gebhart/patrepeval huggingface dataset:
CD4+CD25+FOXP3+ regulatory T cells from human thymus and cord blood suppress antigen‐specific T cell responses (2005)

Activation of self-reactive T cells in healthy adults is prevented by the presence of autoantigen-specific CD4+CD25+ regulatory T cells (CD25+ Treg). To explore the functional development of autoantigen-reactive CD25+ Treg in humans we investigated if thymic CD25+ Treg from children aged 2 months to 11 years and cord blood CD25+ Treg are able to suppress proliferation and cytokine production induced by specific antigens. While CD4+CD25- thymocytes proliferated in response to myelin oligodendrocyte glycoprotein (MOG), tetanus toxoid and beta-lactoglobulin, suppression of proliferation was not detected after the addition of thymic CD25+ Treg. However, CD25+ Treg inhibited interferon (IFN)-gamma production induced by MOG, which indicates that MOG-reactive CD25+ Treg are present in the thymus. In contrast, cord blood CD25+ Treg suppressed both proliferation and cytokine production induced by MOG. Both cord blood and thymic CD25+ Treg expressed FOXP3 mRNA. However, FOXP3 expression was lower in cord blood than in thymic CD25+ T cells. Further characterization of cord blood CD25+ T cells revealed that FOXP3 was highly expressed by CD25+CD45RA+ cells while CD25+CD45RA- cells contained twofold less FOXP3, which may explain the lower expression level of FOXP3 in cord blood CD25+ T cells compared to thymic CD25+ T cells. In conclusion, our data demonstrate that low numbers of MOG-reactive functional CD25+ Treg are present in normal thymus, but that the suppressive ability of the cells is broader in cord blood. This suggests that the CD25+ Treg may be further matured in the periphery after being exported from the thymus.
Hepatic Failure and Lactic Acidosis Due to Fialuridine (FIAU), an Investigational Nucleoside Analogue for Chronic Hepatitis B (1995)

In patients with chronic hepatitis B, treatment with fialuridine induced a severe toxic reaction characterized by hepatic failure, lactic acidosis, pancreatitis, neuropathy, and myopathy. This toxic reaction was probably caused by widespread mitochondrial damage and may occur infrequently with other nucleoside analogues.
Some Effects of Fourier-domain Phase Quantization (1970)

If the Fourier transform of a function g(x) is quantized, the function recovered by inverse transformation differs from g(x). By means of a biased limiter model, the effects of Fourier-domain phase quantization are studied. Amplitude information is assumed fully retained, while phase is quantized to N equally spaced levels. The recovered function is shown to consist of several different contributions, the relative strengths of which depend on the number of phase quantization levels. Several specific examples are given. Motivation and interpretation are presented in terms of digitally constructed holograms.
Identification of Atherosclerotic Lipid Deposits by Diffusion-Weighted Imaging (2007)

Biophysical properties of plaque lipids can confer selective identification by DWI, as opposed to standard T1W and T2W imaging sequences. Successful translation of DWI in vivo could identify of features of vulnerable plaque.
Telomere Length of Transferred Lymphocytes Correlates with In Vivo Persistence and Tumor Regression in Melanoma Patients Receiving Cell Transfer Therapy (2005)

Recent studies have indicated that adoptive immunotherapy with autologous antitumor tumor-infiltrating lymphocytes (TILs) following nonmyeloablative chemotherapy mediates tumor regression in approximately 50% of treated patients with metastatic melanoma, and that tumor regression is correlated with the degree of persistence of adoptively transferred T cells in peripheral blood. These findings, which suggested that the proliferative potential of transferred T cells may play a role in clinical responses, led to the current studies in which telomere length as well as phenotypic markers expressed on the administered TILs were examined. TILs that were associated with objective clinical responses following adoptive transfer possessed a mean telomere length of 6.3 kb, whereas TILs that were not associated with significant clinical responses were significantly shorter, averaging 4.9 kb (p < 0.01). Furthermore, individual TIL-derived T cell clonotypes that persisted in vivo following adoptive cell transfer possessed telomeres that were longer than telomeres of T cell clonotypes that failed to persist (6.2 vs 4.5 kb, respectively; p < 0.001). Expression of the costimulatory molecule CD28 also appeared to be associated with long telomeres and T cell persistence. These results, indicating that the telomere length of transferred lymphocytes correlated with in vivo T cell persistence following adoptive transfer, and coupled with the previous observation that T cell persistence was associated with clinical responses in this adoptive immunotherapy trial, suggest that telomere length and the proliferative potential of the transferred T cells may play a significant role in mediating response to adoptive immunotherapy.
Isolation of Two Complementary Deoxyribonucleic Acid Clones from a Rat Insulinoma Cell Line Based on Similarities to Kex2 and Furin Sequences and the Specific Localization of Each Transcript to Endocrine and Neuroendocrine Tissues in Rats (1991)

