cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract B210: BET inhibitors show superior ability to suppress the progression of tumors containing the Pro47Ser single-nucleotide polymorphism of p53

The tumor suppressor TP53 is the most frequently mutated gene in human cancer and serves to restrict both tumor initiation and progression. Single-nucleotide polymorphisms (SNPs) in the p53 pathway can have a marked impact on p53 tumor suppressor function, and several have been associated with increased cancer risk. We have reported that a naturally occurring SNP affects codon 47 of TP53 (rs1800371, G/A). In most individuals, codon 47 encodes a proline (P47). However, approximately 2.5% of African-Americans express a p53 allele with a serine residue (S47) at this position. In order to compare the ability of the WT and S47 variants of p53 to suppress tumor development, we isolated mouse embryonic fibroblasts (MEFs) from WT and S47 mice and transformed them with the oncogenes E1A and Ras, in order to generate a facile model that would allow us to study responses to therapy. WT and S47 cells grew similarly in 10% serum. However, transformed S47 cells grew significantly better under nutrient-deprived conditions. S47 transformed cells also grew with increased dynamics in a xenograft mouse model and in a tail vein model of metastasis. These data support the premise that the S47 variant of p53 is significantly impaired as a tumor suppressor. We found that, for the majority of conventional genotoxic drugs, S47 tumor cells are resistant, compared to tumor cells with WT p53. In order to identify novel compounds that preferentially target S47 tumor cells, we performed a drug screen on WT and S47 transformed MEFs, using a library of over 200 conventional and experimental chemotherapeutic drugs. We found that S47 cells are far more sensitive to the class of bromodomain inhibitors, specifically BET inhibitors. Using short-term (96 hrs, Alamar Blue) cell viability assays, we found that S47 transformed cells were approximately 5-fold more sensitive to OTX-015, a BET inhibitor currently in clinical trials. We also found that S47 cells were significantly impaired in their ability to form colonies when pretreated for 24 hours with OTX-015. These data highlight the relevance of targeted therapy for patients harboring the S47 variant of p53, and suggest that BET inhibitors may preferentially target S47 tumors. Citation Format: Thibaut Barnoud, Subhasree Basu, Che-Pei Kung, Matthew Reiss, Rugang Zhang, Maureen Murphy. BET inhibitors show superior ability to suppress the progression of tumors containing the Pro47Ser single-nucleotide polymorphism of p53 [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B210.
High salt diet impairs cerebral blood flow regulation via salt-induced angiotensin II suppression.

OBJECTIVES This study sought to determine whether salt-induced ANG II suppression contributes to impaired CBF autoregulation. METHODS Cerebral autoregulation was evaluated with LDF during graded reductions of blood pressure. Autoregulatory responses in rats fed HS (4% NaCl) diet vs LS (0.4% NaCl) diet were analyzed using linear regression analysis, model-free analysis, and a mechanistic theoretical model of blood flow through cerebral arterioles. RESULTS Autoregulation was intact in LS-fed animals as MAP was reduced via graded hemorrhage to approximately 50 mm Hg. Short-term (3 days) and chronic (4 weeks) HS diet impaired CBF autoregulation, as evidenced by progressive reductions of laser Doppler flux with arterial pressure reduction. Chronic low dose ANG II infusion (5 mg/kg/min, i.v.) restored CBF autoregulation between the pre-hemorrhage MAP and 50 mm Hg in rats fed short-term HS diet. Mechanistic-based model analysis showed a reduced myogenic response and reduced baseline VSM tone with short-term HS diet, which was restored by ANG II infusion. CONCLUSIONS Short-term and chronic HS diet lead to impaired autoregulation in the cerebral circulation, with salt-induced ANG II suppression as a major factor in the initiation of impaired CBF regulation.
The US11 Gene of Herpes Simplex Virus 1 Promotes Neuroinvasion and Periocular Replication following Corneal Infection

Herpes simplex virus 1 (HSV-1) cycles between phases of latency in sensory neurons and replication in mucosal sites. HSV-1 encodes two key proteins that antagonize the shutdown of host translation, US11 through preventing PKR activation and ICP34.5 through mediating dephosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). While profound attenuation of ICP34.5 deletion mutants has been repeatedly demonstrated, a role for US11 in HSV-1 pathogenesis remains unclear. We therefore generated an HSV-1 strain 17 US11-null virus and examined its properties in vitro and in vivo In U373 glioblastoma cells, US11 cooperated with ICP34.5 to prevent eIF2α phosphorylation late in infection. However, the effect was muted in human corneal epithelial cells (HCLEs), which did not accumulate phosphorylated eIF2α unless both US11 and ICP34.5 were absent. Low levels of phosphorylated eIF2α correlated with continued protein synthesis and with the ability of virus lacking US11 to overcome antiviral immunity in HCLE and U373 cells. Neurovirulence following intracerebral inoculation of mice was not affected by the deletion of US11. In contrast, the time to endpoint criteria following corneal infection was greater for the US11-null virus than for the wild-type virus. Replication in trigeminal ganglia and periocular tissue was promoted by US11, as was periocular disease. The establishment of latency and the frequency of virus reactivation from trigeminal ganglia were unaffected by US11 deletion, although emergence of the US11-null virus occurred with slowed kinetics. Considered together, the data indicate that US11 facilitates the countering of antiviral response of infected cells and promotes the efficient emergence of virus following reactivation.IMPORTANCE Alphaherpesviruses are ubiquitous DNA viruses and include the human pathogens herpes simplex virus 1 (HSV-1) and HSV-2 and are significant causes of ulcerative mucosal sores, infectious blindness, encephalitis, and devastating neonatal disease. Successful primary infection and persistent coexistence with host immune defenses are dependent on the ability of these viruses to counter the antiviral response. HSV-1 and HSV-2 and other primate viruses within the Simplexvirus genus encode US11, an immune antagonist that promotes virus production by preventing shutdown of protein translation. Here we investigated the impact of US11 deletion on HSV-1 growth in vitro and pathogenesis in vivo This work supports a role for US11 in pathogenesis and emergence from latency, elucidating immunomodulation by this medically important cohort of viruses.
Promoting inclusion in preschool with program-wide positive behaviour supports

