gebhart/patrepeval huggingface dataset:
Co‐expression of TNFα and IL‐1β in human acute pulmonary fibrotic diseases: An immunohistochemical analysis (1996)

To clarify the involvement of TNF alpha and IL-1 beta in the initiation of fibrotic lung diseases, their localization was examined by immunohistochemistry. Fibrotic lung diseases observed were classified into acute and old pulmonary fibrotic changes. The acute fibrotic changes included adult respiratory distress syndrome, acute interstitial pneumonia and idiopathic pulmonary fibrosis with acute exacerbation. Acute pulmonary fibrotic changes histopathologically corresponded to a mixture of the exudative and proliferative phases of diffuse alveolar damage. Both TNF alpha and IL-1 beta were positive in the alveolar macrophages and proliferating type II pneumocytes in acute fibrotic changes. In contrast, positive cells for TNF alpha and IL-1 beta were sparse in the areas of old fibrotic change and in the normal tissue. These findings suggest that TNF alpha and IL-1 beta play an important role in the initiation of pulmonary fibrotic responses and in the architectural remodeling, irrespective of the etiology of fibrotic lung diseases.
The loss of GLUT2 expression by glucose-unresponsive beta cells of db/db mice is reversible and is induced by the diabetic environment. (1992)

Glucose-induced insulin secretion by beta cells of diabetic db/db mice was studied by a pancreas perfusion technique, and the levels of GLUT2 protein in pancreatic islets were assessed by immunofluorescence microscopy and protein blot analysis. Beta cells from diabetic mice had a high basal rate of insulin secretion; they did not respond to glucose stimulation but displayed a normal secretory response to arginine. At the same time, GLUT2 expression by db/db islets was lost whereas beta cells from nondiabetic db/+ mice expressed high levels of this transporter. GLUT2 levels in liver or kidney of diabetic mice were, however, mostly unaltered. Transplanting islets from db/db mice under the kidney capsule of db/+ mice restored normal GLUT2 levels. Conversely, transplantation of db/+ islets into db/db mice induced the disappearance of GLUT2 expression. When islets from db/+ mice were transplanted under the kidney capsule of streptozocin-diabetic mice, the immunodetection of GLUT2 also disappeared. We conclude that: (a) GLUT2 expression is decreased in glucose-unresponsive beta cells from db/db mice; (b) the decreased expression of GLUT2 is reversible; (c) the loss of GLUT2 expression is induced by the diabetic environment of db/db and streptozocin-induced diabetic mice. These observations together with previously published data suggest that a factor different from glucose or insulin regulates the beta cell expression of GLUT2.
Contact transition control: an experimental study (2002)

Several methods for controlling the transition from free motion to constrained motion are examined, with an emphasis on minimizing fingertip load oscillations during the transition. An approach based on input command shaping is discussed and compared with several methods developed in prior research. The various techniques were evaluated on a one-axis impact testbed, and results from those experiments are presented. The input shaping method was found to be comparable, and in some cases superior, to existing techniques of contact transition control.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents (2003)

Elemental diet resulted in striking improvement in both symptoms and histologic evidence of disease in children and adolescents with EoE, as identified by strict diagnostic criteria.
Histones from Dying Renal Cells Aggravate Kidney Injury via TLR2 and TLR4 (2012)

In AKI, dying renal cells release intracellular molecules that stimulate immune cells to secrete proinflammatory cytokines, which trigger leukocyte recruitment and renal inflammation. Whether the release of histones, specifically, from dying cells contributes to the inflammation of AKI is unknown. In this study, we found that dying tubular epithelial cells released histones into the extracellular space, which directly interacted with Toll-like receptor (TLR)-2 (TLR2) and TLR4 to induce MyD88, NF-κB, and mitogen activated protein kinase signaling. Extracellular histones also had directly toxic effects on renal endothelial cells and tubular epithelial cells in vitro. In addition, direct injection of histones into the renal arteries of mice demonstrated that histones induce leukocyte recruitment, microvascular vascular leakage, renal inflammation, and structural features of AKI in a TLR2/TLR4-dependent manner. Antihistone IgG, which neutralizes the immunostimulatory effects of histones, suppressed intrarenal inflammation, neutrophil infiltration, and tubular cell necrosis and improved excretory renal function. In summary, the release of histones from dying cells aggravates AKI via both its direct toxicity to renal cells and its proinflammatory effects. Because the induction of proinflammatory cytokines in dendritic cells requires TLR2 and TLR4, these results support the concept that renal damage triggers an innate immune response, which contributes to the pathogenesis of AKI.
Immunomodulation of Natural Killer Cell Activity by Flavone Acetic Acid: Occurrence Via Induction of Interferon /beta (1988)

