cssi/SciSciGPT-SciSciNet huggingface dataset:
Effect of focal adhesion proteins on endothelial cell adhesion, motility and orientation response to cyclic strain

Focal adhesion proteins link cell surface integrins and intracellular actin stress fibers and therefore play an important role in mechanotransduction and cell motility. When endothelial cells are subjected to cyclic mechanical strain, time-lapse imaging revealed that cells underwent significant morphological changes with their resultant long axes aligned away from the strain direction. To explore how this response is regulated by focal adhesion-associated proteins the expression levels of paxillin, focal adhesion kinase (FAK), and zyxin were knocked down using gene silencing techniques. In addition, rescue of endogenous and two mutant zyxins were used to investigate the specific role of zyxin interactions. Cells with decreased zyxin expression levels and rescue with the mutant lacking zyxin/alpha-actinin binding exhibited lower orientation angles after comparable times of stretching as compared to normal and control cells. However, knockdown of the expression levels of paxillin and FAK and rescue with the mutant lacking zyxin/VASP (vasodilator-stimulated phosphoprotein) binding did not significantly affect the degree of cell orientation. In addition, wound closure speed and cell-substratum adhesive strength were observed to be significantly reduced only for cells with zyxin depletion and the mutation lacking zyxin/alpha-actinin binding. These results suggest that zyxin and its interaction with alpha-actinin are important in the regulation of endothelial cell adhesive strength, motility and orientation response to mechanical stretching.
Mineralogy and Mn geochemistry of laboratory-synthesized dolomite

Abstract Dolomite was synthesized in hydrothermal bombs to assess influences on Mn partitioning into the Mg and Ca sites. Calcite was added to magnesium chloride solutions doped with 0, 10, 20, or 50 ppm Mn. Runs were made for 8 to 241 hr at 192 and 224°C. The calcium content of dolomite increased to 60–64% after 75 hr at 192°C and reverted to stoichiometry thereafter. Increases in the Mn content of the starter solution progressively retarded formation of dolomite. For dolomites formed without added Mn, or formed in less than 40 hr with 10 ppm added Mn, the ESR signals were too broad to permit determination of Mn site distribution ratios. Measurable ratios of Mn in the Mg site to Mn in the Ca site vary as a linear function of time, from 0.3 to 7 for samples prepared at 192°C and from 3 to 16 for those prepared at 224°C. Stoichiometric dolomites have higher Mn partitioning ratios than nonstoichiometric dolomites, as observed in natural systems. Dolomites formed in supratidal/sabkha, early groundwater, and Dorag conditions may differ in their Mn signature from those formed during burial diagenesis.
Man-machine communication in on-line mathematical analysis

During the past four or five years increasing attention has been paid to providing efficient, direct access to digital computing machines. Interactive or "on-line" systems have been implemented on various machines with a variety of programming techniques. Whether the system uses a small computer which can handle only one user-operator or is part of a time-shared multiple-access computing utility, the goal is to permit the user to have direct communication with an operating program. Among other advantages, such an on-line system permits a user to insert decisions during the course of problem solution, with his judgments benefiting from current results.
Monitoring Conformational Changes that Occur to Blood Coagulant Prothrombin as it is Activated to Thrombin

The blood coagulation protein thrombin is originally expressed as the zymogen prothrombin (ProT). Prothrombin contains the F1.2 (Gla + Kringle 1 + Kringle 2) domain and the inactive serine protease prethrombin-2 (PT2). Kringle 2 of F1.2 protects an immature anion binding exosite on ProT called pro-ABE II. The prothrombinase complex converts ProT to thrombin. Cleavage of ProT after R271 releases F1.2 from PT2. Cleavage of PT2 at R320 helps to generate the active, two-chain species thrombin that contains an A and B chain linked by a disulfide. Hydrogen-Deuterium Exchange coupled with MALDI-TOF mass spectrometry was used to monitor the conformational dynamics of ProT, F1.2 + PT2, PT2, and thrombin. During the activation process, the A-chain and the autolysis loop undergo changes in solvent accessibility that respond to the individual R271 and R320 cleavages. The resultant conformational properties aid in creating a protease that can accept substrates at the active site. Importantly, this coagulation protein system also uses anion binding exosites to control its functions. F1.2 protects pro-ABE II on both ProT and PT2 from solvent exposure. Moreover, this binding event exhibits a long-range effect over to pro-ABE I suggesting an influence on development of inter-exosite communication. As F1.2 is removed and PT2 is activated to thrombin, pro-ABE I and II become more solvent exposed and mature into the functional exosites ABE I and II. HSQC NMR titrations with GpIbalpha (269-286, 15N-labeled L275, 15N-labeled D277) demonstrate that ligand binding affinity at pro-ABE II / ABE II increases as ProT is converted to PT2 and then thrombin. The final thrombin enzyme effectively accommodates substrates at its serine protease active site and utilizes its mature exosites to regulate several coagulation related activities.
Enhanced friction of elastomer microfiber adhesives with spatulate tips

