gebhart/patrepeval huggingface dataset:
REDD1 deletion prevents dexamethasone-induced skeletal muscle atrophy (2014)

REDD1 (regulated in development and DNA damage response 1) has been proposed to inhibit the mechanistic target of rapamycin complex 1 (mTORC1) during in vitro hypoxia. REDD1 expression is low under basal conditions but is highly increased in response to several catabolic stresses, like hypoxia and glucocorticoids. However, REDD1 function seems to be tissue and stress dependent, and its role in skeletal muscle in vivo has been poorly characterized. Here, we investigated the effect of REDD1 deletion on skeletal muscle mass, protein synthesis, proteolysis, and mTORC1 signaling pathway under basal conditions and after glucocorticoid administration. Whereas skeletal muscle mass and typology were unchanged between wild-type (WT) and REDD1-null mice, oral gavage with dexamethasone (DEX) for 7 days reduced tibialis anterior and gastrocnemius muscle weights as well as tibialis anterior fiber size only in WT. Similarly, REDD1 deletion prevented the inhibition of protein synthesis and mTORC1 activity (assessed by S6, 4E-BP1, and ULK1 phosphorylation) observed in gastrocnemius muscle of WT mice following single DEX administration for 5 h. However, our results suggest that REDD1-mediated inhibition of mTORC1 in skeletal muscle is not related to the modulation of the binding between TSC2 and 14-3-3. In contrast, our data highlight a new mechanism involved in mTORC1 inhibition linking REDD1, Akt, and PRAS40. Altogether, these results demonstrated in vivo that REDD1 is required for glucocorticoid-induced inhibition of protein synthesis via mTORC1 downregulation. Inhibition of REDD1 may thus be a strategy to limit muscle loss in glucocorticoid-mediated atrophy.
Anti-ceramide antibody prevents the radiation gastrointestinal syndrome in mice (2012)

Radiation gastrointestinal (GI) syndrome is a major lethal toxicity that may occur after a radiation/nuclear incident. Currently, there are no prophylactic countermeasures against radiation GI syndrome lethality for first responders, military personnel, or remediation workers entering a contaminated area. The pathophysiology of this syndrome requires depletion of stem cell clonogens (SCCs) within the crypts of Lieberkühn, which are a subset of cells necessary for postinjury regeneration of gut epithelium. Recent evidence indicates that SCC depletion is not exclusively a result of DNA damage but is critically coupled to ceramide-induced endothelial cell apoptosis within the mucosal microvascular network. Here we show that ceramide generated on the surface of endothelium coalesces to form ceramide-rich platforms that transmit an apoptotic signal. Moreover, we report the generation of 2A2, an anti-ceramide monoclonal antibody that binds to ceramide to prevent platform formation on the surface of irradiated endothelial cells of the murine GI tract. Consequently, we found that 2A2 protected against endothelial apoptosis in the small intestinal lamina propria and facilitated recovery of crypt SCCs, preventing the death of mice from radiation GI syndrome after high radiation doses. As such, we suggest that 2A2 represents a prototype of a new class of anti-ceramide therapeutics and an effective countermeasure against radiation GI syndrome mortality.
Dectin-1 and TLRs Permit Macrophages to Distinguish between Different Aspergillus fumigatus Cellular States (2006)

Aspergillus fumigatus is a common cause of invasive and allergic pulmonary disease. Resting conidia of the filamentous fungus are constantly inhaled, but cause infection only after initiating hyphal growth. In this study, we have explored whether macrophages can distinguish between resting spores and the maturing, potentially invasive form of the fungus. Although macrophages bind and ingest A. fumigatus resting conidia efficiently, there is little inflammatory response; NF-kappabeta is not activated, inflammatory cytokines are not induced, and reactive oxygen species are not produced. However, maturing A. fumigatus conidia and germ tubes stimulate NF-kappabeta, secretion of proinflammatory cytokines and production of reactive oxygen by human monocyte-derived macrophages and murine macrophages from multiple anatomical sites. These responses are in part mediated by dectin-1, which binds cell wall beta-glucan that is not present on the surface of dormant conidia, but is present after cellular swelling and loss of the hydrophobic proteinaceous cell wall. Dectin-1 binding to germ tubes augments, but is not required for, TLR2-mediated inflammatory cytokine secretion. Dectin-1 recognition of germ tubes also stimulates TNF-alpha production in the absence of both TLR2 and MyD88 signaling. These data demonstrate one mechanism by which the pulmonary inflammatory response is tailored toward metabolically active cells, thereby avoiding unnecessary tissue damage with frequent inhalation of ubiquitous spores.
Liver gene therapy by lentiviral vectors reverses anti‐factor IX pre‐existing immunity in haemophilic mice (2013)

