cssi/SciSciGPT-SciSciNet huggingface dataset:
Variation in the ATM gene may alter glycemic response to metformin.

1. GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group; Wellcome Trust Case Control Consortium 2, Zhou K, Bellenguez C, Spencer CC, Bennett AJ, Coleman RL, Tavendale R, Hawley SA, Donnelly LA, Schofield C, Groves CJ, Burch L, Carr F, Strange A, Freeman C, Blackwell JM, Bramon E, Brown MA, Casas JP, Corvin A, Craddock N, Deloukas P, Dronov S, Duncanson A, Edkins S, Gray E, Hunt S, Jankowski J, Langford C, Markus HS, Mathew CG, Plomin R, Rautanen A, Sawcer SJ, Samani NJ, Trembath R, Viswanathan AC, Wood NW; MAGIC Investigators, Harries LW, Hattersley AT, Doney AS, Colhoun H, Morris AD, Sutherland C, Hardie DG, Peltonen L, McCarthy MI, Holman RR, Palmer CN, Donnelly P, Pearson ER. Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes . Nat Genet. 2011;43(2):117–120. PMID: 21186350 . ### Study Hypothesis Metformin has been used for >50 years for the treatment of type 2 diabetes and generally is recommended as first-line therapy. However, glycemic response to the drug varies widely among patients with diabetes, and the mechanism of action of metformin has not …
Ferromagnetic CNT suspended H2O+Cu nanofluid analysis through composite stenosed arteries with permeable wall

Abstract In the present article magnetic field effects for CNT suspended copper nanoparticles for blood flow through composite stenosed arteries with permeable wall are discussed. The CNT suspended copper nanoparticles for the blood flow with water as base fluid is not explored yet. The equations for the CNT suspended Cu–water nanofluid are developed first time in the literature and simplified using long wavelength and low Reynolds number assumptions. Exact solutions have been evaluated for velocity, pressure gradient, the solid volume fraction of the nanoparticles and temperature profile. Effect of various flow parameters on the flow and heat transfer characteristics is utilized. It is also observed that with the increase in slip parameter blood flows slowly in arteries and trapped bolus increases.
Epigenetic and Genetic Factors in the Cellular Responses to Radiations and DNA-damaging Chemicals

DNA-damaging agents are widely used as therapeutic tools for a variety of disease states. Many such agents are considered to produce detrimental side effects. Thus, it is important to evaluate both therapeutic efficacy and potential risk. DNA-damaging agents can be so evaluated by comparison to agents whose therapeutic benefit and potential hazards are better known. We propose a framework for such comparison, demonstrating that a simple transformation of cytotoxicity-dose response patterns permits a facile comparison of variation between cells exposed to a single DNA-damaging agent or to different cytotoxic agents. Further, by transforming data from experiments which compare responses of 2 cell populations to an effects ratio, different patterns for the changes in cytotoxicity produced by epigenetic and genetic factors were compared. Using these transformations, we found that there is a wide variation (a factor of 4) between laboratories for a single agent (UVC) and only a slightly larger variation (factor of 6) between normal cell response for different types of DNA-damaging agents (x-ray, UVC, alkylating agents, crosslinking agents). Epigenetic factors such as repair and recovery appear to be a factor only at higher dose levels. Comparison in the cytotoxic effect of a spectrum of DNA-damaging agents in xeroderma piginentosum, ataxia telangiectasia, and Fanconi's anemia cells indicates significantly different patterns, implying that the effect, and perhaps the nature, of these genetic conditions are quite different.
Catalyst aging studied with isotopic transients: Methanation over Raney nickel

Abstract Abrupt changes in the reaction ambient from 12 CO H 2 to 13 CO H 2 are utilized to obtain transientkinetic information regarding the causes of activity decline in the methanation over Raney nickel. From the responses we infer that the methanation proceeds via at least two parallel pathways. The relative contribution of the two pathways changes with catalyst aging. The gradual development of a less reactive carbonaceous overlayer alone is insufficient to explain the observations. We conclude that aging affects the nickel catalyst itself.
The Koyanagi-Nonomura 1-stage bucket repair of severe hypospadias with and without penoscrotal transposition

AbstractPurpose: We report our experience with 1-stage Koyanagi-Nonomura hypospadias repair, which may be performed even when penoscrotal transposition is present. Repair involves bilateral parameatal skin flaps based on the meatus and urethral plate.Materials and Methods: A total of 14 boys 10 to 20 months old underwent 1-stage Koyanagi-Nonomura repair for severe hypospadias. The meatus was proximal to the penoscrotal junction in all patients, and in 8 penoscrotal transposition was corrected during the same operation.Results: In 7 of the 14 boys 1 or more fistulas developed that were subsequently repaired. In all cases the fistula was on the proximal shaft and/or penoscrotal junction. In no case was there stenosis or breakdown of the distal neourethra.Conclusions: The Koyanagi-Nonomura 1-stage repair provides excellent cosmetic results in severe hypospadias while preserving the available urethral plate tissue. It is particularly suitable when there is associated penoscrotal transposition. Most if not all...
Resolving paradoxical criteria for the expansion and replication of early childhood care and education programs

