cssi/SciSciGPT-SciSciNet huggingface dataset:
Computational study of the thermal conductivity in defective carbon nanostructures

We use nonequilibrium molecular dynamics simulations to study the adverse role of defects including isotopic impurities on the thermal conductivity of carbon nanotubes, graphene, and graphene nanoribbons. We find that even in structurally perfect nanotubes and graphene, isotopic impurities reduce thermal conductivity by up to one half by decreasing the phonon mean-free path. An even larger thermal conductivity reduction, with the same physical origin, occurs in presence of structural defects including vacancies and edges in narrow graphene nanoribbons. Our calculations reconcile results of former studies, which differed by up to an order of magnitude, by identifying limitations of various computational approaches.
Studies on inducers of nerve growth factor: synthesis of the cyathin core.

Compounds that induce the synthesis of nerve growth factor (NGF) are of interest as alternatives to the administration of the native peptide. We have initiated a program to study the NGF synthesis stimulating activity of the erinacine and scabronine diterpenes. Herein, we report an approach to the core cyathin system by sequential application of an oxidative coupling and [4 + 3] cycloaddition.
SEARCH FOR NEW ISLANDS OF FISSION ISOMERISM.

Abstract The spontaneously fissioning isomers of Am and neighboring elements have been explained as nuclei trapped in a secondary minimum in the fission barrier profile. Some recently published calculations suggest the possible existence of another group of such shape isomers near Z = 85, N = 118. An attempt was made to produce isomers of Po, At, Rn and Fr by bombardment of 197 Au with beams of 11 B, 12 C, 14 N, 16 O, from the Berkeley HILAC and to observe their fission mode with Si semiconductor detectors. The cross-section limits were set at 70 nb or less for the half-life range 2 × 10 −9 to 2 × 10 3 s. An attempt was also made to observe fission fragments from nuclei decaying in flight after recoiling out of targets of Ce, Pr, Tm and Au bombarded with heavy ions. No fission fragments were observed from products in the half-life range 1–50 ns above a cross-section limit of ≈ 50 nb. The possible existence of isomers decaying primarily by γ-transitions to the first minimum was not excluded in either set of measurements. The apparatus was tested with known isomers produced by the reactions 238 U(d, pn) 238m U (200 ns) and 238 U( 12 C, α3n) 243m Cm (38 ns).
The Spirit and Religious Pluralism

“Spirit” is a more universally available religious symbol than “Christ,” found in various forms in most of the religions of the world. It helps to open Christian theology to a genuine religious pluralism, and, in the framework of the doctrine of the Trinity, provides a Christian way of construing this pluralism, relating it to the purposes, activity, and being of God. The pneumatic Trinitarianism proposed in this essay contrasts with the christocentric Trinitarianism recommended by advocates of an inclusivist theology of religions. The concrete incarnation of God in Christ is not lost but placed in a larger context. The Spirit proceeds not just from Christ but from the interaction of God and the world, including a diversity of religious figures and practices. The idea that a theology of the Spirit might serve as the basis of a pluralist theology of religions is tested by looking at the modalities of Spirit that are present in Hinduism and Buddhism, and that enrich a Christian understanding of the Spirit.
Epidemiology, Evaluation, and Treatment of Urinary Incontinence in Octogenarian Women

Urinary incontinence (UI) is an extremely common clinical condition in elderly women. Although both the incidence and prevalence tend to increase with advancing age, UI should not be considered a normal or inevitable part of the aging process. UI tends to have negative-associated outcomes for both patients and caregivers in terms of quality of life, social isolation, and burden of care. This paper reviews the recent peer-reviewed literature on epidemiology, diagnostic evaluation, and clinical treatment options for UI in older adult women.
GAMMA /DELTA T LYMPHOCYTES EXPRESS CD40 LIGAND AND INDUCE ISOTYPE SWITCHING IN B LYMPHOCYTES

T cells expressing gamma/delta T cell receptors home to epithelial tissue and may play a role in immunity to infectious agents and foreign antigens. In an effort to understand the role of gamma/delta T cells in directing B cell responses, we investigated the capacity of human gamma/delta T cells to express CD40 ligand (CD40L) and to drive immunoglobulin (Ig) isotype switching in B cells. A multiple step purification procedure resulted in the recovery of highly pure populations of peripheral blood CD4-CD8- gamma/delta T cells. Neither CD40L surface expression nor CD40L mRNA were detected in unstimulated gamma/delta T cells. Stimulation with phorbol ester and ionomycin induced CD40L mRNA and surface CD40L expression by gamma/delta T cells. Both the percentage of CD40L+ cells and the cell surface density of CD40L were significantly lower in gamma/delta T cells compared to unselected T cells. We further demonstrated that in the presence of neutralizing monoclonal antibody to interferon gamma (IFN-gamma), gamma/delta T cells could induce IgE synthesis in B cells, albeit to a lesser extent than unselected T cells. Furthermore, IgE synthesis driven by gamma/delta T cells was inhibited by monoclonal antibody to CD40L. These observations demonstrate that activated gamma/delta T cells express CD40L and can induce isotype switching in B cells.
Best Practices: A Young Professor's Reflections on Higher Education and Democracy for a World Beyond Our Borders

