gebhart/patrepeval huggingface dataset:
Structure and Functional Evaluation of Tendon–Skeletal Muscle Constructs Engineered in Vitro (2006)

During muscle contraction, the integrity of the myotendinous junction (MTJ) is important for the transmission of force from muscle to tendon. We evaluated the contractile and structural characteristics of 3-dimensional (3-D) skeletal muscle constructs co-cultured with engineered self-organized tendon constructs (n = 4), or segments of adult (n = 4) or fetal (n = 5) rat-tail tendon. We hypothesized that the co-culture of tendon and muscle would produce constructs with viable muscle-tendon interfaces that remain intact during generation of force. Construct diameter (lm) and maximum isometric force (microN) were measured, and specific force (kPa) was determined. After measure of force, constructs were loaded at a constant strain rate until failure and surface strains were recorded optically across the tendon, the muscle and the interface and used to determine the tangent modulus (passive stiffness) of the construct. Frozen samples were used for Trichrome Masson staining and immunofluorescent analysis of the MTJ-specific protein paxillin. No differences were observed between the groups with respect to diameter, maximum force, or specific force. The MTJ was robust and withstood tensile loading beyond the physiological strain range. The majority of the constructs failed in the muscle region. At the MTJ, there is an increase in the expression and localization of paxillin. In conclusion, using 3 sources of tendon tissue, we successfully engineered 3-D muscle-tendon constructs with functionally viable MTJ, characterized by structural features and protein expression patterns resembling neonatal MTJs in vivo.
Hypoxia affects mesoderm and enhances hemangioblast specification during early development (2004)

Hypoxia Inducible Factor (HIF), consisting of HIF1alpha and ARNT (HIF1beta) subunits, activates multiple genes in response to oxygen (O(2)) deprivation. Arnt(-/-) mice exhibit substantial defects in blood cell and vessel development. We demonstrate that hypoxia accelerates the expression of Brachyury (a mesoderm-specific transcription factor), BMP4 (a mesoderm-promoting growth factor) and FLK1 (a marker of hemangioblasts, the bipotential progenitor of endothelial and hematopoietic cells) in differentiating ES cell cultures. Significantly, proliferation of embryonic hemangioblasts (BL-CFCs) is regulated by hypoxia, as Arnt(+/+) ES cells generate increased numbers of FLK1(+) cells, and BL-CFCs with accelerated kinetics in response to low O(2). This response is HIF-dependent as Arnt(-/-) ES cells produce fewer FLK1(+) cells and BL-CFCs, under both normoxic and hypoxic conditions. Interestingly, this defect is rescued when Arnt(-/-) ES cells are co-cultured with Arnt(+/+) ES cells. Vegf(+/-)or Vegf(-/-) ES cells generate proper numbers of FLK1(+) cells but fewer BL-CFCs, suggesting that additional factors regulated by HIF (other than VEGF) are involved in these early events. Thus, hypoxic responses are important for the establishment of various progenitor cells, including early mesoderm and its differentiation into hemangioblasts. Together these data suggest that ineffective responses to hypoxia in Arnt(-/-) embryos abrogate proper cardiovascular development during early embryogenesis, including the pathways controlling hemangioblast differentiation.
Use of Functional MRI to Guide Decisions in a Clinical Stroke Trial (2005)

Use of fMRI to guide decision-making in a clinical stroke trial is feasible.
Recognition of incomplete polygonal objects (2003)

A partial-shape recognition technique for polygonal objects is described. Local shape features that are based on a polygonal approximation to the contour of the objects are extracted. Shape recognition is achieved by comparing an unknown object with the members of a library of known objects. This comparison requires finding the best matching sequence of local feature pairs for each known and unknown, a task that is accomplished by a best-first search. Experimental results are presented and discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Reduction of arthritis and pneumonitis in motheaten mice by soluble tumor necrosis factor receptor (1998)

TNFalpha is an important cytokine involved in the pathogenesis of inflammatory disease in me/me mice, resulting in tissue damage and early mortality. Therapies directed at blocking TNF/TNFR interactions, such as the sTNFRI used in these experiments, may be effective in diseases associated with apoptosis defects leading to overutilization of the TNF/TNFR pathway.
Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization (2005)

