gebhart/patrepeval huggingface dataset:
Anti-T Cell Receptor Monoclonal Antibody Prolongs Transgene Expression Following Adenovirus-Mediated In Vivo Gene Transfer to Mouse Synovium (1996)

There are no cures for rheumatoid arthritis (RA) or other inflammatory autoimmune arthropathies. Gene transfer to the synovium would allow administration of anti-inflammatory gene products directly to the articular space where they could exert a local down-regulatory effect on the autoimmune process. Several well-characterized murine models of arthritis closely resemble RA immunologically, genetically, and histopathologically. To determine whether the mouse could serve as a model for gene transfer to the synovium, a methodology was developed to reproducibly inject a 5-microliter volume into the articular space of the mouse knee. Using this approach, Av1LacZ4, an E1a-E3-deleted adenoviral (Ad5) vector expressing the lacZ transgene, was delivered intra-articularly (5 x 10(8) pfu). lacZ expression was observed in the articular synovium for at least 14 days. Biochemical quantitation demonstrated a gradual loss of transgene expression, associated with an early, predominantly neutrophilic, inflammatory response that progressed to a lymphocytic infiltrate, followed by gradual resolution over a 3-week period. Pretreatment with the anti-TCR monoclonal antibody (mAb) H57 resulted in a significant reduction in lymphocytic infiltration and a prolongation of transgene expression. These data demonstrate that transgenes can be delivered to the mouse knee joint space, affording a powerful tool to test the potential of gene therapy as a therapeutic modality for RA. As in other systems, the immune response against recombinant adenoviral vectors may limit the extent and duration of gene expression in the synovium. Anti-T cell mAbs may be useful in inhibiting this immune response.
Cyclic AMP and the pathogenesis of myocardial injury. (1980)

Rabbits were given N6, O2, dibutyryl 3', 5' - cyclic AMP DB-cAMP), 2.5 micrograms/kg/min, i.v. for 90 min. to determine if activation of the cyclic neucleotide system is a potential cause of myocardial injury. They were sacrificed 7 or 14 days after infusion and the hearts examined by light and electron microscopy. Cardiac lesions were uniformly present in all hearts. They were primarily those of myofribrillar degeneration and characterized by hypercontracted muscle fibers with transverse band formation, but no inflammatory response. Additional ultrastructural alterations included foci of myofiber lysis, mitochondrial translocation, and deep scalloping of sarcolemma. The SR and T system showed varying degrees of dilatation. These changes were equally intense 2 weeks after giving DB-cAMP. Similar findings have been reported in catecholamine cardiomyopathy and numerous pathological states. It is suggested that excessive stimulation of the cyclase system can serve as a common mechanism in the pathogensis of myocardial damage by a broad spectrum stimuli.
Photodefinable PDMS thin films for microfabrication applications (2009)

In this work, direct patterning of polydimethylsiloxane (PDMS) is demonstrated by the addition of a UV-sensitive photoinitiator benzophenone. As an improvement to our previous work, patterns with both positive and negative features have been fabricated on the same substrate. Infrared spectroscopy was used to investigate photocrosslinking behavior and reaction chemistry of this new photodefinable PDMS (photoPDMS) material. Several applications of the photoPDMS process have been successfully demonstrated. Multi-layer structures and multi-level microfluidic chips can be easily fabricated using this photopatterning process. Patterned PDMS thin films can also be removed from the underlying substrates and used as shadow masks for defining patterns on both planar and non-planar surfaces. The photopatternable PDMS was also found to be biocompatible once un-reacted benzophenone is extracted from the cured film. Overall, photoPDMS offers a number of critical advantages over conventional PDMS processing, including elimination of master template fabrication, ability to process under ambient light processing conditions, positive-acting tone, low cost, and rapid and easy fabrication.
Task-Driven Tactile Exploration (2010)

This paper presents a decision-theoretic approach to problems that require accurate placement of a robot relative to an object in the world, including grasping and insertion. The decision process is applied to a robot hand with tactile sensors, to localize the object and ultimately achieve a target placement by selecting among grasping and information-gathering trajectories. The process is demonstrated in simulation and on a real robot.
An AAV9 coding for frataxin clearly improved the symptoms and prolonged the life of Friedreich ataxia mouse models (2014)

