cssi/SciSciGPT-SciSciNet huggingface dataset:
Combination Therapy with Histone Deacetylase Inhibitor Vorinostat Plus Aurora Kinase Inhibitor MK-0457 Leads to Enhanced Lymphoma Cell Killing with Stabilization of p53 and Repression of C-Myc, hTERT, and Myc-Responsive miRNAs

Background: Patients with relapsed or refractory Hodgkin (HL) and Non Hodgkin Lymphoma (NHL) have few therapeutic options after salvage therapy and transplant, and new agents are thus needed. MK-0457 is a novel aurora kinase inhibitor (AKI) which leads to polyploidy and G2 arrest by disregulating mitosis. We demonstrate that the addition of vorinostat, a broad spectrum HDACi, leads to the reactivation of proapoptotic and DNA damage response elements leading to enhanced lymphoma cell death. A panel of HL and NHL cell lines was studied with either drug or the combination using MTS, Annexin V, and flow cytometry studies. Results: Vorinostat alone at a dose range of 0.5 – 3 mM reduces cell growth by at least 50% in all lines tested. For example, 1.5 mM vorinostat results in averages of 50% growth reduction and 30% apoptotic cells at 48 hours in the L540 HL cell line. MK-0457 alone at 100 nM – 500 nM results in up to a 50% reduction in cell growth and 20% apoptosis in the tested cell lines. However, the combination of 1.5 mM vorinostat and 100 nM MK-0457 results in 50 – 70% apoptosis of the L540 and KM-H2 Hodgkin cell lines at 48 hours. Cell cycle analyses by FACS show an increased percentage of cells in G2/M with few cells in sub-G1, whereas in combination with vorinostat there is a significant increase in the sub G1 population. Real-time PCR analysis and immunoblotting of L540 cells treated with either single agent or in combination suggest an epigenetic as well as a protein acetylation mechanism for this activity. Prosurvival genes such as bcl-XL and hTERT are downregulated five-fold by combination drug treatment, while the proapoptotic BAK gene is upregulated 1.5 – 2-fold. The p53 tumor suppressor is stabilized both by increased acetylation in response to vorinostat as well as by reduced inhibitory phosphorylation at Ser315 by MK-0457-inhibited aurora kinase, leading to a corresponding increase in the p53 target genes p21 and Noxa. Protein and mRNA levels of c-myc are reduced. Repression of microRNAs (miRNAs) in the myc-regulated polycistronic cluster of miRNAs of chromosome 13, such as miR-17.5p, -17.3p, and 18, is demonstrated with vorinostat and TSA. Conclusions: The HDACi vorinostat leads to both transcriptional and post-transcriptional changes which create a pro-apoptotic milieu, sensitizing the cell to centrosome-acting agents such as the AKI, MK-0457. [We acknowledge Merck Inc for providing Vorinostat, MK-0457, and research support.]<
Achieving RBAC on RESTful APIs for Mobile Apps Using FHIR

Health Information Exchange (HIE) provides a morecomplete health record of an individual that improves patientcare with relevant data gathered from multiple healthinformation technology (HIT) systems. In support of HIE, theHealth Level Seven (HL7) XML standard was developed tomanage, exchange, integrate, and retrieve electronic healthinformation. In 2011, HL7 began drafting a next-generationstandard, Fast Healthcare Interoperable Resources (FHIR), tofacilitate the development and interaction of mobile health(mHealth) apps, HIT data sharing, and common format forinformation modeling. FHIR is based on RESTful APIs andsupported by a FHIR server infrastructure that facilitates theexchange in a cloud computing setting. FHIR while possessing asecurity specification, has yet to define and identify actualsecurity mechanisms for secure data exchange via RESTful APIcalls. In this paper, we incorporate role-based access control(RBAC) into FHIR to support the ability to control access ofwho can call which services of FHIR RESTful APIs that managesensitive healthcare data. The work is demonstrated utilizing amHealth application that communicates with the OpenEMRelectronic health record via the HAPI FHIR server.
Simultaneous and Sequential MS/MS Scan Combinations and Permutations in a Linear Quadrupole Ion Trap

Methods of performing precursor ion scans as well as neutral loss scans in a single linear quadrupole ion trap have recently been described. In this paper we report methodology for performing permutations of MS/MS scan modes, that is, ordered combinations of precursor, product, and neutral loss scans following a single ion injection event. Only particular permutations are allowed; the sequences demonstrated here are (1) multiple precursor ion scans, (2) precursor ion scans followed by a single neutral loss scan, (3) precursor ion scans followed by product ion scans, and (4) segmented neutral loss scans. (5) The common product ion scan can be performed earlier in these sequences, under certain conditions. Simultaneous scans can also be performed. These include multiple precursor ion scans, precursor ion scans with an accompanying neutral loss scan, and multiple neutral loss scans. We argue that the new capability to perform complex simultaneous and sequential MSn operations on single ion populations represents a significant step in increasing the selectivity of mass spectrometry.
Perceptions of Family Members, Nurses, and Physicians on Involving Patients' Families in Delirium Prevention.