ABSTRACTThis article describes a collaborative faculty research project developed to support a university preschool in their transition to becoming an inclusive programme. The project, conducted in...
A TUTELA ADMINISTRATIVA DO MEIO AMBIENTE: O ESTUDO DE IMPACTO AMBIENTAL

O desenvolvimento economico e social influenciou sensivelmente os mecanismos da natureza culminando em uma crise ambiental de repercussoes serias no tocante a qualidade de vida e do proprio meio ambiente. Os anseios da sociedade pela tutela juridica do meio ambiente foram incorporados pela Constituicao Federal de 1988 que reconheceu o direito ao meio ambiente ecologicamente equilibrado, disponibilizando instrumentos juridicos de defesa ambiental e estabelecendo diferentes esferas de responsabilizacao para os infratores da norma ambiental. A pesquisa em tela, aborda a tutela administrativa do meio ambiente enfatizando a importância do estudo previo de impacto ambiental e seu respectivo relatorio, identificados como instrumentos importantes de manutencao do meio ambiente sadio.
Integrating Organizational and Management Variables in the Analysis of Safety and Risk

For decades, despite research and description of modern large-scale technologies as “socio-technical systems”, there has been little headway made in integrating research on both the socio and technical aspects of these systems. Social scientists and engineers continue to have contrasting and often non-intersecting approaches to the analysis of organizational factors and the physical aspects of technologies. This essay argues that an important part of this problem has been the ambiguous and underspecified character of the social science research concepts applied to the analysis of organization and management factors. It suggests an important opportunity to more closely integrate social science research into the understanding of hazardous technologies as socio-technical systems through a strategy of clarifying concepts and definitions (such as “safety”) that allow transforming qualitative organizational and managerial “factors” into variables to create metrics useful in the evaluation of safety management systems. It argues also that practitioners have an important role to play in this process. A final argument addresses the contribution that safety metrics could make to the development of higher resolution safety management across a wider spectrum of scales and time-frames than those currently considered by managers and designers of socio-technical systems.
Mdm2 is a target and mediator of IRP2 in cell growth control.

Iron is an essential element to all living organisms and plays a vital role in many cellular processes, such as DNA synthesis and energy production. The Mdm2 oncogene is an E3 ligase and known to promote tumor growth. However, the role of Mdm2 in iron homeostasis is not certain. Here, we showed that Mdm2 expression was increased by iron depletion but decreased by iron repletion. We also showed that Iron Regulatory Protein 2 (IRP2) mediated iron-regulated Mdm2 expression. Specifically, Mdm2 expression was increased by ectopic IRP2 but decreased by knockdown or knockout of IRP2 in human cancer cells as well as in mouse embryonic fibroblasts. In addition, we showed that IRP2-regulated Mdm2 expression was independent of tumor suppressor p53. Mechanistically, we found that IRP2 stabilized Mdm2 transcript via binding to an iron response element (IRE) in the 3'UTR of Mdm2 mRNA. Finally, we showed that Mdm2 is required for IRP2-mediated cell proliferation and Mdm2 expression is highly associated with IRP2 in both the normal and cancerous liver tissues. Together, we uncover a novel regulation of Mdm2 by IRP2 via mRNA stability and that the IRP2-Mdm2 axis may play a critical role in cell growth.
Trends in MELD-XI between Listing and Transplant are Associated with Poor Outcomes in Heart Transplant Recipients with Stage 3 Chronic Kidney Disease

