gebhart/patrepeval huggingface dataset:
Disruption of REDD1 gene ameliorates sepsis-induced decrease in mTORC1 signaling but has divergent effects on proteolytic signaling in skeletal muscle (2015)

Sepsis-induced skeletal muscle atrophy and weakness are due in part to decreased mTORC1-mediated protein synthesis and increased proteolysis via the autophagy-lysosomal system and ubiquitin-proteasome pathway. The REDD1 (regulated in development and DNA damage-1) protein is increased in sepsis and can negatively regulate mTORC1 activity. However, the contribution of REDD1 to the sepsis-induced change in muscle protein synthesis and degradation has not been determined. Sepsis was produced by cecal ligation and puncture in female REDD1(-/-) or wild-type (WT) mice, and end points were assessed 24 h later in gastrocnemius; time-matched, pair-fed controls of each genotype were included. Sepsis increased REDD1 protein 300% in WT mice, whereas REDD1 was absent in REDD1(-/-) muscle. Sepsis decreased protein synthesis and phosphorylation of downstream targets of mTORC1 (S6K1 Thr(389), rpS6 Ser(240/244), 4E-BP1 Ser(65)) in WT but not REDD1(-/-) mice. However, Akt and PRAS40 phosphorylation was suppressed in both sham and septic muscle from REDD1(-/-) mice despite unaltered PDK1, PP2A, or TSC2 expression. Sepsis increased autophagy as indicated by decreased ULK1 Ser(757) phosphorylation and p62 abundance and increased LC3B-II/I in WT mice, whereas these changes were absent in septic REDD1(-/-) mice. Conversely, REDD1 deletion did not prevent the sepsis-induced decrease in IGF-I mRNA or the concomitant increase in IL-6, TNFα, MuRF1, and atrogin1 mRNA expression. Lastly, 5-day survival in a separate set of septic mice did not differ between WT and REDD1(-/-) mice. These data highlight the central role of REDD1 in regulating both protein synthesis and autophagy in skeletal muscle during sepsis.
Effects of monoclonal antibodies to adhesion molecules on eosinophilic myocarditis inToxocara canis-infected CBA/J mice (1998)

Eosinophilic myocarditis followed by fibrosis of the cardiac muscle was observed in addition to peripheral blood eosinophilia in CBA/J mice infected with Toxocara canis. The infected mice were used as an experimental model of eosinophilic endomyocarditis associated with hypereosinophilic syndrome. Effects of in vivo treatment with MoAbs to adhesion molecules on eosinophilic myocarditis were examined using this experimental model. Expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells of capillaries in myocardium were increased 1 and 2 weeks after infection. Infiltration of very late antigen (VLA)-4+ and/or CD11a+ cells into the cardiac muscles was also observed 1 and 2 weeks after infection. Infiltration of eosinophils into the heart was significantly suppressed by anti-CD18 MoAb and anti-VLA-4 MoAb, and focal fibrosis of the cardiac muscle was also significantly suppressed by combined administration of anti-CD18 and anti-ICAM-1 MoAbs. These results indicate that adhesion molecules may play important roles in eosinophilic myocarditis, and that blockade of interaction between adhesion molecules and their ligands may help to control it.
Characterization of Alzheimer’s-like Paired Helical Filaments from the Core Domain of Tau Protein Using Solid-State NMR Spectroscopy (2008)

The polymerization of the microtubule-associated protein tau into paired helical filaments (PHFs) represents one of the hallmarks of Alzheimer's disease. We employed solid-state nuclear magnetic resonance (NMR) to investigate the structure and dynamics of PHFs formed in vitro by the three-repeat-domain (K19) of protein tau, representing the core of Alzheimer PHFs. While N and C termini of tau monomers in PHFs are highly dynamic and solvent-exposed, the rigid segment consists of three major beta-strands. Combination of through-bond and through-space ssNMR transfer methods with water-edited ((15)N, (13)C) and ((13)C, (13)C) correlation experiments suggests the existence of a fibril core that is largely built by repeat unit R3, flanked by surface-exposed units R1 and R4. Solid-state NMR, circular dichroism, and the fibrillization behavior of a K19 mutant furthermore indicate that electrostatic interactions play a central role in stabilizing the K19 PHFs.
Selective release of the Treponema pallidum outer membrane and associated polypeptides with Triton X-114 (1988)

