cssi/SciSciGPT-SciSciNet huggingface dataset:
Inhibition of diamine oxidase by 1,1-[(methylethanediylidene)-dinitrilo]-bis-(3-aminoguanidine) and 1,1'-[(methylethanediylidene)-dinitrilo]-diguanidine.

Abstract It was found that two inhibitors currently being used to inhibit spermidine formation in mammalian cells were more potent inhibitors of diamine oxidase than of polyamine synthesis. Eukaryotic S-adenosylmethionine decarboxylase is inhibited reversibly by 1,1'-[(methylethanediylidene)-dinitrilo]-diguanidine (MGBG) and irreversibly by 1,1'-[(methylethanediylidene)-dinitrilo]-bis-(3-aminoguanidine) (MBAG). Since this enzyme is essential for the generation of propylamine groups needed to convert putrescine into spermidine, these drugs were used to prevent spermidine synthesis in mammalian cells. It was found that both drugs were potent inhibitors in vitro of pig kidney diamine oxidase activity. MGBG appeared to be a non-competitive inhibitor with a Ki of about 0.1 μM and MBAG was a competitive inhibitor with a Ki of 0.02 μM. Inhibition by MBAG was partially reversible after prolonged dialysis. The period during which diaminc oxidasc activity remained suppressed in the rat after treatment with these inhibitors was determined by measuring the conversion of (1.414C] putrescine to 14CO2. A single dose of MGBG (60 mg/kg body wt) inhibited 14CO2production more than 90 per cent for 21 hr and a single dose of MBAG (50 mg/kg body wt) produced a similar inhibition for 72 hr.
Teaching Geography Using Cooperative Learning

Abstract In the United States geographic knowledge has declined among students. Cooperative learning is an interactive methodology that can foster student group involvement which produces a positive classroom climate through the use of group builders and cooperative projects. The principles of cooperative learning can be and should be applied to the teaching of geography. When cooperative learning is used, students become more involved in the subject and more motivated to learn content. Geographic knowledge can increase among U.S. students when they are more motivated to learn. A variety of cooperative learning lessons can bring about that motivation and increase in knowledge.
Kinetics of a Garnet Granulite Reaction

It is necessary to understand the mechanisms of disequilibrium reactions in metamorphic rocks in order to (1) model the rate of reaction in response to changing state variables during tectonic process, and (2) interpret the assemblages of natural disequilibrium samples in terms of tectonic history. A sample was selected from an area of known tectonic history to examine in detail and document the kinetics of reaction. The sample preserves evidence of the garnet granulite to gabbro transition.
E-NOTE: An E-voting system that ensures voter confidentiality and voting accuracy

In this paper, we propose an E-voting system based on and improved from our previous work (Name and vOte separaTed E-voting system, NOTE). The proposed E-voting system, referred to as Enhanced NOTE (E-NOTE), is enhanced with a new protocol design and watchdog hardware device to ensure voter confidentiality and voting accuracy. In our improved scheme, other than the Election Committee (EC) and Vote Counting Committee (VCC), an impartial third party, Ballot Distribution Center (BDC), is proposed to take the responsibility of distributing ballots. The votes and the candidates' names are separated into two parts when the voters cast their votes. The watchdog device records all voting transactions to prevent voter frauds. Our proposed procedure addresses issues related to voter confidentiality, voter frauds, and voting accuracy, thus providing a framework for fair elections.
Some familiar examples for which the large deviation principle does not hold

For a class of Markov processes (in continuous or discrete time) we show that if the full large deviation holds for normalized occupation time measures Lt(w, ˙) with some rate function J, then the lower semicontinuous regularization of J must agree with the rate function I introduced by M. D. Donsker and S. R. S. Varadhan. As a consequence we show that for processes such as Brownian motion the full large deviation principle for Lt(w, ˙) cannot hold with any rate function.
Improved simulations of snow extent in the second phase of the Atmospheric Model Intercomparison Project (AMIP-2)

[1] Simulations of snow-covered area (SCA) over Northern Hemisphere lands by a suite of general circulation models (GCMs) are evaluated. Results from GCM experiments submitted by an international array of research groups participating in the second phase of the Atmospheric Model Intercomparison Project (AMIP-2) are compared to a data set derived primarily from visible band satellite imagery provided by the United States National Oceanic and Atmospheric Administration. At continental to hemispheric scales we find improvements over AMIP-1 models, including the elimination of temporal and spatial biases in simulations of the seasonal cycle of SCA, as well as improved simulations of the magnitude of interannual variability. At regional spatial scales, while no consistent model biases are identified over North America, regions over Eurasia are identified where models consistently either underestimate or overestimate SCA at the southern boundary of the seasonal snowpack. The region of greatest model bias is eastern Asia. While SCA biases are associated with temperature and precipitation biases, over only one region do we find a relationship between the magnitudes of SCA biases and the magnitudes of temperature and/or precipitation biases.
Paired fractional quantum Hall states and the ν=5/2 puzzle