Background Delirium occurs in up to 80% of patients admitted to an intensive care unit. Nonpharmacologic delirium-prevention strategies, which are commonly used by the bedside nurse, have reduced the incidence and duration of delirium in patients in the intensive care unit. With increasing demands on the nurse, strategies such as including the patient's family in delirium prevention activities should be investigated. OBJECTIVE To determine opinions and willingness of health care providers to involve patients' families in nonpharmacologic delirium-prevention activities in the intensive care unit, and of patients' families to be involved. Methods Two surveys, one for intensive care unit nurses and physicians and one for patients' families, were developed and administered. The provider survey focused on current delirium-prevention practices and opinions about family involvement. The family survey concentrated on barriers and willingness to participate in prevention activities. Results Sixty nurses and 58 physicians completed the survey. Most physicians (93%) and all nurses believed families could assist with delirium prevention. Only 50% reported speaking with family members about delirium and delirium prevention. The family survey was completed by 60 family members; 38% reported a provider spoke with them about delirium. Family members reported high levels of comfort in participating in delirium-prevention activities. Conclusions Health care providers and family members are supportive of the latter performing delirium-prevention activities. Family of patients in the intensive care unit may work collaboratively with nurses to reduce the incidence and duration of delirium in these patients.
Phase I study of oral BKM120 and oral olaparib for high-grade serous ovarian cancer (HGSC) or triple-negative breast cancer (TNBC).

2510 Background: In vivo synergy of the PI3-kinase inhibitor BKM120 and the PARP inhibitor olaparib is seen using a mouse model of BRCA1-related breast cancer (BrCa) and sporadic TNBC (Juvekar et a...
The Geneva Conference of 1954A Case of Tacit Deception

This article uses a game-theoretic model of deception to examine a game played at the Geneva Conference of 1954 by the Western Alliance, the Sino-Soviet bloc and the Vietminh. It argues that if this game were played as a game of complete information, the sophisticated outcome would have been a withdrawal of French forces from Vietnam, followed immediately by an election whose probable winner would have been Ho Chi Minh. For the Western Alliance, especially the United States, this outcome was seen as the least-preferred of the three possible outcomes. However, because the Western Alliance was able to make a false announcement of its preferences, it was able tacitly to deceive the Soviets, Chinese, and Vietminh into believing that its misrepresentation was its true preference. Thus, it was able to induce its second-most-preferred alternative, the partition of Vietnam, as the (manipulated) sophisticated outcome of the game.
Charitable Contributions of Services: Charitable Gift Planning for Non-Itemizers

This Article examines the tax treatment of charitable contributions and concludes that contributors who do not itemize their deductions (nonitemizers) should contribute their services to charity whenever possible rather than contributing cash or property. Charitable donees similarly should embrace opportunities to accept and utilize service contributions from their donor bases, give service contributions as much recognition as money or property contributions, and encourage their lower-income donors to render services rather than giving money earned with performance of services. The Article suggests that nonitemizing taxpayers are the donors who have the most “skin in the game” for charitable contributions in terms of sacrifice. Promoting service rather than money or property contributions maximizes the tax subsidy of the charitable contributions. From the perspective of efficient tax planning for low and moderate-income taxpayers, the tradition of volunteerism in the United States is compelling. Yet, despite the ability to get more “bang for the buck” from service contributions, many charitable organizations that used to rely on volunteers for support increasingly have shifted their operations to reliance on paid staff and pushed even the low-income members of their donor base to contribute money rather than volunteer services.
Pre-pectoral breast reconstruction: a less invasive option

“ Sometimes life brings you full circle to a place you have been before, just to show you how much you have grown. ” –Anonymous.
Predictors of toxic metal exposures among US women of reproductive age.

Arsenic, cadmium, lead, and mercury are ubiquitous toxicants that may be especially harmful to unborn children. We therefore sought to identify temporal trends and predictors of toxic metal biomarkers among US women of reproductive age, including those who were pregnant and/or breastfeeding. Interviews and examinations were performed among a representative sample of women, aged 20–44 years, as part of the 2003–2014 National Health and Nutrition Examination Surveys. A range of sociodemographic, lifestyle, and dietary factors were evaluated as predictors of urinary inorganic arsenic, urinary cadmium, blood mercury, and blood lead concentrations. Levels of all four toxic metal biomarkers declined during the study period. Older age, racial/ethnic minorities, and a birthplace outside of the US were independently associated with higher toxic metal concentrations. Associations were similar for women who were pregnant or breastfeeding and those who were not. US women of reproductive age were exposed to lower levels of toxic metals in 2013–2014 compared to 2003–2004. However, because the long-term health effects of early life exposures are unclear, public health efforts to address toxic metals should pay particular attention to older, nonwhite, and foreign-born women if they are pregnant or planning to become pregnant.
True Colors: Crime, Race and Colorblindness Revisited

