cssi/SciSciGPT-SciSciNet huggingface dataset:
Robotic Excision of Vaginal Remnant/Urethral Diverticulum for Relief of Urinary Symptoms Following Phalloplasty in Transgender Men.

ABSTRACT Objective To describe the technique of robotic remnant vaginectomy/excision of urethral diverticulum in transmen and report postoperative outcomes. Materials and Methods Between 2015 and 2018, 4 patients underwent robotic remnant vaginectomy/excision of urethral diverticulum for relief of urinary symptoms. Patients were of mean age 36 ± 10.1 years (range 26-50) at time of vaginal remnant excision, and were 26 ± 9.1 months (range 20-39) post-op following their primary vaginectomy and radial forearm free flap (n = 3) or anterolateral thigh (n = 1) phalloplasty. All had multiple urologic complications after primary phalloplasty, most commonly urinary retention (n = 4), urethral stricture (n = 3), fistula (n = 3), dribbling (n = 2), and obstruction (n = 2). Indication for revision was obstruction and retention (n =3 ) and/or dribbling (n = 2). In each case, the robotic transabdominal dissection freed remnant vaginal tissue from the adjacent bladder and rectum without injury to these structures. Concurrent first- or second-stage urethroplasty was performed in all cases at a more distal portion of the urethra using buccal mucosa, vaginal, or skin grafts. Intraoperative cystoscopy was used in each case to confirm complete resection and closure of the diverticulum. Results At mean follow-up of 294 ± 125.6 days (range 106-412), no patients had persistence or recurrence of vaginal cavity/urethral diverticulum on cystoscopic follow-up. Of 3 patients who wished to ultimately stand to void, 2 were able to do so at follow-up. Conclusion Robotic transabdominal approach to remnant vaginectomy/excision of urethral diverticulum allows for excision without opening the perineal closure for management of symptomatic remnant/diverticulum in transgender men after vaginectomy.
The Organization and Biochemical Specificity of Afferent Projections to the Paraventricular and Supraoptic Nuclei

Publisher Summary The paraventriculo(PVN)-supraoptico(SON)-neurohypophysial system is the most thoroughly characterized peptidergic system in the brain, both from the electrophysiological and the anatomical points of view. This chapter describes the organization of the neural inputs that relay sensory information from the periphery to the PVN and SON nuclei and presents several conclusions about the organization of central pathways, which regulate the magnocellular neurosecretory system—while many cell groups project to the PVN, relatively few provide inputs that end in the magnocellular division or in the SON, which does not contain a distinct parvocellular division. With the possible exception of a projection from the median preoptic nucleus, inputs to the magnocellular neurosecretory system end preferentially in the areas that are rich either in oxytocin- or in vasopressin-neurons. The major feature that distinguishes the PVN and SON is the association of an elaborately organized parvocellular division with the former, and recent evidence suggests that cells in the parvocellular division project to nearby magnocellular neurons. The chapter describes 10 of these neuroactive substances within cell bodies in the PVN, and there is evidence that both oxytocin and corticotropin releasing factor are found in some magnocellular neurons, while vasopressin and dynorphin are found in others. Although, the functional significance of the co-existence of peptides within neurosecretory neurons is not clear, it is tempting to speculate that inputs from different sources, which release different neuroactive substances, differentially affect the synthesis and (or) release of one or another of the peptides in a particular cell type in the PVN.
Trem2 Splicing and Expression are Preserved in a Human Aβ-producing, Rat Knock-in Model of Trem2-R47H Alzheimer's Risk Variant.

The R47H variant of the Triggering-Receptor-Expressed on Myeloid cells 2 (TREM2) increases the risk of Alzheimer’s disease (AD). Mutagenesis of exon 2 in Knock-in (KI) mouse models of the R47H variant introduced a cryptic splice site, leading to nonsense mediated decay. Since haploinsufficiency does not model Trem2-R47H function, a new rat KI model, the Trem2R47H KI rat was created. Human Aβ has higher propensity to form toxic Aβ species, which are considered the main pathogenic entity in AD, as compared to rodent Aβ, the rat Amyloid Precursor Protein (App) gene was mutated to produce human Aβ. Trem2 splicing and expression was measured in Trem2R47H KI rat brains and microglia by qualitative and quantitative RT-PCR. Trem2 levels and Trem2 processing was assessed by Western analysis. APP metabolite levels were determined by enzyme-linked immunosorbent assay (ELISA), for Human Aβ and soluble APP, and Western analysis, for full length APP, βCTF and αCTF. Trem2 expression and Trem2 levels are unchanged in Trem2R47H KI rats. The artifactual splicing seen in KI mouse models is not present; additionally, two novel isoforms of rat Trem2 are described. Trem2R47H rat brains have lower human Aβ38, sAPPα and sAPPβ levels. Thus, Trem2R47H KI rats may prove valuable to define pathogenic mechanisms triggered by the Trem2 R47H variant, including those mediated by toxic species of human Aβ peptides.
Cognitive test score and 25-Year mortality risk; Does race matter?

