bluuebunny/crossref_metadata_2025 huggingface dataset:
The Full Probabilistic Design Method of the Storm Surge Barrier Near the Port of Rotterdam, The Netherlands
Authors: de Ridder Hennes A. J.
Published: January 2009

After the storm surge disaster in 1953, which caused more than 1800 casualties in the Southwestern part of The Netherlands, a large dyke-strengthening and coastline-shortening programme was agreed upon and laid down by law. Work on the first projects commenced in the early sixties of the last century and the last phase of the programme was planned to start in 1990 and comprised of the dyke-strengthening programme in the Rhine Delta upstream from Rotterdam. This large project encountered growing public resistance as the required safety standards were established at the expense of both social and cultural values as well as ecological values. A feasibility study was started to ensure the required safety requirements of a storm surge barrier. The outcome was positive and the project was started in 1990 and was completed in 1996. In 1987, six contractors were invited to tender for the design and construction of a storm surge barrier, with only four “demand” specifications: (1) Reduction of the design water level in Rotterdam by 1.6 metres. (2) Reduction of the design water level 25 km (15 miles) upstream by 0.6 meter. (3) Lifetime of 100 years. (4) No obstacles to navigation. This set of requirements pertained to failure criteria. Based on this set of requirements, a full probabilistic method was adopted for the design of the storm surge barrier. A breakdown was made, starting from the basic probabilities of failure. The breakdown was based on failure trees with parallel and serial connected components and elements. In that way the design engineers were provided with centrally distributed failure criteria. This full probabilistic method, however, did not appeared to be adequate for several reasons. After a few months the full probabilistic design method was changed into a semi probabilistic method. Nevertheless, for the assessment of the load cases, a probabilistic approach was used, but for the design work on components and elements a traditional method introducing partial safety factors was used. Throughout the design period it was very difficult to prove that the actual designed system as well as, the designed sub systems and designed components met with the basic failure requirements. In order to avoid discussions, the designers embraced higher limits for their dimensioning calculations, resulting in a safer and more reliable storm surge barrier than was initially required.
Riser Recoil Analysis at a Harsh Environment, Deepwater Site
Authors: Stahl Matthew J. , Wishahy Momen , Brekke James N.
Published: January 2009

Riser recoil analysis for drilling at a harsh environment, deepwater site is particularly challenging. Recoil analysis results are used in conjunction with results of other riser analysis to develop a practical and safe riser management plan for drilling with a dynamically-positioned drillship at a site where rapidly-developing, high seastates occur frequently. Details of the recoil analysis are discussed along with brief references to other riser analyses that were carried out. The recoil analysis showed that criteria to avoid contact between the LMRP and BOP stack after disconnect and to limit slack in the riser tensioner ropes governed the selection of top tension settings. These recoil criteria also governed the maximum sea state in which the riser could remain connected. Recoil analysis was an important part of the effort to develop a practical and safe drilling riser management plan for a challenging location.
Bearing Defect Detection Using On-Board Accelerometer Measurements
Authors: Donelson John , Dicus Ronald L.
Published: January 2009

Vibration signatures of defective roller bearings on railroad freight cars were analyzed in an effort to develop an algorithm for detecting bearing defects. The effort is part of a project to develop an on-board condition monitoring system for freight trains. The Office of Research and Development of the Federal Railroad Administration (FRA) is sponsoring the project. The measurements were made at the Transportation Technology Center (TTC) in Pueblo, CO on July 26 – 29, 1999 during the Phase III Field Test of the Improved Wayside Freight Car Roller Bearing Inspection Research Program sponsored by FRA and the Association of American Railroads (AAR). Wheel sets with specific roller bearing defects were installed on a test train consisting of 8 freight cars designed to simulate revenue service. The consist also contained non-defective roller bearings. Accelerometers were installed on the inboard side of the bearing adapters to measure the vibration signatures during the test. Signatures of both defective and non-defective bearings were recorded. The data were recorded on Sony Digital Audio Tape (DAT) Recorders sampling at a rate of 48 K samples per second. We used both ordinary and envelope spectral analysis to analyze the data in an effort to detect features that could be related to known defects. The spectra of non-defective bearings show no remarkable features at bearing defect frequencies. In general, the ordinary spectra of defective bearings do not exhibit remarkable features at the bearing defect frequencies. In contrast, the envelope spectra of defective bearings contain a number of highly resolved spectral lines at these frequencies. In several cases the spectral lines could be related to specific bearing defects. Based on the analysis performed to date, the envelope spectrum technique provides a promising method for detecting defects in freight car roller bearings using an on-board condition monitoring system.
Wheel Flat and Out-of-Round Formation and Growth
Authors: Snyder Todd , Stone D. H. , Kristan Joseph
Published: January 2009

Wheel flats and out-of rounds (OORs) are defects that can cause high impacts that impart damage to track and equipment. This paper presents an analysis of data gathered from wheel impact load detectors on the Union Pacific Railroad and data gathered from the Transportation Technology Center, Inc. (TTCI) Wheel Defect research Consortium.
Representative Terrestrial Solar Brightness Profiles
Authors: Neumann Andreas , Witzke Andreas , Jones Scott A. , Schmitt Gregor
Published: January 2009

