cssi/SciSciGPT-SciSciNet huggingface dataset:
Novel Role for Bioactive Lipids in Mobilization of Bone Marrow Stem Cells During Myocardial Ischemia: Sphingosine-1 Phosphate (S1P) As Potential Therapeutic Target

Abstract Abstract 1911 Background: Bone marrow (BM) contains a variety of stem cells, including mobile pool of hematopoietic stem cells and non-hematopoietic stem cells and acute myocardial infarction (AMI) triggers mobilization of BM-derived stem cells (BMSCs) through poorly understood processes. Recently we have postulated a major role for bioactive lipids such as sphingosine-1 phosphate (S1P) in G-CSF- and AMD3100-induced mobilization of hematopoietic stem cells (HSCs) into peripheral blood (PB) (Leukemia 2010;24:976–85). Hypothesis: We hypothesized that S1P could also play a role in mobilization of BMSCs in patients during tissue and organ injury as seen for example in patients with AMI. Methods: Peripheral blood (PB) samples from matched controls and patients presenting with ST-elevation myocardial infarction (STEMI) were examined i) by employing FACS for a number of circulating in PB lineage negative (Lin-)/CD45-/CD34+ and CD133+ and CXCR4+ BMSCs, ii) PB level of S1P by employing mass spectrometry, iii) SDF-1 level by ELISA and finally iv) BMSCs were tested in Transwell migration assays for their chemotactic responsiveness to S1P gradient in plasma from STEMI patients. Results: Plasma S1P levels were highest within 6 hours of AMI presentation 0.31 ± 0.02 μM and declined to 0.14 ± 0.02 μM in controls (P VPC20139 (10 μM). At the same time to our surprise we did not observed significant chemotactic relevant changes in SDF-1 level in PB plasma. Conclusion: This is the first human study to suggest that elevated S1P level in PB early in the course of AMI mobilizes BMSCs. Furthermore, we demonstrate for the first time that the release of hematopoietic and non-hematopoietic BMSCs into PB correlates in AMI patients with activation of CC and generation of MAC, that may release S1P from erythrocytes and platelets. We postulate that based on these results future studies examining the therapeutic manipulation of S1P and its receptors for myocardial regeneration are warranted. Disclosures: No relevant conflicts of interest to declare.
Nitroglycerin Ointment in the Treatment of Impotence

Topical nitroglycerin ointment has been studied in the laboratory as a possible treatment for impotence of various etiologies. However, there is limited information on the topical administration of nitroglycerin in a natural environment allowing normal sexual function. We report 3 cases of impotence that were successfully treated with topical nitroglycerin ointment.
2016 updates to US Medical Eligibility Criteria for Contraceptive Use and Selected Practice Recommendations for Contraceptive Use: Highlights for adolescent patients.

The US Medical Eligibility Criteria for Contraceptive Use (MEC) and US Selected Practice Recommendations for Contraceptive Use (SPR) provide evidence-based guidance to safely provide contraception counseling and services. Both documents were updated in 2016 and are endorsed by the North American Society for Pediatric and Adolescent Gynecology. The purpose of this mini-review is to highlight updates to the US MEC and US SPR that are most relevant to health care providers of adolescents to support dissemination and implementation of these evidence-based best practices. This document is intended to highlight these changes and to complement, not replace, the detailed practice guidance within the US MEC and US SPR.
Impacts of transportation infrastructure on single-family property values

New or long-standing public infrastructure such as highways, airports, and ports of entry (POE) can increase adjacent property values generating a value premium for private developers and adjacent ...
Talimogene Laherparepvec: An Oncolytic Virus Therapy for Melanoma:

Objective: To review the efficacy and safety of talimogene laherparepvec (T-VEC) as well as its pharmacology, pharmacokinetics, drug-drug interactions, handling procedures, cost considerations, and place in therapy. Data Sources: Searches of PubMed (1966 to February 2017) and Cochrane Library (1999 to February 2017) were conducted using the terms talimogene laherparepvec, T-VEC, OncoVEX, immunotherapy, melanoma, and oncolytic virus. Additional information was determined from bibliographies, manufacturer product labeling and website, meeting abstracts, Food and Drug Administration website, and clinicaltrials.gov. Study Selection and Data Extraction: A total of 79 English-language publications were identified. Articles that assessed T-VEC’s pharmacokinetics, pharmacodynamics, mechanism, dosing, safety, and efficacy were included as well as narrative reviews that provided practical information. Data Synthesis: Clinical trials have confirmed the safety and efficacy of T-VEC as monotherapy for the treatment of...
Interactive dimensions for leadership: an integrative literature review and model to promote ethical leadership praxis in a global society

AbstractThe purpose of this integrative literature review was to draw together recognised streams of knowledge to inform contemporary leadership of school systems in democratic societies. The article integrates scholarship in ethical leadership (EL) and social justice leadership (SJL). The resultant conceptualised model is an expanded version of a preliminary model included in a research brief of an empirical study. The Ethical Leadership Praxis in a Global Society model includes four interactive dimensions: (1) understanding social justice theory and leadership theory, (2) applying state, national and professional ethical/legal standards, (3) engaging in ethical leadership practice and role modelling for culturally responsive leadership (CRL), and (4) employing personal leadership ethics and core values as a cyclical process of self-reflection and decision-making. This article makes an original contribution for building leadership praxis centred on ethical leadership. The model applies ethical and social...
Hybrid Transactional/Analytical Processing: A Survey

