cssi/SciSciGPT-SciSciNet huggingface dataset:
Polycystin-1 Interacts with Intermediate Filaments

Polycystin-1, the protein defective in a majority of patients with autosomal dominant polycystic kidney disease, is a ubiquitously expressed multi-span transmembrane protein of unknown function. Subcellular localization studies found this protein to be a component of various cell junctional complexes and to be associated with the cytoskeleton, but the specificity and nature of such associations are not known. To identify proteins that interact with the polycystin-1 C-tail (P1CT), this segment was used as bait in a yeast two-hybrid screening of a kidney epithelial cell library. The intermediate filament (IF) protein vimentin was identified as a strong polycystin-1-interacting partner. Cytokeratins K8 and K18 and desmin were also found to interact with P1CT. These interactions were mediated by coiled-coil motifs in polycystin-1 and IF proteins. Vimentin, cytokeratins K8 and K18, and desmin also bound directly to P1CT in GST pull-down and in in vitro filament assembly assays. Two observations confirmed these interactions in vivo: (i) a cell membrane-anchored form of recombinant P1CT decorated the IF network and was found to associate with the cytoskeleton in detergent-solubilized cells and (ii) endogenous polycystin-1 distributed with IF at desmosomal junctions. Polycystin-1 may utilize this association for structural, storage, or signaling functions.
Electromagnetic Implosion Using an Array

Summary form only given. This paper considers the use of a spherical array of sources producing a large fast-transient electromagnetic wave near the center of the sphere. The results here complement the results for an electromagnetic implosion due to reflector and lens types of implosion IRAs. There are at least three general ways to construct an IRA (impulse radiating antenna). The basic idea is to make a fast-rising pulse in the form of a plane wave on an antenna aperture. This can be done via a lens at the end of a TEM horn (lens IRA), a paraboloidal reflector driven by a TEM feed, typically four arms (a reflector IRA), and an array of very manv elements at or near the antenna aperture (an array IRA). Lately, IRA technology is being applied to focus a fast pulse on a small target (an IIRA, or implosion IRA). Much attention has been given to the reflector form. A similar effect can be achieved using a lens (which can be massive in a large structure). For completeness, let us consider an array as another alternative. Such is the subject of this paper. There are various forms that an array IRA can take. The array can be planar with the elements triggered in a sequence so as to produce a converging spherical wave. For convenience let us consider a spherical array of radius a on surface Sa . While the present result is for a full spherical distributed source, it can be applied to a half-covered sphere (say -pi/2 < phi < pi/2) using symmetry arguments. This will cut the delta function in half at the origin (when fields would otherwise be arriving from both sides of the target). This depends on the size of the target compared to ctmr . Note that we have not specified the characteristics of the target centered on r = 0. This will change the pulse amplitude based on reflection from the target. One can potentially improve matters with a special lens near the target". Here we do not go into the details of the design of the individual array elements. Note that on Sa one can place conductors on contours of constant thetas. Array elements can be set in bands around the sphere connecting two adjacent such conductors. The element voltages can vary with thetas, and/or the spacing of the constant-thetas conductors can vary with thetas.
The Reading Habits and Literacy Attitudes of Inservice and Prospective Teachers Results of a Questionnaire Survey

This article describes a questionnaire survey of 747 students enrolled in a graduate school of education, who are currently teachers or prospective teachers. The Literacy Habits Questionnaire, deve...
A proposed 4-5 &#181;m energy transfer laser

Experimental evidence is presented which indicates vibrational energy transfer from deuterium (D 2 ) to the C-H stretch vibrational mode of chloroform (CHCl 3 ) in an e -beam sustained discharge. The application of this energy transfer technique to develop a new class of 4-5 \mu m lasers is discussed.
Role of Nonhost Environments in the Lifestyles of Salmonella and Escherichia coli

The gram-negative bacterial species Salmonella enterica and Escherichia coli are members of the family Enterobacteriaceae that spend a good part of their lives as residents of animal hosts. S. enterica is the etiologic agent of gastroenteritis and typhoid fever in humans ([88][1]), whereas E. coli
Isolation of twenty low stutter di‐ and tetranucleotide microsatellites for population analyses of walleye pollock and other gadoids

Fourteen tetra- and six dinucleotide microsatellites, which exhibit minimal stuttering following amplification via PCR were developed from walleye pollock Theragra chalcogramma. Most of these loci were isolated from a library enriched for tetranucleotide microsatellites by hybridization of genomic DNA to (gata)7 oligonucleotides bound to streptavidin-coated paramagnetic beads. The average heterozygosity of these loci is ∼80%, and ranges from 53–95%. Mendelian inheritance was confirmed in five families, each consisting of a minimum of 10 or more offspring. Primer sets for all 20 loci were also evaluated in Arctic cod Boreogadus saida, Pacific cod Gadus macrocephalus, Pacific tomcod Microgadus proximus, sa.ron cod Eleginus gracilis, Pacific hake Merluccius productus, Atlantic cod Gadus morhua, haddock Melanogrammus aeglefinus, blue whiting Micromesistius poutassou, and European hake Merluccius merluccius. In each of these species, 3–19 primer sets amplified variable microsatellite loci. These loci, which exhibit little stutter and moderate to high variability, should be useful population markers in pollock and other gadoid fishes.
Implementation of a GMPLS-based Network with End Host Initiated Signaling