Solar thermal energy systems often use optical imaging concentrators. The image size and shape produced in the focal plane of the concentrator system depends on the solar brightness distribution. Therefore, the forward scattering of solar radiation by the Earth’s atmosphere modifies the solar brightness distribution and creates a circumsolar aureole. The circumsolar ratio, the energy contained in the solar aureole compared to the total solar energy, can have an impact on the performance of these concentrating systems. Based on about 2300 sunshape measurements from sites in France, Germany and Spain made with a camera system developed by the German Aerospace Center (DLR), average solar brightness profiles with a circumsolar ratio of about 0%, 5%, 10%, 20%, 30%, and 40% were generated. These profiles are compared to the measurements taken by the Lawrence Berkeley Laboratory (LBL) in the late 1970’s and a commonly used limb-darkened solar brightness profile, as known from astronomy. A statistical analysis gives information on the frequency of occurrence of each of the average profiles. The profiles combined with the statistical weight should offer a numerical database for calculating the influence of variable conditions of the sunlight scattering on solar concentrating systems. Furthermore, a single average profile was calculated from the DLR data.
Development of Theoretical Contact Width Formulas and a Numerical Model for Curved Rough Surfaces
Authors: Wang Shao
Published: January 2009

The apparent contact area of curved rough surfaces can be larger than that predicted by the Hertz theory due to asperity interaction outside the Hertzian region. In the present study, simple theoretical formulas for the contact semi-width and radius were derived, and a numerical contact model was developed based on an iterative scheme for the elastic deformation of the macroscopic surface profile and the asperity deformation. Both the theoretical formulas and the numerical model are based on a general power-law relationship between the local apparent pressure and real-to-apparent contact ratio. Numerical results of the contact semi-width agree well with the prediction of the formula. The apparent contact region becomes increasingly larger than the Hertzian region as the dimensionless roughness parameter increases, or as the dimensionless load parameter decreases, while the effect of the load exponent is relatively small. The ratio of the contact semi-width to the Hertzian semi-width is mainly determined by a dimensionless contact parameter involving the root-mean-square roughness, the equivalent radius and the Hertzian semi-width or radius. When applied to fractal regular surfaces, the present theory indicates that the influence of the fractal dimension on the contact behavior is due to its effects on both the area-load coefficient and the load exponent.
The Influence of Residual Stress on Micromachine Stiction
Authors: Wan Kai-Tak , Kogut Lior
Published: January 2009

Adhesion plays an important role in microelectromechanical systems (MEMS). It is a major concern in MEMS reliability and oftentimes excessive adhesion forces lead to permanent adherence of MEMS surfaces resulting in microdevice failure. The role of residual stresses in the adhesive contact between a pre-stressed membrane and a rigid flat-ended cylindrical punch is studied. Breaking the contact can be achieved under either fixed-load or fixed-grips configuration. The influence of the residual stress on the pull-off force, punch displacement, and contact area at pull-off is studied. It is shown that residual stresses have significant influence on interfacial contact behavior in MEMS and, hence, should be taken into consideration in formulating the adhesion contact mechanics.
Detection of Molecular Markers of Antiviral Resistance in Influenza A (H5N1) Viruses Using a Pyrosequencing Method
Authors: Deyde Varough M. , Nguyen Tung , Bright Rick A. , Balish Amanda , Shu Bo , Lindstrom Stephen , Klimov Alexander I. , Gubareva Larisa V.
Published: January 2009

Resistance of influenza viruses to antiviral drugs can emerge following medication or may result from natural variation. Two classes of anti-influenza virus drugs targeting either the M2 protein (amantadine and rimantadine) or neuraminidase (NA; oseltamivir and zanamivir) are currently licensed. These drugs are expected to be important in controlling the early stages of a potential pandemic. In the present study, we describe how a pyrosequencing method can be used to rapidly detect established molecular markers of resistance to M2 blockers and NA inhibitors in influenza A (H5N1) viruses. The residues L26, V27, A30, S31, and G34 in the M2 protein were targeted for pyrosequencing. The NA residues for pyrosequencing analysis included the established markers of drug resistance (H274 and N294), as well as residues of less certain relevance (V116, I117, Q136, K150, and I222). A single pair of pyro-reverse transcription (RT)-PCR primers was designed to allow amplification of an approximately 600-nucleotide-long amplicon of the NA genes of H5N1 viruses from various clades/subclades associated with infections in humans. The sensitivity of the assay was demonstrated by the successful pyrosequencing of RNA extracted from samples of serially diluted (10−5to 10−7) virus stocks with initial concentrations ranging from 105to 108PFU/ml. The markers of resistance were detected in samples with threshold cycle values ranging from 32 to 37, as determined by real-time RT-PCR. The pyrosequencing approach may provide a valuable tool for rapid detection of markers of drug resistance in H5N1 viruses and facilitate the elucidation of the role of such changes in natural and acquired drug resistance.
Critical Roles of Inflammation and Apoptosis in Improved Survival in a Model of Hyperoxia-Induced Acute Lung Injury inPneumocystis murina-Infected Mice
Authors: Beck James M. , Preston Angela M. , Wilcoxen Steven E. , Morris Susan B. , Sturrock Anne , Paine Robert
Published: January 2009

