bluuebunny/crossref_metadata_2025 huggingface dataset:
An Approximation to the Effective Beam Weighting Function for Scanning Meteorological Radars with an Axisymmetric Antenna Pattern
Authors: Blahak Ulrich
Published: July 2008

To obtain statistically stable reflectivity measurements by meteorological radars, it is common practice to average over several consecutive pulses during which the antenna rotates at a certain angular velocity. Taking into account the antenna’s continuous motion, the measured reflectivity is determined by an effective beam weighting function, which is different from a single-pulse weighting function—a fact that is widely ignored in applications involving beam weighting. In this paper, the effective beam weighting function is investigated in detail.

The theoretical derivation shows that the effective weighting function is essentially a simple moving sum of single-beam weighting functions. Assuming a Gaussian shape of a single pulse, a simple and easy-to-use parameterization of the effective beam weighting function is arrived at, which depends only on the single beamwidth and the ratio of the single beamwidth to the rotational angular averaging interval. The derived relation is formulated in the “radar system” (i.e., the spherical coordinate system consisting of azimuth and elevation angles) that is often applied in practice. Formulas for the “beam system” (two orthogonal angles relative to the beam axis) are also presented.

The final parameterization should be applicable to almost all meteorological radars and might be used (i) in specialized radar data analyses (with ground-based or satellite radars) and (ii) for radar forward operators to calculate simulated radar parameters from the results of NWP models.
Tornado Detection Using a Neuro–Fuzzy System to Integrate Shear and Spectral Signatures
Authors: Wang Yadong , Yu Tian-You , Yeary Mark , Shapiro Alan , Nemati Shamim , Foster Michael , Andra David L. , Jain Michael
Published: July 2008

Tornado vortices observed from Doppler radars are often associated with strong azimuthal shear and Doppler spectra that are wide and flattened. The current operational tornado detection algorithm (TDA) primarily searches for shear signatures that are larger than the predefined thresholds. In this work, a tornado detection procedure based on a fuzzy logic system is developed to integrate tornadic signatures in both the velocity and spectral domains. A novel feature of the system is that it is further enhanced by a neural network to refine the membership functions through a feedback training process. The hybrid approach herein, termed the neuro–fuzzy tornado detection algorithm (NFTDA), is initially verified using simulations and is subsequently tested on real data. The results demonstrate that NFTDA can detect tornadoes even when the shear signatures are degraded significantly so that they would create difficulties for typical vortex detection schemes. The performance of the NFTDA is assessed with level I time series data collected by the KOUN radar, a research Weather Surveillance Radar-1988 Doppler (WSR-88D) operated by the National Severe Storms Laboratory (NSSL), during two tornado outbreaks in central Oklahoma on 8 and 10 May 2003. In these cases, NFTDA and TDA provide good detections up to a range of 43 km. Moreover, NFTDA extends the detection range out to approximately 55 km, as the results indicate here, to detect a tornado of F0 magnitude on 10 May 2003.
The Van de Casteele Test Revisited: An Efficient Approach to Tide Gauge Error Characterization
Authors: Miguez Belen Martin , Testut Laurent , Wöppelmann Guy
Published: July 2008

The classical question of metrology related to the quality of the tide gauge measurements has become more important this last decade or so as new technologies have emerged and tide gauge networks are modernized. The Global Sea Level Observing System (GLOSS) target of 1-cm accuracy in the individual sea level measurement is motivated by more demanding applications than the traditional hydrographic works and tide predictions, for instance, the monitoring of the long-term trends in sea level or the calibration of satellite radar altimeters. To examine and further assess the performance of modern tide gauge measurements, the Van de Casteele test is revisited. This test is based on a diagram plotting readings taken with a reference probe against the tide gauge readings over at least one tidal cycle. The application of the test to different sets of data at different locations in the world under different environmental conditions shows the test as a simple procedure that immediately gives a qualitative and quantitative illustration of the errors involved in the sea level measurement, capable of sensing the presence of a fault with whatever tide gauge technology is involved. It is recommended that such quality control tests are brought back into fashion and are conducted on a regular basis, in particular following the upgrading of the tide gauge stations.
Stratification Effects in a Bottom Ekman Layer
Authors: Taylor John R. , Sarkar Sutanu
Published: July 2008

