gebhart/patrepeval huggingface dataset:
Stress failure of pulmonary capillaries as a mechanism for exercise induced pulmonary haemorrhage in the horse (1994)

Exercise induced pulmonary haemorrhage (EIPH) is a serious problem in the Thoroughbred industry. The condition apparently occurs essentially in all Thoroughbreds in training but the mechanism has proved elusive. There is now strong evidence that the condition is caused by mechanical failure of the walls of the pulmonary capillaries when the pressure inside them rises to very high levels. It is well known that pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently we have shown that the wall stresses are very large when the capillary transmural pressure is raised, and in anesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mmHg and above. The incidence of stress failure is greatly increased at high lung volumes; and many of the ultrastructural changes are rapidly reversible when the capillary pressure is reduced. The principal forces acting on the capillary have been analysed. The strength of the thin part of the capillary wall can be attributed to the Type IV collagen in the extracellular matrix. The pulmonary vascular pressures of galloping Thoroughbreds reach very high levels. Mean pulmonary artery and left atrial pressures of up to 120 and 70 mmHg respectively have been directly measured with indwelling catheters. The reason for the high pulmonary vascular pressures is that these animals have been selectively bred over hundreds of years to run at great speeds over short distances and their maximal oxygen consumptions are very high. As a consequence, cardiac outputs are substantial, and the left ventricle needs very high filling pressures.(ABSTRACT TRUNCATED AT 250 WORDS)
Human La Antigen Is Required for the Hepatitis C Virus Internal Ribosome Entry Site-mediated Translation (2000)

The 5'-noncoding region (5'-NCR) of the hepatitis C virus (HCV) RNA genome serves as an internal ribosome entry site (IRES) and mediates translation initiation in a cap-independent manner. Previously, we reported the interaction between La antigen and the HCV IRES, which appeared to occur in the context of initiator AUG. It was further shown that HCV IRES-mediated translation was stimulated in the presence of human La antigen. In this study, we have defined the cis- and trans-acting elements responsible for La-5'-NCR interactions and established the dependence of the HCV IRES efficiency on cellular La antigen. During the La-IRES interaction, initiator AUG but not the neighboring codons was found to be the direct target of La binding. The C terminus effector domain-dependent modulation of La binding to the HCV IRES is demonstrated by deletion and substitution mutagenesis of the protein. An RNA systematic evolution of ligands by exponential enrichment (SELEX), generated against La protein that selectively binds La in HeLa lysates and competes for the protein binding to the 5'-NCR, was used to demonstrate the requirement of La for the HCV IRES function in the context of mono- and dicistronic mRNAs. Sequestration of La antigen by the RNA SELEX in HeLa translation lysates blocked the HCV and poliovirus IRES-mediated translation in vitro. The functional requirement of La protein for the HCV IRES activity was further established in a liver-derived cell line and in an add-back experiment in which the inhibited IRES was rescued by recombinant human La. These results strongly argue for the novel role of La protein during selection of the initiator AUG and its participation during internal initiation of translation of the HCV RNA genome.
Psychophysical Rating Of Image Compression Techniques (1989)

Image compression schemes abound with little work which compares their bit-rate performance based on subjective fidelity measures. Statistical measures of image fidelity, such as squared error measures, do not necessarily correspond to subjective measures of image fidelity. Most previous comparisons of compression techniques have been based on these statistical measures. We used a psychophysical method to estimate, for a number of compression techniques, a threshold bit-rate yielding a criterion level of performance in discriminating original and compressed images. The compression techniques studied include Block Truncation, Laplacian Pyramid, Block Discrete Cosine Transform, with and without a human visual system scaling, and Cortex Transform coders.
Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability (2016)

The trimeric HIV-1 envelope glycoprotein (Env) is critical for host immune recognition and neutralization. Despite advances in trimer design, the roots of Env trimer metastability remain elusive. Here we investigate the contribution of two Env regions to metastability. First, we computationally redesign a largely disordered bend in heptad region 1 (HR1) of SOSIP trimers that connects the long, central HR1 helix to the fusion peptide, substantially improving the yield of soluble, well-folded trimers. Structural and antigenic analyses of two distinct HR1 redesigns confirm that redesigned Env closely mimics the native, prefusion trimer with a more stable gp41. Next, we replace the cleavage site between gp120 and gp41 with various linkers in the context of an HR1 redesign. Electron microscopy reveals a potential fusion intermediate state for uncleaved trimers containing short but not long linkers. Together, these results outline a general approach for stabilization of Env trimers from diverse HIV-1 strains.
The expression of human carboxylesterases in normal tissues and cancer cell-lines (2015)