Dr. Khristina Haddad is an assistant professor who has finished her fourth year in the Department of Political Science at Moravian College. Her teaching philosophy and practice are highlighted in our "Best Practices" feature in this issue of the Journal of College and Character. See http://collegevalues.org/pdfs/Haddad.pdf Having completed her Abitur in Stuttgart, Germany, she fell in love with political theory and the liberal arts at Reed College in Portland, Oregon, and continued her political theory studies at McGill University in MontrEal, Canada. Dr. Haddad has taught at the University of Latvia in Riga as an instructor for Civic Education Project. In 2003, she graduated from the Political Science doctoral program at the University of Michigan-Ann Arbor. Her research addresses the political importance of how we think about time.
What Is a Security in the Crowdfunding Era

With the advent of the crowdfunding era, financial interests in business enterprises may look less like investment instruments commonly known as common stock or debentures, and more like loans, gambling bets, rights to consumable products or services or charitable or other nonprofit donations. A closer look at innovations in interests, instruments and offerings in the crowdfunding era preceding the enactment of the Jumpstart Our Business Startups Act (JOBS Act) offers a basis for comparisons and contrasts that raises questions about the categorization of instruments regulated as securities. These and other questions are important to a rethinking of the structure of financial and financially related regulation in and outside the realm of U.S. securities law.Specifically, innovations in financial interests and instruments that immediately preceded the JOBS Act raise a number of important questions about regulatory authority and interpretation. How do we classify the instruments that represent complex or hybrid financial interests in business enterprises? What area of regulation should apply to them? Why? What do the answers to those questions tell us, if anything, about the current (and possible future) structure and function of domestic and international financial regulation? This essay preliminarily explores the features of certain financial instruments in an effort to begin to answer these questions by focusing on what a security — a statutory and regulatory category including specific financial instruments — is and should be under federal securities law.
RESEARCH ARTICLE: GPI Island Style: Localizing the Genuine Progress Indicator to Hawaii

Applying the Genuine Progress Indicator (GPI) to an island setting offers insight into whether and how standardization of subnational GPI models can adequately capture important local conditions an...
Digital mapping of three-dimensional structures of the Chimney Rock fault system, central Utah

Abstract Part of the Chimney Rock fault system, located on the northern San Rafael Swell, Utah, was mapped by integrating air photograph interpretation and differential global positioning system (GPS) location data. Fault slip, slip directions, and hanging wall subsidence/footwall uplift were digitally recorded in the field along and between the normal faults using Trimble PathFinder equipment and software. GPS was used to record (with sub-meter precision) the location of each measurement as well as the UTM coordinates and elevation of stratigraphic markers at the top of the Jurassic Navajo Sandstone and near the base of the overlying Carmel Formation. The fault system, as well as the associated deformation of the sedimentary layers within the fault blocks, have been precisely characterized using this technique. The geographic coordinates and local elevation were transferred to gOcad to produce a three-dimensional surface representation of a selected resistant limestone layer, by interpolating the elevation between the collected data points using imposed constraints such as the dips of the layers and the locations of the major faults. Separations of the selected horizon from the footwall to the hanging wall were used to calculate the dip-slip distribution along the faults. The digital field data were compared with the results of numerical modeling based on continuum mechanics to study the mechanical interaction among intersecting normal faults and the effects of this interaction on slip distribution and direction. This project illustrates the complete circle from digital mapping to data analysis to numerical modeling to quantitative comparison of theoretical models and field data.
Evidence for GABA-mediated control of putative nociceptive modulating neurons in the rostral ventromedial medulla: iontophoresis of bicuculline eliminates the off-cell pause.

This study was undertaken to test the hypothesis that γ-aminobutyric acid (GABA) is an endogeneous neurotransmitter regulating the activity of a class of putative nociceptive modultory neurons (termed “off-cells”) in the rostral ventromedial medulla (RVM) of the barbiturate-anesthetized rat. Off-cells, which are believed to correspond to the RVM output neuron that inhibits nociceptive processing at the level of the spinal cord, exhibit an abrupt pause in firing that begins immediately prior to the occurrence of the tail flick response (TF), a nocifensive reflex evoked by application of noxious heat to the tail.Single-unit recording and iontophoretic techniques were used to examine the ability of the GABAA receptor antagonist bicuculline methiodide (BIC) to antagonize selectively the characteristic off-cell pause. Iontophoretic application of BIC (5-30 nA) blocked the TF-related pause in each of the off-cells tested. This effect of BIC was generally slow in onset, and outlasted the period of application by...
Time dependent breakdown characteristics of parylene dielectric in metal-insulator-metal capacitors

