gebhart/patrepeval huggingface dataset:
Expression of Tissue Factor and Tissue Factor Pathway Inhibitor in situ in Laryngeal Carcinoma (1999)

The blood coagulation mechanism may support tumor progression by several mechanisms including promotion of cell proliferation and angiogenesis. Immunohistochemical procedures were applied to AMeX-fixed sections of twelve cases of squamous cell carcinoma of the larynx obtained at surgical resection to determine the presence and distribution of tissue factor (TF), tissue factor pathway inhibitor (TFPI), other coagulation factors, fibrinogen, and fibrin in situ. TF antigen was present in normal squamous epithelial cells and tumor cells, predominantly in immature tumor cells in the vicinity of the host-tumor interface. Tumor cells stained also for factors VII and X. Staining for TFPI antigen was demonstrated in the connective tissue stroma adjacent to the tumor, in microvascular endothelial cells, and in normal squamous epithelial cells. Fibrinogen and factor XIIIa were distributed throughout the tumor connective tissue stroma. Fibrin (thrombin-cleaved fibrinogen) was detected at the host-tumor interface and along the margins of tumor nodules. Tumor cells in carcinoma of the larynx express a functional, TF-initiated pathway of blood coagulation. Interpretation of these findings together with the results of clinical trials of inhibitors of TF-induced coagulation activation versus effects of inhibitors of TF expression suggest novel approaches to the experimental therapy of laryngeal carcinoma.
High-quality continuous random networks (2000)

The continuous random network (CRN) model is an idealized model for perfectly coordinated amorphous semiconductors. The quality of a CRN can be assessed in terms of topological and configurational properties, including coordination, bond-angle distributions, and deformation energy. Using a variation on the sillium approach proposed 14 years ago by Wooten, Winer, and Weaire, we present 1000-atom and 4096-atom configurations with a degree of strain significantly less than the best CRN available at the moment and comparable to experimental results. The low strain is also reflected in the electronic properties. The electronic density of state obtained from ab initio calculation shows a perfect band gap, without any defect, in agreement with experimental data.
Substantial Reduction in Single Sympathetic Nerve Firing After Renal Denervation in Patients With Resistant Hypertension (2012)

Renal denervation (RDN) has been shown to reduce blood pressure (BP) and muscle sympathetic nerve activity (MSNA) in patients with resistant hypertension. The mechanisms underlying sympathetic neural inhibition are unknown. We examined whether RDN differentially influences the sympathetic discharge pattern of vasoconstrictor neurons in patients with resistant hypertension. Standardized office BP, single-unit MSNA, and multi-unit MSNA were obtained at baseline and at 3-month follow-up in 35 patients with resistant hypertension. Twenty-five patients underwent RDN, and 10 patients underwent repeated measurements without RDN (non-RDN). Baseline BP averaged 164/93 mm Hg (RDN) and 164/87 mm Hg (non-RDN) despite use of an average of 4.8 ± 0.4 and 4.4 ± 0.5 antihypertensive drugs, respectively. Mean office BP decreased significantly by -13/-6 mm Hg for systolic BP (P<0.001) and diastolic BP (P<0.05) with RDN but not in non-RDN at 3-month follow-up. RDN moderately decreased multi-unit MSNA (79 ± 3 versus 73 ± 4 bursts/100 heartbeats; P<0.05), whereas all properties of single-unit MSNA including firing rates of individual vasoconstrictor fibers (43 ± 5 versus 27 ± 3 spikes/100 heartbeats; P<0.01), firing probability (30 ± 2 versus 22 ± 2% per heartbeat; P<0.02), and multiple firing incidence of single units within a cardiac cycle (8 ± 1 versus 4 ± 1% per heartbeat; P<0.05) were substantially reduced at follow-up. BP, single-unit MSNA, and multi-unit MSNA remained unaltered in the non-RDN cohort at follow-up. RDN results in the substantial and rapid reduction in firing properties of single sympathetic vasoconstrictor fibers, this being more pronounced than multi-unit MSNA inhibition. Whether the earlier changes in single-unit firing patterns may predict long-term BP response to RDN warrants further exploration.
A Neural Network-based method for continuous blood pressure estimation from a PPG signal (2013)