Bone cancer pain can be difficult to control, as it appears to be driven simultaneously by inflammatory, neuropathic and tumorigenic mechanisms. As nerve growth factor (NGF) has been shown to modulate inflammatory and neuropathic pain states, we focused on a novel NGF sequestering antibody and demonstrated that two administrations of this therapy in a mouse model of bone cancer pain produces a profound reduction in both ongoing and movement-evoked bone cancer pain-related behaviors that was greater than that achieved with acute administration of 10 or 30 mg/kg of morphine. This therapy also reduced several neurochemical changes associated with peripheral and central sensitization in the dorsal root ganglion and spinal cord, whereas the therapy did not influence disease progression or markers of sensory or sympathetic innervation in the skin or bone. Mechanistically, the great majority of sensory fibers that innervate the bone are CGRP/TrkA expressing fibers, and if the sensitization and activation of these fibers is blocked by anti-NGF therapy there would not be another population of nociceptors, such as the non-peptidergic IB4/RET-IR nerve fibers, to take their place in signaling nociceptive events.
Structural and Functional Characterization of the Product of Disease-Related Factor H Gene Conversion (2012)

Numerous complement factor H (FH) mutations predispose patients to atypical hemolytic uremic syndrome (aHUS) and other disorders arising from inadequately regulated complement activation. No unifying structural or mechanistic consequences have been ascribed to these mutants beyond impaired self-cell protection. The S1191L and V1197A mutations toward the C-terminus of FH, which occur in patients singly or together, arose from gene conversion between CFH encoding FH and CFHR1 encoding FH-related 1. We show that neither single nor double mutations structurally perturbed recombinant proteins consisting of the FH C-terminal modules, 19 and 20 (FH19-20), although all three FH19-20 mutants were poor, compared to wild-type FH19-20, at promoting hemolysis of C3b-coated erythrocytes through competition with full-length FH. Indeed, our new crystal structure of the S1191L mutant of FH19-20 complexed with an activation-specific complement fragment, C3d, was nearly identical to that of the wild-type FH19-20:C3d complex, consistent with mutants binding to C3b with wild-type-like affinity. The S1191L mutation enhanced thermal stability of module 20, whereas the V1197A mutation dramatically decreased it. Thus, although mutant proteins were folded at 37 °C, they differ in conformational rigidity. Neither single substitutions nor double substitutions increased measurably the extent of FH19-20 self-association, nor did these mutations significantly affect the affinity of FH19-20 for three glycosaminoglycans, despite critical roles of module 20 in recognizing polyanionic self-surface markers. Unexpectedly, FH19-20 mutants containing Leu1191 self-associated on a heparin-coated surface to a higher degree than on surfaces coated with dermatan or chondroitin sulfates. Thus, potentially disease-related functional distinctions between mutants, and between FH and FH-related 1, may manifest in the presence of specific glycosaminoglycans.
Production and characterization of N-acyl-D-glutamate amidohydrolase from Pseudomonas sp. strain 5f-1 (1991)

N-Acyl-D-glutamate amidohydrolase from Pseudomonas sp. strain 5f-1 was inducibly produced by D isomers of N-acetylglutamate, glutamate, aspartate, and asparagine. The enzyme has been purified to homogeneity by DEAE-cellulose, (NH4)2SO4 fractionation, and chromatofocusing followed by gel filtration on a Sephadex G-100 column. The enzyme was a monomer with molecular weight of 55,000. The enzyme activity was optimal at pH 6.5 to 7.5 and 45 degrees C. The isoelectric point and the pH stability were 8.8 and 9.0, respectively. N-Formyl, N-acetyl, N-butyryl, N-propionyl, N-chloroacetyl derivatives of D-glutamate and glycyl-D-glutamate were substrates for the enzyme. At pH 6.5 in 100 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer at 30 degrees C, a Km of 6.67 mM and a Vmax of 662 mumol/min/mg of protein for N-acetyl-D-glutamate were obtained. None of the metal ions stimulated the enzyme activity. Na+, K+, Mg2+, and Ba2+ acted as stabilizers. Hg2+, Cu2+, Zn2+, Fe3+, and EDTA were strongly inhibitory.
Signaling pathways in Th2 development (2004)

