gebhart/patrepeval huggingface dataset:
Intradermal Vaccinations With RNA Coding for TAA Generate CD8+ and CD4+ Immune Responses and Induce Clinical Benefit in Vaccinated Patients (2010)

The aim of this phase I/II nonrandomized trial was to assess feasibility, safety as well as immunological and clinical responses of a mRNA-based vaccination in patients with stage IV renal cell cancer using granulocyte-macrophage colony stimulating factor (GM-CSF) as adjuvant. Intradermal injections of in vitro transcribed naked mRNA, which was generated using plasmids coding for the tumor-associated antigens mucin 1(MUC1), carcinoembryonic (CEA), human epidermal growth factor receptor 2 (Her-2/neu), telomerase, survivin, and melanoma-associated antigen 1 (MAGE-A1) were performed in 30 enrolled patients. In the first 14 patients (cohort A) vaccinations were administered on days 0, 14, 28, and 42 (20 µg/antigen) while in the consecutive 16 patients (cohort B) an intensified protocol consisting of injections at days 0-3, 7-10, 28, and 42 (50 µg/antigen) was used. In both cohorts, after this induction period, vaccinations were repeated monthly until tumor progression analyzed by Response Evaluation Criteria In Solid Tumors criteria (RECIST). Vaccinations were well tolerated with no severe side effects and induced clinical responses [six stable diseases (SD) and one partial response in cohort A and nine SD in cohort B]. In cohort A, 35.7% survived 4 years (median survival 24 months) compared to 31.25% in cohort B (median survival 29 months). Induction of CD4(+) and CD8(+) T cell responses was shown for several tumor-associated antigens (TAA) using interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) and Cr-release assays.
The United States, International Humanitarian Law and the Prisoners at Guantanamo Bay (2003)

This article, having established that the United States' military offensive, in Afghanistan, instigated in response to the terrorist attacks of September 11th, constitutes an international armed conflict for the purposes of the application of international humanitarian law, focuses on the actions taken by the United States authorities in relation to those captured during the conflict in Afghanistan. The article considers the status determination of these captives, the conditions of their transfer to Guantanamo Bay, Cuba, and their subsequent confinement there, and finally the legal remedies that are available to the captives pursuant to their detention. On all of these counts the article queries the extent to which the rules of international humanitarian law are being violated, as well as noting the relevant infringements of human rights law that are occurring.
Pathological Proteins in Senile Plaques. (1994)

The beta-amyloid protein deposits of Alzheimer disease, whether in diffuse or consoliated form, are an agglomeration of many extracellular proteins. At least 35 have been reported as components of senile plaques, most of which also occur in diffuse deposits. More than half of these proteins are directly associated with the immune system. Since diffuse deposits are believed to be the precursors of senile plaques, it is important to define the precise molecular events that lead to the transition. Diffuse deposits share with senile plaques the presence of opsonizing components of complement, the complement activators beta-amyloid protein, amyloid P, thrombin, and apolipoprotein E. However, senile plaques contain, in addition, dystrophic neurites, agglomerates of activated microglia, components of the membrane attack complex, and the inhibitors of the membrane attack complex, clusterin, protectin and vitronectin. Microglial cells are professional phagocytes which possess the respiratory burst apparatus when activated. It produces extracellular superoxide molecules which can then form additional toxic products such as hydrogen peroxide and hydroxyl free radicals. It has long been known that opsonized zymosan is a powerful activator of the respiratory burst system. We found this activation could be inhibited by antibodies to complement receptors in the nanomolar range. Dapsone and indomethacin, two antiinflammatory agents that may have therapeutic potential in Alzheimer disease, were weakly inhibitory (10(-4) M range).(ABSTRACT TRUNCATED AT 250 WORDS)
Renal (pro)renin receptor upregulation in diabetic rats through enhanced angiotensin AT1 receptor and NADPH oxidase activity (2008)