The effects of the nonionic detergent Triton X-114 on the ultrastructure of Treponema pallidum subsp. pallidum are presented in this study. Treatment of Percoll-purified motile T. pallidum with a 1% concentration of Triton X-114 resulted in cell surface blebbing followed by lysis of blebs and a decrease in diameter from 0.25-0.35 micron to 0.1-0.15 micron. Examination of thin sections of untreated Percoll-purified T. pallidum showed integrity of outer and cytoplasmic membranes. In contrast, thin sections of Triton X-114-treated treponemes showed integrity of the cytoplasmic membrane but loss of the outer membrane. The cytoplasmic cylinders generated by detergent treatment retained their periplasmic flagella, as judged by electron microscopy and immunoblotting. Recently identified T. pallidum penicillin-binding proteins also remained associated with the cytoplasmic cylinders. Proteins released by Triton X-114 at 4 degrees C were divided into aqueous and hydrophobic phases after incubation at 37 degrees C. The hydrophobic phase had major polypeptide constituents of 57, 47, 38, 33-35, 23, 16, and 14 kilodaltons (kDa) which were reactive with syphilitic serum. The 47-kDa polypeptide was reactive with a monoclonal antibody which has been previously shown to identify a surface-associated T. pallidum antigen. The aqueous phase contained the 190-kDa ordered ring molecule, 4D, which has been associated with the surface of the organisms. Full release of the 47- and 190-kDa molecules was dependent on the presence of a reducing agent. These results indicate that 1% Triton X-114 selectively solubilizes the T. pallidum outer membrane and associated proteins of likely outer membrane location.
Diameter Refinement of Semiconducting Arc Discharge Single-Walled Carbon Nanotubes via Density Gradient Ultracentrifugation (2013)

Arc discharge single-walled carbon nanotubes (SWCNTs) possess superlative optical and electronic properties that are of high interest for technologically important applications including fiber optic communications, biomedical imaging, and field-effect transistors. However, as-grown arc discharge SWCNTs possess a mixture of metallic and semiconducting species in addition to a wide diameter distribution (1.2 to 1.7 nm) that limit their performance in devices. While previous postsynthetic sorting efforts have achieved separation by electronic type and diameter refinement for metallic arc discharge SWCNTs, tight diameter distributions of semiconducting arc discharge SWCNTs have not yet been realized. Herein, we present two advances in density gradient ultracentrifugation that enable the isolation of high purity (>99%) semiconducting arc discharge SWCNTs with narrow diameter distributions centered at ∼1.6 and ∼1.4 nm. The resulting diameter-refined populations of semiconducting arc discharge SWCNTs possess monodisperse characteristics that are well-suited for high-performance optical and electronic technologies.
HELLP syndrome - a multisystemic disorder. (2007)

HELLP syndrome is a multisystemic disorder with an incidence of 0.17-0.85% of all pregnancies. Its etiopathogenesis is not completely understood. The most widely accepted hypotheses are: a change in the immune feto-maternal balance, platelet aggregation, endothelial dysfunction, arterial hypertension and an inborn error of the fatty acid oxidative metabolism. Hepatic involvement occurs by intravascular fibrin deposition and hypovolemia. Materno-fetal complications cause a 6.7-70% perinatal mortality rate and a 1-24% maternal mortality rate. The recognition of HELLP syndrome and the rapid initiation of therapy are required for the improvement of materno-fetal prognosis.
Principles of Operation of the Rubidium VaporMagnetometer (1962)

This paper discusses some of the basic problems involved in designing and using a magnetometer employing optical pumping. Particular attention is given to magnetometers of the self-oscillating type; i.e., those that are analogous to masers in that the resonant properties of the spin system itself are used to sustain continuous oscillation at the resonant frequency. Among the topics treated are amplitude variations with orientation, sensitivity, behavior in extremely weak magnetic fields, and response to rapid field changes.
Cilengitide: an integrin-targeting arginine–glycine–aspartic acid peptide with promising activity for glioblastoma multiforme (2008)

Cilengitide is active and synergizes with external beam radiotherapy in preclinical GBM models. In clinical trials for recurrent GBM, single-agent cilengitide has antitumor benefits and minimal toxicity. Among newly diagnosed GBM patients, single-arm studies incorporating cilengitide into standard external beam radiotherapy/temozolomide have shown encouraging activity with no increased toxicity and have led to a planned randomized Phase III trial.
Subthalamic span of oscillations predicts deep brain stimulation efficacy for patients with Parkinson's disease (2010)