Purpose Non-dialysis dependent patients with renal impairment undergoing heart transplantation (HT) alone are at significantly higher risk of mortality and poor renal outcomes compared with those undergoing heart-kidney transplantation (HKT). It remains unclear what parameters might identify patients who may benefit from HKT compared to HT alone. The Model for End-Stage Liver Disease Excluding INR (MELD-XI) score at the time of HT has been shown to predict early post-HT mortality. We investigated whether trends in the MELD-XI score between listing and transplant among those with stage 3 chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) between 30 and 59 ml/min/1.73 m2) are associated with higher risk of post-HT death or dialysis. Methods We identified 159 patients undergoing HT at our institution between 1/2009 and 2/2018. The following groups were created: Group 1 - MELD-XI ≤ 16 at listing and HT, Group 2 - MELD-XI ≤ 16 at listing and > 16 at HT, Group 3 - MELD-XI > 16 at listing and ≤ 16 at HT, Group 4 - MELD-XI > 16 at listing and HT. A cutoff of 16 was chosen based on the 75th percentile in a normal distribution among those without a composite outcome of post-HT death or dialysis at 1 year. Cox-proportional regression and survival analyses were performed to assess risk of this outcome. Results Average MELD-XI at listing was 14.0 ± 4.9 and at HT was 12.8 ± 4.5 (p 16 was present in 51 (32.1%) at listing and 38 (23.9%) at HT. Group 4 incurred highest risk of composite outcome relative to Group 1 (adjusted hazard ratio 3.67 (95% confidence interval: 1.38-9.76, p Conclusion Changes in MELD-XI between listing and transplantation offer additional risk stratification beyond absolute MELD-XI at time of transplant for death or dialysis at 1 year in patients with stage 3 CKD.
14 – Animal Vaccines

Publisher Summary Rabies in terrestrial animals, primarily carnivores, is caused by the classic genotype 1 rabies virus. Even though the widespread vaccination of domestic dogs has been the one most effective factor in the reduction of human rabies, the number of human deaths worldwide is greater than that of the combined deaths from polio, meningococcal meningitis, Japanese encephalitis, yellow fever, severe acute respiratory syndrome and avian influenze (bird flu).Tools are available in highly efficacious and safe animal and human vaccines. Multiple factors can, however, prevent their use effectively in many areas of the world. For several decades, virtually all rabies nerve tissue origin (NTO) vaccines were inactivated with phenol using the method described by Semple. The NTO vaccines currently in use for mass vaccination campaigns in Africa, Latin America, and the Caribbean are primarily produced from rabies virus-infected suckling mouse brains or lamb brains. These vaccines are shown to be effective in campaigns. However, NTO-killed vaccines for dogs and other animals have often, in the past, resulted in post-vaccinal nervous system reactions that could result in the death of the vaccinated animals.
How Is Quality of Life Assessed in People With Dementia? A Systematic Literature Review and a Primer for Speech-Language Pathologists

Purpose The purpose of this study was to determine how quality of life (QoL) is measured in people with dementia involved in interventions designed to improve well-being and to explore how those measures align with principles of person-centered care. Method A systematic literature review was conducted utilizing PsychInfo, CINAHL, and PubMed and combinations of the search terms: "dementia," "outcome measure," "creative engagement," "creative intervention," "TimeSlips," "art," "quality of life," and "well-being." The search was limited to studies published in peer-reviewed journals that reported outcomes for people with dementia in response to a creative intervention. Results Across the 24 reviewed studies, 30 different outcome measures were reported including eight self-reported, nine observational, and 13 proxy-reported measures. Self-report of QoL was elicited 16 times, observational measures were reported 17 times, and proxy-reported measures were used 28 times. All measures were used with participants across the dementia severity spectrum. Conclusion Current clinical practice of QoL evaluation does not align well with person-centered care principles of self-determination based on the low proportion of self-report. The previously reported limitations of proxy-report have been in part confirmed with this study. Implications of the findings for speech-language pathologists are discussed.
Xanthine oxidoreductase inhibition – A review of computational aspect

Xanthine Oxidoreductase (XOR) exists in a variety of organisms from bacteria to humans and catalyzes the oxidation of hypoxanthine to xanthine and from xanthine to uric acid. Excessive uric acid co...
Eliminating counterexamples: An intervention for improving adolescents’ contrapositive reasoning

Abstract Students’ difficulties with contrapositive reasoning are well documented. Lack of intuition about contrapositive reasoning and lack of a meta-argument for the logical equivalence between a conditional claim and its contrapositive may contribute to students’ struggles. This case study investigated the effectiveness of the eliminating counterexamples intervention in improving students’ ability to construct, critique, and validate contrapositive arguments in a U.S. eighth-grade mathematics classroom. The intervention involved constructing descriptions of all possible counterexamples to a conditional claim and its contrapositive, comparing the two descriptions, noting that the descriptions are the same barring the order of phrases, and finding a counterexample to show the claim is false or viably arguing that no counterexample exists.
Prefacio y Capítulo 5: El poder blando y la política exterior americana, en Soft Power, Public Affairs, New Hampshire, 2004

This fragment of Professor´s Nye famous book introduces the concept and the repercussions of the soft power. Defined as “the ability to get what you want through attraction rather than coercion or payments”, it is of great relevance for the foreign policy of the United States. After exposing the different American foreign policy traditions and the negative consequences of the waste of this kind of power during the Iraq War, Nye underlines the need of using hard power as well as soft power, shaping a new concept of power, the Smart Power.
Global Flash Drought Monitoring Using Surface Soil Moisture

Flash droughts are characterized by an abrupt onset and swift intensification. Global surface soil moisture (θRS) from NASA's Soil Moisture Active Passive (SMAP) satellite can facilitate a near-rea...
Scaling pFET Hot-Electron Injection