In this article, we describe our experiences in implementing an experimental wide-area GMPLS network called CHEETAH (Circuit-Switched End-to-End Transport Architecture). The key concept is to add a complementary end-to-end circuit based service with dynamic call-by-call bandwidth sharing to the connectionless service already available to end hosts via the Internet. The current CHEETAH experimental network consists of off-the-shelf GMPLS-capable SONET switches (with Ethernet interfaces) deployed at three locations, Research Triangle Park, North Carolina, Atlanta, Georgia, and Oak Ridge, Tennessee. We designed and implemented a CHEETAH software package to run on Linux end hosts connected to the CHEETAH network. Among other functions, this software package includes an RSVP-TE client module to enable end users and applications to dynamically initiate requests for dedicated end-to-end circuits and receive/respond to requests for circuits. We present measurements for typical end-to-end circuit setup delays across this network. For example, end-to-end circuit setup delay from a Linux end host in NC to a host in Atlanta is 166ms.
Reliability monitoring and screening issues with ultrathin gate dielectric devices

Installing appropriate quality and reliability monitoring procedures for ultrathin gate dielectrics is of utmost importance. Ensuring the integrity of VLSI products and unwavering customer satisfaction are the top priorities. Several key strategic avenues have been pursued to accomplish those priorities. First, basic tool and processing monitoring and measurement procedures are put into place for categories such as metallic contamination, foreign material control, and semiconductor stress-induced defects such as dislocations and stacking faults. Second, a new voltage ramp breakdown test, especially designed for ultrathin gate dielectrics, is installed based on a one-to-one correlation with TDDB testing, from which a fail criterion for minimum required breakdown voltage of the distribution is defined. The voltage ramp test is capable of identifying weaknesses or failures for either the intrinsic or extrinsic parts of the failure rate distribution. The voltage ramp test is installed at various processing levels starting with post silicide probing (PSP) utilizing very large guide area/perimeter structures (area>0.5 mm/sup 2//chip, and perimeter >1 meter/chip) with both shallow trench isolation (STI) and diffusion perimeters. Third, a voltage breakdown test is put into place for in-line charging effects at various processing levels. The structure used employs minimum polysilicon linewidth devices and contains a nonantenna reference device as well as a variety of antenna structures for various design levels starting with polysilicon and including all via, contact, and metal levels. Such a dielectric breakdown test for charging is also well correlated with other device failure mechanisms such as hot carriers. Fourth, a new methodology was adopted based on a one-to-one quantitative correlation between lifetime as derived from accelerated TDDB testing and the initial value of gate dielectric leakage at a predetermined value(s) of voltage(s). This excellent correlation was verified for gate dielectric thickness ranging from 10 nm to below 3 nm. Fifth, at product level, the standby I/sub ddQ/ and I/sub dd/ currents are measured and tracked for changes under accelerated stress conditions for numerous scan chains. This measurement is a good indicator of the defect level on products and the overall impact of ultrathin gate dielectric on product yield and reliability. Finally, various types of voltage screens and burn-in with duration ranging from few seconds to several hours (at wafer and packaged levels) can be implemented (at least on a selected set of products) to monitor and/ improve the reliability of the final assembly. Accordingly, the body of the text discusses the following topics: monitoring of gate dielectric reliability, monitoring of device stability, monitoring of thin dielectric initial leakage, semiconductor stress induced defects, metallic contamination, and reliability of integrated circuits.
Remembering Nat Schoenfeld

William Nathan Schoenfeld was born in New York City on December 6, 1915, and died in Sun City West, Arizona, on August 3, 1996. He was an undergraduate at the College of the City of New York, where he received a BS degree in 1937. He received his PhD from Columbia University in 1942 and then continued there as a faculty member, advancing from lecturer to full professor. In 1966 he moved to Queens College of the City University of New York, where he remained until his retirement in 1983. During his nyears at Queens, he also took on visiting appointments in Brazil, Mexico, and Venezuela. In retirement, he spent roughly a decade in Israel, where he occasionally taught as a visiting professor at the Hebrew University of Jerusalem. He returned to the United States for his final years. He is survived by his wife, Melanie, their three children, Rivka, Joshua and Naomi, and a son, Mark, from a previous marriage.
A new three phase AC to DC rectifier with active power factor correction

A new three phase AC to DC rectifier system with near unity input power factor and reduced input current harmonics is proposed, The proposed approach employs three SCRs and three active semiconductor switches with anti-parallel diodes to form a three phase bridge. In the proposed approach only two semiconductor device drops are encountered in the power flow path. Also the DC link inductor is unnecessary and three AC side inductors are used instead. It is shown that discontinuous input current is the preferred mode of operation to realize high quality input current. A suitable control strategy is proposed in order to minimize the input current THD. Further, a zero voltage switching strategy is implemented to minimize the switching losses. The SCRs are suitably phase controlled to limit inrush currents during starting and to provide current limiting action under overload or output short circuit conditions. During normal operation the SCRs are gated to function as diodes. A design procedure for the proposed approach to achieve near sinusoidal input currents and zero voltage switching is detailed. Simulation and experimental results on a laboratory prototype system are discussed. >
Host Utilization and Distribution of Nubenocephalid Gregarines (Eugregarinorida: Actinocephalidae) Parasitizing Argia spp. (Odonata: Zygoptera) in the Central United States