Objectives: Despite our knowledge on the effect of cognitive test score on subsequent risk of mortality, few studies have compared Blacks and Whites for this association. The current study was conducted on Black-White differences in the magnitude of the association between baseline cognitive test score and all-cause mortality in a nationally representative sample of adults in the United States over 25 years. Methods: We used data of the Americans’ Changing Lives Study (ACL), 1986 – 2011, a national prospective cohort in U.S. The study followed 3,361 adults (2,205 White and 1,156 Blacks), age 25 and older, for up to 25 years. The independent variable was cognitive test score measured at baseline (1986) using the 4-item version of the Short Portable Mental Status Questionnaire, treated in two different ways (as a dichotomous and as a continuous variable). The dependent variable was time to death (due to all causes) during the follow up period. Covariates included baseline age, gender, education, income, number of chronic diseases, self-rated health, and depressive symptoms. Race (Black versus White) was the focal effect modifier. We used a series of Cox proportional hazards models in the total sample, and by race, in the absence and presence of health variables. Results: Overall, cognitive test score predicted mortality risk. A significant interaction was found between race and baseline cognitive test score suggesting that baseline cognitive test score has a weaker protective effect against all-cause mortality for Blacks in comparison to Whites. In race-stratified models, cognitive test score at baseline predicted risk of all-cause mortality for Whites but not Blacks, in the absence and presence of baseline socio-economic and health variables. The results were similar regardless of how we treated baseline cognitive test score. Conclusions: In the United States, baseline cognitive test score has a weaker protective effect against all-cause mortality over a long period of time for Blacks than Whites. The finding is in line with the Minorities Diminished Returns theory and is probably due to structural and interpersonal racism.
Chapter 7 – Liability for Failure to Train

Publisher Summary Because failure-to-train claims represent a majority of supervisory liability actions, this chapter addresses this critical managerial responsibility. Criminal justice administrators can be held liable if inadequate or improper training causes injury or the violation of an individual's constitutional rights. Ongoing training is critical for avoiding civil litigation and in structuring a defense to legal assertions. Case review reveals that deliberate indifference is a difficult standard for plaintiffs to establish in asserting claims of inadequate training. The trends and the margin for winning civil lawsuits by the police illustrate this point. Police administrators should note specific training categories that may apply to their respective departments. Administrators are encouraged to review the following recommendations in an effort to shore up potential agency deficiencies to insulate the agency, supervisors, and officers from civil liability. First, each administrator should conduct an internal assessment of routine and recurring tasks that officers and supervisors perform. As changes in the law affect job functions, appropriate training should be developed. Based on this assessment, regularly scheduled training should be provided to all officers and supervisors in those activities. At a minimum, each category identified should be a priority addressed through training on a recurring basis. Second, once a training assessment is finalized, administrators are encouraged to revise the policies and procedures that parallel the training topics. Third, to avert future failure-to-train liability and to maintain occupational professionalism, supervisory training should be instituted. And fourth, it is critical that all training be documented and accurate training records be maintained.
Comparative Higher Education Policy Under Nondemocratic Regimes in Argentina and Chile: Similar Paths, Different Policy Choices

Despite their common historical roots, two higher education systems in Latin America differ dramatically in their financing mechanisms. In Argentina, the national government completely subsidizes undergraduate programs in public institutions, while Chile relies mostly on tuition fees charged to individuals attending public institutions. Through quantitative and qualitative secondary sources, this paper shows that class interests (structural approach) and economic policies (ideational approach) played a major role in explaining comparative policy outcomes in these nondemocratic regimes. The article makes an explicit contribution to the understanding of comparative policy choices in nondemocratic regimes.
Efficient Rare-Event Simulation for Multiple Jump Events in Regularly Varying L\'evy Processes with Infinite Activities

In this paper we address the problem of rare-event simulation for heavy-tailed Levy processes with infinite activities. We propose a strongly efficient importance sampling algorithm that builds upon the sample path large deviations for heavy-tailed Levy processes, stick-breaking approximation of extrema of Levy processes, and the randomized debiasing Monte Carlo scheme. The proposed importance sampling algorithm can be applied to a broad class of Levy processes and exhibits significant improvements in efficiency when compared to crude Monte-Carlo method in our numerical experiments.
The Conclusion of Practical Reasoning

According to the Aristotelian Thesis, the conclusion of practical reasoning is an action. Critics argue against it by pointing to cases in which some interference or inability prevents the production of action, yet in which that interference or inability doesn’t impugn the success of an agent’s reasoning. Some of those critics suggest instead that practical reasoning concludes in an intention, while others suggest it concludes in a belief with normative content, such as a belief about what one has conclusive, or sufficient, reason to do. In this paper, I argue that we should allow that practical reasoning could conclude in either an intention or a belief with normative content. I begin by developing an objection to the Aristotelian Thesis, showing how the objection will not also undermine the possibility of practical reasoning concluding in an intention or a belief. I then respond to an argument from Joseph Raz designed to exclude the possibility of intentions as conclusions of practical reasoning. Lastly, I show how the worry that belief isn’t sufficiently “practical” to qualify as a conclusion of practical reasoning is misplaced.
Propositional Constraint Graphs: An Intuitive, Domain-General Tool for Diagramming Knowledge, Assumptions, and Uncertainties:

A diagramming method called Propositional Constraint (PC) graphing was developed as an aid for tasks involving argumentation, planning, and design. Motivated by several AI models of defeasible (or ...
Super generic

This is a film about a character gets sad after being called "super generic" by an art teacher and goes to extremes to get noticed. The note he got and the action he took in the film were representing the relationship between the students and the instructors, which is also how the feedback and note dressing process looks like sometime in the industry.
Improvements and Gaps in Financial Risk Protection Among Veterans Following the Affordable Care Act.