We elaborate on an analytical model of hot-electron injection in pFET’s that uses the Boltzmann transport equation in the drain-to-channel depletion region with impact-ionization and phonon scattering operators. We discuss how impact ionization and hot-electron injection scale with the fabrication process.
Pushing and Pulling on OH-and H3O+ with Electric Fields Across Water’s Surface

We use second harmonic generation (SHG) spectroscopy, molecular dynamics simulation, and theoretical modeling to study the response of the neat liquid water-air interface to changes in the potential of an external electrode positioned above the liquid. We observe a parabolic dependence of second harmonic intensity on applied potential. This dependence is reminiscent of bulk-phase electric field induced second harmonic (EFISH) but more complicated because it combines the second-order response of the topmost water layer and the potential dependent response of the interfacial electrical double-layer. Based on the literature values for these contributions, we derive a physical interpretation of our measurements that reveals new insight into the response of the neat water interface to external electric fields. Specifically, we find that the net dipolar orientation of water molecules within the double-layer is primarily responsive to the internal fields generated by the excess surface concentrations of OH- and H3O+ that arise to screen the external potential. Notably, this interpretation implies that the orientational response of water dipoles at the interface can actually oppose the direction of the external field, a subtle effect that is not captured by traditional models.
Proliferating cell nuclear antigen directly interacts with androgen receptor and enhances androgen receptor‑mediated signaling.

Androgen receptor (AR) and/or its constitutively active splicing variants (AR‑Vs), such as AR‑V7 and ARv567es, is required for prostate cancer cell growth and survival, and cancer progression. Proliferating cell nuclear antigen (PCNA) is preferentially overexpressed in all cancers and executes its functions through interaction with numerous partner proteins. The aim of the present study was to investigate the potential role of PCNA in the regulation of AR activity. An identical consensus sequence of the PCNA‑interacting protein‑box (PIP‑box) was identified at the N‑terminus of human, mouse and rat AR proteins. It was found that PCNA complexes with the full‑length AR (AR‑FL) and AR‑V7, which can be attenuated by the small molecule PIP‑box inhibitor, T2AA. PCNA also complexes with ARv567es and recombinant AR protein. The PCNA inhibitors, PCNA‑I1S and T2AA, inhibited AR transcriptional activity and the expression of AR target genes in LNCaP‑AI and 22Rv1 cells, but not in AR‑negative PC‑3 cells. The knockdown of PCNA expression reduced dihydrotestosterone‑stimulated AR transcriptional activity and abolished the inhibitory effect of PCNA‑I1S on AR activity. The PCNA inhibitor, PCNA‑I1, exerted additive growth inhibitory effects with androgen deprivation and enzalutamide in cells expressing AR‑FL or AR‑FL/AR‑V7, but not in AR‑negative PC‑3 cells. Finally, R9‑AR‑PIP, a small peptide mimicking AR PIP‑box, was found to bind to GFP‑PCNA at Kd of 2.73 µM and inhibit the expression of AR target genes, AR transcriptional activity and the growth of AR‑expressing cells. On the whole, these data strongly suggest that AR is a PCNA partner protein and interacts with PCNA via the PIP‑box and that targeting the PCNA‑AR interaction may represent an innovative and selective therapeutic strategy against prostate cancer, particularly castration‑resistant prostate cancers overexpressing constitutively active AR‑Vs.
Anything, Anytime, Anywhere: Is Antitrust Ready for Flexible Market Arrangements?

The migration of business and social activities from physical to virtual venues, once known as the transition to the “New Economy,” is one of the defining characteristics of the digital revolution. This article explores a relatively underdeveloped aspect of the migration: the proliferation of fluid forms of arrangements, which, in the absence of a better term, I call flexible market arrangements (FMAs). In their essence, FMAs are alternatives to some of the structured arrangements that pervaded the brick-and-mortar economy. The core feature of FMAs—the flexibility—is derived from the elimination of economic constraints that are inherent to activities in physical spaces, such as the location of workers and consumers, capital investments, long-term contracts, employment relations, and preferences for in-person interactions. Concerns about competition in digital and labor markets and long-term trends in income and wealth inequality have shaped debates over antitrust policies in recent years. These debates, I argue, have failed to identify adequately the significance of the increasing prevalence of FMAs. This article explains why the rapid spread of FMAs will become the subject of antitrust litigation, investigations, and legislative proposals. It further reviews changes in antitrust law and antitrust analysis that the proliferation of FMAs is likely to trigger.
Analysis of trends in health care in Dnipropetrovsk oblast of Ukraine