The investigational drug flavone acetic acid (FAA) systemically augments natural killer (NK) cell activity in normal and tumor-bearing mice and in human cancer patients. The results from the present investigation demonstrate that in vivo administration of FAA induces in a dose-dependent manner high levels of serum interferon (IFN) within 4 hours in BALB/c, C57BL/6, and BALB/c nude mice. Antibody neutralization studies indicated that FAA induced IFN of the α/β type, while molecular hybridization studies demonstrated that FAA rapidly stimulated the production of IFN a mRNA in splenic leukocytes. In vivo administration of anti-IFN α/β antibodies to FAA-treated mice inhibited the FAA-induced augmentation of splenic NK cell activity at 4 hours. These results suggest that FAA mediates its anti-tumor effects indirectly by immunomodulation as well as directly by antiproliferative or cytotoxic activity. [J Natl Cancer Inst 1988;80:1226–1231]
Increasing diterpene yield with a modular metabolic engineering system in E. coli: comparison of MEV and MEP isoprenoid precursor pathway engineering (2009)

Engineering biosynthetic pathways in heterologous microbial host organisms offers an elegant approach to pathway elucidation via the incorporation of putative biosynthetic enzymes and characterization of resulting novel metabolites. Our previous work in Escherichia coli demonstrated the feasibility of a facile modular approach to engineering the production of labdane-related diterpene (20 carbon) natural products. However, yield was limited (<0.1 mg/L), presumably due to reliance on endogenous production of the isoprenoid precursors dimethylallyl diphosphate and isopentenyl diphosphate. Here, we report incorporation of either a heterologous mevalonate pathway (MEV) or enhancement of the endogenous methyl erythritol phosphate pathway (MEP) with our modular metabolic engineering system. With MEP pathway enhancement, it was found that pyruvate supplementation of rich media and simultaneous overexpression of three genes (idi, dxs, and dxr) resulted in the greatest increase in diterpene yield, indicating distributed metabolic control within this pathway. Incorporation of a heterologous MEV pathway in bioreactor grown cultures resulted in significantly higher yields than MEP pathway enhancement. We have established suitable growth conditions for diterpene production levels ranging from 10 to >100 mg/L of E. coli culture. These amounts are sufficient for nuclear magnetic resonance analyses, enabling characterization of enzymatic products and hence, pathway elucidation. Furthermore, these results represent an up to >1,000-fold improvement in diterpene production from our facile, modular platform, with MEP pathway enhancement offering a cost effective alternative with reasonable yield. Finally, we reiterate here that this modular approach is expandable and should be easily adaptable to the production of any terpenoid natural product.
Numerical Methods for Unconstrained Optimization and Nonlinear Equations (1996)