Despite public perception, most of the nearly 20 million US veterans have health coverage outside the Veterans Health Administration (VHA), and VHA eligibility and utilization vary across veterans. Out-of-pocket healthcare spending thus remains a potential source of financial hardship for veterans. The Affordable Care Act (ACA) aimed to expand health insurance access, but its effect on veterans’ financial risk protection has not been explored. To evaluate whether ACA implementation was associated with changes in veterans’ risk of catastrophic health expenditures, and to characterize drivers of catastrophic health spending among veterans post-ACA. Using multivariable linear probability regression, we examined changes in likelihood of catastrophic health spending after ACA implementation, stratifying by age (18–64 vs 65+), household income tercile, and payer (VHA vs non-VHA). Among veterans with catastrophic spending post-ACA, we evaluated sources of out-of-pocket spending. Nationally representative sample of 13,030 veterans aged 18+ from the 2010 to 2017 Medical Expenditure Panel Survey. ACA implementation, January 1, 2014. Likelihood of catastrophic health expenditures, defined as household out-of-pocket spending exceeding 10% of household income. Among veterans aged 18–64, ACA implementation was associated with a 26% decrease in likelihood of catastrophic health expenditures (absolute change, −1.4 percentage points [pp]; 95% CI, −2.6 to −0.2; p=0.03), which fell from 5.4% pre-ACA to 3.9% post-ACA. This was driven by a 38% decrease in catastrophic spending among veterans with non-VHA coverage (absolute change, −1.8pp; 95% CI, −3.0 to −0.6; p=0.003). In contrast, catastrophic expenditure rates among veterans aged 65+ remained high, at 13.0% pre- and 12.5% post-ACA. Major drivers of veterans’ spending post-ACA include dental care, prescription drugs, and home care. ACA implementation was associated with reduced household catastrophic health expenditures for younger but not older veterans. These findings highlight gaps in veterans’ financial protection and areas amenable to policy intervention.
Crashworthiness of recycled carbon fiber composites

Abstract The crashworthiness of discontinuous recycled carbon fiber composites was studied. Sinusoidal crush specimens were manufactured of acrylonitrile butadiene styrene, polyphenylene sulfide, and a common structural epoxy reinforced with recycled carbon fibers. Samples were tested at a range of strain rates and temperatures representative of automotive conditions. Crush debris size was quantified using sieving to correlate with energy absorption. The effect of manufacturing flaws such as embedded foreign objects, porosity, and ductile tearing was studied by comparing x-ray computed tomography images with crush test data gathered using digital image correlation. The results show great promise for discontinuous fiber organosheet composites as a novel material for automotive crash structures, exceeding the energy absorption capabilities of many continuous fiber thermosets.
Self-Phased Metasurface Pixels/Cells: Concept, Design and Applications

Metasurfaces can be categorized into two types, i.e., transmission-type and reflection-type. In general, they allow electromagnetic waves either to be transmitted or reflected with the manipulation in phase and or amplitude. The transmission/reflection phase can also be tuned by incorporating active circuit elements into the metasurface pixels/cells' design. This paper presents a self-phased metasurface pixel/cell concept that mainly focuses on the tunability in both the transmission and reflection phase without using lossy active circuit elements. The tunable phase can be realized by using constituent material as the substrate supporting the metasurface. In transmission-type, we propose a unit cell design that consists of three layers of a metallic ring surrounding a metallic patch; all are integrated into a constituent material used as substrates. In reflection-type, the presented pixel/cell design consists of a dual-circular ring, incorporating a meandered slot line, or an interdigitated line, in between. All are also integrated on a dielectric layer with a metal backing used as a constituent material. Simulation results show that the designed unit cells can achieve over 220 degrees of tunable phase with an insertion loss of less than 3 dB in the transmission configuration and 220 degrees of tunable phase with less than 2 dB loss in the reflection configuration. The proposed concept is implemented to design the reconfigurable transmit and reflectarray without lossy phase shifters or active circuit elements.
Targeting Tumor Vasculature Using Adeno-Associated Virus Phage Vectors Coding Tumor Necrosis Factor-α

An advantage of targeted gene therapy is the potential for effectively delivering anti-vascular and antitumor therapy directly to the site of the tumor, thus maximizing therapeutic efficacy and minimizing toxicity. The use of a vector capable of directed cell transduction can result in the sustained expression of the therapeutic agent. This chapter reviews the current status of vector strategies, targeted gene therapy with tumor-specific promoter and antibody and peptide conjugation, and outlines the challenges faced for the next-generation of gene transfer technology. Furthermore, it summarizes the results of preclinical anti-angiogenic gene therapy investigations, which utilize novel targeted tumor necrosis factor-α treatment, and discusses potential clinical applications of this treatment strategy.
Modal logics of higher-order probability