Abstract In this work, we present reliability results of MIM (Metal–Insulator–Metal) capacitors fabricated with parylene as the dielectric, deposited at room temperature. We have evaluated the time dependent dielectric breakdown (TDDB) of parylene-based MIM capacitors as a function of constant DC voltage stress, area and dielectric thickness of the capacitor. Mean-time-to-failure (MTTF) of parylene evaluated at different stress voltages shows a power law distribution over the applied voltage range and device area, with MTTF driven by the number of defects. Defect density in the parylene capacitors is also reported and is calculated to be ∼1.2 × 10 3 defects/cm 2 .
Temporal Requirement for Associative LTP in the Dentate. Dependence On Modeled Rm and Ri Values

The temporal limits of association, at the cellular level, are studied by using a strong input to control LTP induction of a weak input. The preferred temporal ordering is the weak input preceding, or simultaneous with, the strong input. This experimental result is reproduced in our biophysical models. Surprisingly, the preferred temporal ordering predicted by these biophysical models does not depend on whether we use whole-cell or sharp electrode data even though the Rm and input resistance of these data are quite different. (However with different resistivity values, different strong input intensities are required for potentiation to occur). Even with the much larger time constant of whole-cell patch experiments, the NMDA receptor is the arbiter of the temporal limits of associativity.
Evaluating models of speaker head nods for virtual agents

Virtual human research has often modeled nonverbal behaviors based on the findings of psychological research. In recent years, however, there have been growing efforts to use automated, data-driven approaches to find patterns of nonverbal behaviors in video corpora and even thereby discover new factors that have not been previously documented. However, there have been few studies that compare how the behaviors generated by different approaches are interpreted by people. In this paper, we present an evaluation study to compare the perception of nonverbal behaviors, more specifically head nods, generated by different approaches. Studies have shown that head nods serve a variety of communicative functions and that the head is in constant motion during speaking turns. To evaluate the different approaches of head nod generation, we asked human subjects to evaluate videos of a virtual agent displaying nods generated by a human, by a machine learning data-driven approach, or by a hand-crafted rule-based approach. Results show that there is a significant effect on the perception of head nods in terms of appropriate nod occurrence, especially between the data-driven approach and the rule-based approach.
Intraadrenal steroid metabolism in the guinea pig: Guinea pig adrenal microsomes metabolize androstenedione in a manner distinct from liver microsomes

Several immunochemical homologs of hepatic cytochromes P450 (CYPs) capable of steroid catabolism have been identified in the guinea pig adrenal cortex. Their predominance in males suggests a role in sex-differentiated metabolism of androgens. Therefore, we examined the ability of microsomes from male guinea pig adrenals and liver to metabolize androstenedione. Microsomes were incubated in the presence of radiolabeled steroids, the products of the reaction extracted, separated by TLC, and visualized by autoradiography. Metabolites were identified by comigration with commercially available standards in several solvent systems, in one and two dimensional TLC. Microsomes from both tissues metabolized androstenedione. However, the products formed differed markedly in the two tissues. Liver microsomes formed one major metabolite, testosterone. It represented 85% of the metabolized androstenedione. 6β-Hydroxylated androstenedione and testosterone each comprised 3-4% of the liver metabolites. In addition, at leas...
Balancing the Risks and Benefits of Oxygen Therapy in Critically III Adults

Oxygen therapy is an integral part of the treatment of critically ill patients. Maintenance of adequate oxygen delivery to vital organs often requires the administration of supplemental oxygen, sometimes at high concentrations. Although oxygen therapy is lifesaving, it may be associated with deleterious effects when administered for prolonged periods at high concentrations. Here, we review the recent advances in our understanding of the molecular responses to hypoxia and high levels of oxygen and review the current guidelines for oxygen therapy in critically ill patients.
Preparation of a chronic thoracic duct-venous shunt in calves.

SummaryA technique is described for the preparation of a chronic thoracic duct-venous shunt in calves. These shunts remained functional up to 18 days, usually 7 to 10 days. Calves were found to be excellent animals for experiments involving thoracic duct lymph.
A Topological Analysis of the Open Souce Software Development Community

The fast growth of OSS has increased the interest in studying the composition of the OSS community and its collaboration mechanisms. Moreover, the success of a project may be related to the underlying social structure of the OSS development community. In this paper, we perform a quantitative analysis of Open Source Software developers by studying the entire development community at SourceForge. Statistics and social network properties are explored to find collaborations and the effects of different members in the OSS development community. Small world phenomenon and scale free behaviors are found in the SourceForge development network. These topological properties may potentially explain the success and efficiency of OSS development practices. We also infer from our analysis that weakly associated but contributing co-developers and active users may be an important factor in OSS development.
The emotional implications of organizational politics: A process model:

Using affective events theory as a framework, this study examined the role of emotions in mediating the effects of perceived politics on adverse employee outcomes. The authors proposed that frustration translates employees' perceptions of politics into lower levels of performance and increased organizational withdrawal (i.e. turnover intentions) through a mediational path that involves job satisfaction. The proposed model received support with empirical results from 134 subordinate—supervisor dyads sampled across a single government agency. In particular, there was evidence that frustration and job satisfaction mediated the effects of politics perceptions on employee behavioral outcomes.
Redefining the Target: Chemotherapeutics as Antiangiogenics

Angiogenesis, or new blood vessel formation, is now known to play an important role in both growth and metastasis of many cancers. The central importance of angiogenesis and the understanding of how new blood vessels are formed, has led to novel therapies designed to interrupt this process. Though specific antiangiogenic compounds have only recently entered the clinic, they herald a new era, one in which biology is the basis for therapy. The intense interest in angiogenesis has also lead to a re-examination of the activity of many established cytotoxic agents. Claims of antiangiogenic activity abound, unfortunately, with no common criteria and often little evidence of clinical relevance. What are we to think? Have oncologists unknowingly been administering antiangiogenic therapy all these years? If chemotherapeutics are really antiangiogenics in disguise, why have they failed to cure most solid tumors? Might the hard-learned lessons of chemotherapy resistance pertain to the novel antiangiogenics as well? Though we can offer no certain answers to these important questions, we do offer a framework on which to order the rapidly burgeoning literature. We suggest criteria by which a cytotoxic agent might reasonably be considered to have meaningful antiangiogenic activity. Finally, we describe potential mechanisms of resistance to antiangiogenic chemotherapies-some of which may apply to the pure antiangiogenics currently in development.
ON CHARACTERIZING AND ASSESSING THE VALIDITY OF BEHAVIORAL MODELS AND THEIR PREDICTIONS

We present a conceptual framework for the validation of behavioral models and the prediction information derived from them. The setting for this work is a modern product development environment in which design is performed by teams of specialists who exchange information and knowledge. This setting makes validation responsibilities ambiguous and separates users from knowledge relevant to validation. To alleviate these problems, we identify three complementary validation responsibilities—validity characterization, compatibility assessment and adequacy assessment—that together solve the validation problem. We define the responsibilities in terms of formal descriptions of models and predictions that provide accuracy assurances within a welldefined context. Because behavioral models are similar to scientific theories and are a form of knowledge, it is possible to draw upon the philosophy literature to gain insight into validation. We review the relevant epistemology and the philosophy of science literature and identify several conclusions that apply to validation. These conclusions provide perspective on the limitations of the described framework. Although the framework is not a complete solution to the validation problem, it serves as is a conceptual roadmap to understanding and solving the problem. As such, this work raises many fundamental questions about validation and represents a starting point for future investigation.
DNA nanotechnology for nucleic acid analysis: DX motif-based sensor.

A sensor that fluoresces in the presence of specific nucleic acids was designed and characterized. The sensor uses a molecular beacon probe and three adaptor strands to form five-stranded associate, a DX-tile, with a specific analyte. The new sensor can be used as a highly selective and affordable tool for real-time analysis of DNA and RNA.
CREB-mediated alterations in the amygdala transcriptome: coordinated regulation of immune response genes following cocaine

The neuronal circuitry underlying stress- and drug-induced reinstatement of cocaine-seeking has been relatively well characterized; however, less is known regarding the long-term molecular changes following cocaine administration that may promote future reinstatement. The transcription factor cAMP response element-binding protein (CREB) is necessary for stress- but not cocaine-induced reinstatement of conditioned reward, suggesting that different molecular mechanisms may underlie these two types of reinstatement. To explore the relationship between this transcription factor and reinstatement, we utilized the place-conditioning paradigm to examine alterations in gene expression in the amygdala, a neural substrate critically involved in stress-induced reinstatement, following the development of cocaine reward and subsequent extinction. Our findings demonstrate that the amygdala transcriptome was altered by CREB deficiency more than by previous cocaine experience, with an over-representation of genes involved in the immune response. However, a subset of genes involved in stress and immune response demonstrated a drug×genotype interaction, indicating that cocaine produces different long-term alterations in gene expression depending on the presence or absence of CREB. This profile of gene expression in the context of addiction enhances our understanding of the long-term molecular changes that occur throughout the addiction cycle and identifies novel genes and pathways that might lead to the creation of better therapeutic agents.
Coating Life Prediction Under Cyclic Oxidation Conditions