Previous studies have demonstrated that gecko foot-hair inspired elastomer microfibers with spatulate tips have significant adhesion enhancement compared to the flat elastomer surface. In this study, we report the friction enhancement of these highly adhesive fibers and analyze the relation between adhesion and friction of elastomer microfiber arrays with spatulate tips. Fabricated polyurethane fiber arrays with spatulate tips demonstrate macroscale static friction pressures up to 41N∕cm2 for a preload pressure of 1.5N∕cm2 on a 6mm diameter smooth glass hemisphere.
Broadband Spectral Reflectance Models of Turfgrass Species and Cultivars to Drought Stress

The objective of this study was to assess canopy broadband spectral reflectance for turfgrasses under drought stress. Optimum turf quality (TQ) and leaf firing (LF) models were developed and compared based on two, three, and five wavelength bands. Sods of bermudagrass (Cynodon dactylon L. × C. transvaalensis Burtt-Davy), seashore paspalum (Paspalum vaginatum Swartz), zoysiagrass (Zoysia japonica Steud.), and St. Augustinegrass [Stenotaphrum secundatum (Walt.) Kuntze], and seeded tall fescue (Festuca arundinacea Schreb.) were used in this study with three cultivars each of bermudagrass, seashore paspalum, and tall fescue. Traditional vegetation indices (VIs) based on two bands within 660 to 950 nm were not as sensitive as three to five broadband models using a wider band range of 660 to 1480 nm. Optimum models were cultivar specific models, even within a species. The broadband wavelength at R900 and R1200 should be considered in drought sensitive spectral models since they were most often observed and exhibited high partial R2 values. These results suggest that mobile broadband spectral devices to map turfgrass responses to drought stress would benefit by the availability of three to five broadbands that could be user selected for optimum, cultivar specific models.
A SIMPLIFIED UNIT FOR EVALUATION OF SOIL CORE RESPIROMETRIC ACTIVITY

A simplified respirometer capable of measuring oxygen uptake and carbon dioxide evolution of large soil samples over extended experimental periods is described. Respirometric activity is calculated by use of conventional manometric procedures. This unit provides a combination of low cost, simplicity and procedural validity which make it applicable to diverse experiments in soil microbiology.
Retinoids differentially regulate the proliferation of colon cancer cell lines.

Abstract In this study, the proliferative effects of retinoids were examined in the MC-26 and LoVo colon adenocarcinoma cell lines. The proliferation of the LoVo cell line was not altered in the presence of the retinoids all trans -retinoic acid ( at RA) and 9- cis -retinoic acid (9- cis -RA). Both retinoids, however, stimulated the growth, as measured by cell proliferation, of MC-26 cells. at RA and 9- cis -RA were equipotent in increasing MC-26 cell proliferation, suggesting that the growth stimulation is mediated by one or more retinoic acid receptors (RARs). To determine the RAR which might be responsible for this growth stimulatory effect, we characterized the RAR subtypes which were present in both cell lines. mRNA for the RARα, RARβ, and RARγ were detected in the MC-26 cell. Of the RARs present in MC-26 cells, the RARα does not mediate the growth stimulatory effects of retinoids, for a selective RARα antagonist was unable to prevent the retinoid-induced increase in MC-26 cell growth. RARα, RARβ, and RARγ mRNA are also expressed in the LoVo cell line; the lack of growth-stimulation by retinoids in LoVo cells, therefore, does not seem to be due to the absence of RARs. The results obtained in these experiments demonstrate that the growth response elicited by retinoids can vary between colon cancer cells and that the differences in response may not be solely determined by the RAR subtypes which are expressed in a colon cancer cell line.
Synthesis of Threose Nucleic Acid (TNA) Phosphoramidite Monomers and Oligonucleotide Polymers

This unit describes the preparation of dimethoxytrityl (DMTr)-protected α-L-threofuranosyl nucleic acid (TNA) phosphoramidite monomers for A, C, G, T, and diaminopurine, as well as their incorporation into TNA oligonucleotides by solid-phase synthesis. Starting from commercially available L-ascorbic acid, the protected threofuranosyl sugar is obtained in four steps. Vorbruggen-Hilbert-Johnson glycosylation affords the desired threofuranosyl nucleosides, which are converted to their corresponding DMTr-protected phosphoramidite nucleosides in four additional steps. Phosphoramidite monomers are then used to construct TNA oligonucleotides by solid-phase synthesis using a standard DNA synthesizer.
High-Yield Expression in E. coli and Refolding of the bZIP Domain of Activating Transcription Factor 5

Activating transcription factor 5 (ATF5) recently has been demonstrated to play a critical role in promoting the survival of human glioblastoma cells. Interference with the function of ATF5 in an in vivo rat model caused glioma cell death in primary tumors but did not affect the status of normal cells surrounding the tumor, suggesting ATF5 may prove an ideal target for anti-cancer therapy. In order to examine ATF5 as a pharmaceutical target, the protein must be produced and purified to sufficient quantity to begin analyses. Here, a procedure for expressing and refolding the bZIP domain of ATF5 in sufficient yield and final concentration to permit assay development and structural characterization of this target using solution NMR is reported. Two-dimensional NMR and circular dichroism analyses indicate the protein exists in the partially α-helical, monomeric x-form conformation with only a small fraction of ATF5 participating in formation of higher-order structure, presumably coiled-coil homodimerization. Despite the persistence of monomers in solution even at high concentration, an electrophoretic mobility shift assay showed that ATF5 is able to bind to the cAMP response element (CRE) DNA motif. Polyacrylamide gel electrophoresis and mass spectrometry were used to confirm that ATF5 can participate in homodimer formation and that this dimerization is mediated by disulfide bond formation.
Fluorine-18 Radiolabeled PET Tracers for Imaging Monoamine Transporters: Dopamine, Serotonin, and Norepinephrine