Pneumocystisinfections increase host susceptibility to additional insults that would be tolerated in the absence of infection, such as hyperoxia. In an in vivo model using CD4-depleted mice, we previously demonstrated thatPneumocystis murinapneumonia causes significant mortality following an otherwise nonlethal hyperoxic insult. Infected mice demonstrated increased pulmonary inflammation and alveolar epithelial cell apoptosis compared to controls. To test the mechanisms underlying these observations, we examined expression of components of the Fas-Fas ligand pathway inP. murina-infected mice exposed to hyperoxia. Hyperoxia alone increased expression of Fas on the surface of type II alveolar epithelial cells; conversely, infection withP. murinaled to increased lung expression of Fas ligand. We hypothesized that inhibition of inflammatory responses or direct inhibition of alveolar epithelial cell apoptosis would improve survival inP. murina-infected mice exposed to hyperoxia. Mice were depleted of CD4+T cells and infected withP. murinaand then were exposed to >95% oxygen for 4 days, followed by return to normoxia. Experimental groups received vehicle, dexamethasone, or granulocyte-macrophage colony-stimulating factor (GM-CSF). Compared with the vehicle-treated group, treatment with dexamethasone reduced Fas ligand expression and significantly improved survival. Similarly, treatment with GM-CSF, an agent we have shown protects alveolar epithelial cells against apoptosis, decreased Fas ligand expression and also improved survival. Our results suggest that the dual stresses ofP. murinainfection and hyperoxia induce lung injury via activation of the Fas-Fas ligand pathway and that corticosteroids and GM-CSF reduce mortality inP. murina-infected mice exposed to hyperoxic stress by inhibition of inflammation and apoptosis.
Synchronous Gene Expression of theYersinia enterocoliticaYsa Type III Secretion System and Its Effectors
Authors: Walker Kimberly A. , Miller Virginia L.
Published: January 2009

Type III secretion systems (T3SSs) are complex units that consist of many proteins. Often the proteins are encoded as a cohesive unit on virulence plasmids, but several systems have their various components dispersed around the chromosome. TheYersinia enterocoliticaYsa T3SS is such a system, where the apparatus genes, some regulatory genes, and four genes encoding secreted proteins (yspgenes) are contained in a single locus. The remainingyspgenes and at least one additional regulator are found elsewhere on the chromosome. Expression ofysagenes requires conditions of high ionic strength, neutral/basic pH, and low temperatures (26°C) and is stimulated by exposure to solid surfaces. The AraC-like regulator YsaE and the dual-function chaperone/regulator SycB are required to stimulate thesycBpromoter, which transcribessycBand probablyyspBCDAas well. The putative phosphorelay proteins YsrRS (located at the distal end of theysalocus) and RcsB, the response regulator of the RcsBCD phosphorelay system, are required to initiate transcription at theysaEpromoter, which drives transcription of many apparatus genes. In this work, we sought to determine whichyspgenes were coordinately regulated with the genes within theysalocus. We found that six unlinkedyspgenes responded to NaCl and required YsaE/SycB, YsrRS, and RcsB for expression. Threeyspgenes had unique patterns, one of which was unaffected by all elements tested except NaCl. Thus, while theyspgenes were likely to have been acquired independently, most have acquired a synchronous regulatory pattern.
Adolescent exercise associated with long-term superior measures of bone geometry: a cross-sectional DXA and MRI study
Authors: Kato T , Yamashita T , Mizutani S , Honda A , Matumoto M , Umemura Y
Published: January 2009

Objective:

To investigate whether childhood sports participation, particularly weight-bearing sports, has any effect on bone mineral content (BMC), areal bone mineral density (aBMD) and bone geometric characteristics in middle-aged postmenopausal women.

Design/setting:

In this cross-sectional comparison of two groups, 46 middle-aged women (mean age, 60.2 (SD 5.6) years; range, 52–73 years) were grouped according to sport participation during growth: weight-bearing sports, including high-impact weight-bearing activities; and low-impact non-weight-bearing sports or no participation.

Main outcome measures:

Dual energy X-ray absorptiometry (DXA)-measured BMC, aBMD in the lumbar spine and femur. Magnetic resonance imaging (MRI) determined bone geometric characteristics in the femur, such as femoral mid-diaphyseal cross-sectional area, periosteal and endosteal perimeters and maximum and minimum second moment of area.

Results:

Postmenopausal middle-aged women with participation in weight-bearing sports during junior high to high school (12–18 years old) displayed significantly greater BMC in both lumbar spine and femoral neck regions, and also significantly greater femoral mid-diaphyseal bone cross-sectional area, periosteal perimeter and maximum and minimum second moment of area than the non-weight-bearing sports group.

Conclusions:

Adolescent weight-bearing exercise exerts preservational effects on femoral mid-diaphyseal size and shape, while DXA-measured BMC effectively identified the same tendency. Weight-bearing exercise in youth affects bone, and these effects may be preserved as BMC, geometric and structural advantages even after 40 years.
Genetic differences in thermal tolerance of eastern mosqyitofish (Gambusia holbrooki; Poeciliidae) from ambient and thermal ponds
Authors: Meffe Gary K. , Weeks Stephen C. , Mulvey Margaret , Kandl K. L.
Published: January 2009

