gebhart/patrepeval huggingface dataset:
Egress of CD19+CD5+ cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients (2013)

Ibrutinib (PCI-32765) is a highly potent oral Bruton tyrosine kinase (BTK) inhibitor in clinical development for treating B-cell lymphoproliferative diseases. Patients with chronic lymphocytic leukemia (CLL) often show marked, transient increases of circulating CLL cells following ibrutinib treatments, as seen with other inhibitors of the B-cell receptor (BCR) pathway. In a phase 1 study of ibrutinib, we noted similar effects in patients with mantle cell lymphoma (MCL). Here, we characterize the patterns and phenotypes of cells mobilized among patients with MCL and further investigate the mechanism of this effect. Peripheral blood CD19(+)CD5(+) cells from MCL patients were found to have significant reduction in the expression of CXCR4, CD38, and Ki67 after 7 days of treatment. In addition, plasma chemokines such as CCL22, CCL4, and CXCL13 were reduced 40% to 60% after treatment. Mechanistically, ibrutinib inhibited BCR- and chemokine-mediated adhesion and chemotaxis of MCL cell lines and dose-dependently inhibited BCR, stromal cell, and CXCL12/CXCL13 stimulations of pBTK, pPLCγ2, pERK, or pAKT. Importantly, ibrutinib inhibited migration of MCL cells beneath stromal cells in coculture. We propose that BTK is essential for the homing of MCL cells into lymphoid tissues, and its inhibition results in an egress of malignant cells into peripheral blood. This trial was registered at www.clinicaltrials.gov as #NCT00114738.
A fuzzy inference system for detection of obstructive sleep apnea (2005)

A fuzzy inference system (FIS) was developed to detect obstructive sleep apnea (OSA) by analyzing the respiratory airflow signal in adults. The parameters analyzed were the normalized area and the standard deviation of consecutive 3-second intervals of baseline adjusted and rectified airflow signal. Fuzzy logic was used to process these parameters to detect apnea and hypopnea when the output values were within a specified range extracted from OSA patient data. The FIS comprised of three major stages of computation: fuzzification, fuzzy rule evaluation and defuzzification. Seven males and two females with an average age of 48 years (range: 26 - 66 years), an average weight of 102 kg (range: 63 - 159 kg), an average height of 1.7 m (range: 1.5 - 1.8 m) and an average body mass index (BMI) of 33 kg/m/sup 2/ (range: 21 - 42 kg/m/sup 2/) participated in this study. Patients spent at least 8 hours in an accredited sleep laboratory. However, patient data was collected for only part of this time. The total amount of test time for all nine patients was 38.83 hours with an average of 4.31 hours/patient (range: 1.92 - 7.63 hours). The total number of apnea events occurring during this time was 808, and the number of hypopnea events was 694. The membership functions for the FIS were derived by analyzing apnea and hypopnea events in four patients. The data from all nine patients were used in algorithm performance evaluation. The apnea and hypopnea events were scored by a sleep specialist and were used to test the correct detection rate by the FIS. The results demonstrated that the FIS reached an overall correct detection rate of 83% across all patients. The false negative rate was 17% and the false positive rate was 12%. The correct detection rate varied from patient to patient and correct rates greater than 90% were achieved in three patients. This study suggests that fuzzy inference could provide an intelligent algorithm for control of a continuous positive airway pressure (CPAP) machine. It would detect apnea and hypopnea events and automatically adjust the pressure to eliminate them. The performance of the algorithm could be further optimized to give increased detection rates. This could be achieved by performing further studies on a larger OSA patient population and utilizing augmentative methods such as neural networks to better sense the fuzzy patterns in the OSA data.
Xenosis and xenotransplantation: addressing the infectious risks posed by an emerging technology. (1997)

