gebhart/patrepeval huggingface dataset:
Stem Cells and Pulmonary Fibrosis: Cause or Cure? (2012)

Pulmonary fibrosis is a feature of a number of important lung diseases, and alveolar epithelial injury plays a key role in their pathogenesis. Traditionally, type II alveolar epithelial cells have been viewed as the progenitor cells of the alveolar epithelium; however, recent studies have identified a number of other progenitor and stem cell populations that may participate in alveolar epithelial repair. These studies suggest that the injury microenvironment plays a role in regulation of progenitor cell populations. In human idiopathic pulmonary fibrosis, epithelial abnormalities including altered cell cycling characteristics, hyperplasia, and metaplasia are observed, suggesting that dysregulation of epithelial progenitor cells contributes to the characteristic aberrant repair process. Reactivation of developmental signaling pathways such as the Wnt-β-catenin pathway is implicated in the dysregulation of these cells, and targeting these pathways may provide opportunities for therapeutic intervention. There has been a great deal of interest in the delivery of exogenous stem cells as a therapeutic strategy, and various stem and progenitor cell populations have improved outcomes in animal lung fibrosis models. The contributions of these cells to alveolar epithelial regeneration have been variable, and secretion of soluble mediators has been implicated in the beneficial effects. It remains to be seen whether the promising results seen in the preclinical studies will translate to human disease, and the first studies using mesenchymal stem cells in clinical trials for fibrotic lung disease are underway. Strategies using other stem cell populations hold promise, but currently these are a lot further from the bedside.
The Effect of Osmotic and Ionic Stress on the Primary Processes of Photosynthesis inDunaliella tertiolecta (1984)

Cells of the euryhaline unicellular green alga Dunaliella tertiolecta were exposed to a range of osmotic potentials imposed by the addition of NaCl, KCl, sucrose or ethylene glycol to the algal suspending medium. The alga synthesized glycerol in response to increased concentrations of NaCl, KCl or sucrose, but not to increased concentrations of ethylene glycol. The overall process of photosynthesis was inhibited by all four treatments during the first 100 min, but especially by NaCl and KCl. The induction of chlorophyll fluorescence indicated that photosystem Il was inhibited by such treatment although to a lesser extent than the overall process. The size and half-time of decay of the flash-induced field-indicating absorption change at 519 nm were decreased by NaCl and KCl but the effect of sucrose and ethylene glycol on the absorption change was much less. Therefore, the photosynthetic processes in intact Dunaliella cells are more markedly inhibited by the combined osmotic and ionic stresses due to NaCl and KCl than by osmotic stress alone. In most cases some recovery of the inhibition of photosynthesis was seen concomitant with the synthesis of intracellular glycerol, suggesting that the alga has the ability to overcome osmotic and ionic stresses.
420. Adaptation of Baculovirus System for Large-Scale Production of rAAV Vector Serotypes (2004)

Scalable production of rAAV vectors is a technically challenging practice. A recently developed baculovirus-based production protocol (Urabe et al), although potentially promising and elegant, proved to be inconsistent and unreliable. Here we report the modification of the original baculovirus system that is amenable to scale-up and suitable for the production of other AAV serotypes similar to conventionally produced vectors. Both Rep and Cap components of the original system have been modified. The Rep52 and Rep78 transcription units of the original BacRep vector were placed onto two separate vectors thereby greatly enhancing the stability of the rep genes for at least 5 continuous passages. In addition, the capsid genes of the BacVP helper were modified by substituting AAV2 VP1 phospholipase A2 (PLA2) domain for the homologous region in the other serotype baculovirus helpers (for example the AAV8 serotype). The resulting chimeric AAV2/8 VP1 reconstituted the wt AAV2 enzymatic PLA2 activity and, consequently, wt AAV8 infectivity. Examples of scale-up production and experiments in vivo will be discussed in detail.
Neural control of renal circulation. (1989)

