Miracle-dz/UniFAR-FTUs huggingface dataset:
CNS Dopamine Transmission Mediated by Noradrenergic Innervation

The presynaptic source of dopamine in the CA1 field of dorsal hippocampus is uncertain due to an anatomical mismatch between dopaminergic terminals and receptors. We show, in an in vitro slice preparation from C57BL/6 male mice, that a dopamine (DA) D1 receptor (D1R)-mediated enhancement in glutamate synaptic transmission occurs following release of endogenous DA with amphetamine exposure. It is assumed DA is released from terminals innervating from the ventral tegmental area (VTA) even though DA transporter (DAT)-positive fibers are absent in hippocampus, a region with abundant D1Rs. It has been suggested this results from a lack of DAT expression on VTA terminals rather than a lack of these terminals per se. Neither a knockdown of tyrosine hydroxylase (TH) expression in the VTA by THsiRNA, delivered locally, by adeno-associated viral vector, nor localized pharmacological blockade of DAT to prevent amphetamine uptake into DA terminals, has any effect on the D1R synaptic, enhancement response to amphetamine. However, either a decrease in TH expression in the locus ceruleus (LC) or a blockade of the norepinephrine (NE) transporter prevents the DA-mediated response, indicating LC terminals can release both NE and DA. These findings suggest noradrenergic fibers may be the primary source of DA release in hippocampus and corresponding DA-mediated increase in synaptic transmission. Accordingly, these data imply the LC may have a role in DA transmission in the CNS in response to drugs of abuse, and potentially, under physiological conditions.
Genome-Wide Detection of Selective Signature in Chinese Holstein

Selective signatures in whole genome can help us understand the mechanisms of selection and target causal variants for breeding program. In present study, we performed Extended Haplotype Homozygosity (EHH) tests to identify significant core regions harboring such signals in Chinese Holstein, and then verified the biological significance of these identified regions based on commonly-used bioinformatics analyses. Results showed a total of 125 significant regions in entire genome containing some of important functional genes such as LEP, ABCG2, CSN1S1, CSN3 and TNF based on the Gene Ontology database. Some of these annotated genes involved in the core regions overlapped with those identified in our previous GWAS as well as those involved in a recently constructed candidate gene database for cattle, further indicating these genes under positive selection maybe underlie milk production traits and other important traits in Chinese Holstein. Furthermore, in the enrichment analyses for the second level GO terms and pathways, we observed some significant terms over represented in these identified regions as compared to the entire bovine genome. This indicates that some functional genes associated with milk production traits, as reflected by GO terms, could be clustered in core regions, which provided promising evidence for the exploitability of the core regions identified by EHH tests. Findings in our study could help detect functional candidate genes under positive selection for further genetic and breeding research in Chinese Holstein.
A grand theory of human nature and happiness

Purpose - The purpose of this paper is to offer a new theory of human nature to explain the happiness paradox of capitalism. Design/methodology/approach - It is argued that happiness crisis in capitalism stems from the lack of full understanding of human nature which is like a black box from which key assumptions in capitalist market system are derived. The author attempts to unlock this black box in order to understand the failure of capitalism in bringing happiness. Findings - As the success of capitalism comes from its partial understanding of human nature, its failure comes from its partial misunderstanding or exploitation of human nature. This leads to ignoring the needs and desires of certain elements of human nature for the sake of serving only the animal spirit and self-centric ego. The proposed new theory offers a new understanding of happiness and its determinants. Comparing the human body to a luxury recreational vehicle (RV) and the elements of human nature to the companions on this vehicle, the theory suggests that an individual cannot be truly happy if he or she listens only to one of his/her residents while disregarding the others. The new theory offers better explanation for the 2008 financial crisis and the happiness paradox in wealthy nations. It also provides an underlining framework for the existing happiness theories. Research limitations/implications - The new theory needs to be tested through empirical studies. Social implications - The paper theoretically argues that that authentic happiness is possible if individuals listen to the voices of all elements of human nature and try to fulfil their needs and desires in a balanced manner. Originality/value - The paper offers a new comprehensive theory on human nature.
Putting Rac1 on the Path to Glucose Uptake

