Miracle-dz/UniFAR-FTUs huggingface dataset:
Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling

Cerebral cavernous malformations (CCM) are frequent vascular abnormalities caused by mutations in one of the CCM genes. CCM1 (also known as KRIT1) stabilizes endothelial junctions and is essential for vascular morphogenesis in mouse embryos. However, cellular functions of CCM1 during the early steps of the CCM pathogenesis remain unknown. We show here that CCM1 represents an antiangiogenic protein to keep the human endothelium quiescent. CCM1 inhibits endothelial proliferation, apoptosis, migration, lumen formation, and sprouting angiogenesis in primary human endothelial cells. CCM1 strongly induces DLL4-NOTCH signaling, which promotes AKT phosphorylation but reduces phosphorylation of the mitogen-activated protein kinase ERK. Consistently, blocking of NOTCH activity alleviates CCM1 effects. ERK phosphorylation is increased in human CCM lesions. Transplantation of CCM1-silenced human endothelial cells into SCID mice recapitulates hallmarks of the CCM pathology and serves as a unique CCM model system. In this setting, the multikinase inhibitor Sorafenib can ameliorate loss of CCM1-induced excessive microvascular growth, reducing the microvessel density to levels of normal wild-type endothelial cells. Collectively, our data suggest that the origin of CCM lesions is caused by perturbed Notch signaling-induced excessive capillary sprouting, which can be therapeutically targeted.
An attempt at implementing a holistic inclusive development model: Insights from Malaysia's land settlement scheme

This paper examines the influences of Malaysia's Federation Land Development Authority (FELDA) scheme in fostering inclusive rural development. Based on the model of holistic inclusive development, the paper investigates the performance of FELDA from four perspectives: social development, industrialisation, modernisation and basic needs. The main findings of the study indicate that, to a large extent, the scheme has successfully stimulated both the social and economic development of the community. Nonetheless, establishing a strong trust, social cohesion and rapport between the public authorities and community remain the main challenges in determining the success of this state-led agenda. Moreover, keeping traditional values in the modern system will be the key principle for the sustainability of the programme if plans are made to adopt the scheme in other regions.
Evidence for a Role of Nitric Oxide in Hypovolemic Hemorrhagic Shock

Summary: Hypovolemic hemorrhagic shock was induced in rats by intermittently withdrawing blood from an iliac catheter for 20 min until mean arterial blood pressure (MAP) decreased to 30 mm Hg. Survival rate, survival time, plasma myocardial depressant factor (MDF) activity, MAP, and microscopic gastric alterations were then evaluated. NG-nitro-L-arginine methyl-ester (L-NAME), a selective inhibitor of nitric oxide (NO) production from L-arginine, was injected intravenously (i.v.) after the bleeding was discontinued. Untreated hemorrhagic shocked rats died in 27 ± 3.3 min, had enhanced plasma activity of MDF, and exhibited hemorrhagic infiltrates in gastric fundus mucosa. L-NAME (5 and 10 mg/kg) significantly increased survival rate and time, blunted the increase in plasma MDF activity, and protected against the gastric lesions induced by hemorrhagic hypovolemic shock. All these protective effects were reversed by a bolus of L-arginine (30 mg/kg/i.v.), given 2 min after administration of L-NAME. Our findings suggest that NO production plays an important role in the pathophysiology of hemorrhagic shock.
Neuropeptide Y inhibits potassium‐stimulated glutamate release through Y2 receptors in rat hippocampal slices in vitro