Preface 1. Introduction. Problems to be considered Characteristics of 'real-world' problems Finite-precision arithmetic and measurement of error Exercises 2. Nonlinear Problems in One Variable. What is not possible Newton's method for solving one equation in one unknown Convergence of sequences of real numbers Convergence of Newton's method Globally convergent methods for solving one equation in one uknown Methods when derivatives are unavailable Minimization of a function of one variable Exercises 3. Numerical Linear Algebra Background. Vector and matrix norms and orthogonality Solving systems of linear equations-matrix factorizations Errors in solving linear systems Updating matrix factorizations Eigenvalues and positive definiteness Linear least squares Exercises 4. Multivariable Calculus Background Derivatives and multivariable models Multivariable finite-difference derivatives Necessary and sufficient conditions for unconstrained minimization Exercises 5. Newton's Method for Nonlinear Equations and Unconstrained Minimization. Newton's method for systems of nonlinear equations Local convergence of Newton's method The Kantorovich and contractive mapping theorems Finite-difference derivative methods for systems of nonlinear equations Newton's method for unconstrained minimization Finite difference derivative methods for unconstrained minimization Exercises 6. Globally Convergent Modifications of Newton's Method. The quasi-Newton framework Descent directions Line searches The model-trust region approach Global methods for systems of nonlinear equations Exercises 7. Stopping, Scaling, and Testing. Scaling Stopping criteria Testing Exercises 8. Secant Methods for Systems of Nonlinear Equations. Broyden's method Local convergence analysis of Broyden's method Implementation of quasi-Newton algorithms using Broyden's update Other secant updates for nonlinear equations Exercises 9. Secant Methods for Unconstrained Minimization. The symmetric secant update of Powell Symmetric positive definite secant updates Local convergence of positive definite secant methods Implementation of quasi-Newton algorithms using the positive definite secant update Another convergence result for the positive definite secant method Other secant updates for unconstrained minimization Exercises 10. Nonlinear Least Squares. The nonlinear least-squares problem Gauss-Newton-type methods Full Newton-type methods Other considerations in solving nonlinear least-squares problems Exercises 11. Methods for Problems with Special Structure. The sparse finite-difference Newton method Sparse secant methods Deriving least-change secant updates Analyzing least-change secant methods Exercises Appendix A. A Modular System of Algorithms for Unconstrained Minimization and Nonlinear Equations (by Robert Schnabel) Appendix B. Test Problems (by Robert Schnabel) References Author Index Subject Index.
Solution-Phase Bioconjugate Synthesis Using Protected Oligonucleotides Containing 3‘-Alkyl Carboxylic Acids (1998)

Protected oligonucleotides containing 3‘-alkyl carboxylic acids are obtained from a photolabile solid-phase synthesis support (1b). The protected oligonucleotides are efficiently conjugated (>80%) with amines in solution to yield products of high purity under mild reaction conditions. This method is particularly well-suited for the synthesis of oligonucleotide−peptide conjugates containing a covalent linkage between the 3‘ terminus of an oligonucleotide and the amino terminus of a peptide. High yields of nucleopeptides are obtained even when the peptide contains a hindered N-terminal amino acid.
Characterization of reproductive hormonal dynamics in the perimenopause. (1996)

Medical therapy for women in the perimenopausal period is controversial, in part due to varying degrees of ovarian hormone secretion characteristic of this time of life. To extend our understanding of the reproductive endocrine milieu of perimenopausal women, we studied 6 cycling women, aged 47 yr and older, for 6 months with daily collections of first morning voided urine. Five additional older reproductive aged (43-47 yr old) women were studied with daily urine and serum sampling for a single menstrual cycle; their urinary hormone data were combined with the former group for menstrual cycle comparisons. Urine was assayed for LH, FSH, estrone conjugates, and pregnanediol glucuronide and normalized for creatinine (Cr). Eleven midreproductive aged (19-38 yr old) normally cycling women, 5 women with well defined premature ovarian failure, and 5 women aged 54 yr and older who were at least 1 yr postmenopausal were used for comparison. Perimenopausal women had shorter follicular phases (11 +/- 2 days vs. 14 +/- 1 days; P = 0.031) and, hence, shorter menstrual cycles than midreproductive aged controls. FSH excretion in perimenopausal women was greater than that in younger women (range of means, 4-32 vs 3-7 IU/g Cr; P = 0.0005). LH secretion was overall greater than that in younger normal subjects (range of means, 1.4-6.8 vs. 1.1-4.2 IU/g Cr; P < 0.026). Overall mean estrone conjugate excretion was greater in the perimenopausal women compared to that in the younger women [76.9 ng/mg Cr (range, 13.1-135) vs. 40.7 ng/mg Cr (range, 22.8-60.3); P = 0.023] and was similarly elevated in both follicular and luteal phases. Luteal phase pregnanediol excretion was diminished in the perimenopausal women compared to that in younger normal subjects (range for integrated pregnanediol, 1.0-8.4 vs. 1.6-12.7 microg/mg Cr/luteal phase; P = 0.015). Compared to postmenopausal women, perimenopausal women had more overall estrone excretion (2.5-6.2 ng/mg Cr in postmenopausal women; P = 0.02) and lower mean FSH (range of means for postmenopause, 24-85 IU/g Cr; P = 0.017) and LH (range for postmenopause, 4.3-14.8 IU/g Cr; P = 0.041). Compared to women with premature menopause, perimenopausal women again had lower FSH (range of means for premature menopause, 36-82 IU/g Cr; P = 0.0022), lower LH (range of means for premature menopause, 5.5-23.8 IU/g Cr; P = 0.0092), borderline higher mean estrone conjugates (range of means for premature menopause, 4-44 ng/mg Cr; P = 0.064), and far longer periods of ovarian activity (one to two cycles in prematurely menopausal women vs. three to six cycles in perimenopausal women). We conclude that altered ovarian function in the perimenopause can be observed as early as age 43 yr and include hyperestrogenism, hypergonadotropism, and decreased luteal phase progesterone excretion. These hormonal alterations may well be responsible for the increased gynecological morbidity that characterizes this period of life.
Aetiology of meningitis in HIV-infected patients in a referral hospital in Phnom Penh, Cambodia (2003)

