gebhart/patrepeval huggingface dataset:
Acute mental stress elicits delayed increases in circulating inflammatory cytokine levels (2001)

The influence of acute mental stress on cardiovascular responses and concentrations of inflammatory cytokines up to 2 h later was assessed in 12 subjects exposed to stress and in eight control subjects. Beat-by-beat recordings of finger blood pressure and heart rate were made at rest and during two behavioural tasks (colour-word interference and mirror tracing). Blood was drawn after adaptation and at 45 min and 2 h after the tasks, and assayed for interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 receptor antagonist (IL-1Ra), C-reactive protein (CRP) and haematocrit. Saliva was sampled periodically and assayed for free cortisol. The tasks were rated as stressful by the participants. The stress group showed significant increases in systolic and diastolic blood pressure (mean rises of 16.4+/-12.3 and 12.6+/-6.9 mmHg respectively) and heart rate (5.39+/-5.3 beats/min); these values returned to baseline during the recovery period. The IL-6 concentration was increased by 56% at 2 h after the tasks (P<0.05), while IL-1Ra was increased by 12.3% (P<0.01). No changes in cardiovascular variables or cytokine concentrations were observed in the control subjects, and haematocrit did not change. The magnitude of blood pressure responses during tasks was correlated positively with the IL-6 concentration after 45 min (r=0.70, P<0.05), and with the IL-1Ra concentration after 2 h (r=0.63, P<0.05). Increases in TNF-alpha after 2 h were correlated with heart rate responses to tasks (r=0.66, P<0.05). Associations between IL-6 and IL-1Ra concentrations were also recorded. This study indicates that inflammatory cytokines respond to acute mental stress in humans with delayed increases, and suggest that individual differences in cytokine responses are associated with sympathetic reactivity.
Combinatorial chemistry and molecular diversity in drug discovery (1998)

Partial table of contents: COMBINATORIAL CHEMISTRY AND MOLECULAR DIVERSITY: AN INTRODUCTION. Historical Overview of the Developing Field of Molecular Diversity (J. Chabala, et al.). Solid-Phase Peptide Synthesis, Lead Generation, and Optimization (B. Seligman, et al.). Oligonucleotide Libraries as a Source of Molecular Diversity (H.-Y. Mei, et al.). SMALL MOLECULAR LIBRARIES. Protease Inhibitor Libraries (D. Patel & D. Campbell). Scaffolds for Small Molecule Libraries (M. Pavia). Encoded Combinatorial Chemistry (J. Jacobs & Z.-J. Ni). Parallel Organic Synthesis in Array Format (S. Hall). AUTOMATION, ANALYTICAL, AND COMPUTATIONAL METHODS. Automation of Combinatorial Chemistry for Large Libraries (M. Needels & J. Sugarman). Quantifying Diversity (Y. Martin, et al.). BIOLOGICAL DIVERSITY. Protein Scaffolds for Peptide Libraries (R. Hoess). SCREENING. Strategies for Screening Combinatorial Libraries (B. Beutel). COMBINATORIAL DRUG SCREENING AND DEVELOPMENT. Combinatorial Technologies: Prospects and Future Issues (J. Kerwin). Appendix. Index.
MHC class II molecules are required for initiation of positive selection but not during terminal differentiation of human CD4 single positive thymocytes (1997)

Positive selection of T cell precursors is an MHC dependent, multistep process by which functionally mature CD4+8- helper and CD4-8+ cytotoxic single positive (SP) T cells are generated from immature CD4+8+ double positive (DP) thymocytes. We investigated the requirement for TCR/MHC class II interactions during different stages of positive selection of human CD4 SP thymocytes. We show that sorted CD69- CD4+8+ DP preselection thymocytes cultured in fetal thymus lobes of normal mice were subject to positive selection and differentiated to CD3(high) CD69+, mature CD8 SP, and CD4 SP cells. When cultured in thymus lobes from MHC class II-deficient mice, these precursors failed to develop into mature CD4 SP T cells, indicating that in the hybrid cultures, murine MHC class II molecules are required for the development of mature human CD4 SP T cells. We have previously identified CD4 SP intermediate thymocytes that have received at least some of the signals involved in positive selection, since these cells are CD69+, CD3/TCR(high), and CD8beta- but that are still phenotypically and functionally immature. Here we demonstrate that in contrast to preselection thymocytes, these CD4 SP intermediate thymocytes can give rise to phenotypically mature and functionally CD4 SP progeny both in normal and in MHC class II-deficient thymus lobes. These results suggest that TCR/MHC interactions are required for the initial stages of positive selection, but are not essential during terminal differentiation to functionally mature CD4 SP T cells.
A Promising Therapeutic Approach for Multiple Sclerosis: Recombinant T-Cell Receptor Ligands Modulate Experimental Autoimmune Encephalomyelitis by Reducing Interleukin-17 Production and Inhibiting Migration of Encephalitogenic Cells into the CNS (2007)