1 We investigated the effects of neuropeptide Y (NPY), peptide YY (PYY), NPY13–36, NPY18–36, [Leu31][Pro34]NPY and of pancreatic polypeptide Y (PPY) on calcium‐dependent, potassium‐stimulated glutamate release in superfused rat hippocampal slices. 2 NPY, PYY and the Y2 receptor agonist NPY13–36 equipotently inhibited the release of glutamate. The half‐maximal response was observed at about 10 nm in a dose‐dependent manner (3 to 100 nm). Maximal inhibition of 50 to 60% was obtained at 100 nm. At higher concentrations of the peptides (300 nm and 1 μm) this inhibition was partially or entirely reversed. Porcine NPY13–36 and NPY18–36, inhibited glutamate release by about 44% at 100 nm. 3 The specific Y1 receptor agonist, [Leu31][Pro34]NPY, caused an insignificant increase in glutamate release at 100 to 300 nm concentrations. PPY had no effect on potassium‐evoked glutamate release in hippocampal slices at concentrations of 30 nm to 1 μm. 4 The experiments support previous electrophysiological data. They suggest a potent inhibitory action of NPY through NPY‐Y2 receptors on the release of the excitatory amino acid glutamate in rat hippocampus. Especially under conditions of increased NPY synthesis, such as in epilepsy, this mechanism may be of pathophysiological relevance.
[Diagnosis of acute coronary syndrome].

The acute coronary syndrome (ACS) is one of the most frequent differential diagnoses in emergency medicine. The causal mechanism of the ACS most often is an atherosclerotic plaque rupture. The differential diagnosis of ACS is guided by the clinical symptom of chest discomfort. The diagnosis is based on the electrocardiographic, biomarker and imaging findings before targeted therapy can be initiated. Over the last years we have witnessed breakthroughs in imaging techniques and the application of biomarkers such as highly sensitive or ultrasensitive cardiac troponin assays. They permit an early and sensitive diagnosis of ACS. Furthermore, they exhibit a high negative predictive value for a safe rule-out. Trained personnel and optimized structures in chest pain units constitute optimal conditions for a guideline conform therapy of patients with ACS. The number of certified chest pain units in Germany has constantly been increasing.
What Is Health Communication and How Does It Affect the HIV/AIDS Continuum of Care? A Brief Primer and Case Study From New York City

Abstract:This article responds to key questions related to health communication that are commonly asked in the HIV/AIDS arena: “What is health communication? ”; “What is its role beyond HIV prevention? ”; and “How can it be used to achieve better HIV/AIDS outcomes? ” We review how communication scientists think about their own discipline and build on a basic definition of communication as a fundamental human process without which most individual, group, organizational, and societal activities could not happen, including how people think about and respond to health issues such as HIV and AIDS. Diverse factors and processes that drive human behavior are reviewed, including the concept of ideation (what people know, think, and feel about particular behaviors) and the influence of communication at multiple levels of a social ecological system. Four main functions of communication—information seeking and delivery, persuasion, social connection and structural/cultural expression and maintenance—are linked to a modified version of the Department of Health and Human Services Continuum of Care and are used to conceptualize ways in which communication can achieve better HIV/AIDS outcomes. The article provides examples of how communication complements other types of interventions across the HIV/AIDS continuum of care and has effects on HIV-related knowledge, attitudes, social norms, risk perceptions, service delivery quality, and behavioral decisions that affect if and when the virus is transmitted, when and where testing and care are sought, and how well adherence to antiretroviral therapy is maintained. We illustrate this approach with a case study of HIV/AIDS communication conducted by the New York City Health Department during 2005–2013.
Modification of Surface Potential of Silicon by Organic Molecules

The possibility of using an organic layer for controlling surface potential was investigated. The organic layer was formed by immersion in quinhydrone/methanol (QM) solution at room temperature. Surface passivation effects were estimated by lifetime measurements using the microwave photoconductive decay (mu-PCD) method, and the surface condition was estimated by attenuated-total-reflection Fourier transform infrared (ATR-FTIR) measurement. Surface passivation effects due to the organic layer were clearly demonstrated. An increase in the lifetime of the wafer under illumination was observed. Charge trappings at the organic layer/silicon interface and in the organic layer were important for reducing surface recombination velocity. The organic layer can be formed at low temperature, and the formation process is simple. Hence, the application of an organic layer to silicon solar cells is expected for surface passivation films
The Motivation Behind Serial Sexual Homicide: Is It Sex, Power, and Control, or Anger? *