The HIV epidemic in Cambodia is one of the most extensive in Asia. Meningitis accounts for a substantial proportion of HIV-related morbidity and mortality in Cambodia. A retrospective chart review was performed to identify the clinical and spinal fluid characteristics of patients undergoing spinal tap at an AIDS referral hospital in Phnom Penh, Cambodia during a 16-month period. Of 932 charts reviewed, 89 met criteria for analysis. Overall mortality was 49.4%. Cryptococcus was the most commonly identified pathogen (83%), followed by mycobacteria (8%). No pathogen was identified in 9% of charts reviewed. In hospital mortality was similar in all groups.
Live‐attenuated influenza viruses as delivery vectors for Chlamydia vaccines (2007)

Effective delivery systems are needed to design efficacious vaccines against the obligate intracellular bacterial pathogen, Chlamydia trachomatis. Potentially effective delivery vehicles should promote the induction of adequate levels of mucosal T-cell and antibody responses that mediate long-term protective immunity. Antigen targeting to the nasal-associated lymphoid tissue (NALT) is effective for inducing high levels of specific immune effectors in the genital mucosa, and therefore suitable for vaccine delivery against genital chlamydial infection. We tested the hypothesis that live attenuated influenza A viruses are effective viral vectors for intranasal delivery of subunit vaccines against genital chlamydial infection. Recombinant influenza A/PR8/34 (H1N1) viruses were generated by insertion of immunodominant T-cell epitopes from chlamydial major outer membrane protein into the stalk region of the neuraminidase gene. Intranasal immunization of mice with viral recombinants resulted in a strong T helper 1 (Th1) response against intact chlamydial elementary bodies. Also, immunized mice enjoyed a significant state of protective immunity (P > 0.002) by shedding less chlamydiae and rapidly clearing the infection. Furthermore, a high frequency of Chlamydia-specific Th1 was measured in the genital mucosal and systemic draining lymphoid tissues within 24 hr after challenge of vaccinated mice. Moreover, multiple epitope delivery provided a vaccine advantage over single recombinants. Besides, long-term protective immunity correlated with the preservation of a robustly high frequency of specific Th1 cells and elevated immunoglobulin G2a in genital secretions. Because live attenuated influenza virus vaccines are safe and acceptable for human use, they may provide a new and reliable approach to deliver efficacious vaccines against sexually transmitted diseases.
Spin-trapping studies on the free-radical products formed by metabolic activation of carbon tetrachloride in rat liver microsomal fractions isolated hepatocytes and in vivo in the rat (1982)