This article focuses on the development of fluorine-18 radiolabeled PET tracers for imaging the dopamine transporter, serotonin transporter, and norepinephrine transporter. All successful dopamine transporter PET tracers reported to date are members of the 3β-phenyltropane class and are synthesized from cocaine. Currently available carbon-11 serotonin transporter PET tracers come from both the diphenylsulfide and 3β-phenylnortropane class, but so far only the nortropanes have found success with fluorine-18 derivatives. Norepinephrine transporter imaging has so far used carbon-11 and fluorine-18 derivatives of reboxetine but because of defluorination of the fluorine-18 derivatives further research is still necessary.
Defining and computing accessibility radius

In structural molecular biology software, the accessibility of an atom in a molecule to a ball representing solvent is either computed slowly by building a solventaccessible surface, or estimated quickly by counting neighboring atoms within some radius. We believe that techniques from computational geometry, notably retraction motion planning in Voronoi diagrams, can give a more direct measure that is faster than surface computation. We propose an O(nlogn) time algorithm for computing the accessibility radii for sets of points in R 2 , and extend this algorithm to sets of circles in R 2 and sets of spheres in R 3 . We provide results in R 3 that approximates accessibility radii from the power diagram.
Carbon isotopes, time boundaries and evolution

The carbon isotope composition of carbonate rocks in time-boundary zones is interpreted as a reflection of the variations in the total biomass at mass extinction events. Better stratigraphic control and identification of hiatuses can be gained by stable isotope stratigraphic methods than with any other type of stratigraphy. It is suggested that the use of carbon isotopes can help in solving some of the problems confronting palaeontologists and lead to a better understanding of the evolutionary significance of these events.
LDPC coded orthogonal frequency division multiplexing over the atmospheric turbulence channel

LDPC coded optical orthogonal frequency division multiplexing is shown to significantly outperform LDPC coded on-off keying over the atmospheric turbulence channel in terms of both coding gain and spectral efficiency.
Synthesis and Properties of Halogen Derivatives of (sn)x and (ch)x

Abstract : Metallic polymeric sulfur nitride may be halogenated at room temperature to give a series of highly conducting polymers which are also metals. Compositions such as (SNBr0.25)x, (SNBr0.4)x and (SNBr0.55)x may be obtained under varying conditions. The conductivity of (SNBr0.4)x is ten times greater than that of (SN)x itself. Crystalline silvery films of the flexible semiconducting polymer, trans 'polyacetylene', take up halogens with enhanced optical and electrical properties. (CHBr0.05)x and (CHI0.22)x have four and seven orders of magnitude greater room temperature conductivities respectively, than trans-(CH)x.
Polymerase β simulations suggest that Arg258 rotation is a slow step rather than large subdomain motions Per Se

Abstract The large-scale opening motion of mammalian DNA polymerase β is followed at atomic resolution by dynamic simulations that link crystal “closed” and “open” conformations. The closing/opening conformational change is thought to be key to the ability of polymerases to choose a correct nucleotide (through “induced fit”) and hence maintain DNA repair synthesis fidelity. Corroborating available structural and kinetic measurements, our studies bridge static microscopic crystal structures with macroscopic kinetic data by delineating a specific sequence, Phe272 ring flip, large thumb movement, Arg258 rotation with release of catalytic Mg 2+ , together with estimated time-scales, that suggest the Arg258 rearrangement as a limiting factor of large subdomain motions. If similarly slow in the closing motion, this conformational change might be restricted further when an incorrect nucleotide binds and thus play a role in pol β’s selectivity for the correct nucleotide. These results suggest new lines of experimentation in the study of polymerase mechanisms (e.g. enzyme mutants), which should provide further insights into mechanisms of error discrimination and DNA synthesis fidelity.
Experimental evaluation of a model of mental workload

This study was designed to test predictions from a model of mental workload. The model predicts that mental workload grows as perceived distance from a task goal increases and the effective time for action decreases. Decreases in workload can be achieved by actions that bring the task goal into the region of acceptable time/distance constraints for successful resolution. We reported an experiment that tested these assertions using the Timepools performance task. Timepools generates a spatial representation of a shrinking temporal target to assess the effects of path length (i.e., the number of sequential targets to be acquired) and shrink rate (i.e., elapsed time during which the circle is halved in area) on reaction time (RT), movement time (MT), error rate, and the subjective perception of workload. Data from the experiment indicated systematic effects for task-related factors across performance and workload measures. Path length and shrink rate had differential effects on both RT and MT, which were also reflected in the components of the individual workload scales. The results support a general form of the workload model which may help researchers and practitioners in the difficult task of workload prediction. Language: en
Highly sensitive flexible pressure sensors with microstructured rubber dielectric layers