Gregarine host specificity has been the cornerstone of gregarine taxonomy for nearly a century. Several laboratory experiments have accepted strict host specificity by failure to cross-infect distantly related hosts with unrelated gregarine species. These empirical studies are not feasible for all gregarine hosts, especially nondomesticated groups. Additionally, studies of gregarine distributions have always focused on insect hosts of disparate groups, rather than targeting potential hosts species within a single genus and their congeneric gregarines. This study addresses host utilization of nubenocephalid gregarines parasitizing the odonate genus Argia (Odonata: Zygoptera: Coenagrionidae). Populations of 9 species of adult Argia were collected, dissected, and observed for gregarine infection during the April-September flight seasons in 2007 from 17 localities in the central United States. On average, 2.5 species of Argia were collected at each locality. A species of Nubenocephalus—Nubenocephalus nebraskensis, Nubenocephalus secundus, or Nubenocephalus spp.—was collected from every infected population of Argia except for the Argia vivida population at Prairie Dog Town Fork-Red River, Randall County (Co.), Texas, U.S.A. Nubenocephalus secundus utilizes at least 7 of the 9 argid hosts sampled whereas N. nebraskensis was collected from only 2 argid species. Only Argia translata was observed to host both N. secundus and N. nebraskensis. These patterns of host utilization by nubenocephalid gregarines represent an ecotypic gregarine assemblage rather than a vicariant assemblage, demonstrating that nubenocephalid gregarines do not differentiate between species of Argia as hosts.
Internet routing instability

This paper examines the network inter-domain routing information exchanged between backbone service providers at the major U.S. public Internet exchange points. Internet routing instability, or the rapid fluctuation of network reachability information, is an important problem currently facing the Internet engineering community. High levels of network instability can lead to packet loss, increased network latency and time to convergence. At the extreme, high levels of routing instability have lead to the loss of internal connectivity in wide-area, national networks. In this paper, we describe several unexpected trends in routing instability, and examine a number of anomalies and pathologies observed in the exchange of inter-domain routing information. The analysis in this paper is based on data collected from BGP routing messages generated by border routers at five of the Internet core's public exchange points during a nine month period. We show that the volume of these routing updates is several orders of magnitude more than expected and that the majority of this routing information is redundant, or pathological. Furthermore, our analysis reveals several unexpected trends and ill-behaved systematic properties in Internet routing. We finally posit a number of explanations for these anomalies and evaluate their potential impact on the Internet infrastructure.
A case of lithium toxicity with significant QT interval prolongation

Background Lithium toxicity has been associated with electrocardiographic abnormalities, such as QT interval prolongation.
Ação afirmativa nos Estados Unidos: breve síntese da jurisprudência e da pesquisa social científica

Este artigo pretende apresentar sucintamente aos leitores nao familiarizados com a acao afirmativa nos Estados Unidos seus antecedentes historicos e atual status legislativo e, de maneira mais abrangente, abordar questoes empiricas das ciencias sociais relacionadas com a acao afirmativa. Abordam-se especificamente as falhas e/ou limitacoes da pesquisa que sustenta a hipotese da disparidade educacional, da evidencia empirica da "disparidade cientifica", e a afirmacao de que a acao afirmativa baseada em classe social seria tao ou quase tao eficaz na promocao da diversidade racial quanto a acao afirmativa baseada em raca. Examinam-se especificamente os trabalhos de Richard Sander, Richard Kahlenberg, Doug Williams e Peter Arcidiacono. O artigo tambem afirma que o caso Bakke , que apresentou, pela primeira vez, uma decisao da Suprema Corte sobre a acao afirmativa, desvirtuou a jurisprudencia a respeito da acao afirmativa na educacao e as discussoes sobre o tema, de modo a provocar efeitos lamentaveis e duradouros.
Comprehending and Regulating Financial Crises: An Interdisciplinary Approach

The 2008 financial crisis revealed that key players in finance, regulation, and the academy failed to understand realities outside their own area of expertise. Within the academy, scholars from an increasing number of disciplines study finance, and yet few of them seem to be in conversation. Perhaps understandably, given the complexity of a phenomenon such as “financial crisis,” no single discipline has yet offered an adequate analysis of what happened in 2008, or what could help prevent another such systemic threat to the economy. In this article, we argue that developing more effective capacity to comprehend and regulate financial markets requires an interdisciplinary approach that moves beyond pluralism and tolerance of other approaches. Rather, in-depth critical engagement with the underlying assumptions, methods, and findings across fields of research and practice is needed. To advance this argument, we discuss four specific, connected intra-disciplinary projects in progress, and show how key assumptions underlying approaches in each are revealed and revised through systematic engagement with other fields.
Materials Properties and Solvated Electron Dynamics of Isolated Nanoparticles and Nanodroplets Probed with Ultrafast Extreme Ultraviolet Beams