Abstract Work on the problem of the ν =5/2 fractional quantum Hall state is reviewed, with emphasis on recent progress concerning paired states.
MANGANESE STATUS, GUT ENDOGENOUS LOSSES OF MANGANESE, AND ANTIOXIDANT ENZYME ACTIVITY IN RATS FED VARYING LEVELS OF MANGANESE AND FAT

We hypothesized that manganese deficient animals fed high vs moderate levels of polyunsaturated fat would either manifest evidence of increased oxidative stress or would experience compensatory changes in antioxidant enzymes and/or shifts in manganese utilization that result in decreased endogenous gut manganese losses. Rats (females in Study 1, males in Study 2,n = 8/treatment) were fed diets that contained 5 or 20% corn oil by weight and either 0.01 or 1.5 μmol manganese/g diet. In study 2,54Mn complexed to albumin was injected into the portal vein to assess gut endogenous losses of manganese. The manganese deficient rats: 1. Had 30–50% lower liver, tibia, kidney, spleen, and pancreas manganese concentrations than manganese adequate rats; 2. Conserved manganese through ≈70-fold reductions in endogenous fecal losses of manganese; 3. Had lower heart manganese superoxide dismutase (MnSOD) activity; and 4. Experienced only two minor compensatory changes in the activity of copper-zinc superoxide dismutase (CuZnSOD) and catalase.
Theory into Practice: Feedback: The Key to Effective Coaching

(2010). Theory into Practice: Feedback: The Key to Effective Coaching. Strategies: Vol. 23, No. 6, pp. 34-35.
Natural history of idiopathic dilated cardiomyopathy : effect of referral bias and secular trend

Abstract Objectives . The current study was designed to determine the effect of secular trend and referral bias on the natural history of idiopathic dilated cardiomyopathy. Background . In a previous study of 104 patients with idiopathic dilated cardiomyopathy conducted in a referral population at the Mayo Clinic between 1960 and 1973, the 1- and 5-year mortality rates were 31% and 64%, respectively. A recent study of 40 patients with idiopathic dilated cardiomyopathy conducted in a population-based cohort at the Mayo Clinic between 1975 find 1984 reported 1- and 5-year mortality rates of 5% and 20%, respectively. We hypothesized that improvements in diagnosis and therapy have occurred since the original referral cohort was described and that these improvements have altered the apparent natural history of the disease. We refer to this effect as secular trend . Alternatively, the presence of more advanced disease in the referral population ( referral bias ) may also contribute to the differences in survival. Methods . Two sequential referral populations with idiopathic dilated cardiomyopathy seen at the Mayo Clinic between 1976 and 81 (n = 85) and 1982 and 1987 (n = 137) were identified. Outcome was compared between these cohorts and the 1960–1973 referral cohort to examine the effect of secular trend. Outcomes were compared with that of the population-based cohort to examine the effect of referral bias. Results . Survival in the 1976–1981 referral cohort did not differ from that in the 1960–1973 referral cohort, suggesting little impact of secular trend during these time periods. Survival in the more recent 1982–1987 referral cohort was significantly better than that in the earlier referral cohorts, suggesting that improvements in diagnosis and treatment in the 1980s altered the natural history of idiopathic dilated cardiomyopathy. Survival in the 1982–1987 referral cohort was still worse than that of the population-based cohort, suggesting an effect of referral bias on studies of the natural history of idiopathic dilated cardiomyopathy. Conclusions . The current study demonstrates that secular trend and referral bias affect the apparent natural history of idiopathic dilated cardiomyopathy. Survival in referral patients with this disease is significantly better than previously described.
Immune complex-induced integrin activation and L-plastin phosphorylation require protein kinase A.

Integrins in resting leukocytes are poorly adhesive, and cell activation is required to induce integrin-mediated adhesion. We recently demonstrated a close correlation between phosphorylation of Ser5 in L-plastin (LPL), a leukocyte-specific 67-kDa actin bundling protein, and activation of αMβ2-mediated adhesion in polymorphonuclear neutrophils (PMN) (Jones, S. L., Wang, J., Turck, C. W., and Brown, E. J. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 9331–9336). However, the kinase that phosphorylates LPL Ser5 has not been identified. We found that cAMP-dependent protein kinase (PKA), but not a variety of other serine kinases, can specifically phosphorylate LPL and LPL-derived peptides on Ser5 in vitro. The cell-permeable cAMP analog 8-bromo-cAMP and the adenylate cyclase activator forskolin both induce LPL phosphorylation in cells. Two PKA inhibitors, H89 and KT5720, inhibited immune complex (IC)-stimulated LPL phosphorylation as well as IC-induced activation of αMβ2-mediated adhesion in PMN. The dose response of H89 inhibition of PMN adhesion correlated with its inhibition of LPL phosphorylation in response to IC. IC stimulation also transiently increased intracellular cAMP concentration in PMN. Thus, PKA functions in an integrin activation pathway initiated by IC binding to Fcγ receptors in addition to its better known role as a negative regulator of cell activation by G protein-coupled receptors. In contrast, LPL Ser5 phosphorylation and PMN adhesion induced by formylmethionyl-leucylphenylalanine or phorbol myristate acetate were not affected by PKA inhibitors, suggesting that a different kinase(s) is responsible for LPL phosphorylation in response to these agonists. Phosphoinositidyl 3-kinase also is required for FcγR but not formylmethionyl-leucylphenylalanine- or phorbol myristate acetate-induced LPL phosphorylation and activation of αMβ2. Two phosphoinositidyl 3-kinase inhibitors blocked FcγR-induced cAMP accumulation, demonstrating that this kinase acts upstream of PKA. These data demonstrate a necessary role for PKA in IC-induced integrin activation and LPL phosphorylation.
Association of mammographic image feature change and an increasing risk trend of developing breast cancer: an assessment

