cssi/SciSciGPT-SciSciNet huggingface dataset:
Altered spectra of hypermutation in DNA repair–deficient mice

Affinity maturation of the humoral immune response is based on the ability of immunoglobulin variable genes to undergo a process of rapid and extensive somatic mutation followed by antigenic selection for antibodies with higher affinity. While the behaviour of this somatic hypermutation phenomenon has been well characterized over the last 20 years, the molecular mechanism responsible for inserting mutations has remained shrouded. To better understand this mechanism, we studied the interplay between hypermutation and other DNA associated activities such as DNA repair. There was no effect on the frequency and pattern of hypermutation in mice deficient for nucleotide excision repair, base excision repair and ataxia-telangiectasia mutated gene repair of double strand breaks. However, variable genes from mice lacking some components of mismatch repair had an increased frequency of tandem mutations and had more mutations of G and C nucleotides. These results suggest that the DNA polymerase(s) involved in the hypermutation pathway produces a unique spectra of mutations, which is then altered by mismatch repair and antigenic selection. We, also describe the differential pattern of expression of some nuclear DNA polymerases in hypermutating versus non-hypermutating B lymphocytes. The rapidly dividing germinal centre B cells expressed DNA polymerases alpha, beta, delta, epsilon and zeta, whereas the resting non-germinal centre cells did not express polymerases alpha or epsilon at detectable levels, although they did express polymerases beta, delta and zeta. The lack of expression of polymerase epsilon in the non-germinal centre cells suggests that this enzyme has a critical role in chromosomal replication but does not participate in DNA repair in these cells.
Electricity purchase agreements and distributed energy policies for anaerobic digesters

Abstract Anaerobic digestion is increasingly recognized for its ability to produce renewable energy and reduce greenhouse gas emissions from livestock operations. In 2010, there were 2645 U.S. dairy farms with herd sizes large enough to support anaerobic digesters, yet only 156 systems were in operation (U.S. Environmental Protection Agency (U.S. EPA), 2010a. Market Opportunities for Biogas Recovery Systems at U.S. Livestock Facilities. AgSTAR Program; U.S. Environmental Protection Agency (U.S. EPA), 2011. Operational Anaerobic Digesters, Sorted by State (Dairy). AgSTAR Program.). 1 This study analyzes the net present value of digester systems under alternative electricity purchase agreements and how returns are affected by standby charges, net metering policies and the use of feed-in-tariffs. In order for digester potential to be fully realized on a state or national level, changes to distributed energy policy are required. Results indicated that standby charges can reduce revenues from offsetting electricity by an average of nearly 20%. Net metering rules limit participation among larger farms and negatively affect profitability by restricting engine–generator size. Lastly, the effectiveness of a fixed price feed-in-tariff policy for digesters is significantly affected by project size differentiation. Digester energy policies are similar nationwide, making this study useful for government regulatory agencies and digester owners throughout the U.S.
Ultrastructural changes in the liver after chronic exposure to methylmercury.

Abstract Adult male rats were injected daily with 1.0 mg/kg methylmercuric chloride for 5 weeks. Tissue samples from the liver were obtained at time intervals of 1, 2, 3, 4, 5, and 11 weeks for electron microscopic examination. A moderate accumulation of glycogen and proliferation of smooth endoplasmic reticulum was found in many hepatocytes after 1–2 weeks of intoxication. Swelling, pleomorphic, and degenerative changes of the hepatic mitochondria could be observed after the second week of methylmercury administration. After 3–5 weeks of intoxication, increased peribiliary accumulation of lysosomes, and large areas of focal cytoplasmic degradation were prominent pathological findings. Moderate accumulation of lipoprotein granules within dilated cisternae of the smooth endoplasmic reticulum and Golgi vesicle was observed in some hepatocytes after 5 weeks of continuous exposure to methylmercury. Large cytosegresomes containing various degenerating organelles were a frequent observation throughout the experimental period. Many of these cytosegresomes were being extruded into the sinusoidal spaces and engulfed by the Kupffer cells. At the eleventh week (6 weeks of recovery), various degenerative changes still could be found in some hepatocytes. Such long-lasting pathological changes in the liver are believed to be due to the effects of the residual and the recirculating mercury.
Conformational Effects on Reversed-Phase Chromatography of Proteins with Particle Beam LC/FT-IR Spectrometry and Free Solution Capillary Electrophoresis