We present ultrafast photoemission measurements of isolated nanoparticles in vacuum using extreme ultraviolet (EUV) light produced through high harmonic generation. Surface-selective static EUV photoemission measurements were performed on nanoparticles with a wide array of compositions, ranging from ionic crystals to nanodroplets of organic material. We find that the total photoelectron yield varies greatly with nanoparticle composition and provides insight into material properties such as the electron mean free path and effective mass. Additionally, we conduct time-resolved photoelectron yield measurements of isolated oleylamine nanodroplets, observing that EUV photons can create solvated electrons in liquid nanodroplets. Using photoemission from a time-delayed 790 nm pulse, we observe that a solvated electron is produced in an excited state and subsequently relaxes to its ground state with a lifetime of 151 ± 31 fs. This work demonstrates that femotosecond EUV photoemission is a versatile surface-sensit...
Sistemas paralelos de promoção e distribuição

Investimento e a transformacao do dinheiro adquirido pelaempresa por meio de financiamentos ou de vendas de bens,servicos e direitos. (I A). (1) Esta definicao inclui comoinvestimento o dinheiro gasto em campanhas publicita-rias, em pesquisa e desenvolvimento e na formacao depessoal. No sentido estrito, contudo, entende-se por in-vestimento a aquisicao de patrimonios, isto e, de patrimo-nios financeiros e, especialmente, de patrimonios imoveis,seja por meio da cessao de meios pecuniarios (investimen-to puro), ou por intermedio do aumento de passivos (com-binacao de investimento e financiamento).
Projected Impact of Climate Change on the Energy Budget of the Arctic Ocean by a Global Climate Model

The annual energy budget of the Arctic Ocean is characterized by a net heat loss at the air-sea interface that is balanced by oceanic heat transport into the Arctic. The energy loss at the air-sea interface is due to the combined effects of radiative, sensible, and latent heat fluxes. The inflow of heat by the ocean can be divided into two components: the transport of water masses of different temperatures between the Arctic and the Atlantic and Pacific Oceans and the export of sea ice, primarily through Fram Strait. Two 150-year simulations (1950-2099) of a global climate model are used to examine how this balance might change if atmospheric greenhouse gases (GHGs) increase. One is a control simulation for the present climate with constant 1950 atmospheric composition, and the other is a transient experiment with observed GHGs from 1950 to 1990 and 0.5% annual compounded increases of CO2 after 1990. For the present climate the model agrees well with observations of radiative fluxes at the top of the atmosphere, atmospheric advective energy transport into the Arctic, and surface air temperature. It also simulates the seasonal cycle and summer increase of cloud cover and the seasonal cycle of sea-ice cover. In addition, the changes in high-latitude surface air temperature and sea-ice cover in the GHG experiment are consistent with observed changes during the last 40 and 20 years, respectively. Relative to the control, the last 50-year period of the GHG experiment indicates that even though the net annual incident solar radiation at the surface decreases by 4.6 W(per square meters) (because of greater cloud cover and increased cloud optical depth), the absorbed solar radiation increases by 2.8 W(per square meters) (because of less sea ice). Increased cloud cover and warmer air also cause increased downward thermal radiation at the surface so that the net radiation into the ocean increases by 5.0 Wm-2. The annual increase in radiation into the ocean, however, is compensated by larger increases in sensible and latent heat fluxes out of the ocean. Although the net energy loss from the ocean surface increases by 0.8 W (per square meters), this is less than the interannual variability, and the increase may not indicate a long-term trend. The seasonal cycle of heat fluxes is significantly enhanced. The downward surface heat flux increases in summer (maximum 2 of 19 W per square meters or 23% in June) while the upward heat flux increases in winter (maximum of 16 W per square meters or 28% in November). The increased downward flux in summer is due to a combination of increases in absorbed solar and thermal radiation and smaller losses of sensible and latent heat. The increased heat loss in winter is due to increased sensible and latent heat fluxes, which in turn are due to reduced sea-ice cover. On the other hand, the seasonal cycle of surface air temperature is damped, as there is a large increase in winter temperature but little change in summer.
Peripheral Insulin Insensitivity in the Hyperglycemic Athymic Nude Mouse: Similarity to Noninsulin-Dependent Diabetes Mellitus:

Previous studies in the homozygous athymic nude mouse (USC colony) have indicated a diabetic state characterized by spontaneous hyperglycemia, abnormal glucose tolerance, and normal or relatively decreased plasma insulin levels. Pancreatic islet cell population assessed by morphometric and immunohistochemical studies demonstrated normal insulin-secreting cells in the hyperglycemic nude mouse. To further elucidate the pathogenesis of the hyperglycemic state in the athymic nude mouse, we have studied the effects of insulin on the transport of glucose in skeletal muscle by measuring basal and insulin-stimulated uptake of a nonmetabolizable glucose analogue, 2-deoxy-D-glucose by using the perfused hindquarter preparation. Although basal 2-deoxy-D-glucose uptake by peripheral skeletal muscle was similar in the hyperglycemic and control mice, the insulin-stimulated uptake of 2-deoxy-D-glucose was significantly decreased in the athymic nude mouse at both 0.1 milliunits/ml and supraphysiologic concentrations of insulin (1 milliunit/ml) when compared with control mice (P less than 0.05 and P less than 0.001, respectively). This form of peripheral insulin insensitivity with normal pancreatic beta cell reserve, in addition to the lean body mass of the diabetic animal, mimics in part the peripheral insulin insensitivity seen in non-insulin-dependent diabetes mellitus.
Spin-selective charge recombination in complexes of CdS quantum dots and organic hole acceptors

