bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Peak Ductility Demand of Inelastic SDOF Systems in Maximum Elastic Response and Major Principal Directions
Authors: Goda Katsuichiro
Published: February 2012

This study investigates the orientation dependency of the peak ductility demand of inelastic single-degree-of-freedom (SDOF) systems of known strengths by taking the record-to-record variability of seismic effects into account. The probabilistic characteristics of the peak ductility demand in recording directions on the horizontal plane are compared with those in the maximum elastic response direction and the major principal direction. The analysis results indicate that the peak ductility demand depends on how input ground motions are defined in terms of record orientation. The observed orientation dependency can be explained by noting the response spectral shapes of scaled ground motion records in specific directions. The results have important implications for current earthquake engineering practice, suggesting that separate peak ductility demand models should be used for different ground motion directions to evaluate the seismic performance of structures consistently and without bias.
Updated PGA, PGV, and Spectral Acceleration Attenuation Relations for Iran
Authors: Saffari Hamid , Kuwata Yasuko , Takada Shiro , Mahdavian Abbas
Published: February 2012

We have developed updated attenuation relations for peak ground acceleration (PGA), peak ground velocity (PGV), and acceleration response spectra with 5% damping on the basis of the data (78 earthquakes and 351 records) pertaining to strong ground motion in Iran. Moment magnitude, distance, fault mechanism, site class, and zone were the model parameters considered. A term for the saturation of the acceleration amplitude was also used in the model in order to improve the estimations in near-source regions. A nonlinear regression analysis was performed to obtain the coefficients. A comparison between the data set used in the current study for Iran and two next generation attenuation (NGA) models showed good correlation between our model and the Campbell-Bozorgnia NGA model. The model described is applicable for moment magnitudes from 5.0 to 7.3, distances from 15 to 135 km, and site classes with an average shear-wave velocity at a subsurface depth of 30 m (AVS30) of more than 175 m/s.
Proposed Method for Probabilistic Estimation of Peak Component Acceleration Demands
Authors: Clayton Joshua S. , Medina Ricardo A.
Published: February 2012

A probabilistic method is proposed to quantify peak component acceleration (PCA) demands for nonstructural components attached to elastic and inelastic structures. Incremental dynamic analyses and site-specific ground-motion hazard information are used to estimate PCA hazard curves and component uniform hazard spectra (CUHS) based on various structural and nonstructural parameters. For a given structural system, the primary parameters of interest are the location of the component within the structure, the ratio of the period of the component to the modal periods of the primary structure, and the component damping ratio. Representative results for shear wall structures illustrate the value of applying the method to acceleration-sensitive components, as the quantification of CUHS facilitates the implementation of performance-based design and evaluation approaches. The variability in the component responses presented highlights the need for a robust probabilistic seismic demand estimation methodology for nonstructural components in which the major sources of variability are incorporated.
The Effects of Building Characteristics and Site Conditions on the Damage Distribution in Boumerdès after the 2003 Algeria Earthquake
Authors: Meslem Abdelghani , Yamazaki Fumio , Maruyama Yoshihisa , Benouar Djillali , Kibboua Abderrahmane , Mehani Youcef
Published: February 2012

This study highlights the major contributing factors to the observed damage distribution in the city of Boumerdès after the 2003 Algeria earthquake. The results of field investigations and statistical analyses show that a majority of the damaged buildings, mostly mid-rise reinforced concrete (RC) moment-frame systems, were located on steep slopes and small hilltops, along river valleys. The horizontal-to-vertical (H/V) ratios from free-field microtremor measurements at these sites did not show clear results. In contrast, buildings with the same structural characteristics located on flat ground did not suffer much damage, and clear peaks were observed from the H/V ratio curves. The amplification effects of topography have not been incorporated into the revised Algerian seismic code, but the results from this study show the importance of considering this factor when designing new buildings for earthquake resistance.
Obese mice exhibit an altered behavioural and inflammatory response to lipopolysaccharide
Authors: Lawrence Catherine B. , Brough David , Knight Elysse M.
Published: February 2012

Obesity is associated with an increase in the prevalence and severity of infections. Genetic animal models of obesity (ob/ob and db/db mice) display altered centrally-mediated sickness behaviour in response to acute inflammatory stimuli such as lipopolysaccharide (LPS). However, the effect of diet-induced obesity (DIO) on the anorectic and febrile response to LPS in mice is unknown. This study therefore determined how DIO and ob/ob mice respond to a systemic inflammatory challenge. C57BL/6 DIO and ob/ob mice, and their respective controls, were given an intraperitoneal (i.p.) injection of LPS. Compared to controls, DIO and ob/ob mice exhibited an altered febrile response to LPS (100 μg/kg) over 8 h. LPS caused a greater and more prolonged anorexic effect in DIO mice, and in ob/ob mice, LPS induced a reduction in food intake and body weight at an earlier time point. These effects of LPS in obese mice were also seen after a fixed dose of LPS (5 μg). LPS (100 μg/kg) induced c-Fos protein expression in several brain nuclei of control mice, with fewer c-Fos-positive cells observed in the brains of obese mice. An altered inflammatory response to LPS was also observed in obese mice as changes in cytokine expression and release were detected in the plasma, spleen, liver and peritoneal macrophages. In summary, DIO and ob/ob mice displayed an altered behavioural response and cytokine release to systemic inflammatory challenge. These findings could help explain why obese humans show an increased sensitivity to infections.
miR-132 regulates the differentiation of dopamine neurons by directly targeting Nurr1 expression
Authors: Yang Dehua , Li Ting , Wang Yi , Tang Yuanjia , Cui Huijuan , Tang Yu , Zhang Xiaojie , Chen Degui , Shen Nan , Le Weidong
Published: February 2012