In order for an immune response to be successful, it must be of the appropriate type and magnitude. Intracellular residing pathogens require a cell-mediated immune response, whereas extracellular pathogens evoke a humoral immune response. T-helper (Th) cells orchestrate the immune response and are divided into two subsets, Th1 and Th2 cells. Here, we discuss the mechanisms of Th2 development with a focus on signal transduction pathways that influence Th2 differentiation.
Surface modification of poly(ether sulfone) ultrafiltration membranes by low-temperature plasma-induced graft polymerization (1999)

Low-temperature helium plasma treatment followed by grafting of N-vinyl-2-pyrrolidone (NVP) onto poly(ether sulfone) (PES) ultrafiltration (UF) membranes was used to modify commercial PES membranes. Helium plasma treatment alone and post-NVP grafting substantially increased the surface hydrophilicity compared with the unmodified virgin PES membranes. The degree of modification was adjusted by plasma treatment time and polymerization conditions (temperature, NVP concentration, and graft density). The NVP-grafted PES surfaces were characterized by Fourier transform infrared attenuated total reflection spectroscopy and electron spectroscopy for chemical analysis. Plasma treatment roughened the membrane as measured by atomic-force microscopy. Also, using a filtration protocol to simulate protein fouling and cleaning potential, the surface modified membranes were notably less susceptible to BSA fouling than the virgin PES membrane or a commercial low-protein binding PES membrane. In addition, the modified membranes were easier to clean and required little caustic to recover permeation flux. The absolute and relative permeation flux values were quite similar for the plasma-treated and NVP-grafted membranes and notably higher than the virgin membrane. The main difference being the expected long-term instability of the plasma treated as compared with the NVP-grafted membranes. These results provide a foundation for using low-temperature plasma-induced grafting on PES with a variety of other molecules, including other hydrophilic monomers besides NVP, charged or hydrophobic molecules, binding domains, and biologically active molecules such as enzymes and ribozymes. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 72: 1699–1711, 1999
Biological markers in urologic cancer (1987)

Tumor markers (TMs) play an important part in the management of urologic cancer. Alpha-fetoprotein, human chorionic gonadotropin, and occasionally lactic dehydrogenase serological determinations have become indispensable in the management of nonseminomatous germ cell testicular tumor patients, particularly after initial therapy, whereas human chorionic gonadotropin and probably placental alkaline phosphatase are important in seminoma. Prostatic acid phosphatase has long been important for the monitoring of patients with carcinoma of the prostate. The availability of the immunologic assays instead of the enzymatic assays has improved sensitivity somewhat but clinical interpretation has also become more complicated. Prostatic specific antigen is already an important tissue marker for carcinoma of the prostate and promises to be an important serological one, possibly surpassing prostatic acid phosphatase in importance. Analysis of DNA by automated flow cytometry is becoming important in the early detection and follow-up of bladder cancer patients. Studies concerning the tissue analysis of blood group antigens in bladder cancer continue to demonstrate that this approach can provide unique clinical information and interesting biological insights, but its role in routine clinical management remains to be determined. Currently, TMs have little clinical significance in renal cell carcinoma, but the availability of monoclonal antibodies to renal cell carcinoma preferential antigens may change this deficiency soon. In fact, in the near future, monoclonal antibodies will probably reveal many new substances for many urological cancers which can be used for markers serologically, histochemically, and, with their corresponding antibody, for radioimmune imaging and possibly immunotherapy. Now, as then, familiarity with the nuances of the marker and good clinical judgement will be essential.
Physiological and pathological population dynamics of circulating human red blood cells (2010)

The systems controlling the number, size, and hemoglobin concentrations of populations of human red blood cells (RBCs), and their dysregulation in anemia, are poorly understood. After release from the bone marrow, RBCs undergo reduction in both volume and total hemoglobin content by an unknown mechanism [Lew VL, et al. (1995) Blood 86:334-341; Waugh RE, et al. (1992) Blood 79:1351-1358]; after ∼120 d, responding to an unknown trigger, they are removed. We used theory from statistical physics and data from the hospital clinical laboratory [d'Onofrio G, et al. (1995) Blood 85:818-823] to develop a master equation model for RBC maturation and clearance. The model accurately identifies patients with anemia and distinguishes thalassemia-trait anemia from iron-deficiency anemia. Strikingly, it also identifies many pre-anemic patients several weeks before anemia becomes clinically detectable. More generally we illustrate how clinical laboratory data can be used to develop and to test a dynamic model of human pathophysiology with potential clinical utility.
<title>High-throughput NGL electron-beam direct-write lithography system</title> (2000)