We have identified two rat insulinoma cDNAs that code for proteins homologous to the Kex2 dibasic protease of yeast and the mammalian furin gene product. A 5.0-kilobase (kb) cDNA, termed BDP, coding for a 752-amino acid protein and a 2.5-kb cDNA coding for a 636-amino acid protein, which was found to be the rat equivalent of the human insulinoma PC2 protein, were isolated. The proteins encoded by these clones contain a specific N-terminal signal sequence, indicating that both enter the secretory pathway. Neither protein contains a C-terminal transmembrane domain as is found in kex2 and furin, suggesting that the proteins may be soluble. Both proteins contain regions surrounding the active site residues which show amino acid identities to both kex2 (43% for BDP and 41% for RPC2) and furin (57% for BDP and 53% for RPC2). Probes specific for the mRNAs of each protein were used to localize the expression of each protein in endocrine and neuroendocrine tissues.
In vivoestimation of elastic wave parameters using phase-stabilized swept source optical coherence elastography (2012)

We report a highly sensitive method based on phase-stabilized swept source optical coherence elastography (PhS-SSOCE) to measure elastic wave propagation in soft tissues in vivo. The waves were introduced using a mechanical stimulus and were assessed using the phase response of the swept source optical coherence tomography signal. The technique was utilized to measure age-related changes in elastic flexural wave velocity and attenuation in mice cornea in vivo. Results demonstrate that the wave velocity increases with animal age, supporting previous observations that stiffness of mice cornea gradually increases with age. Our studies suggest that the PhS-SSOCE technique could potentially be used to obtain biomechanical properties of ocular tissues in vivo.
Surfactant inhibition by plasma proteins: differential sensitivity of various surfactant preparations (1993)

Leakage of plasma proteins into the alveolar space may inhibit surfactant function. We compared the surface properties and the sensitivity to inhibitory proteins of different organic solvent surfactant extracts and a synthetic surfactant. Experiments were performed in the pulsating bubble surfactometer, with surfactant concentrations ranging between 0.1 and 2 mg.ml-1. Inhibition profiles towards fibrinogen, albumin and haemoglobin were obtained from calf lung surfactant extracts (CLSE), Alveofact, Curosurf and Survanta (all used in clinical, replacement studies in respiratory distress syndrome (RDS) and of an apoprotein-based synthetic phospholipid mixture (PLM-C/B; DPPC:PG:PA = 68.5:22.5:9, supplemented with 2% wt/wt non-palmitoylated human recombinant SP-C and 1% t/wt natural bovine SP-B). In the absence of inhibitory proteins, all surfactants exhibited dose-dependent rapid adsorption (rank order of relative efficacy PLM-C/B = CLSE > Alveofact > Curosurf > Survanta). Minimal surface tension was reduced to near zero values under dynamic compression (rank order PLM-C/B > CLSE > Alveofact = Curosurf) and to approximately 4 mN.m-1 (Survanta). Curosurf and Survanta were dose-dependently inhibited by fibrinogen > haemoglobin > albumin, with far-reaching loss of surface activity at protein-surfactant ratios above 1:1. In contrast, CLSE and Alveofact were only moderately inhibited by fibrinogen, and were not affected by haemoglobin and albumin, up to protein-surfactant ratios of 2:1. PLM-C/B exhibited resistance to fibrinogen, intermediate sensitivity to albumin, and was severely inhibited by haemoglobin. We conclude that various natural surfactant extracts and an apoprotein-based synthetic surfactant mixture markedly differ in their sensitivity to inhibitory plasma proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
Importance of Subtle Amnestic and Nonamnestic Deficits in Mild Cognitive Impairment: Prognosis and Conversion to Dementia (2007)