Although it is well established that embryonic stem (ES) cells have the potential to differentiate into dopamine neurons, the molecular basis of this process, particularly the role of microRNAs (miRNAs), remains largely unknown. Here we report that miR-132 plays a key role in the differentiation of dopamine neurons by directly regulating the expression of Nurr1. First, we constructed a mouse ES cell line CGR8, which stably expresses GFP under the tyrosine hydroxylase (TH)-promoter, so the TH-positive neurons could be easily sorted out by a fluorescence-activated cell sorter (FACS). Then, we performed a miRNA array analysis in the purified TH-positive neurons and found that 45 of 585 miRNAs have expression level change >5 fold during dopamine neuron differentiation. Among the 45 miRNAs, we were particularly interested in miR-132 because this miRNA has been reported as being highly expressed in neurons and having a potential role in neurodegenerative diseases. We found that the direct down-regulation of endogenous miR-132 induced by miR-132 antisense oligonucleotide (miR-132-ASO) promoted the differentiation of TH-positive neurons, while ectopic expression of miR-132 in ES cells reduced the number of differentiated TH-positive neurons but did not change the total number of differentiated neurons. Furthermore, we documented that miR-132-ASO could significantly reverse the miR-132-mediated suppression of TH-positive neuron differentiation. Moreover, through bioinformatics assay we identified Nurr1 gene as a potential molecular target of miR-132. Using luciferase-reporter assay and Western blot analysis, we demonstrated that miR-132 could directly regulate the expression of Nurr1. Collectively, our data provide the first evidence that miR-132 is an important molecule regulating ES cell differentiation into dopamine neurons by directly targeting Nurr1 expression.
Modulation ofgurkenTranslation by Insulin/TOR Signaling in Drosophila
Authors: Ferguson Scott B. , Blundon Malachi A. , Klovstad Martha S. , Schüpbach Trudi
Published: February 2012

Localized Gurken translation specifies the anterior/posterior and dorsal/ventral axes of the developing Drosophila oocyte. spindle-class females lay ventralized eggs resulting from inefficient grk translation. This phenotype is thought to result from inhibition of the Vasa RNA helicase. In a screen for modifiers of the eggshell phenotype in spn-B flies, we identified a mutation in the lnk gene. We show that lnk mutations restore Grk expression, but do not suppress the persistence of double strand breaks nor other spn-B phenotypes. This suppression does not affect Egfr directly, but rather overcomes the translational block of grk messages seen in spindle mutants. Lnk was recently identified as a component of the insulin/insulin-like growth factor signaling (IIS) / TOR pathway. Interestingly, direct inhibition of TOR with rapamycin can also suppress the ventralized eggshell phenotype in spn-B or vasa mutant mothers. When dietary protein is inadequate, reduced IIS/TOR activity inhibits cap-dependent translation by promoting the activity of the translation inhibitor eIF4E binding protein. We hypothesize that reduced TOR activity promotes grk translation independent of the canonical Vasa/cap-dependent mechanism. This model suggests a means by which flies can maintain the translation of developmentally important transcripts during periods of nutrient limitation when bulk cap-dependent translation is repressed.
ERK2 drives tumour cell migration in 3D microenvironments by suppressing expression of Rab17 and Liprin-β2
Authors: von Thun Anne , Birtwistle Marc , Kalna Gabriela , Grindlay Joan , Strachan David , Kolch Walter , von Kriegsheim Alexander , Norman Jim C.
Published: February 2012

Upregulation of the extracellular signal-regulated kinase (ERK) pathway has been shown to contribute to tumour invasion and progression. Since the two predominant ERK isoforms (ERK1 and ERK2) are highly homologous and have indistinguishable kinase activities in vitro, both enzymes were believed to be redundant and interchangeable. To challenge this view, here we show that ERK2 silencing inhibits invasive migration of MDA-MB-231 cells, and re-expression of ERK2 but not ERK1 restores the normal invasive phenotype. A detailed quantitative analysis of cell movement on 3D matrices indicates that ERK2 knockdown impairs cellular motility by decreasing the migration velocity as well as increasing the time that cells spend not moving. We used gene expression arrays to identify rab17 and liprin-β2 as genes whose expression was increased by knockdown of ERK2 and restored to normal levels following re-expression of ERK2, but not ERK1. Both Rab17 and Liprin-β2 play inhibitory roles in the invasive behaviour of three independent cancer cell lines. Importantly, knockdown of either Rab17 or Liprin-β2 restores invasiveness of ERK2-depleted cells, indicating that ERK2 drives invasion of MDA-MB-231 cells by suppressing expression of these genes.
CD151 restricts α6 integrin diffusion mode
Authors: Yang Xiuwei H. , Mirchev Rossen , Deng Xinyu , Yacono Patrick , Yang Helen L. , Golan David E. , Hemler Martin E.
Published: February 2012

