Miracle-dz/UniFAR-FTUs huggingface dataset:
Repeated Administration of Cytosine-Phosphorothiolated Guanine-Containing Oligonucleotides Together with Peptide/Protein Immunization Results in Enhanced CTL Responses with Anti-Tumor Activity1

The development of therapeutic anti-cancer vaccines designed to elicit CTL responses with anti-tumor activity has become a reality thanks to the identification of several tumor-associated Ags and their corresponding peptide T cell epitopes. However, peptide-based vaccines, in general, fail to elicit sufficiently strong CTL responses capable of producing therapeutic anti-tumor effects (i.e., prolongation of survival, tumor reduction). Here we report that repeated administration of synthetic oligonucleotides containing foreign cytosine-phosphorothiolated guanine (CpG) motifs increased 10- to 100-fold the CTL response to immunization with various synthetic peptides corresponding to well-known T cell epitopes. Moreover, repeated CpG administration allowed the induction of CTL to soluble protein even in the absence of additional adjuvant. Our results indicate that the potentiating effect of CpG in CTL responses required the participation of Th lymphocytes. Repeated CpG administration resulted in overt splenomegaly and lymphadenopathy with a significant increase in the numbers of CTL precursors and dendritic cells. Protein vaccination in combination with repeated CpG therapy was effective in delaying tumor cell growth and extending survival in mice bearing melanoma tumors. These findings support the contention that repeated administration of CpG-oligonucleotides enhances the effect of peptide and protein vaccines leading to potent anti-tumor responses, presumably through the induction of Th1 and dendritic cells, which are essential for optimal CTL responses. The immunostimulatory properties of CpG motifs may be key in inducing a consistent long term immunity to tumor-associated Ags when using peptides or proteins as T cell-inducing vaccines.
Opening of Blood–Ocular Barrier Demonstrated by Contrast‐Enhanced MR Imaging

Opening of the blood-ocular barrier following infusion of hyperosmolar agents into the internal carotid artery has been demonstrated by gadolinium enhanced magnetic resonance (MR) imaging. In five rhesus monkeys the disruption of the barrier was shown as increased signal intensity within the aqueous and vitreous humors. These findings suggest a potential use of contrast-enhanced MR imaging for detecting and evaluating the ocular microangiopathy of diabetic and hypertensive retinopathy and other diseases.
Polychlorinated Dibenzo-P-Dioxins and Dibenzofurans from a Grate-Type Municipal Solid Waste Incinerator in China

The emission characteristics of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were evaluated from a grate-type municipal solid waste incinerator (MSWI). The stack flue gas, fly ash and bottom ash samples were sampled and analyzed. Results indicated that the flue gas, fly ash and bottom ash presented their mean dioxin levels of 0.0723 ng I-TEQ/Nm3, 0.614 ng I-TEQ/g and 13.33 ng I-TEQ/kg respectively. The PCDD/Fs congener patterns, in flue gas, fly ash and bottom ash, showed large similarities in both concentration and I-TEQ profiles. The de novo synthesis plays a dominant role in the low-temperature post-combustion zone.
Formation of a Functional Hepatitis B Virus Replication Initiation Complex Involves a Major Structural Alteration in the RNA Template

ABSTRACT The DNA genome of a hepatitis B virus is generated by reverse transcription of the RNA pregenome. Replication initiation does not involve a nucleic acid primer; instead, the hepadnavirus P protein binds to the structured RNA encapsidation signal ɛ, from which it copies a short DNA primer that becomes covalently linked to the enzyme. Using in vitro-translated duck hepatitis B virus (DHBV) P protein, we probed the secondary structure of the protein-bound DHBV ɛ RNA (Dɛ) and observed a marked conformational change compared to free Dɛ RNA. Several initiation-competent mutant RNAs with a different free-state structure were similarly altered, whereas a binding-competent but initiation-deficient variant was not, indicating the importance of the rearrangement for replication initiation and suggesting a mechanistic coupling to encapsidation.
Linking the Power and Transport Sectors—Part 2: Modelling a Sector Coupling Scenario for Germany