Advances in transplantation biology have enhanced the possibility of xenotransplantation as a therapeutic option for end-stage organ failure. The potential spread of animal-derived pathogens to the recipient and to the general population, termed "xenosis," is a potential complication of interspecies transplantation. Recognition of such infections will be complicated by the presence of new pathogens, new clinical syndromes, and altered behavior of these organisms in the immunocompromised xenograft recipient. Particular concern exists over the activation of latent viruses, including retroviruses, from xenograft tissues. Based on experience with human allogeneic transplantation, a strategy is proposed to stratify the risks of known pathogens from animal donors. Those pathogens considered most likely to cause human disease can be excluded prospectively from herds of animals developed for organ donation. Research is needed into the activation and behavior of retroviruses and other potential pathogens in xenotransplantation. Stringent, expert, peer review of clinical protocols must be performed for scientific merit and to enhance the safety of the recipient and of the community at large.
Vanadia Gel Synthesis via Peroxovanadate Precursors. 1. In Situ Laser Raman and 51V NMR Characterization of the Gelation Process (2000)

Vanadium oxide gels derived from aqueous solutions of V2O5 and H2O2 have been investigated using in situ 51V NMR and laser Raman spectroscopic techniques. On the basis of this characterization, a pathway for peroxovanadate decomposition has been proposed, including the presence of two peroxovanadate dimers. New Raman bands and assignments for these species are reported. Gelation was observed to begin both during and after the peroxovanadate decomposition, depending on the initial molar ratios of H2O2/V and the total concentration of vanadium. Experimental 51V NMR evidence suggested that the VO2+ species was directly involved in the formation of the gel.
Dexamethasone decreases xenograft response to paclitaxel through inhibition of tumor cell apoptosis (2006)

Glucocorticoid receptor (GR) activation has recently been implicated in the initiation of anti-apoptotic signaling pathways in epithelial cell lines grown in culture. However, the evidence that GR-mediated inhibition of tumor cell apoptosis is the mechanism that diminishes chemotherapy effectiveness in vivo is limited. We therefore initiated a breast cancer xenograft study to examine whether or not pretreatment with glucocorticoids (GCs) decreases tumor response to chemotherapy by inhibiting tumor cell apoptosis. Here we report a significant decrease in paclitaxel-induced apoptosis in xenografts from mice pretreated with dexamethasone (Dex). A significant difference in apoptosis in xenografts from Dex/paclitaxel versus paclitaxel treated animals was seen eight days following initiation of chemotherapy. Nine days later, mice treated with Dex/paclitaxel had significantly larger tumors compared with those that received paclitaxel alone (p = 0.032). Dex pretreatment did not significantly affect tumor cell proliferation rates. Taken together, these results demonstrate that systemic Dex administration results in significantly reduced breast cancer xenograft apoptosis in the context of chemotherapy treatment. We also found that systemic Dex treatment results in upregulation of the anti-apoptotic gene MKP-1 and downregulation of pro-apoptotic Bid and TRAIL genes in tumor cells six hours following Dex treatment. These in vivo gene expression changes correlated with significant inhibition of chemotherapy-induced apoptosis. Interestingly, the decreased chemotherapeutic response of Dex-pretreated tumors persisted for several weeks following treatment. These data suggest that GR-mediated transcriptional regulation of pro- and anti-apoptotic genes contributes to the mechanism through which GCs decrease paclitaxel-induced apoptosis.
Increased Phytochrome B Alleviates Density Effects on Tuber Yield of Field Potato Crops (2003)

The possibility that reduced photomorphogenic responses could increase field crop yield has been suggested often, but experimental support is still lacking. Here, we report that ectopic expression of the Arabidopsis PHYB (phytochrome B) gene, a photoreceptor involved in detecting red to far-red light ratio associated with plant density, can increase tuber yield in field-grown transgenic potato (Solanum tuberosum) crops. Surprisingly, this effect was larger at very high densities, despite the intense reduction in the red to far-red light ratios and the concomitant narrowed differences in active phytochrome B levels between wild type and transgenics at these densities. Increased PHYB expression not only altered the ability of plants to respond to light signals, but they also modified the light environment itself. This combination resulted in larger effects of enhanced PHYB expression on tuber number and crop photosynthesis at high planting densities. The PHYB transgenics showed higher maximum photosynthesis in leaves of all strata of the canopy, and this effect was largely due to increased leaf stomatal conductance. We propose that enhanced PHYB expression could be used in breeding programs to shift optimum planting densities to higher levels.
Effect of chicken collagen type II on collagen-induced arthritis in mice (2002)