Laminin-binding integrins (α3β1, α6β1, α6β4, α7β1) are almost always expressed together with tetraspanin CD151. In every co-expressing cell analyzed to date, CD151 makes a fundamental contribution towards integrin-dependent motility, invasion, morphology, adhesion and/or signaling. However, there has been minimal mechanistic insight into how CD151 affects integrin functions. In MDA-MB-231 mammary cells, tetraspanin CD151 knockdown impairs α6 integrin clustering and functions without decreasing α6 expression or activation. Furthermore, CD151 knockdown minimally affects α6 diffusion magnitude, as measured using single particle tracking. Instead, CD151 knockdown has a novel and unexpected dysregulating effect on α6 integrin diffusion mode. Control cell α6 shows mostly random/confined diffusion (RCD) and some directed motion (DMO). In sharp contrast, CD151 knockdown cell α6 shows mostly DMO. Control α6 diffusion mode is sensitive to actin disruption, talin knockdown, and phorbol ester stimulation. In contrast, CD151 knockdown cell α6 is sensitive to actin disruption but desensitized to talin knockdown or phorbol ester stimulation, indicating dysregulation. Both phorbol ester and EGF stimulate cell spreading and promote α6 RCD in control cells. In contrast, CD151-ablated cells retain EGF effects but lose phorbol ester-stimulated spreading and α6 RCD. For α6 integrins, physical association with CD151 promotes α6 RCD, in support of α6-mediated cable formation and adhesion. By comparison, for integrins not associated with CD151 (e.g. αv integrins), CD151 affects neither diffusion mode, nor αv function. Hence, CD151 support of α6 RCD is specific and functionally relevant, and likely underlies diverse CD151 functions in skin, kidney, and cancer cells.
TRIM6 interacts with c-Myc and maintains pluripotency of mouse embryonal stem cells
Authors: Sato Tomonobu , Okumura Fumihiko , Ariga Tadashi , Hatakeyama Shigetsugu
Published: February 2012

The proto-oncogene product c-Myc is a master regulator of cell proliferation by specific binding to the E-box motif in genomic DNA. It has been reported that c-Myc plays an important role in the proliferation and maintenance of pluripotency of embryonal stem (ES) cells and that the transcriptional activity of c-Myc is regulated by several posttranslational modifications including ubiquitination. In this study, we showed that TRIM6, one of the TRIM family ubiquitin ligases, is selectively expressed in ES cells and interacts with c-Myc followed by attenuation of transcriptional activity of c-Myc. Knockdown of TRIM6 in ES cells enhanced transcriptional activity of c-Myc and repressed expression of Nanog, resulting in promotion of the differentiation of ES cells. These findings indicate that TRIM6 regulates the transcriptional activity of c-Myc for maintaining pluripotency of ES cells, suggesting that TRIM6 functions as a novel regulator for c-Myc-mediated transcription in ES cells.
Downregulation of BCL2 by miRNAs augments drug induced apoptosis: Combined computational and experimental approach
Authors: Singh Richa , Saini Neeru
Published: February 2012

A number of anti-cancer strategies aim at targeting the mitochondrial apoptotic machinery to induce tumour cell death. Mitochondria play a key role as death amplifiers by releasing apoptogenic factors from the mitochondrial inter-membrane space into the cytosol. BCL2 proteins are known for their ability to regulate both mitochondrial physiology and cell death and their deregulated expression often renders cancer cells insensitive to apoptosis inducing anticancer drugs. Recently a few microRNAs, the novel class of gene regulators, have been identified to regulate expressions of some members of BCL2 family. In the present study we have combined computational and experimental approaches to identify miRNAs which can regulate the anti-apoptotic protein BCL2. Here we report that miR-195, miR-24-2 and miR-365-2 act as negative regulators of BCL2 through direct binding to their respective binding sites in the 3′ UTR of human BCL2 gene. Ectopic expression of miR-195, miR-24-2 and miR-365-2 individually led to significant reduction of BCL2 protein levels. Additionally, we found that over expression of these miRNAs induced dissipation of mitochondrial membrane potential and release of cytochrome c from mitochondria into the cytosol. Furthermore, we demonstrated that over expression of these miRNAs not only caused an increase in apoptosis but also augmented the apoptotic effect of etoposide in breast cancer MCF7 cells. This data not only shows the apoptotic nature of miR-195, miR-24-2 and miR-365-2 but also highlights the therapeutic potential of these miRNAs.
A novel smooth septate junction-associated membrane protein, Snakeskin, is required for intestinal barrier function inDrosophila
Authors: Yanagihashi Yuichi , Usui Tadao , Izumi Yasushi , Yonemura Shigenobu , Sumida Motoyuki , Tsukita Shoichiro , Uemura Tadashi , Furuse Mikio
Published: February 2012

Septate junctions (SJs) are the membrane specializations observed between epithelial cells in invertebrates. SJs play a crucial role in epithelial barrier function by restricting free diffusion of solutes through the intercellular space. In arthropod species, two morphologically different types of SJs have been described: pleated septate junctions (pSJs) and smooth septate junctions (sSJs), which are specific to ectodermal and endodermal epithelia, respectively. In contrast to the recent understanding of pSJ-related proteins, the molecular constituents of sSJs are mostly unknown. Here we report a novel sSJ-specific membrane protein, designated ‘Snakeskin’ (Ssk). Ssk is highly concentrated in sSJs in the Drosophila midgut and Malpighian tubules. Lack of Ssk expression is embryonically lethal in Drosophila and results in defective sSJ formation accompanied by abnormal morphology of midgut epithelial cells. We also show that the barrier function of the midgut to a fluorescent tracer is impaired in Ssk-knockdown larvae. These results suggest that Ssk is required for the intestinal barrier function in Drosophila.
The neuropeptide