This paper discusses the relationship between probability and modal logic. We show that it is both natural and useful to think of probability as a modal operator. Contrary to popular belief in AI, a probability ranging between 0 and 1 represents a range between impossibility and necessity, not between simple falsity and truth. We examine two classes of probability models: flat and staged. The flat models are straightforward generalizations of models for alethic logic. We show that one of the more interesting constraints relating higher- and lower-order probabilities forces all higher-order probabilities in flat models to be either zero or one. We introduce staged models as a means of avoiding this problem. Constraints on the two types of models define various classes of probability logics. We relate some of these probability logics to alethic logic.
Final Report of The Maldivian Penal Law & Sentencing Codification Project: Text of Draft Code (Volume 1) and Official Commentary (Volume 2)

The United Nations Development Programme and the Government of the Maldives commissioned the drafting of a penal code based upon existing Maldivian law, which meant primarily a codification of Shari'a.This is the Final Report of that codification project. A description of the process that produced this Report and the drafting principles behind it, as well as a discussion of the special challenges of codifying Islamic criminal law, are contained in an article at http://ssrn.com/abstract=941443.
Investigations into children's acquisition of the partitive structure

Recent literature suggests that children’s acquisition of DP is a process of gradual feature acquisition (Roeper 2006). This study looks at the acquisition of DP’s barrier feature from the perspective of the acquisition of the syntax of the English partitive construction. This study explores the contrast between the partitive and the pseudopartitive. An adjective preceding the partitive cannot modify the lower noun, but it can in an equivalent pseudopartitive construction. This study shows that children aged 3-5 do not make this distinction, suggesting that children don’t recognize partitive-internal DP as a barrier to adjectival modification.
Inability to consent does not diminish the desirability of stroke thrombolysis

Objective Some have argued that physicians should not presume to make thrombolysis decisions for incapacitated patients with acute ischemic stroke because the risks and benefits of thrombolysis involve deeply personal values. We evaluated the influence of the inability to consent and of personal health-related values on older adults’ emergency treatment preferences for both ischemic stroke and cardiac arrest.
Physical design of the MUSE wafer-scale circuit

MUSE is a wafer-scale adaptive nulling processor which is being implemented using the restructurable VLSI techniques and design tools. The authors describe the physical design of the wafer with emphasis on interconnect redundancy and design for testability during the restructuring process. Power distribution and the wafer floorplan and packaging are also discussed. >
Nitrosylation of Blood Hemoglobin and Renal Nonheme Proteins in Autoimmune MRL-lpr/lpr Mice

Abstract MRL- lpr / lpr mice spontaneously develop manifestations of autoimmunity including arthritis, vasculitis, and glomerulonephritis. The paramagnetic molecule nitric oxide has been implicated as an effector molecule in initiation and propagation of these inflammatory conditions. In this study, we utilized electron paramagnetic resonance spectroscopy to directly detect nitrosylated protein complexes as products of nitric oxide in whole blood and in kidneys of MRL- lpr / lpr mice. Electron paramagnetic resonance spectra of blood samples from MRL- lpr / lpr mice showed nitrosyl hemoglobin species. Amounts of blood nitrosyl hemoglobin in MRL- lpr / lpr mice were significantly increased as compared to age-matched control mice. Electron paramagnetic resonance spectra of MRL- lpr / lpr kidney tissue exhibited a signal characteristic of a dinitrosyl-iron-dithiolate complex at g ∼ 2.04. Formation of nitrosylated nonheme protein in diseased kidneys is associated with development of glomerulonephritis in the autoimmune mice. The presence of nitrosylated nonheme protein indicates the formation of nitric oxide within the kidneys of the diseased mice signifying in situ renal nitric oxide formation.
Immunosuppression of pulmonary natural killer activity by exposure to ozone.

AbstractOzone is an oxidant gas and an ubiquitous oxidant air pollutant with the potential to adversely affect pulmonary immune function with a consequent increase in disease susceptibility. Pulmonary natural killer (NK) activity was measured in order to assess the pulmonary immunotoxicity of continuous ozone exposure. Continuous ozone exposures at 1.0 ppm were performed for 23.5 hours per day for either 1, 5, 7, or 10 consecutive days. Pulmonary immune function was assessed by measuring natural killer (NK) activity from whole-lung homogenates of male Fischer-344 rats. Results of this study indicated that continuous ozone exposure for 1, 5, or 7 days resulted in a significant decrease in pulmonary NK activity. This suppressed pulmonary NK activity returned to control levels after continuous exposure to ozone for 10 days. The suppressed pulmonary NK response was thus attenuated and returned to normal values in the continued presence of ozone gas. This attenuation process is dynamic, complex, and doubtless ...
Paper: Optimum/near-optimum incentive policies for stochastic decision problems involving parametric uncertainty

In this paper we consider a general class of stochastic incentive decision problems in which the leader has access to the control value of the follower and to private as well as common information on the unknown state of nature. The follower's cost function depends on a finite number of parameters whose values are not known accurately by the leader, and in spite of this parametric uncertainty the leader seeks a policy which would induce the desired behavior on the follower. We obtain such policies for the leader, which are smooth, induce the desired behavior at the nominal values of these parameters, and furthermore make the follower's optimal reaction either minimally sensitive or totally insensitive to variations in the values of these parameters from the nominals. The general solution is determined by some orthogonality relations in some appropriately constructed (probability) measure spaces, and leads to particularly simple incentive policies. The features presented here are intrinsic to stochastic decision problems and have no counterparts in deterministic incentive problems.
Alcoholics in Acute Medical Settings Have Increased Risk for other Drug, Mood, and Personality Disorders