A major complication of factor replacement therapy for haemophilia is the development of anti-factor neutralizing antibodies (inhibitors). Here we show that liver gene therapy by lentiviral vectors (LVs) expressing factor IX (FIX) strongly reduces pre-existing anti-FIX antibodies and eradicates FIX inhibitors in haemophilia B mice. Concomitantly, plasma FIX levels and clotting activity rose to 50-100% of normal. The treatment was effective in 75% of treated mice. FIX-specific plasma cells (PCs) and memory B cells were reduced, likely because of memory B-cell depletion in response to constant exposure to high doses of FIX. Regulatory T cells displaying FIX-specific suppressive capacity were induced in gene therapy treated mice and controlled FIX-specific T helper cells. Gene therapy proved safer than a regimen mimicking immune tolerance induction (ITI) by repeated high-dose FIX protein administration, which induced severe anaphylactoid reactions in inhibitors-positive haemophilia B mice. Liver gene therapy can thus reverse pre-existing immunity, induce active tolerance to FIX and establish sustained FIX activity at therapeutic levels. These data position gene therapy as an attractive treatment option for inhibitors-positive haemophilic patients.
Transforming growth factor‐β3–loaded microtextured membranes for skin regeneration in dermal wounds (2004)

Adverse effects of wound healing, such as excessive scar tissue formation, wound contraction, or nonhealing wounds represent a major clinical issue in today's healthcare. Transforming growth factor (TGF)-beta3 has specifically been implicated in wound healing. Our hypothesis was that local administration of TGF-beta3 to excisional dermal wounds would diminish wound contraction and scar formation. Microtextured wound covers, containing different concentrations of TGF-beta3, were placed onto full-thickness excisional skin wounds in guinea pigs. Tattooed reference marks were used to quantify wound contraction. Sixty-four male guinea pigs in four study groups (5 ng TGF-beta3, 50 ng TGF-beta3, no growth factor, sham wound) were followed for up to 6 weeks. We analyzed 19 different parameters of wound healing. Results showed that, in some instances, the 50-ng TGF-beta3 group gave less contraction, whereas the 5-ng TGF-beta3 group gave more contraction. These differences confirm that TGF-beta3 has an optimum working concentration, and suggest this concentration to be closer to 50 ng than to 5 ng TGF-beta3. However, only very few significant differences occurred, and thus we conclude that the clinical relevance of our findings is negligible. Earlier studies, reporting clinically improved wound healing by TGF-beta3, could therefore not be confirmed by this study.
A real-time assay for monitoring nucleic acid cleavage by quadruplex formation (2006)

Direct and straightforward methods to follow nucleic acid cleavage are needed. A spectrophotometric quadruplex formation assay (QFA) was developed, which allows real-time monitoring of site-specific cleavage of nucleic acids. QFA was applied to study both protein and nucleic acid restriction enzymes, and was demonstrated to accurately determine Michaelis-Menten parameters for the cleavage reaction catalyzed by EcoRI. QFA can be used to study the mechanisms of protein-nucleic acid recognition. QFA is also a useful tool for dissecting individual nicking rates of a double-stranded cleavage.
Decreased oxygen uptake with stored blood in the isolated hindlimb (1975)

Storage of red cells in acid-citrate-dextrose (ACD) solution for more than a week has been shown to cause a reduction in red cell 2,3-diphosphoglycerate (2,3-DPG), resulting in a decrease in the half-saturation pressure (P50) of stored blood, thus increasing hemoglobin-oxygen affinity and theoretically decreasing oxygen delivery to the tissues. A method to isolate and perfuse the hindlimb in a dog has been developed and used successfully to compare the difference of oxygen release between banked and fresh ACD blood. Ten dogs were perfused using canine blood collected in standard blood transfusion bags containing ACD and stored at 4 degrees C and fresh blood collected in a similar manner but used immediately. The total oxygen release in the limb during perfusion with fresh blood was significantly greater than during perfusion with stored blood.
Energy-efficient motion planning for mobile robots (2004)