PACAP38

induces dendritic spine remodeling through ADAM10/N-Cadherin signaling pathway
Authors: Gardoni Fabrizio , Di Luca Monica , Malinverno Matteo , Marcello Elena , Verpelli Chiara , Sala Carlo , Di Luca Monica
Published: February 2012

The neuropeptide pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) has been implicated in the induction of synaptic plasticity at the excitatory glutamatergic synapse. In particular, recent studies have shown that it is involved in the regulation of NMDA and AMPA receptor activation. Here we demonstrate the effect of PACAP38 on the modulation of dendritic spine morphology through ADAM10/N-Cadherin/AMPA receptor signaling pathway. Treatment of primary hippocampal neurons with PACAP38 induces an accumulation of ADAM10 at the postsynaptic membrane. This event leads to a significant decrease of dendritic spine head width and to a concomitant reduction of GluR1 co-localization with postsynaptic markers. PACAP38-induced effect on dendritic spine head width is prevented by either treatment with ADAM10 specific inhibitor or transfection of a cleavage-defective N-Cadherin construct, mutated in the ADAM10 cleavage site. Overall, our findings reveal for the first time that PACAP38 is involved in the modulation of dendritic spine morphology in hippocampal neurons and assign to the ADAM10/N-Cadherin signaling pathway a crucial role in this modification of the excitatory glutamatergic synapse.
Microenvironmental control of cell migration: Myosin IIA is required for efficient migration in fibrillar environments through control of cell adhesion dynamics
Authors: Doyle Andrew D. , Kutys Matthew L. , Conti Mary Anne , Matsumoto Kazue , Adelstein Robert S. , Yamada Kenneth M.
Published: February 2012

Recent evidence suggests that organization of the extracellular matrix (ECM) into aligned fibrils or fibril-like ECM topographies promotes rapid migration in fibroblasts. However, the mechanisms of cell migration altered by these changes in microenvironmental topography remain unknown. Here, using 1D fibrillar migration as a model system for oriented fibrillar 3D matrices, we find that fibroblast leading edge dynamics are enhanced by 1D fibrillar micropatterns and demonstrate a dependence on the spatial positioning of cell adhesions. Although 1D, 2D, and 3D matrix adhesions have similar assembly kinetics, both 1D and 3D adhesions are stabilized for prolonged periods, while both paxillin and vinculin show slower turnover rates in 1D adhesions. Moreover, actin in 1D adhesions undergoes slower retrograde flow than the actin present in 2D lamellipodia. These data suggest an increase in mechanical coupling between adhesions and protrusive machinery. Experimental reduction of contractility resulted in loss of 1D adhesion structure and stability, with scattered small and unstable adhesions and an uncoupling of adhesion protein-integrin stability. Genetic ablation of myosin IIA or IIB isoforms revealed that myosin IIA is required for efficient migration in restricted environments as well as adhesion maturation, while myosin IIB helps to stabilize adhesions beneath the cell body. These data suggest that restricted cell environments such as 1D patterns require cellular contraction via myosin IIA to enhance adhesion stability and coupling to integrins behind the leading edge. This increase in mechanical coupling allows for greater leading edge protrusion and rapid cell migration.
A Conserved Role of IQGAP1 in Regulating TOR Complex 1
Authors: Tekletsadik Yemsrach K. , Sonn Robert , Osman Mahasin A.
Published: February 2012

Defining the mechanisms that orchestrate cell growth and division is crucial to understanding cell homeostasis, which impacts human diseases like cancer and diabetes. IQGAP1, a widely conserved effector/regulator of the GTPase CDC42 is a putative oncogene that control cell proliferation, however, its mechanism in tumorigenesis is unknown. The mTOR pathway, the center of cell growth control, is commonly activated in human cancers, but proved ineffective as clinical target due to incomplete understanding of its mechanisms in cell growth inhibition. Using complementary studies in yeast and mammalian cells, here we report a potential role for IQGAP1 in regulating the negative feedback loop (NFL) of the target of rapamycin complex1 (mTORC1) that control cell growth. Two-hybrid screens identified yeast TORC1-specific subunit, Tco89p, as an Iqg1p-binding partner sharing roles in rapamycin-sensitive growth, axial bud-site selection and cytokinesis, thus coupling cell growth and division. Mammalian IQGAP1 binds mTORC1 and Akt1 and in response to epidermal growth factor (EGF), cells expressing the mTORC1/Akt1-binding region, IQGAP1IR-WW, contained attenuated pERK1/2 activity and inactive glycogen synthase kinase 3α/β (pGSK3α/β), which control apoptosis. Interestingly, these cells displayed high level of pAkt1S473, but attenuated level of the mTORC1-dependent kinase, pS6k1T389 and induced mTORC1/Akt1- and EGF-dependent transformed phenotypes. Moreover, IQGAP1 appears to influence cell abscission and its activity is elevated in carcinoma cell lines. These findings support the hypothesis that IQGAP1 acts upstream on the mTORC1/S6K1→Akt1 NFL and downstream of it to couple cell growth and division and thus like a rheostat regulates cell homeostasis, dysregulation of which leads to tumorigenesis or other diseases. These results could have implications on developing the next generation of anticancer therapeutics.
Origin, composition, organization and function of the inner membrane complex of Plasmodium falciparum gametocytes
Authors: Dearnley Megan K. , Yeoman Jeffrey A. , Hanssen Eric , Kenny Shannon , Turnbull Lynne , Whitchurch Cynthia B. , Tilley Leann , Dixon Matthew W. A.
Published: February 2012