The hot gas path section components of land based turbines require materials with superior mechanical properties and good hot corrosion and oxidation resistance. These components are generally coated with either a diffusion coating (aluminide or platinum aluminide) or with an overlay coating (MCrAlY) to provide additional hot corrosion and/or oxidation protection. These coatings degrade due to inward and outward diffusion of elements during service. Outward diffusion of aluminum results in formation of a protective oxide layer on the surface. When the protective oxide spalls, aluminum in the coating diffuses out to reform the oxide layer. Accelerated oxidation and failure of coating occur when the Al content in the coating is insufficient to reform a continuous alumina film. This paper describes development of a coating life prediction model that accounts for both oxidation and oxide spallation under thermal mechanical loading, as well as diffusion of elements that dictate the end of useful life. Cyclic oxidation data for aluminide and platinum aluminide coatings were generated to determine model constants. Applications of this model for predicting cyclic oxidation life of coated materials are demonstrated. Work is underway to develop additional material data and to qualify the model for determining actual blade and vane coating refurbishment intervals.Copyright © 1997 by ASME
The Crystal Structures of Forsterite and Hortonolite at Several Temperatures Up to 900"C

The crystal structures of a pure synthetic forsterite and a natural metamorphic manganoan hortonolite have been refined from three-dimensional intensity data obtained at 20', 300", 600", and 900"C. Both structures show a zeto or slightly negative expansion of silicon-oxygen distances compared with large positive expansions of the octahedral cation-oxygen distances with increasing temperature. The hortonolite refinements indicate a slight preference of Fe, possibly as Fe"*, for the smaller Ml site. This preference appears to increase with increasing temperature.
The WACC User's Guide

The estimation of corporate capital costs is complicated by many practical issues that create numerous degrees of freedom and lead to wide-ranging results. We provide pragmatic solutions including: * A global market risk premium (MRP) of about 5%, based on historical data, market expectations, and a review of the literature * Several methods to derive reliable beta estimates including direct regressions, portfolio regressions, and constructed betas * A normalized nominal riskless rate of about 5%, based on forward looking market data * A value of tax shield framework that implies lower value and higher WACCs for more leveraged or volatile situations * The WACC of a convertible bond, based on its economic decomposition of debt and equity * A framework for global capital costs to supplement the risk analysis and qualitative considerations involved in global investing where risks are subject to rapid change . . . other international risks and costs should be incorporated into the cash flows and sensitivity analysis
Micromechanical Velcro

The authors have developed arrays of micromechanical mating structures, fabricated with silicon micromachining techniques, which act as mechanical adhesives. The microstructures are fabricated on standard silicon wafers, with an areal density of approximately 200000 per cm/sup 2/. The microstructures on two identical surfaces will self-align and interlock with each other under application of adequate external pressure. A tensile strength per unit interlocked area of 1.1 MPa, or 160 psi, has been achieved. In this work, the authors describe the design and fabrication of this micromechanical Velcro; the authors also present results of their experimental tests, a theoretical estimate of the tensile strength, and design constraints. >
Wave propagation in twisted metamaterials

Twisted metamaterials, i.e. arrays of identical planar metasurfaces stacked with a sequential rotation, offer new possibilities for manipulating and engineering wave propagation. This paper presents a generalized Floquet analysis to discuss wave propagation in these kind of structures. The authors show that the eigenmodes support specific circular polarization properties based on a lattice effect even when achiral inclusions are considered.
Inauthentic Dasein and Its Relation to a "Chinese-like 'Constancy'"

It has long been theorized that Heidegger’s idea for Dasein was highly influenced by the Chinese notion of the Dao. This is due to a misinterpretation on behalf of Heideggerian scholars and others of what the Dao represents. In fact, Heidegger, in explicating what he thought to be “the most extreme inversion of φύσης-ουσία [phusis-ousia],” made this equal to “Chinese-like ‘constancy,’” which is the basis of the Dao. Taking what Heidegger interpreted phusis to be (derived from Aristotelian metaphysics and an assumption of pre-Socratic thought) as a process of unconcealment from continuing re-concealment which signals a kind of “truth” of being [phusis], that which calls for constant presence is inauthentic Dasein, rather than authentic Dasein. In other words, Heidegger’s idea of what inauthentic Dasein calls for could be explained within Aristotle’s system as equal to aiming to replace phusis with the know-how of τέχνη [techne]. The Dao, as rightfully understood and utilized by the master craftsman and the Sage, is accessible, constant, and knowable. This could not be in more opposition to Heidegger’s notion of phusis.1
Onset of ocular graft-versus-host disease symptoms after allogeneic hematopoietic stem cell transplantation.