Recombinant T-cell receptor ligands (RTLs) can prevent and reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner and are currently in clinical trials for treatment of subjects with multiple sclerosis (MS). To evaluate regulatory mechanisms, we designed and tested RTL551, containing the alpha1 and beta1 domains of the I-A(b) class II molecule covalently linked to the encephalitogenic MOG-35-55 peptide in C57BL/6 mice. Treatment of active or passive EAE with RTL551 after disease onset significantly reduced clinical signs and spinal cord lesions. Moreover, RTL551 treatment strongly and selectively reduced secretion of interleukin-17 and tumor necrosis factor alpha by transferred green fluorescent protein-positive (GFP+) MOG-35-55-reactive T-cells and almost completely abrogated existent GFP+ cellular infiltrates in affected spinal cord sections. Reduced inflammation in spinal cords of RTL551-treated mice was accompanied by a highly significant downregulation of chemokines and their receptors and inhibition of VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) expression by endothelial cells. Thus, RTL therapy cannot only inhibit systemic production of encephalitogenic cytokines by the targeted myelin oligodendrocyte glycoprotein-reactive T-cells but also impedes downstream local recruitment and retention of inflammatory cells in the CNS. These findings indicate that targeted immunotherapy of antigen-specific T-cells can result in a reversal of CNS lesion formation and lend strong support to the application of the RTL approach for therapy in MS.
Increased expression of the WNT antagonist sFRP-1 in glaucoma elevates intraocular pressure (2008)

Elevated intraocular pressure (IOP) is the principal risk factor for glaucoma and results from excessive impedance of the fluid outflow from the eye. This abnormality likely originates from outflow pathway tissues such as the trabecular meshwork (TM), but the associated molecular etiology is poorly understood. We discovered what we believe to be a novel role for secreted frizzled-related protein-1 (sFRP-1), an antagonist of Wnt signaling, in regulating IOP. sFRP1 was overexpressed in human glaucomatous TM cells. Genes involved in the Wnt signaling pathway were expressed in cultured TM cells and human TM tissues. Addition of recombinant sFRP-1 to ex vivo perfusion-cultured human eyes decreased outflow facility, concomitant with reduced levels of beta-catenin, the Wnt signaling mediator, in the TM. Intravitreal injection of an adenoviral vector encoding sFRP1 in mice produced a titer-dependent increase in IOP. Five days after vector injection, IOP increased 2 fold, which was significantly reduced by topical ocular administration of an inhibitor of a downstream suppressor of Wnt signaling. Thus, these data indicate that increased expression of sFRP1 in the TM appears to be responsible for elevated IOP in glaucoma and restoring Wnt signaling in the TM may be a novel disease intervention strategy for treating glaucoma.
Presynaptic Contributions of Chordin to Hippocampal Plasticity and Spatial Learning (2007)

Recently, several evolutionary conserved signaling pathways that play prominent roles in regulating early neurodevelopment have been found to regulate synaptic remodeling in the adult. To test whether adult neuronal expression of bone morphogenic protein (BMP) signaling components also plays a postnatal role in regulating neuronal plasticity, we modulated BMP signaling in mice both in vivo and in vitro by genetic removal of the BMP inhibitor chordin or by perfusing recombinant BMP signaling pathway components onto acute hippocampal slices. Chordin null mice exhibited a significant increase in presynaptic transmitter release from hippocampal neurons, resulting in enhanced paired-pulse facilitation and long-term potentiation. These mice also showed a decreased acquisition time in a water maze test along with less exploratory activity during Y-maze and open-field tests. Perfusion of BMP ligands onto hippocampal slices replicated the presynaptic phenotype of chordin null slices, but bath application of Noggin, another antagonist of BMP signaling pathway, significantly decrease the frequency of miniature EPSCs. These results demonstrate that the BMP signaling pathway contributes to synaptic plasticity and learning likely through a presynaptic mechanism.
Pharmacokinetics and toxicity of high-dose topical colonic 5-aminosalicylic acid therapy in patients with severely active total ulcerative colitis (1993)