The development of an electronic skin is critical to the realization of artificial intelligence that comes into direct contact with humans, and to biomedical applications such as prosthetic skin. To mimic the tactile sensing properties of natural skin, large arrays of pixel pressure sensors on a flexible and stretchable substrate are required. We demonstrate flexible, capacitive pressure sensors with unprecedented sensitivity and very short response times that can be inexpensively fabricated over large areas by microstructuring of thin films of the biocompatible elastomer polydimethylsiloxane. The pressure sensitivity of the microstructured films far surpassed that exhibited by unstructured elastomeric films of similar thickness, and is tunable by using different microstructures. The microstructured films were integrated into organic field-effect transistors as the dielectric layer, forming a new type of active sensor device with similarly excellent sensitivity and response times.
A FEM Approach to Measure Skempton's B Coefficient for Supercritical CO2-Saturated Rock

Skempton's B coefficient is an important characteristic of a porous medium that describes the way in which pore pressure responds to a change in the mean stress under undrained conditions. This number is well known for many sedimentary rocks under water- and/or oil-saturated conditions. However, due to the difficulty in conducting laboratory tests on supercritical CO2-saturated rock because of the specific requirements in terms of pressure and temperature to ensure the supercritical status of CO2, this number is not available for a supercritical CO2-saturated rock. A finite element method (FEM) approach was developed in an effort to solve this problem. We first calibrated our numerical rock models according to the poroelastic properties of Berea sandstone and Indiana limestone, and conducted a series of numerical tests to measure their Skempton's B coefficients under water-saturated conditions. The test results, which were found to be very close to the laboratory measurements, gave us confidence to extend this testing approach to a CO2-saturated rock by changing the pore fluid from water to supercritical CO2. The numerical test results showed that the Skempton's B coefficient for supercritical CO2-saturated rock is considerably different (lower) than that of water-saturated conditions. This implies that the poromechanical conditions of supercritical CO2-saturated rock are significantly different from those of water- or oil-saturated rock, and the change of pore fluids from water/oil to supercritical CO2 may introduce a significant change in the poromechanical properties of the rock.
B Cell–Specific Deficiencies in mTOR Limit Humoral Immune Responses

Generation of high-affinity Abs in response to Ags/infectious agents is essential for developing long-lasting immune responses. B cell maturation and Ab responses to Ag stimulation require Ig somatic hypermutation (SHM) and class-switch recombination (CSR) for high-affinity responses. Upon immunization with either the model Ag 4-hydroxy-3-nitrophenylacetyl hapten (NP) conjugated to chicken γ globulin lysine (NP-CGG) or heat-killed Streptococcus pneumoniae capsular type 14 protein (Pn14), knock-in (KI) mice hypomorphic for mTOR function had a decreased ability to form germinal centers, develop high-affinity anti-NP-specific or anti-Pn14-specific Abs, and perform SHM/CSR. Hypomorphic mTOR mice also had a high mortality (40%) compared with wild-type (WT) (0%) littermates and had lower pneumococcal surface protein A-specific Ab titers when immunized and challenged with live S. pneumoniae infection. Mice with mTOR deleted in their B cell lineage (knockout [KO]) also produced fewer splenic germinal centers and decreased high-affinity Ab responses to NP-CGG than did their WT littermates. CSR rates were lower in mTOR KI and KO mice, and pharmacologic inhibition of mTOR in WT B cells resulted in decreased rates of ex vivo CSR. RNA and protein levels of activation-induced cytidine deaminase (AID), a protein essential for SHM and CSR, were lower in B cells from both KI and B cell-specific KO mice, concomitant with increases in phosphorylated AKT and FOXO1. Rescue experiments increasing AID expression in KI B cells restored CSR levels to those in WT B cells. Thus, mTOR plays an important immunoregulatory role in the germinal center, at least partially through AID signaling, in generating high-affinity Abs.
A bifurcation study of crack initiation and kinking

Based on a two-dimensional atomistic model, we study the bifurcation associated with crack propagation and kinking. In the study, the varying parameter is the tensile and shear strain applied at the boundary. Both mode-I and mixed mode-I/II loading are considered.
Molecular profiling of breast cancer: clinical implications

Breast cancers are routinely subcategorised on the basis of clinical stage, cellular morphology and immunohistochemical analysis of a small number of markers. The recent development of gene expression microarray and related technologies provides an opportunity to perform more detailed profiling of the disease. It is anticipated that the molecular classification arising from such studies will be more powerful than its pathological predecessor at confining treatment to those patients who are most likely to benefit. It is likely that this will result in a much less frequent use of adjuvant chemotherapy. Furthermore, of those who do receive it, a higher proportion will benefit. If adopted, this will offer considerable patient benefits in terms of reducing unnecessary toxicity and have major health economic implications.
Employment Orientation of Women as a Market Segmentation Variable for Apparel