Two populations of eastern mosquitofish (Gambusia holbrooki; Poeciliidae) in South Carolina, one in an ambient temperature pond and the other in a pond heated to near-lethal temperatures by nuclear reactor effluents for 60–90 mosquitofish generations, offered an excellent opportunity to observe selection for increased thermal tolerance. We performed three experiments. First, we determined the critical thermal maximum of each population and, as predicted, found the thermal population to have a higher one. We then exposed fish from both populations to an acute thermal LD50stress and compared genetic diversity of fish that died and fish that survived. Survivors had higher heterozygosities, indicating that genetic diversity may contribute to thermal tolerance. Finally, we used a half-sib – full-sib experimental design to estimate heritabilities for temperature tolerance in fish from the heated pond. We calculated a narrow-sense heritability for temperature at death of over 32%, indicating that selection has not depleted the population of genetic variation associated with thermal tolerance. Our results have implications for climate change because adaptations to higher thermal regimes must, in part, come from selection on genetic variation for temperature tolerance within populations.
Diet variability and foraging strategies in brown trout (Salmo trutta): an analysis from subpopulations to individuals
Authors: Bridcut Emily E. , Giller Paul S.
Published: January 2009

Field studies were conducted to examine intra- and inter-individual diet variation in subpopulations of brown trout (Salmo trutta) at different spatial scales (between sites, between habitats (riffle and pool) within a site, and between individuals within a habitat) and different temporal scales (within subpopulations and within individuals over time) at four sites in the Glenfinish River, County Cork, Ireland. Electrofishing and stomach flushing techniques were used whereby fish larger than 85 mm were uniquely coded, allowing for repeated capture and diet analysis of individuals. A considerable degree of variation within and between subpopulations and individual diets was apparent. On the basis of novel and recent graphical models of feeding strategies, the trend was for a generalized strategy amongst trout subpopulations occupying riffles throughout most seasons, whilst specialization tended to be more frequent amongst trout occupying pools during summer and autumn. Using similarity indices and dendrograms, we illustrate that individual fish showed both feeding strategies within one habitat over time.
Elimination rate constants of 36 PCBs in zebra mussels (Dreissena polymorpha) and exposure dynamics in the Lake St. Clair - Lake Erie corridor
Authors: Morrison Heather , Lazar Rodica , Haffner G. Douglas , Yankovich Tamara
Published: January 2009

The elimination kinetics of 36 PCB congeners, ranging in log octanol–water partition coefficients (log Kow) from 5.60 to 7.50, were determined in zebra mussels (Dreissena polymorpha) with shell lengths from 1.0 to 1.5 cm. Elimination rate constants, based on lipid-normalized data, ranged from 0.172 to 0.042 day−1 and exhibited a significant negative regression with log Kow. Time to 95% steady state ranged from 17.5 to 71.0 days and was used to determine the period over which mussels integrated exposure concentrations. Bioavailable PCB congener concentrations, calculated with a steady-state model, were determined from mussels collected offshore of Middle Sister Island in western Lake Erie. Chemical concentrations in water, estimated using mussels, were within an order of magnitude of direct measurements for congeners with log Kow < 6.6. The rapid elimination kinetics of zebra mussels suggests that these organisms can closely track temporal fluctuations in ambient chemical concentrations, and therefore have the potential to regulate contaminant cycling in aquatic ecosystems.
PCR-based nuclear markers identify alien blue mussel (Mytilusspp.) genotypes on the west coast of Canada
Authors: Heath Daniel D. , Rawson Paul D. , Hilbish Thomas J.
Published: January 2009

Two blue mussel sibling species, Mytilus edulis and Mytilus galloprovincialis, have been imported to Pacific northwest waters in separate attempts to circumvent early mortality experienced by the native species (Mytilus trossulus) when cultured. Here we describe two novel markers based on the polymerase chain reaction that discriminate the two non-native, or alien, mussel species from the native species. The two markers are inherited in a Mendelian fashion, show no evidence of close linkage, and are highly diagnostic. To screen British Columbian mussel populations for the presence of the alien species, we assayed genotypes at the two marker loci in 482 subtidal mussels collected at 12 sites. Animals with at least one alien allele were present at 9 of 12 sampling sites with an overall frequency of 6.2%. The distribution of alien alleles at the two marker loci differed among sampling sites, suggesting differential introgression. The widespread incidence of alien alleles, combined with evidence of extensive hybridization between the alien and native species, indicates that the introduced alleles will probably persist in British Columbia mussels for some time.
Photochemical formation of hydrogen peroxide in lakes: effects of dissolved organic carbon and ultraviolet radiation
Authors: Scully N. M. , McQueen D. J. , Lean D. R. S. , Cooper W. J.
Published: January 2009

Hydrogen peroxide (H2O2) was measured in situ over periods of 48 or 72 h every 3 h at several depths throughout the water column in six lakes with a wide range of limnological features. These included a comparison of relatively clear Sharpes Bay with more coloured Brookes Bay in Jacks Lake; two softwater lakes, Croche and deeply coloured Cromwell; and large hardwater lakes, Ontario and Erie. From the H2O2 depth profiles, diel patterns of H2O2 were calculated on an areal basis (milligrams per square metre) and corrected for H2O2 decay so that cumulative H2O2 production could be calculated. These values were compared with cumulative H2O2 production values modeled using laboratory-derived H2O2 formation efficiencies, cumulative ultraviolet (280–400 nm) photon fluxes, and ultraviolet attenuation coefficients. Modeled and measured daily cumulative production (milligrams H2O2 per square metre per day) were highly correlated (r = 0.95, p < 0.001). The model developed for these six sites was also used to predict daily cumulative production at other sites. Daily areal cumulative production was found to be independent of dissolved organic carbon concentration of the lake waters (r2 = 0.05, p = 0.417). The daily areal cumulative production of H2O2 did not increase or decrease with dissolved organic carbon concentration.
Grey seal (Halichoerus grypus) from the Northwest Atlantic: female reproductive rates, age at first birth, and age of maturity in males
Authors: Hammill M. O. , Gosselin J. F.
Published: January 2009