“Linking the power and transport sectors—Part 1” describes the general principle of “sector coupling” (SC), develops a working definition intended of the concept to be of utility to the international scientific community, contains a literature review that provides an overview of relevant scientific papers on this topic and conducts a rudimentary analysis of the linking of the power and transport sectors on a worldwide, EU and German level. The aim of this follow-on paper is to outline an approach to the modelling of SC. Therefore, a study of Germany as a case study was conducted. This study assumes a high share of renewable energy sources (RES) contributing to the grid and significant proportion of fuel cell vehicles (FCVs) in the year 2050, along with a dedicated hydrogen pipeline grid to meet hydrogen demand. To construct a model of this nature, the model environment “METIS” (models for energy transformation and integration systems) we developed will be described in more detail in this paper. Within this framework, a detailed model of the power and transport sector in Germany will be presented in this paper and the rationale behind its assumptions described. Furthermore, an intensive result analysis for the power surplus, utilization of electrolysis, hydrogen pipeline and economic considerations has been conducted to show the potential outcomes of modelling SC. It is hoped that this will serve as a basis for researchers to apply this framework in future to models and analysis with an international focus.
Temporal Relationships of Myocardial Lactate Metabolism, Left Ventricular Function, and S‐T Segment Depression During Angina Precipitated by Exercise

Continuous monitoring of myocardial lactate metabolism and the electrocardiogram in association with an assessment of left ventricular function were carried out in a group of 14 patients before, during, and after a period of supine leg exercise. Of the 12 patients who were shown to have coronary artery disease, seven experienced exertional angina whereas five remained free of pain. Marked increases in arterial and coronary sinus lactate concentrations were observed in all subjects early in exercise although arterial lactate levels were higher in the angina group. In the normal subjects and in the non-angina group, myocardial lactate extraction increased to 36.7 and 28.5%, respectively, during exercise. In the angina group, however, lactate extraction remained abnormal during exercise, increasing to only 8.8%, but in this group only two patients showed myocardial lactate production. Left ventricular end-diastolic pressure was consistently elevated during exertional angina and showed a close temporal relationship to ischemic S-T segments. Left ventricular stroke work was unchanged at these elevated filling pressures indicating impaired left ventricular contractility. While correlation of exertional angina, S-T segment depression, and hemodynamic abnormalities was close, it was not possible to relate these changes to metabolic evidence of ischemia since this was obscured by the elevated arterial lactate concentrations.
Protein kinase CK2 modulates synaptic plasticity by modification of synaptic NMDA receptors in the hippocampus

Synaptic plasticity is the foundation of learning and memory. The protein kinase CK2 phosphorylates many proteins related to synaptic plasticity, but whether it is directly involved in it has not been clarified. Here, we examined the role of CK2 in synaptic plasticity in hippocampal slices using the CK2 selective inhibitors 5,6‐dichloro‐1‐β‐d‐ribofuranosylbenzimidazole (DRB) and 4,5,6,7‐tetrabromobenzotriazole (TBB). These significantly inhibited N‐methyl‐d‐aspartate (NMDA) receptor‐dependent long‐term potentiation (LTP). DRB also inhibited NMDA receptor‐mediated synaptic transmission, while leaving NMDA receptor‐independent LTP unaffected. NMDA receptors thus appear to be the primary targets of CK2. Although both long‐term depression (LTD) and LTP are induced by the influx of Ca2+ through NMDA receptors, surprisingly, LTD was not affected by CK2 inhibitors. We postulated that the LTP‐selective modulation by CK2 is due to selective modulation of NMDA receptors, and tested two hypotheses concerning the modulation of NMDA receptors: (i) CK2 selectively modulates NR2A subunits possibly related to LTP, but not NR2B subunits possibly related to LTD; and (ii) CK2 selectively affects synaptic but not extrasynaptic NMDA receptors whose activation is sufficient to induce LTD. DRB decreased NMDA receptor‐mediated synaptic transmission in the presence of selective NR2A subunit antagonist. The former hypothesis thus appears unlikely to be correct. However, DRB decreased synaptic NMDA receptor responses in cultured hippocampal neurons without affecting extrasynaptic NMDA receptor current. These findings support the latter hypothesis, that CK2 selectively affects LTP by selective modification of synaptic NMDA receptors in a receptor‐location‐specific manner.
What is the State of the Science on Physical Activity Interventions for Family Caregivers? A Systematic Review and RE-AIM Evaluation.

