cssi/SciSciGPT-SciSciNet huggingface dataset:
Stress signalling pathways that impair prefrontal cortex structure and function

Stress affects cognition and increases noradrenaline and dopamine levels in the prefrontal cortex (PFC). Amy Arnsten discusses the intracellular signalling pathways that mediate the effects of these catecholamines on PFC function during acute and chronic stress, focusing on working memory. An interview with Amy Arnsten for Neuropod is available for download . The prefrontal cortex (PFC) — the most evolved brain region — subserves our highest-order cognitive abilities. However, it is also the brain region that is most sensitive to the detrimental effects of stress exposure. Even quite mild acute uncontrollable stress can cause a rapid and dramatic loss of prefrontal cognitive abilities, and more prolonged stress exposure causes architectural changes in prefrontal dendrites. Recent research has begun to reveal the intracellular signalling pathways that mediate the effects of stress on the PFC. This research has provided clues as to why genetic or environmental insults that disinhibit stress signalling pathways can lead to symptoms of profound prefrontal cortical dysfunction in mental illness.
Moving an Evidence-Based Intervention Into Routine Mental Health Care: A Multifaceted Case Example

Many evidence-based interventions fail to translate into routine care for individuals experiencing significant mental health disorders. Moving the evidence-based intervention from the controlled research settings to the broader mental health systems is an ongoing challenge for administrators and practitioners in the mental health delivery network. In the United States, the movement to bring evidence-based mental health interventions into the public mental health system to enhance consumer recovery and improve outcomes has been a major thrust of federal and state efforts over the past 10 years (IOM, 2006; New Freedom Commission on Mental Health, 2003; Michigan Mental Health Commission, 2004; U.S. Department of Health and Human Services, 1999). Using a multifaceted case example, this article will address one state's efforts to implement an evidence-based intervention, Family Group Psychoeducation (FPE), into routine care for individuals living with schizophrenia and their families. The Consolidated Framewor...
RS4: A MODEL-BASED EVALUATION OF INHALED STEROIDS IN MILD-TO-MODERATE ASTHMA

OBJECTIVE: To forecast the discounted costs and clinical consequences of inhaled corticosteroids (ICS) in a population of adults with mild-to-moderate asthma. METHODS: We developed a Markov, state-transition simulation of asthma patient care and its pharmacoeconomic impact. We employed this framework to compare quick relievers (e.g., b-agonists) on an as-needed basis to quick relievers plus ICS therapy targeted to one of three severity sub-populations. State-space dimensions included patient age, clinical history, and lung dysfunction (measured via forced expiratory volume in one second, FEV1). Risk functions were estimated from symptom, exacerbation, and hospitalization rates obtained from literature reviews and analyses of primary, cross-sectional data. Systematic review of published trials yielded 16 eligible studies and produced the following outcome ranges for sensitivity analysis: 1%–21% improvement in FEV1; monthly costs of $14–$76; and 0%–4% probability of major toxicity. Societal costs were derived from published economic studies of inpatient and outpatient asthma. We collected preference weights (using standard gambles, time trade-offs, and the Health Utilities Index) in a cross-sectional study of 100 adult asthmatics. RESULTS: The table reports outcomes over a 10-year period. Results were driven by the impact of ICS on quality of life, rather than on mortality. Findings were stable over most input data ranges. However, at efficacy levels below 3% and toxicity rates greater than 2.9%, the cost-effectiveness estimate exceeded $100,000/QALY. CONCLUSION: Results suggest that inhaled steroids deliver good comparative value in mild-to-moderate adult asthma. More research is needed, however, on the impact of ICS toxicity on patient preferences. Strategy Cost QALY $QALY Quick Relievers alone $5,185 6.77 — +ICS in moderate disease $5,961 6.84 $10,300 +ICS in mild disease $7,616 6.93 dominated +ICS in mild/mod. disease $8,392 7.00 $15,000
Impact of automated telephone messaging on zoster vaccination rates in community pharmacies.

Objective To measure the impact of an automated outbound telephone messaging system on herpes zoster (HZ) vaccinations among older adults in the community pharmacy setting. Design Randomized controlled trial. Setting 16 grocery store chain community pharmacies in Georgia and Tennessee, between December 2006 and May 2007. Patients Adults 60 years or older who filled at least one prescription at a participating study pharmacy. Intervention A 30-second automated outbound telephone message was delivered to patient households monthly during the first week of March through May 2007. The message advertised that older adults should speak with their pharmacist about the risk for HZ and the availability of a new vaccine. Main outcome measure HZ vaccinations based on pharmacy profile records. Results After 3 months, 146 and 46 vaccinations were administered to older adults among the study cohort populations, translating into HZ vaccination rates of 2.60% and 0.72% at intervention and control pharmacies, respectively (odds ratio 3.69 [95% CI 2.64–5.15], P Conclusion Use of an automated outbound telephone messaging tool to inform older adults about their risk for HZ and the availability of a vaccine significantly improved vaccination rates in the community pharmacy setting.
Ultrastructures of rabbit corneal stroma: mapping of optical and morphological anisotropies.