In this study, reversed-phase HPLC (RPC), particle beam FT-IR spectrometry, and capillary electrophoresis (CE) were employed to ascertain the dynamic conformational structure empirically of various forms of bovine ribonuclease A (RNase A) to investigate the interdependence of protein conformation and RPC separation. RNase A was analyzed in four conformational states: native, partially denatured, completely unfolded, and completely unfolded and disulfide-reduced (denatured). Each form was analyzed individually and produced similar multizoned RPC profiles composed of several low-response peaks before the primary peak. Particle beam FT-IR spectrometry results from the RPC fractions of the partially denatured and unfolded forms were identical to one another and exhibited a loss of ordered structure. The infrared spectra of the RNase A that was introduced into the HPLC in the denatured and reduced form showed an excess of β-sheet content, particularly the primary peak. We believe this to be a non-native form ...
Pushing the Frontier of High-Definition Ion Mobility Spectrometry Using FAIMS

Differential ion mobility spectrometry (FAIMS) separates ions in gases based on the difference between their mobilities in strong and weak electric fields, captured directly employing a periodic waveform with dissimilar profiles in opposite polarities. As that difference is not tightly correlated with the ion size or mass, FAIMS separations are generally quite orthogonal to both conventional IMS (based on the absolute ion mobility that reflects the physical ion size) and mass spectrometry (based on mass). Until a few years ago, that advantage was largely offset by poor FAIMS resolving power (∼10–20), an order of magnitude below that achieved with conventional (drift-tube) IMS. This article summarizes the major recent technical developments that have raised FAIMS resolving power up to ∼500. These include use of higher and more stable voltages provided by new waveform generators, novel buffer gas compositions comprising high helium or hydrogen fractions, and extended filtering times up to ∼1 s. These advances have enabled previously unthinkable analyses such as broad baseline separations of peptide sequence inversions, localization variants (post-translationally modified peptides with differing PTM attachment sites) even for the larger “middle-down” peptides and smallest PTMs, and lipid regioisomers.
Small-Molecule Analysis with Silicon-Nanoparticle-Assisted Laser Desorption/Ionization Mass Spectrometry

Silicon nanopowder (5−50 nm) was applied as a matrix for the analysis of small molecules in laser desorption/ionization mass spectrometry. In contrast with conventional matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry, the matrix background interference in the low mass range was significantly reduced. Effects of the particle size and sample preparation procedures on the background mass spectra and the analyte signal intensity have been investigated, and an optimized powder and sample preparation protocol was established. Several surface characterization tools have been applied as well. Both positive mode and negative mode laser desorption/ionization have been applied to different analytes including drugs, peptides, pesticides, acids, and others. Detection limits down to the low femtomole per microliter levels were achieved for propafenone and verapamil drugs. The method developed was found relatively tolerant to salt contamination, which allowed the direct analysis of m...
Micro stereo lithography for 3D MEMS devices

Micro Stereo Lithography (MSL) is a poor man's LIGA for fabricating high aspect ratio MEMS devices in UV curable semiconducting polymers using either two computer-controlled low inertia galvanometric mirrors with the aid of focusing lens or an array of optical fibers. This technique has also been successfully used recently for fabricating 3D metallic and ceramic MEMS devices. Microfabrication techniques such as bulk micromachining and surface micromachining currently employed to conceive MEMS are largely derived from the standard IC and microelectronics technology. Even though many MEMS devices with integrated electronics have been achieved by using the traditional micromachining techniques, some limitations have nevertheless to be underlined: (1) these techniques are very expensive and need specific installations as well as a cleanroom environment, (2) the materials that can be used up to now are restricted to silicon and metals, (3) the manufacture of 3D parts having curved surfaces or an important number of layers is not possible. Moreover, for some biological applications, the materials used for sensors must be compatible with human body and the actuators need to have high strain and displacement which the current silicon based MEMS do not provide. It is thus natural for the researchers to 'look' for alternative methods to make 3D sensors and actuators using polymeric based materials. For MSL techniques to be successful as their silicon counterparts, one has to come up with multifunctional polymers. These multifunctional polymers have not only a high sensing capability but also a high strain and actuation performance. With the invention of organic thin film transistor, now it seems possible to fabricate polymeric based MEMS devices with built-in- electronics. Moreover, with combined architecture techniques, one can integrate silicon devices with the polymeric ones without much difficulty. In this paper, the applications of MSL for polymer and ceramic based microstructures and MEMS are discussed with some examples.
Emission characteristics of porous tubing

Abstract Porous irrigation tubing (10 mm dia) (Irrigro®) was tested to characterize the emission rate as a function of supply pressure, particulate content of the water, and start-up pressure. Emission rate declined to a steady value using unfiltered water after about 10 days with a constant pressure. After a start-up pressure of 30 kPa, the relationship between subsequent supply pressures and emission rate was linear with a slope of 0.0777 ml/min per meter of tubing per kPa of supplied pressure. With filtered water, the emission rate was more than 10 times higher for the same supply pressure.
Serial exposure technique for assessing performance of wood preservatives