Objective: Brief medical management and alcohol pharmacotherapy are effective treatments for alcoholic participants enrolled in randomized controlled trials, and this suggests that alcoholism treatment may be delivered successfully in medical settings. However, medical patients may differ from clinical trial participants in ways that suggest a need for more intensive alcoholism treatment. To explore this possibility, this study evaluated the prevalence of mental health disorders in the U.S. population stratified by alcoholism and recent hospitalization or emergency room use. Methods: Data from the National Epidemiological Survey on Alcohol and Related Conditions were analyzed. Subjects with information on alcohol use disorders, emergency room use, hospitalization, and several mental health diagnoses were included (n=41,961). Methods appropriate for complex survey data were used to determine the relative risk for mental health diagnoses as a function of a current alcohol use disorder and receipt of acute medical care (hospitalization or emergency room visits) within the past year. Results: Results showed that, relative to alcoholic adults who did not have an emergency room visit or hospitalization, alcoholic adults with use of these services had an increased prevalence of personality disorders, depression, and other drug use disorders. Conclusion: Research is needed to evaluate if these and other differences will lead to poorer treatment outcomes for this group relative to the more selected populations included in medical management efficacy trials.
Isolation of the Interferon-Inducible RNA-Dependent Protein Kinase Pkr Promoter and Identification of a Novel DNA Element within the 5′-Flanking Region of Human and Mouse Pkr Genes

The RNA-dependent protein kinase (PKR) is inducible by interferon (IFN) and is implicated in the antiviral and antiproliferative actions of IFN. We have now isolated human genomic clones that contain the promoter region required for transcription of the Pkr gene. Transient transfection analyses, using chloramphenicol acetyltransferase (CAT) as the reporter in constructs possessing various 5'-flanking fragments of the Pkr gene, led to the identification of a functional TATA-less promoter that directed IFN-inducible transcription of CAT. Sequence determination and deletion analysis of the promoter region revealed an element (5'GGAAAACGAAACT3') involved in IFN inducibility that corresponds to the consensus sequence of the IFN-stimulated response element (ISRE). Comparison of the promoter sequence of the human Pkr gene to that of the mouse homolog identified a novel element (5'GGGAAGGCGGAGTCC3') immediately upstream of the ISRE element which so far is unique to the human and mouse Pkr gene promoters. We have designated this new motif as KCS, for kinase conserved sequence. Deletion and substitution mutants of the Pkr promoter region showed that the ISRE element was required for transcriptional induction by type I IFN, whereas the KCS motif increased promoter activity mediated by the ISRE. Additional potential regulatory cis-elements were identified in the human Pkr promoter that are commonly associated with growth control regulation and differentiation. Other than the ISRE and novel KCS elements, the overall organization of potential binding sites for transcription factors was not well conserved between the IFN-inducible promoters of the human and mouse Pkr genes. The strict conservation of sequence, distance, and position of KCS, relative to ISRE, together with mutagenesis results, suggest an important functional role for the newly recognized KCS motif.
104 Protective Effect of 17ß-Estradiol Against Oxygen Induced Neurodegeneration in the Developing Rat Brain

Neurologic morbidity often occurs in survivors of premature birth. Clinical studies have identified hyperoxia as a risk factor for cerebral palsy. Short exposure to high oxygen levels can trigger neurodegeneration in the developing rat brain. Toxicity of oxygen is associated with inactivation of intracellular proteins that promote survival and increased expression of the proapoptotic Fas-receptor. In this animal model of neonatal brain damage we tested Estradiol against the detrimental effect of oxygen. This hormone has neuroprotective properties that result from activation of estrogen receptors and cross-talk with signaling pathways that are activated by neurotrophins. 6-day old rats were subjected to 80% oxygen and Estradiol was co-administered (600 μg/kg i.p.) at beginning of exposure. Pups were sacrificed at defined time points and brains were either examined histologically to visualize degenerating cells or were snap frozen for molecular studies. Estradiol conferred significant protection against oxygen-induced neurodegeneration. To explore further possible molecular mechanisms, we investigated the impact of Estradiol on the expression of the death receptor Fas and Fas-Ligand. Following hyperoxia for 12 and 24h increased levels of Fas and Fas-Ligand mRNA were found. In the presence of Estradiol mRNA levels of the Fas-system were reduced. Immunoblot analysis on two signaling pathways (MAPK, PI3-kinase) that control neuronal survival, revealed that co-administration of Estradiol counteracts inactivation of the two key players ERK1/2 and AKT. The downregulation in the expression of Fas and Fas-Ligand and increased levels of active forms of ERK1/2 and AKT may represent important mechanisms that lead to survival of neuronal cells. Our results suggest that Estradiol might be suitable as a neuroprotective agent in preterm and term infants who need to be exposed to oxygen. Especially in preterm infants, who are prematurely deprived of maternal intrauterine estrogen, maintaining physiological plasma levels of 17s-Estradiol may help to protect from potentially neurotoxic triggers.
Human Cytomegalovirus UL135 and UL136 Genes Are Required for Postentry Tropism in Endothelial Cells