Objective: To investigate the pharmcokinetics and toxicity of high-dose topical colonic 5-aminosalicylic acid (5-ASA, mesalazine) therapy in patients with severely active total ulcerative colitis. Design: During colonoscopy, a tube was placed through the instrumentation channel into the caecum; 4 g 5-ASA (enema) was instil led twice daily through the tube for 3 weeks. Patients: Eight patients with severely active total ulcerative colitis were investigated. Methods: 5-ASA and acetylated 5-ASA were monitored in serum (2 days) and urine (5 days). Colonic transport of Tc99m-labelled 5-ASA enema was measured by the nuclear imaging technique on the fifth day. 5-ASA toxicity was clinically and biochemically monitored. Results: Colonic absorption (Cmax on day 1, 1.4 ± 0.3μg/ml; mean ± SEM) and urinary excretion (total recovery on day 1, 10.5 ± 1.6%) of 5-ASA were low. The half-life of 5-ASA was long (t1/2 4.2 ± 0.9 h) and the percentage of unacetylated urinary 5-ASA (17±2%) was high, suggesting saturation of presystemic 5-ASA acetylation. Dose-corrected absorption, acetylation and excretion rates were two- to threefold lower than reported data from patients in remission. Regional radioactivity of Tc99m-labelled 5-ASA enema was high in the ascending colon (37%) and stool (45%) and low in the transverse (7%), descending (7%) and rectosigmoid (6%) colon. Clinical and biochemical monitoring of these eight patients did not reveal any 5-ASA toxicity. Conclusion: Pharmacokinetics of 5-ASA in patients with severely active total ulcerative colitis show low 5-ASA absorption, acetylation and excretion rates. Colonic transit studies suggest rapid transit of the enema through the left-sided colon. High-dose topical colonic 5-ASA therapy seems to be possible without significant toxicity.
Hybrid organic/quantum dot thin film structures and devices (2005)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.
Hormonal Control of Plasminogen Activator Inhibitor-1 Gene Expression and Production in Human Adipose Tissue: Stimulation by Glucocorticoids and Inhibition by Catecholamines1 (1999)

Plasma levels of type 1 plasminogen activator inhibitor (PAI-1), a risk factor for cardiovascular disease, are elevated in obese subjects, especially those with omental fat accumulation. We investigated the hormonal control of PAI-1 gene expression and secretion in cultured human adipose tissue. We more particularly focused on the effects of glucocorticoids, insulin, cAMP, and catecholamines in explants from the omental region. The addition of dexamethasone to the culture medium increased PAI-1 secretion in a time-dependent manner for up to 24 h. The stimulation by the glucocorticoid was preceded by a 2-fold rise in PAI-1 messenger ribonucleic acid levels between 4-8 h of culture. The effectiveness of the glucocorticoid was concentration dependent, with a half-maximal effect within a physiological range. This stimulation was also observed in sc fat, but dexamethasone-stimulated as well as basal PAI-1 secretion rates were always higher in omental fat. Unlike dexamethasone, 24-h insulin did not modify PAI-1 secretion while accelerating glucose consumption. In contrast, 24-h cAMP inhibited PAI-1 gene expression and protein production under basal conditions and in the presence of dexamethasone. This inhibition was already detectable after 1 h and was maximal after 4 h at the level of gene expression. It occurred in both omental and sc adipose tissues. Importantly, epinephrine dose dependently inhibited PAI-1 parameters, an effect that was reproduced by isoproterenol. Dexamethasone- and cAMP-induced changes in PAI-1 messenger ribonucleic acid abundance were similar in explants and isolated fat cells. In isolated stromal-vascular cells, only dexamethasone was effective. In conclusion, we provide evidence for a reciprocal regulation of PAI-1 by dexamethasone (positive effector) and cAMP/catecholamines (negative effectors) in cultured human adipose tissue. The stimulation by glucocorticoids could contribute to enhanced production of PAI-1 by adipose tissue and high plasma levels of PAI-1 associated with central obesity and thereby be a link between this disorder and cardiovascular disease. Impaired inhibition by catecholamines could also contribute, as in vivo adipose tissue responses to these hormones are usually blunted in obese individuals.
Sulfatide-activated type II NKT cells prevent allergic airway inflammation by inhibiting type I NKT cell function in a mouse model of asthma (2011)