Objective To study the factors affecting the time to onset of ocular GVHD in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Application of Theranostics to Measure and Treat Cell Heterogeneity in Cancer

Individualized therapy is a noble anticipation in oncology. It would permit not only to adapt a treatment to an individual’s physiology and characteristics, but also to pinpoint therapeutic features for each neoplasia. The high degree of cell heterogeneity in cancer, with mixtures of cells of different origins and cell populations that evolve toward multiple genomic and epigenomic profiles, makes the precise targeting and treatment of each abnormal cell a priority. The phenotypic nature of heterogeneity in cancer is largely determined by changes in gene transcription requiring the identification of an increasing number of intracellular and even intranuclear markers. Such a requirement brings new challenges for state-of-the-art technology focusing on single-cell analysis and begs for the development of nanotools that can provide the multiplex approach necessary to target cancer locations and reach, detect, and appropriately treat subgroups of cells. In this chapter we introduce the reader to the origins of cell heterogeneity in cancer and discuss how this emerging knowledge has shed light on the difficulties encountered in the management of neoplasias over the past few decades. Our analysis illustrates how nanotheranostics might help effectively address the issue of cell heterogeneity to halt cancer progression, overcome resistance to treatment, and possibly decrease cancer risks among individuals.
What is Special about Special Education? The Crippled Child

This is the sixth of a series of articles compiled by Darrel II. Mase, University of Florida, which deal with the special aspects of educating various types of exceptional children.
Paths to Protecting Patron Privacy

Column Editor's NotesThe “Digital Trends and the Global Library Community” column examines technological advances internal and external to libraries. The focus is on how technology is changing the way services are provided to users, the methodologies used in the provision of those services, and the resulting scope of responsibilities of libraries and parent institutions. Interested authors are invited to submit proposals and articles to the column editor at marta.deyrup@shu.edu. Please include “IILR Submission” in the header.
Panobinostat Inhibits JAK2/STAT3 Pathway in Multiple Myeloma.

Abstract 2849 Poster Board II-825 Histone deacetylase inhibitors (HDACi) are emerging as a potential therapy for Multiple Myeloma (MM). Their antineoplastic activity depends not only on nucleosomal histone acetylation, but also on direct modulation of non-histone proteins, including p53 or HSP90. Previous studies suggest that histone deacetylases inhibitors modulate Jak2/Stat3 signaling pathway, a cascade mediating tumor cell survival. Here we examine how Panobinostat, a class I-HDAC inhibitor currently in phase I/II clinical trial, can modulate the function of the Jak2/ Stat3 pathway in MM. We first observed that Panobinostat inhibited IL6-induced Stat3 phosphorylation (Tyr705) and Jak2 phosphorylation (Tyr 1007/1008) in MM cell lines ( MM1S and INA6) in a dose- and time- depend fashion, associated with induction of Stat3 acetylation (Lys 685). Since acetylation of Stat3 alters the distribution rather than the functional status of Stat3, we next examined whether Panobinostat altered the nuclear versus cytoplasmic localization of Stat3 in MM cell lines. Although total STAT3 protein level did not change, Panobinostat treatment did trigger decreased nuclear Stat3 phosphorylation, suggesting that Panobinostat blocks Stat3 transcriptional activity. We showed by western blot analysis that the down stream pathway induced by Stat3 (Survivin, Bcl XL, c-Myc) was also down regulated after Panobinostat treatment, further confirming inhibition of STAT3 activity. Take together, our results suggest that Panobinostat inhibits the Jak2/Stat3 pathway by inhibiting STAT3 binding to DNA consensus region, rather than modulating nuclear translocation. To establish the molecular mechanism whereby Panobinostat regulates this pathway, we examined IL6/gp130 receptor, which is upstream in the Jak2 /Stat3 pathway. Panobinostat decreased both cell surface and intracellular gp130 protein expression. Interestingly, Panobinostat also inhibited IL6-induced phosphorylation of gp130, suggesting that it can directly inhibit gp130 activation. Our study therefore suggests a dual mechanism of inhibition of the JAK2/Stat3 pathway induced by Panobinostat via modulation of STAT 3 transcriptional function and gp130 -induced STAT3 activation. Finally, we observed upregulation of the MEK/ERK signaling pathway associated with HDAC inhibition, suggesting that combined blockade of these cascades may be useful. Indeed our preliminary data demonstrate enhanced cytotoxicity in MM cell lines (MM1S and INA6) induced by treatment with combined Panobinostat and MEK inhibitors, even in the presence of bone marrow stromal cells or survival cytokines ( IL6 or IGF). Our study therefore suggests a novel mechanism of action of HDAC inhibitors that provides the rationale for clinical evaluation of novel combinations based upon targeting STAT3 signaling pathway. Disclosures: Anderson: Celgene : Research Funding; Novartis: Research Funding; Millennium: Research Funding.
A framework for counterfeit smart grid device detection