ABSTRACT Endothelial cells (ECs) are a critical target of viruses, and infection of the endothelium represents a defining point in viral pathogenesis. Human cytomegalovirus (HCMV), the prototypical betaherpesvirus, encodes proteins specialized for entry into ECs and delivery of the genome to the nuclei of ECs. Virus strains competent to enter ECs replicate with differing efficiencies, suggesting that the virus encodes genes for postentry tropism in ECs. We previously reported a specific requirement for the UL133/8 locus of HCMV for replication in ECs. The UL133/8 locus harbors four genes: UL133 , UL135 , UL136 , and UL138 . In this study, we find that while UL133 and UL138 are dispensable for replication in ECs, both UL135 and UL136 are important. These genes are not required for virus entry or the expression of viral genes. The phenotypes associated with disruption of either gene reflect phenotypes observed for the UL133/8 NULL virus, which lacks the entire UL133/8 locus, but are largely distinct from one another. Viruses lacking UL135 fail to properly envelop capsids in the cytoplasm, produce fewer dense bodies (DB) than the wild-type (WT) virus, and are unable to incorporate viral products into multivesicular bodies (MVB). Viruses lacking UL136 also fail to properly envelop virions and produce larger dense bodies than the WT virus. Our results indicate roles for the UL135 and UL136 proteins in commandeering host membrane-trafficking pathways for virus maturation. UL135 and UL136 represent the first HCMV genes crucial for early- to late-stage tropism in ECs. IMPORTANCE Human cytomegalovirus (HCMV) persists in the majority of the world9s population. While typically asymptomatic in healthy hosts, HCMV can cause significant morbidity and mortality in immunocompromised or naive individuals, particularly transplant patients and patients with congenital infections, respectively. Lifelong persistence of the virus may also contribute to age-related pathologies, such as vascular disease. One aspect of HCMV infection contributing to complex and varied pathogenesis is the diverse array of cell types that this virus infects in the host. The vascular endothelium is a particularly important target of infection, contributing to viral dissemination and likely leading to CMV complications following transplantation. In this work, we identify two viral gene products required for postentry tropism in endothelial cells. Identifying tropism factors required for replication in critical cell targets of infection is important for the development of strategies to restrict virus replication.
Role for microtubules in centrosome doubling in chinese hamster ovary cells

The centrosome must be replicated once, and only once, during each cell cycle. To achieve this somatic cells need to synthesize centrosome proteins, target those centrosome proteins to the parental centrosome, and then assemble the centrosome subunits into a functional organelle. The mechanisms that underlie each of these processes are not known. Studies were performed to investigate whether cellular microtubules are involved in centrosome doubling events. For these experiments, CHO cells were arrested in either hydroxyurea (HU) alone or in HU plus a microtubule inhibitor for 36–40 h. The cells then were induced to enter mitosis and the numbers of spindle poles/centrosomes were counted following processing of the cells for immunofluorescence microscopy using anticentrosome antiserum. These studies demonstrated that centrosome replication events occurred in cells arrested with either HU alone or HU and taxol while centrosome replication did not occur in cells treated with HU and either nocodazole or colcemid. Immunoblot analysis determined that centrosome proteins were synthesized in HU/nocodazole-arrested cells and demonstrated that the role of microtubules in the centrosome replication process is not to ensure the synthesis of centrosome subunits. Rather, our results suggest that microtubules may be involved in the transport/targeting of centrosome subunits to the parental centrosome during duplication events. For microtubules to contribute to the transport of centrosome subunits during centrosome doubling, centrosome subunits would need to be able to bind to microtubules. To test this, co-sedimentation studies were performed and it was determined that the centrosome proteins, though overproduced under these conditions, remained soluble in HU/nocodazole-treated cells and co-pelleted with taxol-stabilized microtubules in the presence of GTP and AMP-PNP. Moreover, co-sedimentation of one of the centrosome proteins, PCM-1, with microtubules could be inhibited by pre-incubation of extracts with antibodies against dynactin. Together, these data suggest that during centrosome replication in somatic mammalian cells, PCM-1, and perhaps other centrosome components, are targeted to the centrosome via transport along microtubules by motor complexes that include dynein/dynactin. Cell Motil. Cytoskeleton 42:60–72, 1999. © 1999 Wiley-Liss, Inc.
Impact Of Medical Loss Regulation On The Financial Performance Of Health Insurers

The Affordable Care Act’s regulation of medical loss ratios requires health insurers to use at least 80–85 percent of the premiums they collect for direct medical expenses (care delivery) or for efforts to improve the quality of care. To gauge this rule’s effect on insurers’ financial performance, we measured changes between 2010 and 2011 in key financial ratios reflecting insurers’ operating profits, administrative costs, and medical claims. We found that the largest changes occurred in the individual market, where for-profit insurers reduced their median administrative cost ratio and operating margin by more than two percentage points each, resulting in a seven-percentage-point increase in their median medical loss ratio. Financial ratios changed much less for insurers in the small- and large-group markets.
An ATP, calcium and voltage sensitive potassium channel in porcine coronary artery smooth muscle cells