A stratified bottom Ekman layer over a nonsloping, rough surface is studied using a three-dimensional unsteady large eddy simulation to examine the effects of an outer layer stratification on the boundary layer structure. When the flow field is initialized with a linear temperature profile, a three-layer structure develops with a mixed layer near the wall separated from a uniformly stratified outer layer by a pycnocline. With the free-stream velocity fixed, the wall stress increases slightly with the imposed stratification, but the primary role of stratification is to limit the boundary layer height. Ekman transport is generally confined to the mixed layer, which leads to larger cross-stream velocities and a larger surface veering angle when the flow is stratified. The rate of turning in the mixed layer is nearly independent of stratification, so that when stratification is large and the boundary layer thickness is reduced, the rate of veering in the pycnocline becomes very large. In the pycnocline, the mean shear is larger than observed in an unstratified boundary layer, which is explained using a buoyancy length scale, u*/N(z). This length scale leads to an explicit buoyancy-related modification to the log law for the mean velocity profile. A new method for deducing the wall stress based on observed mean velocity and density profiles is proposed and shows significant improvement compared to the standard profile method. A streamwise jet is observed near the center of the pycnocline, and the shear at the top of the jet leads to local shear instabilities and enhanced mixing in that region, despite the fact that the Richardson number formed using the mean density and shear profiles is larger than unity.
Progressive Failure Analysis of Composites
Authors: Tay T.E. , Liu G. , Tan V.B.C. , Sun X.S. , Pham D.C.
Published: July 2008

Recent developments in the aircraft industry towards substantially improving fuel economy and extending flight range have accelerated interest in the use of advanced composites as primary structural materials. The airframes of next-generation airliners will have substantial parts made of light-weight composites. This means that the engineering demands on the performance of fiber-reinforced composites will become greater. There is therefore a need to better understand and predict the multiple complex failure mechanisms in composite structures, and to devise more reliable failure theories and damage progression models. There is a large body of literature on progressive damage analysis in composites, much of which employs damage mechanics and material stiffness degradation methods. This article reviews some of the more recent work in this area and describes the issues pertinent to application in composite structures. The authors' ongoing research efforts in modeling and prediction of progressive damage through the relatively novel element-failure method (EFM), which has been coded into a user-defined UEL code in Abaqus, are discussed. In particular, results for notched composite laminates and pin-loaded (PL) analyses are shown and compared to experimental data. Although EFM is the computational platform on which the damage is advanced in the structure, the results are dependent on the choice of the failure criterion. Various failure criteria are used throughout the cases discussed herein, from the more traditional Tsai—Wu (TW) criterion to the very recently proposed micromechanics-based failure (MMF) criterion. The EFM may also be used with cohesive elements, with the former intended for modeling in-plane damage progression, while the latter for delamination onset and propagation. This hybrid EFM-cohesive element approach is illustrated with an analysis of double-notched composite laminate. The computational models are relatively robust up to and including ultimate load, and enable the mapping of extensive damage patterns in composite structures. They represent a suite of computational tools that extend the capability to model damage and failure propagation beyond initial failure prediction.
On the Malleability of Performance
Authors: Horton Sean , Baker Joe , Pearce G. W. , Deakin Janice M.
Published: July 2008