Electron beam lithography systems have historically had low throughput. The only practical solution to this limitation is an approach using many beams writing simultaneously. For single-column multi-beam systems, including projection optics (SCALPEL<SUP>R</SUP> and PREVAIL) and blanked aperture arrays, throughput and resolution are limited by space-charge effects. Multibeam micro-column (one beam per column) systems are limited by the need for low voltage operation, electrical connection density and fabrication complexities. In this paper, we discuss a new multi-beam concept employing multiple columns each with multiple beams to generate a very large total number of parallel writing beams. This overcomes the limitations of space-charge interactions and low voltage operation. We also discuss a rationale leading to the optimum number of columns and beams per column. Using this approach we show how production throughputs &gt;= 60 wafers per hour can be achieved at CDs &lt;EQ 100 nm, independent of both wafer diameter and die size. The Cost-of-Ownership (CoO) advantages of direct-write (maskless) lithography are significant especially for small-volume semiconductor fabrication, for example ASICs, SOCs and MPUs.
Effects of image reconstruction on fiber orientation mapping from multichannel diffusion MRI: Reducing the noise floor using SENSE (2013)

These results highlight the importance of choosing the appropriate image reconstruction method for tractography studies that use multichannel receiver coils for diffusion MRI acquisition.
Purification and characterization of a protein from Saccharomyces cerevisiae that binds tightly to single-stranded DNA and stimulates a cognate strand exchange protein (1989)

A single-stranded DNA binding protein (yeast SSB protein) was purified to near-homogeneity from mitotic Saccharomyces cerevisiae cells. The Mr 34,000 protein specifically eluted at high salt (approximately 1200 mM NaCl) during chromatography on a single-stranded DNA-cellulose column. The protein formed stable complexes with single-stranded DNA in an apparent cooperative fashion. As judged from titration and competition experiments, the affinity of the protein was much higher for single-stranded DNA than for double-stranded DNA or single-stranded RNA. The SSB protein also was found to stimulate the strand exchange reaction between linear M13mp19 RF DNA and circular M13mp19 viral DNA as catalyzed by a yeast strand exchange protein previously purified in this laboratory [Kolodner, R., Evans, D. H., & Morrison, P. T. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5660-5664]. Titration experiments showed maximum stimulation of joint molecule formation at a stoichiometry of about 1 Mr 34,000 monomer yeast SSB per 18 nucleotides of single-stranded DNA. Kinetic experiments demonstrated at least an 18-fold increase in the rate of strand exchange due to the presence of the SSB in reactions where the amount of strand exchange protein was limiting. The yeast SSB protein stimulated the Escherichia coli RecA protein in the strand exchange reaction involving linear M13mp19 RF DNA and circular M13mp19 viral DNA as efficiently as E. coli SSB. However, the E. coli SSB protein did not substitute for the yeast SSB protein in reactions with the yeast strand exchange protein. This suggests that the stimulation of the yeast strand exchange protein by the yeast SSB may involve specific protein/protein interactions.
Reactions of Pseudomonas aeruginosa pyocyanin with reduced glutathione. (2008)

Pseudomonas aeruginosa is the most common cause of chronic and recurrent lung infections in patients with cystic fibrosis (CF) whose sputa contain copious quantities of P. aeruginosa toxin, pyocyanin. Pyocyanin triggers tissue damage mainly by its redox cycling and induction of reactive oxygen species (ROS). The reactions between reduced glutathione (GSH) and pyocyanin were observed using absorption spectra from spectrophotometry and the reaction products analysed by nuclear magnetic resonance imaging. Pyocyanin reacted with GSH non-enzymatically at 37 degrees C resulting in the production of red-brown products, spectophotometrically visible as a 480 nm maximum absorption peak after 24 h of incubation. The reaction was concentration-dependent on reduced glutathione but not on pyocyanin. Minimizing the accessibility of oxygen to the reaction decreased its rate. The anti-oxidant enzyme catalase circumvented the reaction. Proton-NMR analysis demonstrated the persistence of the original aromatic ring and the methyl-group of pyocyanin in the red-brown products. Anti-oxidant agents having thiol groups produced similar spectophotometrically visible peaks. The presence of a previously unidentified non-enzymatic GSH-dependent metabolic pathway for pyocyanin has thus been identified. The reaction between pyocyanin and GSH is concentration-, time-, and O(2)-dependent. The formation of H(2)O(2) as an intermediate and the thiol group in GSH seem to be important in this reaction.
Sitagliptin (MK0431) Inhibition of Dipeptidyl Peptidase IV Decreases Nonobese Diabetic Mouse CD4+ T-Cell Migration Through Incretin-Dependent and -Independent Pathways (2010)