All MCI subtypes are at risk of converting to AD if the groups are carefully defined by an abnormal psychometric domain. All subtypes except subjective memory loss converted to AD at higher than expected rates. Both the A-MCI and AS-MCI subtypes had a similarly high rate of conversion to AD. The deficit on a word list recall task may develop before an abnormality on delayed paragraph recall is evident, at least in some subjects.
Free-space electro-optics sampling of mid-infrared pulses (1997)

We report on the coherent detection of ultra-broadband mid-infrared electromagnetic pulses using a 30-μm-thick ZnTe electro-optic sensor. The detected frequency spectrum exceeds 37 THz, extending from microwave to the mid-infrared. The frequency response can be further improved by reducing the sensor thickness to 10 μm.
Once daily fluticasone propionate aqueous nasal spray is an effective treatment for seasonal allergic rhinitis. (1991)

A multicenter double-blind, randomized, parallel group study was conducted to evaluate the once daily administration of fluticasone propionate, a potent, new corticosteroid preparation, for the treatment of seasonal allergic rhinitis. Adult patients (n = 227) were treated for 2 weeks with fluticasone propionate aqueous nasal spray 200 micrograms QD or 100 micrograms BID or matching placebo during the autumn pollen season. Overall, the administration of fluticasone propionate once daily in the morning was as effective as the twice daily dosage regimen, and either regimen was more effective than placebo. Improvement in clinician-rated and patient-rated nasal symptom scores, including morning nasal obstruction, was evident within three days of fluticasone propionate therapy and continued throughout the treatment period. Fewer patients receiving fluticasone propionate used rescue medication and had nasal eosinophilia compared with patients receiving placebo. Adverse events were similar in frequency and nature in all three treatment groups. Morning plasma cortisol concentrations and response to cosyntropin stimulation were similar across groups and offered no evidence of HPA axis suppression. We conclude that fluticasone propionate aqueous nasal spray administered once daily is a safe and effective treatment for seasonal allergic rhinitis. The convenience of a once daily regimen may encourage better compliance.
Epidemiologie des malignen Melanoms in der Bundesrepublik Deutschland im internationalen Vergleich (1989)

The incidence and mortality of malignant melanoma (MM) has markedly increased in the Federal Republic of Germany. The data available show a doubling of incidence in the past 15 years and a doubling of mortality in the past 30 years. Germany holds a middle range in the incidence list of MM compared to worldwide data: 6-8 MM were registered per 100,000 inhabitants and year in Germany during the mid eighties, whereas 5 x higher incidences where reported from Australia and the southern states of the USA; incidences higher than 6-8/100,000 where found in the Scandinavian countries. While sun exposure is regarded as the most important risk factor in the international epidemiology of MM, a relationship between sun exposure and increasing risk of MM could not be clearly established for the German population. In contrast, the total number of melanocytic nevi (MCN) and the occurrence of dysplastic nevi where found to be significant markers of an increased relative risk for developing MM in the German population. The increase of the relative risk was 16 x for persons with greater than 60 MCN compared to individuals with greater than or equal to 10 MCN and there was an additional 7 x increase of the relative risk for persons with greater than or equal to 1 dysplastic nevus. The course of the disease is lethal in most cases of metastatic malignant melanoma. 90% of all patients in the Federal Republic of Germany, however, were first diagnosed in clinical stage I (= primary tumor alone) and the average 10 years survival rate was 70% in the time period since 1970. Multivariate regression analysis revealed that the most important prognostic factors in stage I MM were tumor thickness and sex. This finding should be taken into consideration for a prognostic classification of stage I MM.
Hydrogen-Peroxide-induced Arachidonic Acid Metabolism in the Rat Alveolar Macrophage (1988)

Mounting evidence suggests that reactive oxygen metabolites can initiate the release and metabolism of arachidonic acid (AA). We therefore examined the effects of hydrogen peroxide (H2O2), a biologically relevant oxygen metabolite, on AA release and cyclooxygenase metabolism by the rat alveolar macrophage (AM). At concentrations between 10(-4) and 10(-3) M, which were largely noncytotoxic as assessed by chromium release, H2O2 exposure for 30 min caused a steep dose-dependent increase in AA release that peaked at approximately 5-fold stimulation at 10(-3) M H2O2. AA release induced by H2O2 was inhibited by the H2O2 scavenger catalase, but not by inactivated catalase or by scavengers of superoxide anion, hydroxyl radical, or ferric iron. An evaluation of cyclooxygenase metabolite formation by specific radioimmunoassays and high performance liquid chromatography demonstrated a greater than 2-fold increment in thromboxane (Tx)A2 (measured as TxB2) synthesis at 10(-4) M H2O2, but no increment in prostaglandin (PG) E2 synthesis. H2O2-induced TxB2 synthesis was cyclooxygenase-dependent, since it was inhibited by indomethacin (1 microM). There was no significant degradation of either PGE2 or TxB2 in AM cultures by H2O2 at concentrations to 10(-2) M. The effect of H2O2 on agonist-induced cyclooxygenase metabolism was also examined. H2O2 at 10(-4) M inhibited PGE2 synthesis induced by zymosan and A23187, whereas agonist-induced TxB2 synthesis was either unaffected (zymosan) or augmented (A23187) by H2O2. These findings suggest inhibition by H2O2 of PGE2 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
High molecular weight stress proteins: Identification, cloning and utilisation in cancer immunotherapy (2013)

