cssi/SciSciGPT-SciSciNet huggingface dataset:
The effects of tubulin-binding agents on stretch-induced ventricular arrhythmias.

Abstract Stretch-activated ion channels have been identified as transducers of mechanoelectric coupling in the heart, where they may play a role in arrhythmogenesis. The role of the cytoskeleton in ion channel control has been a topic of recent study and the transmission of mechanical stresses to stretch-activated channels by cytoskeletal attachment has been hypothesized. We studied the arrhythmogenic effects of stretch in 16 Langendorff-perfused rabbit hearts in which we pharmacologically manipulated the microtubular network of the cardiac myocytes. Group 1 (n=5) was treated with colchicine, which depolymerizes microtubules, and Group 2 (n=6) was treated with taxol, which polymerizes microtubules. Stretch-induced arrhythmias were produced by transiently increasing the volume of a fluid-filled left ventricular balloon with a volume pump driven by a computer-controlled stepper motor. Electrical events were recorded by a contact electrode which provided high-fidelity recordings of monophasic action potentials and stretch-induced depolarizations. The probability of eliciting a stretch-induced arrhythmia increased (0.22±0.11 to 0.62±0.19, p=0.001) in hearts treated with taxol (5 μM), whereas hearts treated with colchicine (100 μM) showed no statistically significant change. We conclude that proliferation of microtubules increased the arrhythmogenic effect of transient left ventricle diastolic stretch. This result indicates a possible mode of arrhythmogenesis in chemotherapeutic patients and patients exhibiting uncompensated ventricular hypertrophy. The data would indicate that the cytoskeleton represents a possible target for antiarrhythmic therapies.
Information collection and spread by networks of patrolling ants

To study how a social group, such as an ant colony, monitors events occurring throughout its territory, we present a model of a network of patrolling ants engaged in information collection and dissemination. In this network, individuals follow independent paths through a region and can exchange signals with each other upon encounter. The paths of the ants are described by correlated random walks. Through simulations and analytic approximations, including a new approach to the spatial logistic equation, we study the efficiency with which such a network discovers a constantly changing stream of "events" scattered throughout the region and the speed with which information spreads to all ants in the network. We demonstrate that efficiency of event discovery and the speed of information spread are enhanced by increased network size and straighter individual ant paths, and that these two effects interact. The results lead to predictions regarding the relations among species-specific movement patterns, colony si...
Understanding bark beetle/host interactions: A means for improving decision strategies1

Improved decision-making capabilities are an important goal in pest management. The need to more fully understand bark beetle/host tree interactions and how this knowledge can be linked to better prediction of Dendroctonus frontalis infestation growth is discussed. The properties of pines which confer resistance to D. frontalis, a primary resin system and hypersensitive tissue response, must be correlated with bark beetle attack success, production and mortality rates. To use information in a management oriented predictive model, resistance properties must also be correlated to easily measurable tree and/or stand characters, which can be used to reparameterize model rates, resulting in improved predictions over a variety of site and stand conditions, thus leading to better management decisions. Zusammenfassung Kenntnis der Wechselwirkungen zwischen Borkenkafern und ihren Wirtsbaumen zur Entwicklung verbesserter Entscheidungsstrategien Verbesserung der Entscheidungsgrundlagen sind ein wichtiges Ziel des Pest Management. Ein besseres Verstandnis der Wechselwirkungen zwischen Borkenkafern und ihren Wirtsbaumen kann genauere Vorhersagen der Befallsentwicklung ermoglichen; dies wird am Beispiel von Dendroctonus frontalis diskutiert. Die Eigenschaften des Harzkanalsystems und die Wundharzbildung, welche die Resistenz der Wirtskiefern begrunden, konnen mit Befallserfolg, Bruterfolg und Mortalitat der Borkenkafer in Beziehung gesetzt werden. Fur ein nutzliches, praxisorientiertes Vorhersagemodell mussen die Resistenzeigenschaften daruber hinaus mit leicht mesbaren Baum-und Bestandsmerkmalen korreliert werden, mit denen die bestehenden Modellansatze fur eine Vielzahl von Standorts- und Bestandeseigenschaften verbesserte Vorhersagen und damit Entscheidungsgrundlagen fur die Praxis liefern konnen.
Polymerase chain reaction detection of the t(11;14) translocation involving the bcl-1 major translocation cluster in mantle cell lymphoma.