The core vision of the smart grid concept is the realization of reliable two-way communications between smart devices (e.g., IEDs, PLCs, PMUs). The benefits of the smart grid also come with tremendous security risks and new challenges in protecting the smart grid systems from cyber threats. Particularly, the use of untrusted counterfeit smart grid devices represents a real problem. Consequences of propagating false or malicious data, as well as stealing valuable user or smart grid state information from counterfeit devices are costly. Hence, early detection of counterfeit devices is critical for protecting smart grid's components and users. To address these concerns, in this poster, we introduce our initial design of a configurable framework that utilize system call tracing, library interposition, and statistical techniques for monitoring and detection of counterfeit smart grid devices. In our framework, we consider realistic counterfeit device scenarios with different smart grid devices and adversarial settings. Our initial results on a realistic testbed utilizing actual smart-grid GOOSE messages with IEC-61850 communication protocol are very promising. Our framework is showing excellent rates on detection of smart grid counterfeit devices from impostors.
Rapidly Aging Populations: Russia/Eastern Europe

Regional dimensions and trends in population aging: Russia/Eastern Europe Population aging is a global phenomenon and countries of Eastern European also experience rapid increase in the proportion of older people. The proportion of elderly people in the Eastern Europe is currently lower than in the European region as a whole. However this population aging is expected to continue over the next few decades, eventually leading to the convergence in the proportion of older people in the countries of Eastern and Western Europe. Aging of population is often measured through an increase in the percentage of elderly people of retirement ages. A society is considered to be relatively old when the fraction of the population aged 65+ years exceeds 8-10% (Kinsella and Velkoff 2001). According to this definition, the populations of the Eastern Europe and Russia are becoming very old, because the percentage of elderly people reached the levels of 14.2% and 13.8% correspondingly in 2005, and it is expected to increase further. The choice of the boundary for old age (65 years and over) is rather arbitrary therefore many demographers who study Eastern European countries also use 60 years cut-off (retirement age for many countries of the Eastern Europe). In this case a population is considered to be old, when the proportion aged 60+ years exceeds 10-12% (Kinsella and Velkoff 2001). Table 1 presents data on the proportion of population age sixty and over for selected countries. Note that populations of Bulgaria, Hungary and Ukraine were older than the population of the European region in 2005. In addition to these three
Shock initiation of explosives: High temperature hot spots explained

We investigated the shock initiation of energetic materials with a tabletop apparatus that uses km s−1 laser-driven flyer plates to initiate tiny explosive charges and obtains complete temperature histories with a high dynamic range. By comparing various microstructured formulations, including a pentaerythritol tetranitrate (PETN) based plastic explosive (PBX) denoted XTX-8003, we determined that micron-scale pores were needed to create high hot spot temperatures. In charges where micropores (i.e., micron-sized pores) were present, a hot spot temperature of 6000 K was observed; when the micropores were pre-compressed to nm scale, however, the hot spot temperature dropped to ∼4000 K. By comparing XTX-8003 with an analog that replaced PETN by nonvolatile silica, we showed that the high temperatures require gas in the pores, that the high temperatures were created by adiabatic gas compression, and that the temperatures observed can be controlled by the choice of ambient gases. The hot spots persist in shock-...
IDRC-TTI Workshop on ‘Rural Urban Transformation in India: Uneasy Neighbours?’

The issue of rural-urban interactions is being increasingly recognised as central to the processes of social, economic, and cultural change in cities and the countryside. Populations and activities that were described either as rural or urban are now more closely linked both across space and sectors than is usually realised and distinctions are becoming arbitrary. This is due to the result of growth in the Indian economy along with the declining significance of the farm sector on one hand and growth in the non-farm sector on the other. Linkages between urban centres and the countryside, including movement of people, goods, capital and other social transactions, are becoming much more important in processes of rural and urban changes than before. Rapid growth in the urban population, migration, and the transformation of human settlements that India is currently witnessing, represent the fundamental changes in the structure of Indian society and are key issues of concern for both academicians and policy makers in the 21st century. It produces new challenges in virtually every aspect of human organisation. It demands a new look at urban planning strategies, infrastructure, and sustainability of natural resources, housing, health care, employment and welfare needs. At the same time this surge in urbanisation is changing the social fabric of society, forcing a rethinking of the relationship between national, state and local governments. It is in this context that IRMA and PAC jointly organised a two-day interdisciplinary workshop on the changing dynamics of the rural-urban relationship in India by reflecting on the nature, pace and trajectory of changes, and its implication for both rural and urban spaces. The workshop brought together academicians, policy makers, and practitioners to explore the possible pathways not only for a better understanding of issues but also to explore the way forward for both urban and rural development.
Experiences with DERIVA: An Asset Management Platform for Accelerating eScience

The pace of discovery in eScience is increasingly dependent on a scientist&#x2019;s ability to acquire, curate, integrate, analyze, and share large and diverse collections of data. It is all too common for investigators to spend inordinate amounts of time developing ad hoc procedures to manage their data. In previous work, we presented DERIVA, a Scientific Asset Management System, designed to accelerate data driven discovery. In this paper, we report on the use of DERIVA in a number of substantial and diverse eScience applications. We describe the lessons we have learned, both from the perspective of the DERIVA technology, as well as the ability and willingness of scientists to incorporate Scientific Asset Management into their daily workflows.
Fear of the Unknown: Judicial Ethics after Caperton