The significance of oscillations that characterize the subthalamic nucleus in Parkinson's disease is still under debate. Here, we analysed the spectral and spatial characteristics of 314 microelectrode trajectories from 128 patients undergoing subthalamic nucleus deep brain stimulation surgery for Parkinson's disease. We correlated the subthalamic nucleus pathophysiology with the outcome of surgery, as evaluated by the third section of the Unified Parkinson's Disease Rating Scale (motor score), which was subdivided into tremor, rigidity, limb-bradykinesia and axial-bradykinesia subscores. beta-oscillatory activity (13-30 Hz) comprised a continuous stretch within the subthalamic nucleus, and was limited to a distinctly-bounded dorsolateral oscillatory region. Although less consistent and more sporadic, low-frequency (3-7 Hz) power was also increased in the dorsolateral oscillatory region. In contrast, the more ventral subthalamic nucleus was characterized by consistently reduced beta and increased gamma (30-100 Hz) activity. Neuronal responses to passive arm movement (analysed by their alignment to goniometer tracing of the joints' angular displacement) were significantly more common in the dorsolateral oscillatory region than the ventral subthalamic nucleus region (62 versus 25% of sites tested respectively, P<0.01). The length of the dorsolateral oscillatory region recorded in the macroelectrode-implanted trajectory predicted a favourable response to subthalamic nucleus deep brain stimulation (R=0.67, P<0.0001). This correlation was also evident for improvement in the specific symptom subscores of rigidity, limb-bradykinesia and axial-bradykinesia (P<0.05). Similarly, increased subthalamic nucleus beta power was associated with postoperative improvement. In contrast, the preoperative response to levodopa did not correlate with dorsolateral oscillatory region length (P=0.33), however, it did tend to be associated with increased beta (and decreased low frequency) subthalamic nucleus power. Finally, the active macroelectrode contact, independently selected by optimal clinical outcome, coincided with the dorsolateral oscillatory region centre. On average, the location of the active contact was not significantly different from the dorsolateral oscillatory region centre (P=0.10), but was significantly different from the subthalamic nucleus centre (P<0.0001). We conclude that the spatial extent of the dorsolateral oscillatory region, which overlaps the motor territories of the subthalamic nucleus, predicts the outcome of subthalamic nucleus deep brain stimulation. Thus the frequency and spatial characteristics of the subthalamic nucleus trajectory may be used for deep brain stimulation outcome optimization.
Joint-dependent local deformations for hand animation and object grasping (1988)

Algorithms and methods are presented for animating the hands of a synthetic actor. The algorithms allow not only to move the hand and grasp objects, but also to compute deformations of the hand as it moves, for example: rounding at joints and muscle inflations. The mapping of surfaces onto the skeleton is based on the concept of Jointdependent Local Deformation (JLD) operators, which are specific local deformation operators depending on the nature of the joints. The major problem in the hand covering process is the calculation of the coordinate bases. The key to our method was to find a model for calculating the bases which was sophisticated enough for the simulation of complex motions. This model was then improved with additional realistic elements such as muscle inflations and joint roundings. The calculation of the coordinate bases of a vertex in 3-space is separated into two cases: single segment covering for the fingers and two-segment covering for the hand palm. For positioning the hand on an object, three processes are described: the calculation of the distance between a hand vertex and an object, the intersection calculation between the hand and the object and the semiautomatic calculation of the flexion angle, also based on the distance process. Several examples are shown and the user interface introduced into the HUMAN FACTORY system is also described.
Ceramic Drug-Delivery Devices (1998)

A variety of ceramics and delivery systems have been used to deliver chemicals, biologicals, and drugs at various rates for desired periods of time from different sites of implantation. In vitro and in vivo studies have shown that ceramics can successfully be used as drug-delivery devices. Matrices, inserts, reservoirs, cements, and particles have been used to deliver a large variety of therapeutic agents such as antibiotics, anticancer drugs, anticoagulants, analgesics, growth factors, hormones, steroids, and vaccines. In this article, the advantages and disadvantages of conventional drug-delivery systems and the different approaches used to deliver chemical and biological agents by means of ceramic systems will be reviewed.
Administration of an anti-interleukin-6 monoclonal antibody to patients with acquired immunodeficiency syndrome and lymphoma: effect on lymphoma growth and on B clinical symptoms (1994)