AIM To investigate the effect of chicken collagen type Ⅱ (CⅡ) on collagen-induced arthritis (CIA) mice. METHODS The model of mice CIA was prepared and the change of the mean of arthritis scores was observed. Meanwhile, ConA and LPS-induced splenocytes proliferation and the production of interleukin (IL)-1 and IL-2 were measured. RESULT CⅡ [5, 10, 20 μg·kg -1 ig×7 d] significantly decreased the mean of arthritis scores, inhibited the increased ConA-induced splenocytes proliferation as well as the elevated production of IL-1 and IL-2. Meanwhile, the pathological examination showed that articulus cartilage degeneration with synovial hyperplasia and inflammatory cells infiltration in CIA mice was suppressed by ig CⅡ. CONCLUSION CⅡ has therapeutical effect on mice CIA which may be related to its immunoregulative function.
Real Time Vehicle License Plate Recognition on Mobile Devices (2013)

Automatic license plate recognition is useful in many contexts such as parking control, law enforcement and vehicle background checking. The high cost and low portability of commercial systems makes them inaccessible to the majority of end users. However, current mobile devices now have processors and cameras that make image processing and recognition applications feasible on them. This thesis investigates high accuracy real-time license plate recognition on a smartphone, taking into account device limitations. It first explores how, using the minimal image processing and simple configurable heuristics based on plate geometry, license plates and their characters can be detected in an image. Then, using minimal training data, it shows that a character recognition package can achieve high levels of accuracy. This approach accurately recognized 99 percent of plates appearing in a test set of videos of vehicles with New Zealand license plates.
At the Crossroads of Genomics and Ecology: The Promise of a Canary on a Chip (2004)

Abstract The application of technologies from functional genomics to ecological research will add new power to the tools that are currently available for the study of an organism's response to the environment. One particularly important area in which this technology will have a large impact is the study of human and environmental health. In the future, scientists may rely on changes in gene or protein expression in an organism as an early warning of exposure to and effects of different stressors in the environment and as an indicator of the overall health of organisms in the environment.
Structural Insights into DNA Replication without Hydrogen Bonds (2013)

The genetic alphabet is composed of two base pairs, and the development of a third, unnatural base pair would increase the genetic and chemical potential of DNA. d5SICS-dNaM is one of the most efficiently replicated unnatural base pairs identified to date, but its pairing is mediated by only hydrophobic and packing forces, and in free duplex DNA it forms a cross-strand intercalated structure that makes its efficient replication difficult to understand. Recent studies of the KlenTaq DNA polymerase revealed that the insertion of d5SICSTP opposite dNaM proceeds via a mutually induced-fit mechanism, where the presence of the triphosphate induces the polymerase to form the catalytically competent closed structure, which in turn induces the pairing nucleotides of the developing unnatural base pair to adopt a planar Watson-Crick-like structure. To understand the remaining steps of replication, we now report the characterization of the prechemistry complexes corresponding to the insertion of dNaMTP opposite d5SICS, as well as multiple postchemistry complexes in which the already formed unnatural base pair is positioned at the postinsertion site. Unlike with the insertion of d5SICSTP opposite dNaM, addition of dNaMTP does not fully induce the formation of the catalytically competent closed state. The data also reveal that once synthesized and translocated to the postinsertion position, the unnatural nucleobases again intercalate. Two modes of intercalation are observed, depending on the nature of the flanking nucleotides, and are each stabilized by different interactions with the polymerase, and each appear to reduce the affinity with which the next correct triphosphate binds. Thus, continued primer extension is limited by deintercalation and rearrangements with the polymerase active site that are required to populate the catalytically active, triphosphate bound conformation.
A Switchable Biocompatible Polymer Surface with Self‐Sterilizing and Nonfouling Capabilities (2008)