Mean age at first birth and reproductive rates were examined in a sample of 526 female grey seal (Halichoerus grypus) reproductive tracts collected between 1968 and 1992. Age of first birth determined from reproductive tracts with a fetus was 5.5 ± 0.12 yr (mean ± SD). No trend over time was observed in mean age at first birth or in pregnancy rates. Pregnancy rates determined from reproductive tracts containing a fetus were 0.18, 0.86, and 0.88 for animals aged 4+, 5+, and >6+ yr, respectively. Pregnancy rates calculated from the presence of a corpus luteum were 0.01, 0.45, 0.9, and 1 for ages 3+, 4+, 5+, and >6+, respectively. Mean age of sexual maturity of males was 5.6 yr as estimated from changes in testes mass in a sample of 89 seals collected during August–September 1992. A marked increase in testes mass was observed among animals aged 3+ yr. By age 7+ yr, virtually all males had attained sexual maturity.
Population differentiation in Pacific salmons: local adaptation genetic drift, or the environment?
Authors: Adkison Milo D.
Published: January 2009

Morphological, behavioral, and life-history differences between Pacific salmon (Oncorhynchus spp.) populations are commonly thought to reflect local adaptation, and it is likewise common to assume that salmon populations separated by small distances are locally adapted. Two alternatives to local adaptation exist: random genetic differentiation owing to genetic drift and founder events, and genetic homogeneity among populations, in which differences reflect differential trait expression in differing environments. Population genetics theory and simulations suggest that both alternatives are possible. With selectively neutral alleles, genetic drift can result in random differentiation despite many strays per generation. Even weak selection can prevent genetic drift in stable populations; however, founder effects can result in random differentiation despite selective pressures. Overlapping generations reduce the potential for random differentiation. Genetic homogeneity can occur despite differences in selective regimes when straying rates are high. In sum, localized differences in selection should not always result in local adaptation. Local adaptation is favored when population sizes are large and stable, selection is consistent over large areas, selective differentials are large, and straying rates are neither too high nor too low. Consideration of alternatives to adaptation would improve both biological research and salmon conservation efforts.
LOCATING THE MEDIAN OF A TREE IN REAL TIME
Authors: NAGY MARIUS
Published: January 2009

Determining the optimal location of a switching center in a tree network of users is accurately modeled by the median problem. A real-time approach is used in this paper to investigate the dynamics of such a communication network in two cases: (1) a growing tree of nodes associated with equal demand rates, and (2) a stream of corrections that arbitrarily change the demand rates at the nodes. The worst-case analysis performed in both situations clearly demonstrates the importance of parallelism in such real-time paradigms. It is shown that the error generated by the best sequential algorithm in the first case can be arbitrarily large. A synergistic behavior is revealed when the quality-up is investigated in the second case.
p-ADIC q-BERNOULLI NUMBERS AND THEIR DENOMINATORS
Authors: KAMANO KEN
Published: January 2009

We define p-adic q-Bernoulli numbers by using a p-adic integral. These numbers have good properties similar to those of the classical Bernoulli numbers. In particular, they satisfy an analogue of the von Staudt–Clausen theorem, which includes information of denominators of p-adic q-Bernoulli numbers.
The TRPC Class of Ion Channels: A Critical Review of Their Roles in Slow, Sustained Increases in Intracellular Ca2+ Concentrations
Authors: Birnbaumer Lutz
Published: January 2009

The realization that there exists a multimembered family of cation channels with structural similarity to Drosophila's Trp channel emerged during the second half of the 1990s. In mammals, depending on the species, the TRP family counts 29 or 30 members which has been subdivided into 6 subfamilies on the basis of sequence similarity. TRP channels are nonselective monovalent cation channels, most of which also allow passage of Ca2+. Many members of each of these families, but not all, are involved in sensory signal transduction. The C-type (for canonical or classical) subfamily, differs from the other TRP subfamilies in that it fulfills two different types of function: membrane depolarization, resembling sensory transduction TRPs, and mediation of sustained increases in intracellular Ca2+. The mechanism(s) by which the C-class of TRP channels—the TRPCs—are activated is poorly understood and their role in mediating intracellular Ca2+ increases is being questioned. Both of these questions—mechanism of activation and participation in Ca2+ entry—are the topics of this review.
Effects of intrafetal IGF-I on growth of cardiac myocytes in late-gestation fetal sheep
Authors: Lumbers Eugenie R. , Kim Min young , Burrell Judith H. , Kumarasamy Vasumathy , Boyce Amanda C. , Gibson Karen J. , Gatford Kathryn L. , Owens Julie A.
Published: January 2009