The utility of polymerase-mediated assays in the detection of the t(11;14) involving the bcl-1 major translocation cluster (bcl-1 MTC) was evaluated by analyzing DNA from 33 patients with mantle cell lymphoma, 14 patients with other non-Hodgkin s lymphomas, and five patients with reactive lymphoid hyperplasia. The polymerase chain reaction (PCR) assay was performed using a consensus immunoglobin heavy-chain joining region primer in conjunction with a chromosome 11 specific oligonucleotide primer flanking the translocation site. The sensitivity and specificity of the assay were confirmed by correlation of the (PCR) assay data with restriction analysis. Rearrangements at the bcl-1 MTC were detected in 13 (39%) of 33 cases of mantle cell lymphoma by PCR and in 13 (48%) of 27 cases by restriction analysis. Amplicons were detectable by PCR in 85% (11 of 13) of the cases shown to be bcl-1 rearranged by restriction analysis. Failure to detect amplification products in DNA samples from non-mantle cell lymphomas and reactive follicular hyperplasia further confirmed the specificity of the assay. Sequential hybridization of the PCR products with oligonucleotide probes 3′ to the bcl-1 MTC primer revealed that the breakpoints in the bcl-1 MTC were clustered around an Sst I restriction site over a range of 170 base pairs. The study demonstrates that PCR-mediated assay for the detection of the t(l1;14) at the bcl-1 MTC is specific and sensitive and can be used as an adjunct to restriction analysis in routine diagnostics.
Longitudinal Analysis of Monocyte/Macrophage Infection in Simian Immunodeficiency Virus-Infected, CD8+ T-Cell-Depleted Macaques that Develop Lentiviral Encephalitis

The histopathological hallmark of lentiviral-associated encephalitis is an abundance of infected and activated macrophages. Why a subset of infected hosts develops lentiviral encephalitis and others do not is unknown. Using a CD8 + T-cell depletion model of simian immunodeficiency virus (SIV)-infected rhesus macaques, we examined the relationship between peripheral SIV infection of monocytes/macrophages and the development of encephalitis. At the same time that cerebral spinal fluid viral load increased in macaques that developed encephalitis, we observed that monocyte-derived macrophages from these macaques produced more virus than those from macaques that did not develop encephalitis. However, during the course of infection, the number of blood monocyte-associated SIV DNA copies did not distinguish macaques that developed simian immunodeficiency virus encephalitis from macaques that did not develop encephalitis. Paradoxically, in this model, macaques that developed encephalitis had fewer SIV-infected macrophages in lungs and thymus at postmortem than macaques that did not develop encephalitis. These findings suggest that inherent differences in host monocyte viral production are related to development of encephalitis.
Development of Coagulation Factor Probes for the Identification of Procoagulant Circulating Tumor Cells

Metastatic cancer is associated with a hypercoagulable state, and pathological venous thromboembolic disease is a significant source of morbidity and the second leading cause of death in patients with cancer. Here we aimed to develop a novel labeling strategy to detect and quantify procoagulant circulating tumor cells (CTCs) from patients with metastatic cancer. We hypothesize that the enumeration of procoagulant CTCs may be prognostic for the development of venous thrombosis in patients with cancer. Our approach is based on the observation that cancer cells are capable of initiating and facilitating cell-mediated coagulation in vitro, whereby activated coagulation factor complexes assemble upon cancer cell membrane surfaces. Binding of fluorescently labeled, active site-inhibited coagulation factors VIIa, Xa, and IIa to the metastatic breast cancer cell line, MDA-MB-231, non-metastatic colorectal cell line, SW480, or metastatic colorectal cell line, SW620, was characterized in a purified system, in anticoagulated blood and plasma, and in plasma under conditions of coagulation. We conclude that a CTC labeling strategy that utilizes coagulation factor-based fluorescent probes may provide a functional assessment of the procoagulant potential of CTCs, and that this strategy is amenable to current CTC detection platforms.
Empirical analysis of supplier selection and involvement, customer satisfaction, and firm performance

Supply chain management as a system of operation continues to evolve. This study employs confirmatory factor analysis and path analysis to examine empirically the relationships among supplier selection criteria (quality, delivery reliability, product performance and unit price), supplier involvement on design teams and in continuous improvement programs, four dimensions of customer satisfaction (competitive pricing, product quality, product variety, and delivery service), and overall firm performance.
Clinical appraisal of deficiencies of the basal analog insulin

The attributes of a perfect basal insulin should include: the ability to provide basal glucose levels at target range; once-daily injection; suitable to be injected at any time of day and still cover the intervening period (up to 48 h); cause no hypoglycemia, weight gain or other serious side effects such as cancer; be consistent in its action; and be inexpensive. Following protamine zinc insulin, neutral protamine Hagedorn was introduced approximately 60 years ago. protamine zinc insulin’s highly variable action was reduced, but not eliminated, by neutral protamine Hagedorn. A total of 10 years ago, insulin glargine was introduced to the American market. It quickly gained market share due the relative lack of a peak action and therefore its lower risk of hypoglycemia, and also due to its long duration of action of 24 h or longer, at least in some patients. Then, 5 years ago, insulin detemir was introduced. Although it still may be questioned as to whether its duration of action is 24 h, it appears to hav...
The capacity of the adrenalectomized rat to secrete hydrogen and ammonium ions.