Although the large stress/heat shock proteins (HSPs), i.e. Hsp110 and Grp170, were identified over 30 years ago, these abundant and highly conserved molecules have received much less attention compared to other conventional HSPs. Large stress proteins act as molecular chaperones with exceptional protein-holding capability and prevent the aggregation of proteins induced by thermal stress. The chaperoning properties of Hsp110 and Grp170 are integral to the ability of these molecules to modulate immune functions and are essential for developing large chaperone complex vaccines for cancer immunotherapy. The potent anti-tumour activity of the Hsp110/Grp170-tumour protein antigen complexes demonstrated in preclinical studies has led to a phase I clinical trial through the National Cancer Institute's rapid access to intervention development (RAID) programme that is presently underway. Here we review aspects of the structure and function of these large stress proteins, their roles as molecular chaperones in the biology of cell stress, and prospects for their use in immune regulation and cancer immunotherapy. Lastly, we will discuss the recently revealed immunosuppressive activity of scavenger receptor A that binds to Hsp110 and Grp170, as well as the feasibility of targeting this receptor to promote T-cell activation and anti-tumour immunity induced by large HSP vaccines and other immunotherapies.
Flavoring Chemicals and Aldehydes in E-Cigarette Emissions (2017)

Regulations on e-cigarettes in the U.S. do not provide guidelines on the chemical content of e-cigarette liquids. We evaluated emissions of aldehydes and flavoring chemicals in e-cigarette vapor under typical usage conditions. We selected 24 e-cigarette flavors from the top selling disposable e-cigarette brands. E-cigarettes were connected to a pump drawing air for two second puffs with sixty-second intervals between puffs. The vapor was analyzed for the presence of aldehydes using high-performance liquid chromatography-ultraviolet detector and for the presence of flavoring chemicals with gas chromatography and an electron capture detector. All e-cigarette emissions tested contained at least one aldehyde and/or flavoring chemical on either the FEMA "High Priority Chemicals" or FDA Harmful and Potentially Harmful Constituents lists when sampled at typical usage conditions. Diacetyl, a known respiratory hazard, along with acetoin, were the most prevalent of the flavoring chemicals in e-cigarette vapor, being found in more than 60% of samples. The presence of propionaldehyde, acetaldehyde and formaldehyde were correlated, corroborating previous work suggesting thermal degradation as a pathway for aldehyde generation in e-cigarette vapors. Median formaldehyde concentrations of 626 μg/m<sup>3</sup> in e-cigarette vapor exceed the ACGIH maximum concentrations allowable for workers of 370 μg/m<sup>3</sup>.
Bioproduction and characterization of a pH responsive self‐assembling peptide (2009)

Peptide P(11)-4 (QQRFEWEFEQQ) was designed to self-assemble to form beta-sheets and nematic gels in the pH range 5-7 at concentrations > or =12.6 mM in water. This self-assembly is reversibly controlled by adjusting the pH of the solvent. It can also self-assemble into gels in biological media. This together with its biocompatibility and biodegradability make P(11)-4 an attractive building block for the fabrication of nanoscale materials with uses in, for example, tissue engineering. A limitation to large-scale production of such peptides is the high cost of solid phase chemical synthesis. We describe expression of peptide P(11)-4 in the bacterium Escherichia coli from constructs carrying tandem repeats of the peptide coding sequence. The vector pET31b+ was used to express P(11)-4 repeats fused to the ketosteroid isomerase protein which accumulates in easily recoverable inclusion bodies. Importantly, the use of auto-induction growth medium to enhance cell density and protein expression levels resulted in recovery of 2.5 g fusion protein/L culture in both shake flask and batch fermentation. Whole cell detergent lysis allowed recovery of inclusion bodies largely composed of the fusion protein. Cyanogen bromide cleavage followed by reverse phase HPLC allowed purification of the recombinant peptide with a C-terminal homoserine lactone (rP(11)-4(hsl)). This recombinant peptide formed pH dependent hydrogels, displayed beta-structure measured by circular dichroism and fibril formation observed by transmission electron microscopy.
Payment switches for open networks (1995)