The most virulent of the human malaria parasites, Plasmodium falciparum, undergoes a remarkable morphological transformation as it prepares itself for sexual reproduction and transmission via mosquitoes. Indeed P. falciparum is named for the unique falciform or crescent shape of the mature sexual stages. Once the metamorphosis is completed the mature gametocyte releases from sequestration sites and enters the circulation making it accessible to feeding mosquitoes. Early ultrastructural studies showed that gametocyte elongation is driven by the assembly of a system of flattened cisternal membrane compartments underneath the parasite plasma membrane and a supporting network of microtubules. Here we describe the molecular composition and origin of the sub-pellicular membrane complex, and show that it is analogous to the inner membrane complex, an organelle with structural and motor functions that is well conserved across the apicomplexa. We identify novel cross-linking elements that may help stabilize the inner membrane complex during gametocyte development. We show that changes in gametocyte morphology are associated with an increase in cellular deformability and postulate that this enables the gametocytes to circulate in the blood stream without being detected and removed by the mechanical filtering mechanisms in the host's spleen.
Regulation of sphingolipid synthesis via Orm1 and Orm2 in yeast
Authors: Liu Ming , Huang Chunjuan , Polu Surendranath R. , Schneiter Roger , Chang Amy
Published: February 2012

Sphingolipids are critical components of membranes and sphingolipid metabolites also serve as signaling molecules. Yeast Orm1 and Orm2 belong to a conserved family of ER membrane proteins that regulate serine palmitoyltransferase, catalyzing the first and rate-limiting step in sphingolipid synthesis. We now show that sphingolipid synthesis via Orm1 is a target of TOR signaling which regulates cell growth in response to nutritional signals. Orm1 phosphorylation is dependent on the Tap42-phosphatase complex which acts downstream of TOR protein kinase complex 1; in temperature-sensitive tap42-11 cells, impaired Orm1 phosphorylation occurs concomitantly with reduced sphingolipid synthesis. A second mechanism regulating sphingolipid synthesis is via controlling Orm2 protein level. Orm2 protein level responds to ER stress conditions, increasing when cells are treated with tunicamycin or DTT, agents that induce the unfolded protein response (UPR). The sphingolipid intermediates, long chain base and ceramide, are decreased when ORM2 is overexpressed, suggesting sphingolipid synthesis is repressed under ER stress conditions. Finally, in the absence of the Orms, the UPR is constitutively activated. Lipid dysregulation in the absence of the Orms may signal to the ER from the plasma membrane as UPR activation is dependent on a cell surface sensor and the MAPK cell wall integrity pathway. Thus, sphingolipid synthesis and the UPR are coordinately regulated.
Design and Operations of Gas Transmission Networks
Authors: Babonneau Frédéric , Nesterov Yurii , Vial Jean-Philippe
Published: February 2012

Problems dealing with the design and operations of gas transmission networks are challenging. The standard approaches lead to a difficult nonlinear nonconvex optimization problem. To get around this difficulty, we use a minimum energy principle to define stationary flows in the network. This solution minimizes the total energy dissipated in the system. We extend the minimization process to the choice of suitable diameters on the reinforcing arcs and add a constraint that limits the monetary cost of investment and of purchase and delivery of gas. Under a suitable and acceptable approximation of the structure of the investment cost function, the new problem turns out to be convex and tractable even for very large networks.
Patterns of Sexual Partnering and Reproductive History: Associations with Timing of First Birth in a Birth Cohort
Authors: van Roode Thea , Dickson Nigel , Sharples Katrina , Paul Charlotte
Published: February 2012

CONTEXT:The associations between timing of first live birth and previous sexual behavior and pregnancies are not well understood.

METHODS: Members of a 1972–1973 New Zealand birth cohort were surveyed at ages 21, 26 and 32 about their sexual and reproductive histories; 506 men and 479 women participated in at least one assessment. Relative risks and 95% confidence intervals were calculated using Poisson regression to examine associations between the likelihood of first live birth at specific ages (prior to age 21, at age 21–25, at age 26–31) and selected characteristics.

RESULTS: Birth prior to age 21 was more likely for men and women who initiated intercourse before age 15 (relative risks, 3.1 and 2.0, respectively), and less likely for those who initiated at age 18 or later (0.3 and 0.1, respectively), than for those aged 15–17 at first coitus. Prior miscarriage was associated (although sometimes marginally) with an elevated likelihood of first birth across genders and ages (1.7–1.8). Prior abortion was associated with an elevated likelihood of first birth at age 21–25 for women (1.6) and a reduced likelihood at age 26–31 for men (0.5). Having multiple sexual partners at age 21–25 was negatively associated with the likelihood of a first birth at age 26–31 for men. Marriage and cohabitation were positively associated with birth timing.