We recently investigated a new mammographic image feature based risk factor to predict near-term breast cancer risk after a woman has a negative mammographic screening. We hypothesized that unlike the conventional epidemiology-based long-term (or lifetime) risk factors, the mammographic image feature based risk factor value will increase as the time lag between the negative and positive mammography screening decreases. The purpose of this study is to test this hypothesis. From a large and diverse full-field digital mammography (FFDM) image database with 1278 cases, we collected all available sequential FFDM examinations for each case including the “current” and 1 to 3 most recently “prior” examinations. All “prior” examinations were interpreted negative, and “current” ones were either malignant or recalled negative/benign. We computed 92 global mammographic texture and density based features, and included three clinical risk factors (woman’s age, family history and subjective breast density BIRADS ratings). On this initial feature set, we applied a fast and accurate Sequential Forward Floating Selection (SFFS) feature selection algorithm to reduce feature dimensionality. The features computed on both mammographic views were individually/ separately trained using two artificial neural network (ANN) classifiers. The classification scores of the two ANNs were then merged with a sequential ANN. The results show that the maximum adjusted odds ratios were 5.59, 7.98, and 15.77 for using the 3rd, 2nd, and 1st “prior” FFDM examinations, respectively, which demonstrates a higher association of mammographic image feature change and an increasing risk trend of developing breast cancer in the near-term after a negative screening.
Staphylococcus aureus Inactivation Using Pulsed UVlight for Continuous Milk Treatment

Staphylococcus aureus is a pathogen frequently associated with milk. Pulsed UV-light is a novel technology which can be used for inactivation of this pathogen in milk in a short time. Pulsed UV-light damages DNA of the bacteria by forming thymine dimmers which leads to bacterial death. This study investigated the efficacy of the pulsed UV-light system for continuous milk treatment for inactivation of S. aureus. The effect of sample distance from the UV-light source, number of passes, and flow rate were investigated. A response surface method was used for design and analysis of the experiments. Milk was treated at 5, 8, or 11 cm distance from UV-light strobe at 20, 30, or 40 ml/min flow rate and treated up to three times by recirculation of milk to find the effect of number of passes on inactivation of pathogenic microorganisms. Log10 reductions varied from 0.55 to 7.26 log10 CFU/ml. Complete inactivation was obtained in two cases and in most conditions, growth was not observed following an enrichment procedure. This research demonstrates that pulsed UV-light has a potential to be used for inactivation of S. aureus in milk.
Redesigning Introductory Biology: A Proposal

With the increasing complexity and expansion of the biological sciences, there has been a corresponding increase in content in the first-year introductory biology course sequence for majors. In general this has resulted in courses that introduce students to large amounts of material and leave little time for practicing investigative science or skill development. Based on our analysis of data compiled from 742 biology faculty at a variety of institutions across the United States, we verified that there is strong agreement on the content appropriate for introductory biology courses for majors. Therefore, we propose that faculty teaching these courses focus primarily on the topics identified in this study, and redesign their courses to incorporate active learning strategies that emphasize the investigative nature of biology and provide opportunities for skill development.
N -(Pyridin-2-yl) arylsulfonamide inhibitors of 11β-hydroxysteroid dehydrogenase type 1: Strategies to eliminate reactive metabolites

N-(Pyridin-2-yl) arylsulfonamides 1 and 2 (PF-915275) were identified as potent inhibitors of 11β-hydroxysteroid dehydrogenase type 1. A screen for bioactivation revealed that these compounds formed glutathione conjugates. This communication presents the results of a risk benefit analysis carried out to progress 2 (PF-915275) to a clinical study and the strategies used to eliminate reactive metabolites in this series of inhibitors. Based on the proposed mechanism of bioactivation and structure-activity relationships, design efforts led to N-(pyridin-2-yl) arylsulfonamides such as 18 and 20 that maintained potent 11β-hydroxysteroid dehydrogenase type 1 activity, showed exquisite pharmacokinetic profiles, and were negative in the reactive metabolite assay.
Law in abandon: jean-luc nancy and the critical study of law