Abstract Pole figures of optic and morphological structures of rabbit corneal stroma have been determined. The birefringence of stroma is non-uniform, but tends to increase in the directions of nose to ear and of periphery to the vertex. There is no obvious symmetry in the local optic axes. Its direction changes from limbus to limbus. Small angle laser scattering showed stroma to have sheaf-like morphology. This texture is consistent with bundles of collagen fibrils which divide and anastomose. The average size of the scattering entities in rabbit corneal stroma is 19–23 μm with sector angles β ranging from 1 to 15°.
Current Development of Collagen-Based Biomaterials for Tissue Repair and Regeneration

Collagens, especially Type I collagen, are the primary structural proteins in the body. They sustain mechanical bodily stresses, support different types of cells, and serve as anchors for various growth factors. The collagen-peptides produced when collagens are cleaved by enzymatic activities also exhibit potent biological activities. As highly biocompatible molecules with potent biological functions, the collagens have garnered wide interest as biomedical materials, in particular, for tissue repair and regeneration. This review first provides a brief introduction to collagen structure and classification, and then primarily focuses on the current development of collagen-based biomaterials, with emphasis on collagen-based scaffolding materials for tissue regeneration.
HIV and HHV-8 negative primary effusion lymphoma in a patient with hepatitis C virus-related liver cirrhosis.

Primary effusion lymphoma (PEL) or body cavity-based lymphoma (BCBL) is a unique subgroup of B-cell lymphomas that exhibits exclusive or dominant involvement of serous body cavities without a detectable tumor mass. We present a case of a PEL/BCBL that exclusively involved the peritoneal cavity of a 58-year-old immunocompetent male with hepatitis C virus (HCV)-related liver cirrhosis. The lymphoma cells were large, highly atypical and expressed CD19, CD20, CD22, CD10, HLA-DR, and CD45 with kappa light chain restriction. Unlike typical PEL/BCBL, human herpesvirus type 8/Kaposi sarcoma herpes virus (HHV-8/KSHV) genomic sequence was not present in the lymphoma cells and there was no serologic evidence of human immunodeficiency virus (HIV) infection. This is the fourth reported case of HHV-8 negative, HIV negative PEL/BCBL in a patient with associated HCV-related cirrhosis and review of these cases showed some consistent clinicopathological features, i.e. exclusive involvement of the peritoneal cavity and phenotypic expression of B-cell associated antigens in contrast to the generally null phenotype PEL/BCBL. The occurrence of these cases suggests that HCV may play an etiological role in a subcategory of PEL/BCBL not associated with HHV-8.
Combined atrial and ventricular parasystole.

Abstract Two cases presenting the very rare combination of atrial and ventricular parasystole have been described. The rates of the atrial and ventricular parasystole were slower than 40/ min. This is not an unusual finding since the parasystolic rate may be slower or faster than the inherent automaticity of impulse formation. However, the question of exit block was also raised in view of the unusually slow rate of the atrial parasystole (17/min.) in the first case.
Preparing STEM Doctoral Students for Future Faculty Careers.

This chapter describes programs created to improve the preparation of future STEM faculty for their roles as educators.
Local Organizing for Environmental Conflict: Explaining Differences between Cases of Participation and Nonparticipation

Grassroots groups continue to compose a large part of the environmental movement in the United States. In this article, I examine 41 attempts by grassroots groups to work with the Sierra Club to participate in local environmental conflicts. I argue that the difference between those groups who participated in a local conflict and those groups who were unable to participate in a conflict can be explained by the ability of a group to mobilize resources, gain access to information, create ties to other participants, control the framing of a conflict, and sustain these four factors across the duration of the conflict. Using Qualitative Comparative Analysis, I argue that having resources and information is useful for participation but not sufficient to guarantee participation. Ultimately, participation occurs when local groups have ties with other participants in the conflict and/or the ability to control the framing of the conflict.
A simple statistical field theory of heteropolymer collapse with application to protein folding

A simple statistical extension of the Flory theory of excluded volume is developed, and applied to random heteropolymer collapse and a simple model of protein folding. Sequence heterogeneity is found to lead to new effects. The nucleation of protein folding is also briefly considered.
Binding of native and reduced and carbamidomethylated hGH to rabbit liver plasma membranes.

The binding properties of reduced and carbamidomethylated hGH (RCAM-hGH) were compared to those of native hGH. The time course of binding to rabbit liver plasma membranes and the response of binding to temperature of both RCAM-hGH and hGH were similar. RCAM-hGH binding exhibited a broad pH optimum for binding which was approximately 50% of the peak of hGH binding at pH 6. RCAM-hGH binding was not enhanced by divalent cations to the same extent as hGH binding, but monovalent cations affected the binding of both hormones similarly. The most striking difference in binding between RCAM-hGH and hGH was observed in the displacement curves of the hormones. Half-maximal displacement of 125I-hGH occurred at 19 and 38 pmoles⁄ml hGH and RCAM-hGH, respectively. In comparison, half-maximal displacement of 125IRCAM- hGH occurred at 26 and 46 pmoles⁄ml RCAM-hGH, respectively. Approximately 30–40% of l25I-RCAM-hGH was nondisplaceable by both RCAM-hGH and hGH compared to 10% for 125I-hGH. Scatchard plots of 125I-hGH bindi...
Congressional Decision Making and the Separation of Powers