Recent studies have demonstrated the presence of the (pro)renin receptor (PRR) in the glomerular mesangium and the subendothelial layer of the renal arteries. We hypothesized that diabetes upregulates PRR expression through enhanced angiotensin subtype 1 (AT1) receptor-NADPH oxidase cascade activity. Using real-time polymerase chain reaction, Western blot analysis and immunostaining, we studied renal localization of the PRR in the streptozotocin-induced diabetic rat model and in response to 1 week of treatment with the AT1 receptor blocker valsartan (10 mg kg(-1) day(-1)), the angiotensin AT2 receptor blocker PD123319 (0.5 mg kg(-1) day(-1)) or the NADPH oxidase inhibitor diphenylene iodonium (DPI; 0.5 mg kg(-1) day(-1)) 6 weeks post-induction of diabetes. Both PRR mRNA and protein were expressed constitutively in the kidneys of normal rat renal cortex and medulla, mainly in glomerular mesangium, proximal, distal and collecting tubules. Compared with normal rats (100%), diabetic rats demonstrated an increase in renal PRR mRNA (184%), protein (228%) and immunostaining. Valsartan and DPI prevented the increase in the PRR mRNA (106 and 126%, respectively), protein (97 and 140%, respectively) and immunostaining that was seen in the kidneys of diabetic rats. The AT2 blocker PD123319 did not have significant effects on PRR mRNA (157%) or protein expression (200%) in the kidneys of diabetic rats. These results demonstrate that the PRR is constitutively expressed in renal glomeruli and tubules. Expression of the PRR is upregulated in diabetes via enhancement of AT1 receptor-NADPH oxidase activity.
Expression of Macrophage Inflammatory Protein-1 Receptors in Human CD34+ Hematopoietic Cells and Their Modulation by Tumor Necrosis Factor- and Interferon-γ (1998)

Macrophage inflammatory protein-1 (MIP-1) can stimulate growth inhibitory and potent chemotactic functions in hematopoietic cells. To investigate whether the action of MIP-1 may be regulated at the cellular receptor level, we studied the expression and modulation of MIP-1 receptors on CD34+ cells isolated from normal bone marrow (NBM), umbilical cord blood (CB), and leukapheresis products (LP). Expression of MIP-1 receptors on CD34+cells was analyzed by two-color flow cytometry using a biotinylated MIP-1 molecule. The mean percentage of LP CD34+ cells expressing the MIP-1 receptors was 67.7 ± 7.2% (mean ± SEM; n = 22) as compared with 89.9 ± 2.6% (n = 10) and 74.69 ± 7.04% (n = 10) in CB and NBM, respectively (P = .4). The expression of the MIP-1 receptor subtypes on LP CD34+ cells was studied by indirect immunofluorescence using specific antibodies for the detection of CCR-1, CCR-4, and CCR-5. Microscopical examination revealed a characteristic staining of the cytoplasmic cell membrane for all three receptor subtypes. Detailed analysis of two LP samples showed that 65.8%, 4.4%, and 30.5% of CD34+ cells express CCR-1, CCR-4, and CCR-5, respectively. Culture of LP CD34+ cells for 24 to 36 hours in the presence of tumor necrosis factor- (TNF-) and interferon-γ (IFN-γ) resulted in a significant increase in MIP-1 receptor expression. TNF- induced MIP-1 receptor upregulation in a time- and concentration-dependent manner. Our results suggest that inhibitory cytokines produced by the bone marrow microenvironment are likely to be involved in the regulation of MIP-1 receptor expression on hematopoietic cells. © 1998 by The American Society of Hematology.
Ge photodetector monolithically integrated with amorphous Si waveguide on wafer-bonded Ge-on-insulator substrate (2018)

We present a proof-of-concept demonstration of a Ge/a-Si hybrid photonic integrated circuit platform utilizing a high-quality Ge-on-insulator (GeOI) wafer fabricated by wafer bonding technology. Amorphous Si (a-Si) formed by PECVD is found to be a promising alternative to conventional Si passive waveguides on a SiO<sub>2</sub> BOX. Taking advantage of the high crystal quality of the Ge active layer and the easy fabrication of an a-Si waveguide, a low-dark-current Ge waveguide PIN photodetector monolithically integrated with an a-Si passive waveguide is successfully demonstrated on a GeOI wafer.
The Degradation of Human Endothelial Cell-derived Perlecan and Release of Bound Basic Fibroblast Growth Factor by Stromelysin, Collagenase, Plasmin, and Heparanases (1996)