The ‘constitutive theory’ of law is in question in this essay. Where the task of external criticism is frequently handed to constitutive theorists of various sorts who engage in the description of ‘historical a priori’ structures that inform the subjects of law, Jean-Luc Nancy’s work leads to the possibility that at the historical a priori is a ‘site of abandonment’. As he uses it, ‘abandonment’ evokes the banishment of being – the singular, shared, openness of being, the resistance to identity that freedom designates – and at the same time evokes abundance. Abandonment is ‘the other of law which constitutes the law’. This essay addresses the importance of these claims for contemporary critical legal thought and concludes that by adopting a perspective informed by this sense of abandonment we approach a different articulation of law, community, and life.
Regulation of glucose-6-phosphatase gene expression in cultured hepatocytes and H4IIE cells by short-chain fatty acids: Role of hepatic nuclear factor-4α

Mechanisms underlying dietary nutrient regulation of glucose-6-phosphatase (Glc-6-Pase) gene expression are not well understood. Here we investigated the effects of short-chain fatty acids on the expression of this gene in primary cultures of rat hepatocytes and H4IIE hepatoma cells. Propionate, butyrate, valerate, and caproate induced severalfold increases in the expression of Glc-6-Pase mRNA. In reporter gene assays, propionate, valerate, caproate, and also octanoate increased Glc-6-Pase promoter activity by 6-16-fold. Butyrate, by itself, had little or no effect on promoter activity, but it induced a robust increase (45-fold) in promoter activity in cells co-transfected with a plasmid expressing the transcription factor HNF-4α (α isoforms of hepatic nuclear factor 4). HNF-4α also enhanced promoter activity induced by other short-chain fatty acids. A dominant negative form of HNF-4α abrogated the fatty acid-induced promoter activity, a finding that accentuates a role for HNF-4α in the transcription process studied here. In cells transfected with HNF-4α, short-chain fatty acids and trichostatin A, an inhibitor of histone deacetylase, synergistically enhanced promoter activity, suggesting that hyperacetylation of histones is an important component of the transactivation of the Glc-6-Pase gene promoter by HNF-4α. Region-751/-466 of this promoter contains seven putative HNF-4α-binding motifs. Binding of HNF-4α to this region was confirmed by electrophoretic mobility shift and chromatin immunoprecipitation assays, indicating that HNF-4α is recruited to the Glc-6-Pase gene promoter during short-chain fatty acid-induced transcription from this promoter.
Infrared photoacoustic spectroscopy of surfaces

Abstract A prototype photoacoustic, computer-controlled spectrometer, and an acoustic cell coupled with a reactor in which samples may be treated with gases to 1000°C, is described. IR photoacoustic spectra of samples consisting of beds of silica and alumina several millimeters thick and catalyst pellets have been recorded after various sur -face modifications were carried out, and IR absorptions of surface species formed at sub-monolayer coverages were observed. The new technique is particularly useful for observing surface species on adsorbents, catalysts, coals, chars and carbons, and corrosion layers.
A New Efficient Algorithm for Computational Aeroacoustics on Parallel Processors

One of the great challenges in computational physics is the prediction of flow associated noise, where the quantities of interest, namely the sound waves can be at high frequencies and are usually orders of magnitude smaller in magnitude than the mean quantities. In order to numerically resolve such small scales governed by the fluid dynamics equations, high resolution schemes are required. Thus solutions of flow noise problems are computationally intensive. An efficient, hybrid, data parallel computational aeroacoustics algorithm has been developed for the prediction of noise radiation and scattering from three-dimensional geometries. The algorithm solves the Euler/NavierÂ?Stokes equations in the interior and nonreflecting boundary conditions on the outer boundaries. A moving surface Kirchhoff method is coupled to the flow solver for far-field predictions. The algorithm uses standard time and spatial discretization techniques but utilizes several new optimization strategies that are highly suitable for single zone solutions on data parallel processors. One strategy, for example, enables simultaneous residual evaluations of the interior and far-field nonreflecting boundary conditions equations, reducing the computational effort spent on them by approximately 60% CPU time savings. The algorithms for the flow solver and the Kirchhoff method and their coupling are described in this paper, and results for some example radiation and scattering problems are presented.
The partial molar volume of water in biological membranes

Abstract A new algorithm is presented for interpreting the hydration dependence of x-ray diffraction measurements. The method assumes that the volume of the hydrocarbon phase of the lipid bilayer is not affected by hydration and that the volume expansion between bilayers at maximum hydration is caused by incorporation of water molecules whose partial molar volume is that of pure bulk water. These simple assumptions lead to a determination of the area expansion (and hence change in hydrocarbon-phase thickness) as a function of hydration. An analysis is made of x-ray data of the L alpha and L beta' phases of dimyristoyl phosphatidylcholine and the L alpha phase of egg phosphatidylcholine. The partial molar volume of water depends critically on the degree of lipid hydration and the presence of voids between the head groups of adjacent lipids. The calculated head-group spacings at minimum hydration are consistent with those obtained from neutron diffraction and indicate that the methyl groups of the choline are almost in contact with corresponding groups in the opposing bilayer. This calls into question the origin of the repulsive forces observed in dehydration experiments.
Cognitive-psychological profiles of gifted adolescents from Ireland and the U.S.: Cross-societal comparisons