The performance of copper-chrome-arsenate (CCA) and two quaternary ammonium compounds as wood preservatives was compared using a serial exposure technique, involving successive 10-week exposures in conventional soil jars. All preservative treatments were successful in preventing decay of Pinus radiata sapwood after the first exposure, but successive 10-week exposures clearly distinguished those treatments likely to offer long-term protection. The progressively increasing times of exposure with test fungi overcame the time lag for decay initiation in wood treated to preservative retentions above the toxic threshold established by conventional laboratory methods. Consequently, an additional and higher toxic threshold could be calculated. Examination of data from field stake tests suggested that a series of toxic thresholds established by a serial exposure technique could be related to preservative retentions which protect wood in the field from decay for increasing periods of time. Results of all tests are discussed in relation to the development of a laboratory procedure which may predict field performance of wood preservatives.
Acetylcholine receptor channels on adult mouse skeletal muscle are functionally identical in synaptic and nonsynaptic membrane

Abstract It has been proposed that acetylcholine receptor channels exhibit a functionally distinct "junctional" form at the region of synaptic contact between nerve and muscle. As a direct test of this idea, we compared acetylcholine-activated single-channel currents from the synaptic membrane to those obtained from nonsynaptic sites on freshly dissociated adult mouse toe muscle. We observed, at locations along the entire length of the cell, openings by a channel with a high conductance (70 pS) and brief open time (approximately 2 msec), characteristic of the classical "junctional type" of acetylcholine receptor. In 8 out of 10 synaptic and in 9 out of 19 nonsynaptic recordings, we also observed infrequent openings by a low-conductance (45-pS) channel traditionally associated only with nonsynaptic regions. In these recordings the low-conductance acetylcholine receptor channel averaged only 3% of the total channel openings. Comparisons of synaptic and nonsynaptic patches indicated no trend toward an increased proportion of low-conductance channel openings with increased distance from the synapse. These findings support the view that the functional properties of the acetylcholine receptor channel do not depend on proximity to the synapse in innervated mouse skeletal muscle.
A hybrid microfluidic-vacuum device for direct interfacing with conventional cell culture methods

Background: Microfluidics is an enabling technology with a number of advantages over traditional tissue culture methods when precise control of cellular microenvironment is required. However, there are a number of practical and technical limitations that impede wider implementation in routine biomedical research. Specialized equipment and protocols required for fabrication and setting up microfluidic experiments present hurdles for routine use by most biology laboratories. Results: We have developed and validated a novel microfluidic device that can directly interface with conventional tissue culture methods to generate and maintain controlled soluble environments in a Petri dish. It incorporates separate sets of fluidic channels and vacuum networks on a single device that allows reversible application of microfluidic gradients onto wet cell culture surfaces. Stable, precise concentration gradients of soluble factors were generated using simple microfluidic channels that were attached to a perfusion system. We successfully demonstrated realtime optical live/dead cell imaging of neural stem cells exposed to a hydrogen peroxide gradient and chemotaxis of metastatic breast cancer cells in a growth factor gradient. Conclusion: This paper describes the design and application of a versatile microfluidic device that can directly interface with conventional cell culture methods. This platform provides a simple yet versatile tool for incorporating the advantages of a microfluidic approach to biological assays without changing established tissue culture protocols.
Learning to talk in a gesture-rich world: Early communication in Italian vs. American children

Italian children are immersed in a gesture-rich culture. Given the large gesture repertoire of Italian adults, young Italian children might be expected to develop a larger inventory of gestures than American children. If so, do these gestures impact the course of language learning? We examined gesture and speech production in Italian and US children between the onset of first words and the onset of two-word combinations. We found differences in the size of the gesture repertoires produced by the Italian vs. the American children, differences that were inversely related to the size of the children's spoken vocabularies. Despite these differences in gesture vocabulary, in both cultures we found that gesture + speech combinations reliably predicted the onset of two-word combinations, underscoring the robustness of gesture as a harbinger of linguistic development.
Magma ocean fractional crystallization and cumulate overturn in terrestrial planets: Implications for Mars

Crystallization of a magma ocean on a large terrestrial planet that is significantly melted by the energy of accretion may lead to an unstable cumulate density stratification, which may overturn to a stable configuration. Overturn of the initially unstable stratification may produce an early basaltic crust and differentiated mantle reservoirs. Such a stable compositional stratification can have important implications for the planet's subsequent evolution by delaying or suppressing thermal convection and by influencing the distribution of radiogenic heat sources. We use simple models for fractional crystallization of a martian magma ocean, and calculate the densities of the resulting cumulates. While the simple models presented do not include all relevant physical processes, they are able to describe to first order a number of aspects of martian evolution. The models describe the creation of magma source regions that differentiated early in the history of Mars, and present the possibility of an early, brief magnetic field initiated by cold overturned cumulates falling to the core- mantle boundary. In a model that includes the density inversion at about 7.5 GPa, where olivine and pyroxene float in the remaining magma ocean liquids while garnet sinks, cumulate overturn sequesters alumina in the deep martian interior. The ages and compositions of source regions are consistent with SNC meteorite data.
The Neuropeptide Saga

