gebhart/patrepeval huggingface dataset:
Imaging robust microglial activation after lipopolysaccharide administration in humans with PET (2015)

Neuroinflammation is associated with a broad spectrum of neurodegenerative and psychiatric diseases. The core process in neuroinflammation is activation of microglia, the innate immune cells of the brain. We measured the neuroinflammatory response produced by a systemic administration of the Escherichia coli lipopolysaccharide (LPS; also called endotoxin) in humans with the positron emission tomography (PET) radiotracer [11C]PBR28, which binds to translocator protein, a molecular marker that is up-regulated by microglial activation. In addition, inflammatory cytokines in serum and sickness behavior profiles were measured before and after LPS administration to relate brain microglial activation with systemic inflammation and behavior. Eight healthy male subjects each had two 120-min [11C]PBR28 PET scans in 1 d, before and after an LPS challenge. LPS (1.0 ng/kg, i.v.) was administered 180 min before the second [11C]PBR28 scan. LPS administration significantly increased [11C]PBR28 binding 30-60%, demonstrating microglial activation throughout the brain. This increase was accompanied by an increase in blood levels of inflammatory cytokines, vital sign changes, and sickness symptoms, well-established consequences of LPS administration. To our knowledge, this is the first demonstration in humans that a systemic LPS challenge induces robust increases in microglial activation in the brain. This imaging paradigm to measure brain microglial activation with [11C]PBR28 PET provides an approach to test new medications in humans for their putative antiinflammatory effects.
Control of Thrombopoietin-Induced Megakaryocytic Differentiation by the Mitogen-Activated Protein Kinase Pathway (1997)

Thrombopoietin (TPO) is the major regulator of both growth and differentiation of megakaryocytes. We previously showed that both functions can be generated by TPO in the megakaryoblastic cell line UT7, in which murine Mpl was introduced, and are independently controlled by distinct regions of the cytoplasmic domain of Mpl. Particularly, residues 71 to 94 of this domain (deleted in the mutant mpl delta3) were found to be required for megakaryocytic maturation but dispensable for proliferation. We show here that TPO-induced differentiation in UT7 cells is tightly dependent on a strong, long-lasting activation of the mitogen-activated protein kinase (MAPK) pathway. Indeed, (i) in UT7-mpl cells, TPO induced a strong activation of extracellular signal-regulated kinases (ERK) which was persistent until at least 4 days in TPO-containing medium; (ii) a specific MAPK kinase (MEK) inhibitor inhibited TPO-induced megakaryocytic gene expression; (iii) the Mpl mutant mpl delta3, which displayed no maturation activity, transduced only a weak and transient ERK activation in UT7 cells; and (iv) TPO-induced megakaryocytic differentiation in UT7-mpl delta3 cells was partially restored by expression of a constitutively activated mutant of MEK. The capacity of TPO to trigger a strong and prolonged MAPK signal depended on the cell in which Mpl was introduced. In BAF3-mpl cells, TPO triggered a weak and transient ERK activation, similar to that induced in UT7-mpl delta3 cells. In these cells, no difference in MAPK activation was found between normal Mpl and mpl delta3. Thus, depending on the cellular context, several distinct regions of the cytoplasmic domain of Mpl and signaling pathways may contribute to generate quantitative variations in MAPK activation.
L’aventure et la provocation (2010)

L’auteur évoque en quoi Cage a revalorisé l’instrumentiste et l’auditeur, et a contribué à la naissance d’une musique américaine dégagée de la tradition européenne.
Hillary Clinton takes up defense of U.S. aid for family planning overseas. (1996)