This paper presents a new approach to find energy-efficient motion plans for mobile robots. Motion planning has two goals: finding the routes and determining the velocities. We model the relationship of motors' speed and their power consumption with polynomials. The velocity of the robot is related to its wheels' velocities by performing a linear transformation. We compare the energy consumption of different routes at different velocities and consider the energy consumed for acceleration and turns. We use experiment-validated simulation to demonstrate up to 51% energy savings for searching an open area.
SIFT-ing through features with ViPR (2006)

Recent advances in computer vision have given rise to a robust and invariant visual pattern recognition technology that is based on extracting a set of characteristic features from an image. Such features are obtained with the scale invariant feature transform (SIFT) which represents the variations in brightness of the image around the point of interest. Recognition performed with these features has been shown to be quite robust in realistic settings. This paper describes the application of this particular visual pattern recognition (ViPR) technology to a variety of robotics applications: object recognition, navigation, manipulation, and human-machine interaction. The paper also describes the technology in more detail and presents a business case for visual pattern recognition in the field of robotics and automation
Fibrin Sealant Adhesive Systems: A Review of Their Chemistry, Material Properties and Clinical Applications (1993)

Fibrin sealants (FS) are the most successful tissue adhesives to date. They have many advantages over adhesive technologies such as cyanoacrylates and marine adhesives in terms of biocompatibility, biodegradation and hemostasis. There are several commercial products in Europe but none in the United States due to the current regulatory stance against pooled plasma blood products. Blood banks and interested investigators have implemented single- and patient autologous-donor production methods with some success. This article will review the history of FS research and development and describe the chemistry of fibrin(ogen) and the production of commercial and research products. Fibrin sealant and purified fibrin characterization is compared and contrasted. The material and adhesive properties are described, and a survey of the clinical applications in which FS has been used is included as well.
Rapid enrichment of HeLa transcription factors IIIB and IIIC by using affinity chromatography based on avidin-biotin interactions. (1986)

Plasmid DNA containing the adenovirus type 2 genes for VA RNA was linearized at a site distal to the gene, end labeled with a biotin-nucleotide analog of TTP, and incubated with avidin to form an avidin-biotinylated DNA complex. HeLa cell S100 extracts containing crude RNA polymerase III and transcription factors (TFs) IIIB and IIIC were programmed with the avidin-biotin-VA DNA to allow stable complex formation (A.B. Lassar, P.L. Martin, and R.G. Roeder, Science 222:740-748, 1983). Chromatography of the programmed extract over a biotin-cellulose affinity resin resulted in the selective, and virtually quantitative, retention of one of two stable preinitiation complexes, either VA-IIIC or VA-IIIC-IIIB, depending on the length of template incubation in the S100 extract. After washing the resin with 0.10 M and 0.25 M KCl to remove RNA polymerase III and nonspecifically bound proteins, respectively, TFIIIC was eluted from the VA-IIIC complex by the addition of 1.5 M KCl. The VA-IIIC-IIIB complex exhibited a higher salt stability. Most of TFIIIB and some TFIIIC were released by the addition of 1.5 M KCl; however, the majority of TFIIIC activity was recovered only after a subsequent 3.0 M KCl elution. The specific activity of the TFIIIC in the 3.0 M KCl fraction was 770-fold higher than that in the S100 extract, while the protein content of the 1.5 and 3.0 M KCl fractions was reduced 7,500- and 100,000-fold, respectively.
Antibiotic loaded chitosan bar. An in vitro, in vivo study of a possible treatment for osteomyelitis. (1999)

A biodegradable drug delivery system of a gentamicin loaded chitosan bar with sustained antibiotic effect is described. Chitosan has proven to be a biocompatible aminopolysaccharide and a matrix for controlled release of pharmaceuticals. Combined crosslinking, solvent evaporation, and a cylinder model cutting technique was used to prepare the chitosan bar. Sustained diffusion of gentamicin into the surrounding medium was seen using a release test in vitro. Approximately 11% gentamicin was released from the bar in the first 24 hours. The gentamicin released from the bar showed significant antibacterial activity. The bar implanted in the proximal portion of the rabbit tibia produced a low blood concentration of gentamicin, but a much higher concentration was produced in local bone and in the hematoma. In all bone tissue around the bar, the gentamicin concentration exceeded the minimum inhibitory concentration for the common causative organisms of osteomyelitis for approximately 8 weeks. The implant caused no systemic side effects. Based on these test results together with the chitosan characteristics of biodegradable, antibiotic, and immunologic activity, the gentamicin loaded chitosan bar seems to be a clinically useful method for the treatment of bone infection. This system has an advantage over other systems in that it avoids a second operation for removal of the carrier.
Stress Control of Si-based PECVD Dielectrics (2006)