Friedreich ataxia (FRDA) is a genetic disease due to increased repeats of the GAA trinucleotide in intron 1 of the frataxin gene. This mutation leads to a reduced expression of frataxin. We have produced an adeno-associated virus (AAV)9 coding for human frataxin (AAV9-hFXN). This AAV was delivered by intraperitoneal (IP) injection to young conditionally knockout mice in which the frataxin gene had been knocked-out in some tissues during embryogenesis by breeding them with mice expressing the Cre recombinase gene under the muscle creatine kinase (MCK) or the neuron-specific enolase (NSE) promoter. In the first part of the study, different doses of virus were tested from 6 × 10(11) v.p. to 6 × 10(9) v.p. in NSE-cre mice and all leading to an increase in life spent of the mice. The higher and the lower dose were also tested in MCK-cre mice. A single administration of the AAV9-hFXN at 6 × 10(11) v.p. more than doubled the life of these mice. In fact the MCK-cre mice treated with the AAV9-hFXN were sacrificed for further molecular investigations at the age of 29 weeks without apparent symptoms. Echography analysis of the heart function clearly indicated that the cardiac systolic function was better preserved in the mice that received 6 × 10(11) v.p. of AAV9-hFXN. The human frataxin protein was detected by ELISA in the heart, brain, muscles, kidney, and liver with the higher dose of virus in both mouse models. Thus, gene therapy with an AAV9-hFXN is a potential treatment of FRDA.
Enzymatic Characterisation of Novamyl®, a Thermostable α-Amylase (1998)

The thermostable -amylase Novamyl® is used in the baking industry as an antistaling agent due to its ability to reduce retrogradation of amylopectin. We have studied its enzymatic properties at pH 5.0. We make two main conclusions: (1) Novamyl® shows sequence homology to cycloglycosyl transferases (CGTases); like these enzymes, Novamyl® cleaves cyclodextrins, forms transglycosylation products and is subject to product inhibition by maltose. Novamyl® has 5 subsites in the active site and is also subject to substrate inhibition. (2) Novamyl® is clearly different from exoglucanases like β-amylase and glucoamylase. It is able to hydrolyse a pentasaccharide with bulky substituents at both ends (INdp5) and is inhibited by the α-amylase inhibitor Trestatin A. Although Novamyl® appears unable to hydrolyse α-1,6-linkages, it is able to degrade amylopectin to a greater extent than β-amylase as well as β-limit dextrins. Novamyl® degrades amylose in such a manner that initially the molecular weight is drastically reduced while β-amylase does not show any detectable effect on the molecular weight of this substrate. Products of the degradation of amylopectin and amylose by Novamyl® are maltose and oligosaccharides, whereas β-amylase and glucoamylase produce only maltose and glucose, respectively. This was shown in baking experiments as well. The new data presented here clearly show that unlike exoamylases, Novamyl® does not require a non-reducing end and attacks amylose, Indp5 and cyclodextrins in an endo-like manner. Based on these results Novamyl® should be reclassified.
Plasma Free Fatty Acids and Peroxisome Proliferator–Activated Receptor α in the Control of Myocardial Uncoupling Protein Levels (2005)

Diabetic patients have abnormal cardiac energy metabolism associated with high plasma free fatty acid (FFA) concentrations. We investigated whether high plasma FFAs increase mitochondrial uncoupling protein (UCP) levels in the mouse heart by activating the nuclear transcription factor peroxisome proliferator-activated receptor (PPAR)alpha. We used Western blotting to measure UCP protein levels in isolated cardiac mitochondria from PPARalpha-/- and diabetic mice. Cardiac UCP2 and UCP3 were significantly lower in the PPARalpha-/- mouse than in the wild type. Treatment with the PPARalpha-specific agonist, WY-14,643, increased cardiac UCP2 and UCP3 levels in wild-type mice but did not alter UCP levels in PPARalpha-/- mice. Inhibition of beta-oxidation with etomoxir increased cardiac UCP2 and UCP3 levels in wild-type mice and UCP2 levels in PPARalpha-/- mice but did not alter UCP3 levels in PPARalpha-/- mice. Streptozotocin treatment, which increased circulating FFAs by 91%, did not alter cardiac UCP2 levels in wild-type or PPARalpha-/- mice but increased UCP3 levels in wild-type, and not in PPARalpha-/-, mice. The diabetic db/db mouse had 50% higher plasma FFA concentrations and elevated cardiac UCP2 and UCP3 protein levels. We conclude that high plasma FFAs activated PPARalpha to increase cardiac UCP3 levels, but cardiac UCP2 levels changed via PPARalpha-dependent and -independent mechanisms.
GENCODE: The reference human genome annotation for The ENCODE Project (2012)