To what extent does the separation of powers affect congressional roll call voting behavior? To answer this question, I offer a strategic model of congressional decision making that asserts members of Congress pursue public policy goals when casting roll call votes. From the equilibrium predictions of a formal model, I generate testable hypotheses by computing the expected net amount of sophisticated (nonsincere) congressional behavior given changes in decision context. I test the predictions of the theoretical model with data from all civil rights roll call votes from the 83d to the 102d Congress. The results demonstrate that both the other legislative chamber and the Supreme Court profoundly constrain House members and senators when casting roll call votes. This is strong evidence of the importance of policy outcomes to members of Congress when voting on the floor.
The effects of acute self-paced exercise and respiration biofeedback on anxiety and affect in high-stress university students

High rates of stress-related problems in college students and low utilization of treatment options show a need for simple, effective interventions for stress management. Both exercise and breathing biofeedback have proven effective in reducing state anxiety in the past, but have never been compared. The purpose of this study was to evaluate the efficacy of brief exercise and breathing biofeedback interventions on altering state anxiety and affect in high-stress, college students. Thirty-two participants (mean age=21.5±3.2 years; 21 female) experienced the following 10-minute interventions on separate days: self-paced walk (EX), breathing biofeedback (BF) and a placebo condition of quiet study (QS). Anxiety and affect data were gathered using the State Anxiety Inventory (SAI) and Activation Deactivation Adjective Checklist (AD-ACL), respectively, before (Pre), immediately after (Post0), and 15 minutes after (Post15) the intervention in each condition. Heart rate variability (HRV) was measured at 2 time points (Preand Post-intervention). Mixed-factor Condition (3) x Time (3) repeated-measures ANOVAs were run on State Anxiety and Affect. Condition (3) x Time (2) ANOVAs were performed on HRV variables. Follow up time (3) repeated-measures ANCOVAs were run on EX and BF conditions for State Anxiety and Affect variables with HRV variables as covariates. Findings demonstrated that BF reduced anxiety, with the effect size for the BF condition nearly double that of the EX condition (Pre to Post15: BF d=-.39, EX d=-.21). Secondly, the EX condition increased Energy from Pre to Post0 (d = .68) that then returned to
Using race as a case-mix adjustment factor in a renal dialysis payment system: potential and pitfalls.

Background: Racial disparities in health care are widespread in the United States. Identifying contributing factors may improve care for underserved minorities. To the extent that differential utilization of services, based on need or biological effect, contributes to outcome disparities, prospective payment systems may require inclusion of race to minimize these adverse effects. This research determines whether costs associated with end-stage renal disease (ESRD) care varied by race and whether this variance affected payments to dialysis facilities. Study Design: We compared the classification of race across Medicare databases and investigated differences in cost of care for long-term dialysis patients by race. Setting & Participants: Medicare ESRD database including 890,776 patient-years in 2004-2006. Predictors: Patient race and ethnicity. Outcomes: Costs associated with ESRD care and estimated payments to dialysis facilities under a prospective payment system. Results: There were inconsistencies in race and ethnicity classification; however, there was significant agreement for classification of black and nonblack race across databases. In predictive models evaluating the cost of outpatient dialysis care for Medicare patients, race is a significant predictor of cost, particularly for cost of separately billed injectable medications used in dialysis. Overall, black patients had 9% higher costs than nonblack patients. In a model that did not adjust for race, other patient characteristics accounted for only 31% of this difference. Limitations: Lack of information about biological causes of the link between race and cost. Conclusions: There is a significant racial difference in the cost of providing dialysis care that is not accounted for by other factors that may be used to adjust payments. This difference has the potential to affect the delivery of care to certain populations. Of note, inclusion of race into a prospective payment system will require better understanding of biological differences in bone and anemia outcomes, as well as effects of inclusion on self-reported race. Am J Kidney Dis 56:928-936. © 2010 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Glutamate receptors localize postsynaptically at neuromuscular junctions in mice.