The purpose of this study was to refine previously established consumer profiles by investigating the influence offemale consumers' employment orientation on apparel decisions and evaluation of imported apparel. A mailing list of 10,000 female consumers, age 25-44, representing all occupations was purchased from The Lifestyle Selector. A random sample of 1,000 female consumers, ages 25-44, was sent questionnaires, resulting in a 43 % (n = 383) return rate. The use of Multivariate Analysis of Variance indicated that employment orientation significantly influenced apparel decisions and the evaluation of imported apparel. Thefour employment orientation groups (Career-Oriented Working Women, Just-a-Job Working Women, Plan-to-Work Housewives, Stay-at-Home Housewives) differed significantly on apparel decisions and the evaluation of imported apparel. Segmentation by employment orientation refined existing consumer profiles, and results reaffirmed that women's employment orientation is an influencing factor in a...
Urokinase-Type Plasminogen Activator in Inflammatory Cell Recruitment and Host Defense against Pneumocystis carinii in Mice

Effective host defense against Pneumocystis carinii depends upon the integrated actions of inflammatory cells and mediators in the lungs. Using immunocompetent and immunosuppressed mice, our laboratory has defined inflammatory changes in the lungs in response to P. carinii. However, the essential molecules and mechanisms required for cellular recruitment and for host defense against P. carinii are undefined. We hypothesized that urokinase-type plasminogen activator (uPA), a protease intimately involved in inflammatory cell migration and activation, is required for clearance of P. carinii. To test this hypothesis in vivo, we compared the intensity of P. carinii infection and inflammation in the lungs of mice lacking the uPA gene (uPA knockout mice) and in the lungs of wild-type mice. After intratracheal inoculation with P. carinii organisms, uPA knockout mice developed uniformly heavy P. carinii pneumonia while wild-type mice cleared the P. carinii inoculum. Bronchoalveolar lavage fluid from uPA knockout mice contained significantly smaller numbers of cells than did lavage fluid from wild-type mice. We conclude that deletion of the uPA gene prevents the clearance of P. carinii and reduces inflammatory cell recruitment. Therefore, uPA is an important participant in the network of inflammatory events required for the clearance of P. carinii, confirming an important role for this molecule in pulmonary host defense against opportunistic pathogens.
The effects of violent video games on aggression.

Violent content video games such as Mortal Kombat and Doom have become very popular among children and adolescents, causing great concern for parents, teachers, and policy makers. This study cumulates findings across existing empirical research on the effects of violent video games to estimate overall effect size and discern important trends and moderating variables. Results suggest there is a smaller effect of violent video games on aggression than has been found with television violence on aggression. This effect is positively associated with type of game violence and negatively related to time spent playing the games. Directions for future programmatic research on video games are outlined. T he arrival of each new communication technology has brought public concern about the influence of the medium on children (Wartella & Reeves, 1985). In the wake of high school tragedies at Paduchah, Kentucky, and Littleton, Colorado, keen public interest has been focused on the effects of violent video games. As has been the case with violent television programs, commentators have lined up to denounce the violence found in video games while the video game industry circles the wagons in defense of its product. Unlike the television controversy, the existing social science research on the impact of video games is not nearly as compelling. Despite over 30 studies, researchers cannot agree if violent-content video games have an effect on aggression. The literature on video game effects is littered with mixed findings from studies that use a wide range of games, treatment exposure times, and subject pools, obscuring clear conclusions. Some researchers claim that playing violent
The Principles and Practice of Evidence-Based Neonatology

Significant strides toward improving the outcome of newborn infants have been observed during the modern era of neonatal-perinatal medicine. One of the challenges that neonatologists and pediatricians face is deciding when to change current practices. New literature is abundant, but it must be critically reviewed and evaluated before changes in practice are made. The evidence-based medicine process can be used to help in changing practices or adopting new practices. It is based on five steps: 1) forming answerable questions; 2) searching for the best evidence; 3) critically appraising the evidence; 4) applying the evidence in practice; and 5) evaluating one's performance. This article reviews the five steps of the evidence-based medicine process. The various levels of evidence, including randomized, controlled trials and systematic reviews, are defined and discussed. An example of a critically appraised topic, a practical tool that can be used as an aid in addressing the first three questions of the evidence-based medicine process, is included. Once the evidence has been evaluated, the decision of whether or not to implement a change in individual practice or in institutional guidelines must be made. These decisions are difficult and require a variety of individual and societal factors to be taken into account. Examples of evidence-based medicine in neonatal and perinatal medicine include the use of antenatal corticosteroids for promotion of lung maturity, the use of surfactant replacement therapy for the treatment and prevention of respiratory distress syndrome, and prophylactic indomethacin for the prevention of intraventricular hemorrhage. Review of these examples provides insight into the strengths and weaknesses of evidence-based medicine.
Simulating Phase Equilibria using Wang-Landau-Transition Matrix Monte Carlo