The GENCODE Consortium aims to identify all gene features in the human genome using a combination of computational analysis, manual annotation, and experimental validation. Since the first public release of this annotation data set, few new protein-coding loci have been added, yet the number of alternative splicing transcripts annotated has steadily increased. The GENCODE 7 release contains 20,687 protein-coding and 9640 long noncoding RNA loci and has 33,977 coding transcripts not represented in UCSC genes and RefSeq. It also has the most comprehensive annotation of long noncoding RNA (lncRNA) loci publicly available with the predominant transcript form consisting of two exons. We have examined the completeness of the transcript annotation and found that 35% of transcriptional start sites are supported by CAGE clusters and 62% of protein-coding genes have annotated polyA sites. Over one-third of GENCODE protein-coding genes are supported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas. New models derived from the Illumina Body Map 2.0 RNA-seq data identify 3689 new loci not currently in GENCODE, of which 3127 consist of two exon models indicating that they are possibly unannotated long noncoding loci. GENCODE 7 is publicly available from gencodegenes.org and via the Ensembl and UCSC Genome Browsers.
The expression of CD18 is increased on Trisomy 21 (Down syndrome) lymphoblastoid cells. (1988)

The monoclonal antibody (MAB) 60.3 reacts with the beta chain (CD18) of lymphocyte function associated antigen (LFA-1), encoded by a gene on chromosome 21. We have used 60.3 to measure the expression of CD18 on lymphoblastoid cell-lines derived from persons with Trisomy 21 (Down syndrome) by quantitative fluorescence flow cytometric analysis. This showed that CD18 expression is increased on Trisomy 21 compared with normal cells, whereas neither HLA-class I, nor transferrin receptor expression are significantly affected. Similar results were obtained with the CD18 MAB MHM 23, and with the CD11a MAB MHM 24 (LFA-1 alpha). These results suggest that the increase in CD18 expression by Trisomy 21 cells is due to gene dosage, and could influence the immune status of persons with Down syndrome.
Structure and properties of carotenoids in relation to function. (1995)

The basic principles of structure, stereochemistry, and nomenclature of carotenoids are described and the relationships between structure and the chemical and physical properties on which all the varied biological functions and actions of carotenoids depend are discussed. The conjugated polyene chromophore determines not only the light absorption properties, and hence color, but also the photochemical properties of the molecule and consequent light-harvesting and photoprotective action. The polyene chain is also the feature mainly responsible for the chemical reactivity of carotenoids toward oxidizing agents and free radicals, and hence for any antioxidant role. In vivo, carotenoids are found in precise locations and orientations in subcellular structures, and their chemical and physical properties are strongly influenced by other molecules in their vicinity, especially proteins and membrane lipids. In turn, the carotenoids influence the properties of these subcellular structures. Structural features such as size, shape, and polarity are essential determinants of the ability of a carotenoid to fit correctly into its molecular environment to allow it to function. A role for carotenoids in modifying structure, properties, and stability of cell membranes, and thus affecting molecular processes associated with these membranes, may be an important aspect of their possible beneficial effects on human health.--Britton, G. Structure and properties of carotenoids in relation to function.
Tau elevations in the brain extracellular space correlate with reduced amyloid-β levels and predict adverse clinical outcomes after severe traumatic brain injury (2011)