Trap, kill, and release: An antimicrobial cationic surface can effectively kill bacterial cells and switch to a nonfouling zwitterionic surface which releases dead microorganisms upon hydrolysis (see picture). This biocompatible nonfouling surface can prevent further attachment of proteins and microorganisms and the formation of a biofilm on the surface. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Distinct effects of thioredoxin and antioxidants onthe activation of transcription factors NF-kappa B and AP-1. (1994)

The transcription factors NF-kappa B and AP-1 have been implicated in the inducible expression of a variety of genes involved in responses to oxidative stress and cellular defense mechanisms. Here, we report that thioredoxin, an important cellular protein oxidoreductase with antioxidant activity, exerts different effects on the activation of NF-kappa B and AP-1. Transient expression or exogenous application of thioredoxin resulted in a dose-dependent inhibition of NF-kappa B activity, as demonstrated in gel shift and transactivation experiments. AP-1-dependent transactivation, in contrast was strongly enhanced by thioredoxin. A similar increase of AP-1 activity was also observed with other, structurally unrelated antioxidants such as pyrrolidine dithiocarbamate and butylated hydroxyanisole, indicating that the thioredoxin-induced increase of AP-1 activation was indeed based on an antioxidant effect. Moreover, the stimulatory effect on AP-1 activity was found to involve de novo transcription of the c-jun and c-fos components but to be independent of protein kinase C activation. These results suggest that thioredoxin plays an important role in the regulation of transcriptional processes and oppositely affects NF-kappa B and AP-1 activation.
Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein. II. Suppression of disease and in vitro immune responses is mediated by antigen-specific CD8+ T lymphocytes. (1989)

We have previously demonstrated that the oral administration of guinea pig myelin basic protein (MBP) protects Lewis rats against the induction of experimental autoimmune encephalomyelitis (EAE) when subsequently immunized with guinea pig MBP in CFA. In addition, animals made orally tolerant to MBP also have diminished proliferative and antibody responses to MBP, but not to other Ag. Nonetheless, the mechanism of oral tolerance to MBP in the EAE model remains undefined. In the present study, we report that T cells isolated from the spleen and mesenteric lymph nodes of MBP orally tolerized animals can adoptively transfer protection against EAE. Furthermore, these T cells are of the CD8+ subclass. In addition, CD8+ T cells from MBP orally tolerized animals also suppress in vitro proliferative responses and antibody responses to MBP in an Ag-specific fashion. These results demonstrate that active cellular mechanisms are initiated after oral administration of an autoantigen that can down-regulate an experimental autoimmune disease and provide the basis for the isolation and characterization of the cells mediating both in vivo and in vitro suppression.
Bone morphogenetic protein-7 release from endogenous neural precursor cells suppresses the tumourigenicity of stem-like glioblastoma cells (2010)

Glioblastoma cells with stem-like properties control brain tumour growth and recurrence. Here, we show that endogenous neural precursor cells perform an anti-tumour response by specifically targeting stem-like brain tumour cells. In vitro, neural precursor cells predominantly express bone morphogenetic protein-7; bone morphogenetic protein-7 is constitutively released from neurospheres and induces canonical bone morphogenetic protein signalling in stem-like glioblastoma cells. Exposure of human and murine stem-like brain tumour cells to neurosphere-derived bone morphogenetic protein-7 induces tumour stem cell differentiation, attenuates stem-like marker expression and reduces self-renewal and the ability for tumour initiation. Neurosphere-derived or recombinant bone morphogenetic protein-7 reduces glioblastoma expansion from stem-like cells by down-regulating the transcription factor Olig2. In vivo, large numbers of bone morphogenetic protein-7-expressing neural precursors encircle brain tumours in young mice, induce canonical bone morphogenetic protein signalling in stem-like glioblastoma cells and can thereby attenuate tumour formation. This anti-tumour response is strongly reduced in older mice. Our results indicate that endogenous neural precursor cells protect the young brain from glioblastoma by releasing bone morphogenetic protein-7, which acts as a paracrine tumour suppressor that represses proliferation, self-renewal and tumour-initiation of stem-like glioblastoma cells.
A Photochemical Crosslinkinig Study of the Subunit Structure of Membrane‐Associated Spectrin (1980)