The violent, racially motivated events of the Charlottesville rally unleashed demons that many Americans believed were long buried. Old Jim Crow-inspired racism came straight through the front door. Yet critics of colorblind policies were not surprised. For them, such an eruption of racial hatred manifested what they had repeatedly argued: colorblind policies neither alter racial predispositions nor affect the unequal treatment of minorities in the United States. In fact, colorblindness has given rise to a modern, latent type of racism. This Article empirically investigates this claim in an unexplored context — the media’s colorblind, crime-related coverage policies. Utilizing a novel dataset spanning ten years of crime coverage under the media’s colorblind policy contrasted with national and state-level crime statistics, this longitudinal study complicates the controversy around colorblindness. First, while explicit racial references in crime reports declined, they were replaced by implicit racial cues, primarily by the use of visuals. Second, racial schemas in the criminal context prevailed with unbalanced representations of black and white perpetrators compared to real crime statistics, both at the local and national level. Through these findings, this Article adds a new dimension to the scholarship on the indivisibility between race and crime in an era of colorblindness. It offers the incognizant liberal trap as a conceptual framework to engage with these findings, and an explanation for the failure of liberal news outlets to combat racially distorted narratives. This Article calls for an “affirmative action” in crime coverage to combat institutional inertia and to allow counter-stereotypical racial schemas to take hold. More broadly, this Article sheds light on the potential links between crime reports and persistent inequalities in the criminal justice system.
Federating Solar, Storage and Communications in the Electric Grid and Internet of things

A futuristic infrastructure model is envisioned with distributed modules that can produce solar energy, have a storage system and provide services of lighting, electric-vehicle charging and communications. A stochastic model is formulated for the solar power production and overall consumption of power. Resource allocation in such a system translates to taking decisions in a foresighted manner while maximizing a social surplus with the goal of serving all power demands optimally. A stochastic dynamic programming approach is formulated for the same and a myopic policy is illustrated while discussing the trade-offs between serving competing demands.
The number of growing microtubules and nucleus-nucleus interactions uniquely regulate nuclear movement in Drosophila muscle

Nuclear movement is a fundamental process of eukaryotic cell biology. Skeletal muscle presents an intriguing model to study nuclear movement because its development requires the precise positioning of multiple nuclei within a single cytoplasm. Furthermore, there is a high correlation between aberrant nuclear positioning and poor muscle function. Although many genes that regulate nuclear movement have been identified, the mechanisms by which these genes act is not known. Using Drosophila melanogaster muscle development as a model system, and a combination of live-embryo microscopy and laser ablation of nuclei, we have found that phenotypically similar mutants are based in different molecular disruptions. Specifically, ensconsin (Drosophila MAP7) regulates the number of growing microtubules that are used to move nuclei whereas bocksbeutel (Drosophila emerin) and klarsicht (Drosophila KASH-protein regulate interactions between nuclei.
Effect of moisture and oxidation status of alkaline rice soils on the adsorption of soil phosphorus by an anion resin

Considerable effort was devoted to experimentally explaining the greater amount of anion resin-adsorbable P (ARAP) in water-saturated alkaline soils relative to moist soils with the purpose of explaining the phenomenon of increased P availability in flooded rice soils. ARAP increased when waterlogged conditions were imposed on soils, but the increase in ARAP occurred before reducing conditions were obtained. Reducing conditions did not increase ARAP. The increase in ARAP in the water-saturated alkaline soils was attributed to the enhanced P diffusion resulting from a decrease in tortuosity, thus indicating that increased P availability upon flooding could be due to increased P diffusion.
The Presumptive Case for Food Biotechnology

Hans Jonas’ principle of responsibility establishes a basic framework for evaluating novel technology in ethical terms. Risk assessment provides a further development of Jonas’s framework as it is applied to agrifood biotechnology. A risk-based approach consists in distinguishing four tasks for implementing technological ethics: hazard identification, exposure quantification, management and communication. The risk-based approach is effective when it operates against the background assumption that technologies passing risk-based tests are at least prima facie acceptable on ethical grounds. However, a complex of social institutions must be in place for this assumption to be valid. These institutions, combined with a risk-based assessment of the potential for unwanted consequences, constitute the presumptive case for agricultural and food biotechnology. This implies that innovators are not ethically required to demonstrate the case for their technology, and that the primary task of ethics is to focus on arguments against the technology. The chapter also discusses some logically and ethically problematic adaptations of the presumptive case.
COVID-19 Dysautonomia

Objective: To report a case series of dysautonomia associated with COVID-19 infection. Methods: This is a retrospective review of patients evaluated in the autonomic clinic at our institution with suspected signs and symptoms of dysautonomia who underwent formal evaluation, including autonomic testing. Results: Six patients were identified with signs and symptoms suggestive of dysautonomia who underwent autonomic testing. All patients had symptoms typical of COVID-19 infection, though none were hospitalized for these or other symptoms. All patients reported symptoms of postural lightheadedness and near-syncope, fatigue, and activity intolerance. Five patients reported the onset of autonomic symptoms concomitant with other COVID-19 symptoms, with the other patient reporting symptom onset 6 weeks following initial COVID-19 symptoms. Autonomic testing demonstrated an excessive postural tachycardia in 4 patients, a hypertensive response with head-up tilt in 3 patients, orthostatic hypotension in 1 patient, and sudomotor impairment in 1 of the patients with excessive postural tachycardia. Conclusions: We present clinical features and results of autonomic testing in 6 patients with a history COVID-19 infection. While all patients reported typical features of orthostatic intolerance, fatigue, and activity intolerance, the results of autonomic testing were heterogenous, with orthostatic hypotension in 1 patient, excessive postural tachycardia typical of postural tachycardia syndrome in 4 patients, and postural hypertension in 3 patients.
Preparing, maintaining, and evaluating remote preceptorships: Considerations for nurse educators