Intrafetal insulin-like growth factor (IGF)-I promotes cardiac hypertrophy in the late-gestation fetal sheep; whether these effects are sustained is unknown. IGF-I was infused for 4 days at 80 μg/h from 121 to 125 days of gestation, and its effects at 128 days, 3 days after the infusion stopped, were determined by comparison with untreated fetal sheep. After IGF-I treatment, fetal weights were similar to those in control fetuses but kidney weights were bigger ( P < 0.05), as were spleen weights of male fetuses ( P < 0.05). Cardiac myocytes were larger in female than male fetal sheep ( P < 0.001). IGF-I increased male ( P < 0.001) but not female myocyte volumes. IGF-I did not alter the proportions of uni- or binucleated right or left ventricular myocytes. Female fetal sheep had a greater proportion of binucleated cardiac myocytes than males ( P < 0.05). IGF-I-treated fetuses had a slightly greater proportion of right ventricular nuclei in cell cycle phase G2/M and a reduced proportion of G0/G1 phase nuclei ( P < 0.1). Therefore, evidence for IGF-I-stimulated cardiac cell hyperplasia in fetal sheep in late gestation was limited. In conclusion, the greater sizes and larger proportion of binucleated cardiac myocytes in female fetal sheep suggest that myocyte maturation may occur earlier in females than in males. This may explain in part the male sex-specific responsiveness of cardiac hypertrophy to IGF-I in late gestation. If IGF-I-stimulated cardiomyocyte growth is accompanied by maturation of contractile function, IGF-I may be a potential therapeutic agent for maintaining cardiac output in preterm males.
Architecture-Level Exploration of Alternative Interconnection Schemes Targeting 3D FPGAs: A Software-Supported Methodology
Authors: Siozios Kostas , Bartzas Alexandros , Soudris Dimitrios
Published: January 2009

In current reconfigurable architectures, the interconnection structures increasingly contribute more to the delay and power consumption. The demand for increased clock frequencies and logic density (smaller area footprint) makes the problem even more important. Three-dimensional (3D) architectures are able to alleviate this problem by accommodating a number of functional layers, each of which might be fabricated in different technology. However, the benefits of such integration technology have not been sufficiently explored yet. In this paper, we propose a software-supported methodology for exploring and evaluating alternative interconnection schemes for 3D FPGAs. In order to support the proposed methodology, three new CAD tools were developed (part of the 3D MEANDER Design Framework). During our exploration, we study the impact of vertical interconnection between functional layers in a number of design parameters. More specifically, the average gains in operation frequency, power consumption, and wirelength are 35%, 32%, and 13%, respectively, compared to existing 2D FPGAs with identical logic resources. Also, we achieve higher utilization ratio for the vertical interconnections compared to existing approaches by 8% for designing 3D FPGAs, leading to cheaper and more reliable devices.
Plasma Kallikrein Mediates Angiotensin II Type 1 Receptor–Stimulated Retinal Vascular Permeability
Authors: Phipps Joanna A. , Clermont Allen C. , Sinha Sukanto , Chilcote Tamie J. , Bursell Sven-Erik , Feener Edward P.
Published: January 2009

Hypertension is a leading risk factor for the development and progression of diabetic retinopathy and contributes to a variety of other retinal diseases in the absence of diabetes mellitus. Inhibition of the renin-angiotensin system has been shown to provide beneficial effects against diabetic retinopathy, both in the absence and presence of hypertension, suggesting that angiotensin II (Ang II) and the Ang II type 1 receptor may contribute to retinal vascular dysfunction. We investigated the effects of the Ang II type 1 receptor antagonist candesartan on retinal vascular permeability (RVP) in normotensive rats with streptozotocin-induced diabetes mellitus and in rats with Ang II–induced hypertension. We showed that candesartan treatment decreased diabetes mellitus– and Ang II–stimulated RVP by 58% (
P
<0.05) and 79% (
P
<0.05), respectively, compared with untreated controls, suggesting that activation of the Ang II type 1 receptor contributes to blood-retinal barrier dysfunction. We found that plasma kallikrein levels are increased in the retina of rats with Ang II–stimulated hypertension and that intravitreal injection of either plasma kallikrein or bradykinin is sufficient to increase RVP. We showed that a novel small molecule inhibitor of plasma kallikrein, 1-benzyl-1H-pyrazole-4-carboxylic acid 4-carbamimidoyl-benzylamide, delivered systemically via a subcutaneous pump, decreased Ang II–stimulated RVP by 70% (
P
<0.05) and ameliorates Ang II–induced hypertension, measured from the carotid artery by telemetry, but did not reduce Ang II–induced retinal leukostasis. These findings demonstrate that activation of the Ang II type 1 receptor increases RVP and suggest that systemic plasma kallikrein inhibition may provide a new therapeutic approach for ameliorating blood-retinal barrier dysfunction induced by hypertension.
Bentonite-Based Organoclays as Innovative Flame Retardants Agents for SBS Copolymer
Authors: Franchini M. Comes , Fabbri P. , Frache A. , Ori G. , Messori M. , Siligardi C. , Ricci A.
Published: January 2009