The article analyses the situation in health care of Dnipropetrovsk region. The key trends of its developmentfrom 2014 to 2018 are identified. It is determined that the people’s health is one of key factors of the region andUkrainian society’s development, the basis of economic and social revival of the nation. It contributes to theincrease of labour productivity and, consequently, the competitiveness of the domestic economy, its transformationinto the knowledge economy, focused on the accumulation of national wealth, effective investment for theachievement of sustainable development goals. Dynamic analysis of the disease prevalence among the populationof Dnipropetrovsk region by classes of diseases in their correlation with the living conditions of the populationand the level of development of medical care and its infrastructure is carried out. It has been shown that thegeneral decline in income of the population, wide spreading of poverty, together with the depopularisation of ahealthy lifestyle and the low level of confidence in the quality of medicine, directly affect the general health of thepopulation, life quality and expectancy. Strategic prospects for the development of health care in Dnipropetrovskregion are identified as follows: promotion of the ‘human health’ brand and activation of the social movement fora healthy lifestyle; enhancing the integration of science and technology into the health care sector; completion ofmedical reform, taking into account the full range of citizen’s problems, gender and age sensitivity, as a socioeconomicneeds.The article is a summary of the situation in the health care of the region, which is carried out in the frameworkof the task of drafting the Strategy of development of Dnipropetrovsk region for the period until 2027.
Smartphone-based app for evaluating cardiothoracic residents: Feasibility and engagement

Purpose Timely and high-quality feedback is important in cardiothoracic (CT) surgery education. Feedback on operative proficiency is an area for improvement in CT surgery programs. Traditional evaluations significantly lag behind operative interactions. We hypothesized that use of the System for Improving and Measuring Procedural Learning (SIMPL) app would improve operative feedback for trainees. Methods Use of SIMPL was evaluated from December 2018 to January, 2021 within an academic CT surgery training program. Ratings include level of supervision, complexity of the operation, and trainee performance. Completion was limited to 72 h after the operation. Descriptive statistics of the users and ratings are presented. Results Over 28 months, 816 evaluations were completed, and of these, 495 had a rating from both the faculty and trainee. There were 19 trainees representing post-graduate years 1-8 and 19 faculty members who received or submitted at least one evaluation over the study period. The number of evaluations for each trainee ranged from 1 to 166 and from 1 to 81 for each of the faculty. The response rate for faculty ranged from 0% to 100%. "Active help" was the most common type of supervision (50.7% by the faculty, 60.4% from the trainees). Conclusions Use of SIMPL within a CT surgery training program was feasible and engagement was observed from both trainees and faculty. SIMPL provided trainees with timely, concise feedback on operative performance. Further work will focus on correlating SIMPL ratings with pre-existing assessments of performance.
Examining the effect of manganese on physiological processes: Invertebrate models.

Abstract Manganese (Mn2+ as MnSO4 &/or MnCl2) is a common and essential element for maintaining life in plants and animals and is found in soil, fresh waters and marine waters; however, over exposure is toxic to organisms. MnSO4 is added to soil for agricultural purposes and people are exposed to Mn2+ in the mining industry. Hypermanganesemia in mammals is associated with neurological issues mimicking Parkinson's disease (PD) and appears to target dopaminergic neural circuits. However, it also seems that hypermanganesemia can affect many aspects of health besides dopaminergic synapses. We examined the effect on development, behavior, survival, cardiac function, and glutamatergic synaptic transmission in the Drosophila melanogaster. In addition, we examined the effect of Mn2+ on a sensory proprioceptive organ and nerve conduction in a marine crustacean and synaptic transmission at glutamatergic neuromuscular junctions of freshwater crayfish. A dose-response effect of higher Mn2+ retards development, survival and cardiac function in larval Drosophila and survival in larvae and adults. MnSO4 as well as MnCl2 blocks stretch activated responses in primary proprioceptive neurons in a dose-response manner. Mn2+ blocks glutamatergic synaptic transmission in Drosophila as well as crayfish via presynaptic action. This study is relevant in demonstrating the effects of Mn2+ on various physiological functions in order to learn more about acute and long-term consequences Mn2+ exposure.
Effective Water Research Programs

Effective research programs are those that support the most interested, informed and competent researchers. In defining the problem to be researched, obtaining detailed data relative to that problem, and testing and applying the research results to the solution of that problem in actual practice, a practitioner is invaluable and should be a full partner in the research endeavor. In coordinating research, particularly interdisciplinary research, the lead researcher must be one who grasps the over-all problem and understands enough of each discipline to coordinate the effort effectively. Over-coordination or over-direction by funding agencies can stifle progress, because freedom to pursue a variety of ideas is generally more productive than is direction along the most promising course. Selection of researchers for contract or grant research projects on the basis of past performance as evaluated by users would appear to lend greater promise than selection by peer review, which tends to perpetuate current lines of scientific thought.
Network Theory--the Emergence of the Creative Enterprise

In both the arts and sciences, there are certain characteristics that set apart creative "dream teams". But can these characteristics be explained mathematically, asks Barabasi in his [Perspective][1]? A new study that mathematically examines the creative teams responsible for Broadway shows and landmark scientific papers reveals the key elements that underpin team creativity and success ([ GuimerAi et al .][2]). [1]: http://www.sciencemag.org/cgi/content/full/308/5722/639 [2]: http://www.sciencemag.org/cgi/content/short/308/5722/697
Using Event Centrality to Predict Depressive Symptoms after a Romantic Conflict: A Prospective Design