This paper describes the mechanisms of charge recombination on both the nanosecond and microsecond time scales in a donor-acceptor system comprising thiol-modified bis(diarylamino)4,4'-biphenyl (TPD) molecules attached to a CdS quantum dot (QD) via the thiolate linker. Transient absorption measurements, in conjunction with EPR and magnetic field effect studies, demonstrate that recombination on the nanosecond time scale is mediated by radical pair intersystem crossing (RP-ISC), as evidenced by the observation of a spin correlated radical ion pair, the formation of the localized (3)*TPD state upon charge recombination, and the sensitivity of the yield of (3)*TPD to an applied magnetic field. These experiments show that the radical spins of the donor-acceptor system have weak magnetic exchange coupling (|2J| < 10 mT) and that the electron donated to the QD is trapped in a surface state rather than delocalized within the QD lattice. The microsecond-time scale recombination is probably gated by diffusion of the trapped electron among QD surface states. This study demonstrates that magneto-optical studies are useful for characterizing the charge-separated states of molecule-QD hybrid systems, despite the heterogeneity in the donor-acceptor geometry and the chemical environment of the radical spins that is inherent to these systems.
The Location of Carotenoid Pigments and Thickness of The Cell Wall In Light- and Dark-Grown Cells of Dacryopinax Spathularia

Light-grown cells of Dacryopinax spathularia contained almost eight times the concentration of carotenoid pigments as did dark-grown cells. That the highest concentration of pigments occurred in th...
Treatment of cyanide poisoning.

The object of this study was to evaluate the effectiveness of five regimens in treating cyanide poisoning. A series of anesthetized adult beagle dogs were instrumented to record hemodynamic and respiratory function and given 2.5 mg/kg sodium cyanide intravenously. The 10 control animals given only cyanide died at from 5 to 7 minutes. Therapy, as described below, was given to other groups at from 2 to 3 minutes following the cyanide administration. Artificial respiration did not alter the lethal effects of cyanide nor prolong survival time in any of the 10 animals. Amyl nitrite given by inhalation or by the intravenous route allowed survival of all 15 animals. Sodium nitrite (20 mg/kg), dimethylaminophenol (DMAP) (5 mg/kg), and hydroxylamine hydrochloride (5 mg/kg) given intravenously with no artificial ventilation also allowed for 100% survival (15 animals). Amyl nitrite, sodium nitrite, and sodium thiosulfate were ineffective when given intramuscularly (I.M.) (0 of 12 dogs); however, I.M. DMAP (5 mg/kg) and I.M. hydroxylamine hydrochloride (50 mg/kg) increased heart rate and blood pressure and restored spontaneous breathing. All 15 animals treated with I.M. doses of either of these drugs survived the lethal dose of cyanide. Results of these studies indicate that intravenous sodium nitrite, DMAP, and hydroxylamine hydrochloride, and amyl nitrite by inhalation, are all effective in reversing the lethal effects of cyanide poisoning. Only DMAP and hydroxylamine hydrochloride are effective when given by the intramuscular route. These results provide data to support an approach to therapy that is more practical and applicable where expert medical care may not be available following cyanide exposure.
Visual Cues in Computer-Mediated Communication: Supplementing Text with Emoticons

AbstractIncreased usage of e-mail brings a variety of communication patterns. One way of clarifying verbal meaning within e-mail messages is through the use of visual symbols, or emoticons. Emoticons are visual cues formed from ordinary typographical symbols that when read sideways represent feelings or emotions. This paper reports results of a study about emoticons that appear in list e-mail traffic in higher education.
Abstract 254: Lung cancer cells growing under prolonged period of serum starvation display increased stemness