Asthma is a common chronic inflammatory disease involving many different cell types. Recently, type I natural killer T (NKT) cells have been demonstrated to play a crucial role in the development of asthma. However, the roles of type II NKT cells in asthma have not been investigated before. Interestingly, type I and type II NKT cells have been shown to have opposing roles in antitumor immunity, antiparasite immunity, and autoimmunity. We hypothesized that sulfatide-activated type II NKT cells could prevent allergic airway inflammation by inhibiting type I NKT cell function in asthma. Strikingly, in our mouse model, activation of type II NKT cells by sulfatide administration and adoptive transfer of sulfatide-activated type II NKT cells result in reduced-inflammation cell infiltration in the lung and bronchoalveolar lavage fluid, decreased levels of IL-4 and IL-5 in the BALF; and decreased serum levels of ovalbumin-specific IgE and IgG1. Furthermore, it is found that the activation of sulfatide-reactive type II NKT cells leads to the functional inactivation of type I NKT cells, including the proliferation and cytokine secretion. Our data reveal that type II NKT cells activated by glycolipids, such as sulfatide, may serve as a novel approach to treat allergic diseases and other disorders characterized by inappropriate type I NKT cell activation.
Premature Dissolution of the Microsporocyte Callose Wall Causes Male Sterility in Transgenic Tobacco (1992)

Dawn Worrall, Diane L. Hird, Rachel Hodge, Wyatt Paul, John Draper, Rod Scott, Premature Dissolution of the Microsporocyte Callose Wall Causes Male Sterility in Transgenic Tobacco, The Plant Cell, Vol. 4, No. 7 (Jul., 1992), pp. 759-771
Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. (1993)

Oxidative stress and expression of the vascular cell adhesion molecule-1 (VCAM-1) on vascular endothelial cells are early features in the pathogenesis of atherosclerosis and other inflammatory diseases. Regulation of VCAM-1 gene expression may be coupled to oxidative stress through specific reduction-oxidation (redox) sensitive transcriptional or posttranscriptional regulatory factors. In cultured human umbilical vein endothelial (HUVE) cells, the cytokine interleukin 1 beta (IL-1 beta) activated VCAM-1 gene expression through a mechanism that was repressed approximately 90% by the antioxidants pyrrolidine dithiocarbamate (PDTC) and N-acetylcysteine (NAC). Furthermore, PDTC selectively inhibited the induction of VCAM-1, but not intercellular adhesion molecule-1 (ICAM-1), mRNA and protein accumulation by the cytokine tumor necrosis factor-alpha (TNF alpha) as well as the noncytokines bacterial endotoxin lipopolysaccharide (LPS) and double-stranded RNA, poly(I:C) (PIC). PDTC also markedly attenuated TNF alpha induction of VCAM-1-mediated cellular adhesion. In a distinct pattern, PDTC partially inhibited E-selectin gene expression in response to TNF alpha but not to LPS, IL-1 beta, or PIC. TNF alpha and LPS-mediated transcriptional activation of the human VCAM-1 promoter through NF-kappa B-like DNA enhancer elements and associated NF-kappa B-like DNA binding proteins was inhibited by PDTC. These studies suggest a molecular linkage between an antioxidant sensitive transcriptional regulatory mechanism and VCAM-1 gene expression that expands on the notion of oxidative stress as an important regulatory signal in the pathogenesis of atherosclerosis.
Organization of the variable region of the immunoglobulin heavy-chain gene locus of the rat (2010)