In Caperton v. A.T. Massey Coal Co., the Court recently found that an elected appellate judge’s participation in a company’s appeal violated due process in light of the substantial financial contributions made by the company’s chairman toward the judge’s election. The Court explained that “there is a serious risk of actual bias” on the judge’s part when, as here, “a person with a personal stake in a particular case had a significant and disproportionate influence in placing the judge on the case.” The dissenting Justices targeted the vagueness of the Court’s standard, predicting that it would result in a flood of recusal motions which would bring the judicial process into disrepute. This Essay examines the dissent’s prediction and offers a host of reasons why it is unlikely to come true.
A Broad-Based Multiliteracies Theory and Praxis for a Diverse Writing Classroom

Abstract This article contends that the writing curriculum for “diverse classrooms” should be responsive to the resources students bring with them to the classroom and cultivate in them the multiple literacies needed to successfully navigate an increasingly global workplace and society. It also presents some findings from an experiment with and investigation into how diverse students in a college writing class responded to a curriculum and pedagogical approach framed around the idea of “a broad-based multiliteracies,” a curricular and pedagogical framework informed by recent developments in some aligned fields of rhetoric and composition—intercultural communication, literacy studies, media studies, and digital/new media studies.
New sources for the emergence of new invaders.

Biological invasions continue to occur worldwide, resulting in substantial impacts on ecosystems as well as human health and economies (1, 2). One of the fundamental tasks associated with managing these invasions is to predict which species are most likely to be future invaders—a task that has become increasingly challenging due to climate change and shifts in the source of potential invaders (3, 4). Scientists have undertaken considerable efforts to manage the potential risk of future invasions by focusing on species that have been introduced previously in other areas, often with considerable impact. Many elegant studies of these repeat offenders have used various combinations of phylogenetic, morphological, and life history characteristics to develop predictive models that predict which species are most likely to invade (5, 6). Most of these studies have relied on the data from the investigations of serial invaders to predict future invasions, and many management programs have placed their emphasis on high-profile invaders that have caused demonstrable damage in other regions (7). In short, scientists and managers have generally relied on information from the track records of previous invasions to predict future invasions. However, a new study in PNAS (8) calls this thinking into question by demonstrating that emerging invaders, species that have never been found outside of their native range, continue to be a significant proportion of new invasions. They also demonstrate that the continuing presence of newly emerging invaders is … [↵][1]1Email: tedgrosholz{at}ucdavis.edu. [1]: #xref-corresp-1-1
A Time-Friendly, Feasible Measure of Nutrition Knowledge in Type 1 Diabetes: The Electronic Nutrition and Carbohydrate Counting Quiz (eNCQ)

Background:Greater knowledge about nutrition and carbohydrate counting are associated with improved glycemic control and quality of life in youth with type 1 diabetes (T1D). However, limited assess...
Variable Energetic Strategies in Disturbed and Undisturbed Rain Forests: Eulemur rubriventer Fecal Cortisol Levels in South-Eastern Madagascar

Habitat disturbance in Madagascar is pervasive. Researchers have assessed anthropogenic impacts on lemurs from alterations in locomotion, behavior, diet, distribution, and density. Such strategies may help lemurs cope with environmental change, but the underlying mechanisms facilitating such flexibility remain poorly understood. To document a physiological response to ecological stress, I investigated stress hormones in wild adult Eulemur rubriventer, the red-bellied lemur, in disturbed and undisturbed rain forests in south-eastern Madagascar over 17 months, from November 2003 to March 2005. My goals were to compile E. rubriventer cortisol excretion profiles, observe E. rubriventer’s response to food fluctuations, and compare these responses among groups in disturbed and undisturbed sites. Fecal glucocorticoid metabolite levels (fGCs) did not differ by sex and were lowest during the prebreeding season when fruit was abundant and highest during parturition and early lactation when fruit was scarce. Though fGC patterns were similar across sites, levels were significantly higher in the undisturbed site, contrary to expectations. fGCs were invariable in the disturbed site, despite lower and less seasonal fruit availability. A severely attenuated response to known ­environmental challenges, coupled with high infant mortality in the disturbed site, indicates that this population may be at risk of decline.
Editing: The Big Picture

The way that a document is drafted and edited varies greatly not only from institution to institution, but also from document to document within the same institution. For short documents, the drafting is often done by a single writer who has expertise on the subject. After that writer drafts the document, the document proceeds through an editing chain, which may be in series or in parallel. Many institutions, for example, have a simple sign-off chain: author to first-level manager to second-level manager and so on. In such a series chain, the author usually makes all the changes at one level before the document proceeds to the next. Once all have signed the document, the document is published.