In spite of numerous and key advances in our understanding of insulin signaling, the molecular basis for impaired insulin-stimulated glucose uptake underlying insulin resistance remains unclear. Because skeletal muscle accounts for the majority of glucose utilization in the postprandial insulin-regulated state, defects in insulin action in muscle can determine whole-body glucose utilization. In muscle and fat cells, overall similarities exist in the signals emanating from the insulin receptor that mobilize glucose transporter GLUT4 to the membrane. Importantly, defects in the signaling network connecting the activated insulin receptor to GLUT4 vesicles are of particular consequence to insulin resistance in muscle, where, unlike the case of fat cells, GLUT4 expression is not significantly reduced. The complex structural organization of muscle tissue and its associated cells have limited the molecular scrutiny of glucose uptake regulation. Instead, cell culture systems have been instrumental in revealing intricacies in the signals and traffic machinery mobilizing GLUT4 to the membrane. This signaling relay is initiated by insulin receptor substrate (IRS)-1 (and not IRS-2)–associated activation of class I phosphatidylinositol-3-kinase (PI3K). At this point, a signal bifurcation takes place, one arm leading to Akt2 activation, inhibition of its substrate AS160 (a GTPase-activating protein for Rabs) and consequent activation of its target Rab GTPases, which in skeletal muscle cells are Rab8A and Rab13 (1). The other arm leads to Rac1, a Rho-family GTPase (2,3) that enacts a dynamic cycle of cortical actin filament remodeling through the Arp2/3 complex and cofilin (4). Joint activation of these distinct signaling arms is required …
What School Factors Raise Achievement in the Third World?

Within industrialized countries, much is known about the relationship between schools’ material inputs or social practices and pupils’ achievement levels. Less is known about school effects in developing countries. In the Third World, the secular school is often a novel institution, operating in social settings where written literacy and formal socialization are relatively recent phenomena. Therefore, even schools with limited material resources appear to have a stronger impact on academic achievement, independent of pupils’ family background, than within industrialized countries. This optimistic claim is undercut, however, by limitations in how pupil background characteristics have been specified within empirical models. I review 60 (multivariate) studies conducted in the Third World that (a) report on the school’s aggregate influence on academic achievement versus the influence of family background and (b) assess the relative influence of alternative school inputs and organizational practices, pointing to more efficient strategies for raising pupil achievement. A framework is introduced to critically evaluate this existing empirical work and to suggest a second generation of questions that researchers might ask in the future.
Estimating the effect of cache misses on the performance of parallel applications using analytical models

In this paper a methodology to characterize the influence of cache misses on the performance of parallel applications is presented. This methodology is based on analytical models provided by the TIA framework. This framework obtains analytical models of given observable quantities by instrumenting the source code and applying model selection techniques. In particular, two metrics related with the performance are considered in this work: the number of cache misses and the elapsed time. Based on both models, the influence in terms of execution time due to the cache misses can be inferred. Two different versions of the parallel product of dense matrices are used as case of study.
Space-Time Analysis of Dynamic Scenes

The main objective of this research is to analyze video data of dynamic scenes based on their behavioral content. This can be done by extracting independent space-time components, and then analyzing and classifying them. Each spatio-temporal component spatially corresponds to a scene component having consistent motion (e.g., a static background scene versus a foreground moving object), and temporally corresponds to consistent behavior over time, i.e., a single action or event. In this thesis we explore two different approaches to extract and classify independent spacetime components. The first approach, which we refer to as the factorization approach or the subspace-based approach, is algebraic in its nature and is based on linear subspace constraints applied to optical flow information collected across multiple frames. To handle more complex activities, over longer temporal extents, we suggest a second approach, to which we refer as the statistical approach. This is a probabilistic approach which regards an event as a stochastic process. It tries to model actions/events by the distribution of motion related features. We have used the developed methods for various applications such as video browsing and indexing, action recognition and dynamic video synthesis. Our approaches and their applications are described in this thesis. My PhD thesis is submitted in the form of a “paper-thesis”, i.e., a thesis organized as a collection of papers. This document presents the general concepts of the thesis and places the attached papers in the appropriate context.
Stress-corrosion mechanisms in silicate glasses

The present review is intended to revisit the advances and debates in the comprehension of the mechanisms of subcritical crack propagation in silicate glasses almost a century after its initial developments. Glass has inspired the initial insights of Griffith into the origin of brittleness and the ensuing development of modern fracture mechanics. Yet, through the decades the real nature of the fundamental mechanisms of crack propagation in glass has escaped a clear comprehension which could gather general agreement on subtle problems such as the role of plasticity, the role of the glass composition, the environmental condition at the crack tip and its relation to the complex mechanisms of corrosion and leaching. The different processes are analysed here with a special focus on their relevant space and time scales in order to question their domain of action and their contribution in both the kinetic laws and the energetic aspects.
Networking, or What the Social Means in Social Media

This article questions the meaning of the social in social media. It does this by revisiting boyd and Ellison’s seminal paper and definition of social network sites. The article argues that social media are not so much about articulating or making an existing network visible. Rather, being social in the context of social media simply means creating connections within the boundaries of adaptive algorithmic architectures. Every click, share, like, and post creates a connection, initiates a relation. The network dynamically grows, evolves, becomes. The network networks. The social in social media is not a fact but a doing.
Drugs that prolong QT interval as an unwanted effect: assessing their likelihood of inducing hazardous cardiac dysrhythmias

