiency is common in the hospital population, we have investigated the possible occurrence of nosocomial carnitine deficiency. Fasting serum carnitine concentration was measured in 16 normal and 247 patients in 16 disease groups. Normal range of carnitine was 55-103 muM. Only the cirrhotic group showed significant (P < 0.05) hypocarnitinemia. 14 of 36 hospitalized cirrhotics had subnormal values for serum carnitine. The creatinine/height index, midarm muscle circumference, and triceps skin-fold thickness indicated protein-calorie starvation in the 14 hypocarnitinemic liver patients. In six of the hypocarnitinemic cirrhotics (average serum level 50% of normal), spontaneous dietary intakes of carnitine, lysine, and methionine were measured and found to be only 5-15% as great as in six normocarnitinemic, healthy controls. When these six cirrhotic and six normal subjects were given the same lysine-rich, methionine-rich, and carnitine-free nutritional intake, the normals maintained normal serum carnitine levels and excreted 100 mumol/day, whereas the cirrhotics' serum level fell to 25% of normal, and urinary excretion declined to 15 mumol/day. Seven hypocarnitinemic cirrhotics died. Postmortem concentrations of carnitine in liver, muscle, heart, kidney, and brain averaged only one-fourth to one-third those in corresponding tissues of eight normally nourished nonhepatic patients who died after an acute illness of a 1-3-day duration. THESE DATA SHOW THAT CARNITINE DEPLETION IS COMMON IN PATIENTS HOSPITALIZED FOR ADVANCED CIRRHOSIS, AND THAT IT RESULTS FROM THREE FACTORS: substandard intake of dietary carnitine; substandard intake of lysine and methionine, the precursors for endogenous carnitine synthesis; and loss of capacity to synthesize carnitine from lysine and methionine.
1283: HIT-Induced Adrenal Hemorrhage and Adrenal Insufficiency In Critically Ill Patients (2020)

1N/A, Whitestown, IN 2Suny Downstate, Brooklyn, NY 3Shifa International Hospital, Islamabad, Islamabad 4N/A, Brooklyn, NY
Study on the effect of broad beans assimilating phosphate for stock of photochemical action (2002)

Broad beans seedling assimilating Phosphate amount at sun-light was bigger than dark condition, and the difference increased as time progressed. The plan reduced for assimilating Phosphate amount even if sun would shine it again. They were both significantly difference for leaf and stem and root and whole plan of two groups. The distribution of Phosphate in broad beans was root>steam>leaf. The percentage of leaves of sun-light group assimilating ~(32)P at the total part not only was bigger than dark group, but the assimilating amount was significantly difference.
Assignment of Weight-Based Immunoglobulin G1 (IgG1) and IgG2 Units in Antipneumococcal Reference Serum Lot 89-S(F) for Pneumococcal Polysaccharide Serotypes 1, 4, 5, 7F, 9V, and 18C (2005)

Weight-based assignments for immunoglobulin G1 (IgG1) and IgG2 subclass antibodies to Streptococcus pneumoniae capsular polysaccharides (PnPs) in antipneumococcal standard reference serum lot 89-S (lot 89-S), also known as lot 89-SF, have been determined for serotypes 1, 4, 5, 7F, 9V, and 18C. This extends the usefulness of lot 89-S beyond the IgG1 and IgG2 subclass assignments for serotypes 3, 6B, 14, 19F, and 23F made previously (A. Soininen, H. Kayhty, I. Seppala, and T. Wuorimaa, Clin. Diagn. Lab. Immunol. 5:561-566, 1998) to cover 11 major serotypes associated with the highest percentage of pneumococcal disease worldwide. A method of equivalence of absorbances in enzyme immunosorbent assays was used to determine the IgG1 and IgG2 antibody concentrations for the additional serotypes in lot 89-S, based on the subclass values previously assigned for PnPs serotypes 6B, 14, and 23F. This cross-standardization method assures consistency with previous antibody assignments in that reference serum. The newly assigned subclass values for serotype 9V, and previously assigned values for serotype 14, were used to quantitate PnPs antibodies in sera from adult and pediatric subjects immunized with a pneumococcal conjugate vaccine. There was a predominance of IgG1 anti-PnPs antibodies in pediatric sera and IgG2 anti-PnPs antibodies in the adult sera. The IgG1 and IgG2 subclass assignments for the 11 PnPs serotypes in antipneumococcal standard reference serum lot 89-S are useful for quantitating and characterizing immune responses to pneumococcal infection and vaccination regimens.
Bilateral nasolacrimal duct atresia in a cria (2008)