CONCLUSIONS: Early sexual initiation and relationship instability may promote parenthood at younger ages, whereas greater relationship stability may do so at older ages.
Case Study to Promote the Use of Industrial Byproducts: The Relevance of Performance Tests
Authors: Gomes Correia A. , Roque António J. , Reis Ferreira S. M. , Fortunato Eduardo
Published: February 2012

Currently, there is strong pressure to use industrial byproducts and recycled materials in the construction of transportation infrastructure and geotechnical works. The reuse of these materials positively affects the environment by reducing deposits and preserving raw materials. The related geotechnical, geoenvironmental, economical, and social issues should be addressed so that these materials can be used in construction to provide sustainable development. This paper presents a study of all of these aspects and focuses on Portuguese electrical arc furnace steel slag. A huge laboratory research program was carried out that addressed four elements of geotechnical and geoenvironmental behavior: ultimate strength under monotonic loading, resilient behavior (stiffness), susceptibility to permanent deformation due to repeated loading, and leachability. These test results were compared with those from the empirical tests used in the national specifications for embankments and structural layers of transportation infrastructures. It was concluded that performance-based laboratory test results show much better material performance than the results based on empirical tests (Los Angeles and micro-Deval). Furthermore, this material shows better mechanical performance than in the mechanical tests of natural unbound granular materials used in road construction. Additionally, leaching test results show that this byproduct is inert, which caused it to become known as “inert steel aggregates for construction” (ISAC). These laboratory conclusions were validated in a full-scale field trial by end performance testing (using devices that measure in situ stiffness through spot tests and continuous monitoring, as well as lysimeters to measure leaching values). This field trial involved raw materials and ISAC. A final remark is made about some socioeconomic aspects that should be taken into account in decision making regarding the use of ISAC in public works.
Shifting the Paradigm in Radiation Safety
Authors: Doss Mohan
Published: February 2012

The current radiation safety paradigm using the linear no-threshold (LNT) model is based on the premise that even the smallest amount of radiation may cause mutations increasing the risk of cancer. Autopsy studies have shown that the presence of cancer cells is not a decisive factor in the occurrence of clinical cancer. On the other hand, suppression of immune system more than doubles the cancer risk in organ transplant patients, indicating its key role in keeping occult cancers in check. Low dose radiation (LDR) elevates immune response, and so it may reduce rather than increase the risk of cancer. LNT model pays exclusive attention to DNA damage, which is not a decisive factor, and completely ignores immune system response, which is an important factor, and so is not scientifically justifiable. By not recognizing the importance of the immune system in cancer, and not exploring exercise intervention, the current paradigm may have missed an opportunity to reduce cancer deaths among atomic bomb survivors. Increased antioxidants from LDR may reduce aging-related non-cancer diseases since oxidative damage is implicated in these. A paradigm shift is warranted to reduce further casualties, reduce fear of LDR, and enable investigation of potential beneficial applications of LDR.
The Chosen Dimensions of Governance of Production Enterprises in the Customer-Supplier Relations
Authors: Kita Jaroslav , Grossmanová Marta , Kita Pavol
Published: February 2012

The Chosen Dimensions of Governance of Production Enterprises in the Customer-Supplier Relations

Good governance of customer-supplier relations is a precondition of a balanced and permanent development of production enterprises. The aim of the article is to characterize the chosen dimensions, namely the trust and engagement of the customer. It consists of two parts. The first part contains the characteristics of approaches to the issue of governance. The second part identifies a specific way of governance of customers in relation to suppliers.
Online Marketing Strategies for Travel Agencies
Authors: Volek Martin
Published: February 2012

Online Marketing Strategies for Travel Agencies

This paper describes the theoretical foundations of marketing in the online environment in which a travel agency may develop an effective strategy for selling their products. In the first part of the article the author is focusing on functions of online marketing as well as on its advantages over traditional marketing instruments. In the next section the author addresses the search engine optimization in order to improve the position of a travel agency when searching for potential customers. In the final section the author describes the key social media as well as the right method how a travel agency should enter them. The basics and experiences described in the paper can be used as a universal guide for all travel agencies intending to successfully manage their marketing activities in the online environment.
A Novel Design and Preliminary Investigation of Composite Material Marine Current Turbine
Authors: Wang Jifeng , Piechna Janusz , Müller Norbert
Published: February 2012

A Novel Design and Preliminary Investigation of Composite Material Marine Current Turbine

A high performance and light-weight wound composite material wheel has been developed and is intended to be used for many purposes. One of these applications is marine current turbine (MCT). Traditionally, major problems influencing the design and operation of MCTs are fatigue, cavitation and corrosion due to the sea water. Considering these factors, implementation of composite materials, especially Kevlar fiber/epoxy matrix, in MCTs is explained in this paper. This novel design pattern of composite material marine current turbine (CMMCT) shows many advantages compared to conventional turbines. This paper investigated several factors which should be considered during this novel turbine design process such as the composite material selection, filament winding of composite wheel and turbine's structural and cavitation analysis. The power coefficient of CMMCT by using CFD is also obtained and the experimental facilities for testing CMMCT in a water towing tank are briefly described.
A Geographical Approach for Measuring the Creative Capital. Case Study: Creative Capital Index of Slovakia
Authors: Murgaš František , Ševčíková Marta
Published: February 2012

A Geographical Approach for Measuring the Creative Capital. Case Study: Creative Capital Index of Slovakia