Medicinal products that, as an unwanted effect, prolong the QT interval of the electrocardiogram (ECG) can trigger episodes of polymorphic ventricular dysrhythmias, called torsades de pointes, which occasionally culminate in sudden death. The accurate measurement of QT interval requires the adoption of appropriate criteria of recording, measurement and data processing. Traditionally, QT interval is standardised to a reference heart rate of 60 beats/min by using the Bazett algorithm. However, this correction method can bias observed QT intervals in either direction. The ECG reflects cardiac electrical currents generated by ions (Na+, K+ and Ca2+) entering and leaving the cytosol mainly via transmembrane channels. Na+ and Ca2+ carry inward depolarising currents (INa, ICa) whereas K+ carries outward repolarising currents (Ito, IKr, IKS and IK1). Sometimes, a prolonged QT interval is a desired drug effect but, more commonly it is not, and reflects abnormalities in cardiac repolarisation heralding torsades de pointes. Furthermore, the potential torsadogenic activity of drugs is favoured by concurrent cardiac risk factors (old age, female gender, bradycardia, electrolyte imbalances, cardiac diseases etc.) which reduce cardiac repolarisation reserve. The evaluation of the cardiac safety of drug candidates can be started by determining their potency as IKr blockers in cloned Human Ether-a-go-go Related Gene (HERG) channels expressed in mammalian cells. Compounds passing successfully this test (desirable cardiac safety index >> 30, calculated as ratio of IC50 against IKr over ED50 determined in an efficacy test) should be further investigated in other relevant human cardiac ion currents, in in vitro animal heart preparations and finally in in vivo pharmacodynamic models. The decision as to whether the potential benefit of a new drug outweighs the cardiac risk inherent in its therapeutic use should be made in the light of the condition that it is expected to treat and with reference to alternative drug therapies. If a drug represents a unique therapeutic advance, non-clinical and clinical signals of unsatisfactory cardiac safety may not constitute sufficient grounds to abandon its development. However, if the drug offers only marginal benefits over existing therapies, decisions concerning its possible development should be taken by corporate policy makers.
A Literature Review

AMELIA MARGARET ANNE MADSEN, BA, BS, RDCS Labor that begins between 20 and 37 weeks gestation is appropriately termed preterm labor. Some of the precipitating factors of preterm labor are changes in cervical status including dilatation and effacement. Until recently, a digital pelvic examination was considered the gold standard for evaluating cervical changes. Current research promotes the use of sonography for the prediction of preterm labor. It is essential for sonographers to become familiar with the various methods of cervical imaging including transabdominal, translabial, and transvaginal approaches. Each technique has its costs and benefits; however, a review of the current literature will show that the transvaginal method of cervical measurement is the most reliable.
Osteal macrophages promote in vivo intramembranous bone healing in a mouse tibial injury model

Bone‐lining tissues contain a population of resident macrophages termed osteomacs that interact with osteoblasts in vivo and control mineralization in vitro. The role of osteomacs in bone repair was investigated using a mouse tibial bone injury model that heals primarily through intramembranous ossification and progresses through all major phases of stabilized fracture repair. Immunohistochemical studies revealed that at least two macrophage populations, F4/80+Mac‐2−/lowTRACP− osteomacs and F4/80+Mac‐2hiTRACP− inflammatory macrophages, were present within the bone injury site and persisted throughout the healing time course. In vivo depletion of osteomacs/macrophages (either using the Mafia transgenic mouse model or clodronate liposome delivery) or osteoclasts (recombinant osteoprotegerin treatment) established that osteomacs were required for deposition of collagen type 1+ (CT1+) matrix and bone mineralization in the tibial injury model, as assessed by quantitative immunohistology and micro–computed tomography. Conversely, administration of the macrophage growth factor colony‐stimulating factor 1 (CSF‐1) increased the number of osteomacs/macrophages at the injury site significantly with a concurrent increase in new CT1+ matrix deposition and enhanced mineralization. This study establishes osteomacs as participants in intramembranous bone healing and as targets for primary anabolic bone therapies. © 2011 American Society for Bone and Mineral Research.
Kinetics of a Criegee intermediate that would survive high humidity and may oxidize atmospheric SO2