A 2-month-old, male alpaca had a 1-month history of mucoid ocular discharge from the left eye. Signalment, history and clinical findings were suggestive of a congenital nasolacrimal outflow obstruction. A dacryocystorhinogram confirmed bilateral nasolacrimal duct atresia, which involved the distal half of both nasolacrimal ducts. In order to establish alternative outflow, a conjunctivomaxillosinusotomy and conjunctivorhinostomy were performed on the right and left eye, respectively. The surgical openings remain patent after 11 months, and there have been no clinical signs of nasolacrimal disease.
Evidence that laminin‐5 is a component of the tooth surface internal basal lamina, supporting epithelial cell adhesion (1999)

Laminin-5 (Ln-5) is an extracellular matrix (ECM) glycoprotein found in epithelial basal laminae. We studied its expression on the surface of rat molars, in relationship to the location of the internal basal lamina (IBL) of the junctional epithelium (JE). In order to avoid disruption of the JE-tooth interface as much as possible, the surface of molars was prepared by mechanical removal of tissue debris and detergent/osmotic lysis of epithelial cell layers, and directly stained by immunohistochemistry, without sectioning. Antibodies to Ln-5 specifically stained a narrow band in the region of the cemento-enamel junction (CEJ), consistent with the expected location of the IBL. Western blotting of ECM material detergent--solubilized from the prepared tooth surfaces confirmed the molecular nature of Ln-5 identified by immunohistochemistry. By the use of a high-definition 3-D microscope, it appeared that Ln-5 coated the most apical part of the enamel and the most coronal portion of the cementum, on either side of the CEJ. In adhesion assays performed directly on tooth surfaces, epithelial cells adhered preferentially to the Ln-5 coated area of the tooth compared to the root surface, which is coated by other ECM components. Adhesion to the Ln-5 coated surface was specifically inhibited by a function-blocking monoclonal antibody to Ln-5. These results suggest that Ln-5 is a component of the IBL, and that it may be important in promoting adhesion of JE cells onto the tooth surface.
Characterization of the Catalase-Peroxidase Gene (katG) and inhA Locus in Isoniazid-Resistant and -Susceptible Strains of Mycobacterium tuberculosis by Automated DNA Sequencing: Restricted Array of Mutations Associated with Drug Resistance (1996)

The catalase-peroxidase gene (katG) and a two-gene locus (inhA) containing mutations associated with resistance to isoniazid in Mycobacterium tuberculosis were sequenced in 34 resistant and 12 susceptible strains. Virtually all resistant organisms had amino acid changes in KatG or nucleotide substitutions upstream of inhA. A region of katG encoding two amino acids frequently altered in resistant strains (residues Ser315 and Arg463) and the inhA locus were sequenced in 10 susceptible and 51 isoniazid-resistant isolates from the Netherlands. Most (84%) of the resistant isolates had mutations in katG or the inhA locus or lacked katG. Together, approximately 75% of isoniazid-resistant isolates had replacements at amino acids 315 or 463 in KatG or nucleotide substitutions upstream of inhA. All 16 strains of Mycobacterium bovis and Mycobacterium microti studied had Leu463 rather than Arg463 in KatG, an observation consistent with the hypothesis that Leu463 is the ancestral condition in M. tuberculosis.
Emerging Analytical Technologies for Biotherapeutics Development (2008)