The popularity of large-scale real-time analytics applications (real-time inventory/pricing, recommendations from mobile apps, fraud detection, risk analysis, IoT, etc.) keeps rising. These applications require distributed data management systems that can handle fast concurrent transactions (OLTP) and analytics on the recent data. Some of them even need running analytical queries (OLAP) as part of transactions. Efficient processing of individual transactional and analytical requests, however, leads to different optimizations and architectural decisions while building a data management system. For the kind of data processing that requires both analytics and transactions, Gartner recently coined the term Hybrid Transactional/Analytical Processing (HTAP). Many HTAP solutions are emerging both from the industry as well as academia that target these new applications. While some of these are single system solutions, others are a looser coupling of OLTP databases or NoSQL systems with analytical big data platforms, like Spark. The goal of this tutorial is to 1-) quickly review the historical progression of OLTP and OLAP systems, 2-) discuss the driving factors for HTAP, and finally 3-) provide a deep technical analysis of existing and emerging HTAP solutions, detailing their key architectural differences and trade-offs.
A Generalized Formulation of Multistage Decision-making and Control Under Fuzziness

Abstract Multistage decision-making(control) under fuzziness consists basically in finding an optimal sequence of controls which maximizes the membership function of the fuzzy decision. The fuzzy decision is mainly the intersection of fuzzy constraints imposed on the successive controls applied and fuzzy goals imposed on the successive states attained. This is equivalent to determining an optimal sequence of controls which “best satisfies the fuzzy constraints and fuzzy goals at all the control stages”. The purpose of this Daper is to propose a model in which the strict “” may be replaced by a milder requirement, e.g., “most”, “much more than 50%”, etc. A calculus of linguistically quantified statements is used.
Physicians’ pharmacogenomics information needs and seeking behavior: a study with case vignettes

Genetic testing, especially in pharmacogenomics, can have a major impact on patient care. However, most physicians do not feel that they have sufficient knowledge to apply pharmacogenomics to patient care. Online information resources can help address this gap. We investigated physicians’ pharmacogenomics information needs and information-seeking behavior, in order to guide the design of pharmacogenomics information resources that effectively meet clinical information needs. We performed a formative, mixed-method assessment of physicians’ information-seeking process in three pharmacogenomics case vignettes. Interactions of 6 physicians’ with online pharmacogenomics resources were recorded, transcribed, and analyzed for prominent themes. Quantitative data included information-seeking duration, page navigations, and number of searches entered. We found that participants searched an average of 8 min per case vignette, spent less than 30 s reviewing specific content, and rarely refined search terms. Participants’ information needs included a need for clinically meaningful descriptions of test interpretations, a molecular basis for the clinical effect of drug variation, information on the logistics of carrying out a genetic test (including questions related to cost, availability, test turn-around time, insurance coverage, and accessibility of expert support).Also, participants sought alternative therapies that would not require genetic testing. This study of pharmacogenomics information-seeking behavior indicates that content to support their information needs is dispersed and hard to find. Our results reveal a set of themes that information resources can use to help physicians find and apply pharmacogenomics information to the care of their patients.
HDAC-4 regulates claudin-2 expression in EGFR-ERK1/2 dependent manner to regulate colonic epithelial cell differentiation

In normal colon, claudin-2 expression is restricted to the crypt bottom containing the undifferentiated and proliferative colonocytes. Claudin-2 expression is also upregulated in colorectal cancer (CRC) and promotes carcinogenesis. However, cellular mechanism/s regulated by increased claudin-2 expression during the CRC and mechanism/s regulating this increase remain poorly understood. Epigenetic mechanisms help regulate expression of cancer-associated genes and inhibition of Histone Deacetylases (HDACs) induces cell cycle arrest and differentiation. Accordingly, based on a comprehensive in vitro and in vivo analysis we here report that Histone Deacetylases regulate claudin-2 expression in causal association with colonocyte dedifferentiation to promote CRC. Detailed differentiation analyses using colon cancer cells demonstrated inverse association between claudin-2 expression and epithelial differentiation. Genetic manipulation studies revealed the causal role of HDAC-4 in regulating claudin-2 expression during this process. Further analysis identified transcriptional regulation as the underlying mechanism, which was dependent on HDAC-4 dependent modulation of the EGFR-ERK1/2 signaling. Accordingly, colon tumors demonstrated marked upregulation of the HDAC-4/ERK1/2/Claudin-2 signaling. Taken together, we demonstrate a novel role for HDAC-4/EGFR/ERK1/2 signaling in regulating claudin-2 expression to modulate colonocyte differentiation. These findings are of clinical significance and highlight epigenetic regulation as potential mechanism to regulate claudin-2 expression during mucosal pathologies including CRC.
AAV-mediated progranulin delivery to a mouse model of progranulin deficiency causes T cell-mediated hippocampal degeneration