Neuropeptides are regulatory molecules produced by neural and non-neural tissues. They are engaged in multiple forms of receptor-mediated intercellular communication,ranging from hormonal (blood-borne) to close-range (synapse-like) signalling. In their neurohormonal capacity, these peptides convey directives from the nervous to the endocrine system, as well as to terminal target tissues. As participants in interneuronal chemical communication, neuropeptides may act as neurotransmitters, or as modulators of signals exchanged between synaptically linked neurons. Outside the realms of neuroendocrinology and neurobiology, peptidergic messenger substances carry out a variety of functions, including autoregulatory and integrative activities in the immune system
Real-time parallel optical analog-to-digital conversion

A technique for optically performing parallel analog-to-digital conversion on incoherent two-dimensional inputs at real-time rates is described. The system uses a birefringent optical real-time input transducer combined with a detector array and optical thresholding. Quantization and bit plane outputs are produced in parallel without scanning. An experimental system with three-bit accuracy is described.
Light adaptation in retinal rods of the rabbit and two other nonprimate mammals.

The responses of rabbit rods to light were studied by drawing a single rod outer segment projecting from a small piece of retina into a glass pipette to record membrane current. The bath solution around the cells was maintained at near 40 degrees C. Light flashes evoked transient outward currents that saturated at up to approximately 20 pA. One absorbed photon produced a response of approximately 0.8 pA at peak. At the rising phase of the flash response, the relation between response amplitude and flash intensity (IF) had the exponential form 1-e-kappa FIF (where kappa F is a constant denoting sensitivity) expected from the absence of light adaptation. At the response peak, however, the amplitude-intensity relation fell slightly below the exponential form. At times after the response peak, the deviation was progressively more substantial. Light steps evoked responses that rose to a transient peak and rapidly relaxed to a lower plateau level. The response-intensity relation again indicated that light adaptation was insignificant at the early rising phase of the response, but became progressively more prominent at the transient peak and the steady plateau of the response. Incremental flashes superposed on a steady light of increasing intensity evoked responses that had a progressively shorter time-to-peak and faster relaxation, another sign of light adaptation. The flash sensitivity changed according to the Weber-Fechner relation (i.e., inversely) with background light intensity. We conclude that rabbit rods adapt to light in a manner similar to rods in cold-blooded vertebrates. Similar observations were made on cattle and rat rods.
Advancing Treatment Options for Influenza: Challenges With the Human Influenza Challenge

Current therapeutic options for the treatment of influenza virus infections are limited. Only 2 classes of agents have licensed products, neuraminidase (NA) inhibitors and M2 inhibitors, and only NA inhibitors are active against currently circulating seasonal viruses. While observational studies show a benefi to f NA inhibitor treatment for hospitalized patients with influenza [1], optimal treatment for severely ill patients and those who are immunocompromised will likely require additional treatment options with a different mechanism of action. Since the 1918 pandemic, convalescent serum or plasma from persons previously infected with influenza virus has been investigated as treatment for individuals with severe influenza virus infection, including, more recently, individuals with human avian influenza and 2009 pandemic A(H1N1) infections [2, 3]. However, receipt of convalescent serum can be associated with severe adverse effects, and the resources necessary to produce such serum in large quantities are prohibitive [2]. Compared with convalescent serum, human monoclonal antibodies (mAbs) against influenza viruses may be more feasible for widespread use, without the adverse effects associated with human blood products. However, identifying a human mAb that can reproduce the clinical anti–influenza virus effects of polyclonal convalescent serum is a challenge. A handful of mAbs against influenza virus proteins are currently in early phases of evaluation for human use [4]. In this issue of The Journal of Infectious Diseases, Ramos et al report results from ah uman influenza challenge study evaluating the effect on clinical illness of a human mAb targeting the external portion (ie, ec
Nucleases: diversity of structure, function and mechanism

Nucleases cleave the phosphodiester bonds of nucleic acids and may be endo or exo, DNase or RNase, topoisomerases, recombinases, ribozymes, or RNA splicing enzymes. In this review, I survey nuclease activities with known structures and catalytic machinery and classify them by reaction mechanism and metal-ion dependence and by their biological function ranging from DNA replication, recombination, repair, RNA maturation, processing, interference, to defense, nutrient regeneration or cell death. Several general principles emerge from this analysis. There is little correlation between catalytic mechanism and biological function. A single catalytic mechanism can be adapted in a variety of reactions and biological pathways. Conversely, a single biological process can often be accomplished by multiple tertiary and quaternary folds and by more than one catalytic mechanism. Two-metal-ion-dependent nucleases comprise the largest number of different tertiary folds and mediate the most diverse set of biological functions. Metal-ion-dependent cleavage is exclusively associated with exonucleases producing mononucleotides and endonucleases that cleave double- or single-stranded substrates in helical and base-stacked conformations. All metal-ion-independent RNases generate 2',3'-cyclic phosphate products, and all metal-ion-independent DNases form phospho-protein intermediates. I also find several previously unnoted relationships between different nucleases and shared catalytic configurations.
Colesevelam hydrochloride for the treatment of type 2 diabetes mellitus.