Abstract Conceptual bases of intervention and policy are often subject to paradoxical dilemmas, such as the need for a coherent program model versus recognition of the diversity of a target population. This article aims to identify underlying paradoxical bases for expansion and replication of early childhood care and education programs, and to suggest potential resolutions of these paradoxes. Clarification of such paradoxes may provide guidance for the many decision points which arise in processes of identifying, expanding, and replicating early childhood programs based on evidence of quality or success. First, a brief history of early childhood care and education in the U.S. from the viewpoint of expansion and replication is presented. A five-fold typology of expansion and replication processes is proposed: staged replication, franchised replication, multi-site demonstrations, mandated replication, and government-supported private sector expansion. Second, paradoxes associated with the process of replication are considered, such as: (1) the “can it work” versus “does it work” paradox; (2) the fidelity versus local cultural relevance paradox; (3) the replication versus addition paradox; (4) the replication versus program improvement paradox; and (5) the representativeness versus feasibility paradox. In a concluding section, recommendations for funders, policy makers, and evaluators are made regarding next steps in expansion and replication of early childhood care and education programs.
The contribution of attenuated selection in utero to small-for-gestational-age (SGA) among term African American male infants.

Abstract Natural selection conserves mechanisms allowing women to spontaneously abort gestations least likely to yield fit offspring. Small gestational size has been proposed as an indicator of fitness observable by maternal biology. Previous research suggests that exposure to ambient stress in utero results in more “culling” of small fetuses and therefore lower rates of small-for-gestational-age (SGA). However, African American women persistently have higher rates of SGA than non-Hispanic white women, despite experiencing more ambient stress. This paper tests whether attenuation of the stress response among highly stressed African American women, as suggested by the weathering hypothesis, may help to explain this apparent inconsistency. We apply time-series modeling to over 2 million African American and non-Hispanic white male term births in California over the period of January 1989 through December 2010. We test for the parabolic (i.e., “U” shaped) relationship, implied by an attenuated stress response, between unusually strong labor market contraction and the rate of SGA among African American term male infants, and a linear relationship among non-Hispanic whites. We find the hypothesized parabolic relationship among term male African American infants. As expected, we find a linear relationship between unexpected layoffs and the rate of SGA among term male non-Hispanic whites. These results are robust to sensitivity analyses. These results may help to explain the high rates of SGA among term male African American infants, despite greater maternal exposure to ambient stress during pregnancy.
Intravenous beta-blockers in acute myocardial infarction: perceived versus actual use by cardiologists and emergency physicians

This study sought to determine the relationship between perceived and actual use of intravenous beta-blockers by cardiologists and emergency physicians for patients with acute myocardial infarction (AMI). The charts of 35 patients who presented to the emergency department of a community hospital with AMI during a 6-month period were retrospectively reviewed. Members of the departments of cardiology and emergency medicine were mailed a one-page survey pertaining to their use of intravenous beta-blockers in AMI. Of the 35 patients only 4 (11%) received an intravenous beta-blocker. Three of these 4 patients were either hypertensive or tachycardic and none had a contraindication to beta-blockade. A contraindication was present in 15 (48%) of those who did not get intravenous beta-blockade. The survey was completed by 11 (100%) of the emergency physicians and 68 (69%) of the cardiologists. Emergency physicians were significantly less likely to report using intravenous beta-blockers in AMI patients who were normotensive with normal heart rates (P=.007) and most (9 of 11) deferred the decision to the cardiologist. Although the majority of cardiologists reported giving an intravenous beta-blocker to at least 50% of AMI patients with normal blood pressure and pulse rates, the actual frequency was only 8% (1 of 13). In this institution, cardiologists overestimated the frequency of intravenous beta-blocker administration to patients with AMI. Emergency physicians usually deferred the decision on intravenous beta-blockers to cardiologists and reported a frequency of use that was much closer to actual practice.
Scaled-energy spectra and closed classical orbits of the hydrogen atom in parallel electric and magnetic fields

Rydberg atoms in strong fields have scaling properties that allow detailed interpretation of photoabsorption spectra in terms of classical trajectories. The classical dynamics remains invariant if a spectrum is obtained at constant scaled energy. Since each orbit which is closed at the nucleus produces a sinusoidal modulation in the absorption spectrum, its signature is a peak in the Fourier transform of a scaled-energy spectrum. This paper identifies the effect of closed orbits in the computed spectrum of the hydrogen atom in parallel electric and magnetic fields in a region where chaos is just beginning to develop.
The power of totalistic cellular automata and totalistic systolic networks

A systolic network is an array of synchronized processors. It is totalistic if the states of its processors are integers and the next state of each processor is determined by the sum of all the states in its neighborhood including its own. Our main result is that every uniform regular network can be simulated by a totalistic systolic network.
Induction of neural differentiation in cultures of amphibian undetermined presumptive epidermis by cyclic AMP derivatives