Calculation of creativity index is a part of a modern quantification wave, in some cases also formulation of the spatial differentiation of social and economic phenomena required from the academic sphere by the decisive sphere. Policy makers have interest by this means to help themselves in obtaining public for their objectives. The creative capital as a sum of quantifiable creativity indicators is in this contribution operationalized including the social capital, which is out of accord with a traditional understanding of creativity following the Florida's concept of the creative class. Methods for creativity index formation are introduced at the global level of states as well as at the regional level of a given state. There are substantial differences among both indexes results and statistical data on export of creative goods (UNCTAD) that are well documented on example of USA and China. Terminological chaos associated with the concepts of creative class and economy is thus extended with a chaos in the interpretation of findings, what contributes to the critique of the Florida's concept of creative class. There arise doubts that the quantification of creativity indexes with correlation quantification with other economic and social factors as GDP, entrepreneurship, inequality, Index HDI1) (Florida 2011); is maybe right in terms of mathematics, but it does not reveal the casual connections. The research purpose of the contribution is a geographical approach to the creative capital. The case study incorporates the Slovak regions, creativity index calculation and its spatial differentiation in form of map expression. The scientific goal lies in a confirmation of hypothesis about a dominant position of Bratislava region, and thus the capital of Slovakia. A limit of calculation is the choice of indicators which were strongly determined by the accessibility of statistical data.
On the Structure of the Domain of a Symmetric Jump-type Dirichlet Form
Authors: Schilling René L. , Uemura Toshihiro
Published: February 2012

We characterize the structure of the domain of a pure jump-type Dirichlet form which is given by a Beurling{Deny formula. In particular, we obtain sufficient conditions in terms of the jumping kernel guaranteeing that the test functions are a core for the Dirichlet form and that the form is a Silverstein extension. As an application we show that for recurrent Dirichlet forms the extended Dirichlet space can be interpreted in a natural way as a homogeneous Dirichlet space. For reflected Dirichlet spaces this leads to a simple purely analytic proof that the active reflected Dirichlet space (in the sense of Chen, Fukushima and Kuwae) coincides with the extended active reflected Dirichlet space.
Algebraic Local Cohomology Classes Attached to Unimodal Singularities
Authors: Tajima Shinichi , Nakamura Yayoi
Published: February 2012

Algebraic local cohomology classes and holonomic systems attached to non-quasihomogeneous isolated unimodal singularities are considered in the context of algebraic analysis. Holonomic systems and their algebraic local cohomology solution spaces attached to a unimodal singularity are studied in a constructive manner. The holonomic system constructed from linear partial differential operators of order at most two that annihilate the given algebraic local cohomology is proven to be simple for the case of non-quasihomogeneous unimodal singularities.
A Numerical Characterization of Polarized Manifolds $(X,\mathcal{L})$ with $K_{X}=-(n-i)\mathcal{L}$ by the $i$th Sectional Geometric Genus and the $i$th $\Delta$-genus
Authors: Fukuma Yoshiaki
Published: February 2012

Let

(X,\mathcal{L})

be a polarized manifold of dimension

n

. In this paper, by using the

i

th sectional geometric genus and the

i

th

\Delta

-genus, we will give a numerical characterization of

(X,\mathcal{L})

with

K_{X}=-(n-i)\mathcal{L}

for the following cases (i)

i=2

, (ii)

i=3

and

n\geq 5

, (iii)

\mathrm{max}\{ 2, \dim \mathrm{Bs}|\mathcal{L}|+2\}\leq i\leq n-1

.
Hutchinson–Weber Involutions Degenerate Exactly when the Jacobian is Comessatti
Authors: Ohashi Hisanori
Published: February 2012

We consider the Jacobian Kummer surface

X

of a genus two curve

C

. We prove that the Hutchinson–Weber involution on

X

degenerates if and only if the Jacobian

J(C)

is Comessatti. Also we give several conditions equivalent to this, which include the classical theorem of Humbert. The key notion is Weber hexads, which are special sets of 2-torsion points of the Jacobian. We include an explanation of them and discuss the dependence between the conditions of the main theorem for various Weber hexads. It results in "the dual six equivalence". We also give a detailed description of relevant moduli spaces. As an application, we give a conceptual proof of the computation of the patching subgroup for generic Hutchinson–Weber involutions.
Multidegrees of Tame Automorphisms in Dimension Three
Authors: Sun Xiaosong , Chen Yan
Published: February 2012

We discuss when a sequence of positive integers can be the multidegree of some tame automorphism in dimension three, and we also relate these investigations to the problem of whether there exists a tame automorphism admitting a reduction of type II or type III.
Problème de Cauchy et Goursat Analytique
Authors: Hamada Yûsaku , Ōkaji Takashi , Takei Yoshitsugu
Published: February 2012

We study singularities and analytic continuations of the solution of the Cauchy and Goursat problem in the complex domain and give some examples.
The Tick Salivary Protein Sialostatin L Inhibits the Th9-Derived Production of the Asthma-Promoting Cytokine IL-9 and Is Effective in the Prevention of Experimental Asthma
Authors: Horka Helena , Staudt Valérie , Klein Matthias , Taube Christian , Reuter Sebastian , Dehzad Nina , Andersen John F. , Kopecky Jan , Schild Hansjörg , Kotsyfakis Michalis , Hoffmann Markus , Gerlitzki Bastian , Stassen Michael , Bopp Tobias , Schmitt Edgar
Published: February 2012

Ticks developed a multitude of different immune evasion strategies to obtain a blood meal. Sialostatin L is an immunosuppressive cysteine protease inhibitor present in the saliva of the hard tick Ixodes scapularis. In this study, we demonstrate that sialostatin L strongly inhibits the production of IL-9 by Th9 cells. Because we could show recently that Th9-derived IL-9 is essentially involved in the induction of asthma symptoms, sialostatin L was used for the treatment of experimental asthma. Application of sialostatin L in a model of experimental asthma almost completely abrogated airway hyperresponsiveness and eosinophilia. Our data suggest that sialostatin L can prevent experimental asthma, most likely by inhibiting the IL-9 production of Th9 cells. Thus, alternative to IL-9 neutralization sialostatin L provides the basis for the development of innovative therapeutic strategies to treat asthma.
JAB1 Is Essential for B Cell Development and Germinal Center Formation and Inversely Regulates Fas Ligand and Bcl6 Expression
Authors: Sitte Selina , Gläsner Joachim , Jellusova Julia , Weisel Florian , Panattoni Martina , Pardi Ruggero , Gessner André
Published: February 2012