Abstract Background: Colesevelam hydrochloride is a bile acid sequestrant approved in January 2008 by the US Food and Drug Administration (FDA) for the treatment of adult patients with type 2 diabetes mellitus (DM) in combination with a sulfonylurea, metformin, and/or insulin therapy. Objective: The purpose of this article was to review the pharmacology, pharmacokinetics, efficacy, adverse effects and tolerability, drug-drug interactions, contraindications/precautions, dosage and administration, pharmacoeconomics, and the overall role of colesevelam in the management of adult patients with type 2 DM. Methods: A literature search using MEDLINE (1966–October 27, 2008), PubMed (1950–October 27, 2008), Science Direct (1994–October 27, 2008), Web of Science (1980–October 27, 2008), American Diabetes Association Scientific Abstracts (2004–2008), and International Pharmaceutical Abstracts (1970–October 27, 2008) was performed using the term colesevelam . English-language, original research and review articles were examined, and citations from these articles were assessed. Manufacturer prescribing information and the FDA review of the new drug application for colesevelam were also examined. Results: Colesevelam is a hydrophilic, water-insoluble polymer, with negligible absorption and systemic distribution, that is excreted primarily in the feces. Through a mechanism still under investigation, colesevelam effectively lowers glycosylated hemoglobin (HbA 1c ) when used in combination with a sulfonylurea, metformin, and/or insulin therapy. Three completed, published Phase III clinical trials investigating colesevelam for the treatment of type 2 DM were evaluated for information, data, and conclusions. At dosing of 1.875 g BID or 3.75 g once daily in combination with one of the aforementioned agents versus placebo, reductions in HbA 1c in all 3 Phase III clinical trials of colesevelam ranged from 0.5% to 0.7% ( P Conclusions: When used in combination with a sulfonylurea, metformin, and/or insulin therapy, colesevelam has been reported to significantly reduce HbA 1c in adult patients with type 2 DM. Colesevelam's role in the management of type 2 DM remains undefined, however; further investigation into its mechanism of action and long-term efficacy and safety should be performed.
Ultraviolet radiation in North American lakes: Attenuation estimates from DOC measurements and implications for plankton communities

Climate warming in North America is likely to be accompanied by changes in other environmental stresses such as UV-B radiation. We apply an empirical model to available DOC (dissolved organic C) data to estimate the depths to which 1% of surface UV-B and UV-A radiation penetrate for several major regions of North America. UV attenuation depths are also estimated from DOC data collected from treatment and reference basins during the experimental acidification of Little Rock Lake, Wisconsin. In some regions of North America 25% of the lakes have 1% attenuation depths for UV-B radiation on the order of 4 m or more (western and northwestern U.S., Newfoundland). In other regions, 75% of the lakes have 1% attenuation depths for UV-B shallower than 0.5 m (Florida, upper midwestern U.S., northwestern Ontario, Quebec, and Nova Scotia). Attenuation depths for UV-A radiation are -2.5 times as deep as those for UV-B. Experimental acidification approximately doubled the estimated 1% attenuation depths for UV radiation in Little Rock Lake. The strong dependence of 1% attenuation depth on DOC below the l-2 mg liter-l DOC range suggests that UV attenuation in low DOC lakes is highly sensitive to even very small changes in DOC. We conclude that changes in climate, lake hydrology, acid deposition, and other environmental factors that alter DOC concentrations in lakes may be more important than stratospheric ozone depletion in controlling future UV environments in lakes.
Hypermedia EIS and the World Wide Web

Today the need to be nimble in and adaptive to a turbulent business environment is greater than ever. Environmental intelligence is critical to making effective strategic decisions. Strategic decision-making is based on the collection and interpretation of information from the environment. Executives must continually scan and monitor the business environment for relevant and timely information. This paper argues that a hypermedia executive information system (HEIS) can provide facilities needed to support the process and products of strategic intelligence. HEISs extend traditional executive information systems (EISs). A HEIS is designed to facilitate reconnaissance in both the internal and external environments using hypermedia and artificial intelligence technologies. It is oriented toward business intelligence, which recognizes the need for managerial vigilance. >
TNF-α regulates myogenesis and muscle regeneration by activating p38 MAPK