It has long been appreciated that renal nerves influence renal hemodynamics. Direct or reflex activation of renal nerves causes vasoconstriction, with the degree of vasoconstriction being proportional to the magnitude of stimulation. Conversely, removal of enhanced nerve activity ameliorates renal vasoconstriction. The effector loci within the renal microcirculation have been identified and include afferent and efferent arterioles as well as the glomerular capillary bed itself. The hemodynamic changes have been corroborated by morphological studies which reveal that the lumen of arterioles constrict and the glomerular capillary tuft contracts following an increase in neural activity. Moreover, mesangial cells, which are the putative vectors of regulation of hemodynamics within the glomerular capillary bed, constrict in response to the neurotransmitter, norepinephrine.
Monaural Speech Segregation Based on Pitch Tracking and Amplitude Modulation (2004)

Segregating speech from one monaural recording has proven to be very challenging. Monaural segregation of voiced speech has been studied in previous systems that incorporate auditory scene analysis principles. A major problem for these systems is their inability to deal with the high-frequency part of speech. Psychoacoustic evidence suggests that different perceptual mechanisms are involved in handling resolved and unresolved harmonics. We propose a novel system for voiced speech segregation that segregates resolved and unresolved harmonics differently. For resolved harmonics, the system generates segments based on temporal continuity and cross-channel correlation, and groups them according to their periodicities. For unresolved harmonics, it generates segments based on common amplitude modulation (AM) in addition to temporal continuity and groups them according to AM rates. Underlying the segregation process is a pitch contour that is first estimated from speech segregated according to dominant pitch and then adjusted according to psychoacoustic constraints. Our system is systematically evaluated and compared with pervious systems, and it yields substantially better performance, especially for the high-frequency part of speech.
Auricular Acupuncture and Vagal Regulation (2012)

Auricular acupuncture has been utilized in the treatment of diseases for thousands of years. Dr. Paul Nogier firstly originated the concept of an inverted fetus map on the external ear. In the present study, the relationship between the auricular acupuncture and the vagal regulation has been reviewed. It has been shown that auricular acupuncture plays a role in vagal activity of autonomic functions of cardiovascular, respiratory, and gastrointestinal systems. Mechanism studies suggested that afferent projections from especially the auricular branch of the vagus nerve (ABVN) to the nucleus of the solitary tract (NTS) form the anatomical basis for the vagal regulation of auricular acupuncture. Therefore, we proposed the "auriculovagal afferent pathway" (AVAP): both the autonomic and the central nervous system could be modified by auricular vagal stimulation via projections from the ABVN to the NTS. Auricular acupuncture is also proposed to prevent neurodegenerative diseases via vagal regulation. There is a controversy on the specificity and the efficacy of auricular acupoints for treating diseases. More clinical RCT trials on auricular acupuncture and experimental studies on the mechanism of auricular acupuncture should be further investigated.
Calcium-induced inhibition of phosphoserine phosphatase in insulin target cells is mediated by the phosphorylation and activation of inhibitor 1. (1992)

In this study, we examined the mechanism of inhibition of phosphoserine phosphatase (PSPase) activity by elevated [Ca2+]i in insulin target cells. In in vitro studies, isolated rat adipocytes were incubated with either 40 mM K+ or parathyroid hormone (PTH) (20 ng/ml) for 1 h. In in vivo studies, rats were injected with PTH (three hourly injections of 40 micrograms intraperitoneally) prior to isolation of either adipocytes or skeletal muscle. Under these conditions, intracellular [Ca2+]i changed from 100 +/- 8.7 to 263 +/- 10.5 nM. There was a concomitant 30% decrease in adipocyte PSPase activity and a 35% decrease in skeletal muscle PSPase activity, assayed using 32P-labeled phosphorylase "a" as a substrate. The inhibition of PSPase was accompanied by a 60% increase in adipocytes (p less than 0.05) and a 118% increase (p less than 0.01) in skeletal muscle inhibitor 1 (I1) activities, respectively. Since I1 is active only in the phosphorylated state, we studied the effect of [Ca2+]i on I1 phosphorylation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of heat treated extracts immunoprecipitated with I1 antibody revealed significant increase in 32P incorporation (45-60%, p less than 0.05) into I1 protein in cells with elevated [Ca2+]i. Nitrendipine, a calcium channel blocker, completely prevented increases in I1 phosphorylation and activity in cells exposed to K+ but was only partially effective in the PTH-treated cells. In contrast, a cyclic AMP antagonist, RpcAMP, prevented both the K(+)-and the PTH-induced increases in I1 phosphorylation and activity, even though it failed to block the elevations in [Ca2+]i in these cells. We conclude that [Ca2+]i-induced and cAMP-mediated phosphorylation and activation of I1 results in inhibition of PSPase activity in insulin target cells. The inhibition of PSPases may cause inappropriate serine dephosphorylation of substrates of insulin action resulting in insulin resistance.
Delayed Tissue-Plasminogen Activator Therapy in a Rabbit Model of Thromboembolic Stroke (1995)

