Miracle-dz/UniFAR-FTUs huggingface dataset:
A preclinical and clinical rationale for quetiapine in mood syndromes

The main objective of this review is to discuss results from preclinical studies that aim to elucidate the putative mechanistic basis of the antidepressant action of quetiapine. Results from pivotal, randomized clinical trials in bipolar depression are also briefly reviewed. The authors conducted a PubMed search of all English-language articles published between January 1990 and December 2006. The key search term was quetiapine paired with: serotonin, dopamine, noradrenaline, glutamate, γ-aminobutyric acid, signal transduction, neurogenesis, oxidative stress, glucocorticoid, antidepressant, major depressive disorder, bipolar disorder and randomized controlled trial. The search was augmented with a manual review of relevant article reference lists. Articles selected for review were based on author consensus, adequacy of sample size, the use of standardized experimental procedures, validated assessment measures and overall manuscript quality. Quetiapine enhances central serotonergic neurotransmission via its high affinity for serotonergic receptors (e.g., 5-HT2A receptor antagonism and partial agonistic activity at the 5-HT1A receptor). Activation of the 5HT1A receptor results in an increase in prefrontal cortex dopaminergic neurotransmission. Affinity for the α2-adrenoceptor mediates a relative increase in extracellular noradrenergic release in the prefrontal cortex. Emerging evidence indicates that quetiapine's principal, active, human plasma metabolite, N-desalkyl quetiapine, has high affinity for, and is a potent inhibitor of, the noradrenergic transporter. This latter finding is a point of commonality with other conventional antidepressant agents and may differentiate quetiapine from other atypical antipsychotics. Activity at other intracellular targets (e.g., signal transduction pathways and nerve growth transcription factors), neurotransmitters, inflammatory and oxidative stress networks, and endocrine systems may also mediate the antidepressant effects of quetiapine. The in vitro pharmacodynamic profile of quetiapine is predictive of antidepressant activity in mood syndromes. Available clinical evidence has established quetiapine as an effective monotherapy in bipolar depression.
Determinants of Public Support for International Climate Finance in Donor Countries

The adoption of the Warsaw mechanism on loss and damage has again highlighted the North-South divide in the part of the UNFCCC negotiations dealing with international climate finance. Current estimates put required funding from rich countries at 50 to 100 billion Euros per year to induce non-Annex I countries to take on greenhouse gas limitation commitments and to assist highly vulnerable countries. Results from survey-embedded conjoint experiments can help policy-makers anticipate opportunities and pitfalls in designing large-scale climate funding schemes. We implemented such experiments in the United States and Germany to better understand what institutional design characteristics are likely to garner more public support for climate funding among citizens in key developed countries. We find that climate funding receives more public support if it flows to efficient governments, funding decisions are made jointly by donor and recipient countries, funding is used both for mitigation and adaptation, and other donor countries contribute a large share. Contrary to what one might expect, climate change damage levels, income, and emissions in/of potential recipient countries have no significant effect on public support. These findings suggest that finance mechanisms that focus purely on compensating developing countries, without contributing to the global public good of mitigation, will find it hard to garner public support.
Familial Clustering of Tonsillectomies and Adenoidectomies

Eighty-one children undergoing tonsillectomies and adenoidectomies (T and A) were compared with a control group of 88 hospital patients. A significantly higher incidence of prior T and A was found to have been performed on the siblings and parents of the T and A group than the controls. Environmental, genetic or attitudinal factors could be responsible for this familial clustering.
Optimization and design sensitivity of SISO and MISO wireless power transfer systems

The maximum achievable power transfer efficiency (PTE) of a multi-transmitter wireless power transfer (WPT) system can be obtained directly from its impedance matrix and the load at the receiver through closed-form expressions. This opens the way to both evaluating the performance of a system or an operating mode as well as relating permissible performance degradation to component tolerances. The latter also gives insight into the complexity of realizing and optimally operating a particular system in practice.
Balancing Competing Logics in For-Profit Social Enterprises: A Need for Hybrid Governance