We will examine the strengths and weaknesses of the Wang-Landau and transition matrix Monte Carlo methods for simulating phase equilibria of continuous molecular systems alone and as a combined Wang-Landautransition matrix Monte Carlo algorithm. Although a combined Wang-Landau transition matrix Monte Carlo algorithm has been previously reported in the literature, the details of the method and a discussion of its performance for phase equilibria simulations has not been presented. The hybrid method combines the rapid initial estimate of the density of states from the Wang-Landau algorithm with the continual improvement in convergence of transition matrix Monte Carlo. The hybrid Wang-Landau-transition matrix (WL-TM) algorithm is found to be more efficient and has much better convergence properties than the Wang-Landau algorithm and is more robust than the transition matrix algorithm, enabling the simulations to reach relatively low reduced temperatures with ease.
Local Character of Readthrough Activation in Adenovirus Type 5 Early Region 1 Transcription Control

Wild-type early activity of the adenovirus 5 E1b gene promoter requires readthrough transcription originating from the adjacent upstream E1a gene. This unusual mode of viral transcription activation was identified by genetic manipulation of the mouse βmaj-globin gene transcription termination sequence (GGT) inserted into the E1a gene. To facilitate further study of the mechanism of readthrough activation, the activities of GGT and a composite termination sequence CT were tested in recombinant adenoviruses containing luciferase reporters driven by the E1b promoter. There was a strict correlation between readthrough and substantial downstream gene expression, indicating that interference with downstream transcription was not a unique property of GGT. Blockage of readthrough transcription of E1a had no apparent effect on early expression of the major late promoter, the next active promoter downstream of E1b. A test for epistatic interaction between termination sequence insertions and E1a enhancer mutations suggested that readthrough activation and E1a enhancer activation of the E1b promoter are mechanistically distinct. In addition, substitution of the human cytomegalovirus major immediate-early promoter for the E1b promoter suppressed the requirement for readthrough. These results suggest that readthrough activation is a “local” effect of a direct interaction between the invading transcription elongation complex and the E1b promoter. DNase I hypersensitivity footprinting provided evidence that this interaction altered an extensive E1b promoter DNA-protein complex that was assembled in the absence of readthrough transcription.
Complete-k-distinguishability for retiming and resynthesis equivalence checking without restricting synthesis

Iterative retiming and resynthesis is a powerful way to optimize sequential circuits but its massive adoption has been hampered by the hardness of verification. This paper tackles the problem of retiming and resynthesis equivalence checking on a pair of circuits. For this purpose we define the Complete-k-Distinguishability (C-k-D) property for any natural number k based on C-1-D. We show how the equivalence checking problem can be simplified if the circuits satisfy this property and prove that the method is complete for any number of retiming and resynthesis steps. We also provide a way to enforce C-k-D on the circuits without restricting the optimization power of retiming and resynthesis or increasing their complexity. Experimental results demonstrate that enforcing C-k-D property can speed up the verification process.
A single copy of apolipoprotein B-48 is present on the human chylomicron remnant

Individuals homozygous for the e2 allele encoding apolipoprotein E exhibit a remnant removal defect and accumulate substantial levels of intestinally derived particles containing apolipoprotein B-48 (apoB-48). Such lipoproteins were isolated from the plasma of E2/E2 individuals, and further purified by affinity chromatography using a polyclonal antibody specific for selective binding and removal of apoB-100-containing lipoproteins. The unbound lipoproteins, termed chylomicron remnants, were particles with average hydrated diameters of 31.2 nm as determined by dynamic light scattering. They contained apoB-48 and ApoE as their only protein components. The number of apoB-48 molecules on each lipoprotein was assessed by counting the number of antibody molecules bound to the surface of the chylomicron remnants, using either a monoclonal antibody specific for a single epitope on apoB-48 or a mixture of two such monoclonal antibodies specific for widely separated epitopes. The results of this analysis seem unambiguous: no more than one apoB-48 resides on the chylomicron remnant. Because apoB appears to be unable to transfer among lipoprotein particles, it may be inferred that nascent chylomicrons also contain a single copy of apoB-48.
Measuring the lipid content of live animals using cyclopropane gas

The cyclopropane technique was validated, and it accurately estimated the lipid mass of six pond turtles (Trachemys scripta). This technique provided more accurate estimates of lipid mass and lipid-free mass (by difference) than other nonfatal techniques. This technique was accurate despite the turtles' low lipid contents (0.71-3.5% of body mass), variable water contents (65-74% of body mass), and variable body temperatures (approximately 23-31 degrees C). A computer model of the cyclopropane technique revealed that an analytical error of 1% in variables measured (e.g., body water content and body temperature) may cause errors of less than 1-6% in lipid estimates.
ACT Workcover and the Failed 1997 Implosion: A Case Study of the Role of the Inspectorate