Induction of neural differentiation in cultures of undetermined presumptive epidermis from three amphibian species was achieved by the addition of 1 millimolar dibutyryl adenosine 3',5'-monophosphate, 8-bromadenosine 3',5'-monophosphate, or adenosine C',E'-monophosphate together with theophylline. Adenosine 5'-monophosphate, adenosine 2',3'-monophosphate, dibutyryl guanosine 3',5'-monophosphate, and butyrate at 1 millimolar are ineffective. These results suggest that the action of the primary inductor or inductors may be mediated via adenosine 3',5'-monophosphate.
Soil Erosion Awareness and Use of Conservation Tillage for Water Quality Control

Water pollution through loss of topsoil from farmland continues to be a major problem, despite nearly 50 years of providing farmers technical and financial assistance for soil and water conservation. The technology for controlling erosion and water pollution is available, but farmers have been slow in implementing control practices. Past research has shown that farmers tend to be unaware of the seriousness of the erosion problem on their own operations. Using a random sample of farmers from central Iowa, the relationship is examined between awareness of a soil erosion problem and the use of conservation tillage. Results indicate that awareness of a soil erosion problem effects the use of conservation tillage, and that awareness can be enhanced by experiential educational strategies such as the development and implementation of a soil and water conservation plan.
How many queries are needed to learn

We investigate the query complexity of exact learning in the membership and (proper) equivalence query model. We give a complete characterization of concept classes that are learnable with a polynomial number of polynomial sized queries in this model. We give applications of this characterization, including results on learning a natural subclass of DNF formulas, and on learning with membership queries alone. Query complexity has previously been used to prove lower bounds on the time complexity of exact learning. We show a new relationship between query complexity and time complexity in exact learning: If any “honest” class is exactly and properly learnable with polynomial query complexity, but not learnable in polynomial time, then P = NP. In particular, we show that an honest class is exactly polynomial-query learnable if and only if it is learnable using an oracle for Gp4.
Quantitative determination of the monoclinic crystalline phase content in polyethylene by 13C n.m.r.

Abstract Solid-state 13 C n.m.r. spectroscopy involving the techniques of cross-polarization (CP), magic angle spinning (MAS), and high power proton decoupling, has been used to determine quantitatively the ratio of monoclinic to orthorhombic crystalline phases in compression moalded ultra-high molecular weight polyethylene (UHMWPE) sheet which had been stretched uniaxially. Criteria for expecting quantitative relative intensities in 13 C CP-MAS spectra are discussed. Attenuation of the non-crystalline (NC) signals relative to crystalline signals was observed. Experiments were therefore carried out to ascertain whether measurable relative intensity distortions exist between the monoclinic crystalline phase (MCP) and the orthorhombic crystalline phase (OCP) resonances due to possible differences in proton ‘spin diffusion’ between the NC and the two crystalline phases during cross-polarization. No relative intensity distortions were detected. This result, coupled with experiments in which spin diffusion was monitored at times longer than those used for cross-polarization, suggests that the average distance from the protons in a given crystalline phase to the nearest protons in the NC regions is the same for the MCP and the OCP. Finally, non-spinning 13 C spectra of the deformed polyethylene were recorded to determine the orientation of the chains in the crystalline and NC regions. The Hermans orientation function, F c , was determined independently for the crystalline (combined OCP and MCP) and NC regions, and found to be 0.66 + 0.06 and 0.23 + 0.04 respectively. The occurrence of orientation in the NC regions may be evidence for internal stresses, which, it is suggested, also stabilize the metastable MCP in the stretched sample.
Americanism, Popular Culture and the Primitive: Johannes Vilhelm Jensen, Madame D'Ora (1904)

Johannes V. Jensen's novels Madame D'Ora (1904) and Hjulet (The Wheel, 1905) represented some of the most popular works of early twentieth-century Americanist fiction in Europe. Taking Jensen's first novel, Madame D'Ora, as my focus, I show how his work participated in an ambivalent construction of America as an imaginary space of both danger and cultural renewal, one that combined the modern (technology) with a dangerous, ‘atavistic’ influence. Through an investigation of Jensen's use of tropes of primitivity, in particular, I argue that such literary Americanism in fact represented an effort to work through changes taking place within Europe itself. Specifically, Madame D'Ora deals with the rise of new forms of mass culture and popular entertainment – such as the cinema – and their effect on traditional European intellectuals. Within this context, Jensen represents the new ‘American’ forms of technology and popular culture both as a hope for overcoming European decadence and as a dangerous form of cultural and psychic primitivization.
The opioid growth factor (OGF) and low dose naltrexone (LDN) suppress human ovarian cancer progression in mice

Abstract Objective The opioid growth factor (OGF) and its receptor, OGFr, serve as a tonically active inhibitory axis regulating cell proliferation in normal cells and a variety of cancers, including human ovarian cancer. Blockade of OGF and OGFr with the nonselective opioid receptor antagonist naltrexone (NTX) upregulates expression of OGF and OGFr. Administration of a low dosage of NTX (LDN) blocks endogenous opioids from opioid receptors for a short period of time (4–6h) each day, providing a window of 18–20h for the upregulated opioids and receptors to interact. The present study investigated the repercussions of upregulating the OGF–OGFr axis by treatment with OGF or LDN on human ovarian tumorigenesis in vivo . Methods Female nude mice were transplanted intraperitoneally with SKOV-3 human ovarian cancer cells and treated on a daily basis with OGF (10mg/kg), LDN (0.1mg/kg), or an equivalent volume of vehicle (saline). Tumor burden, as well as DNA synthesis, apoptosis, and angiogenesis was assessed in tumor tissue following 40days of treatment. Results OGF and LDN markedly reduced ovarian tumor burden (tumor nodule number and weight). The mechanism of action was targeted to an inhibition of tumor cell proliferation and angiogenesis; no changes in cell survival were noted. Conclusions This study shows that a native opioid pathway can suppress human ovarian cancer in a xenograft model, and provides novel non-toxic therapies for the treatment of this lethal neoplasia.
METHEMOGLOBINEMIA INDUCED BY BENZOCAINE SPRAY PRIOR TO ESOPHAGEAL MANOMETRY IN AN ADOLESCENT. 751