Abstract This paper reports a case study of a for-profit award-winning social enterprise that faced bankruptcy two years after founding. The findings show that the firm's overemphasis on the social employment logic and the increasing disregard of the commercial market logic led to the failure. This imbalance in response to the two competing logics was fuelled by the entrepreneurs’ strong social values, stakeholder reinforcement, and lack of appropriate governance. This study shows that hybrid organizations need to pay attention to the governance of the tension between competing demands inside as well as outside the organization. Hybrid organizations therefore require a hybrid governance model. By presenting a case of failure of a social enterprise, the paper counterbalances the dominance of optimistic idealism in social entrepreneurship literature.
Three Explanations of Marital Status Differences in Suicide Rates: Social Integration, Marital Status Integration, and the Culture of Suicide

Our first goal is to link empirical measures of three theoretical explanations of marital status differences to the variation in male and female standardized suicide difference coefficients SSDCs in 12 developed countries, circa 1960. We include predictors of Durkheim's social integration hypothesis, Gibbs and Martin's concept of marital status integration, and norms on suicide acceptability. All three are significantly related to variation in male and female SSDCs. The second goal is to examine how our empirical indicators impact age-specific differences in the male minus female SSDC—differences that vary by age in all 12 of our study populations. The strongest predictor of these differences is the male minus female difference in the percent married.
Numerical simulation of flow field between gas turbine blades, GE F9 model

In this paper flow field between the first-stage of gas turbine blades, GE F9 model is simulated and analysed using Computational Fluid Dynamics. Two-dimensional model is considered and by applying appropriate boundary conditions for both steady and unsteady state cases are solved. Due to complexity of flow field Reynolds Stress Model is used as a turbulence model. Finally, flow pattern is achieved and shows that pressure in the stationary blades (Nozzles) and the moving blades is reduced and velocity increases in the nozzles and decreases in the blades. It is be noted that complete grid study is done to achieve grid-independent solution.
Effect of neu differentiation factor isoforms on neonatal oligodendrocyte function

Previous studies have suggested that neu differentiation factor (NDF), a member of the neuregulin (NRG) family of growth factors, may regulate the development of PNS and CNS glial cells. There is limited information concerning the potential role of NDF on the development of neonatal (immature) oligodendrocytes (OLG) into adult OLG. We now report the effect of the two major isoform families of NDF (NDFα and NDFβ) on the development of cultured rat neonatal OLG. Immunocytochemical and western blot analyses of neonatal OLG using anti‐erb‐B antibodies revealed that these immature OLG express all four members of NRG (erb‐B) receptors. Treatment of neonatal OLG with varying concentrations of either NDFα or NDFβ did not have a mitogenic effect on cultured neonatal OLG. Pretreatment of immature OLG with either of the NDF isoforms also did not influence the subsequent mitogenicity of other known OLG mitogens. However, treatment of neonatal OLG with either isoform of NDF influenced the survival of these cells by protecting the cells from apoptosis. Additionally, treatment of neonatal OLG with either NDFα or NDFβ resulted in more extensive process formation compared to control, non‐treated OLG. J. Neurosci. Res. 50:755–768, 1997. © 1997 Wiley‐Liss, Inc.
Epidemiology of left ventricular hypertrophy in hypertension: implications for the clinic

ABSTRACT Introduction: Left ventricular hypertrophy (LVH) is a common complication to hypertension, indicating the presence of hypertensive heart disease, which puts the patient at a very high risk for subsequent clinical cardiovascular events like sudden cardiac death, stroke, myocardial infarction and heart failure. Areas covered: The epidemiology of LVH has changed in recent years as a consequence of the development of new diagnostic tools and demographic changes in hypertensive populations. Expert commentary: In individual hypertensive patients, the presence and type of LVH and associated systolic and diastolic myocardial dysfunction is modified by the co-presence of other cardiovascular risk factors and comorbidities and as well as activation of the reninangiotensin-aldosterone system and other molecular mechanisms involved in LVH pathophysiology. The purpose of this review is to give a clinical update on LVH in hypertension.
Towards Decision Making Systems from Data Ethnography for Agent-Based Simulation using Computational Intelligence

