Miracle-dz/UniFAR-FTUs huggingface dataset:
HLA A2.1-restricted cytotoxic T cells recognizing a range of Epstein-Barr virus isolates through a defined epitope in latent membrane protein LMP2

Cytotoxic T-lymphocyte (CTL) responses induced by persistent Epstein-Barr virus (EBV) infection in normal B-lymphoid tissues could potentially be directed against EBV-positive malignancies if expression of the relevant viral target proteins is maintained in tumor cells. For malignancies such as nasopharyngeal carcinoma and Hodgkin's disease, this will require CTL targeting against the nuclear antigen EBNA1 or the latent membrane proteins LMP1 and LMP2. Here we analyze in detail a B95.8 EBV-reactivated CTL response which is specific for LMP2 and restricted through a common HLA allele, A2.1. We found that in vitro-reactivated CTL preparations from several A2.1-positive virus-immune donors contained detectable reactivity against A2.1-bearing target cells expressing either LMP2A or the smaller LMP2B protein from recombinant vaccinia virus vectors. Peptide sensitization experiments then mapped the A2.1-restricted response to a single epitope, the nonamer CLGGLLTMV (LMP2A residues 426 to 434), whose sequence accords well with the proposed peptide binding motif for A2.1. Most Caucasian and African virus isolates (whether of type 1 or type 2) were identical in sequence to B95.8 across this LMP2 epitope region, although 2 of 12 such isolates encoded a Leu-->Ile change at epitope position 6. In contrast, most Southeast Asian and New Guinean isolates (whether of type 1 or type 2) constituted a different virus group with a Cys-->Ser mutation at epitope position 1. CTLs raised against the B95.8-encoded epitope were nevertheless able to recognize these variant epitope sequences in the context of A2.1 whether they were provided exogenously as synthetic peptides or generated endogenously in B cells transformed with the variant viruses. A CTL response of this kind could have therapeutic potential in that it is directed against a protein expressed in many EBV-positive malignancies, is reactive across a range of virus isolates, and is restricted through a relatively common HLA allele.
Group I Metabotropic Glutamate Receptors: A Potential Target for Regulation of Proliferation and Differentiation of an Immortalized Human Neural Stem Cell Line

Human neural stem cells (NSCs) from the developing embryo or the subventricular zone of the adult brain can potentially elicit brain repair after injury or disease, either via endogenous cell proliferation or by cell transplantation. Profound knowledge of the diverse signals affecting these cells is, however, needed to realize their therapeutic potential. Glutamate and group I metabotropic glutamate receptors (mGluRs) affect proliferation and survival of rodent NSCs both during embryonic and post‐natal development. To investigate the role of group I mGluRs (mGluR1 and mGluR5) on human NSCs, we differentiated an immortalized, forebrain‐derived stem cell line in the presence or absence of glutamate and with addition of either the group I mGluR agonist DHPG or the selective antagonists, MPEP (mGluR5) and LY367385 (mGluR1). Characterization of differentiated cells revealed that both mGluR1 and mGluR5 were present on the cells. Addition of glutamate to the growth medium significantly increased cell proliferation and reduced cell death, resulting in increased cell numbers. In the presence of glutamate, selective activation of group I mGluRs reduced gliogenesis, whereas selective inhibition of group I mGluRs reduced neurogenesis. Our results substantiate the importance of glutamate signalling in the regulation of human NSCs and may as such be applied to promote proliferation and neuronal differentiation.
Effects of all‐trans retinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia

Summary. We studied the pathogenesis of the bleeding disorder in acute promyelocytic leukemia by measuring procoagulant, profibrinolytic, and proinflammatory mediators in peripheral blood and bone marrow cells from 25 previously untreated patients. Patients were induced with either all‐trans retinoic acid (ATRA) or chemotherapy. Plasma levels of fibrinopeptide A (FPA), fibrin d‐dimer, thrombin antithrombin (TAT) complex, prothrombin fragment 1.2 (F1.2), urokinase‐type plasminogen activator (uPA), tissue‐type plasminogen activator (t‐PA) and plasminogen activator‐inhibitor 1 (PAI‐1) were measured before and after therapy, as was the cellular expression of the genes for tissue factor (TF) and interleukin‐1β (IL‐1β). The mean plasma levels of fibrin d‐dimer, F1.2, TAT and FPA were markedly elevated prior to therapy and declined during the first 30 days of treatment with either ATRA or chemotherapy, but more rapidly and to a greater extent in patients treated with ATRA. ATRA treatment was associated with a significant decrease in TF gene expression in bone marrow cells during the first 30 days of treatment, whereas IL‐1β gene expression, which decreased in the cells of six patients treated with either chemotherapy or ATRA, actually increased in the remaining six patients treated with either chemotherapy or ATRA. In patients with APL, treatment with either chemotherapy or ATRA rapidly ameliorates the coagulopathy, as indicated by an abrupt decline in markers of clotting activation. An increase in cytokine gene expression (e.g. IL‐1β) may provide an explanation for the persistent hypercoagulability observed in some patients with APL, regardless of therapeutic approach. Our data confirms and extends earlier observations by others that ATRA is more effective than chemotherapy alone in rapidly reducing the procoagulant burden of APL tumor cells. However, our data also suggests that cytokine expression in some patients may be accelerated by either chemotherapy or ATRA. The implications of this observation for understanding the retinoic acid syndrome will require further studies.
Climate change impacts on the power generation potential of a European mid-century wind farms scenario

Wind energy resource is subject to changes in climate. To investigate the impacts of climate change on future European wind power generation potential, we analyze a multi-model ensemble of the most recent EURO-CORDEX regional climate simulations at the 12 km grid resolution. We developed a mid-century wind power plant scenario to focus the impact assessment on relevant locations for future wind power industry. We found that, under two greenhouse gas concentration scenarios, changes in the annual energy yield of the future European wind farms fleet as a whole will remain within ±5% across the 21st century. At country to local scales, wind farm yields will undergo changes up to 15% in magnitude, according to the large majority of models, but smaller than 5% in magnitude for most regions and models. The southern fleets such as the Iberian and Italian fleets are likely to be the most affected. With regard to variability, changes are essentially small or poorly significant from subdaily to interannual time scales.
Timing of Supplementation With the Antioxidant N-Acetyl-L-Cysteine Reduces Tumor Multiplicity in Novel, Cancer-Prone p53 Haploinsufficient Tg.AC (v-Ha-ras) Transgenic Mice but Has No Impact on Malignant Progression

Epidemiological studies support the protective role of dietary antioxidants in preventing cancer. However, emerging evidence suggests that antioxidant supplements may actually exacerbate carcinogenesis. We explored this paradox in a model containing two common genotypic characteristics of human cancers. We selected p53 haploinsufficient Tg.AC (v-Ha-ras) mice as a model, because it contains an activated, carcinogen-inducible ras oncogene and an inactivated p53 tumor suppressor gene. These mice develop chemically induced benign and malignant skin tumors rapidly. Mice were fed basal diet with or without 3% N-acetyl-L-cysteine (NAC) before and after topical application of the carcinogen benzo[a]pyrene (64 μg twice per week for 7 wk) until 50% of mice within a group displayed at least one lesion. Half each of mice fed the basal and the NAC-supplemented diet were then switched to the alternate diet. Mice fed the NAC-supplemented diet or switched from the NAC-supplemented to the basal diet displayed 38% and 26% reductions, respectively, in tumor multiplicity and a 15% reduction if switched from the basal to the NAC-supplemented diet. Although latency was unaffected, NAC induced a lag in tumor incidence, which exceeded 90% at 10 wk for all groups. The timing of NAC supplementation did not affect malignant progression. Thus dietary NAC was chemoprotective by slowing tumorigenesis but did not affect malignant conversion.
Stock Prices Reaction to Dividend Announcements: A Study on Listed Companies in the Damascus Securities Exchange