Esophageal manometry is best performed without anesthesia or sedation. However, with particularly anxious patients, some form of topical anesthetic or sedation may be used. Benzocaine spray, thought to be a safe topical anesthetic, has been reported to induce methemoglobinemia in adults(Gastroenterology 1990;98:211-213). However, this has not been reported to occur in children. We report an 11½-year-old Caucasian male with a history of achalasia. He developed methemoglobinemia as a result of topical benzocaine sprayed onto his pharynx prior to esophageal manometry at 10:10 a.m. (see table). Within 25 minutes of receiving the benzocaine spray, his oxygen saturation (%) dropped from 98% to 88%, and he became cyanotic. His oxygen saturation continued to drop even though he was receiving oxygen therapy and maintained a Po2 of> 300 mmHg. He remained awake and alert. Arterial blood (AB) for oxygen content was noted to be brown, and the diagnosis of methemoglobinemia was made. Blood for methemoglobin concentration showed an increase to 16% and 24% on two occasions(<1% WNL). Intravenous methylene blue (M.B.) was administered; 2 doses of 35 mg each (1 mg/kg ×2). Within 12 minutes of the second dose, the patient was pink, and after 22 minutes his oxygen saturation was 91%.
Mesoporous Carbon Materials: Synthesis and Modification

Porous carbon materials are of interest in many applications because of their high surface area and physicochemical properties. Conventional syntheses can only produce randomly porous materials, with little control over the pore-size distributions, let alone mesostructures. Recent breakthroughs in the preparation of other porous materials have resulted in the development of methods for the preparation of mesoporous carbon materials with extremely high surface areas and ordered mesostructures, with potential applications as catalysts, separation media, and advanced electronic materials in many scientific disciplines. Current syntheses can be categorized as either hard-template or soft-template methods. Both are examined in this Review along with procedures for surface functionalization of the carbon materials obtained.
Stratification of the space of unimodal interval maps

The space of ‘quadratic-like’ (unimodal) maps of a compact interval to itself is shown to decompose in a ‘nice’ way (stratify) according to a dynamical property of such maps (the existence of a homoclinic periodic orbit with given period). This decomposition is refined by that discovered by Sarkovskii. Orbit structure and bifurcation properties are also discussed.
Racial and ethnic disparities in Alzheimer's disease pharmacotherapy exposure: an analysis across four state Medicaid populations.

Abstract Background Treatment disparities in Alzheimer's disease (AD) have received little attention. Determining whether disparities exist in this subpopulation is an important health policy issue. Objective The aim was to determine whether an association existed between race/ethnicity and exposure to AD pharmacotherapy across 4 state Medicaid populations. Methods Data from the Centers for Medicare and Medicaid Services (CMS) were used in this retrospective study. Persons with AD enrolled in California, Florida, New Jersey, or New York Medicaid programs on January 1, 2004, and remained in that program for 1 year. Individuals had an AD diagnosis based on the ICD-9-CM code 331.0. Outcomes of interest were exposure to a cholinesterase inhibitor (ChEI) or memantine. Multivariate logistic regression was used to test for the association between race/ethnicity and exposure to a ChEI or memantine. Variables of interest included demographic characteristics and resource utilization factors. The Oaxaca-Blinder decomposition method was used to test for disparities to determine whether exposure to AD pharmacotherapy was influenced by race. Results Race, age, long-term care admittance, inpatient care admittance, state of residence, and sex were significant predictors of AD pharmacotherapy exposure (P Conclusions Disparities in AD pharmacotherapy exposure among minority populations are just as prevalent, if not of greater magnitude, than minority/white disparities.
Neuroscience: Accurate maps of visual circuitry

Such is the brain's complexity that even small neural circuits contain hundreds of neurons making thousands of connections. Connectivity and optical analyses provide close-up views of two such circuits. See Articles p.168 , p.175 & Letter p.212 Three papers in this issue of Nature use the retina as a model for mapping neuronal circuits from the level of individual synaptic contacts to the long-range scale of dendritic interactions. Helmstaedter et al. used electron microscopy to map a mammalian retinal circuit of close to a thousand neurons. The work reveals a new type of retinal bipolar neuron and suggests functional mechanisms for known visual computations. The other two groups study the detection of visual motion in the Drosophila visual system — a classic neural computation model. Takemura et al. used semi-automated electron microscopy to reconstruct the basic connectome (8,637 chemical synapses among 379 neurons) of Drosophila's optic medulla. Their results reveal a candidate motion detection circuit with a wiring plan consistent with direction selectivity. Maisak et al. used calcium imaging to show that T4 and T5 neurons are divided into specific subpopulations responding to motion in four cardinal directions, and are specific to 'ON' versus 'OFF' edges, respectively.
Whither Pentecostal Theology? Why a Catholic is Interested