IT IS generally recognized that reductions in sodium and chloride concentration and increase in potassium concentration constitute major abnormalities in plasma composition in adrenal insufficiency (Loeb 1932; Harrop et al., 1933, 1936). Somewhat less generally appreciated but no less significant are reductions in plasma pH and bicarbonate concentration, indicative of a metabolic type of acidosis (Swingle and Wenner, 1927; Hastings and Compere, 1931). These findings imply that deficiencies exist in renal mechanisms for regulation of acid base balance, as well as in those concerned with regulation of total electrolyte concentration (Jimenez-Diaz, 1936). It seemed profitable therefore to investigate the capacity of the adrenalectomized animal to excrete titratable acid and ammonia under normal conditions and under conditions of acid stress. It has been observed that these renal responses are deficient in either circumstance, facts which may account for chronic acidosis and poor tolerance to acid stress in t...
Immunopathology of Murine Infection with Schistosoma mansoni: Relationship of Genetic Background to Hepatosplenic Disease and Modulation

The influence of genetic factors on the manifestations of disease associated with infection with Schistosoma mansoni (portal hypertension, liver granulomas, hepatosplenomegaly) and their modulation were studied in inbred strains of mice. Three groups were identified according to the degree of portal hypertension: high (portal venous pressure, 19.1 cm H2O: DBA/1J), intermediate (8.9-13.4 cm H2O; BALB/cJ, DBA/2J, CBA/CaJ, C3H/HeJ, and BUB/BnJ), and low responders (6.1 cm H2O; C57BL/6J). Granuloma size, organomegaly, and portal venous pressure were strain dependent and not H-2 dependent and were determined by more than one gene. Studies of schistosomiasis in the F1 generation of high and low responders indicated that more than one gene is involved. Modulation of portal venous pressure between eight and 20 weeks of infection occurred in C57BL/6J but not in BALB/cJ mice and was transferable with immune lymphoid cells. These data indicate that disease associated with infection with S. mansoni and its modulation in mice are influenced by the genetic (non-H-2) background of the host and dependent in part on cell-mediated immunity.
Disparate effects of serum on basal and evoked NFAT activity in primary astrocyte cultures

Abstract In astrocytes, the Ca 2+ -dependent protein phosphatase calcineurin (CN) strongly regulates neuro-immune/inflammatory cascades through activation of the transcription factor, nuclear factor of activated T cells (NFAT). While primary cell cultures provide a useful model system for investigating astrocytic CN/NFAT signaling, variable results may arise both within and across labs because of differences in culture conditions. Here, we determined the extent to which serum and cell confluency affect basal and evoked astrocytic NFAT activity in primary cortical astrocyte cultures. Cells were grown to either ∼50% or >90% confluency, pre-loaded with an NFAT-luciferase reporter construct, and maintained for 16 h in medium with or without 10% fetal bovine serum (FBS). NFAT-dependent luciferase expression was then measured 5 h after treatment with vehicle alone to assess basal NFAT activity, or with Ca 2+ mobilizers and IL-1β to assess evoked activity. The results revealed significantly higher levels of basal NFAT activity in FBS-containing medium, regardless of cell confluency. Conversely, evoked NFAT activation was significantly lower in serum-containing medium, with an even greater inhibition observed in confluent cultures. Application of 10% FBS to serum-free astrocyte cultures quickly evoked a roughly seven-fold increase in NFAT activity that was significantly reduced by co-delivery of neutralizing agents for IL-1β, TNFα, and/or IFNγ, suggesting that serum occludes evoked NFAT activation through a cytokine-based mechanism. Together, the results demonstrate that the presence of serum and cell confluency have a major impact on CN/NFAT signaling in primary astrocyte cultures and therefore must be taken into consideration when using this model system.
Impact of environmental and genetic factors on expression of maize gene classes: Relevance to grain composition

Abstract Regulatory proteins, such as transcription factors, have markedly influenced plant phenotype during crop domestication, and breeding and modifying their expression through modern biotechnology may prove valuable in the development of improved agricultural traits. Crops improved through biotechnology-derived traits are subject to comparisons of chemical and nutrient composition with that of conventional crops prior to commercialisation. These comparisons are typically framed in the context of natural variation of analyte components. This study reports on an evaluation of natural variation in maize ( Zea mays L.) gene expression based on a survey of 2200 genes in order to better understand heterogeneity in levels of transcription factor gene expression under a range of genomic and environmental conditions. This evaluation was conducted on leaf tissue collected from hybrids of 48 genetically diverse inbred lines each crossed with one of two tester inbred lines and grown at three different field sites in Iowa, USA. The data show that expression of transcription factor genes in the overall population was highly variable across this range of genomic and environmental factors, though no more so than expression of other gene functional classes, despite the profound influence transcription factors have exerted on plant phenotype during crop domestication and breeding. By comparison, levels of grain components (oil, protein, total amino acid and fatty acid levels) were generally consistent with values recorded in the literature. Thus, the results highlight that heterogeneity of gene expression in response to diverse genomic and environmental factors is not unique to genes for transcription factors and that such variation in gene expression does not correlate with differences in grain composition.
A priori L r error estimates for Galerkin approximations to porous medium and fast diffusion equations