According to the signaling theory, dividend announcements are usually considered as a signal to the investors, about firm's future performance, that results in stock prices changes. This study attempts to investigate the stock prices response to dividend announcement in the Damascus Securities Exchange. The purpose of the study is to identify whether there are any significant abnormal returns around the public announcement of dividend. An event study methodology is used for an event window of forty days surrounding the announcement day. Research results indicate that most average abnormal returns are statistically insignificant, whereas the cumulative average abnormal returns are statistically significant for the whole event window. The downward drift of the cumulative average abnormal returns six days after the announcement suggests that prices don't adjust immediately to dividend information. The stock reactions appear within post-event window gradually in response to the dividends announcement.
Reasoning as a Pedagogical Strategy in Infant-Addressed Talk in Early Childhood Education Centres: Relationships with Educators’ Qualifications and Communicative Function

ABSTRACT Research Findings: This study examines the frequency of reasoning talk used by 56 educators during their naturally occurring play interactions with infants in their early childhood education and care (ECEC) centers. Using Hasan’s semantic framework, reasons were coded as social (based on social rules) or logical (based on rules of nature). The communicative function of reasoning talk was coded as regulatory (when the reason served to regulate infants’ behavior) or non-regulatory. On average, educators’ reasoning talk comprising only 4.43% of their total talk, with social reasoning used slightly more frequently than logical reasoning. Educators used significantly more social reasoning when regulating infants’ behavior, whereas logical reasoning occurred more frequently during non-regulatory interactions. Educators’ qualification level explained individual differences. Bachelor-qualified educators used significantly more reasoning talk than lower-qualified educators, and this finding was explained by their more frequent use of both social and logical reasoning when regulating infants’ behavior. Practice or Policy: The study identifies reasoning talk as an important element of language environment quality in ECEC infant rooms, and highlights the learning potential of language used for different communicative purposes. Findings demonstrate that well-qualified educators appear well versed to capitalize on the educative potential of this type of talk.
Correlations Between Allergen-Specific IgE Serum Levels in Patients With Ocular Allergy

Purpose: To evaluate ocular allergies in patients at the Hospital do Servidor Publico Estadual de Sao Paulo (HSPE) and the correlations with serum allergen-specific immunoglobulin E levels. Methods: We performed a longitudinal study of patients with ocular allergies who were treated at the Cornea and Immunology and Allergy Department. Patients underwent an ophthalmologic examination to identify their primary presenting signs and symptoms. The allergy types were divided into 4 groups. We conducted the following laboratory tests and measurements: blood count, eosinophil count, total serum IgE, and specific IgE. Results: Among 61 patients, 16 (26.2%) had a clinical diagnosis of seasonal allergic conjunctivitis, 23 (37.7%) had perennial allergic conjunctivitis, 19 (31.1%) had vernal keratoconjunctivitis, and 3 (4.9%) had atopic keratoconjunctivitis. Mixed dust mites were positive in 94.9% of patients. Dermatophagoides pteronyssinus (dp) and Dermatophagoides farinae (df) antigens were positive in 93.2% of patients followed by Blattella germanica, Blomia tropicalis, and mixed animal epithelia (81%, 75.9%, and 25.8%, respectively). Conclusions: Perennial allergic conjunctivitis was the most prevalent disorder and demonstrated higher positivity in class V/VI for specific antigens (mixed dust mites, dp, and df), indicating high antigenicity. Dust mites, D. pteronyssinus, D. farinae, B. germanica, and B. tropicalis were the primary triggers of the studied ocular allergies.
Glycogen Storage Disease Type II: Birth Prevalence Agrees with Predicted Genotype Frequency