Adeno-associated virus (AAV)-mediated gene replacement is emerging as a safe and effective means of correcting single-gene mutations, and use of AAV vectors for treatment of diseases of the CNS is increasing. AAV-mediated progranulin gene (GRN) delivery has been proposed as a treatment for GRN-deficient frontotemporal dementia (FTD) and neuronal ceroid lipofuscinosis (NCL), and two recent studies using focal intraparenchymal AAV-Grn delivery to brain have shown moderate success in histopathologic and behavioral rescue in mouse FTD models. Here, we used AAV9 to deliver GRN to the lateral ventricle to achieve widespread expression in the Grn null mouse brain. We found that despite a global increase in progranulin throughout many brain regions, overexpression of GRN resulted in dramatic and selective hippocampal toxicity and degeneration affecting both neurons and glia. Histologically, hippocampal degeneration was preceded by T cell infiltration and perivascular cuffing, suggesting an inflammatory component to the ensuing neuronal loss. GRN delivery with an ependymal-targeting AAV for selective secretion of progranulin into the cerebrospinal fluid (CSF) similarly resulted in T cell infiltration as well as ependymal hypertrophy. Interestingly, overexpression of GRN in wild-type animals also provoked T cell infiltration. These results call into question the safety of GRN overexpression in the CNS, with evidence for both a region-selective immune response and cellular proliferative response following GRN gene delivery. Our results highlight the importance of careful consideration of target gene biology and cellular response to overexpression in relevant animal models prior to progressing to the clinic.
Ideas of Race in the Canonical History of Philosophy

A philosophical understanding of race begins with the canon. In the Republic, Socrates proposed telling youth that they are born with traits of leaders, soldiers, or workers. Aristotle accepted slavery as natural and described enslaved Asians as lacking in spirit. Saint Paul and Saint Aquinas accepted slavery in this world. John Locke reserved slavery for captives taken in a just war. Hume said that nonwhites, especially Africans, are inferior to whites. Kant posited racial essences as determining moral worth and intellectual capabilities. Hegel posited geography as determining human difference and called Africa “the land of childhood.” Nietzsche assumed racial hierarchy and proposed a new blonde ruling race. John Stuart Mill reserved liberty for mature individuals and societies advanced in civilization.
Focus on eye care in schizophrenia.

Schizophrenia, a neurodevelopmental mental disorder with heterogeneous features, poses major social and health‐care challenges in Australia and worldwide. Ophthalmic findings in patients with schiz...
Antecedents and consequences of apparel involvement: a multi-attribute model

x CHAPTER 1: INTRODUCTION ! Purpose 4 Objectives of the Study 4 Definitions of Terms 5 Dissertation Organization 6 CHAPTER 2: LITERATURE REVIEW 7 Involvement 7 Definition and conceptualization 7 Dimensionality issues and measures 8 Structure of involvement subdimensions 12 Apparel Involvement 13 Level of involvement 13 Previous research 15 Dimensions of apparel involvement 16 Measures 17 Related Variables 19 Commonly studied outcome variables of involvement 19 Demographic characteristics 22 The S-O-R Paradigm of Involvement 23 Proposed Model 28 Research Hypotheses 29 Preliminary data analysis 29 Research hypothesis 30 CHAPTER 3: METHOD 32 Apparel Involvement Measure Development 32 Initial item pool of apparel involvement 32 Development of apparel involvement measure for pretest 33 Apparel involvement measure 33 Data Collection Questionnaire 35 Apparel involvement treatment 35 Apparel involvement 36 Zaichkowsky's PII 36 Behavioral consequences 37 Demographic variables 37
Cardiac microtubules in health and heart disease

Cardiomyocytes are large (∼40,000 µm3), rod-shaped muscle cells that provide the working force behind each heartbeat. These highly structured cells are packed with dense cytoskeletal networks that ...
Cognitive Behavioral Therapy in Primary Care

The substantial proportion of individuals with co-occurring physical and behavioral problems has led to the recommendation that behavioral health becomes integrated within primary care. Such an approach to behavioral health generally, and CBT services specifically, would improve the availability of effective services and increase access to behavioral health care. In this chapter, we review why an integrated care model would be beneficial, consider several models of integrated care, discuss future research directions, and explore how to apply current approaches within two clinical vignettes. These vignettes present examples for the clinical integration of CBT components to address behavioral health concerns within the primary care context. The vignettes include treatment for a youth with eczema and treatment for a child with combined-type ADHD.
Voltage Amplification of Radio Frequency Signals With Pitch-Asymmetric Acoustic Delay Lines

We present the conceptual approach, theoretical simulations, and experimental results of a novel device based on acoustic delay lines with different pitch between transmitter and receiver (dubbed pitch-asymmetric delay lines) for passive voltage amplification of radio frequency signals. The theoretical results show that it is possible to attain very high voltage gains in this new class of asymmetrical delay lines. The experimental results validate the ability to produce voltage gain, but significantly below theoretical predictions. We attribute this discrepancy to the high admittance at the nulls of the experimental response of the interdigital transducers. We investigate the maximum admittance at the nulls compatible with obtaining high voltage gains ( $>20~dB$ ) and find that it is two order of magnitude lower than that achieved in this work. [2019-0209]
Leadership Competencies Leadership competencies and job satisfaction among Aviation employees of Pakistan International airline (PIA)