Galerkin approximations to solutions of a Cauchy-Dirichlet problem governed by the generalized porous medium equation formulamath on bounded convex domains are considered. The range of the parameter ρ includes the fast diffusion case 1 < ρ < 2. Using an Euler finite difference approximation in time, the semi-discrete solution is shown to converge to the exact solution in L∞(0,T; L ρ (Ω)) norm with an error controlled by O(Δt1/4) for 1 < ρ < 2 and O(Δt1/2ρ) for 2 < ρ < ∞. For the fully discrete problem, a global convergence rate of O(Δt1/4) in L 2 (0,T;L ρ (Ω)) norm is shown for the range 2N/N + 1 < ρ < 2. For 2 < ρ < ∞, a rate of O(Δt1/2ρ) is shown in L ρ (0, T; L ρ (Ω)) norm.
Partial Reversal of the Thymineless State in vivo

METHOTREXATE (amethopterin) blocks the activity of the enzyme dihydrofolic reductase and thereby interferes with a number of metabolic reactions involving the transfer of carbon atoms, including the production of thymidylate, de novo purine biosynthesis, and inter-conversions of several amino-acids. Partial reversal of toxicity induced by antifolics such as methotrexate by the addition of purine and thymine sources has been reported for amphibian1 and avian2,3 embryos, but similar experiments with rat embryos were unsuccessful4. The deficiencies induced by methotrexate can be completely reversed in mammalian tissue culture systems, however, by the inclusion in the nutrient fluid of a purine source, certain amino-acids, and a thymine source, usually thymidine5–8. If thymidine is omitted from the medium, a deficiency develops, sometimes called the thymineless state, in which the cells begin to die after approximately one generation time. It seemed desirable to attempt to reproduce this condition in vivo, in order better to define the mode of action of methotrexate, as well as to provide information which might be used to control cell growth in vivo.
Calibration and adjustment of the EGRET coincidence/time-of-flight system

Abstract The coincidence/time-of-flight system of the energetic gamma ray experiment telescope (EGRET) on NASA's Gamma Ray Observatory (GRO) consists of two lay
Geographic variation in song composition of the indigo bunting, Passerina cyanea

Abstract Samples of indigo bunting song from Michigan, Kentucky, and New York have yielded 118 different types of figures. A high degree of geographical figure dispersion is indicated, as all sample populations are comprised mainly of figures also recorded at the George Reserve. New figures (those not previously seen at the George Reserve, Michigan) include eighteen from Kentucky and one from Rouge Park, Michigan, but were lacking in the Ithaca, New York sample. This implies a limit to a number of figure-types occurring within any given population of indigo buntings, and the species as a whole is probably similarly limited. Average song length (in terms of the total number of figures and of the number of figure-types) is slightly greater in denser populations, while figure repetition is lower. It is suggested that new figures arise from alteration of existing figures in the learning process. The number of existing figure-types suggests that there is available to the species a finite number of different song patterns such that each bird could conceivably have a unique song. However, in nature this limit is not realized; the same song pattern is often sung by more than one bird.
Gender differences in neural mechanisms underlying moral sensitivity

Researchers have proposed that females and males differ in the structure of their moral attitudes, such that females tend to adopt care-based moral evaluations and males tend to adopt justice-based moral evaluations. The existence of these gender differences remains a controversial issue, as behavioral studies have reported mixed findings. The current study investigated the neural correlates of moral sensitivity in females and males, to test the hypothesis that females would show increased activity in brain regions associated with care-based processing (posterior and anterior cingulate, anterior insula) relative to males when evaluating moral stimuli, and males would show increased activity in regions associated with justice-based processing (superior temporal sulcus) relative to females. Twenty-eight participants (14 females) were scanned using fMRI while viewing unpleasant pictures, half of which depicted moral violations, and rated each picture on the degree of moral violation that they judged to be present. As predicted, females showed a stronger modulatory relationship between posterior cingulate and insula activity during picture viewing and subsequent moral ratings relative to males. Males showed a stronger modulatory relationship between inferior parietal activity and moral ratings relative to females. These results are suggestive of gender differences in strategies utilized in moral appraisals.
Microwave imaging radar system for detecting buried objects

A time-domain microwave imaging radar system for nondestructive evaluation purposes has recently been developed at the University of Illinois. This system will be used for rapid nondestructive evaluation and quality control of civil structures. This paper describes both the radar system development and the inverse scattering algorithm used for imaging shallow buried objects in a concrete slab.
Vastus Medialis Oblique/Vastus Lateralis Muscle Activity Ratios for Selected Exercises in Persons With and Without Patellofemoral Pain Syndrome

Background and Purpose. The purpose of this study was to determine which of selected exercises with and without the feet free to move would enhance vastus medialis oblique muscle (VMO) activity over that of the vastus lateralis muscle (W) and whether the use of taping would increase VMO activity. Subjects. Twenty-one subjects without patellofemoral pain (PFP) syndrome and 10 subjects with PFP syndrome, aged 19 to 43 years @=26, SD= 71, participated. Metbods. Subjects were studied for the normalized, integrated electromyographic (IEMG) activity of their MO, W, and adductor magnus muscle (subjects without PFP syndrome) and the VMOm ratio using wire electrodes. Results. One exercise demonstrated greater activation of the VMO over the W when compared with similar exercises in subjects without PFP syndrome. The mean VMOhT activity ratio for terminal knee extension was 1.2 (SD= 0.5) with the hip medially rotated and 1.0 (SD= 0.4) with the hip laterally rotated. Although subjects reported that patellar taping decreased pain 94% during the step-down exercise, the VMOm ratio was not changed. Conclusion and Discussforr The results suggest that neither exercises purported to selectively activate VMO activity nor patellar taping improve the VMOm ratio over similar exercises. lCerny K. Vastus medialis oblique/vastus lateralis muscle activity ratios for selected exercises in persons with and without patellofemoral pain syndrome. Phys Ther. 1995; 75672- 683.1
Desenvolvendo ação direta de desobediência civil e não violenta em favor dos famintos: “Comida e não Bombas” e o reaparecimento da Democracia Radical nos EUA