Summary Using cross-sectional analyses, event centrality has been shown to be related to a number of poor psychological outcomes, including depressive symptoms and posttraumatic stress disorder symptoms. In the current study, we examined the ability of event centrality of a recent conflict in or breakup of a romantic relationship to prospectively predict depressive symptoms. Replicating previous findings, ratings of event centrality to a recent romantic conflict or breakup were significantly associated with depressive symptoms and posttraumatic stress disorder symptoms at Time 1. These relationships remained significant after controlling for closure and perceived insight. In addition, Time 1 event centrality prospectively predicted Time 2 depressive symptoms, particularly for participants who were split from their romantic partners at Time 2. This prediction remained significant after controlling for Time 1 depressive symptoms. The results of the study suggest that levels of event centrality for romantic conflicts prospectively predict subsequent mental health outcomes. Copyright © 2014 John Wiley & Sons, Ltd.
Numerical solution of natural convection flow past a non-isothermal vertical flat plate

The problem of natural convection over a semi-infinite flat plate with non-uniform wall temperature is studied by using a numerical method. The local rates of heat transfer as a function of the distance along the plate are tabulated for a range of Prandtl numbers (0.01 to 100) and for a few cases of wall temperature distributions. Such tabulations serve as a reference against which other approximate solutions can be compared in the future.
The intrafamilial transmission of rheumatoid arthritis. II. An interview measure of rheumatoid arthritis.

Abstract Our conclusion is that we have a very usable instrument in the 4-point RA measure, and that if our assumptions are correct, the associations to be presented in subsequent papers are just as true as if the respondents had been examined by a physician equipped with X-ray and laboratory facilities. In some senses this is an affirmation of the medical dictum that the history is by all odds the most important part of a medical evaluation.
Emotional Dampening in Persons with Elevated Blood Pressure: Affect Dysregulation and Risk for Hypertension

Persons with higher blood pressure have emotional dampening in some contexts. This may reflect interactive changes in central nervous system control of affect and autonomic function in the early stages of hypertension development. The purpose of this study is to determine the independence of cardiovascular emotional dampening from alexithymia to better understand the role of affect dysregulation in blood pressure elevations. Ninety-six normotensives were assessed for resting systolic and diastolic (DBP) blood pressure, recognition of emotions in faces and sentences using the Perception of Affect Task (PAT), alexithymia, anxiety, and defensiveness. Resting DBP significantly predicted PAT emotion recognition accuracy in men after adjustment for age, self-reported affect, and alexithymia. Cardiovascular emotional dampening is independent of alexithymia and affect in men. Dampened emotion recognition could potentially influence interpersonal communication and psychosocial distress, thereby further contributing to BP dysregulation and increased cardiovascular risk.
Multipipeline networking for compound vector processing

An efficient vector-processing technique is proposed; it is based on a novel concept of multipipeline networking, which is generalized from the techniques of pipeline chaining and systolization. The authors also present the design principles of pipeline nets and provide programming, compiling and run-time techniques for converting scientific programs into pipeline net implementations. Performance analysis of the pipeline net is provided with projected performance of various Livermore loops implemented with pipeline nets of various sizes. >
The Lie groups of simple feedback systems

In this paper we classify linear time invariant control systems according to the symmetery properties they display with respect to output feed-back. Our results show that there are just four possibilities which are easily distinguishable from the transfer functions itself. These results have important implications for feedback stability studies, for the investigation of parametric controllability, and for the construction of special, highly structured, state variable representations.
A New interpretation of Michael Polanyi's theory of tacit knowing: Integrative philosophy with ‘Intellectual Passions’

Abstract According to my interpretation, based on the entirety of Michael Polanyi's epistemological works, his theory of tacit knowing is conceived of as three models tied together by the central feature of Intellectual Passions as integrator. The models are progressively refined forms of his first conception of tacit knowing: ‘we know more than we can tell’. The three models are: the Gestalt-Perception Model based on the gestalt notion of part-whole relations, the Action-Guiding Model incorporating the phenomenological-existential notion of intentional action, and the Semiotic Model, an abstract conception of action directed to meaning showing that tacit knowing has a ‘from-to structure’ (from subsidiary awareness to focal awareness). In the Semiotic Model integration is named by the logical term ‘inference’. Polanyi's conception of reality and his theory of truth are introduced linked to the models, to show why his epistemology is not subjectivist and his theory of truth is not relativist.
Comparison of Butyric Acid, Ethanol, Lactic Acid, and Propionic Acid as Hydrogen Donors for the Reductive Dechlorination of Tetrachloroethene

Previous studies indicated that dechlorinators can utilize H2 at lower concentrations than can methanogens. This suggests a strategy for selective enhancement of dechlorinationmanaging H2 delivery so as to impart a competitive advantage to dechlorinators. Four H2 donorsbutyric and propionic acids, which can only be fermented when the H2 partial pressure is lower than 10-3.5 or 10-4.4 atm, respectively, and ethanol and lactic acid, which are readily fermented at H2 partial pressures 2−3 orders of magnitude higherwere administered to anaerobic mixed cultures. Comparison of the resulting enrichment cultures during time-intensive, short-term tests showed significant differences in patterns of donor degradation, H2 production and use, and distribution of reduction equivalents between dechlorination and competing methanogenesis. Amendment with butyric and propionic acids resulted in less methanogenesis than did amendment with ethanol or lactic acid, which generated much higher H2 levels. Ethanol did not support...
The Small Ice Cap Instability in Diffusive Climate Models