Objectives: To compare the overall birth prevalence of diagnosed glycogen storage disease type II (GSD II) with the predicted frequency based on mutation screening, in order to determine whether GSD II is an underdiagnosed condition, and to analyze which medical disciplines recognize GSD II. Methods: Retrospective data on all enzymatic diagnoses of GSD II were collected from diagnostic labs throughout the Netherlands, covering the period from January 1, 1972 to December 31, 1996. Age-specific diagnostic incidence rates were calculated for the entire study period. By adding together the diagnostic incidences for all age groups, we calculated the birth prevalence of diagnosed GSD II and compared these figures with the predicted frequency based on mutation screening in a random sample from the general population. The medical specialization of the referring clinicians was also recorded. Results: GSD II was diagnosed in 154 individuals, including 11 prenatal diagnoses. The birth prevalences of the various phenotypes were 1/101,000 (infantile form), 1/720,000 (juvenile form) and 1/53,000 (adult form). The birth prevalence of the adult and infantile phenotype together was 1/35,000. Eighty-two percent of the patients were diagnosed in university hospitals. Of the patients with infantile GSD II, 71% were diagnosed by a pediatrician, whereas most patients with adult GSD II were diagnosed by a neurologist (80%). Conclusions: There is no evidence for the underdiagnosis of GSD II in the Netherlands, as the calculated birth prevalences of the disease are consistent with previous predictions based on mutation screening in a random sample of newborns. The worldwide birth prevalence of the disease may well be higher than 1 in 100,000. GSD II is mainly diagnosed in university hospitals.
New bis(SATE) prodrug of AZT 5'-monophosphate: in vitro anti-HIV activity, stability, and potential oral absorption.

The in vitro anti-HIV activity, stability, and potential for oral absorption of a phosphotriester derivative of AZT (zidovudine; 3'-azido-2',3'-deoxythymidine) bearing a new esterase-labile S-acyl-2-thioethyl (SATE) group as transient phosphate protection are reported. The biolabile protection is characterized by the presence of a hydroxyl function in the acyl chain. In accordance with previously reported data in the bis(SATE) prodrug series, the present results demonstrate that the studied bis(hydroxytBuSATE)phosphotriester exerts its biological effects via intracellular delivery of the 5'-monophosphate of AZT. The hydroxyl function confers a high resistance against esterase hydrolysis, and the studied prodrug is able to cross the Caco-2 cell monolayers in intact form, suggesting that its further development as a possible anti-HIV pronucleotide candidate is warranted.
Conditional reconstruction: An alternative strategy in digital rock physics

Digital rock physics (DRP) is a newly developed method based on imaging and digitizing of 3D pore and mineral structure of actual rock and numerically computing rock physical properties, such as permeability, elastic moduli, and formation factor. Modern high-resolution microcomputed tomography scanners are used for imaging, but these devices are not widely available, and 3D imaging is also costly and it is a time-consuming procedure. However, recent improvements of 3D reconstruction algorithms such as crosscorrelation-based simulation and, on the other side, the concept of rock physical trends have provided some new avenues in DRP. We have developed a modified work flow using higher order statistical methods. First, a high-resolution 2D image is divided into smaller subimages. Then, different stochastic subsamples are generated based on the provided 2D subimages. Eventually, various rock physical parameters are calculated. Using several subsamples allows extracting rock physical trends and better capturing the heterogeneity and variability. We implemented our work flow on two DRP benchmark data (Berea sandstone and Grosmont carbonate) and a thin-section image from the Grosmont carbonate formation. Results of realization models, pore network modeling, and autocorrelation functions for the real and reconstructed subsamples reveal the validity of the reconstructed models. Furthermore, the agreement between static and dynamic methods indicates that subsamples are representative volume elements. Average values of the subsamples’ properties follow the reference trends of the rock sample. Permeability trends pass the actual results of the benchmark samples; however, elastic moduli trends find higher values. The latter can be due to image resolution and voxel size, which are generated by imaging tools and reconstruction algorithms. According to the obtained results, this strategy can be introduced as a valid and accurate method where an alternative method for standard DRP is needed.
Gastric Fluid pH in Patients Receiving Sodium Citrate