Two organophilic bentonites, based on nitrogen-containing compounds, have been synthesised via ion exchange starting from pristine bentonite with octadecyltrimethylammonium bromide (OTAB) and with synthetic melamine-derived N2,N4-dihexadecyl-1,3,5-triazine-2,4,6-triamine (DEDMEL). The
chemical and morphological characterization of the organoclays was based on XRD, TEM, Laser Granulometry, X-Ray Fluorescence and CEC capacity. Copoly(styrene-butadiene-styrene)-nanocomposites (SBS-nanocomposites) were obtained by intercalation of the SBS-copolymer into these new organoclays
by melt intercalation method. XRD and TEM analysis of the organoclays and of the micro/nano-composites obtained are presented. The effect of the organoclays on the SBS-nanocomposite's flammability properties was investigated using cone calorimeter. An encouraging decrease of 20% in the peak
heat released rate (PHRR) has been obtained confirming the important role of melamine's based skeleton and its derived organoclays to act as effective fire retardants and for the improvement of this important functional property in SBS copolymers.
A New Synergic-Assembly Strategy Towards Three-Dimensional (3D) Hollow Nanoarchitectures
Authors: Wu Changzheng , Xie Yi
Published: January 2009

Large-scale synthesis and assembly of meso-, micro- and nanostructured building blocks with the desired orientations are of great interest for the next-generation nanoarchitecture design. On the consideration that the traditional synthetic methodologies for nanostructures often produce
tangled nanounits, how to align the nanounits into the ordered orientation at high production yield is a great challenge to current methods. The present review describes a facile and controllable way to grow and assemble the 3D hollow nanoarchitectures, with the utilization of the synergic
effects of hollowing process from the self-produced templates and the highly anisotropic growth of nanounits of the target materials in one-pot reaction. In this process, the building block nanounits spontaneously in-situ form owing to their highly anisotropic internal structure, while
the self-produced templates act as the supporter and growth-direction guidance for the in-situ formed nanounits. Therefore, the whole assembly process is simple, controllable and without the complicated manipulations. Herein, in the light of the different kinds of self-produced templates
involved in the assembly process, recent developments based on the new synergic-assembly strategy are reviewed according to the classifications: (1) self-produced gas bubble template strategy; (2) self-produced homogeneous solid template strategy; (3) self-produced heterogeneous solid template
strategy. Notably, the synergic-assembly methodology described in this review provides a newly essential way to construct and assemble nanoarchitectures facilely and controllably, and is also a crucial step for the next-generation of nanoarchitecture design in the near future. In conclusion,
the challenges and prospects for the future are discussed.
Redox biology of Mycobacterium tuberculosis H37Rv: protein-protein interaction between GlgB and WhiB1 involves exchange of thiol-disulfide
Authors: Garg Saurabh , Alam Md Suhail , Bajpai Richa , Kishan KV Radha , Agrawal Pushpa
Published: January 2009

Background

Mycobacterium tuberculosis, an intracellular pathogen encounters redox stress throughout its life inside the host. In order to protect itself from the redox onslaughts of host immune system, M. tuberculosis appears to have developed accessory thioredoxin-like proteins which are represented by ORFs encoding WhiB-like proteins. We have earlier reported that WhiB1/Rv3219 is a thioredoxin like protein of M. tuberculosis and functions as a protein disulfide reductase. Generally thioredoxins have many substrate proteins. The current study aims to identify the substrate protein(s) of M. tuberculosis WhiB1.

Results

Using yeast two-hybrid screen, we identified alpha (1,4)-glucan branching enzyme (GlgB) of M. tuberculosis as a interaction partner of WhiB1. In vitro GST pull down assay confirmed the direct physical interaction between GlgB and WhiB1. Both mass spectrometry data of tryptic digests and in vitro labeling of cysteine residues with 4-acetamido-4' maleimidyl-stilbene-2, 2'-disulfonic acid showed that in GlgB, C95 and C658 are free but C193 and C617 form an intra-molecular disulfide bond. WhiB1 has a C37XXC40 motif thus a C40S mutation renders C37 to exist as a free thiol to form a hetero-disulfide bond with the cysteine residue of substrate protein. A disulfide mediated binary complex formation between GlgB and WhiB1C40S was shown by both in-solution protein-protein interaction and thioredoxin affinity chromatography. Finally, transfer of reducing equivalent from WhiB1 to GlgB disulfide was confirmed by 4-acetamido-4' maleimidyl-stilbene-2, 2'-disulfonic acid trapping by the reduced disulfide of GlgB. Two different thioredoxins, TrxB/Rv1471 and TrxC/Rv3914 of M. tuberculosis could not perform this reaction suggesting that the reduction of GlgB by WhiB1 is specific.

Conclusion

We conclude that M. tuberculosis GlgB has one intra-molecular disulfide bond which is formed between C193 and C617. WhiB1, a thioredoxin like protein interacts with GlgB and transfers its electrons to the disulfide thus reduces the intra-molecular disulfide bond of GlgB. For the first time, we report that GlgB is one of the in vivo substrate of M. tuberculosis WhiB1.
Thermodynamic scaling behavior in genechips
Authors: Ferrantini Alessandro , Allemeersch Joke , Van Hummelen Paul , Carlon Enrico
Published: January 2009

Background

Affymetrix Genechips are characterized by probe pairs, a perfect match (PM) and a mismatch (MM) probe differing by a single nucleotide. Most of the data preprocessing algorithms neglect MM signals, as it was shown that MMs cannot be used as estimators of the non-specific hybridization as originally proposed by Affymetrix. The aim of this paper is to study in detail on a large number of experiments the behavior of the average PM/MM ratio. This is taken as an indicator of the quality of the hybridization and, when compared between different chip series, of the quality of the chip design.