Abstract Simple climate models employing diffusive heat transport and ice cap albedo feedback have equilibrium solutions with no stable ice cap smaller than a certain finite size. For the usual parameters used in these models the minimum cap has a radius of about 20 degrees on a great circle. Although it is traditional to remove this peculiar feature by various ad hoc mechanisms, it is of interest because of its relevance to ice age theories. This paper explains why the phenomenon occurs in these models by solving them in a physically appealing way. If an ice-free solution has a thermal minimum and if the minimum temperature is just above the critical value for formation of ice, then the artificial addition of a patch of ice leads to a widespread depression of the temperature below the critical freezing temperature; therefore, a second stable solution will exist whose spatial extent is determined by the range of the influence function of a point sink of heat, due to the albedo shift in the patch. The rang...
Stimulation by Parathyroid Hormone of Interleukin-6 and Leukemia Inhibitory Factor Expression in Osteoblasts Is an Immediate-early Gene Response Induced by cAMP Signal Transduction

Parathyroid hormone and other agents that stimulate bone resorption function, at least in part, by inducing osteoblasts to secrete cytokines that stimulate osteoclast differentiation and activity. We previously demonstrated that parathyroid hormone induces expression by osteoblasts of interleukin-6 and leukemia inhibitory factor without affecting the 16 other cytokines that were examined. We also showed that stimulation of osteoclast activity by parathyroid hormone is dependent on activation of the cAMP signal transduction pathway and secretion of interleukin-6 by osteoblasts. In the current study, we demonstrate that the rapid and transient stimulation of interleukin-6 and leukemia inhibitory factor is inhibited by actinomycin D and superinduced by protein synthesis inhibitors, the classical characteristics of an immediate-early gene response. Moreover, activation of cAMP signal transduction by parathyroid hormone and parathyroid hormone-related protein is necessary and sufficient to induce both interleukin-6 and leukemia inhibitory factor. In addition, cAMP analogues as well as vasoactive intestinal peptide and isoproterenol, two neuropeptides that stimulate bone resorption by activating cAMP signal transduction in osteoblasts, also induce interleukin-6 and leukemia inhibitory factor in these cells. Taken together with our previous results, this study suggests that interleukin-6 is crucial for stimulation of bone resorption not only by parathyroid hormone, but also by parathyroid hormone-related protein, vasoactive intestinal peptide, and β-adrenergic agonists, like isoproterenol.
Similarity in joint function limitation in Type 3 von Willebrand's disease and moderate haemophilia A

Type 3 von Willebrand's disease (VWD) is a rare bleeding diathesis with complete or near complete deficiency of von Willebrand factor (VWF) and low factor VIII (FVIII) levels. In contrast, only FVIII is decreased in haemophilia A (HA). Both disorders are complicated by arthropathy. The purpose of this study was to further clarify the roles of FVIII and VWF: Antigen (VWF:Ag) in joint range of motion (ROM) loss over time. We compared joint ROM loss and other bleeding manifestations in 100 Type 3 VWD subjects (FVIII<5%) and 1814 moderate HA subjects (FVIII 1-5%) within the U.S. Universal Data Collection (UDC) database. High rates of bleeding were reported at baseline. During follow-up, moderate HA patients reported a joint (46% vs. 34%, P < 0.0001) or muscle bleed (27% vs. 16%, P < 0.0001) in a higher proportion of visits than VWD patients. Other bleeds, including mucosal, were reported in a greater proportion of visits among patients with Type 3 VWD than among those with HA (49% vs. 32%, P < 0.0001). Multivariate analysis revealed no difference in joint ROM loss over time in the Type 3 VWD vs. moderate HA populations. A higher FVIII level was protective in both VWD and HA (P < 0.001). Our findings support the hypothesis of primacy of the FVIII level in determining risk of joint haemorrhage, and may help target therapy in Type 3 VWD and moderate HA to prevent joint disability.
Effects of neuropeptide Y (NPY) and NPY agonists on lordosis in the female guinea pig.

We have previously shown that an NPY antagonist decreases lordosis behavior and that this decrease can be reversed with NPY administration. The present experiments examined whether intracerebroventricular (icv) administration of NPY would facilitate lordosis behavior and whether it would increase feeding behavior in the female guinea pig. Additionally, we examined whether icv administration of a more specific NPY Y1 and/or Y2 receptor agonist would facilitate lordosis behavior. Although NPY (1 μg) increased feeding behavior when it was administered to the lateral ventricle of ovariectomized (ovx) estrogen (i.e., estradiol benzoate; EB) and progesterone- (P) treated guinea pigs, it had no facilitatory effect on lordosis behavior at any of the doses tested (0.5, 1, 5, or 10μg). In fact, the lower doses had a small, delayed inhibitory effect. NPY also had no effect on lordosis in females treated with EB alone. In contrast, the NPY Y1 agonist (Leu31Pro34) NPY significantly facilitated lordosis in ovx EB- and P-treated females. It had no effect in ovx females treated with EB alone. The NPY Y2 agonist NPY (13–36) had a slight, delayed inhibitory effect in ovx EB- and P-treated females. These data are consistent with the hypothesis that NPY can act at a number of receptor subtypes to affect lordosis behavior, and that NPY can facilitate lordosis behavior by acting at Y1 receptors. Furthermore, it appears that this facilitatory effect of Y1 receptors is an effect on some progesterone-mediated component of lordosis, as the Y1 agonist facilitated EB- and P-induced lordosis, but not that induced with EB alone.
Optimal surgical approach for repair of aortopulmonary window.