LEVEL: INTERMEDIATE A major goal of pharmaceutical development is to characterize pathways of chemical and physical instability and then to develop strategies to minimize them. Deamidation and oxidation are examples of the former, aggregation a result of the latter. The potential for the presence of multiple variants in protein-based pharmaceuticals highlights a need for analytical methods capable of reliably and accurately identifying and measuring those variants. The ideal analytical method would be sensitive, accurate, linear over a broad range, resistant to sample-matrix interference, capable of measuring all possible structural variants of a protein, and would allow for high throughput. Needless to say, such a method does not yet exist. So multiple methods are used to study the different characteristics of each protein. Chromatography and electrophoretic techniques have traditionally been the analytical “work horses” for measuring and monitoring protein quality. They are used in all stages of research and development including formulation development, comparability assessment, and commercial-product quality testing (release and stability). Although several of these methods have long been common in biotechnology product development, motivation for continued advancement stems from the desire to improve their sensitivity, accuracy, and specificity and adapt them to changing sample characteristics (e.g., highconcentration formulations) as well as higher throughput. We focus here on methods to detect, measure, and/or characterize protein aggregates and particles as well as advances in highthroughput technologies.
Calcium Release-activated Calcium Current (I CRAC) Is a Direct Target for Sphingosine (1998)

Whole cell patch-clamp recordings were made to study the regulation of the store-operated calcium release-activated calcium current (ICRAC) by metabolites involved in the sphingomyelin pathway in RBL-2H3 cells. Sphingosine, a regulator of cell growth, inhibits ICRAC completely within 200 s and independently from conversion to either sphingosine 1-phosphate or ceramide. Structural analogs of sphingosine, including N,N-dimethylsphingosine, DL-threo-dihydrosphingosine, and N-acetylsphingosine (C2-ceramide) also block ICRAC. This effect is always accompanied by an elevation of whole cell membrane capacitance. These sphingolipids appear, therefore, to accumulate in the plasma membrane and directly block ICRAC channels. Sphingosylphosphorylcholine also increases capacitance but does not inhibit ICRAC, demonstrating structural specificity and that the elevation of capacitance is necessary but not sufficient for block. Nerve growth factor, which is known to break down sphingomyelin, inhibits ICRAC, and this inhibition can be antagonized by reducing sphingosine production with L-cycloserine, suggesting that ICRAC is a physiologically relevant and direct target of sphingosine. We propose that sphingosine directly blocks ICRAC, suggesting that the sphingomyelin pathway is involved in ICRAC regulation.
Early History of Emmetsburg (1967)

with his team, to take us on a trip to the western part of Iowa.We traveled via Calmar and Charles City to Mason City, following the line of the McGregor & Missouri River Railway (now the Chicago, Milwaukee & St. Paul Railway) which that year had begun building its line west from Calmar.At Mason City we visited with W. H. Lyttle and Gil Church (both Clayton County men) who had started a small private bank -the Mason City Bank.Lyttle showed us several lots in the city, then a town of probably 300 inhabitants, on the main street, ranging in price from $150 to $200.He also showed us a quarter section of nice land two miles southwest of the city at $5 an acre.From Mason City we came to Clear Lake and remained there one day, expecting to do some
Attainable regions for reaction with separation (1997)

Abstract The attainable region approach for reaction – mixing systems is combined with geometric methods for the feasibility of separations. The result is a systematic approach to identify the feasible compositions that can be achieved in processes combining simultaneous reaction, mixing, and separation. An activity‐based formulation for both nonideal VLE and reaction‐rate expressions is applied to develop hybrid reactor–separator models for the multiphase CSTR and PFR with simultaneous vapor removal. A reaction–separation vector is defined that satisfies the same geometric properties as the reaction vector. Therefore, the attainable region can be constructed following the existing procedure for reaction–mixing systems. This approach provides a method to generate feasible process alternatives. The technique is demonstrated on two nonideal ternary mixtures: the production of dimethyl ether by dehydration of methanol, and the production of methyl tert‐butyl ether from isobutene and methanol. It is shown that for hybrid reaction–separation devices the entire composition space is not always attainable. In such cases, combining a hybrid device with traditional nonreactive separation is required to attain certain products.
Determination of factors affecting kinetics of solid-state transformation of fluconazole polymorph II to polymorph I using diffuse reflectance Fourier transform spectroscopy (2010)