Carboxylesterases (CESs) are serine esterases and are known to hydrolyze a variety of substances. CESs have been used to activate drugs that target a host of ailments, ranging from cancer to influenza. Although, CESs play an important role in drug therapy, little is known about their tissue distribution. Five different carboxylesterases have been identified in humans and each shows tissue specific expression. It is hypothesized that the effectiveness of chemotherapeutic prodrugs could be increased if the levels of CESs were known in different cancer tissues. This study measures the CES mRNA expression for all of the human CESs and compares the CES expression levels between normal human tissues and cancer cell-lines. We found that CESs have variable mRNA expression in human tissues and cancer cell-lines, and that CES expression decreases in cancer. The decrease in mRNA expression levels in cancer may explain why CESs are less effective in hydrolyzing carboxylester bonds in chemotherapeutic agents.
Testing for drugs of abuse in saliva and sweat (1998)

The detection of marijuana, cocaine, opiates, amphetamines, benzodiazepines, barbiturates, PCP, alcohol and nicotine in saliva and sweat is reviewed, with emphasis on forensic applications. The short window of detection and lower levels of drugs present compared to levels found in urine limits the applications of sweat and saliva screening for drug use determination. However, these matrices may be applicable for use in driving while intoxicated and surveying populations for illicit drug use. Although not an illicit drug, the detection of ethanol is reviewed because of its importance in driving under the influence. Only with alcohol may saliva be used to estimate blood levels and the degree of impairment because of the problems with oral contamination and drug concentrations varying depending upon how the saliva is obtained. The detection of nicotine and cotinine (from smoking tobacco) is also covered because of its use in life insurance screening and surveying for passive exposure.
Noise Correlation of Magnetic Thin Film Media (1991)

We have experimentally observed a linear relationship between the correlation coefficient of the noise voltages read on a saturated magnetic thin film rigid disk by a magnetic recording head at different radii, and the radial offset of the head between readings, in both longitudinal and perpendicular media. This linear relationship indicates that for the length of the data stream used in the experiments, the noise voltages from adjacent narrow longitudinal strips that could be denoted pseudo microtracks are uncorrelated. The experiments indicate that the correlation length between the pseudo microtracks is less than 0.5 µm. We have used the linear relationship as the basis for a track following scheme that follows an 11.3 µm wide track with 0.3 µm accuracy.
Putative virulence factors of Aspergillus fumigatus (2000)

Various putative virulence factors of Aspergillus fumigatus have been studied over the past decades. A. fumigatus gliotoxin is a potent inhibitor of the mucociliary system. Several fungal metabolites interfere with phagocytosis and opsonization including toxins, 'conidial inhibitory factor', 'A. fumigatus diffusible product' and 'complement inhibitory factor'. A. fumigatus can bind specifically to different host tissues components, whereas toxins give a general and significant immunosuppressive effect on host defences. Circumstantial evidence links the production of elastinolytic proteases with the ability to cause disease. However, none of the reports demonstrates conclusively a decisive role for any of the virulence factors described thus far. It is conceivable that proteolytic enzyme activities such as those expressed by AFAlp are one of a number of factors, each with a minor effect, that combine to facilitate disease progression.
In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9 (2014)

Probing gene function in the mammalian brain can be greatly assisted with methods to manipulate the genome of neurons in vivo. The clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated endonuclease (Cas)9 from Streptococcus pyogenes (SpCas9) can be used to edit single or multiple genes in replicating eukaryotic cells, resulting in frame-shifting insertion/deletion (indel) mutations and subsequent protein depletion. Here, we delivered SpCas9 and guide RNAs using adeno-associated viral (AAV) vectors to target single (Mecp2) as well as multiple genes (Dnmt1, Dnmt3a and Dnmt3b) in the adult mouse brain in vivo. We characterized the effects of genome modifications in postmitotic neurons using biochemical, genetic, electrophysiological and behavioral readouts. Our results demonstrate that AAV-mediated SpCas9 genome editing can enable reverse genetic studies of gene function in the brain.
Systemic, Mucosal, and Heterotypic Immune Induction in Mice Inoculated with Venezuelan Equine Encephalitis Replicons Expressing Norwalk Virus-Like Particles (2002)