Jun activation domain-binding protein 1 (JAB1) regulates ubiquitin-dependent protein degradation by deneddylation of cullin-based ubiquitin ligases and, therefore, plays a central role in regulating proliferation and apoptosis. Because these processes are decisive for B cell development, we investigated JAB1 functions in B cells by establishing a mouse strain with a B cell-specific JAB1 deletion. We show that JAB1 is essential for early B cell development, because the ablation of JAB1 expression blocks B cell development between the pro-B and pre-B cell stages. Furthermore, JAB1 deletion leads to aberrant expression of the apoptosis-triggering protein Fas ligand in pro-B cells. Concomitant B cell-specific overexpression of the antiapoptotic protein Bcl2 partially reverses the block in B cell development; rescued JAB1-deficient B cells reach the periphery and produce protective class-switched Abs after Borrelia burgdorferi infection. Interestingly, B cell-rescued mice exhibit no germinal centers but a striking extrafollicular plasma cell accumulation. In addition, JAB1 is essential for Bcl6 expression, a transcriptional repressor required for germinal center formation. These findings identify JAB1 as an important factor in checkpoint control during early B cell development, as well as in fate decisions in mature Ag-primed B cells.
Modulation of Antigen Presentation and B Cell Receptor Signaling in B Cells of Beige Mice
Authors: Chatterjee Priyadarshini , Tiwari Ritesh Kumar , Rath Satyajit , Bal Vineeta , George Anna
Published: February 2012

Binding of Ag by B cells leads to signal transduction downstream of the BCR and to delivery of the internalized Ag–BCR complex to lysosomes where the Ag is processed and presented on MHC class II molecules. T cells that recognize the peptide–MHC complexes provide cognate help to B cells in the form of costimulatory signals and cytokines. Recruitment of T cell help shapes the Ab response by facilitating isotype switching and somatic hypermutation, and promoting the generation of memory cells and long-lived plasma cells. We have used the beige (Bg) mouse, which is deficient in endosome biogenesis, to evaluate the effect of potentially altered Ag presentation in shaping the humoral response. We show that movement of the endocytosed Ag–BCR complex to lysosomes is delayed in Bg B cells and leads to relatively poorer stimulation of Ag-specific T cells. Nevertheless, this does not affect Bg B cell activation or proliferation when competing with wild-type B cells for limiting T cell help in vitro. Interestingly, Bg B cells show more prolonged phosphorylation of signaling intermediates after BCR ligation and proliferate better to low levels of BCR cross-linking. Primary Ab responses are similar in both strains, but memory responses and plasma cell frequencies in bone marrow are higher in Bg mice. Further, Bg B cells mount a higher primary Ab response when competing with wild-type cells in vivo. Thus, the intensity and duration of BCR signaling may play a more important part in shaping B cell responses than early Ag presentation for T cell help.
Alternaria Induces STAT6-Dependent Acute Airway Eosinophilia and Epithelial FIZZ1 Expression That Promotes Airway Fibrosis and Epithelial Thickness
Authors: Doherty Taylor A. , Khorram Naseem , Sugimoto Kotaro , Sheppard Dean , Rosenthal Peter , Cho Jae Youn , Pham Alexa , Miller Marina , Croft Michael , Broide David H.
Published: February 2012

The fungal allergen, Alternaria, is specifically associated with severe asthma, including life-threatening exacerbations. To better understand the acute innate airway response to Alternaria, naive wild-type (WT) mice were challenged once intranasally with Alternaria. Naive WT mice developed significant bronchoalveolar lavage eosinophilia following Alternaria challenge when analyzed 24 h later. In contrast to Alternaria, neither Aspergillus nor Candida induced bronchoalveolar lavage eosinophilia. Gene microarray analysis of airway epithelial cell brushings demonstrated that Alternaria-challenged naive WT mice had a >20-fold increase in the level of expression of found in inflammatory zone 1 (FIZZ1/Retnla), a resistin-like molecule. Lung immunostaining confirmed strong airway epithelial FIZZ1 expression as early as 3 h after a single Alternaria challenge that persisted for ≥5 d and was significantly reduced in STAT6-deficient, but not protease-activated receptor 2-deficient mice. Bone marrow chimera studies revealed that STAT6 expressed in lung cells was required for epithelial FIZZ1 expression, whereas STAT6 present in bone marrow-derived cells contributed to airway eosinophilia. Studies investigating which cells in the nonchallenged lung bind FIZZ1 demonstrated that CD45+CD11c+ cells (macrophages and dendritic cells), as well as collagen-1–producing CD45− cells (fibroblasts), can bind to FIZZ1. Importantly, direct administration of recombinant FIZZ1 to naive WT mice led to airway eosinophilia, peribronchial fibrosis, and increased thickness of the airway epithelium. Thus, Alternaria induces STAT6–dependent acute airway eosinophilia and epithelial FIZZ1 expression that promotes airway fibrosis and epithelial thickness. This may provide some insight into the uniquely pathogenic aspects of Alternaria-associated asthma.