Increased interleukin-6 (IL-6) production and expression by malignant cells of the IL-6 receptor has been evidenced in a subgroup of non-Hodgkin's lymphomas, suggesting that this cytokine plays a role in lymphoma growth and in B clinical symptoms. In this study, the effect of the administration of an anti-IL-6 monoclonal antibody (MoAb) was analyzed in 11 patients seropositive for human immunodeficiency virus-1 and suffering from an immunoblastic or a polymorphic large-cell lymphoma. The antibody (BE-8, 10 to 40 mg/day) was administered for 21 days. Neutralization of in vivo IL-6 effect was assessed by monitoring C-reactive protein levels in the serum. In 5 patients, the lymphoma progressed during treatment. Among them were the 2 patients in whom endogenous IL-6 effect was not neutralized. Five patients experienced a stabilization, and 1 a partial remission. This effect on lymphoma growth lasted for 8 to 28 weeks. The anti-IL-6 MoAb had a clear effect on lymphoma-associated fever and cachexia. The mean body weight increase was 1.4 +/- 0.5 kg between day 1 and day 21, and reached 12 kg in 120 days in 1 patient who received three courses of treatment. Side effects were a consistent but moderate thrombocytopenia, and an occasional and moderate decrease of neutrophil counts. Immunization against the MoAb was observed in only 2 patients. These results indicate that in some cases of lymphomas growth of malignant cells may be partially IL-6-dependent and that neutralizing endogenous effect of IL-6 completely abrogates B clinical symptoms.
Transcriptional activation by oestrogen receptors. (1998)

The oestrogen receptor belongs to a superfamily of nuclear receptors that function as hormone-dependent transcription factors. Transcriptional activation is mediated by two activation regions: AF-1 in the N-terminal domain and AF-2 in the ligand binding domain. AF-1, whose activity is also regulated by epidermal growth factor and insulin-like growth factor-I, varies considerably between receptors, whereas AF-2 seems to be conserved in nuclear receptors. From recent structural analysis of the ligand binding domains of two retinoid receptors and the thyroid hormone receptor, it appears that this domain contains a common fold that generates a conserved ligand binding pocket. As a consequence of ligand binding, a C-terminal helix is realigned over the ligand binding pocket to form a novel interacting surface to which co-activators are likely to bind. Several candidate proteins have been identified, including receptor-interacting protein (RIP)-140, RIP-160, transcription intermediary factor (TIF)-1, suppressor of gal4D lesions (SUG)-1 and steroid receptor co-activator (SRC)-1. These proteins interact with receptors only in the presence of their respective hormonal ligands; moreover, their interaction with a series of mutant receptors correlates with their transcriptional activity, suggesting that they may play a role in transcriptional activation. However, only SRC-1 stimulates the transcriptional activity of receptors in transfected mammalian cells, implying that the proteins have different functions. The properties of RIP-140 and SRC-1 will be described and their potential role and mechanism of action discussed.
Sporadic colorectal cancer â role of the commensal microbiota (2005)

There are vast numbers of bacteria present within the human colon that are essential for the host's well being in terms of nutrition and mucosal immunity. While certain members of the colonic microbiota have been shown to promote the host's health there are also numerous studies that have implicated other members of the colonic microbiota in the development of colorectal cancer, a prominent malignancy within the western world. In this review we consider the evidence for the role of bacteria in colorectal cancer from molecular and animal model studies. We focus on some of the mechanisms by which the colonic microbiota drives the progression towards colorectal malignancy including generation of reactive metabolites and carcinogens, alterations in host carbohydrate expression and induction of chronic mucosal inflammation.
Differential Phospholipid Binding by Site 3 and Site 4 Toxins (2005)

It has been shown recently that polypeptide toxins that modulate the gating properties of voltage-sensitive cation channels are able to bind to phospholipid membranes, leading to the suggestion that these toxins are able to access a channel-binding site that remains membrane-restricted (Lee, S.-Y., and MacKinnon, R. (2004) Nature 430, 232-235). We therefore examined the ability of anthopleurin B (ApB), a sea anemone toxin that selectively modifies inactivation kinetics of Na(V)1.x channels, and ProTx-II, a spider toxin that modifies activation kinetics of the same channels, to bind to liposomes. Whereas ProTx-II can be quantitatively depleted from solution upon incubation with phosphatidylcholine/phosphatidylserine liposomes, ApB displays no discernible phospholipid binding activity. We therefore examined the activities of structurally unrelated site 3 and site 4 toxins derived from Leiurus and Centruroides venoms, respectively, in the same assay. Like ApB, the site 3 toxin LqqV shows no lipid binding activity, whereas the site 4 toxin Centruroides toxin II, like ProTx-II, is completely bound. We conclude that toxins that modify inactivation kinetics via binding to Na(V)1.x site 3 lack the ability to bind phospholipids, whereas site 4 toxins, which modify activation, have this activity. This inherent difference suggests that the conformation of domain II more closely resembles that of the K(V)AP channel than does the conformation of domain IV.
Cardiac neural crest cells contribute to the dormant multipotent stem cell in the mammalian heart (2005)