Popular stereotypes of aging affect the performance of seniors in a number of different domains, from memory performance to physiological response. The authors undertook a review of this area, in which they examined 17 studies that looked at the impact of stereotype primes on older individuals' cognitive, physical, physiological and psychological performance. Analyses included investigating the effects of both positive and negative age stereotypes, and implicit and explicit priming methodologies. The authors utilized a meta-analytic technique on a subset of studies that examined the impact of priming on memory performance. This yielded an effect size of 0.38. The results suggest that popular stereotypes of aging (and the corresponding subtle changes in the testing environment) are important variables to consider for those researchers testing performance of seniors.
Viral hepatitis and HIV-associated tuberculosis: Risk factors and TB treatment outcomes in Thailand
Authors: Sirinak Chawin , Kittikraisak Wanitchaya , Pinjeesekikul Duangporn , Charusuntonsri Pricha , Luanloed Phinai , Srisuwanvilai La-ong , Nateniyom Sriprapa , Akksilp Somsak , Likanonsakul Sirirat , Sattayawuthipong Wanchai , Burapat Channawong , Varma Jay K
Published: July 2008

Background

The occurrence of tuberculosis (TB), human immunodeficiency virus (HIV), and viral hepatitis infections in the same patient poses unique clinical and public health challenges, because medications to treat TB and HIV are hepatotoxic. We conducted an observational study to evaluate risk factors for HBsAg and/or anti-HCV reactivity and to assess differences in adverse events and TB treatment outcomes among HIV-infected TB patients.

Methods

Patients were evaluated at the beginning, during, and at the end of TB treatment. Blood samples were tested for aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (BR), complete blood count, and CD4+ T lymphocyte cell count. TB treatment outcomes were assessed at the end of TB treatment according to international guidelines.

Results

Of 769 enrolled patients, 752 (98%) had serologic testing performed for viral hepatitis: 70 (9%) were reactive for HBsAg, 237 (31%) for anti-HCV, and 472 (63%) non-reactive for both markers. At the beginning of TB treatment, 18 (26%) patients with HBsAg reactivity had elevated liver function tests compared with 69 (15%) patients non-reactive to any viral marker (p = 0.02). At the end of TB treatment, 493 (64%) were successfully treated. Factors independently associated with HBsAg reactivity included being a man who had sex with men (adjusted odds ratio [AOR], 2.1; 95% confidence interval [CI], 1.1–4.3) and having low TB knowledge (AOR, 1.8; CI, 1.0–3.0). Factors most strongly associated with anti-HCV reactivity were having injection drug use history (AOR, 12.8; CI, 7.0–23.2) and living in Bangkok (AOR, 15.8; CI, 9.4–26.5). The rate of clinical hepatitis and death during TB treatment was similar in patients HBsAg reactive, anti-HCV reactive, both HBsAg and anti-HCV reactive, and non-reactive to any viral marker.

Conclusion

Among HIV-infected TB patients living in Thailand, markers of viral hepatitis infection, particularly hepatitis C virus infection, were common and strongly associated with known behavioral risk factors. Viral hepatitis infection markers were not strongly associated with death or the development of clinical hepatitis during TB treatment.
Awareness of health effects of cooking smoke among women in the Gondar Region of Ethiopia: a pilot survey
Authors: Edelstein M , Pitchforth E , Asres G , Silverman M , Kulkarni N
Published: July 2008

Background

The burning of biomass fuels results in exposure to high levels of indoor air pollution, with consequent health effects. Possible interventions to reduce the exposure include changing cooking practices and introduction of smoke-free stoves supported by health education. Social, cultural and financial constraints are major challenges to implementation and success of interventions. The objective of this study is to determine awareness of women in Gondar, Ethiopia to the harmful health effects of cooking smoke and to assess their willingness to change cooking practices.

Methods

We used a single, administered questionnaire which included questions on household circumstances, general health, awareness of health impact of cooking smoke and willingness to change. We interviewed 15 women from each of rural, urban-traditional and middle class backgrounds.

Results

Eighty percent of rural women cooked indoors using biomass fuel with no ventilation. Rural women reported two to three times more respiratory disease in their children and in themselves compared to the other two groups. Although aware of the negative effect of smoke on their own health, only 20% of participants realised it caused problems in children, and 13% thought it was a cause for concern. Once aware of adverse effects, women were willing to change cooking practices but were unable to afford cleaner fuels or improved stoves.