Abstract The Myers-Briggs Type Indicator (MBTI) was administered to 1,247 gifted adolescents from the United States and a comparable sample of 309 gifted Irish adolescents, all of whom were attending summer programs for the academically talented. Strikingly similar patterns of cognitive and psychological styles were found for the gifted students in both Ireland and the U.S. These patterns are quite different than those found in normative samples of U.S. students. The most consistent finding was that the majority of gifted students score highly on N (Intuition), indicative of a preference for the abstract and theoretical. This is in contrast to studies showing the majority of U.S. students from the general population have a preference for the factual and pragmatic. Many of the gifted students from both societies showed preferences for modes of thinking and learning that may be at odds with typical instructional styles. Implications for educational practices and policy are suggested.
Do food-hoarding animals have a cache recovery advantage? Determining recovery of stored food

Food stored by animals can either be recovered by the hoarder or pilfered, but it is very difficult to distinguish between these possibilities under natural conditions. We tested the hypothesis that yellow pine chipmunks, Tamias amoenus, have a recovery advantage (i.e. a greater probability of finding a cached item than does a naive forager). We allowed chipmunks to cache radiolabelled pine seeds and then established artificial caches nearby. Paired artificial and real caches were identical in number of seeds, depth and microsite. Caches (393 pairs at 10 sites) were monitored during autumn 1997, 1999 and 2002. Removal of real caches represented the activity of the hoarder, foraging using spatial memory, plus the activities of pilferers, whereas the removal of artificial caches represented the activities of pilferers. We used these two measures in a competing risks model, which estimated that seed-caching chipmunks retrieved 74% of the food they stored in 1997 and 56% of the food they stored in 1999–2002. Seed-hoarding chipmunks were removed at four of the 10 sites immediately after they prepared caches. Where the seed-hoarders remained, animals took real caches 3.4 to 6.5 times faster than artificial caches, an effect that we attribute to the activity of the hoarder. Where the caching chipmunk was removed, there were no significant differences in the rates of removal of real versus artificial caches. We suggest that artificial caches can be used to estimate the proportion of caches retrieved by a seed-hoarding animal versus the proportion discovered by pilferers.
KINKY MICROTUBULES : BENDING AND BREAKING INDUCED BY FIXATION IN VITRO WITH GLUTARALDEHYDE AND FORMALDEHYDE

We have employed video-enhanced light microscopy to study alterations of the overall shape of microtubules that are produced by the aldehyde fixation methods commonly employed to study them in vitro. Changes brought about by these methods include deformation and breakage. The severity of the effects depends on the fixative employed and increases with its concentration, and with the time of fixation. The changes are observed under a variety of conditions, such as brief exposure to 3.7% formaldehyde, or somewhat longer exposure to glutaraldehyde at concentrations as low as 0.05%. The observed distortion explains why microtubules usually appear curved or sinuous in electron micrographs while appearing relatively rigid and linear in video-enhanced light microscopy. The observed breakage implies that caution must be used in inferring length distributions from measurements of aldehyde-fixed microtubules.
Line Positions and Strengths of N2O between 3515 and 7800 cm−1

The line positions and strengths of N(sub 2)O were measured from spectra obtained at high spectral resolution (0.011 cm(sup -1)) in the region between 3515 nad 7800cm(sup -1).
Beta-naphthoflavone causes an AhR-independent inhibition of invasion and intracellular multiplication of Listeria monocytogenes in murine hepatocytes.

We recently reported a heretofore unknown role for the aryl hydrocarbon receptor in host resistance to listeriosis in mice. Hepatocytes are an important site for Listeria monocytogenes multiplication in vivo. In this study, we investigated whether activation of AhR in TIB73 murine embryonic hepatocytes affects the ingestion and intracellular multiplication of L. monocytogenes. Treatment of TIB73 cells with the AhR agonist β-naphthoflavone (BNF) significantly inhibited the ingestion and intracellular growth of L. monocytogenes. The inhibitory effects of BNF were dose-dependent and correlated with up-regulation of CYP1A1. Surprisingly, pretreatment with AhR antagonists (3′-MNF or α-naphthoflavone) or knocking-down of AhR with siRNA did not abolish the inhibitory effects of BNF. Moreover, the inhibitory effects of BNF on invasion and intracellular growth of L. monocytogenes by BNF were observed in AhR-deficient (CRL-2710), or ARNT-dysfunctional (CRL-2717) Hepa cells. We also observed similar inhibitory effects of BNF treatment using primary hepatocytes recovered from AhR+/− or AhR−/− mice. Moreover, the prototypic AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) did not inhibit the invasion and intracellular growth of L. monocytogenes in TIB73 cells. Mechanistic studies demonstrated that ROS, but not TNF-α or iNOS, plays an important role in mediating BNF-induced inhibition. In conclusion, BNF caused an AhR-independent inhibition of ingestion and intracellular multiplication of L. monocytogenes in murine hepatocytes, mediated in part by production of ROS.
Cardiac rehabilitation in African Americans: evidence for poorer outcomes compared with whites, especially in women and diabetic participants.