Purpose: Resistance to anticancer drugs is a common cause of failure in chemotherapy. We recently found that adherent cells growing under prolonged periods (7-12 days) of serum starvation become highly resistant to conventional anticancer drugs such as Paclitaxel, Hydroxyurea and Colchicine but retain sensitivity to therapeutic levels of the cardiac glycoside Digitoxin. Objectives: The main goal of this study is to characterize the biological properties of cells growing under prolonged periods of serum starvation (PPSS), and to elucidate the underlying mechanism of chemoresistance to Paclitaxel and sensitivity to Digitoxin with particular emphasis on Sox2 and the PI3K/AKT signaling pathway. Experimental setup: Distribution of cell cycle was characterized by flow cytometry. Cell viability was assessed using the MTT assay. Western blotting was employed to evaluate the expression of several key protein markers of cancer stemness (Sox2, Wnt), multidrug resistance (MDR1, ABCG2), epithelial mesenchymal transition (Vimentin), and cell survival (Bcl-2, XIAP, PI3K/AKT). Results: Cells grown under PPSS showed a higher proportion of cells in G1/S and G2 compared to cells growing under routine culture conditions (RCCs). Western blot analysis showed that these cells expressed higher levels of Sox2, MDR1, ABCG2, Bcl-2 compared to cells growing under RCCs. Pretreatment of cells for 3 h with Verapamil or Sorafenib (MDR1 and ABCG2 inhibitors, respectively) followed by co-incubation with Paclitaxel for 72 h did not overcome Paclitaxel resistance. Obatoclax (a Bcl-2 inhibitor), Wortmannin or LY294002 (PI3K inhbitors) also failed to overcome Paclitaxel resistance. It was interesting to observe that cells growing under PPSS were highly resistant to Obatoclax, Wortmannin and LY294002 compared to cells growing under RCCs. However, these cells were highly sensitive to treatment with Digitoxin. Conclusions: It is likely that multiple mechanisms (increased stemness, overexpression of multidrug resistance protein and prosurvival proteins) contributes to the resistance of cells under PPSS to Paclitaxel, Obatoclax and PI3K inhibitors. Preliminary results indicates that Digitoxin exerts its antiproliferative effect in part by downregulating Sox2. However, the lack of effect of Wortmannin and LY294002 on Paclitaxel resistance suggests that this effect is not via the PI3K/AKT pathway. Adherent cells growing under PPSS provide a simple yet powerful system to screen for drugs targeting cancer stemness. Citation Format: Rajkumar Venkatadri, Juan Sebastian Yakisich, Neelam Azad, Anand Krishnan V. Iyer. Lung cancer cells growing under prolonged period of serum starvation display increased stemness. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 254.
Effect of oral sodium bicarbonate on fibroblast growth factor-23 in patients with chronic kidney disease: A pilot study

The regulation of fibroblast growth factor-23 (FGF23) secretion in patients with chronic kidney disease (CKD) is incompletely understood. An in vitro study showed that metabolic acidosis increased FGF23 in mouse bone. The objective of this study is to evaluate the effect of oral sodium bicarbonate on circulating FGF23 levels in patients with CKD. This was a single-blind pilot study. Twenty adults with estimated glomerular filtration rate between 15–45 mL/min/1.73 m2 and serum bicarbonate between 20–24 mEq/L were treated with placebo for 2 weeks, followed by increasing doses of oral sodium bicarbonate (0.3, 0.6 and 1.0 mEq/kg/day) in 2 week intervals for a total of 6 weeks. C-terminal FGF23 levels were measured at the initial visit, after 2 weeks of placebo and after 6 weeks of bicarbonate therapy. Wilcoxon matched-pairs signed-rank test was used to compare FGF23 before and after sodium bicarbonate. After 6 weeks of oral sodium bicarbonate, the median FGF23 increased significantly from 150.9 RU/mL (IQR 107.7–267.43) to 191.4 RU/mL (IQR 132.6–316.9) (p = 0.048) and this persisted after excluding participants who received activated vitamin D. FGF23 increased after short-term oral sodium bicarbonate therapy in patients with CKD and mild metabolic acidosis. It is unclear whether this was due to the alkalinizing effect of sodium bicarbonate or other factors. The study was registered at ClinicalTrials.gov ( NCT00888290 ) on April 23, 2009.
Host-Seeking Phenology of Ixodes pacificus (Acari: Ixodidae) Nymphs in Northwestern California in Relation to Calendar Week, Woodland Type, and Weather Conditions

Local knowledge of when humans are at elevated risk for exposure to tick vectors of human disease agents is required both for the effective use of personal protection measures to avoid tick bites and for implementation of control measures to suppress host-seeking ticks. Here, we used previously published data on the seasonal density of host-seeking Ixodes pacificus Cooley and Kohls nymphs, the primary vectors of Lyme disease spirochetes in the far western USA, collected across a broad habitat and climate gradient in northwestern California to identify predictors of periods of time within the year when questing nymphal density is elevated. Models based on calendar week alone performed similarly to models based on calendar week and woodland type, or meteorological variables. The most suitable model for a given application will depend on user objectives, timescale of interest, and the geographic extent of predictions. Our models sought not only to identify when seasonal host-seeking activity commences, but also when it diminishes to low levels. Overall, we report a roughly 5–7 month period in Mendocino County during which host-seeking nymphal densities exceed a low threshold value.
Optimization and Validation of High-Resolution Mass Spectrometry Data Analysis Parameters