Abstract There is increasing interest in the roles played by potassium channels of smooth muscle in protecting against ischemic and anoxic insults. Hence, potassium-selective channels were studied in freshly dispersed porcine coronary artery smooth muscle cells using the inside-out variant of the patch-clamp technique. The most abundant potassium channel had a conductance of 148 pS in a 5.4 140 mM K+ gradient, at 0 mV, and was regulated by cytoplasmic ATP (0.05 – 3.0 mM), cytoplasmic Ca2+ (0.1–10 μM) and voltage. ATP and AMP-PNP (0.5 mM) reduced the probability of channel opening (P0) by 87 and 92%, respectively. This inhibition was partially reversed by the addition of 0.5 mM ADP. ADP on its own (2 mM) reduced P0 by 46%. It appears, therefore, that this channel shares properties with both the ATP-sensitive and the calcium-regulated potassium channels, raising the possibility that it plays a central role in the regulation of coronary blood flow.
Effects of Tasks, Salaries, and Shocks on Job Satisfaction Among MIS Professionals

This paper contrasts attitudes and attributes of current and former positions of IT professionals who have changed jobs within the IT field. It also examines relationships among key variables of tasks performed, salary, job satisfaction, and external influences or "shocks" that may have precipitated turnover. Survey data were collected from 169 MIS professionals. Results showed significant changes in task, salary, and job satisfaction between former and current jobs. Detailed examination shows significant increases in project management and business analysis and decrease in 3GL and maintenance programming as well as differences in the amount of change for different elements of job satisfaction. A number of significant relationships among variables between some tasks and salary, some tasks and job satisfaction, and low former job satisfaction and response to particular "shocks" relative to turnover emerged from the data.
Bleaching: Is it safe and effective?

Abstract Bleaching is an effective method of whitening teeth. It is not predictable and has a sufficient history of adverse effects to warrant concern by the profession. Above all, procedures used in dental practice should preserve and protect the oral tissues environment. To date the clinical safety of bleaching has not been demonstrated. Most of the published research indicates that there should be concern for its safety when used in prolonged treatment.
Spatial autocorrelations: a reply to Bebber.

Bebber provides an introduction to the vast and powerful geostatistics literature, which, as he correctly points out, has been applied to a variety of problems in geology, forestry, ecology and more over the past several decades. These techniques generally focus on measuring and understanding the spatial heterogeneity of samples taken at one point in time. In contrast, my review1xKoenig, W.D. Trends Ecol. Evol. 1999; 14: 22–26Abstract | Full Text | Full Text PDF | PubMed | Scopus (337)See all References1 focused explicitly on phenomena that vary from one year (or other relevant time period) to the next.Such data can be analysed by traditional means, and I thank Bebber for clarifying this. However, traditional variography techniques are limited because they measure spatial autocorrelation relative to the overall dataset, whereas when multiple samples over a period of time are available one can also test for significant absolute spatial synchrony between samples or sites a given distance apart2xKoenig, W.D. and Knops, J.M.H. Ecography. 1998; 21: 423–429CrossrefSee all References2. For example, based on samples taken in a single year, traditional geostatistical methods can be used for the analysis of spatial heterogeneity of relative seed production by coniferous trees to answer the following question: are seed crops more similar between sites that are closer together? But, with multiple years of data from each site, we can also ask whether synchrony between sites 1000 km apart (or any other given distance) is statistically greater than zero3xKoenig, W.D. and Knops, J.M.H. Nature. 1998; 396: 225–226CrossrefSee all References3. One can readily forgive geologists for not considering such data; after all, ore levels do not change much from one year to the next. However, questions involving phenomena that vary in both time and space are currently the focus of considerable work by an increasing number of ecologists. It is this rapidly developing area, not traditional spatial methods, that I covered in my review.
Laminin γ1 is critical for Schwann cell differentiation, axon myelination, and regeneration in the peripheral nerve

Laminins are heterotrimeric extracellular matrix proteins that regulate cell viability and function. Laminin-2, composed of α2, β1, and γ1 chains, is a major matrix component of the peripheral nervous system (PNS). To investigate the role of laminin in the PNS, we used the Cre–loxP system to disrupt the laminin γ 1 gene in Schwann cells. These mice have dramatically reduced expression of laminin γ1 in Schwann cells, which results in a similar reduction in laminin α2 and β1 chains. These mice exhibit motor defects which lead to hind leg paralysis and tremor. During development, Schwann cells that lack laminin γ1 were present in peripheral nerves, and proliferated and underwent apoptosis similar to control mice. However, they were unable to differentiate and synthesize myelin proteins, and therefore unable to sort and myelinate axons. In mutant mice, after sciatic nerve crush, the axons showed impaired regeneration. These experiments demonstrate that laminin is an essential component for axon myelination and regeneration in the PNS.
Microbial pathogenesis and host defense in the nematode C. elegans

Epithelial cells line the surfaces of the body, and are on the front lines of defense against microbial infection. Like many other metazoans, the nematode Caenorhabditis elegans lacks known professional immune cells and relies heavily on defense mediated by epithelial cells. New results indicate that epithelial defense in C. elegans can be triggered through detection of pathogen-induced perturbation of core physiology within host cells and through autophagic defense against intracellular and extracellular pathogens. Recent studies have also illuminated a diverse array of pathogenic attack strategies used against C. elegans. These findings are providing insight into the underpinnings of host/pathogen interactions in a simple animal host that can inform studies of infectious diseases in humans.
Dihydrogen activation by a diruthenium analogue of the Fe-only hydrogenase active site.