Based on statistics, the Prout-Tompkins model provided the best fit for the transformation. The activation energy (E(a)) value derived from the rate constants of the Prout-Tompkins model was 329 kJ/mol. Model-independent analysis was also applied to the experimental results. The average values calculated using both methods were not significantly different. Factors affecting kinetics of transformation such as mechanical factors, relative humidity, and the effect of seeding were also studied. Mechanical factors, which included trituration and compression, proved to enhance transformation rate significantly. Relative humidity proved to transform both polymorphs to monohydrate form. The presence of seed crystals of polymorph I was proved not to affect the transformation process of polymorph II to polymorph I. Effect of solvent of crystallization (dichloromethane) was studied. A significant change of the rate of transformation was proved in the presence of solvent vapors, and a change on the mechanism was proposed.
Amphiregulin, an Epidermal Growth Factor Receptor Ligand, Plays an Essential Role in the Pathogenesis of Transforming Growth Factor-β-induced Pulmonary Fibrosis (2012)

Dysregulated amphiregulin (AR) expression and EGR receptor (EGFR) activation have been described in animal models of pulmonary fibrosis and in patients with idiopathic pulmonary fibrosis. However, the exact role of AR in the pathogenesis of pulmonary fibrosis has not been clearly defined. Here, we show that a potent profibrogenic cytokine TGF-β1 significantly induced the expression of AR in lung fibroblasts in vitro and in murine lungs in vivo. AR stimulated NIH3T3 fibroblast cell proliferation in a dose-dependent manner. Silencing of AR expression by siRNA or chemical inhibition of EGFR signaling, utilizing AG1478 and gefitinib, significantly reduced the ability of TGF-β1 to stimulate fibroblast proliferation and expression of α-smooth muscle actin, collagen, and other extracellular matrix-associated genes. TGF-β1-stimulated activation of Akt, ERK, and Smad signaling was also significantly inhibited by these interventions. Consistent with these in vitro findings, AR expression was impressively increased in the lungs of TGF-β1 transgenic mice, and either siRNA silencing of AR or chemical inhibition of EGFR signaling significantly reduced TGF-β1-stimulated collagen accumulation in the lung. These studies showed a novel regulatory role for AR in the pathogenesis of TGF-β1-induced pulmonary fibrosis. In addition, these studies suggest that AR, or AR-activated EGFR signaling, is a potential therapeutic target for idiopathic pulmonary fibrosis associated with TGF-β1 activation.
Genetic polymorphisms of matrix metalloproteinases and their inhibitors in potentially malignant and malignant lesions of the head and neck (2010)

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that are capable of cleaving all extra cellular matrix (ECM) substrates. Degradation of matrix is a key event in progression, invasion and metastasis of potentially malignant and malignant lesions of the head and neck. It might have an important polymorphic association at the promoter regions of several MMPs such as MMP-1 (-1607 1G/2G), MMP-2 (-1306 C/T), MMP-3 (-1171 5A/6A), MMP-9 (-1562 C/T) and TIMP-2 (-418 G/C or C/C). Tissue inhibitors of metalloproteinases (TIMPs) are naturally occurring inhibitors of MMPs, which inhibit the activity of MMPs and control the breakdown of ECM. Currently, many MMP inhibitors (MMPIs) are under development for treating different malignancies. Useful markers associated with molecular aggressiveness might have a role in prognostication of malignancies and to better recognize patient groups that need more antagonistic treatment options. Furthermore, the introduction of novel prognostic markers may also promote exclusively new treatment possibilities, and there is an obvious need to identify markers that could be used as selection criteria for novel therapies. The objective of this review is to discuss the molecular functions and polymorphic association of MMPs and TIMPs and the possible therapeutic aspects of these proteinases in potentially malignant and malignant head and neck lesions. So far, no promising drug target therapy has been developed for MMPs in the lesions of this region. In conclusion, further research is required for the development of their potential diagnostic and therapeutic possibilities.
The role of Csk in the dynamic negative regulation of T cell receptor signaling (2013)