Dlg (Discs Large) and its mammalian homologs are members of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins that contain multiple protein interaction domains. Drosophila dlg mutant NMJs have mislocalized inward-rectifying potassium channels and functional deficits resulting from a specific decrease of glutamate receptors.5,8 The mammalian ortholog of Dlg (SAP97 in rat; hDlg in human; mDlg in mouse; hereafter referred to as Dlg) interacts with and is capable of regulating the trafficking and synaptic activity of AMPA and NMDA glutamate receptors in experiments conducted in neuronal cultures and hippocampal slices.1,6,12,22,24,27,28,31,33,36,37 Dlg PDZ domains also interact with inward-rectifying potassium channels of the Kir2 family at postsynaptic densities and axons in the mammalian central nervous system (CNS).11,14,21,39 We have recently shown that Dlg is present at the postsynaptic membrane of the NMJ, raising the question of whether any of its interactors at other synapses are present postsynaptically at the mammalian NMJ.35 Mammalian cholinergic neuromuscular junctions (NMJs) have been contrasted with CNS synapses where a diversity of glutamatergic receptors are present.34 However, glutamatergic NMDA receptor subunit 1 (NR1) has been shown to localize to the mammalian NMJ, although its specific subcellular localization was not investigated.2,13,23 Mature postsynaptic skeletal muscle membranes are topologically complex structures where proteins differentially localize (Fig. 1A) (reviewed in Refs. 16,18). For instance, acetylcholine receptors (AChRs) are concentrated in the primary gutter and Na+ channels are concentrated at the depths of secondary folds.10 FIGURE 1 Localization of glutamate receptors and potassium channels at NMJs. A: Schematic of the mammalian NMJ shows a Schwann cell (blue), the axon terminal (orange), and the skeletal muscle postsynaptic membrane composed of the primary gutter where AChRs localize ... Here we show that NR1 and NR2A NMDA receptor subunits, along with AMPA receptor subunits GluR1 and GluR2/3, specifically localize postsynaptically at the NMJ. Both these glutamate receptors and potassiumchannels of the Kir2 family are not coincident with AChRs, but instead show overlapping localization with Dlg. The localization of glutamate and its receptors at the NMJ suggests the presence of mechanisms that have not yet been elucidated at this synapse.
IlliTC – low-temperature cracking model for asphalt pavements

Low-temperature cracking (LTC) is a major distress and cause of failure for asphalt pavements located in regions with cold climate; however, most pavement design methods do not directly address LTC. The thermal cracking model (TCModel) utilised by American Association of State Highway and Transportation Officials Mechanistic-Empirical Pavement Design Guide relies heavily on phenomenological Paris law for crack propagation. The TCModel predictions are primarily based on tensile strength of asphalt mixture and do not account for quasi-brittle behaviour of asphalt concrete. Furthermore, TCModel utilises a simplified one-dimensional viscoelastic solution for the determination of thermally induced stresses. This article describes a newly developed comprehensive software system for LTC prediction in asphalt pavements. The software system called ‘IlliTC’ utilises a user-friendly graphical interface with a stand-alone finite-element-based simulation programme. The system includes a preanalyser and data input gene...
Analysis of investment choices for retirement: a new approach and perspective

Abstract This paper evaluates deductible individual retirement accounts (IRAs), Roth IRAs, non-deductible IRAs, and open taxable investments using equal initial after-tax investments for the different choices. The concept of a break-even tax rate at the time of withdrawal of funds is used to analyze optimal choice between the deductible IRA and the Roth IRA. The break-even tax rate is seen to be a decreasing function of rate of return on the investment and the investment horizon. Regarding non-deductible IRAs, and open taxable investments, the findings indicate that the non-deductible IRA is the optimal choice for individuals with long investment horizons.
Amorphous Al(Ni) alloy formation by pulsed-electron-beam quenching

The microstructural transition from the epitaxial crystalline to amorphous state as a function of Ni concentration is examined in Al(Ni) alloys formed by ion implantation and e-beam melt quenching. The evolution from epitaxial crystalline Al at less than or equal to 3.5 at. % Ni to amorphous phase formation at 15 to 30 at. % Ni is characterized in detail for 8, 10 and 12% Ni uniform concentration samples by ion channeling and transmission electron microscopy. The transition occurs via complete loss of epitaxial regrowth at 9 at. % and the formation of a fine-grained polycrystalline Al, with grain size decreasing with increasing Ni from 20 to 100 A at 10% Ni concentration to less than or equal to 10 to 50 A at 12% Ni.
Combinatorics of theq-Basis of Symmetric Functions

A basis of symmetric functions, which we denote byq?(X; q, t), was introduced in the work of Ram and King and Wybourne in order to describe the irreducible characters of the Hecke algebras of type A. In this work we give combinatorial descriptions of the expansions of the functionsq?(X; q, t) in terms of the classical bases of symmetric functions and apply these results in determining the determinant of the character table of the Iwahori?Hecke algebras and in giving a generating function for certain permutation statistics.
Discovery of a T dwarf binary with the largest known J-band flux reversal

We present Keck laser guide star observations of two T2.5 dwarfs—2MASS J11061197+2754225 and 2MASS J14044941� 3159329—using NIRC2 on Keck II and find 2MASS J14044941� 3159329 to be a 0.13 00 binary. This system has a secondary that is 0.45 mag brighter than the primary in J band, but 0.49 mag fainter in H band and 1.13 mag fainter in Ks band. We use this relative photometry along with near-infrared synthetic modeling performed on the integrated light spectrum to derive component types of T1 � 1for the primary and T5� 1f or the secondary. Optical spectroscopy of this system obtained with Magellan/LDSS-3 is also presented. This is the fourth L/T transition binary to show a flux reversal in the 1Y1.2 � m regime, and this one has the largest flux reversal.Unlessthesecondaryisitself anunresolvedbinary,theJ-bandmagnitudedifferencebetweenthesecondary and primary shows that the J-band ‘‘bump’’ is indeed a real feature and not an artifact caused by unresolved binarity. Subject headingg binaries: close — binaries: general — stars: individual (2MASS J11061197+2754225, 2MASS J14044941� 3159329) — stars: low-mass, brown dwarfs — techniques: high angular resolution — techniques: spectroscopic
British Colonial Education in Africa: Policy and Practice in the Era of Trusteeship