ABSTRACT: Controversy exists in the literature and society regarding what motivates serial sexual killers to commit their crimes. Hypotheses range from the seeking of sexual gratification to the achievement of power and control to the expression of anger. The authors provide theoretical, empirical, evolutionary, and physiological support for the argument that serial sexual murderers above all commit their crimes in pursuit of sadistic pleasure. The seeking of power and control over victims is believed to serve the two secondary purposes of heightening sexual arousal and ensuring victim presence for the crime. Anger is not considered a key component of these offenders' motivation due to its inhibitory physiological effect on sexual functioning. On the contrary, criminal investigations into serial sexual killings consistently reveal erotically charged crimes, with sexual motivation expressed either overtly or symbolically. Although anger may be correlated with serial sexual homicide offenders, as it is with criminal offenders in general, it is not causative. The authors further believe serial sexual murderers should be considered sex offenders. A significant proportion of them appear to have paraphilic disorders within the spectrum of sexual sadism. “sexual sadism, homicidal type” is proposed as a diagnostic subtype of sexual sadism applicable to many of these offenders, and a suggested modification of DSM criteria is presented.
Effect of fertilization antigen (FA‐1) DNA vaccine on fertility of female mice

Vaccination of female mice with recombinant fertilization antigen (FA‐1) causes a long‐term reversible contraceptive effect. Also, a DNA vaccine based upon a dodecamer sequence YLP12 present in sperm causes a reduction in fertility. In the present study, the effects of FA‐1 DNA vaccine alone, and FA‐1 and YLP12 DNA vaccines together were examined. FA‐1 495‐bp DNA was cloned into pVAX1 vector to prepare the DNA vaccine. Four groups of female mice were immunized intradermally by using a gene gun with FA‐1 DNA, FA‐1 DNA + YLP12 DNA, FA‐1 DNA + YLP12 DNA mixed with exogenous synthetic CpG oliogodeoxynucleotide (ODN), or vector DNA alone, respectively. Vaccination with all three formulations caused a significant reduction in fertility, with FA‐1 DNA + YLP12 DNA mixed with exogenous synthetic CpG ODN showing the highest reduction. Vaccination with all three formulations raised antibody response in both the sera as well as locally in the vaginal tract, with ODN mixed group demonstrating the highest titers. There was no antibody response in the mice injected with the vector alone. In sera, the highest titers were obtained for the IgG class for all vaccine formulations followed by the IgA class. In vaginal washing, the highest titers were obtained by the IgA class followed by the IgG class. Within the IgG class, the titers for the IgG2a subclass were significantly greater than the IgG1 subclass. The immunocontraceptive effects were long‐lasting over 1 year of the observation period and increased with time. These novel findings indicate that the intradermal immunization with a sperm‐specific FA‐1 DNA vaccine causes a long‐term circulating and local immune response resulting in immunocontraceptive effects in female mice. The anti‐fertility effects were enhanced when FA‐1 DNA vaccine was combined with YLP12 DNA vaccine and injected with ODN. Mol. Reprod. Dev. 73: 1473–1479, 2006. © 2006 Wiley‐Liss, Inc.
The effect of reactive oxygen species on equine sperm motility, viability, acrosomal integrity, mitochondrial membrane potential, and membrane lipid peroxidation.