BACKGROUND Family caregivers are an important health care resource and represent a significant proportion of Canadian and US populations. Family caregivers suffer physical and psychological health problems because of being in the caregiver role. Interventions to support caregiver health, including physical activity (PA), are slow to be investigated and translated into practice. PURPOSE To examine the evidence for PA interventions in caregivers and determine factors hampering the uptake of this evidence into practice. METHODS A systematic review and evaluation of internal and external validity using the RE-AIM (Reach, Efficacy/Effectiveness, Adoption, Implementation, and Maintenance) framework was conducted. Randomized controlled trials or pretest/posttest studies of PA interventions were included. RESULTS Fourteen studies were published between 1997 and 2015. Methodological quality of studies and risk of bias was variable. External validity criteria were often not reported. Mean reporting levels were 1) reach, 53%; 2) efficacy/effectiveness, 73%; 3) adoption, 18%; 4) implementation, 48%; and 5) maintenance, 2%. CONCLUSIONS The lack of reporting of components of internal and external validity hinders the integration of caregiver PA interventions into clinical or community settings. Researchers should focus on standardized outcomes, accepted reporting criteria, and balancing factors of internal and external validity, to advance the state of the science.
Modelling and mathematical analysis in thermomechanics

El objetivo de esta tesis doctoral es el estudio de ciertos problemas termomecanicos acoplados no lineales de la mecanica de solidos, los cuales surgen de procesos reales bajo fuertes gradientes de temperatura. Con esta tematica en comun, se aborda la modelizacion y el analisis matematico de varios submodelos en termomecanica. Concretamente se deducen varios modelos termomecanicos acoplados para materiales termoviscoelasticos con memoria larga y con tensiones dependientes de la temperatura. Estos permiten modelar, por ejemplo, los procesos de solidificacion de coladas, de extrusion de piezas de metal y de laminacion de metales y aleaciones. Ademas, se realiza un estudio de la existencia, unicidad y regularidad de solucion de dos submodelos termomecanicos. En el primero se considera el submodelo mecanico con parametros dependientes de la temperatura, con una ley de comportamiento no lineal de tipo Maxwell-Norton y condiciones de contorno mixtas, suponiendo que el campo de temperaturas es conocido. Bajo este contexto se pueden modelar las deformaciones mecanicas sufridas por una estructura de aleacion expuesta al fuego. En el segundo se analiza un problema termoelastico completamente acoplado con condiciones de contorno mixtas, incluyendo una condicion de contorno tipo Robin, para el submodelo termico. Este modelo permite realizar una primera aproximacion de las deformaciones termomecanicas de una estructura expuesta al fuego.
Randomized controlled trial of a preventive intervention for perinatal depression in high-risk Latinas.

OBJECTIVE A randomized controlled trial was conducted to evaluate the efficacy of a cognitive-behavioral (CBT) intervention to prevent perinatal depression in high-risk Latinas. METHOD A sample of 217 participants, predominantly low-income Central American immigrants who met demographic and depression risk criteria, were randomized into usual care (UC; n = 105) or an 8-week CBT group intervention during pregnancy and 3 individual booster sessions during postpartum (n = 112). Participants completed measures assessing depressive symptoms (Center for Epidemiological Studies Depression Scale at baseline; Beck Depression Inventory, Second Edition [BDI-II]) and major depressive episodes (Mood Screener) at 5 time points throughout the perinatal period. RESULTS Intent-to-treat analyses indicated that intervention participants had significantly lower depressive symptoms and fewer cases of moderate depression (BDI-II ≥ 20) at Time 2 than UC participants. These effects were stronger for women who fully participated in the intervention (≥ 4 classes). The cumulative incidence of major depressive episodes was not significantly different between the intervention (7.8%) and UC (9.6%) groups. CONCLUSIONS A CBT intervention for low-income, high-risk Latinas reduced depressive symptoms during pregnancy but not during the postpartum period. Low levels of depressive symptoms and lower than expected rates of clinical depression in both groups may partially be due to methodological issues. As perinatal depression is a significant public health problem, more work is needed to prevent perinatal depression in low-income, ethnically diverse women.
Sources of Performance Improvements in Privatized Firms: A Clinical Study of the Global Telecommunications Industry