Historians continue to debate the role of the colonial state in the history of Africa and whether and how the state addressed problems of social welfare. In the early twentieth century, plans for Native Education were central to the construed mission of the state to serve as “Trustees for native peoples.” This article surveys the theories, aims, and practice of British education in Africa, focusing on the period between WWI and WWII when the colonial state took an unprecedented role in crafting an education policy for the whole of its African territory. It examines the role of American philanthropy, the controversy of English vs. vernacular language education, the relationship between settler communities and African labor, and African and metropolitan social movements in forming and executing education policy.
Evaluating the Mechanisms of Improved Glucose Homeostasis after Bariatric Surgery in Ossabaw Miniature Swine

Background. Roux-en-Y gastric bypass (RYGB) is the most common bariatric operation; however, the mechanism underlying the profound weight-independent effects on glucose homeostasis remains unclear. Large animal models of naturally occurring insulin resistance (IR), which have been lacking, would provide opportunities to elucidate such mechanisms. Ossabaw miniature swine naturally exhibit many features that may be useful in evaluating the anti diabetic effects of bariatric surgery. Methods. Glucose homeostasis was studied in 53 Ossabaw swine. Thirty-two received an obesogenic diet and were randomized to RYGB, gastrojejunostomy (GJ), gastrojejunostomy with duodenal exclusion (GJD), or Sham operations. Intravenous glucose tolerance tests and standardized meal tolerance tests were performed prior to, 1, 2, and 8 weeks after surgery and at a single time-point for regular diet control pigs. Results. High-calorie-fed Ossabaws weighed more and had greater IR than regular diet controls, though only 70% developed IR. All operations caused weight-loss-independent improvement in IR, though only in pigs with high baseline IR. Only RYGB induced weight loss and decreased IR in the majority of pigs, as well as increasing AUCinsulin/AUCglucose. Conclusions. Similar to humans, Ossabaw swine exhibit both obesity-dependent and obesity-independent IR. RYGB promoted weight loss, IR improvement, and increased AUCinsulin/AUCglucose, compared to the smaller changes following GJ and GJD, suggesting a combination of upper and lower gut mechanisms in improving glucose homeostasis.
The drawbacks and dangers of active defense

The growing prevalence of cyber-attacks on states, businesses, and individuals has raised new and urgent questions about the legal framework that governs states' capacity to respond such attacks. An issue that has proven particularly vexing is what actions a state may take in response to attacks that fall into the gap between the actions that constitute a prohibited “use of force” under Article 2(4) of the UN Charter and the “armed attacks” to which a state has a right to respond with force in self defense under Article 51. Intrusions that constitution an illegal “use of force” but do not meet the “armed attack” threshold for triggering a legal forceful response-sometimes known as “below the threshold” cyber-operations-are extraordinarily common. Indeed, nearly all cyber-attacks by one state on another fall below the “armed attack” threshold. If states cannot legally use their right to self-defense to respond to such unlawful attacks, what can they do? There is a growing consensus that the answer can be found in countermeasures doctrine. Yet countermeasures doctrine was never intended to be applied to actions that constitute uses of force. There is good reason for this: if forceful countermeasures were allowed, there would be a serious danger that the system restricting illegal use of force would spin out of control. Improper countermeasures are inevitable, and escalation of confl ict only a matter of time. This paper outlines the legal principles governing the use of force in international affairs, describes the exceptions to the broad prohibition on the use of military force, outlines the doctrine of countermeasures, and-in its key contribution to the debate-outlines reasons for concern about aggressive countermeasures. The paper concludes by briefl y considering non-forceful responses that states may take in response to cyber-attacks.
Domain Wall Pinning and Corresponding Energy Barrier in Percolated Perpendicular Medium

The domain wall pinning processes in a percolated perpendicular medium are studied using micromagnetic modeling. With a given nonmagnetic pinning site, the energy barrier of the pinned domain wall reaches a maximum when the domain wall width is about twice the size of the pinning site. For transitions in the percolated perpendicular medium, the energy barrier for the transition shift is sensitive to the pinning site spacing. Considering regularly distributed pinning sites with 4.7-nm center-to-center spacing, the energy barrier for the transition shift is about twice the energy barrier of the domain wall pinned by one pinning site. The domain stability in percolated perpendicular medium is also discussed with an analytic model
Novel Targets for Pancreatic Cancer Therapy

Pancreatic adenocarcinoma (PDA) is one of the cancers that is resistant to most conventional anticancer therapies. PDA-affected patients show a poor prognosis. The 5-year survival rate for PDA is 5% and has changed little over the past few decades. This has prompted extensive research to identify new agents that can be used for anticancer therapy. The only cytotoxic drug that has been approved by the Food and Drug Administration (FDA) is gemcitabine, which offers marginal benefits to patients in terms of symptom control and prolongation of life. Various strategies like targeting the epidermal growth factor receptor pathway and vascular endothelial growth factor receptor pathway have been researched upon. But these strategies have not provided promising results and none of the FDA-approved targeted agents have added any substantial clinical benefit to gemcitabine except for a marginal benefit from erlotinib. This article discusses various possible new targets and new agents for the anticancer therapy for PDA.
Comparison of Activities of Broad-Spectrum β-Lactam Compounds against 1,128 Gram-Positive Cocci Recently Isolated in Cancer Treatment Centers