Although p38 MAPK activation is essential for myogenesis, the upstream signaling mechanism that activates p38 during myogenesis remains undefined. We recently reported that p38 activation, myogenesis, and regeneration in cardiotoxin-injured soleus muscle are impaired in TNF-alpha receptor double-knockout (p55(-/-)p75(-/-)) mice. To fully evaluate the role of TNF-alpha in myogenic activation of p38, we tried to determine whether p38 activation in differentiating myoblasts requires autocrine TNF-alpha, and whether forced activation of p38 rescues impaired myogenesis and regeneration in the p55(-/-)p75(-/-) soleus. We observed an increase of TNF-alpha release from C2C12 or mouse primary myoblasts placed in low-serum differentiation medium. A TNF-alpha-neutralizing antibody added to differentiation medium blocked p38 activation and suppressed differentiation markers myocyte enhancer factor (MEF)-2C, myogenin, p21, and myosin heavy chain in C2C12 myoblasts. Conversely, recombinant TNF-alpha added to differentiation medium stimulated myogenesis at 0.05 ng/ml while inhibited it at 0.5 and 5 ng/ml. In addition, differentiation medium-induced p38 activation and myogenesis were compromised in primary myoblasts prepared from p55(-/-)p75(-/-) mice. Increased TNF-alpha release was also seen in cardiotoxin-injured soleus over the course of regeneration. Forced activation of p38 via the constitutive activator of p38, MKK6bE, rescued impaired myogenesis and regeneration in the cardiotoxin-injured p55(-/-)p75(-/-) soleus. These results indicate that TNF-alpha regulates myogenesis and muscle regeneration as a key activator of p38.
Reliability-Based Design Using Saddlepoint Approximation

Reliability-based design optimization is much more computationally expensive than deterministic design optimization. To alleviate the computational demand, the First Order Reliability Method (FORM) is usually used in reliability-based design. Since FORM requires a nonlinear transformation from non-normal random variables to normal random variables, the nonlinearity of a constraint function may increase. As a result, the transformation may lead to a large error in reliability calculation. In order to improve accuracy, a new reliability-based design method with Saddlepoint Approximation is proposed in this work. The strategy of sequential optimization and reliability assessment is employed where the reliability analysis is decoupled from deterministic optimization. The accurate First Order Saddlepoint method is used for reliability analysis in the original random space without any transformation, and the chance of increasing nonlinearity of a constraint function is therefore eliminated. The overall reliability-based design is conducted in a sequence of cycles of deterministic optimization and reliability analysis. In each cycle, the percentile value of the constraint function corresponding to the required reliability is calculated with the Saddlepoint Approximation at the optimal point of the deterministic optimization. Then the reliability analysis results are used to formulate a new deterministic optimization model for the next cycle. The solution process converges within a few cycles. The demonstrative examples show that the proposed method is more accurate and efficient than the reliability-based design with FORM.Copyright © 2006 by ASME
Modelling of flocculation and transport of cohesive sediment from an on-stream stormwater detention pond

A new model to predict the transport characteristics of suspended sediment from an on-stream stormwater management pond is presented. It is based on Krishnappan's model of flocculated settling in still water, which was extended to dynamic conditions and verified by experiments with stormwater pond sediment in a laboratory rotating flume. The model was derived from first principles, but some input parameters, such as floc properties, had to be obtained by calibration, and input parameters describing flow field properties were obtained from a kappa-epsilon turbulence model. Simulated suspended concentrations vs. time and the size distribution of the flocculated sediment, produced with the calibrated model, agreed well with flume measurements.
Meeting Mandatory Infectious Disease Reporting Requirements: The Department of Veterans Affairs’ Plan

In response to pending legislation, the Department of Veterans Affairs (VA) recently issued a new Directive that requires mandatory reporting of infectious diseases to public health authorities. One potential implementation strategy is to use the VA's Healthcare Acquired Infection and Influenza Surveillance System - an electronic biosurveillance system that will soon be released nationally - which would not only build on existing technology, optimize reporting, and minimize work burdens on VA staff but also allow the VA to comply with Meaningful Use requirements.
The controlled evolution of a polymer single crystal

We present a method for controlling the initiation and kinetics of polymer crystal growth using dip-pen nanolithography and an atomic force microscope tip coated with poly-dl-lysine hydrobromide. Triangular prisms of the polymer epitaxially grow on freshly cleaved mica substrates, and their in-plane and out-of-plane growth rates can be controlled by raster scanning the coated tip across the substrate. Atomic force microscope images were concomitantly recorded, providing a set of photographic images of the process as it spans the nanometer- to micrometer-length scales as a function of environmental conditions.
Synchronizing Finite Automata on Eulerian Digraphs

?erný's conjecture and the road coloring problem are two open problems concerning synchronization of finite automata. We prove these conjectures in the special case that the vertices have uniform in- and outdegrees.
One-layer neural-network controller with preprocessed inputs for autonomous underwater vehicles