Background Cardiac rehabilitation (CR) improves coronary artery disease risk factors and mortality. Outcomes after CR in African Americans (AAs) compared with whites have not been studied extensively. Methods A total of 1,096 patients (169 AAs, 927 whites) were enrolled in a 36-session CR program for ischemic heart disease or postcardiac surgery. The program consisted of exercise, lifestyle modification, and pharmacotherapy. Results After CR, quality of life, blood pressure, and low-density lipoprotein cholesterol improved significantly in both AAs and whites, although to a lesser degree in AAs. Whites also had significant improvements in weight and triglyceride concentrations. Overall, mean peak exercise capacity, measured in metabolic equivalents (METs), improved by only 1.6 (95% CI 1.3–1.8) in AAs compared with 2.4 (2.3-2.6) in CCs ( P Conclusion African Americans derive a significant benefit from CR, but not to the same degree as whites, based on changes in risk factors and in exercise capacity. Within both ethnic groups, both women and diabetic patients appeared to have markedly less improvement.
Dynamic, large-scale profiling of transcription factor activity from live cells in 3D culture.

Background Extracellular activation of signal transduction pathways and their downstream target transcription factors (TFs) are critical regulators of cellular processes and tissue development. The intracellular signaling network is complex, and techniques that quantify the activities of numerous pathways and connect their activities to the resulting phenotype would identify the signals and mechanisms regulating tissue development. The ability to investigate tissue development should capture the dynamic pathway activity and requires an environment that supports cellular organization into structures that mimic in vivo phenotypes. Taken together, our objective was to develop cellular arrays for dynamic, large-scale quantification of TF activity as cells organized into spherical structures within 3D culture. Methodology/Principal Findings TF-specific and normalization reporter constructs were delivered in parallel to a cellular array containing a well-established breast cancer cell line cultured in Matrigel. Bioluminescence imaging provided a rapid, non-invasive, and sensitive method to quantify luciferase levels, and was applied repeatedly on each sample to monitor dynamic activity. Arrays measuring 28 TFs identified up to 19 active, with 13 factors changing significantly over time. Stimulation of cells with β-estradiol or activin A resulted in differential TF activity profiles evolving from initial stimulation of the ligand. Many TFs changed as expected based on previous reports, yet arrays were able to replicate these results in a single experiment. Additionally, arrays identified TFs that had not previously been linked with activin A. Conclusions/Significance This system provides a method for large-scale, non-invasive, and dynamic quantification of signaling pathway activity as cells organize into structures. The arrays may find utility for investigating mechanisms regulating normal and abnormal tissue growth, biomaterial design, or as a platform for screening therapeutics.
VPAF: a flexible framework for establishing and monitoring prolonged authorization relationships

We describe a generic framework for determining and monitoring access rights derived from credential documents. Distributed authorization systems intended to support collaborative coalitions (such as Trust Management systems) typically incorporate mechanisms to both validate credentials, and to determine authorization. This conjunction of distinct functions increases complexity of both components and limits overall flexibility. Furthermore, while authorization decisions frequently enable the commencement of a prolonged relationship, current authorization systems are designed to authorize instantaneous transactions and provide no mechanisms to detect and propagate revocation after an authorization decision is made. VPAF (a Validated and Prolonged Authorization Framework) will separate these duties in a manner that permits credential validation and authorization decisions to be managed separately. VPAF is intended to enable vigilant monitoring of prolonged authorization relationships that span mutually distrustful administrative domains such as is common when multiple organizations collaborate.
The Future Burden of CKD in the United States: A Simulation Model for the CDC CKD Initiative

Background Awareness of chronic kidney disease (CKD), defined by kidney damage or reduced glomerular filtration rate, remains low in the United States, and few estimates of its future burden exist. Study Design We used the CKD Health Policy Model to simulate the residual lifetime incidence of CKD and project the prevalence of CKD in 2020 and 2030. The simulation sample was based on nationally representative data from the 1999 to 2010 National Health and Nutrition Examination Surveys. Setting & Population Current US population. Model, Perspective, & Timeline Simulation model following up individuals from current age through death or age 90 years. Outcomes Residual lifetime incidence represents the projected percentage of persons who will develop new CKD during their lifetimes. Future prevalence is projected for 2020 and 2030. Measurements Development and progression of CKD are based on annual decrements in estimated glomerular filtration rates that depend on age and risk factors. Results For US adults aged 30 to 49, 50 to 64, and 65 years or older with no CKD at baseline, the residual lifetime incidences of CKD are 54%, 52%, and 42%, respectively. The prevalence of CKD in adults 30 years or older is projected to increase from 13.2% currently to 14.4% in 2020 and 16.7% in 2030. Limitations Due to limited data, our simulation model estimates are based on assumptions about annual decrements in estimated glomerular filtration rates. Conclusions For an individual, lifetime risk of CKD is high, with more than half the US adults aged 30 to 64 years likely to develop CKD. Knowing the lifetime incidence of CKD may raise individuals' awareness and encourage them to take steps to prevent CKD. From a national burden perspective, we estimate that the population prevalence of CKD will increase in coming decades, suggesting that development of interventions to slow CKD onset and progression should be considered.
Deadlock-avoidance in a page-parallel rasterizer