Benefits of sitagliptin treatment in diabetic NOD mice may be mediated through selective effects on subpopulations of T-cells that are related to autoimmunity.
The Reaction between Nitrite and Deoxyhemoglobin (2005)

Recent evidence suggests that the reaction between nitrite and deoxygenated hemoglobin provides a mechanism by which nitric oxide is synthesized in vivo. This reaction has been previously defined to follow second order kinetics, although variable product stoichiometry has been reported. In this study we have re-examined this reaction and found that under fully deoxygenated conditions the product stoichiometry is 1:1 (methemoglobin:nitrosylhemoglobin), and unexpectedly, the kinetics deviate substantially from a simple second order reaction and exhibit a sigmoidal profile. The kinetics of this reaction are consistent with an increase in reaction rate elicited by heme oxidation and iron-nitrosylation. In addition, conditions that favor the "R" conformation show an increased rate over conditions that favor the "T" conformation. The reactivity of nitrite with heme is clearly more complex than has been previously realized and is dependent upon the conformational state of the hemoglobin tetramer, suggesting that the nitrite reductase activity of hemoglobin is under allosteric control.
Differential Expression of Tissue Inhibitors of Metalloproteinases in the Failing Human Heart (1998)

These studies demonstrated a selective downregulation of TIMPs along with upregulation of MMP-9 and gelatinolytic activity in the failing hearts, alterations that favor matrix degradation and turnover. These findings might be of pathophysiological significance and might suggest new therapeutic targets for limiting the ventricular remodeling and dilatation process characteristic of the failing human heart.
Structures of Human Genes Coding for Cytokine LD78 and Their Expression (1990)

LD78 is a member of a newly identified superfamily of small inducible proteins involved in inflammatory responses, wound healing, and tumorigenesis. Southern blot analysis of the EcoRI-digested human genomic DNAs, using previously isolated LD78 cDNA as a probe, showed that in each individual there are 4.2- and 4.8-kilobase-pair (kb) fragments and that some have an additional 6.5-kb fragment. The 4.2-kb fragment contained genomic DNA sequences corresponding to the LD78 cDNA and was named the LD78 alpha gene. The 4.8-kb fragment contained similar sequences, showing 94% homology to the LD78 alpha gene, and was named the LD78 beta gene. The LD78 alpha gene was present in a single or a few copies per haploid genome, whereas the copy number of the LD78 beta gene and of the 6.5-kb fragment hybridizable to LD78 cDNA varied among the samples tested. Treatment of human myeloid cell lines HL-60 and U937 with phorbol 12-myristate 13-acetate (PMA) increased within 2 h cellular levels of the RNA hybridizable to LD78 cDNA. The human glioma cell line U105MG and primary culture of human fibroblasts also expressed the hybridizable RNA in response to PMA. Addition of cycloheximide had no apparent effect on this response in U937 cells and inhibited the response in fibroblasts, whereas it stimulated the response in HL-60 and U105MG cells. mRNA phenotyping experiments revealed that the LD78 alpha and LD78 beta genes were both transcribed in PMA-stimulated U937 cells.
Coding sequence of humanrhocDNAs clone 6 and clone 9 (1988)

Journal Article Coding sequence of human rho cDNAs clone 6 and clone 9 Get access P. Chardin, P. Chardin Search for other works by this author on: Oxford Academic PubMed Google Scholar P. Madaule, P. Madaule 1CNRS Laboratoire de Physiologic Nerveuse Dpt 191190 Gif sur Yvette, France Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Tavitian A. Tavitian Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 16, Issue 6, 25 March 1988, Page 2717, https://doi.org/10.1093/nar/16.6.2717 Published: 25 March 1988 Article history Received: 26 February 1988 Published: 25 March 1988