Conclusion

Increasing the awareness of the health-effects of indoor biomass cooking smoke may be the first step in implementing a programme to reduce exposure.
Evidence against PALB2 involvement in Icelandic breast cancer susceptibility
Authors: Gunnarsson Haukur , Arason Adalgeir , Gillanders Elizabeth M , Agnarsson Bjarni A , Johannesdottir Gudrun , Johannsson Oskar Th , Barkardottir Rosa B
Published: July 2008

Several mutations in the PALB2 gene (partner and localizer of BRCA2) have been associated with an increased risk of breast cancer, including a founder mutation, 1592delT, reported in Finnish breast cancer families. Although most often the risk is moderate, it doesn't exclude families with high-risk mutations to exist and such observations have been reported. To see if high-risk PALB2-mutations may be present in the geographically confined population of Iceland, linkage analysis was done on 111 individuals, thereof 61 breast cancer cases, from 9 high-risk non-BRCA1/BRCA2 breast cancer families, targeting the PALB2 region. Also, screening for the 1592delT founder mutation in the 9 high-risk families and in 638 unselected breast cancer cases was performed. The results indicate no linkage in any of the high-risk families and screening for the 1592delT mutation was negative in all samples. PALB2 appears not to be a significant factor in high-risk breast cancer families in Iceland and the 1592delT mutation is not seen to be associated with breast cancer in Iceland.
Unexpected limited chronic dissection of the ascending aorta
Authors: Venturini Andrea , Zoffoli Giampaolo , Mangino Domenico , Ascione Raimondo , Terrini Alberto , Asta Angiolino , Angelini Gianni , Polesel Elvio
Published: July 2008

We report a rare case of a limited chronic dissection of the ascending aorta that was accidentally discovered at operation performed for severe aortic stenosis and moderate to severe dilatation of the ascending aorta. Preoperative investigations such as transoesophageal echocardiography and cardiac catheterization missed the diagnosis of dissection. Intraoperative findings included a 3.5 cm eccentric bulge of the ascending aorta and a 5 mm circular shaped intimal tear comunicating with a limited hematoma or small dissection of the media layer. (The rarety of the report is that the chronic dissection is limited to a small area (approximatively 3.5 × 2.5 cm) of the ascending aorta).
Epigenetic mapping and functional analysis in a breast cancer metastasis model using whole-genome promoter tiling microarrays
Authors: Rodenhiser David I , Andrews Joseph , Kennette Wendy , Sadikovic Bekim , Mendlowitz Ariel , Tuck Alan B , Chambers Ann F
Published: July 2008

Introduction

Breast cancer metastasis is a complex, multi-step biological process. Genetic mutations along with epigenetic alterations in the form of DNA methylation patterns and histone modifications contribute to metastasis-related gene expression changes and genomic instability. So far, these epigenetic contributions to breast cancer metastasis have not been well characterized, and there is only a limited understanding of the functional mechanisms affected by such epigenetic alterations. Furthermore, no genome-wide assessments have been undertaken to identify altered DNA methylation patterns in the context of metastasis and their effects on specific functional pathways or gene networks.

Methods

We have used a human gene promoter tiling microarray platform to analyze a cell line model of metastasis to lymph nodes composed of a poorly metastatic MDA-MB-468GFP human breast adenocarcinoma cell line and its highly metastatic variant (468LN). Gene networks and pathways associated with metastasis were identified, and target genes associated with epithelial–mesenchymal transition were validated with respect to DNA methylation effects on gene expression.

Results

We integrated data from the tiling microarrays with targets identified by Ingenuity Pathways Analysis software and observed epigenetic variations in genes implicated in epithelial–mesenchymal transition and with tumor cell migration. We identified widespread genomic hypermethylation and hypomethylation events in these cells and we confirmed functional associations between methylation status and expression of the CDH1, CST6, EGFR, SNAI2 and ZEB2 genes by quantitative real-time PCR. Our data also suggest that the complex genomic reorganization present in cancer cells may be superimposed over promoter-specific methylation events that are responsible for gene-specific expression changes.