Results

About 250 different GeneChip hybridizations performed at the VIB Microarray Facility for Homo sapiens, Drosophila melanogaster, and Arabidopsis thaliana were analyzed. The investigation of such a large set of data from the same source minimizes systematic experimental variations that may arise from differences in protocols or from different laboratories. The PM/MM ratios are derived theoretically from thermodynamic laws and a link is made with the sequence of PM and MM probe, more specifically with their central nucleotide triplets.

Conclusion

The PM/MM ratios subdivided according to the different central nucleotides triplets follow qualitatively those deduced from the hybridization free energies in solution. It is shown also that the PM and MM histograms are related by a simple scale transformation, in agreement with what is to be expected from hybridization thermodynamics. Different quantitative behavior is observed on the different chip organisms analyzed, suggesting that some organism chips have superior probe design compared to others.
Activation of the steroid and xenobiotic receptor, SXR, induces apoptosis in breast cancer cells
Authors: Verma Suman , Tabb Michelle M , Blumberg Bruce
Published: January 2009

Background

The steroid and xenobiotic receptor, SXR, is an orphan nuclear receptor that regulates metabolism of diverse dietary, endobiotic, and xenobiotic compounds. SXR is expressed at high levels in the liver and intestine, and at lower levels in breast and other tissues where its function was unknown. Since many breast cancer preventive and therapeutic compounds are SXR activators, we hypothesized that some beneficial effects of these compounds are mediated through SXR.

Methods

To test this hypothesis, we measured proliferation of breast cancer cells in response to SXR activators and evaluated consequent changes in the expression of genes critical for proliferation and cell-cycle control using quantitative RT-PCR and western blotting. Results were confirmed using siRNA-mediated gene knockdown. Statistical analysis was by t-test or ANOVA and a P value ≤ 0.05 was considered to be significant.

Results

Many structurally and functionally distinct SXR activators inhibited the proliferation of MCF-7 and ZR-75-1 breast cancer cells by inducing cell cycle arrest at the G1/S phase followed by apoptosis. Decreased growth in response to SXR activation was associated with stabilization of p53 and up-regulation of cell cycle regulatory and pro-apoptotic genes such as p21, PUMA and BAX. These gene expression changes were preceded by an increase in inducible nitric oxide synthase and nitric oxide in these cells. Inhibition of iNOS blocked the induction of p53. p53 knockdown inhibited up-regulation of p21 and BAX. We infer that NO is required for p53 induction and that p53 is required for up-regulation of cell cycle regulatory and apoptotic genes in this system. SXR activator-induced increases in iNOS levels were inhibited by siRNA-mediated knockdown of SXR, indicating that SXR activation is necessary for subsequent regulation of iNOS expression.

Conclusion

We conclude that activation of SXR is anti-proliferative in p53 wild type breast cancer cells and that this effect is mechanistically dependent upon the local production of NO and NO-dependent up-regulation of p53. These findings reveal a novel biological function for SXR and suggest that a subset of SXR activators may function as effective therapeutic and chemo-preventative agents for certain types of breast cancers.
Ebp1 expression in benign and malignant prostate
Authors: Gannon Philippe O , Koumakpayi Ismaël Hervé , Le Page Cécile , Karakiewicz Pierre I , Mes-Masson Anne-Marie , Saad Fred
Published: January 2009

Background

ErbB3-binding protein 1 (Ebp1) is a member of the PA2G4 family of proliferation-regulated proteins that is expressed in multiple malignant and non-malignant cells. ErbB3 and other members of the EGFR family have been implicated in cancer progression, it however remains unknown whether Ebp1 participate in prostate cancer progression in vivo. Therefore, the present study examines Ebp1 expression in cancerous and non-cancerous prostates tissues. Ebp1 expression was also correlated to known Ebp1 regulated proteins (Androgen receptor (AR), Cyclin D1 & ErbB3) and the proliferation marker Ki67. Furthermore we evaluated whether Ebp1 expression correlated with biochemical recurrence (BCR) following radical prostatectomy.

Methods

The expression of Ebp1, AR, Cyclin D1, ErbB3 and Ki67 were evaluated by immunohistochemistry using three separate tissue micro-arrays containing normal prostate tissues, non-cancerous tissue adjacent to the primary tumor, hormone-sensitive and hormone-refractory cancerous tissues. Multivariate COX regression analysis was performed with four clinical parameters in order to correlate Ebp1 expression with PCa progression.

Results

The expression of Ebp1 significantly increased with the progression from normal to hormone sensitive and to hormone refractory PCa. Furthermore, we observed strong correlation between Ebp1 expression and the nuclear expression of AR, Cyclin D1 and ErbB3 in both normal adjacent and cancer tissues. The expression of AR, Cyclin D1 and ErbB3 in normal adjacent tissues correlated with PSA relapse, whereas Ebp1 on its own did not significantly predict PSA relapse. Finally, in a multivariate analysis with a base clinical model (Gleason, Pre-op PSA, surgical margins and P-stage) we identified the multi-marker combination of Ebp1+/Cyclin D1- as an independent predictor of PSA relapse with a hazard ratio of 4.79.

Conclusion

Although not related to disease recurrence, this is the first in vivo study to report that Ebp1 expression correlates with PCa progression.