Norwalk-like viruses (NLVs) are a diverse group of single-stranded, nonenveloped, positive-polarity RNA viruses and are the leading cause of epidemic acute gastroenteritis in the United States. In this study, the major capsid gene of Norwalk virus, the prototype NLV, has been cloned and expressed in mammalian cells using a Venezuelan equine encephalitis (VEE) replicon expression system. Upon infection of baby hamster kidney (BHK) cells with VEE replicon particles (VRPs), the Norwalk virus capsid proteins self-assemble to generate high titers of Norwalk virus-like particles (VLPs) that are morphologically and antigenically analogous to wild-type Norwalk virus. Mice inoculated subcutaneously with VRPs expressing the Norwalk virus capsid protein (VRP-NV1) developed systemic and mucosal immune responses to Norwalk VLPs, as well as heterotypic antibody responses to the major capsid protein from another genogroup I NLV strain (NCFL) isolated from a recent outbreak. A second Norwalk virus capsid clone (NV2) containing three amino acid codon mutations from the NV1 clone was also expressed using VEE replicons (VRP-NV2), but upon infection of BHK cells failed to confer VLP self-assembly. Mice inoculated with VRP-NV2 elicited reduced systemic and mucosal immune responses to Norwalk VLPs, demonstrating the importance and potential utility of endogenous VLP presentation for maximum immune induction. Inoculation with either VRP-NV1 or VRP-NV2 resulted in serum antibody responses far superior to the induction in mice dosed orally with VLPs that were prepared using the VEE-NV1 replicon construct, a regimen similar to current models for NLV vaccination. Expression of NLV VLPs in mammalian cells offers a powerful approach for the design of novel NLV vaccines, either alone or in combination with current vaccination models.
A System to Integrate Electrical Stimulation With Robotically Controlled Treadmill Training to Rehabilitate Stepping After Spinal Cord Injury (2012)

A functional electrical stimulation (FES) system was engineered to integrate information from a robotically controlled position during stepping in order to time stimulation to continuous gait information in a rodent model of spinal cord injury (SCI). In contrast to conventional FES systems which have a fixed timing pattern relative to gait cycle onset (i.e., toe off/heel off or paw contact/heel strike), this system allows adaptation of stimulation to a robotically controlled position. Rationale for the system design is presented along with bench-test results verifying the timing of the stimulation with respect to hindlimb position. This robotically timed FES system will enable studies investigating the capability of this FES therapy to encourage rehabilitation by way of spinal plasticity.
Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo (2001)

These data demonstrate that relaxin modulates effective collagen deposition by HSC, at least in part, due to changes in the pattern of matrix degradation.
Congenital Disorder of Glycosylation Id Presenting with Hyperinsulinemic Hypoglycemia and Islet Cell Hyperplasia (2005)

Our findings underscore the importance of proper glycosylation in several major organ systems and emphasize that CDG should be ruled out in patients with persistent hyperinsulinemic hypoglycemia of unknown etiology.
Reversal of severe angioproliferative pulmonary arterial hypertension and right ventricular hypertrophy by combined phosphodiesterase-5 and endothelin receptor inhibition (2014)

Combined therapy with two vasodilators that are approved for the treatment of human PAH provides unprecedented efficacy in the rat SU-Hx preclinical model of severe, angioproliferative PAH.
The architecture of Metricom's MicroCellular Data Network/sup TM/ (MCDN) and details of its implementation as the second and third generation Ricochet/sup TM/ wide-area mobile data service (2003)

We describe the architecture of the MicroCellular Data Network/sup TM/ (MCDN) - a wide-area, wireless, data network. This network is designed to provide its users with fast, mobile, data access to any of the available wired data networks, typically the Internet or a corporate LAN, solving the first-mile problem. Metricom sold the first generation implementation of this architecture as the Utilinet line of private networks. We do not describe it here. We describe the second-generation implementation of this architecture, currently deployed in Washington DC, Seattle, and the San Francisco Bay Area and sold as a service under the brand name Ricochet. We also describe the third-generation implementation, based on the MCDN(3G) architecture, which provides 10x improvements in performance and is currently deployed nationwide in 14 metropolitan areas covering over 35 million people [1]. We show some laboratory measurements of the throughput and fairness of the system. Finally, we address the possibilities of extending the architecture to a fourth generation with another factor of 10x improvement.
IL-2 up-regulates but IFN-gamma suppresses IL-8 expression in human monocytes. (1993)

IL-2 has pleiotropic properties and is a potent activator of monocytic functions. Since monocytes are an important source of the chemoattractant cytokine IL-8, we studied the effects of IL-2 on the expression of IL-8 in human monocytes. IL-8 mRNA expression was detectable in resting human monocytes. Treatment of monocytes with IL-2 increased IL-8 mRNA expression by a protein synthesis-independent process. The augmentation of IL-8 mRNA by IL-2 was associated with an increase in IL-8 secretion. The expression of IL-8 mRNA was not a nonspecific response to any stimulus of monocyte activation. In fact, IFN-gamma, which is also a potent monocyte activator, not only failed to induce IL-8 expression but inhibited the stimulation of IL-8 by IL-2. Nuclear run-on experiments demonstrated that both the enhancement of IL-8 mRNA expression and its down-regulation by IFN-gamma occurred at the transcriptional level. These results show for the first time that in fresh human monocytes, IL-8 expression is differentially regulated by IL-2 and IFN-gamma and suggest that the interactions among IL-2, IL-8, and IFN-gamma may be important for the development and control of the inflammatory response.
Site-specific mutagenesis using asymmetric polymerase chain reaction and a single mutant primer (1990)