In November 1996 during her address to the Sixth Conference of Wives of Heads of State and Government of the Americas in La Paz, Colombia, and in her weekly newspaper column, US first lady Hillary Rodham Clinton pledged her own and the Clinton administration's complete support for reversing the severe reduction in funds for the international family planning program imposed by the 104th Congress. This revelation reflected the administration's preparation for a strong and vocal defense of the international family planning program, which will be facing its greatest political test in February 1997. Bolivia has the highest maternal mortality rate in South America, and half the deaths are due to illegal, unsafe abortions. Mrs. Clinton presented a $2.25 million USAID award to a $5 million Pan American Health Organization program that aims to reduce maternal mortality. In her December 3, 1996, column, she used family planning campaigns in Bolivia as an illustration of sensible, cost-effective, and long-term strategies for improving women's health, strengthening families, and reducing the abortion rate. Such programs educate people about the benefits of birth spacing, breast feeding, good nutrition, prenatal and postpartum visits, and safe deliveries. Mrs. Clinton has also visited other poor countries to learn about the special needs and conditions of women's lives. UN Ambassador Madeleine Albright has recently been nominated to be the first female Secretary of State. Many people see her commitment to improving the status of women through development efforts and her recognition of the close relationship between development and diplomacy as encouraging. The concern and commitment of these two powerful women could prove valuable in the upcoming test for international family planning aid. Congress must vote on a resolution to approve Clinton's report that the reduced funding is having a negative impact no later than February 28. If both the House and the Senate pass the resolution, already appropriated funds will be released in March rather than in July.
Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice (2013)

These observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice.
Increasing Running Step Rate Reduces Patellofemoral Joint Forces (2013)

Increasing step rate is an effective strategy to reduce patellofemoral joint forces and could be effective in modulating biomechanical factors that can contribute to patellofemoral pain.
X-linked immunodeficient mice spontaneously produce lupus-related anti-RNA helicase A autoantibodies, but are resistant to pristane-induced lupus (2003)

Murine lupus can occur spontaneously or be induced by hydrocarbons, such as pristane. Spontaneous disease in MRL and NZB/W F 1 mice is suppressed by the xid (X-linked immunodeciency) mutation, which greatly diminishes T cell-independent type 2 responses as well as the number of peritoneal B1 cells. The present study asked whether lupus induced by i.p. injection of pristane likewise is inhibited by the xid defect. Male CBA/N (xid) mice were refractory to the induction of autoantibodies by pristane, whereas 23% of pristane-treated male CBA/CaJ controls produced anti-nRNP/Sm, -Su and/or -OJ (isoleucyl tRNA synthetase) antibodies. Unexpectedly, 43% (12 of 28) of the xid mice spontaneously produced anti-nuclear antibodies that proved highly specic for the lupus antigen RNA helicase A (RHA). Strikingly, this specicity was absent in CBA/CaJ mice (none of 51). Moreover, pristane treatment suppressed the production of anti-RHA antibodies when administered prior to the onset of autoantibody production, but enhanced anti-RHA levels when given after the onset of autoantibody production, suggesting that pristane interferes with anti-RHA production at an early stage. Large amounts of IgG1 anti-RHA autoantibodies were detected in the sera of xid mice, whereas pristane-induced anti-nRNP/Sm and -Su autoantibodies were almost exclusively IgG2a. Cytokine production within the peritoneal cavity reected the predominant isotypes: IL-12 and IFN-g predominated in pristane-treated mice, whereas IL-4 and IL-6 were more predominant in untreated xid mice. The spontaneous production of anti-RHA by xid mice and its suppression by pristane treatment at the level of autoantibody induction supports the idea that lupus autoantibodies may be generated through a variety of mechanisms.
Mapping major and minor T-cell epitopes in vitro and their immunogenic or tolerogenic effect in vivo in non-human primates. (1993)