The objective of this study was to examine the influence of reactive oxygen species (ROS), generated through the use of the xanthine (X)-xanthine oxidase (XO) system, on equine sperm motility, viability, acrosomal integrity, mitochondrial membrane potential, and membrane lipid peroxidation. Equine spermatozoa were separated from seminal plasma on a discontinuous Percoll gradient, and spermatozoa were incubated with 0.6 mM X and 0.05 U/mL XO for 30 minutes. Catalase (150 U/mL), superoxide dismutase (SOD, 150 U/mL), or glutathione (GSH, 1.5 mM) were evaluated for their ability to preserve sperm function in the presence of the induced oxidative stress. At the end of the 30-minute incubation, sperm motility was determined by computer-assisted semen analysis. Viability and acrosomal integrity were determined by Hoechst-Pisum sativum staining, and mitochondrial membrane potential was determined by staining with JC-1. Incubation with the X-XO system led to a significant (P < .01) increase in hydrogen peroxide production and an associated decrease (P < .01) in motility parameters. Total motility was significantly (P < .01) lower in the presence of X-XO compared with the case of the control (29%+/-9% vs 73%+/-1%, respectively). Catalase, but not SOD, prevented a decline in motility secondary to oxidative stress (71%+/-4% vs 30%+/-3%, respectively). The addition of glutathione had an intermediate effect in preserving sperm motility at the end of the 30-minute incubation (53%+/-3%). No influence of X-XO could be determined on viability, acrosomal integrity, or mitochondrial membrane potential. In order to promote lipid peroxidation, samples were incubated with ferrous sulfate (0.64 mM) and sodium ascorbate (20 mM) for 2 hours after the X-XO incubation. No increase in membrane lipid peroxidation was detected. This study indicates that hydrogen peroxide is the major ROS responsible for damage to equine spermatozoa. The decrease in sperm motility associated with ROS occurs in the absence of any detectable decrease in viability, acrosomal integrity, or mitochondrial membrane potential or of any detectable increase in lipid peroxidation.
A Theory of Transformative Agency in Linked Social-Ecological Systems

We reviewed the literature on leadership in linked social-ecological systems and combined it with the literature on institutional entrepreneurship in complex adaptive systems to develop a new theory of transformative agency in linked social- ecological systems. Although there is evidence of the importance of strategic agency in introducing innovation and transforming approaches to management and governance of such systems, there is no coherent theory to explain the wide diversity of strategies identified. Using Holling's adaptive cycle as a model of phases present in innovation and transformation of resilient social- ecological systems, overlaid by Dorado's model of opportunity context (opaque, hazy, transparent) in complex adaptive systems, we propose a more coherent theory of strategic agency, which links particular strategies, on the part of transformative agents, to phases of system change.
Stimulation of IRS-1-associated Phosphatidylinositol 3-Kinase and Akt/Protein Kinase B but Not Glucose Transport by β1-Integrin Signaling in Rat Adipocytes*

The signal transduction pathway by which insulin stimulates glucose transport is not understood, but a role for complexes of insulin receptor substrate (IRS) proteins and phosphatidylinositol (PI) 3-kinase as well as for Akt/protein kinase B (PKB) has been proposed. Here, we present evidence suggesting that formation of IRS-1/PI 3-kinase complexes and Akt/PKB activation are insufficient to stimulate glucose transport in rat adipocytes. Cross-linking of β1-integrin on the surface of rat adipocytes by anti-β1-integrin antibody and fibronectin was found to cause greater IRS-1 tyrosine phosphorylation, IRS-1-associated PI 3-kinase activity, and Akt/PKB activation, detected by anti-serine 473 antibody, than did 1 nm insulin. Clustering of β1-integrin also significantly potentiated stimulation of insulin receptor and IRS-1 tyrosine phosphorylation, IRS-associated PI 3-kinase activity, and Akt/PKB activation caused by submaximal concentrations of insulin. In contrast, β1-integrin clustering caused neither a change in deoxyglucose transport nor an effect on the ability of insulin to stimulate deoxyglucose uptake at any concentration along the entire dose-response relationship range. The data suggest that (i) β1-integrins can engage tyrosine kinase signaling pathways in isolated fat cells, potentially regulating fat cell functions and (ii) either formation of IRS-1/PI 3-kinase complexes and Akt/PKB activation is not necessary for regulation of glucose transport in fat cells or an additional signaling pathway is required.
COL.diesis: Transforming Colour into Melody and Implementing the Result in a Colour Sensor Device

This paper represents a system which explores the reality of colour in relation to sound and dedicated firstly to blind people, the challenges they live with, their psychology and their emotions. It’s an exploration of the infinite range of colours that they have either never been able to see or that they have lost the possibility to see. The system developed is based on the concept of synesthesia: a ‘liaison’ between colour and sound, colour that becomes sound. This paper synthesizes a wider range of study regarding people with diverse psychological and movement conditions. It represents a new method of expression and of self development through music therapy and game, dedicated mainly to children aged between 5 and 13. Finally we conclude with a portable prototype device that has been validated and patented. It is capable of detecting colour and transforming it into sound: a colour sensor identifies colours and transforms this data into musical notes. The prototype is totally adaptable to the requirements of the end user meaning that the user can choose the best combination between colour and sound in order to improve their communication with the environment. We are now developing a mathematical theoretical background in order to formalize the correspondence between colour and musical space.
Anti - Corruption Crusade in a Post - Colonial State : Problems and Challenges