Axonal injury is believed to be a major determinant of adverse outcomes following traumatic brain injury. However, it has been difficult to assess acutely the severity of axonal injury in human traumatic brain injury patients. We hypothesized that microdialysis-based measurements of the brain extracellular fluid levels of tau and neurofilament light chain, two low molecular weight axonal proteins, could be helpful in this regard. To test this hypothesis, 100 kDa cut-off microdialysis catheters were placed in 16 patients with severe traumatic brain injury at two neurological/neurosurgical intensive care units. Tau levels in the microdialysis samples were highest early and fell over time in all patients. Initial tau levels were >3-fold higher in patients with microdialysis catheters placed in pericontusional regions than in patients in whom catheters were placed in normal-appearing right frontal lobe tissue (P = 0.005). Tau levels and neurofilament light-chain levels were positively correlated (r = 0.6, P = 0.013). Neurofilament light-chain levels were also higher in patients with pericontusional catheters (P = 0.04). Interestingly, initial tau levels were inversely correlated with initial amyloid-β levels measured in the same samples (r = -0.87, P = 0.000023). This could be due to reduced synaptic activity in areas with substantial axonal injury, as amyloid-β release is closely coupled with synaptic activity. Importantly, high initial tau levels correlated with worse clinical outcomes, as assessed using the Glasgow Outcome Scale 6 months after injury (r = -0.6, P = 0.018). Taken together, our data add support for the hypothesis that axonal injury may be related to long-term impairments following traumatic brain injury. Microdialysis-based measurement of tau levels in the brain extracellular space may be a useful way to assess the severity of axonal injury acutely in the intensive care unit. Further studies with larger numbers of patients will be required to assess the reproducibility of these findings and to determine whether this approach provides added value when combined with clinical and radiological information.
High-level resistance to (-) enantiomeric 2'-deoxy-3'-thiacytidine in vitro is due to one amino acid substitution in the catalytic site of human immunodeficiency virus type 1 reverse transcriptase (1993)

Passage of human immunodeficiency virus type 1 in the presence of increasing 2'-deoxy-3'-thiacytidine (3TC) concentrations results in high-level (> 100-fold) 3TC-resistant viruses. All 3TC-resistant viruses possess a substitution at the second codon (from a methionine into an isoleucine) at position 184 within the highly conserved motif (YMDD) of human immunodeficiency virus type 1 reverse transcriptase. 3TC-resistant viruses were cross-resistant to the (-) enantiomer of the fluorinated derivative of BCH-189 but remained susceptible to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine. The susceptibilities of the 3TC-resistant viruses to the (+) enantiomers of BCH-189 and the fluorinated derivative of BCH-189 demonstrate an enantiomeric specificity for viruses selected under these conditions. Introduction of an isoleucine substitution at codon 184 into a background of two known 3'-azido-3'-deoxythymidine resistance mutations (amino acids 41 and 215) restored the susceptibility of this virus to 3'-azido-3'-deoxythymidine.
HPSm, a high performance restricted data flow architecture having minimal functionality (1998)

Our recent work in microarchitecture has identified a new model of execution, restricted data Bow, in which data flow techniques are used to coordinate out-of-order execution of sequential instruction streams. We believe that the restricted data flow model has great potential for implementing very high performance computing engines. This paper defines a minimal functionality variant of our model, which we are calling HPSm. The instruction set, data path, timing and control of HPSm are all described. A simulator for HPSm has been written, and some of the Berkeley RISC benchmarks have been executed on the simulator. We report the measurements obtained from these benchmarks, along with the measurements obtained for the Berkeley RISC II. The resulb are encouraging.
Large bandwidth frequency-converted Nd:glass laser at 527 nm with Δν/ν=2% (1993)

Large bandwidth in lasers for inertial confinement fusion is potentially capable of controlling laser-plasma instabilities. We have demonstrated the efficient generation of large bandwidth, \ensuremath{\Delta}\ensuremath{\nu}/\ensuremath{\nu}=2%, in a frequency-doubled Nd:glass laser in 527 nm, using stimulated rotational Raman scattering in atmospheric pressure nitrogen gas. Its use in a fusion laser would involve the use of a multilens array to produce multiple foci where the broadband conversion takes place. This technique is also effective for frequency tripled or quadrupled lasers at 351 or 263 nm.
Defect reduction of GaAs epitaxy on Si (001) using selective aspect ratio trapping (2007)