Job satisfaction and leadership style has always been tested and correlated in the past to understand the impact of the leadership on the degree of job satisfaction of employees. Since the passage of time employee satisfaction has become a great aspect of organizational success, therefore, different theories of management and leadership have been proposed. In the recent contest, theory of leadership competencies has been developed that measures the different competencies of the managers and leaders. In the current study, three independent variables namely emotional quotient (EQ), intelligence quotient (IQ), and managerial quotient (MQ) are being tested on the employee’s job satisfaction level of PIA. Data was gathered by questionnaires and 212 responses were received. SPSS were applied for analysis of data and there is a confirming connection amid job satisfaction and the EQ, MQ, and IQ of PIA employees along with the positive relationship between the Leadership competencies (LC) and the job satisfaction and lastly the significant relationship between job satisfactions.
Using ecological momentary assessment (EMA) to explore mechanisms of alcohol‐involved HIV risk behavior among men who have sex with men (MSM)

BACKGROUND AND AIMS Heavy drinking is associated with increased risk of incident HIV infection among men who have sex with men (MSM). Past studies suggest that this association may be due to the tendency for intoxication to interfere with condom use. However, research on potential causal mechanisms explaining this relationship has been limited primarily to laboratory studies. In this study, we tested several potential mediators of the relationship between alcohol use level and HIV risk behavior. DESIGN Ecological momentary assessment (EMA) methods conducted over a 30-day period. SETTING AND PARTICIPANTS/CASES MSM (n = 100) in the northeastern United States. MEASUREMENTS Participants completed daily diary surveys and up to six experience sampling surveys randomly prompted throughout the day. FINDINGS Very heavy levels of drinking (12+ drinks) increased the odds of engaging in any sex [odds ratio (OR) = 1.87, P < 0.001]. Coefficient products and 95% confidence intervals indicated that both subjective sexual arousal (OR = 1.52, P < 0.001) and sex intentions (OR = 1.74, P < 0.001) significantly mediated the association between very heavy drinking and the odds of sex. When participants reported sex, the odds of engaging in high-risk condomless anal sex (CAS) increased incrementally after drinking heavily (five to 11 drinks; OR = 3.27, P = 0.006) and very heavily (12+ drinks; OR = 4.42, P < 0.001). Only subjective sexual arousal significantly mediated the association between alcohol use level and high-risk CAS (OR = 1.16, P = 0.040). CONCLUSIONS Increases in subjective sexual arousal after drinking heavily appear to partly account for alcohol-related HIV risk behaviors in the daily lives of men who have sex with men. Alcohol's role in strengthening motivationally consistent emotional states may therefore play a more important role in facilitating alcohol-involved HIV risk than explicit sexual motivation.
Small Molecule ER Proteostasis Regulators Reduce Amyloidogenic Immunoglobulin Light Chain Secretion Through an On-Target, ATF6-Independent Mechanism

SUMMARY The aberrant plasma cell secretion and toxic aggregation of destabilized, amyloidogenic immunoglobulin light chains (LCs) causes organ proteotoxicity associated with Light Chain Amyloidosis (AL). We recently identified small-molecule endoplasmic reticulum (ER) proteostasis regulators such as compound 147, that reduce the secretion and toxic aggregation of amyloidogenic LCs implicated in AL pathogenesis (Plate, Cooley et al., 2016). Compound 147 covalently modifies a subset of ER protein disulfide isomerases (PDIs) to promote ER proteostasis remodeling through the preferential activation of the ATF6 unfolded protein response (UPR)-associated signaling pathway (Paxman, Plate et al., 2018). Here, we show that compound 147 reduces the secretion of an amyloidogenic LC from AL patient plasma cells through a mechanism independent of ATF6 activation. Instead, our results indicate that 147 reduces amyloidogenic LC secretion through an on-target mechanism involving covalent PDI modification. These results reveal pharmacologic targeting of PDIs as a potential strategy to ameliorate LC-associated proteotoxicity in AL. Furthermore, our results demonstrate that compounds like 147 can influence ER proteostasis through multiple on-target mechanisms including ATF6 activation and PDI modification, highlighting their broad potential for correcting pathologic imbalances in ER proteostasis implicated in diverse diseases.
Current situation and prospect of early rehabilitation of children in pediatric intensive care unit

Early rehabilitation of critically ill children can promote the recovery of physical function and improve the clinical outcome.This paper mainly describes the status quo of early rehabilitation nursing for critically ill children, and provides countermeasures for the implementation of early rehabilitation in children intensive care unit (PICU) in the future. Key words: Early rehabilitation; Survey
GPU Acceleration of the HemeLB Code for Lattice Boltzmann Simulations in Sparse Complex Geometries