A method is described for preparing site-specific mutants using a polymerase chain reaction (PCR) based protocol. The protocol requires a single mutant primer, and has been used to introduce mutations into DNA fragments ranging in size from 200 bp to 1569 bp in length in the GM-CSF, beta-actin, human growth hormone and erythropoietin genes. Sequence analysis of PCR derived mutant fragments shows an error rate of less than one bp change per 1500 bp incorporated. Single base pair mutations have been introduced into these genes which create unique restriction sites. We demonstrate that these mutant templates may be used for competitive PCR to quantitate mRNA and DNA. This method thus offers a rapid means for producing competitive templates for use in quantitative PCR.
Two long‐chain acyl‐CoA synthetases from Arabidopsis thaliana involved in peroxisomal fatty acid β‐oxidation (2002)

Post-germinative growth of oilseeds is dependent on the breakdown of the stored lipid reserves. Long-chain acyl-CoA synthetase activities (LACS) are critically involved in this process by activating the released free fatty acids and thus feeding the beta-oxidation cycle in glyoxysomes. Here we report on the identification of two LACS genes, AtLACS6 and AtLACS7 from Arabidopsis thaliana coding for peroxisomal LACS proteins. The subcellular localization was verified by co-expression studies of spectral variants of the green fluorescent protein (GFP). While AtLACS6 is targeted by a type 2 (PTS2) peroxisomal targeting sequence, for AtLACS7 a functional PTS1 as well as a PTS2 could be demonstrated. Possible explanations for this potentially redundant targeting information will be discussed. Expression studies of both genes revealed a strong induction 1 day after germination resembling the expression pattern of other genes involved in beta-oxidation. Analysis of the substrate specificities of the two LACS proteins demonstrated enzymatic activity for both enzymes with the whole spectrum of fatty acids found in stored lipid reserves. These results suggest that both LACS proteins might have overlapping functions and are able to initiate beta-oxidation in plant peroxisomes.
Cellular Localization, Expression, and Structure of the Nuclear Dot Protein 52 (1997)

Nuclear dots containing PML and Sp100 proteins (NDs) play a role in the development of acute promyelocytic leukemia, are modified after infection with various viruses, and are autoimmunogenic in patients with primary biliary cirrhosis (PBC). PML and Sp100 gene expression is strongly enhanced by interferons (IFN). Based on immunostaining with a monoclonal antibody (mAb C8A2), a third protein, nuclear dot protein 52 (NDP52), was recently localized in NDs. Here we analyzed the cellular localization, expression, and structure of NDP52 in more detail. Our NDP52-specific sera revealed mainly cytoplasmic staining but no ND pattern, neither in untreated nor in IFN-treated cells. Cells transfected with NDP52 expression vectors showed exclusively cytoplasmic staining. In subcellular fractionation experiments, NDP52 was found in cytoplasmic and nuclear fractions. Unlike as described for Sp100 and PML, NDP52 mRNA and protein levels were only marginally enhanced by IFN gamma and not enhanced at all by IFN beta. NDP52 homodimerization but no heterodimerization with Sp100 or PML could be demonstrated. None of the 93 PBC sera tested contained autoantibodies against NDP52. Finally, mAb C8A2 reacted not only with NDP52 but also with a conformation-dependent epitope on the Sp100 protein. These data imply that NDP52 forms homodimers but no heterodimers with Sp100 and PML, lacks autoantigenicity in PBC, localizes mainly in the cytoplasm, and is associated with the nucleus, but not with NDs. Finally, unlike Sp100 and PML, NDP52 expression is neither markedly enhanced nor localization detectably altered by type I and II IFNs.
Progress in supercritical CO2 cleaning (1993)

Over the next few years, supercritical carbon dioxide (SCCO2) will play a vital role in helping industry meet government-mandated schedules for eliminating CFCs and other ozone-depleting compounds. Research has shown that SCCO2 can be used effectively for many cleaning applications in the aerospace industry. The 10-yr evolution of SCCO2 cleaning technology at Hughes culminated last year with the implementation of a commercial-scale cleaning unit. Currently, we are developing equipment and processes to meet a broad range of industrial cleaning needs, both inside and outside the aerospace sector. 8 refs.
Cell-Specific Targeting by Heterobivalent Ligands (2011)

Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.