A rasterizer converts a document described in some page-description language into a sequence of full-page bitmaps (pagemaps), which can then be printed or displayed. The page-parallel rasterizer harnesses multiple processors to work on the same document. Any given page, however, is processed by a single processor, hence the name. For performance reasons, it is desirable to permit out-of-order rasterization. However, this can result in deadlock. It is shown how to pace the rasterizer so as to avoid deadlock without being overly restrictive. To do this, previously-proposed deadlock-avoidance schemes are extended to cases that seem to be outside their scope. The approach may also be useful in other applications. >
State reduction for network intervention in probabilistic Boolean networks

Motivation: A key goal of studying biological systems is to design therapeutic intervention strategies. Probabilistic Boolean networks (PBNs) constitute a mathematical model which enables modeling, predicting and intervening in their long-run behavior using Markov chain theory. The long-run dynamics of a PBN, as represented by its steady-state distribution (SSD), can guide the design of effective intervention strategies for the modeled systems. A major obstacle for its application is the large state space of the underlying Markov chain, which poses a serious computational challenge. Hence, it is critical to reduce the model complexity of PBNs for practical applications. Results: We propose a strategy to reduce the state space of the underlying Markov chain of a PBN based on a criterion that the reduction least distorts the proportional change of stationary masses for critical states, for instance, the network attractors. In comparison to previous reduction methods, we reduce the state space directly, without deleting genes. We then derive stationary control policies on the reduced network that can be naturally induced back to the original network. Computational experiments study the effects of the reduction on model complexity and the performance of designed control policies which is measured by the shift of stationary mass away from undesirable states, those associated with undesirable phenotypes. We consider randomly generated networks as well as a 17-gene gastrointestinal cancer network, which, if not reduced, has a 217 × 217 transition probability matrix. Such a dimension is too large for direct application of many previously proposed PBN intervention strategies. Contact: [email protected] Supplementary information: Supplementary information are available at Bioinformatics online.
An EMG frequency-based test for estimating the neuromuscular fatigue threshold during cycle ergometry

The purposes of this investigation were twofold: (1) to determine if the model used for estimating the physical working capacity at the fatigue threshold (PWC(FT)) from electromyographic (EMG) amplitude data could be applied to the frequency domain of the signal to derive a new fatigue threshold for cycle ergometry called the mean power frequency fatigue threshold (MPF(FT)), and (2) to compare the power outputs associated with the PWC(FT), MPF(FT), ventilatory threshold (VT), and respiratory compensation point (RCP). Sixteen men [mean (SD) age = 23.4 (3.2) years] performed incremental cycle ergometer rides to exhaustion with bipolar surface EMG signals recorded from the vastus lateralis. There were significant (p < 0.05) mean differences for PWC(FT) [mean (SD) = 168 (36) W] versus MPF(FT) [208 (37) W] and VT [152 (33) W] versus RCP [205 (84) W], but no mean differences for PWC(FT) versus VT or MPF(FT) versus RCP. The mean difference between PWC(FT) and MPF(FT) may be due to the effects of specific metabolites that independently influence the time and frequency domains of the EMG signal. These findings indicated that the PWC(FT) model could be applied to the frequency domain of the EMG signal to estimate MPF(FT). Furthermore, the current findings suggested that the PWC(FT) may demarcate the moderate from heavy exercise domains, while the MPF(FT) demarcates heavy from severe exercise intensities.
Immunohistochemical analysis of primary sensory neurons latently infected with herpes simplex virus type 1.

We characterized the populations of primary sensory neurons that become latently infected with herpes simplex virus (HSV) following peripheral inoculation. Twenty-one days after ocular inoculation with HSV strain KOS, 81% of latency-associated transcript (LAT)-positive trigeminal ganglion (TG) neurons coexpressed SSEA3, 71% coexpressed TrkA (the high-affinity nerve growth factor receptor), and 68% coexpressed antigen recognized by monoclonal antibody (MAb) A5; less than 5% coexpressed antigen recognized by MAb KH10. The distribution of LAT-positive, latently infected TG neurons contrasted sharply with (i) the overall distribution of neuronal phenotypes in latently infected TG and (ii) the neuronal distribution of viral antigen in productively infected TG. Similar results were obtained following ocular and footpad inoculation with KOS/62, a LAT deletion mutant in which the LAT promoter is used to drive expression of the Escherichia coli lacZ gene. Thus, although all neuronal populations within primary sensory ganglia appear to be capable of supporting a productive infection with HSV, some neuronal phenotypes are more permissive for establishment of a latent infection with LAT expression than others. Furthermore, expression of HSV LAT does not appear to play a role in this process. These findings indicate that there are marked differences in the outcome of HSV infection among the different neuronal populations in the TG and highlight the key role that the host neuron may play in regulating the repertoire of viral gene expression during the establishment of HSV latent infection.
Folk management and local knowledge: Lobster fishing and tourism at caye caulker, Belize