Endemic corruption has become an issue of major political and economic relevance in recent years. This has led to a resurgence of interest in analyzing the phenomenon and the diverse forms that it assumes in developing polities with an expectation that democratization and economic liberalization offer potential routes to dealing with the problem. As Nigeria moves towards her 51 st independence anniversary, the polity is at crossroads in its fight against graft. Aside from its internal battle to fight corruption, recent revelations on mega bribery scandals being perpetrated by the ruling elites have confirmed that corruption is a cancer that may stunt the nation’s growth. In spite of the effort s of the Economic and Financial Crime Commission (EFCC) and the Independent Corrupt Practices and other related Offences Commission (ICPC) stem the rising tide of corruption in the country. The socioeconomic menace has continued to maintain it’s upwards trend, especially among public servants and political appointees. Critiques of the anti-corruption agencies blame the ugly trend on the mode of operation and of the agencies, which according them should be restructured. Some observers have also put the threshold on the criminal justice system and call for the creation of a separate court with the jurisdiction to try all allegations of corruption. The paper examines in a thematic form the various forms and types of corruption. The article also identifies various reasons that inhibit the graft war in Nigeria and the implications for governance. The paper concludes by positing that the recent political history of corruption in Nigeria suggests that corruption is not new, and that, indeed, corrupt practices have been part and parcel of Nigerian politics from inception.
Footprint Analysis of the RAG Protein Recombination Signal Sequence Complex for V(D)J Type Recombination

ABSTRACT We have studied the interaction between recombination signal sequences (RSSs) and protein products of the truncated forms of recombination-activating genes (RAG) by gel mobility shift, DNase I footprinting, and methylation interference assays. Methylation interference with dimethyl sulfate demonstrated that binding was blocked by methylation in the nonamer at the second-position G residue in the bottom strand and at the sixth- and seventh-position A residues in the top strand. DNase I footprinting experiments demonstrated that RAG1 alone, or even a RAG1 homeodomain peptide, gave footprint patterns very similar to those obtained with the RAG1-RAG2 complex. In the heptamer, partial methylation interference was observed at the sixth-position A residue in the bottom strand. In DNase I footprinting, the heptamer region was weakly protected in the bottom strand by RAG1. The effects of RSS mutations on RAG binding were evaluated by DNA footprinting. Comparison of the RAG-RSS footprint data with the published Hin model confirmed the notion that sequence-specific RSS-RAG interaction takes place primarily between the Hin domain of the RAG1 protein and adjacent major and minor grooves of the nonamer DNA.
Wisconsin Card Sorting Test in chronic severe traumatic brain injury: factor structure and performance subgroups

Objective : The present study further investigated the factor structure of the WCST in traumatic brain injury and investigated the construct validity and relationships among scores through the use of cluster analysis. Design : Participants were 68 survivors of chronic severe TBI, living at a residential brain injury rehabilitation facility. Methods and procedures : Three sets of WCST scores were submitted to factor analysis; the regression factor scores based on the standard WCST were examined using cluster analysis. Results : Factor analysis of the WCST raw scores replicated the three-factor solution which has been previously reported. When t -scores were analysed, two-to-four-factor solutions could be justified. The cluster analysis identified four groups representing: (1) impaired response maintenance; (2) problem-solving deficits; (3) intact WCST performance; and (4) deficits in set shifting. Conclusions : The results support previous research indicating that the WCST is sensitive to three distinct cognitive processes: cognitive flexibility, problem-solving, and response maintenance. However, unlike the cognitive processes underlying WCST performance, the WCST scores representing these processes are not independent. The potential clinical relevance of these results is discussed.