Abstract Clinical learning, a critical element of nursing education, allows students to apply theory to practice and refine nursing skills. Clinical nursing education remains relatively unchanged from past educational approaches even though healthcare, higher education, and students have changed. The global pandemic has further compounded issues confronting clinical nursing education and is forcing educators to re-examine traditional clinical teaching approaches. A potential clinical learning alternative that may transform clinical teaching while meeting learners’ needs involves the innovative use of preceptorships, completed either partially or totally remote. Remote preceptorships (RPs) hold promise in helping students achieve learning outcomes in the current environment; however, educators may not be comfortable implementing this innovative, online clinical teaching model. Thus, this article offers considerations for educators as they implement nursing RPs.
Phosphorylation of murine mammary tumor virus precursor polypeptides.

Abstract Phosphorylation of the murine mammary tumor virus (MuMTV) structural proteins was studied in an MuMTV-infected epithelial cell line derived from a BALB/cf C3H mouse mammary tumor. Immunoprecipitation of 32P-labeled cell extracts with monospecific anti-p27 serum revealed that phosphorylation occurred at the stage of the core-protein polyprotein precursor prp75. Two forms of phosphorylated prp75 were found: one migrating with an apparent molecular weight of 80,000, and the other with a molecular weight of 76,000. The 80,000-molecular-weight species was found to be the most heavily phosphorylated. In addition, a relatively stable phosphorylated processing intermediate of 34,000 molecular weight was observed as well. Tryptic peptide mapping analysis of the 32P-labeled viral proteins indicated a precursor product relationship between the intracellular phosphorylated, high-molecular-weight peptides and the mature MuMTV phosphoproteins p23 and p27. Phosphopeptide analysis also suggested that phosphorylation of the viral proteins occurred in discrete steps and that the attached phosphate groups were conserved throughout the processing steps.
The Synthesis of a Di-N-acetylchitobiose Asparagine Derivative, 2-Acetamido-4-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-1-N-(4-l-aspartyl)-2-deoxy-β-d-glucopyranosylamine

Abstract The crystalline glycosyl chloride obtained by treatment of α-chitobiose octaacetate with dry hydrogen chloride in acetyl chloride solution was treated with silver azide to give the crystalline β-1-azido derivative of peracetylated chitobiose. This compound was hydrogenated in the presence of platinum oxide into the crystalline β-1-amino derivative, which was condensed with 1-benzyl N-(benzyloxycarbonyl)-l-aspartate to give the crystalline benzyl ester, N-(benzyloxycarbonyl), penta-O-acetyl derivative of 2-acetamido-4-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-1-N-(4-l-aspartyl)-2-deoxy-β-d-glucopyranosylamine. The latter compound was obtained in crystalline form by catalytic hydrogenation in the presence of palladium on charcoal, followed by saponification of the resulting crystalline amino acid derivative with lithium hydroxide. It was characterized by its melting point and optical rotation, by thin layer chromatography, and by mass spectrometry of the per(trimethylsilyl) derivative.
Human mutations in glucose 6-phosphate dehydrogenase reflect evolutionary history

Glucose 6-phosphate dehydrogenase (G6PD) is a cytosolic enzyme encoded by a housekeeping X-linked gene whose main function is to produce NADPH, a key electron donor in the defense against oxidizing agents and in reductive biosynthetic reactions. Inherited G6PD deficiency is associated with either episodic hemolytic anemia (triggered by fava beans or other agents) or life-long hemolytic anemia. We show here that an evolutionary analysis is a key to understanding the biology of a housekeeping gene. From the alignment of the amino acid (aa) sequence of 52 glucose 6-phosphate dehydrogenase (G6PD) species from 42 different organisms, we found a striking correlation between the aa replacements that cause G6PD deficiency in humans and the sequence conservation of G6PD: two-thirds of such replacements are in highly and moderately conserved (50-99%) aa; relatively few are in fully conserved aa (where they might be lethal) or in poorly conserved aa, where presumably they simply would not cause G6PD deficiency. This is consistent with the notion that all human mutants have residual enzyme activity and that null mutations are lethal at some stage of development. Comparing the distribution of mutations in a human housekeeping gene with evolutionary conservation is a useful tool for pinpointing amino acid residues important for the stability or the function of the corresponding protein. In view of the current explosive increase in full genome sequencing projects, this tool will become rapidly available for numerous other genes.
Management of Difficult Embryo Transfers