Metal-organic chemical vapor deposition growth of GaAs on Si was studied using the selective aspect ratio trapping method. Vertical propagation of threading dislocations generated at the GaAs∕Si interface was suppressed within an initial thin GaAs layer inside SiO2 trenches with aspect ratio &amp;gt;1, leading to defect-free GaAs regions up to 300nm in width. Cross-sectional and plan-view transmission electron microscopies were used to characterize the defect reduction. Material quality was confirmed by room temperature photoluminescence measurements. This approach shows great promise for the fabrication of optoelectronic integrated circuits on Si substrates.
Promoter specificity in Pseudomonas aeruginosa quorum sensing revealed by DNA binding of purified LasR (2004)

Along with their cognate acyl-homoserine lactone signals, the quorum sensing regulators LasR and RhlR control the expression of hundreds of genes in the opportunistic human pathogen Pseudomonas aeruginosa. This extensive, overlapping regulatory network affords the opportunity to systematically investigate the sequence requirements and specificity determinants of large families of target promoters. Many of the P. aeruginosa quorum-controlled genes possess conserved palindromic promoter elements predicted to be binding sites for either one or both transcriptional regulators, but biochemical proof has not been reported. We have purified native LasR and characterized binding to various quorum-controlled promoters in vitro. Purified LasR was a dimer in solution that irreversibly bound two molecules of 3-oxo-C12-homoserine lactone. LasR bound several las-responsive promoters specifically and with high affinity, interacting cooperatively with some promoters and noncooperatively with others. LasR recognized some, but not all, of the predicted binding sites, and also bound to several unexpected sites. In contrast to predictions from genetic data, we found that the recognition sequences of las-specific promoters showed little overall sequence conservation and did not require dyad symmetry. We found distinct differences in sequence composition between las-specific noncooperative, las-specific cooperative, and rhl-responsive promoters. These results provide the basis for defining promoter specificity elements in P. aeruginosa quorum sensing. Insights into the molecular mechanism of LasR function have implications for the development of quorum-sensing targeted antivirulence compounds.
Very strong antiferromagnetic interlayer exchange coupling with iridium spacer layer for perpendicular magnetic tunnel junctions (2017)

We systematically studied the interlayer exchange coupling (IEC) in a perpendicular synthetic antiferromagnetically coupled structure having an Ir spacer layer for perpendicular magnetic tunnel junctions (p-MTJs). We found a broader peak in IEC energy density (Jex) versus spacer thickness (tIr) compared with the case of using a Ru spacer. The highest IEC energy density was 2.6 erg/cm2 at a tIr of about 5 nm. The p-MTJ nanopillars had a high magnetoresistance ratio (131%) as well as a high spin-transfer torque (STT) switching efficiency (about 2). An Ir spacer can be used to make a stable reference layer for STT magnetoresistive random access memory.
Expression profiling reveals hepsin overexpression in prostate cancer. (2001)

Prostate cancer is the most commonly diagnosed noncutaneous cancer in men. Despite this fact, many of the genetic changes that coincide with prostate cancer progression remain enigmatic. We have addressed this problem by characterizing the expression profiles of several benign and malignant human prostate samples, and we have identified several genes that are differentially expressed between benign and malignant glands. One gene that was overexpressed encodes the serine protease hepsin. We used an independent sample set to confirm that hepsin is overexpressed in prostate tumors, and in situ hybridization demonstrates that hepsin is specifically overexpressed in the carcinoma cells themselves. These facts, together with the molecular properties of hepsin, make it an ideal target for prostate cancer therapy.
Correlates of Sexually Related Personal Distress in Women with Low Sexual Desire (2009)

Age has a curvilinear relationship with distress, and the strongest correlate of sexual distress was having a current partner. Sexual distress and dissatisfaction with sex life are strongly correlated. Distress is higher in women with low sexual desire in a partner relationship; further research on this factor is needed.