1. The metabolic activation of carbon tetrachloride to free-radical intermediates is an important step in the sequence of disturbances leading to the acute liver injury produced by this toxic agent. Electron-spin-resonance (e.s.r.) spin-trapping techniques were used to characterize the free-radical species involved. 2. Spin trapping was applied to the activation of carbon tetrachloride by liver microsomal fractions in the presence of NADPH, and by isolated intact rat hepatocytes. The results obtained with the spin trap N-benzylidene-2-methylpropylamine N-oxide ('phenyl t-butyl nitrone') (PBN) and [13C]carbon tetrachloride provide unequivocal evidence for the formation and trapping of the trichloromethyl free radical in these systems. 3. With the spin trap 2-methyl-2-nitrosopropane, however, the major free-radical species trapped are unsaturated lipid radicals produced by the initiating reaction of lipid peroxidation. 4. Although pulse radiolysis and other evidence support the very rapid formation of the trichloromethyl peroxy radical from the trichloromethyl radical and oxygen, no clear evidence for the trapping of the peroxy radical was obtainable. 5. The effects of a number of free-radical scavengers and metabolic inhibitors on the formation of the PBN-trichloromethyl radical adduct were studied, as were the influences of changing the concentration of PBN and incubation time. 6. High concentrations of the spin traps used were found to have significant effects on cytochrome P-450-mediated reactions; this requires caution in interpreting results of experiments done in the presence of PBN at concentrations greater than 50 mM.
On the Seeding and Oligomerization of pGlu-Amyloid Peptides (in vitro) (2006)

Oligomerization of amyloid beta (Abeta) peptides is the decisive event in the development of Alzheimer's disease (AD), the most common neurogenerative disorder in developed countries. Recent evidence links this conformation-driven process to primary- and secondary-structure modifications of Abeta. The N and C terminus of deposited Abeta has been shown to possess conspicuous heterogeneity. While the C-terminally longer form of Abeta, i.e., Abeta (42), is considered more amyloidogenic, the role of the N-terminal modifications, e.g., truncation and glutamate cyclization accounting for the majority of the deposited peptides, is less understood. In the present study, we characterized the oligomerization and seeding capacity of pGlu-amyloid peptides using two unrelated techniques based on flow cytometry or flourescence dye binding. Under different conditions and irrespective of the C terminus of Abeta, i.e., Abeta40 or 42, pGlu-modified peptides displayed an up to 250-fold accelerated initial formation of aggregates compared to unmodified Abeta. The accelerated seed formation is accompanied by a change in the oligomerization kinetics because of N-terminal pGlu formation. Furthermore, the formation of mixed aggregates consisting of either pGlu-Abeta (3-42) or ADan or ABri and Abeta (1-42) was investigated by Abeta fluorescence labeling in flow cytometry. The results suggest that pGlu-modified peptides are potential seeding species of aggregate formation in vivo. The data presented here and the abundance of pGlu peptides in amyloidoses, such as FBD and AD, suggest pGlu-amyloid peptides as a species with biophysical characteristics that might be in particular crucial for the initiation of the disease.
Intestinal fluid accumulation induced by oral challenge with Vibrio cholerae or cholera toxin in infant mice (1977)

The diarrheal response of orally inoculated infant mice to viable Vibrio cholerae and purified cholera toxin was quantitated by means of a fluid accumulation (FA) ratio. The FA ratio is defined as the gut weight/remaining body weight. FA ratios were determined in relation to time of exposure and dose. Onset of fluid accumulation with viable cells of strains CA401 and 569B occurred 8 h postinoculation and reached a near maximum of 16 h. A dose of 4 x 10(6) colony-forming units of strain CA401 was required for a positive response 16 to 18 h postinoculation. Several other classical cholera strains demonstrated a similar dose-related response. Strain 569B, however, required a 100-fold higher dose to give a positive response. Several mutant cholera strains were decreased virulence in other model systems elicited FA ratios decreased from wild-type values. Onset of fluid accumulation which cholera toxin occurred 6 to 8 h postinoculation and reached a maximum by 10 h. A dose of 0.5 microng was required for a positive response 10 to 12 h postinoculation. The positive response to toxin could be inhibited by preincubation with specific antitoxin.