Perlecan is a modular heparan sulfate proteoglycan that is localized to cell surfaces and within basement membranes. Its ability to interact with basic fibroblast growth factor (bFGF) suggests a central role in angiogenesis during development, wound healing, and tumor invasion. In the present study we investigated, using domain specific anti-perlecan monoclonal antibodies, the binding site of bFGF on human endothelial perlecan and its cleavage by proteolytic and glycolytic enzymes. The heparan sulfate was removed from perlecan by heparitinase treatment, and the approximately 450-kDa protein core was digested with various proteases. Plasmin digestion resulted in a large fragment of approximately 300 kDa, whereas stromelysin and rat collagenase cleaved the protein core into smaller fragments. All three proteases removed immunoreactivity toward the anti-domain I antibody. We showed also that perlecan bound bFGF specifically by the heparan sulfate chains located on the amino-terminal domain I. Once bound, the growth factor was released very efficiently by stromelysin, rat collagenase, plasmin, heparitinase I, platelet extract, and heparin. Interestingly, heparinase I, an enzyme with a substrate specificity for regions of heparan sulfate similar to those that bind bFGF, released only small amounts of bFGF. Our findings provide direct evidence that bFGF binds to heparan sulfate sequences attached to domain I and support the hypothesis that perlecan represents a major storage site for this growth factor in the blood vessel wall. Moreover, the concerted action of proteases that degrade the protein core and heparanases that remove the heparan sulfate may modulate the bioavailability of the growth factor.
Long-term effects of flexible work (2005)

The central aim of this book is to consider to what extent changes in organisations and in the nature of jobs are compatible with the need, increasingly expressed by employees, for greater integration between work and family life. The book questions what sort of dilemmas modern and future employees face, in terms of shaping their careers and organising their lives at home. The authors formulate answers to these problematic questions by shedding light on relevant developments in the European labour markets, the European workplaces, in (flexible) working patterns, changing preferences for working hours and in gender relations at work.
Randomized, Double-Blind Six-Month Trial of Prednisone in Duchenne's Muscular Dystrophy (1989)

We performed a randomized, double-blind, controlled six-month trial of prednisone in 103 boys with Duchenne's muscular dystrophy (age, 5 to 15 years). The patients were assigned to one of three regimens: prednisone, 0.75 mg per kilogram of body weight per day (n = 33); prednisone, 1.5 mg per kilogram per day (n = 34); or placebo (n = 36). The groups were initially comparable in all measures of muscle function. Both prednisone groups had significant improvement of similar degree in the summary scores of muscle strength and function. Improvement began as early as one month and peaked by three months. At six months the high-dose prednisone group, as compared with the placebo group, had improvement in the time needed to rise from a supine to a standing position (3.4 vs. 6.2 seconds), to walk 9 m (7.0 vs. 9.7 seconds), and to climb four stairs (4.0 vs. 7.1 seconds), in lifting a weight (2.1 vs. 1.2 kg), and in forced vital capacity (1.7 vs. 1.5 liters) (P less than 0.001 for all comparisons). There was an increase in urinary creatinine excretion (261 vs. 190 mg per 24 hours), which suggested an increase in total muscle mass. However, the prednisone-treated patients who had required long-leg braces (n = 5) or wheelchairs (n = 11) continued to require them. The most frequent side effects were weight gain, cushingoid appearance, and excessive hair growth. We conclude from this six-month study that prednisone improves the strength and function of patients with Duchenne's muscular dystrophy. However, further research is required to identify the mechanisms responsible for these improvements and to determine whether prolonged treatment with corticosteroids may be warranted despite their side effects.
Vaccination against the HER-2/neu oncogenic protein. (2002)