The failed implosion of the old Canberra Hospital buildings on Sunday 13 July 1997 resulted in an explosion which blasted masonry and steel debris beyond the 200 metre exclusion zone to where thousands of spectators stood watching on the shore of Lake Burley Griffin. A young spectator, Katie Bender, was killed instantly when struck by a fragment of that debris. At the Bender Inquest the Coroner, Mr Shane Madden, described the implosion project as having failed systemically. He attributed the failure to: the Project Manager’s and contractors’ lack of appropriate competencies; the absence of input from independent engineers and explosives experts; inappropriate action by the ACT Chief Minister’s Office and Department in promoting the implosion as a public event; and failure of the regulatory agencies to properly discharge their functions. It is clear, in retrospect, that the wholesale underestimation of the risk to public safety was a significant factor in this litany of failures. The public safety risk inherent in the implosion project as it was implemented, was unrecognized, discounted or underestimated by all the parties involved at all stages of the project. This study, with the great benefit of hindsight, examines why this occurred and how it affected the role of ACT WorkCover and those inspectors directly involved. Specifically it examines how the particular circumstances of the implosion project combined with the situation and practice of WorkCover to influence the inspectors’ assessment of the inherent risks and the exercise of their regulatory enforcement powers.
Whole-animal imaging with high spatio-temporal resolution

We developed isotropic multiview (IsoView) light-sheet microscopy in order to image fast cellular dynamics, such as cell movements in an entire developing embryo or neuronal activity throughput an entire brain or nervous system, with high resolution in all dimensions, high imaging speeds, good physical coverage and low photo-damage. To achieve high temporal resolution and high spatial resolution at the same time, IsoView microscopy rapidly images large specimens via simultaneous light-sheet illumination and fluorescence detection along four orthogonal directions. In a post-processing step, these four views are then combined by means of high-throughput multiview deconvolution to yield images with a system resolution of ≤ 450 nm in all three dimensions. Using IsoView microscopy, we performed whole-animal functional imaging of Drosophila embryos and larvae at a spatial resolution of 1.1-2.5 μm and at a temporal resolution of 2 Hz for up to 9 hours. We also performed whole-brain functional imaging in larval zebrafish and multicolor imaging of fast cellular dynamics across entire, gastrulating Drosophila embryos with isotropic, sub-cellular resolution. Compared with conventional (spatially anisotropic) light-sheet microscopy, IsoView microscopy improves spatial resolution at least sevenfold and decreases resolution anisotropy at least threefold. Compared with existing high-resolution light-sheet techniques, such as lattice lightsheet microscopy or diSPIM, IsoView microscopy effectively doubles the penetration depth and provides subsecond temporal resolution for specimens 400-fold larger than could previously be imaged.
Engineering a Bioartificial Liver Device (Keynote)

Fulminant hepatic failure is a clinical syndrome associated with a high mortality rate. Orthotopic liver transplantation is the only clinically proven effective treatment for patients with end-stage liver disease who do not respond to medical management. A major limitation of this treatment modality is the scarcity of donor organs available, resulting in patients dying while waiting for a donor liver. An extracorporeal bioartificial liver (BAL) device containing viable hepatocytes has the potential to provide temporary hepatic support to liver failure patients, serving as a bridge to transplantation while awaiting a suitable donor. In some patients, providing temporary hepatic support may be sufficient to allow adequate regeneration of the host liver, thereby eliminating the need for a liver transplant. Although the BAL device is a promising technology for the treatment of liver failure, there are several technical challenges that must be overcome in order to develop systems with sufficient processing capacity and of manageable size. In this overview, the authors describe the critical issues involved in developing a BAL device. They also discuss their experiences in hepatocyte culture optimization within the context of a microchannel flat-plate BAL device.Copyright © 2005 by ASME
Supercritical Fischer-Tropsch Synthesis: Heavy Aldehyde Production and the Role of Process Conditions

Supercritical Fischer-Tropsch Synthesis (SC-FTS) using a potassium-promoted iron-based catalyst has been shown to produce large amounts of heavy (C10+) aldehydes and methyl ketones, while traditional gas phase FTS does not produce these compounds in significant amounts under either fixed or slurry bed operation. In order to better understand this behavior, a series of studies was undertaken to determine the effect of process conditions (H2/CO ratio, temperature, pressure, and supercritical hexanes media ratio) on the performance of iron-based SC-FTS generally, and on aldehyde formation specifically. Over the range of process conditions studied, heavy aldehyde selectivity was found to decrease with increasing temperature, while both elevated pressure and increased media ratio favored aldehyde production. Changes in the H2/CO ratio had little influence on syncrude functionality. The role of potassium promotion was also investigated by operating a potassium-free iron-based catalyst under SC-FTS conditions. I...
Discharge clinical characteristics and 60-day readmission in patients hospitalized with heart failure