Representing human decisions is of fundamental importance in agent-based models. To describe the individual decision-making of an Agent-Based Simulation (ABS), is recommended that should include the implementation details of subjects and objects of decisions and the multiple levels of decisions making. Decisions rules and uncertainty could be relevant to the problem rationality and, therefore, necessary for the decision-making system. On this work, we overview computational intelligence to propose approaches to ABS and ethnography. The human decision systems could be explored from an ethnography point of view, due data mining qualitative sources and discovering patterns that could represent cultural aspects of a group of individuals. We show how text analysis could be used to discover and build decision-making systems and simulate human decisions on ABS.
Activating communities for health promotion: a process evaluation method.

OBJECTIVES To date, evaluations of community-based prevention programs have focused on assessing outcomes, not the process of organizing communities for health promotion. An approach was developed to analyze community organization efforts aimed at advancing community health objectives. These organizational processes are referred to as community activation. METHODS Information was gathered from 762 informants through a key informant survey conducted in 28 western communities. The data collected included informant ratings of community activation and information about interorganizational activities analyzed through network analytic techniques. RESULTS Activation levels, as measured by informant ratings, varied across communities. Program coordination, as measured by network analysis, occurred, on average, approximately 30% of the time. Higher income communities tended to be more activated than lower income communities. CONCLUSIONS There is a widely recognized need for improved information about health-related community organization activities. It appears possible to gather such information through key informant surveys and to develop measures of community organization status that can be used in the evaluation of community health promotion programs.
The concept of the quiescent centre and how it found support from work with X-rays. II. The molecular aftermath

With the advent of the molecular era of plant biology, the location and activity of the quiescent centre (QC) within the root meristem were reappraised with respect to the transport and distribution of hormones, especially auxin. Later, when methods for probing gene activity became established, the genes and their regulators that were identifiably specific to the QC were also actively studied, at first in relation to the establishment of the root and its QC in the proembryo and later in relation to the interaction of the QC with neighbouring meristem cells. Auxin distribution in and around the QC was found to be associated with co-located oxidative enzymes which established a redox system within the root apex. This system is pivotal in both maintenance of quiescence and the activation of cell proliferation in the QC via the generation of reactive oxygen species (ROS) and their interaction with mitochondria. These and other features of QC biology are summarised.
The Herpes Simplex Virus Type 1 UL17 Gene Encodes Virion Tegument Proteins That Are Required for Cleavage and Packaging of Viral DNA

ABSTRACT Previous studies have suggested that the UL17 gene of herpes simplex virus type 1 (HSV-1) is essential for virus replication. In this study, viral mutants incorporating either a lacZexpression cassette in place of 1,490 bp of the 2,109-bp UL17 open reading frame [HSV-1(ΔUL17)] or a DNA oligomer containing an in-frame stop codon inserted 778 bp from the 5′ end of the UL17 open reading frame [HSV-1(UL17-stop)] were plaque purified on engineered cell lines containing the UL17 gene. A virus derived from HSV-1(UL17-stop) but containing a restored UL17 gene was also constructed and was designated HSV-1(UL17-restored). The latter virus formed plaques and cleaved genomic viral DNA in a manner indistinguishable from wild-type virus. Neither HSV-1(ΔUL17) nor HSV-1(UL17-stop) formed plaques or produced infectious progeny when propagated on noncomplementing Vero cells. Furthermore, genomic end-specific restriction fragments were not detected in DNA purified from noncomplementing cells infected with HSV-1(ΔUL17) or HSV-1(UL17-stop), whereas end-specific fragments were readily detected when the viruses were propagated on complementing cells. Electron micrographs of thin sections of cells infected with HSV-1(ΔUL17) or HSV-1(UL17-stop) illustrated that empty capsids accumulated in the nuclei of Vero cells, whereas DNA-containing capsids accumulated in the nuclei of complementing cells and enveloped virions were found in the cytoplasm and extracellular space. Additionally, protein profiles of capsids purified from cells infected with HSV-1(ΔUL17) compared to wild-type virus show no detectable differences. These data indicate that the UL17 gene is essential for virus replication and is required for cleavage and packaging of viral DNA. To characterize the UL17 gene product, an anti-UL17 rabbit polyclonal antiserum was produced. The antiserum reacted strongly with a major protein of apparent M r 77,000 and weakly with a protein of apparent M r 72,000 in wild-type infected cell lysates and in virions. Bands of similar sizes were also detected in electrophoretically separated tegument fractions of virions and light particles and yielded tryptic peptides of masses characteristic of the predicted UL17 protein. We therefore conclude that the UL17 gene products are associated with the virion tegument and note that they are the first tegument-associated proteins shown to be required for cleavage and packaging of viral DNA.
hOGGl Ser326Cys polymorphism, interaction with environmental exposures, and gastric cancer risk in Japanese populations