The cytoplasmic tyrosine kinase, C-terminal Src kinase (Csk), negatively regulates T cell receptor (TCR) signaling by inhibiting Src family kinase (SFK) activity. Its function in T cells is poorly defined since genetic ablation in the T lineage causes abnormal thymic development. To circumvent this, we have generated a novel allele of Csk, CskAS, that can be inhibited rapidly and specifically by an analog of the common kinase inhibitor, PP1. We further generated bacterial artificial chromosome (BAC) transgenic mice expressing the CskAS allele in the absence of endogenous Csk expression. Initial characterization of CskAS by ectopic expression in Jurkat T cells revealed that in the basal state, Csk actively restrains Lck activity. Inhibition of CskAS induced ligand-independent initiation of TCR signaling and downstream activation events, indicating the presence of a feedback circuit sensitive to the basal signaling state. Dok-1 was identified as a candidate protein involved in this feedback rewiring. In contrast, we observed a block in TCR signaling at the level of PLCγ1 hydrolysis of phosphatidylinositol-(4,5)-bisphsophate (PIP2) following inhibition of CskAS in the BAC transgenic murine thymocytes. This implies that in primary thymocytes, activation of SFKs alone is insufficient for full TCR signaling . We further demonstrate that actin remodeling, most likely mediated by CD28 costimulation, is necessary for downstream propogation of proximal TCR signals by PLCγ1 to the calcium and MAPK pathways.
Recombinant human platelet‐derived growth factor and transforming growth factor‐β mediated contraction of human dermal fibroblast populated lattices is inhibited by Rho/GTPase inhibitor but does not require phosphatidylinositol‐3′ kinase (2002)

Matrix reorganization and tissue contraction are essential for wound healing. However, the intracellular signals that mediate these processes are largely unknown. We investigated cytokine-induced signaling and its potential role in contraction of adult human dermal fibroblast populated collagen lattices. The results document that recombinant human platelet-derived growth factor-BB and transforming growth factor-1 individually stimulate contraction of fibroblast populated collagen lattices, while a combination of the two cytokines leads to increased contraction. Although recombinant human platelet-derived growth factor-BB promoted collagen contraction, it failed to stimulate phosphatidylinositol-3' kinase in the human dermal fibroblasts. An inhibitor for phosphatidylinositol 3' kinase, wortmannin, had no effect on the cytokine-mediated collagen contraction. In addition, this failed activation of phosphatidylinositol 3' kinase is consistent with absence of tyrosine phosphorylation of the platelet-derived growth factor receptor when the cells are in a collagen matrix. In contrast, tyrosine phosphorylation of the platelet-derived growth factor receptor was readily detected in the dermal fibroblasts in monolayers. We also probed the potential role of Rho/GTPase in the cytokine-mediated contraction of fibroblast populated collagen lattices. Toxin B from Clostridium difficile at picomolar concentrations blocked both recombinant human platelet-derived growth factor and transforming growth factor-5 induced contraction. Further, this inhibition was correlated with the inhibition of cell spreading in collagen, which suggests the formation of actin fibers inside the cells is essential for cytokine-mediated contraction of fibroblast populated collagen lattices. Taken together, these results imply that Rho/GTPase signaling but not phosphoinositol-3' kinase is involved in the cytokine-mediated contraction of fibroblasts populated collagen lattice. These findings suggest a potential mechanism for these signaling components during human wound contraction.