The photochemical reaction of Ru2(S2C3H6)(CO)4(PCy3)2 (1) and H2 gives the dihydride Ru2(S2C3H6)(μ-H)(H)(CO)3(PCy3)2 (2). NMR and crystallographic studies reveal mutually trans basal phosphine ligands and both bridging and terminal hydrides. Ru2(S2C2H4)(CO)4(PCy3)2 behaves similarly. Other HX substrates undergo photoaddition to 1, affording Ru2(S2C3H6)(μ-H)(X)(CO)3(PCy3)2 for X = OTs (3a), Cl (3b), and SPh (3c). Treatment of Ru2(S2C3H6)(μ-H)(H)(CO)3(PCy3)2 with [H(OEt2)]BArF4 (ArF = B(C6H3-3,5-(CF3)2) in CD2Cl2 gives [Ru2(S2C3H6)(μ-H)(CO)3(PCy3)2(H2)]+ (4), which catalyzes H2−D2 exchange. The reaction of 2 with [D(OEt2)]BArF4 gave [Ru2(S2C3H6)(μ-H)(CO)3(PCy3)2(HD)]+ (JH-D = 31 Hz). These studies provide the first models for the Fe-only hydrogenases that bear dihydrogen and terminal hydrido ligands.
ORIENTATIONAL PROPERTIES OF THE THIRD ORDER NONLINEAR POLARIZATION FOR DEGENERATE OPTICAL INTERACTIONS IN ZINC-BLENDE SEMICONDUCTORS

The orientational dependence of the third order nonlinear optical polarization density for degenerate optical interactions in zinc-blende semiconductors has been derived, corresponding to two-photon absorption and Kerr refraction. A specific emphasis is put on the role of the anisotropic property of the third order optical susceptibility in optical interactions. Significant modulations by the anisotropy on the induced polarization densities are demonstrated for situations of single- and two-beam irradiation. The reduced forms in the isotropic limit are discussed as well. Furthermore for two-beam irradiation in the isotropic limit, we have determined numerical factors of 2 and 2/3 for cross-modulations corresponding to parallel and orthogonal polarizations of the two waves, respectively, with respect to self-modulation.
Central corneal thickness does not correlate with TonoLab-measured IOP in several mouse strains with single transgenic mutations of matricellular proteins.

Abstract Accurate and reliable measurement of intraocular pressure (IOP) is crucial in the study of glaucoma using the mouse model. The purpose of this study was to determine the relationship between TonoLab-measured IOP and central corneal thickness (CCT) in mouse strains with single gene mutations of matricellular proteins. Wild-type (WT) and transgenic mouse strains with single gene mutations (KO) of thrombospondin-1 (TSP-1), thrombospondin-2 (TSP-2), osteopontin (OPN), hevin, and s ecreted p rotein a cidic r ich in c ysteine (SPARC) were imaged at six weeks using optical coherence tomography (Stratus, Zeiss) to determine CCT. IOP was measured between 11am and 3pm using TonoLab, one week later. For all measurements, mice were anesthetized using intraperitoneal injection ketamine:xylazine. CCT and IOP were measured in 583 mice (TSP-1 n = 71 and 41, TSP-2 n = 60 and 32, OPN n = 81 and 50, hevin n = 59 and 76, SPARC n = 54 and 59, WT and KO, respectively). Mean CCT was 5–6% lower in three KO strains—TSP-1, OPN, and SPARC—compared to their corresponding WT (p = 1.55 × 10−7, 1.63 × 10−11, and 1.91 × 10−7, respectively). The mean IOP was 8.3%, 6.6%, and 15.1% lower in three KO strains—TSP-1, TSP-2, and SPARC—compared to corresponding WT (p = 2.11 × 10−5, 2.93 × 10−3, and 3.76 × 10−9, respectively. Linear regression of IOP versus CCT yielded no statistically significant within-strain correlations for TSP-1 (p = 0.12 and 0.073), TSP-2 (p = 0.473 and 0.92), OPN (p = 0.212 and 0.916), Hevin (p = 0.746 and 0.257), and SPARC (p = 0.080 and 0.056), reported as p-values considering a null hypothesis of zero slope (WT and KO, respectively). Neither C57-derived strains (TSP-1 and OPN) nor 129-derived strains (TSP-2, hevin, SPARC) demonstrated a correlation between mean IOP and mean CCT across different strains (p = 0.75 and p = 0.53, respectively). Taken together, these results indicate that CCT is not required to interpret TonoLab IOP readings in the mice when CCT varies 10% about the mean. This does not exclude the possibility of an IOP-CCT correlation for CCT values outside this range or for inter-strain comparisons where the mean CCT differs more than 10%.