Conclusion

This is the first whole-genome approach to identify genome-wide and gene-specific epigenetic alterations, and the functional consequences of these changes, in the context of breast cancer metastasis to lymph nodes. This approach allows the development of epigenetic signatures of metastasis to be used concurrently with genomic signatures to improve mapping of the evolving molecular landscape of metastasis and to permit translational approaches to target epigenetically regulated molecular pathways related to metastatic progression.
Follicle-Stimulating Hormone Responses to Kisspeptin in the Female Rat at the Preovulatory Period: Modulation by Estrogen and Progesterone Receptors
Authors: Roa J. , Vigo E. , Castellano J. M. , Gaytan F. , García-Galiano D. , Navarro V. M. , Aguilar E. , Dijcks F. A. , Ederveen A. G. H. , Pinilla L. , van Noort P. I. , Tena-Sempere M.
Published: July 2008

Ovulation is triggered by the preovulatory surge of gonadotropins that, in rodents, is defined by the concomitant rise in circulating LH and FSH at the afternoon of proestrus (primary surge), followed by persistently elevated FSH levels at early estrus (secondary surge). In recent years, kisspeptins, products of the KiSS-1 gene that act via G protein-coupled receptor 54, have emerged as an essential hypothalamic conduit for the generation of the preovulatory LH surge by conveying positive feedback effects of estradiol onto GnRH neurons, an event that involves not only estradiol-induced transcription of the KiSS-1 gene at the anteroventral periventricular nucleus but also its ability to modulate GnRH/LH responses to kisspeptin. However, little is known about the potential modulation of FSH responsiveness to kisspeptin by sex steroids in the cyclic female. We report herein analyses on the consequences of selective blockade of estrogen receptors (ER)-α and -β, as well as progesterone receptor (PR), on the ovulatory surges of FSH and their modulation by kisspeptin. Antagonism of ERα or PR equally blunted the primary and secondary surges of FSH and nullified FSH responses to kisspeptin at the preovulatory period. Conversely, selective blockade of ERβ failed to induce major changes in terms of endogenous FSH surges, yet it decreased FSH responses to exogenous kisspeptin. In contrast, FSH responses to GnRH were fully conserved after ERβ blockade and partially preserved after inhibition of ERα and PR signaling. Finally, secondary FSH secretion was rescued by kisspeptin in females with selective blockade of ERα but not PR. In sum, our results substantiate a concurrent, indispensable role of ERα and PR in the generation of FSH surges and the stimulation of FSH responses to kisspeptin at the ovulatory period. In addition, our data suggest that ERβ might operate as a subtle, positive modulator of the preovulatory FSH responses to kisspeptin, a role that is opposite to its putative inhibitory action on kisspeptin-induced LH secretion and might contribute to the dissociation of gonadotropin secretion at the ovulatory phase in the cyclic female rat.
In Vivo Profiling of Estrogen Receptor/Specificity Protein-Dependent Transactivation
Authors: Wu Fei , Xu Rui , Kim Kyounghyun , Martin James , Safe Stephen
Published: July 2008

17β-Estradiol (E2) activates the estrogen receptor (ER) through multiple genomic and nongenomic pathways in various tissues/organs. ERα/specificity protein-dependent activation of E2-responsive genes containing GC-rich promoters has been identified in breast and other cancer cell lines, and in this study, we describe transgenic animals overexpressing a transgene containing three tandem GC-rich sites linked to a minimal TATA or thymidine kinase promoter and a luciferase gene. Several mouse lines expressing the transgenes were characterized and, in line 15, E2 induced a 9-fold increase in luciferase activity in the female mouse uterus, and the synthetic estrogens bisphenol A and nonylphenol also induced uterine luciferase activity. The pure antiestrogen ICI 182,780 induced luciferase activity in the mouse uterus, and similar results were observed for ICI 182,780 in breast cancer cells transfected with this construct. Differences in the ER agonist and antagonist activities of E2, nonylphenol, bisphenol A, and ICI 182,780 were investigated in the male testis and penis and the male and female stomach in line 15 transgenic mice. All of these tissues were hormone responsive; however, the patterns of induced or repressed luciferase activity were ligand structure, tissue, and sex dependent. These results demonstrate for the first time hormonal activation or repression of a GC-rich promoter in vivo, and the results suggest that the ERα/specificity protein pathway may contribute to E2-dependent induction and repression of genes.
Systemidentifikation mittels Glaubenskalkül (System Identification with Belief Calculus)
Authors: Dürrbaum Axel , Scherm Wolfgang , Sommer Hanns
Published: July 2008