We present an implementation and scaling analysis of a GPU-accelerated kernel for HemeLB, a high-performance Lattice Boltzmann code for sparse complex geometries. We describe the structure of the GPU implementation and we study the scalability of HemeLB on a GPU cluster under normal operating conditions and with real-world application cases. We investigate the effect of CUDA block size and GPU over-subscription on the single-GPU performance, and we present a strong-scaling analysis of multi-GPU parallel simulations using two different hardware models (P100 and V100) and a variety of large cerebral aneurysm geometries. We find that HemeLB-GPU achieves single-GPU speedups of $50\times$ (P100) and $100\times$ (V100) compared to a single CPU core, with good scalability up to 32 GPUs. We also discuss strategies to improve both the kernel performance as well as the scalability of HemeLB-GPU to a larger number of GPUs. The GPU implementation supports the LBGK collision kernel, boundary conditions for walls and inlets/outlets, and several lattice types (D3Q15, D3Q19, D3Q27), and it integrates seamlessly with the existing infrastructure in HemeLB for graph partitioning and parallelization via MPI. It is expected that the GPU implementation will enable users of the HemeLB code to make better utilization of heterogeneous high-performance computing systems for large-scale lattice Boltzmann simulations.
Estradiol regulation of the prelimbic cortex and the reinstatement of cocaine seeking in female rats

Relapse susceptibility in women with substance use disorders (SUDs) has been linked to the estrogen, 17β-estradiol (E2). Our previous findings in female rats suggest that the influence of E2 on cocaine seeking can be localized to the prelimbic prefrontal cortex (PrL-PFC). Here, we investigated the receptor mechanisms through which E2 regulates the reinstatement of extinguished cocaine seeking. Sexually mature female rats underwent intravenous cocaine self-administration (0.5 mg/inf; 14 × 2 h daily) and extinction, and then were ovariectomized before reinstatement testing. E2 (10 µg/kg, i.p.) alone did not reinstate cocaine seeking, but it potentiated reinstatement when combined with an otherwise subthreshold priming dose of cocaine. A similar effect was observed following intra-PrL-PFC microinfusions of E2 and by systemic or intra-PrL-PFC administration of the estrogen receptor (ER)β agonist, DPN, but not agonists at ERα or the G-protein-coupled ER1 (GPER1). By contrast, E2-potentiated reinstatement was prevented by intra-PrL-PFC microinfusions of the ERβ antagonist, MPP, or the GPER1 antagonist, G15, but not an ERα antagonist. Whole-cell recordings in PrL-PFC layer (L)5/6 pyramidal neurons revealed that E2 decreases the frequency, but not amplitude, of GABAA-dependent miniature IPSCs (mIPSC). As was the case with E2-potentiated reinstatement, E2 reductions in mIPSC frequency were prevented by ERβ and GPER1, but not ERα, antagonists and mimicked by ERβ, but not GPER1, agonists. Altogether, the findings suggest that E2 activates ERβ and GPER1 in the PrL-PFC to attenuate the GABA-mediated constraint of key outputs that mediate cocaine seeking.
MiR-378b Modulates Chlamydia-Induced Upper Genital Tract Pathology.

Genital Chlamydia trachomatis infection causes severe reproductive pathologies such as salpingitis and pelvic inflammatory disease that can lead to tubal factor infertility. MicroRNAs (miRNAs) are evolutionarily conserved regulators of mammalian gene expression in development, immunity and pathophysiologic processes during inflammation and infection, including Chlamydia infection. Among the miRNAs involved in regulating host responses and pathologic outcome of Chlamydia infection, we have shown that miR-378b was significantly differentially expressed during primary infection and reinfection. In this study, we tested the hypothesis that miR-378b is involved in the pathological outcome of Chlamydia infection. We developed miR-378b knockout mice (miR-378b−/−) using Crispr/Cas and infected them along with their wild-type (WT) control with Chlamydia to compare the infectivity and reproductive pathologies. The results showed that miR-378b−/− mice were unable to clear the infection compared to WT mice; also, miR-378b−/− mice exhibited a relatively higher Chlamydia burden throughout the duration of infection. However, gross pathology results showed that miR-378b−/− mice had significantly reduced uterine dilatations and pathologic lesions after two infections compared to WT mice. In addition, the pregnancy and fertility rates for infected miR-378b−/− mice showed protection from Chlamydia-induced infertility with fertility rate that was comparable to uninfected WT mice. These results are intriguing as they suggest that miR-378b is important in regulating host immune responses that control Chlamydial replication and drive the inflammation that causes complications such as infertility. The finding has important implications for biomarkers of Chlamydial complications and targets for prevention of disease.
A NEW approach for characterizing mouse urinary pathophysiologies.

The void spot assay (VSA) is a cost-effective method for evaluating and quantifying mouse urinary voiding phenotypes. The VSA has been used to differentiate voiding behaviors between experimental groups, but not as a diagnostic assay. To build toward this goal, we used the VSA to define voiding patterns of male mice with diabetic diuresis (BTBR.Cg-Lepob /WiscJ mice), irritative urinary dysfunction (E. coli UTI89 urinary tract infection), and obstructive urinary dysfunction (testosterone and estradiol slow-release implants) compared to their respective controls. Many studies compare individual VSA endpoints (urine spot size, quantity, or distribution) between experimental groups. Here, we consider all endpoints collectively to establish VSA phenomes of mice with three different etiologies of voiding dysfunction. We created an approach called normalized endpoint work through (NEW) to normalize VSA outputs to control mice, and then applied principal components analysis and hierarchical clustering to 12 equally weighted, normalized, scaled, and zero-centered VSA outcomes collected from each mouse (the VSA phenome). This approach accurately classifies mice based on voiding dysfunction etiology. We used principal components analysis and hierarchical clustering to show that some aged mice (>24 m old) develop an obstructive or a diabetic diuresis VSA phenotype while others develop a unique phenotype that does not cluster with that of diabetic, infected, or obstructed mice. These findings support use of the VSA to identify specific urinary phenotypes in mice and the continued use of aged mice as they develop urinary dysfunction representative of the various etiologies of LUTS in men.
High-Resolution Mödssbauer Spectroscopy with Tantalum-181