Este estudo examina os esforcos de um dos movimentos sociais (anarquista) que cresce mais rapidamente no mundo “FNB” (Food and not bombs) Comida e nao Bombas, para redefinir a politica urbana contra a fome nos EUA. A visao e para entender como a FNB contesta a politica e os processos relativos a contencao dos pobres, desprezando os esforcos para desenvolver um novo metodo de biopolitica. Como principal alvo de seu sucesso, este estudo examina os esforcos de um dos movimentos sociais (anarquista) que cresce mais rapidamente no mundo, “Comida e nao Bombas” (FNB) Food Not Bombs, para redefinir politicas urbanas contra a fome nos EUA. O objetivo e para entender como a FNB contesta o desprezo das politicas e procedimentos com relacao as classes pobres e seus esforcos, foca-se em como a FNB usa a acao direta de desobediencia civil nao-violenta para obter uma resposta da base alternativa ao direcionamento destrutivo do imperativo mercado capitalista neoliberal. O caso da FNB prove exemplos de potencial continuo para ajuda mutua e cooperativismo na cidade e da mesma forma contra o pano de fundo das crescentes injusticas sociais dentro de universo cada vez mais globalizado. Finalizando, o estudo demonstra que a FNB oferece exemplos de varios tipos de resistencia necessaria para assegurar o direito fundamental inerente a cidade, o qual e o direito a comida e sobrevivencia nas cidades.
Fragmentation of a highly purified monoclonal antibody attributed to residual CHO cell protease activity

Monoclonal antibody (mAb) fragmentation can be a widespread problem across the biotechnology industry and there is a current need to better understand the underlying principles. Here, we report an example of a high-purity human IgG1 mAb prepared from CHO cells exhibiting fragmentation that can be attributed to residual proteolytic enzyme activity. The concomitant occurrence of proteolytic and non-proteolytic peptide bond cleavage is shown and the respective fragmentation patterns characterized using high-resolution LC-MS. Fragmentation rates are monitored by SE-HPLC and SDS-PAGE over the pH range 4-6 and characterized in the presence and absence of pepstatin A, an inhibitor of acidic proteases. After 20 days at 40°C, pH 4, ∼60% decrease in BIIB-mAb monomer peak occurred attributed to residual proteolytic activity. At pH 5, this value was ∼13%. These results have implications for formulation design studies and the interpretation of accelerated stability data. A simple method to screen for acidic protease activity using the proteolytic enzyme inhibitor pepstatin A is described.
Methanol Electro-Oxidation on Pt-Ru Alloy Nanoparticles Supported on Carbon Nanotubes

Carbon nanotubes (CNTs) have been investigated in recent years as a catalyst support for proton exchange membrane fuel cells. Improved catalyst activities were observed and attributed to metal-support interactions. We report a study on the kinetics of methanol electro-oxidation on CNT supported Pt-Ru alloy nanoparticles. Alloy catalysts with different compositions, Pt53Ru47/CNT, Pt69Ru31/CNT and Pt77Ru23/CNT, were prepared and investigated in detail. Experiments were conducted at various temperatures, electrode potentials, and methanol concentrations. It was found that the reaction order of methanol electro-oxidation on the PtRu/CNT catalysts was consistent with what has been reported for PtRu alloys with a value of 0.5 in methanol concentrations. However, the electro-oxidation reaction on the PtRu/CNT catalysts displayed much lower activation energies than that on the Pt-Ru alloy catalysts unsupported or supported on carbon black (PtRu/CB). This study provides an overall kinetic evaluation of the PtRu/CNT catalysts and further demonstrates the beneficial role of CNTs.
MODELING THE CUMULATIVE DISTRIBUTION FUNCTION OF SPIKES IN NEURAL NETWORKS

Important components of neural networks are input synapses, action potential generators and output synapses. Rather than modeling a whole neuron in terms of a few ionic channels or as having Hodgkin–Huxley, Morris–Lecar or FitzHugh–Nagumo dynamics, we describe a neuron's action potential generator (APG). An APG may be at the hillock region at the base of an axon or another specific region of a cell. We model it using bifurcation theory based on observations by A. F. Hodgkin about membrane excitability. The result is a simplified model that leads us to view a neural network as comprising input and output synapses (electrical or chemical) that network APGs. These centers of activity are coupled by transfer functions from input synapses to an APG and from an APG to output synapses. The transfer functions account for time delays and signal attenuation that result from input and output structures. While this falls far short of a complete biophysical model of specific neurons in a network, it is consistent with empirical data, it is easily formulated, it is analytically tractable, and computer simulations based on it are straightforward. One outcome is a precise description of the cumulative distribution function (CDF) of action potentials. Since records of cell firing amount to collections of CDFs, the model is for a variable that is accessible to experimental observation. This methodology is applied here to describe bursting neural circuits and embedded loop networks similar to those occurring in basal ganglia.
Abstract IA06: Adaptive designs and adaptive learning for biomarker-based clinical trials for targeted therapies.