Navigating, guiding, and controlling autonomous underwater vehicles (AUVs) are challenging and difficult tasks compared to the autonomous surface-level operations. Controlling the motion of such vehicles require the estimation of unknown hydrodynamic forces and moments and disturbances acting on these vehicles in the underwater environment. In this paper, a one-layer neural-network (NN) controller with preprocessed input signals is designed to control the vehicle track along a desired trajectory, which is specified in terms of desired position and attitude. In the absence of unknown disturbances and modeling errors, it is shown that the tracking error system is asymptotically stable. In the presence of any bounded ocean currents or wave disturbances, the uniformly ultimately boundedness of the tracking error and NN weight estimates are given. The NN does not require an initial offline training phase and weight initialization is straightforward. Simulation results are shown by using a scaled version of the Naval Post-Graduate School's AUV. Results indicate the superior performance of the NN controller over conventional controllers. Providing offline NN training may improve the transient performance.
Phonetic Inventories and Phonological Patterns of African American Two-Year-Olds A Preliminary Investigation

This pilot study investigated the phonological skills of 8 African American English (AAE)—speaking 2-year-olds. Spontaneous language samples were transcribed and phonological data were entered into the Interactive System for Phonological Analysis (Masterson & Pagan, 1993) for analyses of phonetic inventory, phonological processes, and word shapes. Data were examined to determine if the phonological patterns seen in AAE-speaking children are indicative of emerging dialectal patterns. Findings provide evidence that 2-year-old AAE-speaking children acquire and use the same phonemes and phonological processes as described in the literature for both AAE-speaking toddlers and toddlers speaking Standard American English (SAE). Although the study participants demonstrated frequent use of phonological patterns consistent with AAE, the results could not categorically distinguish typical phonological development from emergent dialectal features. Clinical implications suggest that although assessment of an African Am...
Rosiglitazone: safety and efficacy in combination with insulin in poorly controlled type 2 diabetes mellitus patients treated with insulin alone

Abstract Aims To assess the safety and efficacy of rosiglitazone and insulin treatment in combination in poorly controlled insulin-treated type 2 diabetes mellitus (T2DM) patient. Method In this prospective, open-labelled, nonrandomised study, rosiglitazone was added to the insulin therapy in T2DM patients with baseline HbA 1c ≥7.5%. Patients were followed for 12 months. Insulin dosage was adjusted as necessary. Results Insulin and rosiglitazone combination was used in 53 patients (29 male, 24 female) for 12 months. Baseline vs. 12-month results shown as mean±S.D.: HbA 1c reduction 1.53% (9.82±1.12 vs. 8.29±1.45, P =.0001), insulin dosage reduction 10 U (74±34 vs. 64±34 U), percentage insulin dose reduction 13.53%, and weight gain 1.0 kg only (84±19.93 vs. 85±25.73 kg, P =.1). Systolic blood pressure 144±22.9 vs. 134±15.8 mm Hg ( P =.03), total cholesterol 6.18±4.15 vs. 4.75±2.71 μmol/L, triglyceride 2.62±1.49 vs. 2.07±1.44 μmol/L, and HDL cholesterol 1.43±0.71 vs. 1.63±0.36 μmol/L ( P =.02). Alanine transaminase actually reduced significantly from 26±22 to 19±9 IU/L ( P =.001). Improved glycaemic control was associated with favourable reduction in cardiovascular risk factors. Rosiglitazone was discontinued only in nine patients (weight gain—4, no improvement noticed—4, ankle swelling—1). No hepatotoxicity was observed. Conclusion Rosiglitazone+insulin combination is safe and effective in inadequately controlled insulin-treated T2DM patients.
Invasive Filamentous Growth of Candida albicans Is Promoted by Czf1p-Dependent Relief of Efg1p-Mediated Repression

Filamentation of Candida albicans occurs in response to many environmental cues. During growth within matrix, Efg1p represses filamentation and Czf1p relieves this repression. We propose that Czf1p interacts with Efg1p, altering its function. The complex regulation of filamentation may reflect the versatility of C. albicans as a pathogen.
Air Research Monitoring Station System

Equipment used to monitor pollution and meteorological conditions concurrently with the observation of change in health of normally healthy individuals is evaluated. Shortcomings and useful features of the original equipment, modifications and changes required, and the problems of operation and maintenance are presented. Unique features of the program including vertical profile monitoring on a continuous sequential cycle, satellite stations, and supplementary wet method sampling and analysis are demonstrated. Methodology of multidiscipline studies relating pollution levels, meteorology, and medical findings by means of computer programs are examined with primary emphasis on interrelations of the first two. Three episodes in New York City are investigated.
The ICC and Amnesty in Uganda