Difficult embryo transfers are associated with reduced pregnancy and live birth rates in IVF cycles. Numerous factors including physiological and anatomical variations can influence the ease of an embryo transfer. In this chapter, we review how to perform a uterine evaluation, the variables that influence an embryo transfer, and how to address obstacles to a successful transfer.
Emerging mHealth and eHealth interventions for serious mental illness: a review of the literature

AbstractBackground: Serious mental illness (SMI) is one of the leading causes of disability worldwide. Emerging mobile health (mHealth) and eHealth interventions may afford opportunities for reaching this at-risk group.Aim: To review the evidence on using emerging mHealth and eHealth technologies among people with SMI.Methods: We searched MEDLINE, PsychINFO, CINAHL, Scopus, Cochrane Central, and Web of Science through July 2014. Only studies which reported outcomes for mHealth or eHealth interventions, defined as remotely delivered using mobile, online, or other devices, targeting people with schizophrenia, schizoaffective disorder, or bipolar disorder, were included.Results: Forty-six studies spanning 12 countries were included. Interventions were grouped into four categories: (1) illness self-management and relapse prevention; (2) promoting adherence to medications and/or treatment; (3) psychoeducation, supporting recovery, and promoting health and wellness; and (4) symptom monitoring. The interventions...
A high intensity H2+ multicusp ion source for the isotope decay-at-rest experiment, IsoDAR

The Isotope Decay-At-Rest (IsoDAR) experimental program aims to decisively test the sterile neutrino hypothesis. In essence, it is a novel cyclotron based neutrino factory that will improve the frontiers in both high-intensity cyclotrons and electron flavor anti-neutrino sources. By using a source in which the usual H(-) ions are replaced with the more tightly bound H2(+) ions, we can negate the effects of Lorentz stripping in a cyclotron, reduce the overall perveance due to the space-charge effect, and deliver twice the number of protons per nuclei on target. To produce the H2(+), we are currently developing a dedicated multicusp ion source, MIST-1 (generation-1 Multicusp Ion Source Technologies at MIT), and a low-energy beam transport system for the IsoDAR cyclotron. This will increase the overall H2(+) current leading up to the cyclotron and improve the emittance of the beam injected into the cyclotron.
Root Cause Analysis of Rebleeding Events following Transjugular Intrahepatic Portosystemic Shunt Creation for Variceal Hemorrhage

Abstract Purpose To identify fundamental causes underlying recurrent variceal hemorrhage (VH) after transjugular intrahepatic portosystemic shunt (TIPS) to ascertain opportunities for improvement of TIPS-based management of VH and prevention of rebleeding. Materials and Methods This single-center retrospective study comprised 166 patients (male-to-female ratio 101:65; median age, 52 y; median Model for End-Stage Liver Disease score, 14) who had TIPS created for VH in 1998–2014. Medical record review was used to identify patients who had recurrent VH events, and root cause analysis allowed identification of the most probable causal factors. A 5-person interventional radiology physician group generated quality improvement (QI) recommendations for process changes to address causal factors, with consensus achieved using a modified Delphi method. Results Variceal rebleeding occurred after TIPS in 25 (15%) patients. The 1-, 3-, and 5-year variceal rebleeding incidence was 17%, 21%, and 21%, respectively. Variceal rebleeding was associated with high 90-day all-cause mortality incidence (10/25; 40%). Male sex ( P = .018) and Model for End-Stage Liver Disease score ( P = .009) were statistically associated with variceal rebleeding. The most common primary and secondary causes of recurrent VH were lack of or insufficient variceal embolization (64%). Other causal factors included TIPS stenosis or occlusion (28%) with recurrent portosystemic gradient (PSG) elevation (20%), severe coagulopathy (20%), inadequate portosystemic gradient reduction (12%), and TIPS underdilation (4%). To potentially address variceal rebleeding, 14 preventive QI recommendations were developed. Conclusions Although recurrent VH rates after TIPS are not trivial, rebleeding may be related to addressable underlying causal factors. Further investigation may assess the efficacy of QI-based procedure methodologic enhancements in reducing rebleeding incidence after TIPS.
P2P-Based, Multi-Attribute Resource Discovery under Real-World Resources and Queries

Collaborative peer-to-peer (P2P), grid, and cloud computing rely on resource discovery (RD) solutions to aggregate groups of multi-attribute, dynamic, and distributed resources. However, specific characteristics of real-world resources and queries, and their impact on P2P-based RD, are largely unknown. We analyze the characteristics of resources and queries using data from four real-world systems. These characteristics are then used to qualitatively and quantitatively evaluate the fundamental design choices for P2P-based multi-attribute RD. The datasets exhibit several noteworthy features that affect the performance. For example, compared to uniform queries, real-world queries are relatively easier to resolve using unstructured, superpeer, and single-attribute-dominated query-based structured P2P solutions, as queries mostly specify only a small subset of the available attributes and large ranges of attribute values. However, all the solutions are prone to significant load balancing issues, as the resources and queries are highly skewed and correlated. The implications of our findings for improving RD solutions are also discussed.
Trifluoperazine: a rynodine receptor agonist