Abstract not Available.
but Not JAK1 Activation of JAK3Is Critical to Interleukin-4 (IL4) Stimulated Proliferation and Requires a Membrane-proximal Region of IL4 Receptor α (1995)

The tyrosine kinases JAK1 and JAK3 have been shown to undergo tyrosine phosphorylation in response to interleukin-2 (IL), IL4, IL7, and IL9, cytokines which share the common IL2 receptor gamma-chain (IL2R gamma), and evidence has been found for a preferential coupling of JAK3 to IL2R gamma and JAK1 to IL2R beta. Here we show, using human premyeloid TF-1 cells, that IL4 stimulates JAK3 to a larger extent than JAK1, based upon three different evaluation criteria. These include a more vigorous tyrosine phosphorylation of JAK3 as measured by anti-phosphotyrosine immunoblotting, a more marked activation of JAK3 as determined by in vitro tyrosine kinase assays and a more manifest presence of JAK3 in activated IL4-receptor complexes. These observations suggest that IL4 receptor signal transduction does not depend on equimolar heterodimerization of JAK1 and JAK3 following IL4-induced heterodimerization of IL4R alpha and IL2R gamma. Indeed, when human IL4R alpha was stably expressed in mouse BA/F3 cells, robust IL4-induced proliferation and JAK3 activation occurred without detectable involvement of JAK1, JAK2, or TYK2. The present study suggests that JAK1 plays a subordinate role in IL4 receptor signaling, and that in certain cells exclusive JAK3 activation may mediate IL4-induced cell growth. Moreover, mutational analysis of human IL4R alpha showed that a membrane-proximal cytoplasmic region was critical for JAK3 activation, while the I4R motif was not, which is compatible with a role of JAK3 upstream of the recruitment of the insulin receptor substrate-1/4PS signaling proteins by IL4 receptors.
Csk Homologous Kinase, a Novel Signaling Molecule, Directly Associates with the Activated ErbB-2 Receptor in Breast Cancer Cells and Inhibits Their Proliferation (1998)

Substantial evidence exists supporting direct roles for ErbB-2/neu and Src kinase activation in breast cancer. The Csk homologous kinase (CHK) is a recently identified tyrosine kinase which, like Csk, phosphorylates the C-terminal tyrosine of Src kinases, resulting in inactivation of these enzymes. Recently, we observed that CHK is associated with the ErbB-2/neu receptor upon heregulin stimulation of breast cancer cells. Here, we report that CHK expression was observed in 70 out of 80 primary breast cancer specimens but not in normal breast tissues (0/19). Confocal microscopy analysis revealed co-localization of CHK with ErbB-2 in these primary specimens (6/6). In addition, we observed that the cytoplasmic domain of the ErbB-2/neu receptor is sufficient for its interaction with the CHKSH2 domain. Phosphopeptide inhibition of the in vitro interaction of CHKSH2 or native CHK with ErbB-2/neu, as well as site-directed mutagenesis of ErbB-2/neu, indicated that CHKSH2 binds to Tyr1253 of ErbB-2/neu. Interestingly, autophosphorylation at this site confers oncogenicity to this receptor. Moreover, CHK was able to down-regulate ErbB-2/neu-activated Src kinases. Overexpression of CHK in MCF-7 breast cancer cells markedly inhibited cell growth and proliferative response to heregulin as well as decreased colony formation in soft agar. These studies indicate that CHK binds, via its SH2 domain, to Tyr1253 of the activated ErbB-2/neu and down-regulates the ErbB-2/neu-mediated activation of Src kinases, thereby inhibiting breast cancer cell growth. These data strongly suggest that CHK is a novel negative growth regulator in human breast cancer.
Zidovudine ameliorates pathology in the mouse model of Duchenne muscular dystrophy via P2RX7 purinoceptor antagonism (2018)