Rapid advancements in genomics have changed the landscape of target identification and drug development for targeted therapies. Targeted agents work well when drugs are given to patients with the actionable targets. For example, TKI works well for lung cancer patients with EGFR mutation and crizotinib is highly effective for patients with EML4-ALK translocation. Targeted agents, however, do not work for everyone and may not work at all. Hence, the goals for developing target agents include (1) testing the treatment efficacy, (2) identifying prognostic and predictive markers, and (3) providing better treatments to patients enrolled in the trial. Several novel designs have been introduced to achieve these objectives. For example, Bayesian adaptive designs can assign more patients to the more effective treatments based on the available data at the time via the outcome-adaptive randomization. More frequent interim monitoring can drop the ineffective treatments early for futility. New treatments can be added, and effective treatments can graduate for further evaluation. The concepts of the basket design and the N-of-1 design have also been proposed to study the targeted agents based on patients9 genomic profiles across different disease sites. Information collected from such trials can be put together to form a continuously updated knowledge database for adaptive learning. Statistical methods such as the hierarchical model and Individual level meta-analysis can be applied to model data collected in the knowledge database to estimate the treatment effect, the marker effect, and their interactions. A platform of a clinical trial infrastructure can be established to facilitate the conduct of such trials. In the talk, pros and cons of various designs will be discussed. Examples and lessons learned from the recently completed BATTLE trial and the on-going BATTLE-2 trial in non-small cell lung cancer will be given. Citation Format: J. Jack Lee. Adaptive designs and adaptive learning for biomarker-based clinical trials for targeted therapies. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr IA06.
Phase Selection During Pulsed Laser Annealing of Fe-V Alloys

Pulsed laser melting of the low-temperature σ (tetragonal, D8b) phase has been used to generate a liquid undercooled with respect to the melting point of the higher-temperature, equilibrium α (bcc) solid solution in equiatomic Fe-V alloys. From calculations based on reported thermodynamic data and equilibrium transformation temperatures, the metastable melting point of the σ phase is about 1720 K for an Fe-50 at.% V alloy, which is 54 K below the melting temperature of the α phase. During rapid heating of well-annealed σ-phase material with a 30 ns laser pulse to above melt threshold, the σ → α reaction is suppressed, so that the melt zone is undercooled by ∼ 54 K with respect to the equilibrium α phase. The α phase nucleates from the undercooled molten surface layer and is retained during the subsequent rapid cooling (∼ 1010 K/s) because of the relatively sluggish α → σ transformation. X-ray diffraction (Read camera) and TEM identified the α phase in the near-surface after melting σ with incident laser energies (1.0–1.41 J/cm2) which are well above the melt threshold as determined by changes in reflectivity (∼ 0.7 J/cm2). The α phase nucleated from the undercooled liquid within ∼ 20 ns.
Vagabond Abroad: Mark Twain's 1895 Visit to New Zealand

In 1895, an elderly, tired, and creatively challenged Samuel Clemens embarked upon a worldwide lecture tour whose primary purpose was to retire the debt which had driven him into bankruptcy. His personal woes were largely ignored by enthusiastic New Zealand audiences, which packed the halls and reveled in Clemens as Mark Twain. Some of Twain's novels preceded him, but his success in New Zealand owed more to his stage presence than to his literary prowess. This essay shows how Clemens performed Mark Twain to bridge cultural gaps halfway around the globe. In doing so, it highlights reading differences in English-speaking lands and between social classes. It also casts light on Twain's underappreciated skill in live performance, shows him as a flexible figure responding to particular audiences, and underscores the ways in which aspects of his stage show anticipate the shift to a celebrity-based culture.
A simple method for filling and storing glass micro-electrodes.

Abstract A rack and filling system for glass micro-electrodes is described which can be used for current filling techniques or the technique described here. The time to make more than 100 micro-electrodes is less than 1 h.
Coloring heuristics for register allocation

We describe an improvement to a heuristic introduced by Chaitin for use in graph coloring register allocation. Our modified heuristic produces better colorings, with less spill code. It has similar compile-time and implementation requirements. We present experimental data to compare the two methods.
A study on non-octave scalable coding using motion compensated inter-frame wavelet transform

JPEG2000, an international standard for still image compression, has three main features: 1) high coding performance; 2) unified lossless/lossy compression; and 3) resolution and SNR scalability. Resolution scalability is especially promising given the popularity of super high definition (SHD) images like digital-cinema. Unfortunately, the resolution scalability of its current implementation is restricted to powers of two. In this paper, we introduce non-octave scalable coding with a motion compensated interframe wavelet transform. By using the proposed algorithm, images of rational scales can be decoded from a compressed code stream. Experiments on SHD digital cinema test sequences show the effectiveness of the proposed algorithm.
The effect of total body water on the relationship between alcohol consumption and carbohydrate-deficient transferrin.