THIS STUDY INVESTIGATED the efficacy and safety of delayed therapy with tissue-plasminogen activator (t-PA) in a rabbit model of thromboembolic stroke. The t-PA therapy was started 3, 4, or 5 hours after autologous clot embolization. New Zealand rabbits were randomized to receive a 2-hour intravenous infusion of either t-PA (6.3 mg/kg) or a saline solution (0.9% saline) after an autologous clot had embolized the anterior cerebral circulation. Regional cerebral blood flow (rCBF), intracranial pressure (ICP), and infarct size were measured to determine the effects of the delayed administration of the t-PA after intracranial embolization. Additionally, the following physiological parameters were monitored throughout the protocol: mean arterial pressure, hematocrit, arterial blood gases, glucose, and core and brain temperatures. All animals were studied for 4 hours after the administration of the t-PA or control solution; thus, the duration of each experiment was 7, 8, or 9 hours after autologous clot embolization. In control animals, brain infarct size and final ICP values were directly related to the length of time studied after clot embolization; among control animals, the largest infarct size and greatest rise in ICP were seen 9 hours after embolization. The start of the t-PA therapy 3 hours after clot embolization was associated with a trend toward smaller mean brain infarct size (31.6 ± 6.4% [n = 10] versus 44.2 ± 8.6% [n = 10] of the infarcted hemisphere; the mean ± the standard error of the mean) and a significantly lower mean ICP (15.5 ± 2.8 versus 22.0 ± 3.1 mm Hg, P = 0.02). A trend toward restoration of rCBF was also noted with the t-PA therapy given 3 hours after embolization. No benefit was noted for any parameter studied (ICP, infarct size, or rCBF) with further delay to the t-PA therapy (4 or 5 h). In the group receiving t-PA 4 hours after embolization, ICP (measured 8 h after embolization) was significantly higher (31.3 ± 5.2 versus 21.6 ± 2.6 mm Hg, P = 0.01), although no significant difference in ICP was detected between the two groups at 9 hours after embolization. In this rabbit model of thromboembolic stroke, the administration of t-PA 3 hours after autologous clot embolization was associated with a reduction in brain injury. Despite significant clot lysis by t-PA in all groups, no benefit was noted when the t-PA therapy was delayed longer (4–5 h after embolization); no return of rCBF was noted in the t-PA group at 9 hours after embolization.
Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles (2016)

Structures of BG505 SOSIP.664 trimer in complex with broadly neutralizing antibodies (bNAbs) have revealed the critical role of trimeric context for immune recognition of HIV-1. Presentation of trimeric HIV-1 antigens on nanoparticles may thus provide promising vaccine candidates. Here we report the rational design, structural analysis and antigenic evaluation of HIV-1 trimer-presenting nanoparticles. We first demonstrate that both V1V2 and gp120 can be presented in native-like trimeric conformations on nanoparticles. We then design nanoparticles presenting various forms of stabilized gp140 trimer based on ferritin and a large, 60-meric E2p that displays 20 spikes mimicking virus-like particles (VLPs). Particle assembly is confirmed by electron microscopy (EM), while antigenic profiles are generated using representative bNAbs and non-NAbs. Lastly, we demonstrate high-yield gp140 nanoparticle production and robust stimulation of B cells carrying cognate VRC01 receptors by gp120 and gp140 nanoparticles. Together, our study provides an arsenal of multivalent immunogens for HIV-1 vaccine development.
Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes (2006)