The essay explores the future direction of Pentecostal theology by posing a dialogue question that emerges in the conversation between Catholics and Pentecostals. This concerns the "supernatural" character of grace as understood and experienced in both traditions. How is this character preserved as it engages all dimensions of our humanity? Two aspects of this affirmation are explored. First, grace perfects all aspects of human nature including human agency, thus our common emphasis on transformation and Christian perfection. Second, the Church's mission ad extra embraces its witness in the secular realm in the arenas of culture, justice, peace, and the integrity of creation. The challenge to both traditions is how to preserve the supernatural gratuity of grace as the church enacts this mission in the transit from church to world.
Cumulative Environmental Risk and Youth Maladjustment: The Role of Youth Attributes

Using data from 5,070 youth ages 11 to 18 years old who participated in the National Longitudinal Study of Adolescent Health, concurrent and longitudinal associations among cumulative risk, protective factors, and youth maladjustment were examined. Cumulative risk was associated with concurrent conduct problems and depressed mood. For conduct problems, a compensatory effect was found for scholastic achievement and problem-solving ability. For depressed mood, a compensatory effect was found for scholastic achievement. A protective-reactive effect of self-esteem was found for both forms of maladjustment. Youth gender, grade, and ethnicity moderated these associations. Cumulative risk predicted change over time in depressed mood. Scholastic achievement and self-esteem compensated for this risk. Findings indicate that youth attributes offer limited protection when adolescents experience risk factors across life domains.
Clinical syndromes and biochemical alterations following mescaline, lysergic acid diethylamide, psilocybin and a combination of the three psychotomimetic drugs

Summary Twenty-four volunteer subjects were treated with mescaline (5 mg./K), LSD-25 (1.5 mcg./K), psilocybin (225 mcg./K) or a combination of all three drugs using one-third doses of each. The four treatments were given orally in a latin-square order. Clinical effects as assessed by a 75-item questionnaire, the Clyde Mood Scale and the Hoffer-Osmund Diagnostic (HOD) test were remarkably alike for all 4 treatments. Somatic effects or varying degrees of intellectual impairment were most apparent on the questionnaire; many perceptual and psychic symptoms were denied. Of the six factors on the Clyde Mood Scale, three (friendly, energetic and clear-thinking) were uniformly decreased by the drugs in the first two to four hours; three other factors (aggressive, jittery and depressed) tended to be increased by the drugs, both early and late. Questions most often answered positively on the HOD test were concerned with somatic effects or perceptual alterations (fluctuating time sense, increased auditory and tactile acuity, and visual effects); once again, frankly psychotic symptoms were seldom reported. All treatments increased plasma free fatty acids, but the degree of mobilization of FFA was not related to the severity of the clinical reaction. All treatments decreasea urinary creatinine clearance slightly; clearance of inorganic phosphorus was more substantially reduced, along with increased serum phosphorus. Little effect was noted on urinary calcium excretion, serum calcium, plasma glucose, or serum triglycerides. Levels of circulating eosinophils declined, but not to a significant degree. The biochemical alterations probably represent nonspecific reactions to stress.
Controversies surrounding glucocorticoid-mediated cell death in the hippocampus

The adrenal gland releases mineralocorticoids (MCs) and glucocorticoids (GCs) in response to a variety of stimuli, including stress. Once released, these adrenal steroids mediate a plethora of physiological responses in both the periphery and the central nervous system. The collective actions of GCs in the brain are paradoxical, however, in that basal levels of GCs are essential for neuronal development, plasticity and survival, while stress levels of GCs produce neuronal loss. Aging represents another contradictory function of GCs in the brain, since lifelong exposure to GCs has been implicated as a causative factor in senescent neuronal loss. In addition, glucocorticoids have also been shown to intensify neuronal damage in the hippocampus during ischemia and excitotoxicity through mechanisms that modulate synaptic glutamate concentrations. Conversely, the absence of adrenal steroids has been shown to regulate both neurogenesis and neuronal loss in the dentate gyrus of the hippocampus. Evidence continues to accumulate which suggests that GC-induced neuronal death in all these physiological and pathophysiological settings occurs by apoptosis. Accordingly, this review will examine the pharmacological, cellular and molecular mechanisms through which glucocorticoids mediate or contribute to neuronal remodeling and, ultimately, neuronal death.
The Potential for Combination Treatment Using STAT-C Drugs

Given the limitations of pegylated interferon (IFN) and ribavirin (RBV) therapy for chronic hepatitis C virus (HCV) infection, new antiviral medication and treatment approaches are sought. Specifically targeted antiviral therapies for hepatitis C (STAT-C) refers to the use of these new inhibitors, either in combination with IFN and RBV or other STAT-C agents, to improve therapy for HCV. Although many classes of inhibitors are being developed, NS3 protease and NS5B polymerase inhibitors are likely to be among the first STAT-C agents approved. The preclinical and clinical characteristics of HCV protease and polymerase inhibitors are reviewed in this article. Strengths and weaknesses of each class in the context of developing future all–STAT-C regimens are explored, with a particular focus on viral resistance and the prospects for eliminating IFN and/or RBV.
Cachexia-like symptoms predict a worse prognosis in localized t1 renal cell carcinoma.