Trifluoperazine (TFP), a phenothiazine, is a commonly used antipsychotic drug whose therapeutic effects are attributed to its central anti-adrenergic and anti-dopaminergic actions. However, TFP is also a calmodulin (CaM) antagonist and alters the Ca(2+) binding properties of calsequestrin (CSQ). The CaM and CSQ proteins are known modulators of sarcoplasmic reticulum (SR) Ca(2+) release in ventricular myocytes. We explored TFP actions on cardiac SR Ca(2+) release in cells and single type-2 ryanodine receptor (RyR2) channel activity in bilayers. In intact and permeabilized ventricular myocytes, TFP produced an initial activation of RyR2-mediated SR Ca(2+) release and over time depleted SR Ca(2+) content. At the single channel level, TFP or nortryptiline (NRT; a tricyclic antidepressant also known to modify CSQ Ca(2+) binding) increased the open probability (Po) of CSQ-free channels with an EC(50) of 5.2 microM or 8.9 microM (respectively). This Po increase was due to elevated open event frequency at low drug concentrations while longer mean open events sustained Po at higher drug concentrations. Activation of RyR2 by TFP occurred in the presence or absence of CaM. TFP may also inhibit SR Ca uptake as well as increase RyR2 opening. Our results suggest TFP and NRT can alter RyR2 function by interacting with the channel protein directly, independent of its actions on CSQ or CaM. This direct action may contribute to the clinical adverse cardiac side effects associated with these drugs.
The Dual Track Theory of Moral Decision-Making: a Critique of the Neuroimaging Evidence

The dual-track theory of moral reasoning has received considerable attention due to the neuroimaging work of Greene et al. Greene et al. claimed that certain kinds of moral dilemmas activated brain regions specific to emotional responses, while others activated areas specific to cognition. This appears to indicate a dissociation between different types of moral reasoning. I re-evaluate these claims of specificity in light of subsequent empirical work. I argue that none of the cortical areas identified by Greene et al. are functionally specific: each is active in a wide variety of both cognitive and emotional tasks. I further argue that distinct activation across conditions is not strong evidence for dissociation. This undermines support for the dual-track hypothesis. I further argue that moral decision-making appears to activate a common network that underlies self-projection: the ability to imagine oneself from a variety of viewpoints in a variety of situations. I argue that the utilization of self-projection indicates a continuity between moral decision-making and other kinds of complex social deliberation. This may have normative consequences, but teasing them out will require careful attention to both empirical and philosophical concerns.
The effects of lag and category membership on recognition memory in very young children

Children 13-30 months of age were briefly shown common objects on familiarization trials that later reappeared paired with new objects on test trials. The new objects were similar in shape, shared a common basic-level label, or were perceptually and conceptually unrelated to the familiarized stimuli. In the first of two experiments, children even as young as 13 months of age displayed significant preferences for novel stimuli in all test conditions. Length of lag between familiarization and test trial was not found to influence attentional preference. A second experiment confirmed the findings of a significant novelty preference by 1-year-olds. In both experiments, older subjects displayed stronger preferences for novel over familiar stimuli when they were conceptually unrelated than when they were related. However, this greater preference was not consistently significant, as found in previous studies.
Cognitive response to pharmacological treatment for depression in Alzheimer disease: Secondary outcomes from the depression in Alzheimer's disease study (DIADS)

Objective The authors assessed the cognitive effects of depression treatment with sertraline in patients with Alzheimer disease (AD) and major depression. Methods Forty-four patients with probable AD and major depression were enrolled in a double-blind, placebo-controlled clinical trial of sertraline. Cognitive testing was done at baseline and at 3-week intervals throughout the 12-week study. At the 12th week, subjects were categorized by treatment response (full, partial, or no response). Cognitive data from 41 participants who completed three or more testing sessions and 36 who completed all five study visits were included in the analyses. Results Neither improved mood nor use of sertraline was associated with cognitive change over time in AD patients. Post-hoc exploration of the data, however, suggested a sex difference in cognitive response to sertraline such that women treated with sertraline demonstrated improved cognition compared with women on placebo, whereas men treated with sertraline worsened significantly in cognition compared with men on placebo. Conclusions In this study, among depressed AD patients after treatment with sertraline or placebo, there was no evidence that improved mood was associated with cognitive improvement. Future studies aimed at increasing power to detect mood as well as medication effects will be valuable in determining the relationship between cognition and treatment of depression in AD patients.
Comparative Study of Optimization Techniques for Shock and Vibration Isolation

Abstract : Several optimum and sub-optimum isolators are discussed with respect to three different criteria appropriate to shock and vibration isolation. In attempting to show the limitations of performance of a system optimized according to one criterion when considered from the point of view of another criterion, a number of advantages and disadvantages of the optimum systems are made evident. The results are presented in trade-off diagrams which allow a continuous range of choice in penalizing measures of relative displacement and force or acceleration of the isolated element. (Author)
An immunochemical comparison of brain microtubule protein (tubulin) with tubulin and actomyosin-like protein from the adrenal medulla