Selectin-dependent cell adhesion mediates inflammatory extravasation and routine homing of lymphocytes. Most resting peripheral T lymphocytes lack expression of sialyl Lewis X, the carbohydrate ligand for selectins, and are induced to strongly express it upon activation. T helper 1 (Th1) cells are known to more preferentially express sialyl Lewis X as compared with T helper 2 (Th2) cells upon activation. The molecular basis for this preferential expression, however, has not been elucidated to date. Here we show that the gene for fucosyltransferase VII (FUT7), the rate-limiting enzyme for sialyl Lewis X synthesis, is a unique example of the human genes with binding sites for both GATA-3 and T-bet, two opposing factors for Th1 and Th2 development, and is regulated transcriptionally by a balance of the two interacting transcription factors. T-bet promotes and GATA-3 represses FUT7 transcription. Our results indicated that T-bet interferes with the binding of GATA-3 to its target DNA, and also that GATA-3 significantly interferes with the binding of T-bet to the FUT7 promoter. T-bet has a binding ability to GATA-3, CBP/P300, and Sp1 to form a transcription factor complex, and GATA-3 regulates FUT7 transcription by phosphorylation-dependently recruiting histone deacetylase (HDAC)-3/HDAC-5 and by competing with CBP/P300 in binding to the N terminus of T-bet. Suppression of GATA-3 activity by dominant-negative GATA-3 or repressor of GATA (ROG) was necessary to attain a maximum expression of FUT7 and sialyl Lewis X in human T lymphoid cells. These results indicate that the GATA-3/T-bet transcription factor complex regulates the cell-lineage-specific expression of the lymphocyte homing receptors.
Phylogenetic distribution of streptococcal superantigen SSA allelic variants provides evidence for horizontal transfer of ssa within Streptococcus pyogenes (1996)

Phylogenetic analyses recently found the gene encoding the streptococcal superantigen SSA of Streptococcus pyogenes to occur in several well-differentiated clones comprising 10 (12.5%) of 80 clonal lineages examined. To determine if distinct clonal lineages carried the same ssa coding sequence or harbored a group of allelic variants, ssa was sequenced from 23 S. pyogenes strains representing the 10 clones identified by multilocus enzyme electrophoresis. Three alleles of ssa were found in natural populations of S. pyogenes. ssa-1 and ssa-3 differed by a single synonymous substitution in codon 94; both encoded SSA-1. Each of these alleles was present in phylogenetically diverse clones that had not shared a recent common ancestor. ssa-2 was present in a single clonal lineage. It was identical to ssa-3 at codon 94 but had a nonsynonymous substitution at codon 28 that changed the second amino acid of the mature protein from serine to arginine. This substitution altered the predicted isoelectric point and affected the apparent molecular mass during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Despite sequence variation both upstream of and within the ssa locus, all ssa-positive lineages expressed either SSA-1 or SSA-2. The observed patterns of ssa allele-clone distribution provide evidence for individual incidences of horizontal transfer and recombination of ssa among distinct group A streptococcal lineages. Although the extensive homology of SSA to the staphylococcal superantigen SEB raises the possibility of intergeneric gene transfer, a search for ssa in 68 genetically diverse clones of Staphylococcus aureus did not identify the gene. Moreover, the absence of ssa among 119 representative strains of Lancefield group B, C, or G streptococci suggests that ssa is confined to S. pyogenes.
Sensitivity and Specificity of the Pap Smear for Glandular Lesions of the Cervix and Endometrium (2007)

This study confirmed the good overall specificity of the Pap smear for glandular lesions in general. It also confirmed the good sensitivity for glandular lesions of the cervix and the poor sensitivity for glandular lesions of the endometrium. It thus confirmed that the Pap smear is not an effective screening tool for endometrial AC, and that the quest for alternative screening methods should continue.
Engineering a Synthetic Dual-Organism System for Hydrogen Production (2009)

Molecular hydrogen produced biologically from renewable biomass is an attractive replacement for fossil fuels. One potential route for biological hydrogen production is the conversion of biomass into formate, which can subsequently be processed into hydrogen by Escherichia coli. Formate is also a widely used commodity chemical, making its bioproduction even more attractive. Here we demonstrate the implementation of a formate-overproducing pathway in Saccharomyces cerevisiae, a well-established industrial organism. By expressing the anaerobic enzyme pyruvate formate lyase from E. coli, we engineered a strain of yeast that overproduced formate relative to undetectable levels in the wild type. The addition of a downstream enzyme, AdhE of E. coli, resulted in an additional 4.5-fold formate production increase as well as an increase in growth rate and biomass yield. Overall, an 18-fold formate increase was achieved in a strain background whose formate degradation pathway had been deleted. Finally, as a proof of concept, we were able to produce hydrogen from this formate-containing medium by using E. coli as a catalyst in a two-step process. With further optimizations, it may be feasible to use S. cerevisiae on a larger scale as the foundation for yeast-based biohydrogen.
Broadband ultrasonic location systems for improved indoor positioning (2006)