There is a relation, not always linear, between the blood pressure and the pulse duration, obtained from photoplethysmography (PPG) signal. In order to estimate the blood pressure from the PPG signal, in this paper the Artificial Neural Networks (ANNs) are used. Training data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care waveform database for better representation of possible pulse and pressure variation. In total there were analyzed more than 15000 heartbeats and 21 parameters were extracted from each of them that define the input vector for the ANN. The comparison between estimated and reference values shows better accuracy than the linear regression method and satisfy the American National Standards of the Association for the Advancement of Medical Instrumentation.
PD-1 and its ligands are important immune checkpoints in cancer (2016)

// Yinan Dong 1 , Qian Sun 1 and Xinwei Zhang 1 1 Cell Immunology Lab, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of &ldquo;Cancer Prevention and therapy&rdquo;, Key Laboratory of Immunology and Cancer Biotherapy, Tianjin, China Correspondence to: Xinwei Zhang, email: // Keywords : PD-1, PD-L1, PD-L2, T cell anergy, immune checkpoint blockade Received : April 14, 2016 Accepted : November 21, 2016 Published : December 10, 2016 Abstract Checkpoint programmed death-1 (PD-1)/programmed cell death ligands (PD-Ls) have been identified as negative immunoregulatory molecules that promote immune evasion of tumor cells. The interaction of PD-1 and PD-Ls inhibits the function of T cells and tumor-infiltrating lymphocytes (TIL) while increasing the function of immunosuppressive regulatory T cells (Tregs). This condition causes the tumor cells to evade immune response. Thus, the blockade of PD-1/PD-L1 enhances anti-tumor immunity by reducing the number and/or the suppressive activity of Tregs and by restoring the activity of effector T cells. Furthermore, some monoclonal antibodies blockading PD-1/PD-Ls axis have achieved good effect and received Food and Drug Administration approval. The role of PD-1/PD-Ls in tumors has been well studied, but little is known on the mechanism by which PD-1 blocks T-cell activation. In this study, we provide a brief overview on the discovery and regulatory mechanism of PD-1 and PD-L1 dysregulation in tumors, as well as the function and signaling pathway of PD-1 and its ligands; their roles in tumor evasion and clinical treatment were also studied.
Borrelia burgdorferi strain-specific Osp C-mediated immunity in mice (1997)

Antibodies to the outer surface proteins (Osps) A, B, and C of the spirochete Borrelia burgdorferi can prevent infection in animal models of Lyme borreliosis. We have previously demonstrated that immune serum from mice infected with B. burgdorferi N40 can also prevent challenge infection and induce disease regression in infected mice. The antigens targeted by protective and disease-modulating antibodies are presently unknown, but they do not include Osp A or Osp B. Because Osp C antibodies are present in immune mouse serum, we investigated the ability of hyperimmune serum to recombinant Osp C (N40) to protect mice against challenge infection with N40 spirochetes. In both active and passive immunization studies, Osp C (N40) antiserum failed to protect mice from challenge infection with cultured organisms. Mice actively immunized with recombinant Osp C (N40) were susceptible to tick-borne challenge infection, and nymphal ticks remained infected after feeding on Osp C-hyperimmunized mice. In contrast, similar immunization studies performed with Osp C (PKo) antiserum prevented challenge infection of mice with a clone of PKo spirochetes pathogenic for mice. Both Osp C (N40) and Osp C (PKo) antisera showed minimal in vitro borreliacidal activity, and immunofluorescence studies localized Osp C beneath the outer membrane of both N40 and PKo spirochetes. We conclude that Osp C antibody-mediated immunity is strain specific and propose that differences in Osp C surface expression by spirochetes in vivo may account for strain-specific immunity.
MAGE-12 and MAGE-6 are frequently expressed in malignant melanoma (2000)