Oxidative DNA damage caused by reactive oxygen species (ROS) generated by Helicobacter pylori (H. pylori) infection or smoking may be a cause of gastric cancer development. 8‐Hydroxydeoxyguanine (8‐OHdG) formation is one of the most common types of oxidative DNA damage, while human oxoguanine glycosylase 1 (hOGGl) is responsible for repairing 8‐OHdG lesions. Among several hOGGl gene polymorphisms, the SerCys polymorphism at position 326 is related to biological function. To investigate the association between Ser326Cys hOGGl polymorphism and gastric cancer in relation to the potential risk factors of gastric cancer and antioxidant dietary or nutrient intakes, we conducted a case‐control study with 142 histologically‐confirmed gastric cancer cases and 271 age, sex‐matched healthy controls in Japanese populations. Overall, neither the hOGG1 Ser/Cys nor the Cys/Cys genotype was associated with risk of gastric cancer, compared with the Ser/Ser genotype. A significant interaction was observed between hOGGl Ser/Cys or Cys/Cys genotype and atrophic gastritis (P for interaction =0.03). No significant interaction was found between hOGGl genotype and antioxidant dietary or nutrient intakes. The results of the present study suggest that patients with atrophic gastritis in conjunction with the hOGGl Cys allele might have a higher susceptibility to gastric cancer.
The effect of captopril and losartan on the electrophysiology of myocardial cells of myocardial ischemia rats.

OBJECTIVE This study aims to investigate the effect of captopril and losartan on the electrophysiology of myocardial cells parameters in ventricular vulnerable period and effective refractory period of myocardial ischemia rats. METHODS 96 wistar rats were enrolled in the study and divided into six groups: Captopril myocardial ischemia group, losartan myocardial ischemia group, myocardial ischemia control group, captopril normal group, losartan normal group and normal control group (n=16). We observed morphological changes of myocardial tissue in each group. The cardiac electrophysiological parameters in effective refractory period of each group were measured. Creatine kinase (CK), alanine aminotransferase (GOT), lactate dehydrogenase (LDH), the expression of Cardiotrophin 1 (CT-1) and malonaldehyde (MDA) were detected. RESULTS Compared the losartan and captopril group with the control group, (P<0.05). Losartan and captopril can shorten the ventricular vulnerable period of the normal group and ischemic group. There was no interaction effect between losartan and captopril group and the acute myocardial ischemia group. The effect of losartan and captopril on time window in ventricular vulnerable period showed that compared with the control group (P<0.05). Losartan and captopril had a significant effect on prolonged effective refractory period of normal and ischemic rats. There was no interaction effect between losartan and captopril group and the acute myocardial ischemia group. Compared with the myocardial ischemia control group, CK, GOT, LDH and MDA decreased in captopril and losartan myocardial ischemia groups (P<0.05). CONCLUSION Losartan and captopril had a significant effect on prolonged effective refractory period and shorten ventricular vulnerable period, they can also effectively prevent arrhythmias.
Human endogenous retrovirus HERV‐K(HML‐2) activity in prostate cancer is dominated by a few loci