ABSTRACTPurpose: Although cachexia is a common sequela of advanced and metastatic renal cell carcinoma (RCC), cachexia-like symptoms may also represent a paraneoplastic finding. We assessed the prognostic significance of these symptoms in patients with stage T1 RCC.Materials and Methods: Using the kidney cancer database at our institution 250 patients were identified who underwent partial or radical nephrectomy for T1N0M0 RCC between 1989 and 2001. The prognostic significance of the symptoms present at diagnosis and findings on preoperative laboratory evaluation were examined.Results: Mean and median followup was 33 and 43 months, respectively. Malaise, weight loss, anorexia and hypoalbuminemia were cachexia related findings that were significant predictors of worse disease specific survival (DSS). DSS in patients with 1 vs greater than 1 cachexia related symptoms was not significantly different (p = 0.077). Therefore, any patient with at least 1 cachexia related finding was considered to be positive for ...
A declarative specification and semantics for visual languages

A key issue in visual languages is the specification of the relationship between pictures and their meaning. To do this, we introduce a class of declarative, constraint-based picture specification languages. These extend previous approaches to picture specification based on constraints and grammar formalisms. As the languages are defined as instances of an abstract language scheme, we ensure they share a common declarative semantics and operational semantics. The declarative semantics allows both people and machines easily to reason about a specification independently of any underlying implementation. The operational semantics permit both the generation and recognition of pictures defined by the specification.
Legal aspects of interface accessibility in the U.S.

Accessible information technology is not just good design and a clever way to win new users, it is the law.
Imaging adhesion forces on proteins with the atomic force microscope

We investigated the adhesion forces between single protein molecules and the silicon-nitride tip of an atomic force microscope. Force curves were taken on a sample with single adsorbed proteins while the tip was raster scanned laterally. Out of these force maps we can calculate several images showing for instance the topography or the adhesion force as a function of lateral position. Two systems were investigated here: actin adsorbed on mica and tubulin adsorbed on positively charged silanized surfaces, the adhesion force of the tip on the protein was smaller by about a factor of three to five compared to the force measured on the substrate. This is in agreement with previous studies of lysozyme and DNA adsorbed on mica. The data were analyzed by estimating the van der Waals force between the tip and a single protein and between the tip and a flat substrate. The measured adhesion force between the tip and the substrate can be understood by van der Waals. However in the case of the proteins the observed adhesion is larger than expected by only van der Waals forces. So we conclude that there are additional interactions determining the adhesion between the tip and the protein.
Relict colluvial boulder deposits as paleoclimatic indicators in the Yucca Mountain region, southern Nevada

Early to middle Pleistocene boulder deposits are common features on southern Nevada hillslopes. These darkly varnished, ancient colluvial deposits stand but in stark contrast to the underlying light-colored bedrock of volcanic tuffs, and they serve as minor divides between drainage channels on modern hillslopes. To demonstrate the antiquity of these stable hillslope features, six colluvial boulder deposits from Yucca Mountain, Nye County, Nevada, were dated by cation- ratio dating of rock varnish accreted on boulder surfaces. Estimated minimum ages of these boulder deposits range from 760 to 170 ka. Five additional older deposits on nearby Skull and Little Skull Mountains and Buckboard Mesa yielded cation-ratio minimum-age estimates of 1.38 Ma to 800 ka. An independent cosmogenic chlorine-36 surface exposure date was obtained on one deposit, which confirms an estimated early to middle Quaternary age. These deposits have provided the oldest age estimates for unconsolidated hillslope deposits in the southwestern United States. We suggest that the colluvial boulder deposits were produced during early and middle Pleistocene glacial/pluvial episodes and were stabilized during the transition to drier interglacial climates. By comparison to modern periglacial environments, winter minimum monthly temperatures of -3 to -5 °C were necessary to initiate freeze-thaw conditions of such vigor to physically weather relatively large volumes of large boulders from the upper hillslopes of the Yucca Mountain area. These conditions imply that early and middle Pleistocene glacial winter temperatures were at least 1 to 3 °C colder than existed during the last Pleistocene glacial episode and 7 to 9 °C colder than present. We conclude that at least several early and middle Pleistocene glacial episodes were colder, and perhaps wetter, than glacial episodes of the late Pleistocene in the southern Great Basin. Geomorphic processes necessary to form these colluvial boulder deposits are not active on modern hillslopes in the southern Great Basin. In addition, the lack of young, relatively unvarnished colluvial boulder deposits on these hillslopes suggests that boulder-forming conditions did not exist during the late Pleistocene in this region. Modern semiarid hillslope processes primarily erode colluvium during infrequent high-intensity storms. The preservation of old, thin hillslope deposits and the less-than-2-m incision by hillslope runoff adjacent to these deposits, however, indicate that extremely low denudation rates have occurred on resistant volcanic hillslopes in the southern Great Basin during Quaternary time.
Optical systems for efficient triple-matrix-product processing.