Arodent cardiac side population cell fraction formed clonal spheroids in serum-free medium, which expressed nestin, Musashi-1, and multi-drug resistance transporter gene 1, markers of undifferentiated neural precursor cells. These markers were lost following differentiation, and were replaced by the expression of neuron-, glial-, smooth muscle cell-, or cardiomyocyte-specific proteins. Cardiosphere-derived cells transplanted into chick embryos migrated to the truncus arteriosus and cardiac outflow tract and contributed to dorsal root ganglia, spinal nerves, and aortic smooth muscle cells. Lineage studies using double transgenic mice encoding protein 0-Cre/Floxed-EGFP revealed undifferentiated and differentiated neural crest-derived cells in the fetal myocardium. Undifferentiated cells expressed GATA-binding protein 4 and nestin, but not actinin, whereas the differentiated cells were identified as cardiomyocytes. These results suggest that cardiac neural crest-derived cells migrate into the heart, remain there as dormant multipotent stem cells-and under the right conditions-differentiate into cardiomyocytes and typical neural crest-derived cells, including neurons, glia, and smooth muscle.
Was the vasectomy necessary after all? [letter] (1986)

Dr. Lloyd Nicholass personal paper (1 March p. 604) provides the profession with a useful warning against treating serious disease as mere routine. However the practical issue he raises of fertility after orchidectomy and postoperative radiotherapy is also important. Many children have been fathered by men in this group. Although patients with previous testicular tumors may be subfertile they should not be regarded as irretrievably sterile. Aspermia induced by low dose radiation recovers as a function of both time and dose. With modern sharp beam linear accelerators and appropriate shielding testicular dosage should be in the 0.2-1.5 Gy range. In Dr. Nicholass case his vasectomy almost certainly was necessary. (full text)
Identification and Characterization of Prolylcarboxypeptidase as an Endothelial Cell Prekallikrein Activator (2002)

Our recent investigations have postulated a human umbilical vein endothelial cell (HUVEC)-associated prekallikrein activator (PKA). When prekallikrein (PK) assembles on high molecular weight kininogen on HUVEC, PK is activated to kallikrein. PKA was found in the 15,800 × <i>g</i> pellet of HUVEC lysates using an assay that measures PK activation only when bound to high molecular weight kininogen linked to microtiter plates. Sequential DEAE, wheat germ lectin affinity, and hydroxyapatite chromatography resulted in four protein bands on SDS-PAGE. One protein in the 73-kDa band was identified by amino acid sequencing as prolylcarboxypeptidase (PRCP). On gel filtration, PKA activity was a single homogenous peak identical in migration to the 73-kDa immunoblot of PRCP. Anti-PRCP inhibits PKA activity and PK activation on HUVEC. Purified PKA was blocked by diisopropyl fluorophosphate (1 mm), phenylmethylsulfonyl fluoride (3 mm), leupeptin (100 μm), antipain (IC<sub>50</sub> = 2 μm), HgCl<sub>2</sub> (IC<sub>50</sub> = 500 μm), Z-Pro-Pro-aldehyde-dimethyl acetate (IC<sub>50</sub> = 1 μm), and corn trypsin inhibitor (IC<sub>50</sub> = 40 nm). PKA did not correct the coagulant defect in factor XII deficient plasma, was purified from HUVEC cultured in factor XII-deficient serum, was not detected by antibody to factor XII, did not activate FXI, and was not inhibited by a neutralizing antibody to FXII. Angiotensin II (IC<sub>50</sub> = 2 μm) or bradykinin (IC<sub>50</sub> = 100 μm), but not angiotensin II-(1–7) or bradykinin<sub>1–5</sub>, and the prolyl oligopeptidase inhibitor Fmoc-Ala-Pyr-CN (IC<sub>50</sub> = 50 nm) also blocked purified PKA activation of PK. The <i>K</i><sub>m</sub> of PK activation by PRCP is 6.7 nm. PRCP antigen is present on the membrane of fixed but not permeabilized HUVEC. PRCP appears to be a HUVEC-associated PK activator.