In response to the decades-long conflict in its northern districts, the Ugandan government enacted a broad amnesty to encourage those conscripted into the rebel Lords Resistance Army to defect. Thousands of rebels took advantage of the amnesty, laying down arms and returning home. In 2003, however, the Ugandan government referred its situation to the International Criminal Court, which subsequently handed down indictments for rebel leadership. In 2012, the successful amnesty program was ended by the government, leaving some captured rebels in limbo. This paper investigates the relationship between the ICC involvement and the end of the amnesty program, arguing that the government of Uganda used the ICC indictments as an excuse to abandon amnesty in favor of military action. The paper also discusses the military-judicial solution to the conflict for which the ICC and the Ugandan government have advocated.
Should the IDEFICS outcomes have been expected

Summary The Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS (IDEFICS) study evaluated with a large sample a comprehensive carefully planned obesity prevention intervention targeting multiple levels of influence that were culturally adapted to the situations in eight European countries. Despite the great effort and attention to detail, the IDEFICS study did not achieve its targeted adiposity or behaviour change objectives. Should we be surprised that the IDEFICS trial did not have its intended effects? We think not, and would have been surprised if it did. Recent research has revealed the lack of consistent meaningful relationships between several apparently obesogenic behaviours and adiposity, weak or no relationships among behavioural change procedures, mediating variables and targeted behaviours and inadequate attention to moderating effects. Future obesity prevention interventions would benefit from a more thorough understanding of the complex relationships that have been hypothesized and the interrelationships with biological factors. While systems modelling has been proposed as providing the solution, important less complex identification of new constructs, new relationships and community interventions are still needed, both to find innovative solutions and to provide input into the systems models. We should question results from cross-sectional studies and be satisfied only with longitudinal or experimental tests of relationships.
Optomechanical effects of two-level systems

Two-level systems are observed to affect quantum measurements with superconducting electromechanical systems via Kerr-like nonlinearity and excess phase noise. We propose a magnetic electromechanical coupling scheme as its solution.
Fabrication and Characterization of Nife Thin Film Composition Modulated Alloys

Described are results showing that an oscillating flow-field can induce spatially periodic composition variations in electrodeposited NiFe films. Flow-induced NiFe composition modulated alloys (CMA’s) were deposited on the disk of a rotating disk electrode by oscillating the disk rotation rate during galvanostatic plating. Deposit composition and structure were investigated using potentiostatic stripping voltammetry and scanning probe microscopy. Results illustrate a linear relationship between the composition modulation wavelength and the flow oscillation period. CMA’s with wavelengths less than 10 nm can be fabricated when plating with a disk rotation rate oscillation period less than 3 seconds.
Design of a CET Net-Examination System Based on Object Technology

Through analysing the features of net-examination and the advantages of object technology, we bring up the model using the object technology to design the examination system.Taking CET test as an example, the paper describes the process of analysing and modeling with object technology,and gives in detail the methods for object extraction and object interaction. Based on these, the design and implementation of a software for automatic CET net-examin-ation is introduced.
Gardens of Grief: Lucy Hutchinson’s “Elegies,” the Garden of Gethsemane, and Formal Uses of Betrayal

Lucy Hutchinson’s “Elegies,” which were written in the late seventeenth century, mourn the loss of the poet’s husband, Colonel John Hutchinson, and the loss of a republican form of government in the face of the Restoration. The garden landscapes in the poems that invoke Hutchinson’s estate at Owthorpe are typically read as a figure for a lost Eden. I argue for a different biblical garden, however, the Garden of Gethsemane. Examining the poems’ language of betrayal and grief alongside seventeenth-century exegesis on the Gethsemane episode, I show the correspondence between garden spaces, affect, and sympathetic textual and personal engagement. Using the psychoanalytic concept of conveyance, particularly in its gendered articulation in Julia Kristeva’s Black Sun, I yoke exegesis to poetry in order to argue that mediating environments are capable of producing both subjects and affective experiences. Moreover, these formal products are contingent, depending on a continuous betrayal of the original lost object.
Time-Resolved Electron Temperature in an Argon Theta Pinch by Line Ratio Methods

Pulsed inductive argon plasma in an 80-J, 15-kV, 490-kHz theta pinch is interrogated using spectroscopic methods. Time-resolved electron temperature is obtained by coupling line intensity ratios with steady-state corona and collisional-radiative (CR) models. Neutral excited state argon transitions from the 2p to 1s subshells were utilized. The backfill pressures of 50 and 100 mtorr are of primary focus. Time-resolved electron temperature estimates are presented ranging from 1 to 11.1 eV for the corona model up to an excess of 80 eV for the CR model. Near-IR spectral emission is seen to increase rapidly near the first zero crossing of the oscillating discharge current while electron temperature increase lags by roughly one full discharge cycle later near the third zero crossing. An analysis of long exposures provides an account of substantial second-order diffracted spectra. Weak spectral signal quality for the short exposures of 0.25-μs yielded time-resolved spectral intensity trend lines of a low accuracy with an average percent difference of 69% between raw data and trend lines.