The immunogenicity of synthetic peptides of in vitro mapped T- and B-cell epitopes from a Streptococcus mutans cell-surface antigen were investigated in non-human primates. Peptide (1-15) contains T-cell (7-15) and B-cell (8-13) epitopes, but is only immunogenic if dimerized (1-15)2 or linked to the carrier tetanus toxoid (1-15)TT. Monomers and dimers of T- and B-cell epitopes were prepared and used to immunize macaques. Immunogenicity was assayed in lymphocytes by the uptake of [3H]thymidine and serum antibodies by a solid-phase radioimmunoassay. Macaques immunized with the dimerized (1-15)2 or carrier-linked peptide (1-15)TT exhibited in vitro T-cell proliferative responses to peptides (1-15) and (7-15). T cells from animals immunized with peptides (1-15), (7-15) or (7-15)2 failed to elicit an immune response. In order to establish if these non-immunogenic peptides might induce tolerance, the same macaques were challenged with the immunogenic peptide (1-15)TT. The results suggest that T-cell responses to peptide (1-15) were reestablished, but instead of responding to peptide (7-15) they were stimulated by a hitherto silent epitope (1-7). Tolerance to the major T-cell epitope (7-15) and the expression of a minor (silent) T-cell epitope (1-7) was associated with B-cell tolerance, suggesting that T-cell help for antibodies resides in the major T-cell epitope (7-15). However, short-term T-cell lines revealed T-cell responses to peptides (1-7) and (7-15) in both tolerized and immunized macaques, but the relative frequency of the minor epitope (1-7)-reactive lines was significantly higher in tolerized animals, whilst that for the major epitope (7-15) was higher in immunized animals. These findings suggest that the silent epitope (1-7) is really cryptic, in that it can be detected if the cell lines are first expanded in vitro with the whole peptide (1-15) and then stimulated with the truncated peptides (1-7) or (7-15). The results are consistent with the concept of a hierarchy of major and minor T-cell epitopes, now demonstrated in non-human primates, in which tolerance to the major T-cell epitope is associated with tolerance to antibody formation and the emergence of a minor T-cell epitope.
TGF-beta receptors. (1991)

TGF-beta binds specifically and with high affinity to all cell types with few exceptions. The binding parameters vary because the dissociation constants range from 1 pM to 60 pM. There may be as few as 200 or as many as 100,000 receptors per cell, depending on the cell type. Several cell surface proteins that specifically bind TGF-beta 1 and TGF-beta 2 have been characterized as putative receptors and have been classified on the basis of their size. Type I receptors have an Mr of approximately 50,000, type II receptors an Mr of approximately 80,000. Both type I and II receptors are glycoproteins and TGF-beta-induced responses appear to be mediated by one or both types. The most abundant and largest of the cell surface TGF-beta binding proteins is a membrane-bound proteoglycan that is a dimer of subunits each with Mr of approximately 250,000 (beta-glycan). This protein is plentiful on primary cells of mesenchymal origin but absent on primary epithelial and endothelial cells. It does not appear to be associated with TGF-beta-mediated cell responses and its function remains unknown. There are multiple cellular responses to TGF-beta and accordingly there appear to be multiple pathways for signal transduction. A guanine nucleotide binding protein-dependent pathway is involved in transmission of the signal for at least one TGF-beta-induced response while there is evidence that other responses are mediated through an independent pathway. TGF-beta receptor purification and cloning efforts will be rewarded with valuable information on the mechanisms of signal transmission.
Intraocular Pressure–Lowering Effects and Safety of Topical Administration of a Selective ROCK Inhibitor, SNJ-1656, in Healthy Volunteers (2008)

Objective: To investigate the effects and safety of topical administration of an ophthalmic solution of a selective Rho-associated coiled coil-forming protein kinase (ROCK) inhibitor, SNJ-1656, 0.003% to 0.1%, in healthy male adult volunteers.Design: Randomized, double-masked, group-comparison, phase 1 clinical study.In the initial singleinstillation trial, 45 healthy volunteers were randomly subdivided into 5 groups and treated with SNJ-1656 in concentrations of 0.003%, 0.01%, 0.03%, 0.05%, and 0.1% in stepwise fashion.In the repeated-instillation trial, 36 healthy volunteers were assigned to receive SNJ-1656 ophthalmic solution at the following concentrations and dosages: 0.05% once daily, 0.1% once daily, 0.05% twice daily, or 0.1% twice daily.In our studies, the administration of the solution and subsequent examinations (including intraocular pressure [IOP] measurements) were performed in a double-masked fashion.Results: After single instillation of placebo or SNJ-1656, in concentrations of 0.003%, 0.01%, 0.03%, 0.05%, and 0.1%, the changes in IOP from the baseline were -0.91, -1.18, -1.48, -2.20 (P = .04vs placebo), -1.48, and -1.98 mm Hg, respectively, at 2 hours, and -0.63,-0.95,-1.79, -2.26 (P = .01vs placebo), -1.95, and -3.00 mm Hg (PϽ .001vs placebo) respectively, at 4 hours.Significant IOP reductions after repeated instillation were also found.On slitlamp examination during the trial, there were no significant adverse findings except hyperemia of the bulbar and palpebral conjunctiva after instillation. Conclusion:This clinical study demonstrated that SNJ-1656 is a safe topical agent effective in reducing IOP in human eyes.
Metabolic abnormalities in the cancer patient (1985)