MAGE proteins have been identified as potential specific targets for cancer vaccination. Although MAGE-6 and MAGE-12 were originally identified in malignant melanoma there are no studies reporting the frequency of expression of these antigens in this malignancy. These are of relevance particularly for MAGE-6 as recent studies have identified CTL activity against several epitopes. We have studied MAGE-1, -2, -3, -4, -6 and -12 gene expression using reverse transcription-polymerase chain reaction in 47 melanoma samples and 11 melanoma cell lines established from these tumours. The tumour samples expressed MAGE-12 (74%) and MAGE-6 (64%) mRNA at much higher frequencies than the other MAGE genes. MAGE-12 and MAGE-6 were expressed at the highest frequencies, relative to the other MAGE antigens, in early stage lesions. The frequency of expression of all the MAGE genes was found to be higher in samples from metastatic deposits compared to those from locoregional disease. The cell lines all expressed the same or more MAGE antigens than the tumours from which they were derived. In only one cell line was expression of a MAGE antigen lost. Certain recurring patterns of MAGE expression were observed in the tumour samples. MAGE-6 and/or -12 expression were detected in all of those 26 tumour samples that were positive for one or more of MAGE-1, -2, -3 and -4. Twenty of these 26 samples expressed both antigens. These findings suggest that protocols targeting MAGE-12 and -6 would permit many more patients to be included into clinical cancer vaccination trials.
Identification and characterization of a high-affinity granulocyte- macrophage colony-stimulating factor receptor on primary rat oligodendrocytes (1993)

We previously showed the presence of receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) on tumor tissues and tumor cell lines that are derived from the neural crest. To determine whether normal neural cells express functional GM-CSF receptors, we isolated and analyzed primary rat brain cells, including microglia, astrocytes, and oligodendrocytes. Scatchard analysis of equilibrium binding of 125I-GM-CSF to primary rat oligodendrocytes showed an average of 1,110 GM-CSF binding sites per cell, with a kd of 20 pmol/L. In six separate experiments, no specific binding was detectable on the astrocyte population. Microglia were used in competitive binding experiments with oligodendrocytes, and addition of microglia did not increase the specific binding of labeled ligand to oligodendrocytes. In dose-response assays, we measured 3H-thymidine uptake in rat oligodendrocytes, microglia and control murine 32D cells stimulated with various concentrations of GM-CSF. Over concentration ranges of 0.025 to 1000 pmol/L, cell proliferation and peak 3H-thymidine incorporation was observed at approximately 30 pmol/L for both the control cells and the oligodendrocytes. However, the microglial cells did not proliferate in response to GM-CSF. These data indicate the presence of a functional receptor for GM-CSF on primary rat oligodendrocytes, and suggest that hematopoietic growth factors such as GM-CSF may play a role in nerve cell development, function, or response to injury.
On-Chip Nanoliter-Volume Multiplex TaqMan Polymerase Chain Reaction from A Single Copy Based on Counting Fluorescence Released Microchambers (2004)

A novel method for multiplex TaqMan PCR in nanoliter volumes on a highly integrated silicon microchamber array is described. Three different gene targets, related to beta-actin, sex-determining region Y (SRY), and Rhesus D (RhD) were amplified and detected simultaneously on the same chip by using three different types of human genomic DNA as the templates. The lack of cross-contamination and carryover was shown using alternate dispensing of mineral oil-coated microchambers containing template and those without template. To confirm the specificity of our system to beta-actin, SRY, and RhD genes, we employed the larger volume PCR samples to a commercial real-time PCR system, SmartCycler. The samples were cycled with the same sustaining temperatures as with the microchamber array. Instead of the conventional method of DNA quantification, counting the number of the fluorescence released microchambers in consequence to TaqMan PCR was employed to our chip. This simple method of observing the end point signal had provided a dynamic quantitative range. Stochastic amplification of 0.4 copies/reaction chamber was achieved. The microfabricated PCR chip demonstrated a rapid and highly sensitive response for simultaneous multiple-target detection, which is a promising step toward the development of a fully integrated device for the "lab-on-a-chip" DNA analysis.
2′-Hydroxylation of nicotine by cytochrome P450 2A6 and human liver microsomes: Formation of a lung carcinogen precursor (2000)