Im vorliegenden Aufsatz wird im ersten Abschnitt auf die grundlegende Vorgehensweise zur Systemidentifikation eingegangen, um deren Probleme aufzuzeigen. Im zweiten Abschnitt wird das algorithmische Verfahren zur glaubensbasierten Identifikation hergeleitet. Dabei soll insbesondere der Nachweis geführt werden, dass hier im Gegensatz zu Identifikationsverfahren, die auf der Wahrscheinlichkeitstheorie basieren, alle Freiheitsgrade mittels Anwenderanforderungen eindeutig festgelegt werden können. Im dritten Abschnitt wird das Verfahren zur Prognose des Haltbarkeitsendes der Werkzeuge beim Gewindebohren eingesetzt.
Mutations of CXorf6 are associated with a range of severities of hypospadias
Authors: Kalfa Nicolas , Liu Benchun , Ophir Klein , Audran Francoise , Wang Ming-Hsieh , Mei Cao , Sultan Charles , Baskin Laurence S
Published: July 2008

Objective

Mutations in chromosome X open reading frame 6 (CXorf6), a recently described candidate gene involved in the development of male genitalia, have been found in patients with complex 46,XY disorders of sexual development (46,XY DSD) including micropenis, bifid scrotum, and penoscrotal hypospadias. The objective of this work was to identify genomic variants of CXorf6 in patients with isolated hypospadias, severe or non-severe.

Design and methods

Forty-one patients with glandular to perineal hypospadias and thirty controls were studied. Direct sequencing for coding exons 3–6 of CXorf6 and their flanking splice sites was performed on DNA extracted from foreskin collected from surgery. Secondary and tertiary structures of the protein were predicted using NNpredict and Protein Homology/analogY Recognition Engine engines.

Results

Four mutations (9.7% of cases) were identified. One missense mutation (1295T>C, V432A) and two deletions (325delG, predicted to cause a stop codon L121X) occurred in patients with penoscrotal and proximal hypospadias. One patient with subcoronal hypospadias had CAG-repeat amplification in the second polyglutamine domain of CXorf6. Secondary structure prediction indicated that this insertion occurred in a helix element of the protein. The tertiary structure prediction showed an alteration of the shape of the protein and crowding between domains.

Conclusion

CXorf6 mutations are associated with isolated hypospadias of varying severity. However, the pathophysiology of these mutations and the function of the CXorf6 gene product remain to be investigated.
The Changing College and University Library Market for University Press Books and Journals: 1997–2004
Authors: Greco Albert N. , Jones Robert F. , Wharton Robert M. , Estelami Hooman
Published: July 2008

This article evaluates the economic structure of academic and non-academic libraries; the impact of the ‘serials crisis’ on academic and non-academic library budgets and non-profit university presses; the impact of libraries on the academic life of universities; the impact of the electronic distribution of scholarly content on libraries, academics, students, and university presses; the response of the library community to scholarly book and journal pricing structures; the potential impact of changes in library configurations; the possible impact of the Open Access movement; and the potential impact of the ‘work for hire’ theory.
The Aperture Problem for Visual Motion and Its Solution in Primate Cortex
Authors: Pack Christopher C.
Published: July 2008