Many malnourished patients with cancer fail to gain weight with what appears to be adequate nutritional support. Metabolic abnormalities resulting from remote effects of the tumor on host metabolism have been postulated to increase energy requirements in such cancer patients. In the current study, 44 patients with lung cancer who had significant weight loss (16 +/- 2% of usual body weight) were studied under metabolic ward conditions. Whole body glucose production rates were significantly elevated in cancer patients compared to age-matched healthy controls. Blood glucose levels 2 hours after a standard oral glucose challenge were also significantly increased, but insulin levels were not different at this time. Fasting glucose and insulin levels were not different. Fasting plasma alanine levels were significantly decreased in these patients, while branched-chain amino acids were not different. Increased alanine flux for gluconeogenesis is likely to reflect a basic metabolic abnormality in patients with cancer and could be explained on the basis of a resistance to insulin action in such patients.
The Catabolism of Amino Acids to Long Chain and Complex Alcohols in Saccharomyces cerevisiae (2003)

The catabolism of phenylalanine to 2-phenylethanol and of tryptophan to tryptophol were studied by (13)C NMR spectroscopy and gas chromatography-mass spectrometry. Phenylalanine and tryptophan are first deaminated (to 3-phenylpyruvate and 3-indolepyruvate, respectively) and then decarboxylated. This decarboxylation can be effected by any of Pdc1p, Pdc5p, Pdc6p, or Ydr380wp; Ydl080cp has no role in the catabolism of either amino acid. We also report that in leucine catabolism Ydr380wp is the minor decarboxylase. Hence, all amino acid catabolic pathways studied to date use a subtly different spectrum of decarboxylases from the five-membered family that comprises Pdc1p, Pdc5p, Pdc6p, Ydl080cp, and Ydr380wp. Using strains containing all possible combinations of mutations affecting the seven AAD genes (putative aryl alcohol dehydrogenases), five ADH genes, and SFA1, showed that the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.)
Partial Phosphorylation of the N-Formyl Peptide Receptor Inhibits G Protein Association Independent of Arrestin Binding (2001)

It is now well accepted that G protein-coupled receptors activated by agonist binding become targets for phosphorylation, leading to desensitization of the receptor. Using a series of phosphorylation deficient mutants of the N-formyl peptide receptor (FPR), we have explored the role of phosphorylation on the ability of the receptor to interact with G proteins and arrestins. Using a fluorometric assay in conjunction with solubilized receptors, we demonstrate that phosphorylation of the wild type FPR lowers its affinity for G protein, whereas mutant receptors lacking four potential phosphorylation sites retain their ability to couple to G protein. Phosphorylated mutant receptors lacking only two potential phosphorylation sites are again unable to couple to G protein. Furthermore, whereas stimulated wild type FPR in whole cells colocalizes with arrestin-2, and the solubilized, phosphorylated FPR binds arrestin-2, the stimulated receptors lacking four potential phosphorylation sites display no interaction with arrestin-2. However, the mutant receptors lacking only two potential phosphorylation sites are restored in their ability to bind and colocalize with arrestin-2. Thus, there is a submaximal threshold of FPR phosphorylation that simultaneously results in an inhibition of G protein binding and an induction of arrestin binding. These results are the first to demonstrate that less than maximal levels of receptor phosphorylation can block G protein binding, independent of arrestin binding. We therefore propose that phosphorylation alone may be sufficient to desensitize the FPR in vivo, raising the possibility that for certain G protein-coupled receptors, desensitization may not be the primary function of arrestin.
Variables affecting the yields of fatty esters from transesterified vegetable oils (1984)