Smokers or people undergoing nicotine replacement therapy excrete approximately 10% of the nicotine dose as 4-oxo-4-(3-pyridyl)butanoic acid (keto acid) and 4-hydroxy-4-(3-pyridyl)butanoic acid (hydroxy acid). Previously, these acids were thought to arise by secondary metabolism of the major nicotine metabolite cotinine, but our data did not support this mechanism. Therefore, we hypothesized that nicotine is metabolized by 2'-hydroxylation, which would ultimately yield keto acid and hydroxy acid as urinary metabolites. This pathway had not been established previously in mammalian systems and is potentially significant because the product of nicotine 2'-hydroxylation, 4-(methylamino)-1-(3-pyridyl)-1-butanone (aminoketone), can be converted to the potent tobacco-specific lung carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Incubation of nicotine with cytochrome P450 2A6 and cofactors did indeed produce aminoketone, which was identified as its N-benzoyl derivative by GC-MS. The rate was 11% of that of cotinine production. Incubation of human liver microsomes with nicotine gave keto acid by using aminoketone as an intermediate; keto acid was not formed from cotinine. In 10 human liver samples, rates of formation of keto acid were 5.7% of those of cotinine and production of these metabolites correlated. These results provide definitive evidence for mammalian 2'-hydroxylation of nicotine and elucidate a pathway by which endogenous formation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone could occur in humans.
Role of vaccinations as risk factors for ill health in veterans of the Gulf war: cross sectional study (2000)

Among veterans of the Gulf war there is a specific relation between multiple vaccinations given during deployment and later ill health. Multiple vaccinations in themselves do not seem to be harmful but combined with the "stress" of deployment they may be associated with adverse health outcomes. These results imply that every effort should be made to maintain routine vaccines during peacetime.
Methicillin-resistantStaphylococcus aureusin Europe, 1999–2002 (2004)

We explored the variation in proportions of methicillinresistant Staphylococcus aureus (MRSA) between and within countries participating in the European Antimicrobial Resistance Surveillance System and temporal trends in its occurrence. This system collects routine antimicrobial susceptibility tests for S. aureus. We examined data collected from January 1999 through December 2002 (50,759 isolates from 495 hospitals in 26 countries). MRSA prevalence varied almost 100-fold, from <1% in northern Europe to >40% in southern and western Europe. MRSA proportions significantly increased in Belgium, Germany, Ireland, the Netherlands, and the United Kingdom, and decreased in Slovenia. Within countries, MRSA proportions varied between hospitals with highest variance in countries with a prevalence of 5% to 20%. The observed trends should stimulate initiatives to control MRSA at national, regional, and hospital levels. The large differences between hospitals indicate that efforts may be most effective at regional and hospital levels.
Effects of CB1 Cannabinoid Receptor Blockade on Ethanol Preference After Chronic Ethanol Administration (2001)