The HER-2/neu oncogenic protein is a well-defined tumor antigen. HER-2/neu is a shared antigen among multiple tumor types. Patients with HER-2/neu protein-overexpressing breast, ovarian, non-small cell lung, colon, and prostate cancers have been shown to have a pre-existent immune response to HER-2/neu. No matter what the tumor type, endogenous immunity to HER-2/neu detected in cancer patients demonstrates two predominant characteristics. First, HER-2/neu-specific immune responses are found in only a minority of patients whose tumors overexpress HER-2/neu. Secondly, immunity, if detectable, is of low magnitude. These observations have led to the development of vaccine strategies designed to boost HER-2/neu immunity in a majority of patients. HER-2/neu is a non-mutated self-protein, therefore vaccines must be developed based on immunologic principles focused on circumventing tolerance, a primary mechanism of tumor immune escape. HER-2/neu-specific vaccines have been tested in human clinical trials. Early results demonstrate that significant levels of HER-2/neu immunity can be generated with active immunization. The T-cell immunity elicited is durable after vaccinations have ended. Furthermore, despite the generation of CD8(+) and CD4(+) T-cells responsive to HER-2/neu in a majority of patients, there is no evidence of autoimmunity directed against tissues that express basal levels of the protein. Cancer vaccines targeting the HER-2/neu oncogenic protein may be useful adjuvants to standard therapy and aid in the prevention of relapse in patients whose tumors overexpress the protein. Furthermore, boosting HER-2/neu-specific T-cell frequencies via active immunization may allow the ex vivo expansion of HER-2/neu-specific T-cells for use in adoptive immunotherapy, a therapeutic strategy directed against the treatment of established disease.
Long‐Term Prognosis of Lennox‐Gastaut Syndrome (1996)

We investigated the long-term prognosis of Lennox-Gastaut syndrome (LGS) in 72 patients followed up for > 10 years. Long-term seizure and intellectual outcomes were poor, as previously reported. The diagnosis of LGS was first made in the age range from 2 to 15 years with peak occurrence at 5 years. Progressive IQ score deterioration with age was apparent. At the last examination, 33% of patients with cryptogenic and 55% with symptomatic LGS had lost the characteristics of LGS, and their seizure disorders were classifiable as symptomatic generalized epilepsies, severe epilepsy with multiple independent spike foci, or localization-related epilepsies. Disabling drop attacks appeared in 46% of patients and tended to occur at older than 10 years. Gait deterioration was recognized in 12 patients and seemed to be due largely to progression of the epileptic encephalopathy. The gait disturbances, as well as increased frequency of violent drop attacks, were disabling in daily life and resulted in some patients being wheelchair bound.
Efficient HTTP-based Adaptive Streaming of Linear and Interactive Videos (2018)

Online video streaming has gained tremendous popularity over recent years and currently constitutes the majority of Internet traffic. As large-scale ondemand streaming continues to gain popularity, several important questions and challenges remain unanswered. This thesis addresses open questions in the areas of efficient content delivery for HTTP-based Adaptive Streaming (HAS) from different perspectives (client, network and content provider) and in the design, implementation, and evaluation of interactive streaming applications over HAS.
Serum and in vitro production of IL-1 receptor antagonist correlate with C-reactive protein levels in newly diagnosed, untreated lupus patients. (2002)

In lupus patients, serum IL-1 beta, IL-6 or TNF-alpha levels failed to correlate with low CRP levels. This indicates a complicated CRP production process, which can not be explained solely by single cytokines as reported previously. Both serum and in vitro produced IL-1ra may be applied clinically as a surrogate CRP marker in untreated lupus patients as they are both correlated with serum CRP.
EPHB2 germline variants in patients with colorectal cancer or hyperplastic polyposis (2006)

We detected novel germline EPHB2 alterations in patients with colorectal tumors. The results suggest a limited role for these EPHB2 variants in colon tumor predisposition. Further studies including functional analyses are needed to confirm this.
Moisture as a Regulator of Physiological Reaction in Seeds (1989)

This chapter provides a brief review of the thermodynamic status of water in dry seeds and describes examples of reactions that apparently occur within the various regions defined by the thermodynamic properties of water. The survival of a seed in dry storage depends upon its moisture content more than on any other factor. Within the moisture range in which water is bound, regions with different water-binding characteristics can be defined using moisture isotherms. The chapter examines an array of physiological reactions in dry seeds for possible association with the three regions of water binding. They are nonenzymatic reactions, enzyme reactions, and light absorption by pigments. The chapter also describes how the nature of reactions change with moisture region; thus, it is likely that the mechanisms of aging change with hydration level. It reviews the role of water potential as a regulator of seed growth and development.
Detection of subjects with higher self-reporting stress scores using heart rate variability patterns during the day (2008)