This paper examines the financial and operating performance of 31 national telecommunication companies in 25 countries that were fully or partially privatised through public share offering between October 1981 and November 1998. Using conventional pre- versus post-privatisation comparisons, we find that profitability, output, operating efficiency and capital investment spending increase significantly after privatisation, while employment and leverage decline significantly. However, these univariate comparisons do not account for separate regulatory and ownership effects (retained government stake), and almost all telecoms are subjected to material new regulatory regimes around the time they are privatised. We examine these separate effects using both random and fixed-effect panel data estimation techniques for a seven-year period around privatisation. We verify that privatisation is significantly related to higher profitability, output and efficiency, and with significant declines in leverage. However, we also find numerous separable effects for variables measuring regulation, competition, retained government ownership and foreign listing (on U.S. and U.K. exchanges). Competition significantly reduces profitability, employment and, surprisingly, efficiency after privatisation, while creation of an independent regulatory agency significantly increases output. Mandating third party access to an incumbent - network is associated with a significant decrease in the incumbent - investment and an increase in employment. Retained government ownership is associated with a significant increase in leverage and a significant decrease in employment, while price regulation significantly increases profitability. Major efficiency gains result from better incentives and productivity, rather than from wholesale firing of employees and profitability increases appear to be caused by significant reductions in costs - rather than price increases. On balance, we conclude that the financial and operating performance of telecommunications companies improves significantly after privatisation, but that a sizeable fraction of the observed improvement results from regulatory changes - alone or in combination with ownership changes - rather than from privatisation alone.
Single-Nucleotide Polymorphisms of TNFA and IL 1 in Allergic Rhinitis

Background: Allergic rhinitis is a complex polygenic disorder of the upper respiratory tract. Given that proinfl ammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL) 1 seem to play a role in the development of allergic rhinitis, we evaluated the associations between various single-nucleotide polymorphisms (SNPs) of the TNF and IL1 genes in a case-control study. Methods: The study population comprised 98 patients with allergic rhinitis. Genotyping was performed using polymerase chain reaction with sequence-specifi c primers for 2 TNFA promoter variants (rs1800629 and rs361525), 1 variant in the promoter region of IL1A (rs1800587), 2 SNPs in the IL1B gene (rs16944 and rs1143634), 1 variant in the IL1 receptor (rs2234650), and 1 in IL1RA (rs315952). Results: Patients who were homozygous for the T allele of rs16944 in IL1B had an 8.1-fold greater risk of allergic rhinitis than those with the C allele. In TNFA, a signifi cant relationship was also detected between rs1800629 and rs361525 and allergic rhinitis. Except for rs1800587 in IL1A and rs315952 in IL1RA, signifi cant differences were found between the patient and control groups for all other SNPs. Conclusions: We found that allelic variants in the TNFA and IL1 genes were not only associated with the risk of developing allergic rhinitis, but also affected disease course and severity.
Intermittent (every-other-day) drinking induces rapid escalation of ethanol intake and preference in adolescent and adult C57BL/6J mice.