An improvement of the resolution that may be obtained with the Mossbauer method is of considerable interest. The few Mossbauer resonances with lifetimes in the microsecond region have therefore attracted special attention. These are the 93 keV γ transition of 67Zn (T1/2 = 9.3 μs), the 6.2 keV γ transition of 181Ta (T1/2 = 6.8 μs), and the 13.6 keV γ transition of 73Ge (T1/2 = 4.6 μs). Only for the first two cases has the Mossbauer resonance been observed up to now [1,2].
Solitary Wave Solutions of Generalized Korteweg-De Vries Equations

Publisher Summary This chapter discusses solitary wave solutions of generalized Korteweg-de Vries (KdV) equations. The chapter begins with a discussion of the existence of solitary wave solutions of the scalar Korteweg-deVries (KdV) and modified Korteweg-de Vries equations, including the derivation of formulas for wave amplitude and speed when the waves move against a nonzero “background.” This is followed by a consideration of related questions for system analogs of (KdV). The approach involves the consistent use of the asymptotic theory of second-order singularly perturbed boundary value problems, and hence it offers a convenient alternative to more traditional analytical and numerical methods. The solitary waves in each component evolve independently of each other.
“Positive Contrast” Inversion-Recovery With Oxide Nanoparticles-Resonant Water Suppression Magnetic Resonance Imaging: A Change for the Better?

The identification and characterization of atherosclerotic lesions prone to rupture in asymptomatic individuals remains a major focus of diagnostic imaging research. Although ischemic events often result from severely stenotic lesions in the peripheral arteries, the majority of atherosclerotic
Context Building Information-Centric Decision-Support Systems

As the volume of data and human-centered information available to decision-makers continues to increase at an ever-accelerating rate, the need to represent information in software-processable formats becomes more apparent. At the same time, the availability of information from diverse sources through the World Wide Web provides the opportunity to widen the scope of input to decision-support systems, if this information can be made accessible through automated means. Past approaches to information-centric interoperability have been based on the use of a shared static object model, but this becomes impractical when we consider the loosely-coupled decentralized nature of the Web. This paper discusses the motivations driving a change from static to dynamic information models. It defines a representative use case, and describes a service-based architecture that allows for extending existing information sources to allow programmatic access. The proposed architecture uses existing and emerging Web Service specifications, enhanced by an ontology definition language, to create an environment that does not require information service providers to use static shared models, while allowing information consumers to learn ontologies from the services themselves. Clients such as decisionsupport systems can thus build their own information context at run-time based on models received from multiple sources.
The Magnetic Variable Stars

The peculiar A stars were first noted as peculiar because they exhibit anomalously strong lines of one or more of the elements Si, Cr, Mn, Sr, and Eu. These diverse objects are all called Ap stars because their assigned spectral types fall predominantly in the range B9-F0. Recent studies have suggested, however, that the Ap stars should be subdivided into two groups. The stars characterized by enhanced lines of Mn, and usually Hg as well, differ from the remaining Ap stars in composition and binary frequency; there are no confirmed spectrum, photometric, or magnetic variations in any Hg-Mn stars; and the upper limit on the magnetic field strengths of the Hg-Mn stars is about 200 gauss. Because of these differences, many observers (e.g. Sargent and Searle 1967; Preston 1971b; Wolff and Wolff 1974) have suggested that the Hg-Mn stars are fundamentally different in their properties, and possibly in their origin and evolution, from the SiCrEuSr stars. We shall be concerned today only with this latter group of stars, and in the review that follows only members of the SiCrEuSr class of stars will be referred to as Ap stars.
HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging

The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity.
Therapeutic Strategies for Xenotransplantation

To achieve successful xenotransplantation, it is necessary to overcome the immunological barriers that evolution has built up between different species. In contrast to allotransplantation, where the cellular response is the main hurdle, in xenotransplantation both humoral and cellular responses have to be overcome. In attempts to achieve successful pig-to-human xenotransplantation, several approaches are currently being evaluated. Genetic engineering techniques are being applied to the problems of xenotransplantation. To achieve successful xenotransplantation, it will probably be necessary to combine several therapeutic techniques and/or agents, as is the case with allotransplantation today. Xenotransplantation offers the first opportunity for modifying the donor as opposed to the recipient, which opens up new possibilities in this era of rapidly developing techniques such as genetic engineering, gene transfer, and cloning. The breeding of a pig with a vascular endothelial structure against which humans have no preformed antibodies would be a major advance. In the recipient, however, it will still be necessary to inhibit the production of induced antibodies, as well as the strong cellular response, either by some form of immunosuppressive therapy or by the induction of tolerance.
Growth and characterization of superconducting spinel oxide LiTi2O4 thin films