Abstract Transesterification reaction variables that affect yield and purity of the product esters from cottonseed, peanut, soybean and sunflower oils include molar ratio of alcohol to vegetable oil, type of catalyst (alkaline vs acidic), temperature and degree of refinement of the vegetable oil. With alkaline catalysts (either sodium hydroxide or methoxide), temperatures of 60 C or higher, molar ratios of at least 6 to 1 and with fully refined oils, conversion to methyl, ethyl and butyl esters was essentially complete in 1 hr. At moderate temperatures (32 C), vegetable oils were 99% transesterified in ca. 4 hr with an alkaline catalyst. Transesterification by acid catalysis was much slower than by alkali catalysis. Although the crude oils could be transesterified, ester yields were reduced because of gums and extraneous material present in the crude oils.
Common Mutations in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Patients of Different Origins (1998)

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; OMIM *240300, also called APS 1,) is a rare autosomal recessive disorder that is more frequent in certain isolated populations. It is generally characterized by two of the three major clinical symptoms that may be present, Addison's disease and/or hypoparathyroidism and/or chronic mucocutaneous candidiasis. Patients may also have a number of other clinical symptoms including chronic gastritis, gonadal failure, and rarely, autoimmune thyroid disease and insulin-dependent diabetes mellitus. We and others have recently identified the gene for APECED, which we termed AIRE (for autoimmune regulator). AIRE is expressed in thymus, lymph nodes, and fetal liver and encodes a protein containing motifs suggestive of a transcriptional regulator, including two zinc finger motifs (PHD finger), a proline-rich region, and three LXXLL motifs. Six mutations, in cluding R257X, the predominant Finnish APECED allele, have been defined. R257X was also observed in non-Finnish APECED patients occurring on different chromosomal haplotypes suggesting different mutational origins. Here we present mutation analyses in an extended series of patients, mainly of Northern Italian origin. We have detected 12 polymorphisms, including one amino acid substitution, and two additional mutations, R203X and X546C, in addition to the previously described mutations, R257X, 1096-1097insCCTG, and a 13-bp deletion (1094-1106del). R257X was also the common mutation in the Northern Italian patients (10 of 18 alleles), and 1094-1106del accounted for 5 of 18 Northern Italian alleles. Both R257X and 1094-1106del were both observed in patients of four different geo-ethnic origins, and both were associated with multiple different haplotypes using closely flanking polymorphic markers showing likely multiple mutation events (six and four, respectively). The identification of common AIRE mutations in different APECED patient groups will facilitate its genetic diagnosis. In addition, the polymorphisms presented provide the tools for investigation of the involvement of AIRE in other autoimmune diseases, particularly those affecting the endocrine system.
Organization, evolutionary conservation, expression and unusual Alu density of the human gene for pigment epithelium-derived factor, a unique neurotrophic serpin. (1996)

PEDF is a neurotrophic serpin that promotes a neuronal phenotype and augments neuronal cell survival. The isolation, sequence and structural analysis of the human PEDF gene and its promoter along with its evolutionary conservation and expression in human tissues are now described. The gene spans approximately 16 kb and is divided among 8 exons and 7 introns, the junctions of which conform to the AG/GT consensus rule. PEDF appears to fall into the ovalbumin/PAI-2 subgrouping of serpins and is structurally far different from GDN/PN-1, the only other neurotrophic serpin reported to date. The immediate 5'-flanking region is dominated by a dense cluster of Alu repeats in which are embedded several promoter consensus sequences. A CAAT box is present at -43. The putative promoter region is also far different from that reported for GDN/PN-1. Comparable hybridization signals of 23 kb EcoRI fragments containing the PEDF gene are observed by Southern blot analysis in all primate, mammal and avian species examined; conservation is particularly evident among the primates. Northern blot analysis confirms the presence of the PEDF transcript in a broad range of human fetal and adult tissues including almost all brain areas examined, underscoring differences with GDN/PN-1 which, in the adult brain, is only expressed in glia and a subset of neurons.
Application of Radiation Force in Noncontact Measurement of the Elastic Parameters (1999)

Ultrasound-stimulated vibro-acoustic spectrography is a recently-developed method that employs the radiation force of two intersecting continuous ultrasound beams to remotely vibrate an object at an arbitrary low frequency. Object vibration produces a sound field (acoustic emission) in the medium, which is a function of object mechanical properties. By measuring the acoustic emission field, one can obtain information about the mechanical parameters of the object. In this paper, we use this method for remote (noncontact) measurement of the dynamic Young's modulus of a rod based on its fundamental resonance frequency. Experimental results on an aluminum rod agree with the published data.