High-resolution mass spectrometry (HRMS) has gained recognition as a valuable tool for comprehensive drug screening in a variety of biological matrices. HRMS instruments collect untargeted, accurate mass data, which permit identification of known and unknown compounds in a single analytical run. One of the most challenging aspects of implementing an HRMS drug screen is establishing appropriate data analysis parameters for identifying compounds. Unlike other types of mass spectrometry data, guidelines for HRMS data analysis and acceptability criteria have not been established. Although many laboratories have published on the utility of HRMS for drug screening, few have included details on how they determined allowable errors and set positivity criteria. Previously, we developed and validated a comprehensive 169-compound drug screen on a high-resolution quadrupole time of flight mass spectrometer. Here we report the detailed procedure that we used to determine appropriate positivity criteria for our screening procedure. Our approach was empirical; we collected data and analyzed it with commonly available software. We found that a combined scoring approach using a threshold of 70, with 70% weight given to library match and 10% weight given to each of mass error, retention time error and isotope pattern difference provided optimum drug identification efficiency of 99.2%. Our results demonstrate the importance of library matching in accurately identifying compounds, and underscore the utility of robust product ion spectra that contain information on the lineage, mass and relative abundance of fragments. The method we describe is easily adaptable to include alternative parameters that may be available in software associated with a variety of HRMS platforms. With careful selection of error limits and positivity criteria, HRMS instruments are capable of producing high-quality, high-confidence results that may reduce the need for confirmatory testing.
Nivolumab in the Treatment of Hodgkin Lymphoma

Despite an extensive immune infiltrate that is recruited to the tumor by malignant Reed-Sternberg cells in Hodgkin lymphoma, the antitumor immune response is ineffective and unable to eradicate the malignant cells. The ineffective immune response is in part due to PD-1 signaling that renders intratumoral immune cells anergic. Reed-Sternberg cells have been shown to upregulate expression of the PD-1 ligands, PD-L1 and PD-L2, due to either genetic alterations at chromosome 9p24.1 or Epstein-Barr virus infection, and these ligands suppress the function of PD-1+ intratumoral T cells. Blockade of PD-1 signaling has proven to be a highly successful therapeutic approach, and the use of the anti-PD-1 mAb nivolumab recently received accelerated approval by the FDA for patients with classical Hodgkin lymphoma that has relapsed or progressed after autologous stem cell transplant and posttransplantation brentuximab vedotin. Initial clinical trials using nivolumab in this patient population resulted in high response rates that were durable. Adverse events associated with nivolumab included immune-mediated adverse reactions and infusion reactions, but these were well tolerated, allowing for continued nivolumab administration. Clinical trials are now in progress to test the use of nivolumab in combination with standard chemotherapy or with novel agents with a goal of improving the outcome of patients with Hodgkin lymphoma. Clin Cancer Res; 23(7); 1623-6. ©2016 AACR.
Lightweight hardware architectures for fault diagnosis schemes of efficiently-maskable cryptographic substitution boxes

As we are close to the advent of quantum computing capability, the potential use of resistant algorithms, i.e., code-based, lattice-based, hash-based, multivariate-quadratic-equations, and symmetric-key cryptographic algorithms, depends on many sensitive factors including resistance against natural and malicious faults. Active side-channel analysis attacks (SCAs) such as fault analysis attacks and passive ones, e.g., power analysis attacks, have been effective to compromise algorithmically-secure crypto-solutions including the emerging lightweight block ciphers. Nevertheless, one can provide fault diagnosis approaches to ameliorate the former and use efficient masking mechanisms for the latter. There has been recent work to account for power analysis attacks resistivity before developing new lightweight block ciphers; nonetheless, in this paper, we present error detection approaches for such ciphers and present insights towards future directions for potential, combined power and fault analysis attacks resistivity as a major deciding factor in developing SCA-resistant lightweight block ciphers. Through error simulations, the theoretical back-bone of the presented error detection scheme for a lightweight block cipher case study is benchmarked. The proposed design factor can be tailored based on the required security, fault resistivity, and overhead tolerance of both classical and post-quantum cryptography.
Fundamental Challenges Toward Making the IoT a Reachable Reality: A Model-Centric Investigation

Constantly advancing integration capability is paving the way for the construction of the extremely large scale continuum of the Internet where entities or things from vastly varied domains are uniquely addressable and interacting seamlessly to form a giant networked system of systems known as the Internet-of-Things (IoT). In contrast to this visionary networked system paradigm, prior research efforts on the IoT are still very fragmented and confined to disjoint explorations of different applications, architecture, security, services, protocol, and economical domains, thus preventing design exploration and optimization from a unified and global perspective. In this context, this survey article first proposes a mathematical modeling framework that is rich in expressivity to capture IoT characteristics from a global perspective. It also sets forward a set of fundamental challenges in sensing, decentralized computation, robustness, energy efficiency, and hardware security based on the proposed modeling framework. Possible solutions are discussed to shed light on future development of the IoT system paradigm.
Fiduciary Duty, Contract, and Waiver in Partnerships and Limited Liability Companies