Significance Ozonolysis of alkenes produces highly reactive Criegee intermediates. Whereas water dimer efficiently scavenges the simplest Criegee intermediate CH2OO in the troposphere, this study clear demonstrates that water vapor does not react with dimethyl substituted Criegee intermediate (CH3)2COO, at least not fast enough to significantly consume (CH3)2COO in the troposphere. On the other hand, (CH3)2COO reacts with SO2 three times faster than CH2OO does, indicating Criegee intermediates of a structure similar to (CH3)2COO are potential candidates for an efficient oxidant in the atmospheric SO2 oxidation. Criegee intermediates are thought to play a role in atmospheric chemistry, in particular, the oxidation of SO2, which produces SO3 and subsequently H2SO4, an important constituent of aerosols and acid rain. However, the impact of such oxidation reactions is affected by the reactions of Criegee intermediates with water vapor, because of high water concentrations in the troposphere. In this work, the kinetics of the reactions of dimethyl substituted Criegee intermediate (CH3)2COO with water vapor and with SO2 were directly measured via UV absorption of (CH3)2COO under near-atmospheric conditions. The results indicate that (i) the water reaction with (CH3)2COO is not fast enough (kH2O < 1.5 × 10−16 cm3s−1) to consume atmospheric (CH3)2COO significantly and (ii) (CH3)2COO reacts with SO2 at a near–gas-kinetic-limit rate (kSO2 = 1.3 × 10−10 cm3s−1). These observations imply a significant fraction of atmospheric (CH3)2COO may survive under humid conditions and react with SO2, very different from the case of the simplest Criegee intermediate CH2OO, in which the reaction with water dimer predominates in the CH2OO decay under typical tropospheric conditions. In addition, a significant pressure dependence was observed for the reaction of (CH3)2COO with SO2, suggesting the use of low pressure rate may underestimate the impact of this reaction. This work demonstrates that the reactivity of a Criegee intermediate toward water vapor strongly depends on its structure, which will influence the main decay pathways and steady-state concentrations for various Criegee intermediates in the atmosphere.
Src Continues Aging: Current and Future Clinical Directions

Aberrant activation of members of the Src family of nonreceptor protein tyrosine kinases is common in solid tumor malignancies and may contribute to the development and/or progression of these tumors. As a result, four Src inhibitors are now in more than 50 clinical trials for at least 14 different types of solid tumors. In this review, we briefly discuss the preclinical rationale for Src inhibitors, the development strategies most likely to be successful in the clinic, and the rationale for Src inhibitors in combination with other agents as part of a more comprehensive therapeutic strategy. As the use of Src family inhibitors in clinical trials on solid tumors is in its infancy, further studies on the roles of Src family kinases in tumor progression, chemoresistance, epidermal-to-mesenchymal transition, and other properties of tumor progression will be important in designing the most effective clinical trials using these inhibitors.
Evaluating a novel approach to enhancing dysphagia management: workplace-based, blended e-learning.

AIMS AND OBJECTIVES To evaluate the learning effect and resource use cost of workplace-based, blended e-learning about dysphagia for stroke rehabilitation nurses. BACKGROUND Dysphagia is a potentially life-threatening problem that compromises quality of life. In many countries, nurses play a crucial role in supporting the management of patients with swallowing problems, yet the literature reports a need for training. DESIGN A single-group, pre- and post-study with mixed methods. METHODS Each blended e-learning session comprised a needs analysis, e-learning programmes, practical skills about modifying fluids and action planning to transfer learning into practice. Participants were the population of registered nurses (n = 22) and healthcare assistants (n = 10) on a stroke rehabilitation ward in a large, teaching hospital in England between August 2010-March 2011. Data collection comprised observation (34 hours), questionnaires administered at four time points to examine change in attitude, knowledge and practice, and estimating the resource use cost for the service. Nonparametric tests and content analysis were used to analyse the data. RESULTS All participants achieved a nationally recognised level of competence. The learning effect was evident on the post- and follow-up measures, with some items of dysphagia knowledge and attitude achieving significance at the p ≤ 0·05 level. The most common self-reported changes in practice related to medicines management, thickening fluids and oral hygiene. The resource use cost was estimated at £2688 for 108 hours training. CONCLUSIONS Workplace-based, blended e-learning was an acceptable, cost effective way of delivering essential clinical knowledge and skills about dysphagia. RELEVANCE TO CLINICAL PRACTICE Dysphagia should be viewed as a patient safety issue because of the risks of malnutrition, dehydration and aspiration pneumonia. As such, it is pertinent to many members of the interdisciplinary team. Consideration should be given to including dysphagia management in initial education and continuing professional development programmes.
Sexual satisfaction in committed relationships

This article provides an overview of the recent interdisciplinary research on the connection between sexual satisfaction and overall relationship happiness for couples. The authors discuss the literature on same- and opposite-sex couples and, cognizant of gender, race, and class differences, state a case for how specific aspects of sexuality, such as frequency of sex, emotion, and orgasm, affect individual and couple satisfaction.