Epitaxial films of LiTi{sub 2}O{sub 4} on single crystalline substrates of MgAl{sub 2}O{sub 4}, MgO, and SrTiO{sub 3} provide model systems to systematically explore the effects of lattice strain and microstructural disorder on the superconducting state. Lattice strain that affects bandwidth gives rise to variations in the superconducting and normal state properties. Microstructural disorder, such as antiphase boundaries that give rise to Ti network disorder, reduces the critical temperature, and Ti network disorder combined with Mg interdiffusion lead to a much more dramatic effect on the superconducting state. Surface sensitive X-ray absorption spectroscopy has identified Ti to retain site symmetry and average valence of the bulk material regardless of film thickness.
Comparison of Diagnostic Methods for Optimizing Epilepsy Surgery Outcome Including Magnetoencephalography (P6.198)

OBJECTIVE: To evaluate concordance of scalp EEG with intracranial EEG, MRI, PET, SPECT, MEG in post-surgical epilepsy outcomes. BACKGROUND: Multiple tests are used in presurgical evaluations. Initial video EEG monitoring and MRI are supplemented by PET, SPECT, MEG, and invasive monitoring. However, not all testing is completed in all patients. Optimized presurgical evaluation based on highly concordant test results should lead to cost effectiveness, as measured in Engel class I/II surgical outcomes. DESIGN/METHODS: We conducted a retrospective review of adult and pediatric epilepsy surgical evaluations including scalp +/- invasive EEG, MRI, MEG, PET and SPECT. Study included 24 patients at Wake Forest Baptist Hospital between 2010 and 2013. Surgeries include resections and laser ablation, but excluded corpus callosotomies. We reviewed chart notes for subsequent seizure control. We compared localization by testing with temporal or extratemporal surgical location. RESULTS: Of 24 patients, 17 were Engel Class I or II outcome after follow up of 6 -36 months. By scalp EEG, 9/17 had a single focus, most of these with mesial temporal sclerosis. All 17 patients had MEG and 7 patients also had invasive EEG. 15 had PET, and 14 had ictal SPECT. Of the 7 patients with suboptimal surgical outcome all had a MEG, 5 had invasive EEG and 7 had PET, 6 had ictal SPECT. MEG and/or invasive EEG which were concordant with initial scalp EEG more frequently predicted better outcomes than SPECT and PET. CONCLUSIONS: While presurgical epilepsy evaluations consist of multiple tests, physician and patient preferences, convenience and even insurance authorization determine which tests can be performed for an individual. Although we found all tests contributed potentially useful information, we conclude that MEG and invasive monitoring yield information more likely to predict good outcome. Further study is needed to define MEG utility, especially in non-lesional compared to lesional epilepsy. Disclosure: Dr. Boles has nothing to disclose. Dr. Boggs has received research support from Visualase. Dr. Valerie has nothing to disclose. Dr. O9Donovan has received research support from UCB Pharma and Visualase.
States as Gender Equality Activists: The Evolution of Quota Laws in Latin America

This article examines two decades of strengthening, expansion, and diffusion of gender quota laws in Latin America. The analysis departs from studies of quotas' adoption, numerical effectiveness, or policy impacts, instead focusing on states' use of coercive power to integrate women into public and private institutions. Viewing these policies in light of feminist theories of the poststructuralist state reveals how state institutions act to restructure government and promote gender equality. In building this argument, the article presents an up-to-date empirical survey and conceptual understanding of quota evolution in Latin America, including recent developments in countries such as Chile, Colombia, Bolivia, Ecuador, Mexico, Nicaragua, and Uruguay.
Indocyanine green (ICG) fluorescence-guided laparoscopic adrenalectomy.

Objective Laparoscopic adrenalectomy has become the standard of care for many adrenal tumors. However, the success of the operation hinges on identifying the adrenal vein and complete tumor resection. We demonstrate the use of a commercially available near infrared fluorescent imaging system to clearly delineate the vascular anatomy of adrenal neoplasms and enhance the border between tumor and normal tissue. We hypothesize that this will increase the safety of laparoscopic adrenalectomy. Materials and Methods We performed laparoscopic adrenalectomy utilizing indocyanine green (ICG) and a specialized laparoscopic fluorescence imaging system on four consecutive patients undergoing laparoscopic adrenalectomy over a 4-month period. Results The adrenal arteries and vein were vividly enhanced with ICG fluorescence guidance, and the border between tumor and adjacent tissue was clearly demarcated. The operations were performed safely with minimal blood loss and short operative times. There were no complications. Conclusions Adrenal neoplasms can be resected laparoscopically under ICG fluorescence guidance and can be used to clearly identify vascular structures and enhance the borders of the tumor. This technique allows for clear identification of the adrenal vein and has the potential to improve the safety of laparoscopic adrenalectomy. J. Surg. Oncol. 2015;112:650–653. © 2015 Wiley Periodicals, Inc.
Cutting Edge: IL-2 Is Essential for TGF-β-Mediated Induction of Foxp3+ T Regulatory Cells