We report the in vitro activities of broad-spectrum β-lactam antimicrobials tested against 1,128 gram-positive pathogens recently isolated from cancer patients. Cefepime and imipenem were more active than ceftazidime and ceftriaxone against these organisms. Only vancomycin demonstrated reliable activity against oxacillin-resistant staphylococci, Enterococcus spp., and Corynebacterium spp. The spectrum of gram-positive organisms against which cefepime and imipenem have activity provides an advantage over ceftazidime as empiric therapy for cancer patients, potentially reducing the need for the empiric addition of glycopeptides.
Studies of multibaseline spaceborne interferometric synthetic aperture radars

The authors have utilized a set of Seasat synthetic aperture radar (SAR) data that were obtained in nearly repeat ground-track orbits to demonstrate the performance of spaceborne interferometric SAR (INSAR) systems. An assessment of the topography measurement capability is presented. A phase measurement error model is described and compared with the data obtained at various baseline separations and signal-to-noise ratios. Finally, the implications of these results on future spaceborne INSAR design are discussed. >
REDUCED COLD-HARDINESS OF PEAR PSYLLA (HOMOPTERA: PSYLLIDAE) CAUSED BY EXPOSURE TO EXTERNAL WATER AND SURFACTANTS

Overwintering pear psylla, Cacopsylla pyricola (Foerster), were misted with water or with one of several dilute solutions of water and surfactant, and then exposed to a range of subzero temperatures for 24 h. Misted psylla had significantly greater mortality than unmisted controls. Increases in mortality occurred at temperatures as warm as −6°C, a temperature well within the range of conditions in the field. At extreme low temperatures (−18°C) there was virtually no mortality in the unmisted controls, whereas mortality approached or reached 100% in several of the misted groups. Temperatures necessary to kill 50% of insects estimated for topically treated psylla ranged between −2.6 and −12.7°C for surfactant-treated insects, and below −18°C for water-treated or control insects. The possibility of using surfactants and water for control of overwintering pear psylla is discussed.
Performing embodied identity in virtual worlds

Embodied identity, that is, who we are as a result of our interactions with the world around us with and through our bodies, is increasingly challenged in online environments where identity performances are seemingly untethered from the user's body that is sitting at the computer. Even though disembodiment has been severely criticized in the literature, most conceptualizations of the role of users’ bodies in virtuality nevertheless reflect a representational logic, which fails to capture contemporary users’ experience of cyborgism. Relying on data collected from nine entrepreneurs in the virtual world Second Life (SL), this paper asks how embodied identity is performed in virtual worlds. Contrasting representationalism with performativity, this study highlights that the SL entrepreneurs intentionally re-presented in their avatars some of the attributes of physical bodies, but that they also engaged in habitual practices in-world, thereby unconsciously enacting embodied identities in both their ‘real’ and virtual lives.
Visual information processing from multiple displays

Objective: In this study, we examined how effectively people can monitor new stimuli on a peripheral display while carrying out judgments on an adjacent central display. Background: Improved situation awareness is critical for improved operator performance in aviation and many other domains. Given the limited extent of foveal processing, acquiring additional information from peripheral vision offers high potential gains. Method: Participants carried out a sequence of central perceptual judgments while simultaneously monitoring the periphery for new stimuli. Peripheral detection was measured as a function of central-judgment difficulty, the relative timing of the two tasks, and peripheral event rate. Results: Participants accurately detected and located peripheral targets, even at the highest eccentricity explored here (~30°). Peripheral detection was not reduced by increased central-task difficulty but was reduced when peripheral targets arrived later in the processing of central stimuli and when peripheral events were relatively rare. Conclusion: Under favorable conditions—high-contrast stimuli and high event rate—people can successfully monitor peripheral displays for new events while carrying out an unrelated continuous task on an adjacent display. Application: In many fields, such as aviation, existing displays were designed with low-contrast stimuli that provide little opportunity for peripheral vision. With appropriate redesign, operators might successfully monitor multiple displays over a large visual field. Designers need to be aware of nonvisual factors, such as low event rate and relative event timing, that can lead to failures to detect peripheral stimuli.
Single-walled carbon nanotube interactions with HeLa cells.