Background: This is a review of the experience over 26 year in a single institution with surgical repair of aortopulmonary window. Methods: Between July 1973 and March 1999, 38 patients underwent surgery for aortopulmonary window at a median age of 5 weeks, and with a median weight of 3.9 kg. Median follow-up was 6.6 years, with a range from 0.8 to 26 years. Additional defects were present in 25 (65%) patients, including interruption of the aortic arch in 7, tetralogy of Fallot in 7, ventricular septal defect in 5, functionally univentricular anatomy in 3, aortic coarctation in 2, and anomalous origin of a coronary artery in 1. We approached via an aortotomy in 45%, an incision through the defect in 31%, and using a pulmonary arteriotomy in 24% of patients. Closure was achieved using a single patch in 30 patients (79%). Results: There were 3 (7.9%) in-hospital deaths. Actuarial patient survival was 88% at 10 years. Three patients required reinterventions for stenoses of the great arteries. Freedom from any reintervention was 70% at 10 years. By multivariate analysis, the approach through a pulmonary arteriotomy was shown to result in a higher need for reintervention (p = 0.01). Conclusions: Repair of aortopulmonary window can be done with excellent results. A pulmonary arteriotomy should be avoided.
eIF4E-Targeted Suicide Gene Therapy in a Minimal Residual Mouse Model for Metastatic Soft-Tissue Head and Neck Squamous Cell Carcinoma Improves Disease-Free Survival

Background Translation initiation factor eIF4E unwinds long 5′-untranslated regions of certain tightly regulated mRNAs and, thereby, facilitates their translation into proteins. eIF4E has been shown to be overexpressed in a majority of solid tumors, including head and neck cancers. To exploit this dysregulation, a long 5′-untranslated region was spliced upstream of a thymidine kinase (Tk) gene to enhance translation of this “suicide” gene within cells overexpressing eIF4E. We investigated the efficacy of therapy with an adenovirus incorporating this novel suicide gene (Ad-HSV-UTk) following cytoreductive tumor surgery in improving disease-free and overall survival in a mouse soft-tissue metastasis model for head and neck squamous cell carcinoma. Materials and methods SCC-7 (orally-derived mouse SCCa) cells were treated with Ad-HSV-Tk, Ad-HSV-UTk, Ad-null, or saline and characterized for eIF4E and Tk levels by Western blot analysis. Cytotoxicities for cells treated with Ad-HSV-Tk, Ad-HSV-UTk, or Ad-null were quantified by MTS assay. Mice bearing SCC-7-induced tumors received cytoreduction followed by Ad-HSV-UTk + ganciclovir (GCV) or control treatment and were followed for disease-free and overall survival. Results SCC-7 cells showed uniformly high levels of eIF4E but elevated Tk for Ad-HSV-Tk- and Ad-HSV-UTk-treated cells over Ad-null-treated cells. Cytotoxicities for Ad-HSV-Tk- and Ad-HSV-UTk-treated cells were, correspondingly, observed to be 100-fold more sensitive than Ad-null-treated cells to GCV treatment. Cytoreduced mice receiving Ad-HSV-UTk + GCV treatment showed significantly longer disease-free survival ( P = 0.0045) than control arm mice. Conclusions Ad-HSV-UTk suicide gene therapy prolonged disease-free survival in a mouse minimal residual soft-tissue head and neck squamous cell carcinoma metastasis model.
Automated administration of the Wolf Motor Function Test for post-stroke assessment

The advent of new health sensing technologies has presented us with the opportunity to gain richer data from patients undergoing clinical interventions. Such technologies are particularly suited for applications requiring temporal accuracy. The Wolf Motor Function Test (WMFT) is one such application. This assessment is an instrument used to determine functional ability of the paretic and non-paretic limbs in individuals post-stroke. It consists of 17 tasks, 15 of which are scored according to both time and a functional ability scale. We propose a technique that uses wearable sensors and performance sensors to estimate the timing of seven of these tasks. We have developed a sensing framework and an algorithm to automatically detect total movement time. We have validated the system's accuracy on the seven selected WMFT tasks. We also suggest how this framework can be adapted to the remaining tasks.
The numerical solution of the three-dimensional inverse scattering problem for time harmonic acoustic waves

The inverse scattering problem under consideration is to determine the shape of an acoustically soft obstacle in $\mathbb{R}^3 $ from a knowledge of the time harmonic incident wave and the far field pattern of the scattered wave. It is assumed that the frequency is in the resonance region, i.e. high frequency asymptotic methods are not available. A method for solving this problem is presented which is based on the theory of Herglotz wave functions and avoids the use of integral equations. Numerical examples are given showing the practicality of this approach.