TGF-beta is a pluripotent cytokine that is capable of inducing the expression of Foxp3 in naive T lymphocytes. TGF-beta-induced cells are phenotypically similar to thymic-derived regulatory T cells in that they are anergic and suppressive. We have examined the cytokine and costimulatory molecule requirements for TGF-beta-mediated induction and maintenance of Foxp3 by CD4(+)Foxp3(-) cells. IL-2 plays a non-redundant role in TGF-beta-induced Foxp3 expression. Other common gamma-chain-utilizing cytokines were unable to induce Foxp3 expression in IL-2-deficient T cells. The role of CD28 in the induction of Foxp3 was solely related to its capacity to enhance the endogenous production of IL-2. Foxp3 expression was stable in vitro and in vivo in the absence of IL-2. As TGF-beta-induced T regulatory cells can be easily grown in vitro, they may prove useful for the treatment of autoimmune diseases, for the prevention of graft rejection, and graft versus host disease.
From cells on up

A star is born: the Temasek Life Science Laboratory (TLL) in Singapore hosted its first annual symposium between 14 and 15 February 2003, entitled ‘Cell Biology of Development and Disease’. The TLL is Singapore's newest biological research institute, established in 2002 by Temasek Holdings, the investment holding arm of the Singapore government. This short but intense meeting brought together speakers from Asia, Europe and the USA to discuss the function of cells, both in isolation and in the broader contexts of development and pathogenesis. ![][1] The Temasek Life Science Laboratory (TLL) aims to create a vibrant and interactive intellectual community by placing young scientists on an equal footing with established group leaders and by promoting collaborations between all its researchers. This unusual and stimulating meeting combined the three main areas of research at the TLL: cell biology, developmental biology and pathogenesis. Although these separate areas are usually represented by their own separate meetings, this symposium proved that, in fact, these topics fit together extremely well. This is because the cell provides a unifying principle that connects development and disease with more basic molecular biological processes. ### Expounding the cell‐cycle sutra The first session, ‘Cytoskeleton and polarity’, opened with a keynote address by M. Bornens of the Institut Curie in Paris, France. His talk raised the philosophical issue of individuation—how a daughter cell becomes a separate individual that is distinct from its parent cell. Bornens focused on the centriole as a determinant of cell individuation, which is logical given that these structures undergo a discrete duplication preceding each cell division. Importantly, when a centriole duplicates, the daughter centriole that forms is functionally and structurally distinct from the original mother centriole. Both mother and daughter centrioles are able to nucleate microtubules during the G1 phase, but these are retained by the mother centriole, whereas the daughter releases its … [1]: /embed/graphic-1.gif
Endothelin-induced changes in intracellular pH and Ca2+ in coronary smooth muscle: role of Na(+)-H+ exchange.

Abstract The relationship between endothelin-1 (ET-1)-induced stimulation of Na(+)-H+ exchange and intracellular free Ca2+ ([Ca2+]i) was examined in primary cultures of porcine coronary artery smooth muscle cells. Intracellular pH (pHi) and [Ca2+]i were measured using 2,7-bis-carboxyethyl-5(6)-carboxyfluorescein and the acetoxymethyl ester of fura-2 respectively. In HCO3(-)-free buffer (pH = 7.4), ET-1 (0.1-50 nM) induced a sustained, dose-dependent increase in pHi. ET-1 (10 nM) increased pHi from 6.83 +/- 0.01 to 6.93 +/- 0.02 (P 90% inhibited by EIPA (3 microM), confirming the presence of an ET-1-responsive Na(+)-H+ exchanger. Coronary smooth muscle cells responded to ET-1 with a dose-dependent, biphasic increase in [Ca2+]i which was not inhibited by manipulations (EIPA pretreatment or Na(+)-free media) shown to block the Na(+)-H+ exchanger. The ET-1-mediated alkalinization was not inhibited by removal of extracellular Ca2+ ([Ca2+]o). However, complete blockade of the ET-1-mediated [Ca2+]i response using the intracellular Ca(2+)-chelator, [bis-(2-amino-5-methylphenoxy)ethane-NNN'N'-tetraacetic acid tetraacetoxymethyl ester] (MAPTAM), in [Ca2+]o-free media, demonstrated that an increment in [Ca2+]i is required for activation of the Na(+)-H+ exchanger by ET-1. The ET-1-induced rise in [Ca2+]i was not associated with a rise in pHi in the presence of CO2/HCO3-. We conclude that: (1) activation of Na(+)-H+ exchange by ET-1 requires an increment in [Ca2+]i; and (2) ET-1 stimulates EIPA-sensitive Na(+)-H+ exchange, but this stimulation does not modulate ET-1-induced changes in [Ca2+]i.
Collaborative Teaming: OT and SLP Co-treatment of Autism Spectrum Disorder

A collaborative approach between speech-language pathologists (SLPs) and occupational therapists (OTs) is a highly effective treatment strategy, as the combination of the two therapeutic approaches allows therapists to address most of the core deficits and differences attributed to autism spectrum disorder (ASD). Effective collaborative treatment between OTs and SLPs lies in integrating sensory strategies into communication and evidence-based strategies, to allow individuals to maintain arousal, sustain optimal attention, react with expected emotions and affect, and engage purposefully in action as a response.