Three different optical systems are developed for efficient evaluation of a triple-matrix product of the form [U][G][V]. One system uses a purely space-integrating architecture, whereas the other two use hybrid time- and space-integrating architectures. Each of these three systems has a distinct format for input [using one-dimensional (1-D) and two-dimensional (2-D) spatial light modulators] and output (using either 1-D or 2-D time-integrating detector arrays or high-bandwidth single-element detectors) devices, thus permitting a trade-off between parameters such as speed and dynamic range. Potential applications for these systems include image data compression and orthogonal transforms of coefficient matrices encountered in linear systems analysis.
Effect of band anticrossing on the optical transitions in GaAs 1 − x N x / GaAs multiple quantum wells

Interband transitions in ${\mathrm{GaAs}}_{1\ensuremath{-}x}{\mathrm{N}}_{x}/\mathrm{GaAs}$ multiple quantum wells were studied at room temperature by photomodulated reflectance spectroscopy as a function of well width (3--9 nm), the nitrogen concentration $(0.012lxl0.028),$ and hydrostatic pressure (0--64 kbar). All experimental data can be quantitatively explained using the dispersion relationship obtained from a band anticrossing model to calculate electron confinement effects in a finite depth quantum well. The results are consistent with a nitrogen-induced large increase of the electron effective mass in the GaAsN quantum wells.
Hollow silicone obturators for patients after total maxillectomy

One technical approach for the treatment of a patient after complete removal of the hard palate and other supportive structures has been presented. This technique offers a means of obtaining a detailed impression of the defect and promptly provides the patient with a lightweight and flexible tissue-tolerant obturator. The patient can ultimately be provided with a hollow dental prosthesis attached to a removable hollow obturator.
Test bench for emulating electric-drive vehicle systems using equivalent vehicle rotational inertia

In this paper, a new approach for emulating an electric-drive vehicle (EDV) system on a test bench setup consisting of a dynamometer, flywheel, and an electric propulsion unit is investigated. The equivalent rotational inertia of a vehicle is used to obtain a suitable control method based on vehicle and test bench dynamics. MATLAB/Simulink is used to model the test bench and simulate the control scheme for a standard driving schedule. Moreover, the effect of eliminating the large flywheel from the test model is investigated and changes to the control scheme are discussed. Simulation results of both cases are presented and compared. The results obtained from MATLAB/Simulink are validated using the ADVISOR software and found to be almost the same with minor deviations.
Incorporating Information on Bioavailability of Soil-Borne Chemicals into Human Health Risk Assessments

ABSTRACT Definition of the term bioavailability varies in the environmental sciences. In human health risk assessment, bioavailability is defined as the fraction of the dose of chemical delivered that is absorbed into the systemic circulation. Bioavailability can be expressed as either absolute or relative bioavailability, and both are important in calculating risks from contaminants in soils. Bioavailability of chemicals is addressed in all risk assessments, although not always in a transparent manner. Because data on bioavailability are limited, approximations and assumptions regarding chemical uptake are extensively used. The risk assessment process could benefit from new information on the bioavailability of chemicals, but there are important questions about the best means to develop this information and how it should be used. To foster discussion on these issues, three articles are presented in this issue of the journal offering different perspectives on bioavailability method development, validation...
Raman Measurement of Lattice Temperature during Pulsed Laser Heating of Silicon

The ratio of Stokes-to-anti-Stokes phonon Raman scattering of a proble laser pulse at 405 nm is used to obtain a direct measure of the lattice temperature in silicon within 10 nsec after a heating pulse at 485 nm. A lattice temperature rise of only 300\ifmmode^\circ\else\textdegree\fi{}C is found with a heat pulse power density of \ensuremath{\sim}1 J/${\mathrm{cm}}^{2}$. Since silicon melts at 1412\ifmmode^\circ\else\textdegree\fi{}C, this result is direct evidence that strictly thermal melting models of laser annealing are inappropriate.
The decreased phosphorylation of cyclic adenosine monophosphate (cAMP) response element binding (CREB) protein in the central amygdala acts as a molecular substrate for anxiety related to ethanol withdrawal in rats.