This work concerns exposing cultured human epithelial-like HeLa cells to single-walled carbon nanotubes (SWNTs) dispersed in cell culture media supplemented with serum. First, the as-received CoMoCAT SWNT-containing powder was characterized using scanning electron microscopy and thermal gravimetric analyses. Characterizations of the purified dispersions, termed DM-SWNTs, involved atomic force microscopy, inductively coupled plasma – mass spectrometry, and absorption and Raman spectroscopies. Confocal microRaman spectroscopy was used to demonstrate that DM-SWNTs were taken up by HeLa cells in a time- and temperature-dependent fashion. Transmission electron microscopy revealed SWNT-like material in intracellular vacuoles. The morphologies and growth rates of HeLa cells exposed to DM-SWNTs were statistically similar to control cells over the course of 4 d. Finally, flow cytometry was used to show that the fluorescence from MitoSOX™ Red, a selective indicator of superoxide in mitochondria, was statistically similar in both control cells and cells incubated in DM-SWNTs. The combined results indicate that under our sample preparation protocols and assay conditions, CoMoCAT DM-SWNT dispersions are not inherently cytotoxic to HeLa cells. We conclude with recommendations for improving the accuracy and comparability of carbon nanotube (CNT) cytotoxicity reports.
HOSPITALIZATION, INPATIENT PHYSICAL THERAPY AND INSTITUTIONALIZATION AFTER HOSPITAL DISCHARGE OF PROSTATE CANCER PATIENTS IN SOUTH FLORIDA

AbstractPurpose: Explaining survival variation in prostate cancer requires the identification of new predictive factors, of which physical function is attractive hypothetically. To understand physical dysfunction in prostate cancer better, we examined medical claims. Our aims were to describe the consumption of inpatient resources, examine the association of physical therapy institutionalization after hospital discharge and determine the association of disease stage with frequency of hospitalization, inpatient physical therapy and discharge to a skilled nursing facility.Materials and Methods: We used 1994 Medicare claims for patients in South Florida who had prostate cancer. To examine the association of disease stage with use of health services, we inferred disease stage from stage specific treatment. Multiple linear regression was used to examine the interaction of inferred disease stage with health services while adjusting for age.Results: A total of 22,279 residents of South Florida a mean of 78.3 yea...
Outcome measurement in sleep medicine practice and research. Part 2: assessment of neurobehavioral performance and mood

Neurobehavioral performance and alterations in mood consequent to sleep disorders and their treatment has recently been the focus of clinical investigations. Primarily in patients with obstructive sleep apnea (OSA), there has been increased interest in the effects of sleep fragmentation and hypoxemia on the brain's ability to process information and to alter affect. The purpose of the second part of this two-part series is to describe measures that could be applied to document the impact of sleep disorders on neurobehavioral performance and mood, discuss factors affecting the selection of measures for research and practice, and to describe evidence generated by the use of these instruments in research. The neurobehavioral deficits that accompany sleep deprivation can be categorised as decrements in cognitive throughput, working memory and sustained attention. Usually evaluated using tasks of short duration, impairments associated with OSA have included impaired information processing and decline in the total number of completed and/or correct responses per unit time. Using assessments of working memory, including short recall maneuvers involving words or paragraphs, investigators have documented in sleep apnea patients the inability to consolidate and recall material producing deficits in the recollection and retention of new information. Evaluations of sustained attention appraise reaction time, the ability to remain on task, and the number of errors of omission and false responses. Evidence suggests that OSA patients display slowing of response time as well as increased errors, lapses and number of false responses. Similar deficits have been documented with sustained and divided attention tasks that present the respondent with challenges in tracking and reaction response, tasks required for driving. Although untreated sleep apnea patients were more impaired than normal controls, their performance on such tasks was greatly enhanced following CPAP treatment. In addition to substantial clinically meaningful improvements in many areas of neurobehavioral performance, changes in mood have also accompanied treatment for sleep apnea. 2001 Harcourt Publishers Ltd
Microscopic model for fracture of crystalline Si nanopillars during lithiation

Abstract Silicon (Si) nanostructures are attractive candidates for electrodes for Li-ion batteries because they provide both large specific charging capacity and less constraint on the volume changes that occur during Li charging. Recent experiments show that crystalline Si anodes expand highly anisotropically through the motion of a sharp phase boundary between the crystalline Si core and the lithiated amorphous Si shell. Here, we present a microscopic model to describe the size-dependent fracture of crystalline Si nanopillars (NPs) during lithiation. We derive a traction–separation law based on the plastic growth of voids, which, in turn, is used in a cohesive zone-finite element model. The model allows for both the initiation of cracking and crack growth. The initial size and spacing of the nanovoids, assumed to be responsible for the fracture, together with the computed facture toughness, are chosen to conform to recent experiments which showed the critical diameter of Si NPs to be 300–400 nm. The anisotropy of the expansion is taken into account and that leads naturally to the observed anisotropy of fracture. The computed work of fracture shows good agreement with recent experimental results and it may be possible to use it to describe the failure for other loading and geometries.
Pleiotropic effects on mandibular morphology I. Developmental morphological integration and differential dominance.