We have mapped and annotated the variable region of the immunoglobulin heavy (IGH) gene locus of the Brown Norway (BN) rat (assembly V3.4; Rat Genomic Sequence Consortium). In addition to known variable region genes, we found 12 novel previously unidentified functional IGHV genes and 1 novel functional IGHD gene. In total, the variable region of the rat IGH locus is composed of at least 353 unique IGHV genes, 21 IGHD genes, and 5 IGHJ genes, of which 131, 14, and 4 are potentially functional genes, respectively. Of all species studied so far, the rat seems to have the highest number of functional IGHV genes in the genome. Rat IGHV genes can be classified into 13 IGHV families based on nucleotide sequence identity. The variable region of the BN rat spans a total length of approximately 4.9 Mb and is organized in a typical translocon organization. Like the mouse, members of the various IGHV gene families are more or less grouped together on the genome, albeit some members of IGHV gene families are found intermingled with each other. In the rat, the largest IGHV gene families are IGHV1, IGHV2, and IGHV5. The overall conclusion is that the genomic organization of the variable region of the rat IGH locus is strikingly similar to that of the mouse, illustrating the close evolutionary relationship between these two species.
Nanoscale Intermolecular Interactions between Human Serum Albumin and Alkanethiol Self-Assembled Monolayers (2003)

To study the molecular origins of hemocompatibility, the blood plasma protein human serum albumin (HSA) was covalently grafted to a nanosized probe tip at the end of a soft, microfabricated cantilever force transducer. The net force versus separation distance between the HSA-modified probe tip and three different model surfaces, including (1) gold; (2) a hydrophobic, CH3-terminated alkanethiol self-assembling monolayer (SAM); and (3) a hydrophilic, COO--terminated alkanethiol SAM in aqueous sodium phosphate buffer solution (PBS, ionic strength (IS) = 0.01 M, pH = 7.4), was recorded and compared to the values of various theoretical models. The approach interaction of the HSA probe tip on the COO--terminated SAM and Au substrates was found to be purely repulsive for D < 15 nm, nonlinear with decreasing separation distance, and consistent with electrostatic double layer repulsion. The approach interaction of the HSA probe tip on the CH3-terminated SAM substrate was found to be purely attractive, long range (D < 80 nm), nonlinear with decreasing separation distance, and much greater in magnitude and range than that known for van der Waals interactions between hydrocarbon SAMs terminated with hydrophilic chemical groups on Au. Large adhesive energies were observed for the HSA probe tip on both the CH3-terminated SAM and Au surfaces (≤−29 mN/m, −22 to −73kBT/protein), while smaller adhesive energies were observed on the COO--terminated SAM surface (≤ −4.9 mN/m, −5.3 to −12kBT/protein). It was shown that short-range adhesive contacts between the HSA chain segments and these surfaces give rise to energy dissipating mechanisms, such as HSA entropic molecular elasticity and enthalpic unfolding forces (deformation and rupture of noncovalent intramolecular bonds) and noncovalent bond rupture of the HSA chain segments adsorbed to the surface.
Genetically Engineering Plants for Crop Improvement (1989)

Dramatic progress has been made in the development of gene transfer systems for higher plants. The ability to introduce foreign genes into plant cells and tissues and to regenerate viable, fertile plants has allowed for explosive expansion of our understanding of plant biology and has provided an unparalleled opportunity to modify and improve crop plants. Genetic engineering of plants offers significant potential for seed, agrichemical, food processing, specialty chemical, and pharmaceutical industries to develop new products and manufacturing processes. The extent to which genetically engineered plants will have an impact on key industries will be determined both by continued technical progress and by issues such as regulatory approval, proprietary protection, and public perception.
Antitumor Activities of PSMA×CD3 Diabodies by Redirected T-cell Lysis of Prostate Cancer Cells (2012)

Both diabody formats showed a highly efficient and specific T cell-mediated killing of prostate cancer cells and are encouraging for further development in preclinical and clinical studies.
Generic Bill-of-Materials-and-Operations for High-Variety Production Management (2000)

High-variety production like mass customization is facing the challenge of effective variety management, which needs to deal with numerous variants of both product and process in order to accommodate diverse customer requirements. To utilize commonality underlying product diversity and process variation, it has been widely accepted as a practice to develop product families, in which a set of similar variants share common product and process structures and variety differentiates within these common structures. Based on such variety implication, this paper proposes a data structure, called generic Bill-of-Materials-and-Operations (BOMO), by unifying Bills- of-Materials (BOM) and routing data into a single set in order to synchronize multiple perspectives on variety such as customer ordering, product engineering, and operations planning. A generic structure is accordingly developed for characterizing variety effectively. The merits of the generic BOMO for integrated product and production data management are detailed in terms of order processing, engi neering change control, production job planning, cost accounting, as well as integrated material and capacity planning. An implementa tion of the proposed generic BOMO methodology in customized souvenir clock manufacturing is also reported.