Background: Several lines of evidence indicate a high comorbidity between anxiety and alcohol abuse. This study investigated the molecular mechanisms in the amygdaloid neurocircuitry governing anxiety related to ethanol withdrawal and also the phenomenon of alcohol preference. Methods: Male Sprague Dawley® rats were treated with ethanol or control diet for 15 days, and ethanol-fed rats were withdrawn for 0 and 24 hr. Ethanol-withdrawn or control diet-fed rats were bilaterally infused into central or basolateral amygdala with artificial cerebrospinal fluid or protein kinase A (PKA) activator or inhibitor. These rats were used to measure anxiety levels by the elevated plus-maze test. Protein levels of various signaling molecules related to cyclic adenosine monophosphate (cAMP)-response element binding (CREB) protein signaling in amygdaloid structures were determined by gold immunolabeling procedure. The messenger RNA levels of neuropeptide Y were determined by in situ polymerase chain reaction procedure. Results: Ethanol withdrawal (24 hr) after chronic exposure (15 days) produced anxiety in rats as measured by elevated plus-maze test. Ethanol withdrawal but not treatment significantly decreased the phosphorylation of CREB protein and protein levels of Ca2+/calmodulin-dependent protein kinase IV without modulating the protein levels of total CREB and α-catalytic subunit of protein kinase A (PKA-Cα) in the central and medial amygdala. However, these changes were not observed in the basolateral amygdala. We also investigated the effects of manipulation of the phosphorylation status of CREB in the central amygdala by infusion of the PKA activator (Sp-cAMPS) or inhibitor (Rp-cAMPS) on anxiety levels in rats during ethanol withdrawal. When Sp-cAMPS is specifically infused into the central amygdala, it dose-dependently normalizes the decrease in CREB phosphorylation and prevents the development of anxiety in rats during ethanol withdrawal. On the other hand, Rp-cAMPS infusions into the central or basolateral amygdala decrease CREB phosphorylation, but only infusion into the central amygdala provokes anxiety and increases alcohol preference in normal rats. We also found that alcohol preference provoked by decreased CREB phosphorylation is related to decreased expression of the neuropeptide Y gene in the central amygdala. Conclusions: These novel results suggest the possibility that decreased CREB phosphorylation in the central amygdala acts as a common molecular correlate for anxiety and alcohol-drinking behaviors and also is correlated with anxiety related to ethanol withdrawal.
The reaction of gelatin/gum arabic coacervate gels with glutaraldehyde

Abstract The consumption of glut by various gelatin/gum arabic (GGA) coacervate gels has been examined over a range of conditions. Both acid- and alkali-precursor gelatins were used to form the coacervates. Glut consumptions by several gelatin gels were also determined. All gels examined consumed 0.3 to 1.6 mmole glut/g gelatin. Acid and alkali GGA gels had similar glut uptakes at 4°C. Glut consumption by acid-precursor GGA gels increased significantly with increasing gelation temperature (4–28°C) due to temperature-dependent changes in gel structure. The use of commercial versus redistilled glut had no detectable effect upon glut uptakes. Reaction of a gel with glut caused a high degree of insolubilization as a result of intermolecular crosslink formation. Most treated gels were at least 85 wt% insoluble at 55°C in phosphate buffer after 4–28 days extraction. That fraction of a gel solubilized by the extraction process contained both gelatin and gum arabic. Thus, despite the fact that gum arabic has little tendency to react with glut, it is effectively entrapped in the crosslinked GGA gel structure. Gels with lowest glut uptakes were the most soluble ones. They also were the only ones with solubilities that increased upon treatment with NaHSO 3 before the gel fraction extraction process. Insolubilization of GGA gels by glut causes their swelling behavior and composition to become essentially independent of pH. Composition and swelling behavior of uncrosslinked gels vary markedly with pH due to the reversible nature of the intermolecular bridges responsible for gelation.
Global notes: diapers and the deserts. What is the connection?

The technology of modern diapers has evolved through extensive research over the last 40 years. The idea was to have a material that absorbs the water (urine of the baby) rapidly and that holds water in large enough quantity to minimize mother's work of frequent cleansing of the infant.
Nearly Tight Bounds for the Continuum-Armed Bandit Problem

In the multi-armed bandit problem, an online algorithm must choose from a set of strategies in a sequence of n trials so as to minimize the total cost of the chosen strategies. While nearly tight upper and lower bounds are known in the case when the strategy set is finite, much less is known when there is an infinite strategy set. Here we consider the case when the set of strategies is a subset of ℝd, and the cost functions are continuous. In the d = 1 case, we improve on the best-known upper and lower bounds, closing the gap to a sublogarithmic factor. We also consider the case where d > 1 and the cost functions are convex, adapting a recent online convex optimization algorithm of Zinkevich to the sparser feedback model of the multi-armed bandit problem.
Neural correlates of arithmetic calculation strategies

Recent research into math cognition has identified areas of the brain that are involved in number processing (Dehaene, Piazza, Pinel, & Cohen, 2003) and complex problem solving (Anderson, 2007). Much of this research assumes that participants use a single strategy; yet, behavioral research finds that people use a variety of strategies (LeFevre et al., 1996; Siegler, 1987; Siegler & Lemaire, 1997). In the present study, we examined cortical activation as a function of two different calculation strategies for mentally solving multidigit multiplication problems. The school strategy, equivalent to long multiplication, involves working from right to left. The expert strategy, used by “lightning” mental calculators (Staszewski, 1988), proceeds from left to right. The two strategies require essentially the same calculations, but have different working memory demands (the school strategy incurs greater demands). The school strategy produced significantly greater early activity in areas involved in attentional aspects of number processing (posterior superior parietal lobule, PSPL) and mental representation (posterior parietal cortex, PPC), but not in a numerical magnitude area (horizontal intraparietal sulcus, HIPS) or a semantic memory retrieval area (lateral inferior prefrontal cortex, LIPFC). An ACT-R model of the task successfully predicted BOLD responses in PPC and LIPFC, as well as in PSPL and HIPS.