Background: Chronic ethanol administration results in neurobiological alterations similar to those observed after chronic cannabinoid exposure. The purpose of this study was to investigate alcohol drinking and the withdrawal responses after pulmonary chronic alcoholization with intraperitoneal or oral administration of a cannabinoid CB1 receptor antagonist. Methods: The cannabinoid receptor antagonist SR141716A, 1, 3 or 10 mg/kg/day intraperitoneally or orally, was administered to Wistar rats either during a 30-day chronic ethanol exposure or at the cessation of this procedure. Motility was recorded during 18 hr after the cessation of chronic alcoholization just before the beginning of the free-choice paradigm (water versus alcohol 10% v/v). Results: A significant increase in ethanol preference was observed during the free-choice paradigm after chronic alcoholization with concurrent SR141716A administration (3 or 10 mg/kg/day). A significant decrease in withdrawal motility after administration of SR141716A was observed with only the highest dose (10 mg/kg/day). The administration of SR141716A, 3 or 10 mg/kg/day, after chronic pulmonary alcoholization significantly decreased the preference for alcohol. Finally, a significant decrease in ethanol preference was seen during the free-choice paradigm of nonalcoholized rats treated with SR141716A, 3 or 10 mg/kg/day, during 30 days before the free-choice paradigm. Conclusions: The concurrent administration of the CB1 antagonist together with the chronic alcoholization increases the preference for ethanol. Also, the administration of the CB1 antagonist after the chronic alcoholization or at the time of withdrawal drastically diminishes the ethanol preference.
A Placebo- and Midazolam-Controlled Phase I Single Ascending-Dose Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Remimazolam (CNS 7056) (2011)

Remimazolam provided sedation with rapid onset and offset, and was well tolerated. There was no supplemental oxygen or ventilation required. On the basis of these data, further studies on the potential utility of remimazolam for sedation/anesthesia are warranted.
An Anycast Communication Model for Data Offloading in Intermittently-Connected Hybrid Networks (2015)

For billions of people, mobile phones have become essential communication means to produce and share multimedia contents. Most current sharing solutions rely on centralized online solutions, requiring a permanent Internet connectivity, with the conse- quence of increasing –and sometimes of overloading– the networks of mobile operators. This paper presents an anycast communication model allowing to offload data in wide intermittently-connected hybrid networks, using a peer-to-peer approach. Such networks combine an infrastructure part that relies on fixed equipments with intermittently or partially connected parts formed by mobile devices. This model has been implemented in a middleware platform called Nephila. Simulation results confirm that, with Nephila, thousands of people roaming a medium-size city center can share multimedia con- tents, using a combination of stable and transient transmission links.
LEDs for Solid-State Lighting: Performance Challenges and Recent Advances (2009)

Over the past decade, advances in LEDs have enabled the potential for wide-scale replacement of traditional lighting with solid-state light sources. If LED performance targets are realized, solid-state lighting will provide significant energy savings, important environmental benefits, and dramatically new ways to utilize and control light. In this paper, we review LED performance targets that are needed to achieve these benefits and highlight some of the remaining technical challenges. We describe recent advances in LED materials and novel device concepts that show promise for realizing the full potential of LED-based white lighting.
The negative charge of Glu-111 is required to activate the cleavage center of EcoRI endonuclease (1989)

King et al. (King, K., Benkovic, S. J., and Modrich, P. (1989) 264, 11807-11815) have shown that Glu-111 is required for DNA cleavage by EcoRI endonuclease and have suggested that this residue is required for activation of the cleavage center upon specific recognition. We have substituted Gln or Asp for Glu-111 by oligonucleotide-directed mutagenesis. First and second strand cleavage rate constants are reduced by a factor of more than 10(4) by the Gln-111 substitution. However, these rate constants are enhanced 9-fold when pH is increased from 7.6 to 8.5, which enhances strand cleavage at EcoRI sites by wild type endonuclease to a similar degree. The specific affinity of Gln-111 endonuclease for EcoRI sites is 1000 times greater than that of wild type enzyme reflecting a decrease in the rate constant governing specific complex dissociation. In contrast to Gln-111 endonuclease, the equilibrium specific affinity of Asp-111 endonuclease for the EcoRI sequence is similar to that of wild type enzyme, and first and second strand cleavage rate constants are reduced only 100-fold relative to wild type enzyme. These results suggest that a negative charge on residue 111 is required for strand cleavage and are consistent with participation of Glu-111 in activation of the DNA cleavage center, with energy associated with specific sequence recognition driving this process.