The subunit structure of membrane-associated spectrin was investigated by crosslinking human erythrocyte membranes with a variety of cleavable photosensitive heterobifunctional reagents by flash photolysis millisecond crosslinking. Crosslinked complexes were analyzed on agarose-polyacrylamide gels whose high exclusion limit the resolution of molecular with Mr larger than 10(6). Crosslinking of membrane ghosts produced a series of new bands with apparent molecular weights of approximately 420 000, 170 000 and 910 000, as well as a band at the top of the gels. No significant bands were detectable between the 910 000-Mr band and the material at the gel top. The molecular weights of the three bands correspond to spectrin dimer, trimer, and tatramer, suggesting a limiting tetrameric stoichiometry for membrane-associated spectrin. The rate of formation of spectrin oligomers was examined by increasing crosslinking time. Dimers accumulate before trimer and tetramer, and as tetramer increased, dimer diminished. A simple kinetic model is employed which is also consistent with spectrin tetramer existing on the cytoplasmic surface of the erythrocyte membrane as the basic structural unit.
Bronchoalveolar lavage in interstitial lung disease (2001)

Bronchoalveolar lavage (BAL) has become a standard diagnostic procedure for the majority of patients with interstitial disease. The technique is safe, minimally invasive, and reveals specific information in some disorders such as pulmonary alveolar proteinosis, Langerhans cell histiocytosis, alveolar hemorrhage, malignant infiltrates, or dust exposure. Here BAL can often replace lung biopsy. The results of BAL cell differentials with a lymphocytic, a neutrophilic, an eosinophilic, or a mixed cellular pattern can be used as an adjunct to diagnosis. If a BAL finding is compatible with the suspected diagnosis in the context of an appropriate disease history and clinical and radiologic findings, this can then be sufficient for disease confirmation. Recent research focused on the pathogenesis of various types of interstitial lung disorders. In this regard, BAL findings contributed to the characterization of idiopathic pulmonary fibrosis (IPF) as a condition with a predominant T-helper-2 (Th2) cytokine profile, whereas BAL findings in sarcoidosis and hypersensitivity pneumonitis are characterized by a Th1-dominant profile. The clinical value of BAL to assess the activity of disease processes and to provide prognostic information is still under debate. The routine performance of serial BAL is not recommended at present.
New developments in antiplatelet therapy (2008)

The P2Y12 receptor plays a central role in platelet aggregation, and the clinical effectiveness of the thienopyridine clopidogrel, an irreversible P2Y12 antagonist, in preventing thrombosis provides proof that P2Y12 blockade is a sound strategy in reducing thrombotic risk. Drawbacks of clopidogrel treatment include prolonged time to onset and offset of effect and a variable inhibition of platelet aggregation (IPA). New P2Y12 antagonists have been developed to overcome these drawbacks. Prasugrel is a new thienopyridine that is more efficiently metabolized to its active form than clopidogrel, providing more rapid onset of effect and greater and more consistent IPA. AZD6140 is a reversible oral P2Y12 antagonist that does not require metabolic activation. AZD6140 provides more rapid onset and offset of effect than clopidogrel and greater and more consistent IPA, with a level of IPA depending on plasma drug concentrations. Cangrelor is a direct, reversible intravenous P2Y12 antagonist that has rapid onset and offset of action. Phase 2 trials of these agents have provided some evidence of potential clinical benefits in patients at risk of thrombotic events. Recent and ongoing Phase 3 trials will provide important information on how to improve clinical outcomes with P2Y12 inhibition: the TRITON-TIMI 38 trial comparing prasugrel with clopidogrel in 13 608 patients with acute coronary syndromes (ACS) and planned percutaneous coronary intervention (PCI); the PLATO trial comparing AZD6140 with clopidogrel in approximately 18 000 patients with ACS undergoing medical management, PCI, or coronary artery bypass grafting; and the CHAMPION PCI trial of cangrelor vs. clopidogrel in patients with ACS or stable coronary disease undergoing PCI.