We describe the first operational Internet payment switch that provides real-time authorization suitable for direct use by merchant servers. A payment switch is a server that creates digital representations of conventional financial instruments, and forwards authentic payment orders on these instruments to their corresponding conventional financial networks and institutions. Our payment switch provides support for time-based and item-based pricing, implements switch based authorization and settlement aggregation for micropayments, and includes an extensive customer support system in order to provide a high level of customer confidence in electronic commerce. Fraud control is based on a transaction-specific multi-level security model that accommodates existing Internet browsers. Multiple authentication technologies are applied to every transaction.
CMSM: An efficient and effective Code Management for Software Managed Multicores (2013)

As we scale the number of cores in a multicore processor, scaling the memory hierarchy is a major challenge. Software Managed Multicore (SMM) architectures are one of the promising solutions. In an SMM architecture, there are no caches, and each core has only a local scratchpad memory. If all the code and data of the task mapped to a core do not fit on its local scratchpad memory, then explicit code and data management is required. In this paper, we solve the problem of efficiently managing code on an SMM architecture. We extend the state of the art by: i) correctly calculating the code management overhead, ii) even in the presence of branches in the task, and iii) developing a heuristic CMSM (Code Mapping for Software Managed multicores) that results in efficient code management execution on the local scratchpad memory. Our experimental results collected after executing applications from MiBench suite [1] on the Cell SPEs (Cell is an SMM architecture) [2], demonstrate that correct management cost calculation and branch consideration can improve performance by 12%. Our heuristic CMSM can reduce runtime in more than 80% of the cases, and by up to 20% on our set of benchmarks.
Pharmacokinetic and pharmacodynamic interactions between metoprolol and dronedarone in extensive and poor CYP2D6 metabolizers healthy subjects (2004)

As dronedarone a new noniodinated antiarrhythmic agent structurally related to amiodarone could inhibit CYP2D6 and is planned to be associated with beta-blockers, interactions with CYP2D6 metabolized beta-blockers such as metoprolol, have to be studied. Forty-nine healthy male subjects genotyped for CYP2D6 were included in a randomized, double-blind, placebo-controlled study. Metoprolol was administrated during 13 days (200 mg/day). After the initial 5 days, subjects received placebo (n = 12), 800 mg (n = 6), 1200 mg (n = 9), or 1600 mg (n = 17) of dronedarone daily during eight additional days. Pharmacokinetic parameters of metoprolol were investigated at day 5 and at day 13 in 44 subjects, 39 extensive metabolizers and five poor metabolizers for CYP2D6. Cardiac contractility function was evaluated by the rate-corrected electromechanical systole duration (QS2i) and the mean velocity of endocardial circumferential fiber shortening (Vcfmean). Cmax and AUC0--24 h of metoprolol increased from days 5 to 13 in proportion to dronedarone dose only in CYP2D6 extensive metabolizers genotyped subjects (P < 0.001). In all subjects, from days 5 to 13, Vcfmean decreased and QS2i significantly increased in dronedarone groups. The Vcfmean changes were however significant only with the 1600 mg dronedarone dose compared with placebo while QS2i changes induced by addition of dronedarone were significant compared with placebo at all dose levels. Between days 5 and 13, QS2i and Vcfmean changes were significantly correlated with both dronedarone concentrations at day 13 and with metoprolol concentration changes between days 5 and 13. Plasma metoprolol concentrations were highest in poor metabolizer subjects and dronedarone did not further increase their level but increased QS2i in the two subjects receiving the 1600 mg dose. Addition of dronedarone (800-1600 mg daily) to metoprolol (200 mg daily) increases bioavailability of metoprolol in CYP2D6 extensive metabolizers and induces an additive dronedarone dose-dependent negative inotropic effect. Nevertheless at 800 mg daily (anticipated therapeutic dose) these effects were modest.