Ultrasonic location systems are a popular solution for the provision of fine-grained indoor positioning data. Applications include enhanced routing for wireless networks, computer-aided navigation, and location-sensitive device behavior. However, current ultrasonic location systems suffer from limitations due to their use of narrowband transducers, This paper investigates the use of broadband ultrasound for indoor positioning systems. Broadband ultrasonic transmitter and receiver units have been developed and characterized. The utilization of these units to construct two positioning systems with different architectures serves to highlight and affirm the concrete, practical benefits of broadband ultrasound for locating people and devices indoors.
A Mutation in the Srrm4 Gene Causes Alternative Splicing Defects and Deafness in the Bronx Waltzer Mouse (2012)

Sensory hair cells are essential for hearing and balance. Their development from epithelial precursors has been extensively characterized with respect to transcriptional regulation, but not in terms of posttranscriptional influences. Here we report on the identification and functional characterization of an alternative-splicing regulator whose inactivation is responsible for defective hair-cell development, deafness, and impaired balance in the spontaneous mutant Bronx waltzer (bv) mouse. We used positional cloning and transgenic rescue to locate the bv mutation to the splicing factor-encoding gene Ser/Arg repetitive matrix 4 (Srrm4). Transcriptome-wide analysis of pre-mRNA splicing in the sensory patches of embryonic inner ears revealed that specific alternative exons were skipped at abnormally high rates in the bv mice. Minigene experiments in a heterologous expression system confirmed that these skipped exons require Srrm4 for inclusion into the mature mRNA. Sequence analysis and mutagenesis experiments showed that the affected transcripts share a novel motif that is necessary for the Srrm4-dependent alternative splicing. Functional annotations and protein-protein interaction data indicated that the encoded proteins cluster in the secretion and neurotransmission pathways. In addition, the splicing of a few transcriptional regulators was found to be Srrm4 dependent, and several of the genes known to be targeted by these regulators were expressed at reduced levels in the bv mice. Although Srrm4 expression was detected in neural tissues as well as hair cells, analyses of the bv mouse cerebellum and neocortex failed to detect splicing defects. Our data suggest that Srrm4 function is critical in the hearing and balance organs, but not in all neural tissues. Srrm4 is the first alternative-splicing regulator to be associated with hearing, and the analysis of bv mice provides exon-level insights into hair-cell development.
Whispering-gallery-mode resonators as frequency references II Stabilization (2007)

We show theoretically that the absolute frequency stability of a solid-state millimeter-scale whispering gallery mode resonator can reach one part per 10−14 per 1 s integration time if proper crystalline material as well as proper stabilization technique is selected. Both the fluctuations of the resonator temperature and the fluctuations of the temperature in the mode volume can be measured with the sensitivity better than the fundamental thermodynamic limit and actively compensated.
Cytopathogenicity of a pestivirus correlates with a 27-nucleotide insertion (1996)

Cytopathogenic (cp) bovine viral diarrhea virus (BVDV) strains are generated in cattle persistently infected with noncytopathogenic (noncp) BVDV.cp BVDV strains are considered crucial for the development of fatal mucosal disease. Comparative analysis of cp and noncp BVDV strains isolated from one animal suffering from mucosal disease revealed that the genomes of the cp BVDV strain (CP7) and the corresponding noncp BVDV strain (NCP7) are highly homologous. However, only the genome of CP7 contains an insertion of 27 nucleotides in the NS2 coding region. The inserted sequence represents a duplication of bases 4064 to 4090 of the viral genome, located between the formerly neighboring nucleotides 4353 and 4354. Parts of the viral polyproteins of CP7 and NCP7 were expressed in the T7 vaccinia virus system. These studies revealed that the insertion identified in the CP7 genome is necessary and sufficient for the induction of NS2-3 cleavage. Since the expression of NS3 is strictly correlated to cp BVDV, the insertion identified in the genome of BVDV CP7 represents most likely the relevant mutation leading to the evolvement of CP7 from NCP7.