Pleiotropy refers to a single genetic locus that affects more than one phenotypic trait. Pleiotropic effects of genetic loci are thought to play an important role in evolution, reflecting functional and developmental relationships among phenotypes. In a previous study, we examined pleiotropic effects displayed by quantitative trait loci (QTLs) on murine mandibular morphology in relation to mandibular structure and function. In replicating most of our previous QTLs and increasing our sample size, this study strengthens and extends our earlier results. As in our previous study, we find that QTL effects tend to be restricted to developmentally or functionally related traits. In addition, we examine patterns of differential dominance for pleiotropic QTL effects. Differential dominance occurs when dominance patterns for a single locus vary among traits. We find that multivariate overdominance is a common and substantial phenomenon, and may potentially provide an explanation for the persistence of heterozygosity in natural populations.
Abstract 2305: Endothelin-1 Alters Nitric Oxide-Dependent Cerebrovascular Responses by Modulating The Phosphorylation State of eNOS via Rho Kinase

Hypertension (HTN) alters vital homeostatic mechanisms regulating cerebral blood flow (CBF) and increases the risk of stroke and dementia. HTN exerts some of its damaging effects by counteracting the beneficial vascular actions of nitric oxide (NO). The potent vasoconstrictor endothelin-1 (ET1) has been implicated in the pathogenesis of HTN, but its role in the cerebrovascular effects of HTN is unknown. We examined whether ET1 disrupts CBF regulation. CBF (laser-Doppler flowmetry) was assessed in the somatosensory cortex in anesthetized male C57Bl/6 mice (n=5/group) equipped with a cranial window. ET1 (35 pmol/kg/min; i.v. for 45 min) increased mean arterial pressure from 72±4 to 99±6 mmHg (p 0.05). However, ET1 attenuated the CBF increase produced by neocortical application of the endothelium-dependent vasodilator acetylcholine (ACh; -37±1%; p 0.05) indicating that ET1 did not act by compromising smooth muscle relaxation. The effects of ET1 were prevented by the ET type A (ET A ) receptor antagonist BQ123 (1µM; p B antagonist BQ788 (100nM; p>0.05). ET-1 did not affect the CBF increase produced by the NO donor SNAP and did not increase free radicals, suggesting that ET-1 did not act by reducing NO vasoactivity or bioavailability. However, in brain endothelial cell cultures ET1 (10-100nM) attenuated the NO production induced by ACh (-49±4% at 50nM; p A receptors may be a valuable target to counteract the deleterious cerebrovascular actions of HTN.
Containing Multitudes: Walt Whitman and the British literary tradition

In his preface, Gary Schmidgall argues that the term influence fails to capture the American poet’s engagement with his British forebears and contemporaries, so he emphasizes instead Walt Whitman’s...
Rapid Enabling of Negishi Couplings for a Pair of mGluR5 Negative Allosteric Modulators

A pair of end game Negishi reactions was developed for the large-scale synthesis of two mGluR5 negative allosteric modulators from a common template. Key developmental aspects include the preparation of the core iodide and organozinc reagents, the management of an exotherm during cross-coupling by switching from a batch process to a semibatch process, and the removal of metals (Pd, Zn, Mg) from the Negishi products. Various aqueous workups, carbon treatments, and Si-Thiol were screened for the purging of heavy metals to regulatory limits, a task made more challenging by the metal coordinating abilities of both drug substances. In the case of one API, a series of crystallizations was required to provide the drug substance with the desired purity and solid form. Both of these Negishi couplings were implemented on hectogram to kilogram scale under the aggressive timelines of early process development.
A method to visualize harlequin stained chromosomes without interference by autoradiographic grains.

If autoradiograms of tritium labeled harlequin chromosomes are stained with the fluorescent dye acridine orange, it is possible to see clearly a fluorescent image of the chromosomes without the silver grains obscuring the image. If fluorescent and bright field microscopy are alternated, the chromosomes and the autoradiogram can be studied repeatedly without having to resort to the study of sequential photographs. The technique is particularly useful for the study of heavily labeled chromosomes.
Engineering HSV-1 Vectors for Gene Therapy.

Virus vectors have been employed as gene transfer vehicles for various preclinical and clinical gene therapy applications, and with the approval of Glybera (alipogene tiparvovec) as the first gene therapy product as a standard medical treatment (Yla-Herttuala, Mol Ther 20: 1831-1832, 2013), gene therapy has reached the status of being a part of standard patient care. Replication-competent herpes simplex virus (HSV) vectors that replicate specifically in actively dividing tumor cells have been used in Phase I-III human trials in patients with glioblastoma multiforme, a fatal form of brain cancer, and in malignant melanoma. In fact, T-VEC (talimogene laherparepvec, formerly known as OncoVex GM-CSF) displayed efficacy in a recent Phase III trial when compared to standard GM-CSF treatment alone (Andtbacka et al. J Clin Oncol 31: sLBA9008, 2013) and may soon become the second FDA-approved gene therapy product used in standard patient care. In addition to the replication-competent oncolytic HSV vectors like T-VEC, replication-defective HSV vectors have been employed in Phase I-II human trials and have been explored as delivery vehicles for disorders such as pain, neuropathy, and other neurodegenerative conditions. Research during the last decade on the development of HSV vectors has resulted in the engineering of recombinant vectors that are totally replication defective, nontoxic, and capable of long-term transgene expression in neurons. This chapter describes methods for the construction of recombinant genomic HSV vectors based on the HSV-1 replication-defective vector backbones, steps in their purification, and their small-scale production for use in cell culture experiments as well as preclinical animal studies.