Abstract A functional relationship between microtubule protein (tubulin) and contractile protein has been observed previously. In the present study and immuniological technique, microcomplement fixation, was used to compare vinblastine-precipitated tubulin from brain with tubulin and contractile protein from the adrenal medulla. Antiserum against brain tubulin cross-reacts with adrenal tubulin but not with adrenal actomyosin. Antiserum against adrenal actomyosin cross-reacts with adrenal tubulin, but shows minimal cross-reaction with brain tubulin. The presence of dual antigenic components of the adrenal tubulin suggests that adrenal tubulin may be involved in contractile complexes.
B. U. Ö. Sonnerup—New JGR-Blue editor

‘JGR is the foremost place to publish research in space physics. You really can't be in this field without having the journal right at your elbow,’ said Bengt U. O. Sonnerup, the new editor of the space physics section of the Journal of Geophysical Research. He will formally begin his 4-year term on January 1, succeeding George Siscoe. Sonnerup has been receiving articles for the journal since October 1.
Quantitative histochemical assessment of the changes produced in hamster mammary tissue mast cells by the estrus cycle.

Abstract The Alcian Blue-Safranin (AB-S) staining method, which distinguishes four histochemical types or stages (I–IV) of mast cells on the basis of their relative content of granules containing either incompletely sulfated heparin (Stages I–III) or fully sulfated heparin (Stage IV), was employed in combination with quantitative histological analysis to characterize the mast cell population of normal female hamster (LSH/SsLAK) mammary tissue. (1) It was found that the mast cells associated with mammary tissue in the hamster undergo striking fluctuation in both percent frequency distribution by AB-S stage and in numbers/high power field by AB-S stage in phase with the estrus cycle. At estrus the frequency distribution of mast cells in mammary tissue was composed predominantly of Stage IV cells. During early-middle diestrus the distribution of mast cells shifted toward a population composed largely of Stages I–III, with Stage II cells predominating. By late diestrus the frequency distribution of mast cells was again composed predominantly of Stage IV cells. (2) The mast cell population of a tissue remote from mammary tissue and not known to respond to ovarian hormones (tongue) showed no significant fluctuation in the distribution of AB-S stages at different phases of the estrus cycle. (3) Mast cells in the uterus showed a minor shift in the AB-S frequency distribution toward Stages II–III at middle diestrus. (4) Incorporation of tritiated thymidine by mammary epithelium was highest at late estrus, intermediate at metestrus, and lowest at early-middle diestrus. This decrease paralleled the alterations observed in mammary mast cells. These data were interpreted to indicate a cyclical secretion of heparin by the mast cells of mammary tissue occurring under the influence of the estrus cycle and probably involving both ovarian hormones and proliferative activity of mammary epithelium.
GHz Bandwidth (GaAI)As Semiconductor Lasers And Optical Detectors For Signal Processing Applications

The potential application of (GaAl)As injection lasers and high speed optical detectors in future Ghz bandwidth communication, microwave and computer fiber-optic systems requires an extensive knowledge of simple and accurate characterization techniques, high frequency characteristics of existing commercial lasers and high speed optical detectors.© (1982) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Mass spectra of proteins and other biomolecules recorded using a handheld instrument

Abstract Proteins (myoglobin and cytochrome C), peptides (bradykinin and melittin), alkaloids in complex plant materials, and mixtures of phospholipids from a bacterial extract all give characteristic electrospray mass spectra using a handheld tandem mass spectrometer, Mini 10. The mass/charge range of the 10 kg Mini 10 was extended to m/z 2000 using resonant ion ejection at low frequency allowing analysis of proteins with molecular weights up to 17,000 Da. Fragmentation of peptides and proteins was observed.
Are we explaining consciousness yet

Theorists are converging from quite different quarters on a version of the global neuronal workspace model of consciousness, but there are residual confusions to be dissolved. In particular, theorists must resist the temptation to see global accessibility as the cause of consciousness (as if consciousness were some other, further condition); rather, it is consciousness. A useful metaphor for keeping this elusive idea in focus is that consciousness is rather like fame in the brain. It is not a privileged medium of representation, or an added property some states have; it is the very mutual accessibility that gives some informational states the powers that come with a subject's consciousness of that information. Like fame, consciousness is not a momentary condition, or a purely dispositional state, but rather a matter of actual influence over time. Theorists who take on the task of accounting for the aftermath that is critical for consciousness often appear to be leaving out the Subject of consciousness, when in fact they are providing an analysis of the Subject, a necessary component in any serious theory of consciousness.
Cellular transport and homeostasis of essential and nonessential metals

Metals can have a number of detrimental or beneficial effects in the cell, but first they must get in. Organisms have evolved transport mechanisms to get metals that are required, or essential into the cell. Nonessential metals often enter the cell through use of the machinery provided for essential metals. Much work has been done to advance our understanding of how these metals are transported across plasma and organelle membranes. This review provides an overview of essential and nonessential metal transport and homeostatic processes.
An Optical Search For Supernova Remnants in NGC 2403