Fishers from Caye Caulker, Belize, practice a territorial folk management system, which has contributed to level production of lobsters for over 30 years. This, in association with cooperative organization, has brought high economic returns to fishers. Tourism development on the caye has created a new market for lobsters, which has motivated some fishers to harvest undersized, prereproductive lobsters to sell to local restaurants. Data from interviews and observations suggest that this local system of resource management may be threatened, because of a local market for lobsters which has emerged with the growth of tourism at Caye Caulker. These unsustainable practices, coupled with an underfunded, understaffed, and in the fishers ‘ experience, usually uncooperative Fisheries Department makes enforcement of state‐level fisheries laws next to impossible. Caye Caulker fishers face challenging questions concerning how they will practice in and perceive the fishery, which includes participation with and percep...
Applying justice in clinical trials for diverse populations.

Background Considerable attention has focused on increasing clinical trial participation for members of “underrepresented groups”. However, doing so involves clarifying how to meet the demands of j...
Terahertz Spectroscopy of Short-Chain Polypeptides

Terahertz (THz) absorption and neutron vibrational spectra for solid-phase short-chain peptide sequences at 77 and 298 K are reported. We demonstrate that a high degree of spectral and structural information exists for these systems in the 1–15 THz (33–500 cm � 1 ) spectral range. The density and uniqueness of distinct spectral features for each system suggests that sequence-dependent structural information can potentially be extracted from these spectra using quantum mechanical solid-state modeling and theories. Published by Elsevier Science B.V.
Evaluation of Human Surrogate Models for Rollover

Anthropomorphic test dummies (ATDs) have been validated for the analysis of various types of automobile collisions through pendulum, impact, and sled testing. However, analysis of the fidelity of ATDs in rollover collisions has focused primarily on the behavior of the ATD head and neck in axial compression. Only limited work has been performed to evaluate the behavior of different surrogate models for the analysis of occupant motion during rollover. Recently, Moffatt et al. examined head excursions for near- and far-side occupants using a laboratory-based rollover fixture, which rotated the vehicle about a fixed, longitudinal axis. The responses of both Hybrid III ATD and human volunteers were measured. These experimental datasets were used in the present study to evaluate MADYMO ATD and human facet computational models of occupant motion during the airborne phase of rollover. Occupant motion predicted by the Hybrid III ATD computation models provided a good match to the temporal movement patterns and corridors of torso and head excursion measured in the volunteers. Differences in torso and head-neck posture were attributed to active muscle contractions in the volunteers. Simulations performed using the TNO human facet model, in the absence of muscle tone, predicted large head excursions and lateral neck and torso bending. These findings were attributed to the stiffer Hybrid III ATD neck and torso as compared to the spinal model incorporated in the human facet model. Although it is possible to model active muscle forces using the TNO human facet model, the appropriate control schemes for coordinating muscle activity in the rollover environment have not been established. Without the implementation of appropriate muscular controls, the TNO human model appears to be best suited to high-force environments or low-force environments where the occupant is unconscious or incapacitated. Our results indicate that among the currently available human computational surrogate models, the Hybrid III ATD provides the best prediction of occupant motion when compared to the available human volunteer data. These results have provided us the impetus to study future human models that incorporate active muscle control.
Racism: In Defense of Garcia

Luc Faucher and Edouard Machery’s recent article in this journal uses evidence from psychological studies to criticize Jorge Garcia’s view of racism. This brief response argues that their critique ...
On the histrograms of the correlation functions of product codes

This paper studies the correlation properties of a family of product codes, obtained as the product of two distinct m-sequences. First we define a set of primary product codes in terms of the two m-sequences. The collection of the auto-correlation functions of the primary product codes are divided into ensembles. It is shown that these ensembles are cyclic shifted versions of the cross-correlation function between the two m-sequences that generate the product code. The relationships between these ensembles are also derived. The auto-correlation histograms of a set of primary product codes corresponding to an integer class are shown to be equal. For the special case of product codes referred to as the Gold codes, obtained as the product of two preferred m-sequences, the amount of unbalance in the autocorrelation histograms of the primary Gold codes are related to the cross-correlation between the preferred m-sequences.
Causality in Life Course Studies

The central premise of life course research is the presumption that no period of life can be understood in isolation from prior experiences, as well as individual’s aspirations for the future. This chapter discusses causal inference methods as they relate to life course research, including regression, propensity score matching, instrumental variables, fixed effects, and quasi-experimental designs. We also discuss strategies for incorporating variation in response to treatment according to heterogeneity, time-variation, and mediation, which are important components to estimating effects over the life course with a causal framework. The chapter aims to explain the assumptions behind the methods we present, and includes intuitive explanations. We also demonstrate the use of the methods discussed with an empirical example using constructed data with a known data generating process of the effects of exposure to violence on educational attainment.
A Rapid Tunable Wavelength Converter Using a GCSR Laser

High speed switching of wavelength converted 10Gb/s data is demonstrated using a Grating Assisted Coupler Sampled Reflector laser. High extinction ratio (>20dBm) and small power penalty over the 30nm wavelength range were observed.