Gastric fluid pH was measured following induction of anesthesia and placement of an endotracheal tube in 30 surgical patients undergoing elective operations. None of the patients received an anticholinergic drug before surgery. Fifteen patients who had been given 15 ml of sodium citrate 15 to 20 minutes before induction of anesthesia had a mean pH of 6.2 ± 0.8. The control group, which also consisted of 15 patients, had a mean pH of 2.1 ± 1.4. The increase in gastric pH noted following sodium citrate would result in reduced pulmonary reaction should aspiration occur.
Psychological debriefing for adults

Psychological debriefing (PD) was widely advocated for routine use following major traumatic events during the 1980s and 1990s. Several methods of PD have been described, including critical incident stress debriefing and multiple stressor debriefing. Most researchers have considered a PD to be a singlesession, semistructured crisis intervention designed to reduce and prevent unwanted psychological sequelae following traumatic events by promoting emotional processing through the ventilation and normalization of reactions and preparation for possible future experiences. PD was initially described as a group intervention, one part of a comprehensive, systematic, multicomponent approach to the management of traumatic stress, but it has also been used with individuals and as a stand-alone intervention. Its purpose is to review the impressions and reactions of clients shortly after a traumatic incident. The focus of a PD is on the present reaction of those involved. Psychiatric labeling is avoided, and emphasis is placed on normalization. Participants are assured that they are normal people who have experienced an abnormal event.
Human acid ceramidase is overexpressed but not mutated in prostate cancer

The human acid ceramidase gene, that causes Farber disease, is located in 8p22, a region frequently altered in several cancers, including prostate cancer. Acid ceramidase catalyzes the hydrolysis of ceramide, a potent lipid second messenger molecule that promotes apoptosis and inhibits cellular proliferation. It is not known whether this gene, or its expression, is altered in prostate cancer. Here, we report the structural organization of the human gene, its expression in human tissues, and the identification of several single nucleotide polymorphisms. No cancer‐related mutations were found in the gene in a panel of prostate tumor DNAs analyzed, but increased expression was observed in prostate tumor tissues when compared with matched normals. This increase was observed in all three prostate tumor cell lines tested (DU145, LnCAP, and PC3) when compared to a BPH (benign prostatic hyperplasia) cell line and 15/36 prostate tumors. These results suggest that acid ceramidase may play an important role in prostate carcinogenesis. © 2000 Wiley‐Liss, Inc.
Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity

Objective Current research has focused upon the potential links between novel markers of vascular risk such as endothelial dysfunction, oxidative stress, inflammation and insulin resistance in the pathogenesis of Type 2 diabetes and its complications. Grape seed extract (GSE), a flavonoid‐rich product, is a potential moderator of these markers. This study aimed to test the hypothesis that GSE may improve these markers in high‐risk cardiovascular subjects with Type 2 diabetes.
Two regimens of lithium prophylaxis and renal function

ABSTRACT— Two regimens of lithium prophylaxis with different pharmacokinetic characteristics were compared under double‐blind conditions in 25 bipolar patients in remission already stabilized on lithium, to determine the relative effects of each regimen on renal function. Once‐daily lithium carbonate (Priadal), which gives a peak lithium plasma level 2–3 h post‐administration with a low level 24 h later, was compared with twice‐daily lithium citrate (Litarex), which maintains a steadier 24 h plasma level. Patients were allocated randomly to one of the 2 regimens. They were seen monthly for clinical ratings over the course of 12 months. A comprehensive battery of renal function tests was undertaken at the start of the trial, between 6–9 months after the start and again after 1 year. No significant differences were observed in clinical outcome, side effects or renal function between the 2 regimens.
On attaining the prescribed quality of a controlled fourth order system

Abstract In this paper, we discuss a method of auxiliary controlled models and its application to solving some robust control problems for a system described by differential equations. As an illustration, a system of nonlinear differential equations of the fourth order is used. A solution algorithm, which is stable with respect to informational noise and computational errors, is presented. The algorithm is based on a combination of online state/input reconstruction and feedback control methods.