We present the results of an optical search for supernova remnants (SNRs) in the Scd galaxy NGC 2403 using image and spectral observations of a ? 8' ? 8' field covering nearly all of this galaxy. Our SNR identification technique consisted of constructing continuum-subtracted H? and [S II] ??6716, 6731 images, obtaining spectra of a few [S II]-bright emission nebulae found in these images, and then using the [S II]/H? ratios obtained from these spectra to correct the image [S II]/H? ratios. Thirty-five emission nebulae with [S II]/H? ? 0.45 were identified as SNRs and have diameters of 20-200 pc, reddening-corrected H? intensities of 2.2 ? 10-15 to 1.4 ? 10-13 ergs cm-2 s-1, [S II]/H? ratios of 0.45-1.11, and a variety of optical morphologies (shell, arc, and filled). Spectra of 15 of these remnants were obtained and are presented. The two NGC 2403 SNRs previously identified by D'Odorico, Dopita, & Benvenuti were among the 35 SNRs detected. Our final NGC 2403 SNR sample appears biased against detecting large, faint remnants, and no SNRs were detected inside bright H II regions. An examination of the [S II]/H? values for all the nebulae measured in NGC 2403 shows no sharp dividing line between SNRs and H II regions, similar to what was found in M31, NGC 300, and NGC 7793 (Walterbos & Braun; Blair & Long). We estimate roughly that there are about 4 times more SNRs in NGC 2403 than we detected, which, assuming the observable lifetime of a SNR is ~20,000 yr, yields a crude rate of 1 SN in 150 yr. Analysis of the 15 SNR spectra show a detectable nitrogen gradient, a larger scatter in oxygen abundances than in nitrogen, and a lower mean oxygen abundance than from published H II region data, all of which have been seen in previous SNR studies of other galaxies.
Metformin does not improve survival in patients with hepatocellular carcinoma

CONCLUSION: Although the literature suggests a chemotherapeutic effect in other malignancies, our study demonstrates no survival benefit to the use of metformin in diabetic patients with HCC.
On the Relationship Between the H-Tensor and the Concentration Tensor and Their Bounds

For composite materials, two quantities that are useful for characterizing the contribution of inhomogeneities in a matrix material to the overall properties are (1) the individual H-tensor, Hi, which describes the contribution of a single inhomogeneity and (2) the overall strain concentration tensor, which describes the relationship between the overall volumetric strain to the average strain of all of the inhomogeneities. In this paper, we develop a relationship expressing the overall H-tensor, \({\mathcal{H}}\) , in terms of the overall strain concentration tensor. An important feature of the derivation is that it allows for rigorous upper and lower bounds on the overall H-tensor. In the special case that the inhomogeneities are all the same, with the same orientation, then \({\mathcal{H} = {\bf H}_i}\) , and the results derived for \({\mathcal{H}}\) also hold for Hi.
BIPASS: Design of alternative splicing services

We analyse the motivations that led the development of services to support alternative splicing studies. We discuss data modelling issues and illustrate them with the BioInformatics Pipeline for Alternative Splicing Services (BIPASS). We identify the specific needs that an alternative splicing service should address, and compare existing services with respect to a common matrix of functionalities. We conclude with a discussion on future work needed to offer a more complete suite of services.
Racial/ethnic differences in housing outcomes for first‐time, low‐income home buyers: Findings from a National homeownership education program

Abstract Federal housing policies aimed at making homeownership more accessible through education and affordable lending have been successful in raising the homeownership rate among minorities. By marketing homeownership to underserved populations and helping them overcome financial and informational obstacles, such programs might be expected to promote equality in housing outcomes, including housing quality, neighborhood composition, and neighborhood conditions, for minority homeowners. This article examines the experience of participants in a national home‐ownership education program. While the transition to homeownership has been associated with modest progress, it does not overcome persistent disparities in housing quality. Homeownership appears to lead to poorer neighborhood conditions for all lower‐income buyers—not just minorities—and may be exacerbating social and spatial isolation rather than helping to overcome it. Differences in neighborhood outcomes, however, may be due to locational preferenc...
Critical Literacy and Beyond: Lessons Learned from Students and Workers in a Vocational Program and on the Job

This article reports a study of students' experiences in a community college vocational program in banking and finance and the jobs the students got and lost in the data center of a bank. The study is situated in current concerns about the presumed literacy problems of North American workers and the relationship between skills and competitiveness in the global economy. The discontinuities between such concerns and the situations of the vocational students in this study are discussed, as are calls for “functional context” and “critical” literacy programs. An argument is made for the educational, social, and political importance of studies of work in juxtaposition to studies of schooling.
Linear transconductor based on crosscoupled CMOS pairs

A circuit technique based on two CMOS crosscoupled pairs for realising a linear CMOS transconductor of class AB is presented. Design tradeoffs are discussed and a circuit example is presented. SPICE simulation results show that, for a power supply of ±5 V, the linearity error is controlled to ±1% over a ±3 V input range.