Among the controversies swirling around the promulgations of new uniform statutes governing partnerships and LLCs is the question whether and to what extend fiduciary duties should be made mandatory or waivable. Although courts and commentators have not traditionally focused on the costs of fiduciary duties, the costs are significant in that such duties may preclude agents from engaging in other legitimate ventures. Indeed, fiduciary duty may be used by those to whom it is owed to prevent competition or extort side benefits form participants. Mandatory duties effectively require participants who may identify multiple business opportunities to overinvest their human capital by forcing them to choose one and only one venture in a given market, and thus my preclude economic ventures from being undertaken by precisely those potential participants who have the most to offer. The thesis here is that the approach taken in RUPA and ULLCA, which allows for the broad waiver of fiduciary duties, but only to the extent specific in the partnership agreement or operating agreement, is eminently sound. The approach taken in the new uniform acts encourages disclosure and negotiation by effectively placing the burden on the agent who anticipates engaging in other ventures to negotiate for specific waivers of fiduciary duties. Because the partnership and LLC forms are likely to be used for a wide variety of ventures for which competition may be more or less worrisome, it is vitally important that a flexible approach to fiduciary duty be adopted. The new uniform acts do precisely that without sacrificing the protection of advance disclosure and negotiation to those who may have less bargaining power in connection with the formation of business ventures.
Control of Clostridium difficile infection by defined microbial communities

Each year in the United States, billions of dollars are spent combating almost half a million Clostridium difficile infections (CDIs) and trying to reduce the ∼29,000 patient deaths in which C. difficile has an attributed role. In Europe, disease prevalence varies by country and level of surveillance, though yearly costs are estimated at €3 billion. One factor contributing to the significant health care burden of C. difficile is the relatively high frequency of recurrent CDIs. Recurrent CDI, i.e., a second episode of symptomatic CDI occurring within 8 weeks of successful initial CDI treatment, occurs in ∼25% of patients, with 35 to 65% of these patients experiencing multiple episodes of recurrent disease. Using microbial communities to treat recurrent CDI, either as whole fecal transplants or as defined consortia of bacterial isolates, has shown great success (in the case of fecal transplants) or potential promise (in the case of defined consortia of isolates). This review will briefly summarize the epidemiology and physiology of C. difficile infection, describe our current understanding of how fecal microbiota transplants treat recurrent CDI, and outline potential ways that knowledge can be used to rationally design and test alternative microbe-based therapeutics.
In vivo tracking of the tropism of mesenchymal stem cells to malignant gliomas using reporter gene-based MR imaging

Mesenchymal stem cells (MSCs) have emerged as a promising cellular vehicle for gene therapy of malignant gliomas due to their property of tumor tropism. However, MSCs may show bidirectional and divergent effects on tumor growth. Therefore, a robust surveillance system with a capacity for noninvasive monitoring of the homing, distribution and fate of stem cells in vivo is highly desired for developing stem cell-based gene therapies for tumors. In this study, we used ferritin gene-based magnetic resonance imaging (MRI) to track the tumor tropism of MSCs in a rat orthotopic xenograft model of malignant glioma. MSCs were transduced with lentiviral vectors expressing ferritin heavy chain (FTH) and enhanced green fluorescent protein (eGFP). Intra-arterial, intravenous and intertumoral injections of these FTH transgenic MSCs (FTH-MSCs) were performed in rats bearing intracranial orthotopic C6 gliomas. The FTH-MSCs were detected as hypointense signals on T2- and T2*-weighted images on a 3.0 T clinical MRI. After intra-arterial injection, 17% of FTH-MSCs migrated toward the tumor and gradually diffused throughout the orthotopic glioma. This dynamic process could be tracked in vivo by MRI up to 10 days of follow-up, as confirmed by histology. Moreover, the tumor tropism of MSCs showed no appreciable impact on the progression of the tumor. These results suggest that FTH reporter gene-based MRI can be used to reliably track the tropism and fate of MSCs after their systemic transplantation in orthotopic gliomas. This real-time in vivo tracking system will facilitate the future development of stem cell-based therapies for malignant gliomas.
Election observers and electoral fraud

Election observation - the deployment of trained personnel to monitor the compliance of political parties with electoral laws - has become a prominent feature of polls in countries across the world. Observers are usually deployed by multi-national organizations (international observers) or by local civil society groups (domestic observers). International election observers were present in 86 percent of the national elections organized in 95 newly democratic, or competitive authoritarian regimes, between 1989 and 2002.1 Today, domestic election observation groups are active in at least 60 countries.2 The main purpose of election observers is to detect and deter electoral fraud and violence. Do observers achieve this goal? At the national level, establishing the causal effect of observers on fraud is difficult because governments usually self-select into the treatment (i.e. allow themselves to be monitored). In this case, an association between observers and low levels of fraud does not prove observers reduce fraud, because the countries that choose to have observers may have cleaner elections to begin with compared to countries that are not open to observers. Similarly, within countries, if civil society groups deploy observers to historically troublesome regions, a comparison of outcomes at monitored and unmonitored polling stations may underestimate observers’ impacts.
Pharmacotherapy of Autism: A Review and Clinical Approach

Although there is a proliferating literature on the pharmacotherapy of autism, the results of these studies are often conflicting. A definitive medical intervention for the core symptoms of autism continues to elude us. In the absence of a definitive research-based pathway for the pharmacotherapeutic treatment of autism, our approach is necessarily clinically based and research informed. Common medication side effects also may confound the clinical picture. A major factor in the application of our approach is an awareness of conditions comorbid with autism in an individual patient. These comorbid conditions then serve as a guide in choice of specific drug therapies. Use of medication must be guided by an awareness of habilitative, behavioral, social, administrative, and ethical issues.