Heart rate variability (HRV) has been well established to measure instantaneous levels of mental stress. Circadian patterns of HRV features have been reported but their use to estimate levels of mental stress were not studied thoroughly. In this study, we investigated time dependent variations of HRV features to detect subjects under chronic mental stress. Sixty eight subjects were divided into high (n=10) and low stress group (n=43) depending on their self-reporting stress scores. HRV features were calculated during three different time periods of the day. High stress group showed decreased patterns of HRV features compared to low stress group. When logistic regression analysis was performed with raw multiple HRV features, the classification was 63.2% accurate. A new % deviance score reflecting the degree of difference from normal reference patterns increased the accuracy to 66.1%. Our data suggested that HRV patterns obtained at multiple time points of the day could provide useful data to monitor subjects under chronic stress.
Fumarate Reductase and Succinate Oxidase Activity of Escherichia coli Complex II Homologs Are Perturbed Differently by Mutation of the Flavin Binding Domain (2006)

The Escherichia coli complex II homologues succinate:ubiquinone oxidoreductase (SQR, SdhCDAB) and menaquinol:fumarate oxidoreductase (QFR, FrdABCD) have remarkable structural homology at their dicarboxylate binding sites. Although both SQR and QFR can catalyze the interconversion of fumarate and succinate, QFR is a much better fumarate reductase, and SQR is a better succinate oxidase. An exception to the conservation of amino acids near the dicarboxylate binding sites of the two enzymes is that there is a Glu (FrdA Glu-49) near the covalently bound FAD cofactor in most QFRs, which is replaced with a Gln (SdhA Gln-50) in SQRs. The role of the amino acid side chain in enzymes with Glu/Gln/Ala substitutions at FrdA Glu-49 and SdhA Gln-50 has been investigated in this study. The data demonstrate that the mutant enzymes with Ala substitutions in either QFR or SQR remain functionally similar to their wild type counterparts. There were, however, dramatic changes in the catalytic properties when Glu and Gln were exchanged for each other in QFR and SQR. The data show that QFR and SQR enzymes are more efficient succinate oxidases when Gln is in the target position and a better fumarate reductase when Glu is present. Overall, structural and catalytic analyses of the FrdA E49Q and SdhA Q50E mutants suggest that coulombic effects and the electronic state of the FAD are critical in dictating the preferred directionality of the succinate/fumarate interconversions catalyzed by the complex II superfamily.
Synthesis of 2′-deoxy-2′-α-monofluoromethyl and trifluoromethyl Nucleosides (1994)

Coupling of 2′-deoxy-2′-α-monofluoromethyl and trifluoromethyl ribose derivatives with bissilylated thymine afforded a mixture of α- and β- nucleosides which were further transformed into their corresponding pure β-phosphoramidites.
Converting enzyme inhibition in essential hypertension: the hypotensive response does not reflect only reduced angiotensin II formation. (1979)

To determine the relative importance of hormonal factors in mediating the hypotensive response to converting enzyme inhibition (CEI), plasma renin activity (PRA), angiotensin II, and bradykinin responses to SQ20,881 were measured in 20 supine patients with essential hypertension in balance on a 10 mEq sodium diet. Patients were divided into two groups according to their diastolic blood pressure response: responders had a decrement in diastolic pressure which exceeded 9 mm Hg, the upper value of the 95% confidence limits for normotensive patients studied under similar conditions; nonresponders did not. Compared to the nonresponders, responders not only had a higher control PRA (8.7 +/- 1.7 ng/ml/hr vs 4.8 +/- 2.1, p < 0.05) and larger decrement in plasma angiotensin II (18.7 +/- 4.9 pg/ml vs 3.2 +/- 1.7, p < 0.01), but also had a higher control bradykinin (3.2 +/- 0.7 ng/ml vs 1.1 +/- 0.2, p < 0.05) and larger increment in bradykinin (4.5 +/- 1.3 ng/ml vs 1.0 +/- 0.4, p < 0.05) following SQ20,881. Because SQ20,881 altered both angiotensin II and bradykinin concentrations, we assessed the contribution of blockade of angiotensin II formation by administering angiotensin II infusions to seven responders during coverting enzyme blockade, with the angiotensin II dose adjusted to restore diastolic pressure to control levels. The plasma angiotensin II level required to return blood pressure to control was 45 +/- 15 pg/ml higher than the control plasma angiotensin II level (p < 0.01), suggesting that some other factor(s), perhaps bradykinin, are also responsible for the hypotensive response to converting enzyme inhibition.