Background Clinicians agree that alcoholism commonly is overlooked in their patients, and that treating the symptoms without directing therapy to the underlying cause at best delays an inevitable decline in the patient's general health and well-being. The current analysis focused on carbohydrate-deficient transferrin (CDT), a promising biological marker of dangerous alcohol consumption. Methods Included in our study were men (730) and women (613) from study sites in Canada, Brazil, and Japan. All subjects were participants in the WHO/ISBRA Study on State and Trait Markers of Alcoholism, who completed an extensive demographic, medical, and behavioral survey and provided blood samples for determination of CDT levels. ANOVA and χ2 test for equality were used to examine the effect of total body water (TBW) on the alcohol consumption/CDT relationship. To examine whether accounting for differences in TBW improved the diagnostic properties of CDT when used as a state marker for alcohol consumption, odds ratios were calculated for men and women separately. Results Our results show that accounting for individual differences in TBW significantly influenced the alcohol consumption/CDT dose-response relationship. The effect of TBW was different for men compared with women. When we used a consumption cutoff value of 40 g/day and the CDTect® recommended cutoffs (20 for men; 27 for women), adjusting for differences in TBW significantly increased diagnostic performance of CDT in men but not women. Conclusions The dependence of CDT measures on body water content needs to be taken into account to maximize the performance of CDT as an effective state marker of alcohol consumption in males.
A probabilistic mesoscale damage detection in polycrystals using a random matrix approach

This article is concerned with a probabilistic mesoscale damage detection in polycrystals. For this purpose, we make use of a stochastic model describing the linear elasticity matrix of material at the mesoscale. The model is constructed using a maximum entropy principle and random matrix theory and allows one to directly construct a probabilistic model for the system random matrices characterizing the constitutive behavior of the system. First, the theoretical framework and upscale scheme in the construction of the model are briefly reviewed. For each case of healthy and damaged materials, where the damage is introduced in the form of intergranular microcavities, the random matrix model is calibrated by performing simulations on an ensemble of statistical volume elements of microstructure. The calibrated models are then used in a simple coarse-scale simulation in order to explore the sensitivity of the model in detecting the location of mesoscale damages. The result shows that in most cases, one can iden...
Arsenic exposure inhibits myogenesis and neurogenesis in P19 stem cells through repression of the β-catenin signaling pathway

Epidemiological studies have correlated embryonic arsenic exposure with adverse developmental outcomes such as stillbirths, neonatal mortality, and low birth weight. Additionally, arsenic exposure reduces neuronal cell migration and maturation, and reduces skeletal muscle cell formation, alters muscle fiber subtype, and changes locomotor activity. This study used P19 mouse embryonic stem cells to examine whether arsenic exposure could alter their differentiation into skeletal muscles and neurons. When P19 cells were exposed to 0.1, 0.5, or 1.0μM sodium arsenite, embryoid body (EB) formation was not altered. However, arsenic suppressed their differentiation into muscles and neurons, as evidenced by morphological changes accompanied by a significant reduction in myosin heavy chain and Tuj1 expression. Real-time PCR, immunofluorescence, and immunoblotting were used to confirm that the altered differentiation was due to the repression of muscle- and neuron-specific transcription factors such as Pax3, Myf5, MyoD, myogenin, neurogenin 1, neurogenin 2, and NeuroD in the arsenite-exposed cells. The reductions in transcription factors expression appear to be caused by repressed Wnt/β-catenin signaling pathways in early embryogenesis, as evidenced by decreased β-catenin expression in the arsenic-exposed EBs on differentiation days 2 and 5. Interestingly, the expression of Nanog, a transcription factor that maintains the pluripotency of stem cells, was increased after arsenite exposure, indicating that arsenite inhibits their differentiation but not proliferation. This study demonstrates that arsenic can perturb the embryonic differentiation process by repressing the Wnt/β-catenin signaling pathway. More importantly, this study may provide insight into how arsenic exposure affects skeletal and neuronal differentiation during embryogenesis.
The cost-effectiveness of a nursing demonstration project, Part II

The Milieu Enhancement Project was funded for 3 years by the Division of Nursing, Department of Health and Human Services. The goals, setting, project personnel, roles, and implementation activities are described. This project allowed faculty and graduate students to practice independently in a children's residential setting. A needs assessment identified problems related to organizational, academic, and sex- and health-related concerns. These concerns were addressed and outcome measurements identified. A cost-effectiveness framework was used to describe the interventions in terms of improvement. Statistical analyses supported the effectiveness of several project activities.
The Rational Design of International Institutions