Increased expression of human endogenous retroviruses, especially HERV‐K(HML‐2) proviruses, has recently been associated with prostate carcinoma progression. In particular, a HML‐2 locus in chromosome 22q11.23 (H22q) is upregulated in many cases. We therefore aimed at delineating the extent and repertoire of HML‐2 transcription in prostate cancer tissues and cell lines and to define the transcription pattern and biological effects of H22q.
Oral L-arginine improves endothelial function in healthy individuals older than 70 years

Ageing is associated with progressive endothelial dysfunction in normal humans. Flow-mediated dilation (FMD) of the brachial artery is impaired in elderly individuals with cardiovascular disease and vascular nitric oxide (NO) bioavailability is reduced. We investigated whether oral L-arginine, the substrate for NO synthesis, can improve impaired FMD in healthy very old people. In a prospective, double-blind, randomized crossover trial, 12 healthy old subjects (age 73.8 6 2.7 years) took L-arginine (8 g p.o. two times daily) or placebo for 14 days each, separated by a wash-out period of 14 days. FMD was determined by high-resolution ultrasound in the brachial artery during reactive hyperaemia. Baseline artery diameter was 3.88 6 0.18 mm. l-Arginine signifi cantly improved FMD (to 5.7 6 1.2%, p, 0.0001), whereas placebo had no effect (-0.25 6 0.7%; n.s.). After L-arginine, plasma levels of L-arginine increased signifi cantly (114.9 6 11.6 versus 57.4 6 5.0 mmol/l), but placebo had no effect. As NO synthesis can be antagonized by its endogenous inhibitor asymmetric dimethyl L-arginine (ADMA), we determined ADMA plasma concentrations, which were elevated at baseline in comparison to healthy middle-aged individuals (3.9 6 0.2 versus 1.0 6 0.1 mmol/l; p, 0.0001). ADMA remained unchanged during treatment, but L-arginine supplementation normalized the L-arginine/ADMA ratio (p, 0.05). We conclude that in healthy very old age endothelial function is impaired and may be improved by oral L-arginine supplementation, probably due to normalization of the L-arginine/ADMA ratio.
Uptake and Internalization of Exogenous Apolipoprotein E3 by Cultured Human Central Nervous System Neurons

Apolipoprotein E (apoE) has been confirmed as a risk factor for late-onset Alzheimer's disease (AD) and is associated with neurofibrillary tangles and senile plaques, the microscopic pathological characteristics of AD. There has been no direct evidence that human central nervous system neurons can take up and internalize exogenous apoE, which may be important in order for apoE to be involved in the development of the disease. This paper demonstrates by immunohistochemistry and confocal microscopy that cultured human brain neurons can take up and internalize exogenous recombinant human apoE3. We confirm that neurons express the low-density lipoprotein receptor-related protein (LRP) but do not express the low-density lipoprotein receptor. We also demonstrate that the LRP mediates the neuronal uptake of apoE.
Corticostriatal brain‐derived neurotrophic factor dysregulation in adult rats following prenatal stress

Prenatal stress represents a well‐established experimental protocol resembling some features of schizophrenia, including deficits in social interactions, disruption of prepulse inhibition and enhanced response to psychomotor stimulants. In order to evaluate molecular changes that could participate in long‐lasting effects on brain function, we analysed the effects of prenatal stress on the expression of brain‐derived neurotrophic factor (BDNF), an important molecular determinant of synaptic plasticity and cellular homeostasis, in adult male rats under basal conditions as well as in response to a chronic stress. The main finding is that BDNF expression is reduced in the prefrontal cortex and striatum of prenatally stressed rats. Furthermore, when exposed to chronic stress in adulthood, these rats display an altered regulation of BDNF expression in these brain structures, implying that adverse life events during gestation may interfere with the expression and function of this neurotrophin at adulthood in a region‐specific manner. The dysregulation of corticostriatal BDNF expression might thus contribute to permanent alterations in brain functions leading to heightened susceptibility to psychiatric disorders.