Background Heart failure is a clinical syndrome that incurs a high prevalence, mortality, morbidity, and economic burden in our society. Patients with heart failure may experience hospitalization because of an acute exacerbation of their condition. Recurrent hospitalizations soon after discharge are an unfortunate occurrence in this patient population. Objective The purpose of this study was to explore the clinical and diagnostic characteristics of individuals hospitalized with a primary diagnosis of heart failure at the time of discharge and to compare the association of these indicators in individuals who did and did not experience a heart failure hospitalization within 60 days of the index stay. Methods The study is a descriptive, correlational, quantitative study using a retrospective review of 134 individuals discharged with a primary diagnosis of heart failure. Records were reviewed for sociodemographic characteristics, health histories, clinical assessment findings, and diagnostic information. Results Significant predictors of 60-day heart failure readmissions were dyspnea (β = 0.579), crackles (β = 1.688), and assistance with activities of daily living (β = 2.328), independent of age, gender, and multiple other factors. By using hierarchical logistical regression, a model was derived that demonstrated the ability to correctly classify 77.4% of the cohort, 78.2% of those who did have a readmission (sensitivity of the prediction), and 76.7% of the subjects in whom the predicted event, readmission, did not occur (specificity of the prediction). Conclusion Hospitalizations for heart failure are markers of clinical instability. Future events after hospitalization are common in this patient population, and this study provides a novel understanding of clinical characteristics at the time of discharge that are associated with future outcomes, specifically 60-day heart failure readmissions. A consideration of these characteristics provides an additional perspective to guide clinical decision making and the evaluation of discharge readiness.
Identification of a previously unobserved dissociative ionization pathway in time-resolved photospectroscopy of the deuterium molecule.

Citation: Cao, W., Laurent, G., Ben-Itzhak, I., & Cocke, C. L. (2015). Identification of a Previously Unobserved Dissociative Ionization Pathway in Time-Resolved Photospectroscopy of the Deuterium Molecule. Physical Review Letters, 114(11), 5. doi:10.1103/PhysRevLett.114.113001
Design and application of PDM system based on Web

PDM is the technology that manages the product information and process. It is helpful for enterprise to manage and control product data in the lifecycle of PDM. First, this paper introduces the concept and architecture of PDM based on Web technology. Secondly, the workflow of development and advantage of Web-based PDM system are presented. Finally, the projects of PDM system are showed by an example.
Fos is required for EGF stimulation of the gastrin promoter

Gastrin gene expression is regulated by developmental cues, pH, and inflammation. These processes are mediated by various extracellular ligands, e.g., growth factors, cytokines, and neuropeptides that also stimulate c-fos gene expression. Therefore, to determine whether Fos is required for stimulation of the gastrin promoter, a c-fos sense expression vector was coexpressed with a gastrin reporter construct in a GH4 rat pituitary cell line. We found that epidermal growth factor (EGF) and tumor necrosis factor-alpha (TNF-alpha) transiently stimulate an increase in Fos protein that precedes stimulation of the gastrin promoter. However, the induction mediated by TNF-alpha was weaker than that mediated by EGF, indicating minimal overlap of the signaling pathways activated by EGF and TNF-alpha. Accordingly, overexpression of c-fos mRNA facilitated primarily EGF rather than TNF-alpha induction of the gastrin promoter. Expression of the c-fos gene in the absence of ligand did not stimulate the gastrin promoter. Thus c-fos gene expression is required but is not sufficient for induction of the gastrin promoter by EGF.
Domestic Inequality and Carbon Emissions in Comparative Perspective

Drawing from multiple bodies of literature, the authors investigate the relationship between consumption-based carbon emissions and domestic income inequality for 67 nations from 1991 to 2008. Results of two-way fixed-effects longitudinal models indicate that the relationship between national-level emissions and inequality changes through time and varies for nations in different macroeconomic contexts. For high-income nations, the relationship shifts from negative to positive, suggesting that in recent years, income inequality in such nations increases carbon emissions. For middle-income nations, the association is negative, and becomes increasingly negative in the later years of the study. For low-income nations, the relationship between carbon emissions and domestic income inequality is null for the entire 1991 to 2008 period. These diverse results hold, net of the effects of other well-established human drivers of emissions, including population size, level of economic development, and urbanization. The authors conclude by emphasizing the need for future research on greenhouse gas emissions and domestic inequality, and the central role that sociology should play in this emerging area of inquiry.
Cutting Edge: Commensal Microbiota Has Disparate Effects on Manifestations of Polyglandular Autoimmune Inflammation

Polyglandular autoimmune inflammation accompanies type 1 diabetes (T1D) in NOD mice, affecting organs like thyroid and salivary glands. Although commensals are not required for T1D progression, germ-free (GF) mice had a very low degree of sialitis, which was restored by colonization with select microbial lineages. Moreover, unlike T1D, which is blocked in mice lacking MyD88 signaling adaptor under conventional, but not GF, housing conditions, sialitis did not develop in MyD88(-/-) GF mice. Thus, microbes and MyD88-dependent signaling are critical for sialitis development. The severity of sialitis did not correlate with the degree of insulitis in the same animal and was less sensitive to a T1D-reducing diet, but it was similar to T1D with regard to microbiota-dependent sexual dimorphism. The unexpected distinction in requirements for the microbiota for different autoimmune pathologies within the same organism is crucial for understanding the nature of microbial involvement in complex autoimmune disorders, including human autoimmune polyglandular syndromes.
Report on the National Commission: Good as Gold

The National Commission for the Protection of Human Subjects of Bio-medical and Behavioral Research ended its work by substantially endorsing the status quo which places primary reliance on local Institutional Review Boards for subject protection. This was predictable because of the commission's researcher-dominated composition which permitted it to assume that(1) research is good;(2) experimentation is almost never harmful to subjects; and (3) researcher-dominated IRBs can adequately protect the interests of human subjects. The successor Presidential Commission can learn much by reexamining these premises.