Why do international institutions vary so widely in terms of such key institutional features as membership, scope, and flexibility? We argue that international actors are goal-seeking agents who make specific institutional design choices to solve the particular cooperation problems they face in different issue-areas. In this article we introduce the theoretical framework of the Rational Design project. We identify five important features of institutions—membership, scope, centralization, control, and flexibility—and explain their variation in terms of four independent variables that characterize different cooperation problems: distribution, number of actors, enforcement, and uncertainty. We draw on rational choice theory to develop a series of empirically falsifiable conjectures that explain this institutional variation. The authors of the articles in this special issue of International Organization evaluate the conjectures in specific issue-areas and the overall Rational Design approach.
Patterns in computed tomography utilization among emergency physicians in an urban, academic emergency department

We sought to determine if CT utilization rates varied by characteristics of the physician. A chart review was performed at an urban academic emergency department (ED) to identify all the CT scans ordered and patients seen for subjects 21 years of age and older by physicians between January 2001 and December 2008. “Years of experience” was defined as years of practice after residency. Various experience cutoffs were determined a priori. Physicians were labeled “academic” if they had reduced clinical hours for academic duties and “clinical” if they were physicians without “protected time.” We categorized physicians as “high users” (top quartiles) and “low users” (bottom quartiles), and compared utilization rates from 2001 to 2003 to utilization rates from 2005 to 2007. There were 280 physician-years of practice, with an average experience of 6.1 years. When comparing groups of physicians with more or less than 3, 5, 10, and 15 years of experience, there were no statistically significant differences between the number of CT scans per 1,000 visits (p = 0.85; p = 0.21; p = 0.57; p = 0.08, respectively). Comparison between clinical and academic physicians yielded no differences (clinical = 98.4, academic = 104.2, p = 0.10). Low users ordered 78 CT scans per 1,000 patient visits (95 % CI 76.6–78.5), as compared to the high users that ordered 135 CT scans per 1,000 patient visits (95 % CI 131.8–139.0). We found that all of physicians stayed within their quartiles except one. While there was substantial variation among CT utilization rates by physicians at this urban emergency department, our data shows no differences between physicians with more or less clinical experience and no change in individual utilization patterns during the study period.
Identification of a novel repressive element in the proximal lck promoter.

The T-cell-specific protooncogene lck, a src-related tyrosine kinase, is under the control of two promoters that give rise to transcripts differing only in their 5′-untranslated regions. The distal promoter is transcriptionally active in both peripheral and thymic T-cells, whereas expression of the proximal promoter is highest in developing thymocytes. The proximal promoter has also been shown to be selectively activated in a number of colon carcinoma cell lines. Approximately 570 base pairs of proximal promoter sequence is required for expression in both T-cells and colon carcinoma cell lines. Protein binding studies were initiated with an oligonucleotide homologous to a region that, when deleted, causes an increase in promoter activity in transgenic animals. Two proteins with approximate molecular masses of 35 and 75 kDa were found to bind to this region as determined by UV cross-linking studies. Absence of specific protein binding is correlated with a high level of proximal promoter expression. Competitive gel retardation analysis identified a 9-base pair binding site within the proximal lck promoter that is necessary for repression of transcription in cells that contain specific binding activity. Mutants of this binding site do not repress transcription. Repression does not occur in a cell line that expresses lck and lacks this activity. These data support the hypothesis that activation of lck transcription in colon carcinoma is due, at least in part, to the loss of a transcriptional repressor.
An entropy based robust speech boundary detection algorithm for realistic noisy environments

This paper addresses the issue of automatic word/sentence boundary detection in both noiseless and noisy backgrounds. We present our proposed speech boundary detection algorithm using a time-domain entropic contrast function. The entropic contrast exhibits well-behaved characteristics as compared to energy-based methods resulting in immunity to endpoint cut-of issues for the latter. This algorithm is capable of estimating the speech boundaries both in noiseless and distinctive noise backgrounds such as a fan, car engine, radio etc. For the case of wide-spectrum colored background noise such as jazz, opera, songs, rock music etc., we further propose a modification in the preprocessing stage by incorporating a frequency-weighting scheme to emphasize the speech contents. This improved scheme provides proper speech segmentation even in the presence of wide-spectral background noise with no change in the computational cost versus our earlier proposed algorithm. A complete time-domain implementation is sought due to its lower computational burden and its suitability for real-time implementations using DSPs, FPGAs, ASICs etc. The algorithm improves the accuracy of word boundary estimates by a factor of at least 25% for the case of isolated (and 16% for connected) speech. For continuous speech, the algorithm can determine sentence boundaries thus allowing for power efficient implementation of speech recognition engines by rejecting extended periods of silence.
Energetics of muscarinic stimulation of smooth muscle.

Urinary bladder contraction is mediated primarily via the stimulation of muscarinic receptors (1). The contractile response to bethanechol stimulation can be dissociated from the metabolic response through the use of diltiazem (calcium channel blockade) (2). KCl stimulates contraction in isolated strips by directly depolarizing the membrane rather than by binding to specific membrane receptors. The current study directly compares the metabolic and contractile activities of bethanechol (muscarinic stimulation) with KCl (direct membrane depolarization).