BACKGROUND Using adult C57BL/6J (B6) mice, we previously developed a procedure that causes a progressive increase in ethanol intake and preference (i.e., alcohol escalation effect) following weekly (intermittent) access to ethanol (Melendez et al., 2006). A limitation of this procedure is that it requires many weeks of testing, which limits its use to study ethanol escalation (i.e., binge-like drinking) during adolescence. Previous studies have shown that intermittent every-other-day (EOD) access to ethanol is sufficient to induce ethanol escalation in rats. The objective of this study was to verify whether EOD access is sufficient to induce escalated levels of ethanol intake and preference in adult and adolescent B6 mice. METHODS Male B6 mice received free-choice 24-hour access to 15% ethanol and water on an EOD or daily basis for 2 weeks. Food and water were available at all times. Using adult mice, Experiment 1 characterized the induction of ethanol escalation following EOD access at 6 (i.e., drinking in the dark) and 24-hour intervals, whereas Experiment 2 determined whether daily drinking reverses escalation induced by EOD drinking. Experiment 3 compared ethanol-drinking capacity following daily versus EOD drinking in adolescent (P30-45) and adult (P70-85) mice. RESULTS Experiment 1 revealed that EOD drinking leads to a significant (nearly 2-fold) increase in ethanol intake and preference over mice given daily access. Experiment 2 demonstrated that EOD-elicited escalation is blocked and subsequently reversed following daily drinking. Experiment 3 revealed that ethanol drinking was greater in adolescent mice compared with adults following daily drinking and EOD (escalated) drinking. Although the escalated levels of ethanol intake were greater in adolescent mice, the rate or onset of escalation was comparable between both age-groups. CONCLUSIONS This study is the first to demonstrate that EOD drinking leads to escalation of ethanol intake and preference in adolescent and adult mice. Moreover, our results indicate that daily ethanol reverses ethanol escalation induced by intermittent drinking. The study also revealed that adolescent mice have a greater capacity to drink ethanol under both daily (controlled) and EOD (escalated) conditions, which further supports the notion of adolescent's susceptibility to heavy drinking.
Isolation and Biological and Molecular Characterization of Toxoplasma gondii from Canine Cutaneous Toxoplasmosis in Brazil

ABSTRACT Cutaneous toxoplasmosis is a rare manifestation. This study represents a case report of an immunosuppressed dog that developed nodular dermal lesions caused by Toxoplasma gondii. The isolate (TgDgBr20) was characterized as mouse virulent and was genotyped as type BrI (ToxoDB genotype 6) using PCR-restriction fragment length polymorphism (RFLP) and as Africa 1 through microsatellite analysis.
Two-year multicomprehensive secondary prevention program: favorable effects on cardiovascular functional capacity and coronary risk profile after acute myocardial infarction

Background Cardiac rehabilitation includes interventions aimed at facilitating physical, psychological and emotional recovery following the acute phase of myocardial infarction (AMI). To date, optimal cardiac rehabilitation program duration and frequency of patient contact has yet to be identified. Objective The present study was performed to evaluate the effects of two different strategies of secondary prevention (2 years, multifactorial continued educational and behavioral intervention versus usual care) implemented into a cardiac rehabilitation setting on several cardiovascular endpoints indicating cardiovascular functional exercise capacity and coronary risk profile in patients with recent AMI. Methods This was a prospective randomized study including 52 postinfarction patients. Initially, all patients were enrolled in a 3-month outpatient cardiac rehabilitation program. Thereafter, they were randomly subdivided into two groups (I = intervention group; C = control group), each composed of 26 patients, and followed for 24 months. Results At the end of the 3-month outpatient cardiac rehabilitation program, both groups showed a significant (P < 0.05) improvement in cardiopulmonary parameters (maximal oxygen consumption, maximal workload) and in cardiovascular risk profile (BMI, lipid profile). During the 24-month study period, group I showed stabilization or even improvement (P < 0.05) of both cardiopulmonary parameters and cardiovascular risk profile, whereas group C patients showed a deterioration or significant impairment (P < 0.05) of the same parameters. Clinical events occurred in 27% of patients in the control group (n = 7) and in 11% in the training group (n = 3) (P < 0.05). Conclusion Long-term, multifactorial educational and behavioral intervention maintained for 2 years in a multicomprehensive cardiac rehabilitation setting represents a valid strategy for improving long-term cardiovascular functional capacity and cardiovascular risk profile in postinfarction patients.
A projected gradient method for optimization over density matrices

An ensemble of quantum states can be described by a Hermitian, positive semidefinite and unit trace matrix called density matrix. Thus, the study of methods for optimizing a certain function (energy, entropy) over the set of density matrices has a direct application to important problems in quantum information and computation. We propose a projected gradient method for solving such problems. By exploiting the geometry of the feasible set, which is the intersection of the cone of Hermitian positive semidefinite matrices with the hyperplane defined by the unit trace constraint, we describe an efficient procedure to compute the projection onto this set using the Frobenius norm. Some important applications, such as quantum state tomography, are described and numerical experiments illustrate the effectiveness of the method when compared to previous methods based on fixed-point iterations or semidefinite programming.