Duchenne muscular dystrophy (DMD) is the most common inherited muscle disorder that causes severe disability and death of young men. This disease is characterized by progressive muscle degeneration aggravated by sterile inflammation and is also associated with cognitive impairment and low bone density. Given that no current treatment can improve the long-term outcome, approaches with a strong translational potential are urgently needed. Duchenne muscular dystrophy (DMD) alters P2RX7 signaling in both muscle and inflammatory cells and inhibition of this receptor resulted in a significant attenuation of muscle and non-muscle symptoms in DMD<sup>mdx</sup> mouse model. As P2RX7 is an attractive target in a range of human diseases, specific antagonists have been developed. Yet, these will require lengthy safety testing in the pediatric population of Duchenne muscular dystrophy (DMD) patients. In contrast, Nucleoside Reverse Transcriptase Inhibitors (NRTIs) can act as P2RX7 antagonists and are drugs with an established safety record, including in children. We demonstrate here that AZT (Zidovudine) inhibits P2RX7 functions acting via the same allosteric site as other antagonists. Moreover, short-term AZT treatment at the peak of disease in DMD<sup>mdx</sup> mice attenuated the phenotype without any detectable side effects. Recovery was evident in the key parameters such as reduced sarcolemma permeability confirmed by lower serum creatine kinase levels and IgG influx into myofibres, decreased inflammatory cell numbers and inflammation markers in leg and heart muscles of treated mice. Moreover, this short-term therapy had some positive impact on muscle strength in vivo and no detrimental effect on mitochondria, which is the main side-effect of Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Given these results, we postulate that AZT could be quickly re-purposed for the treatment of this highly debilitating and lethal disease. This approach is not constrained by causative DMD mutations and may be effective in alleviating both muscle and non-muscle abnormalities.
Physical Interaction between Replication Protein A and Rad51 Promotes Exchange on Single-stranded DNA (2004)

Replication protein A (RPA) is displaced from single-stranded DNA (ssDNA) by Rad51 during the initiation of homologous recombination. Interactions between these proteins have been reported, but the functional significance of the direct RPA-Rad51 interaction has yet to be elucidated. We have identified and characterized the interaction between DNA-binding domain A of RPA (RPA70A) and the N-terminal domain of Rad51 (Rad51N). NMR chemical shift mapping showed that Rad51N binds to the ssDNA-binding site of RPA70A, suggesting a competitive mechanism for the displacement of RPA from ssDNA by Rad51. A structure of the RPA70A-Rad51N complex was generated by experimentally guided modeling and then used to design mutations that disrupt the binding interface. Functional ATP hydrolysis assays were performed for wild-type Rad51 and a mutant defective in binding RPA. Rates of RPA displacement for the mutant were significantly below those of wild-type Rad51, suggesting that a direct RPA-Rad51 interaction is involved in displacing RPA in the initiation stage of genetic recombination.
Artificial Ribozyme Switches Containing Natural Riboswitch Aptamer Domains (2009)

RNA Lego: The use of natural riboswitch aptamers in synthetic RNA switches (see picture) should broaden the scope of artificial RNA regulators dramatically. It is shown that thiamine pyrophosphate (TPP) aptamers can be used in engineered devices as very sensitive switches of gene expression in unmodified organisms. The approach demonstrates that intrinsic metabolites can be utilized as external effectors of cellular functions.
Microscale Bioanalytical Systems (2002)

Microfluidic phenomena are present in all of nature9s exquisitely designed biological systems. Without microfluidic channels and diffusion transport systems, life as we know it would not be possible (1). Manmade microfluidic systems have been made possible by microfabrication methods developed for the electronics industry. Microfluidic systems are of intense interest due to their characteristic controlled mixing that expedites chemical reactions, reduced consumption of expensive materials, high sensitivity, and efficient product yields. In this article, we aim to share a summary of the applications and design of microfluidic devices.
New Flavonol Tetraglycosides from Astragalus caprinus. (2002)

A new flavonol tetraglycoside, together with four acylated derivatives, were isolated from the leaves of Astragalus caprinus. Their structures were elucidated by spectroscopic methods, mainly 2D NMR, as kaempferol-3-O-[[beta-D-xylopyranosyl(1-->3)-alpha-L-rhamnopyranosyl(1-->6)][alpha-L-rhamnopyranosyl(1-->2)]]-beta-D-galactopyranoside (1), its 3(Gal)-p-coumaric (2) and 3(Gal)-ferulic (3) esters, and its 4(Gal)-p-coumaric (4) and 4(Gal)-ferulic (5) esters.