A primary function of the visual system is to analyze the trajectories of moving objects. This seemingly simple process is complicated by theoretical considerations, which show that measurements of the velocity of a moving object are inevitably confounded with the spatial arrangement of its edges. This type of confusion is likely to be detrimental to an organism's survival, and so must be resolved. This review describes some recent experiments that demonstrate the existence and time-course of a solution in the visual cortex of the macaque brain. Related work on perception, behavior, and computational theory is discussed.
Inflammatory Bowel Disease: Is the Intestine a Trojan Horse?
Authors: Basset Christelle , Holton John
Published: July 2008

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory condition of the intestines that is clinically heterogenous. The cause(s) of IBD are currently unknown but the mechanisms of injury are immunological. Increasingly there is an emphasis on the study of the complex interactions at the interface of self and non-self- the gastrointestinal epithelial surface- in relationship to the pathogenesis of disease. There is mounting evidence that a lack of tolerance to the normal commensal flora of the intestine may underly the disease pathogenesis. Several genetic loci that are markers of disease susceptibility have been identified. These loci map to areas of the genome that are concerned with antigen presentation or cytokine secretion and suggest a genetic heterogeneity that underlies the clinical differences. Overall a picture is emerging of defects in epithelial barrier function and, or immunoregulation leading to immune responses that are triggered or exaggerated by the antigenic components of the normal flora.
Prospects for Generating New Antibiotics
Authors: Waugh Alastair C.W. , Long Paul F.
Published: July 2008

A plethora of human pathogens are now resistant to all clinically significant antibiotics causing a crisis, in the treatment and management of infectious diseases, but also presenting a clear danger to future public health. If drug resistance is going to be tackled successfully, new antibiotics must be continually developed to counteract the processes of evolution and natural selection in these populations of pathogens. Despite the introduction of powerful new technologies such as high throughput screening platforms and combinatorial chemistry, natural products still offer structural diversity worthy of screening for biological activity. Functional genomics can revolutionise rational drug design providing new targets for antimicrobial drug discovery. The clusters of genes, encoding enzymes that form biosynthetic pathways leading to the synthesis of many natural products including polyketides and nonribosomal peptides, are amenable to modern genetic engineering. Repositioning, deleting and replacing genes in these biosynthetic clusters has resulted in the synthesis of many ‘un-natural’ natural products. This review examines the engineering of proteins involved in chain initiation on polyketide synthases culminating in the production at high yield of a biologically active erythromycin derivative.
Helicobacter Pylori: Current Status and Future Prospects
Authors: O'Mahony Rachel , Vaira Dino , Holton John , Basset Christelle
Published: July 2008

Helicobacter pylori is a global pathogen that causes severe gastrointestinal diseases leading to a significant morbidity and mortality. There is an effective treatment for peptic ulcer disease, however, this is being compromised by an increase in the prevalence of antibiotic resistance. Although alternative rescue regimens have been advocated, the best strategy would be to prevent disease, especially in the case of gastric cancer for which there is still no treatment. One approach is to inhibit the first step in the pathogenic process – adhesion of the organism to the host tissue. Another and probably a better approach is vaccination, but clinical trials have so far been unsuccessful. There is still a large uncertainty in relation to how H. pylori causes disease. Knowledge from genomics, proteomics, and the relationship between polymorphism of the bacterium and the host, as well as the continuing investigation of the role played by important virulence factors in the outcome of the disease, will help both in understanding pathogenesis of disease and in the design of the best vaccine.
Thoracic stenosis causing lateral compression of the spinal cord in two immature Dogues de Bordeaux
Authors: Pratt J. N. J. , Smith P. M. , Jeffery N. D. , Stalin C. E.
Published: July 2008

This case report describes a novel developmental vertebral malformation in two young Dogues de Bordeaux, which was diagnosed by magnetic resonance imaging. Both dogs were treated surgically with reasonable success.
Synthesis, Characterization, Two‐Photon Absorption, and Optical Limiting Properties of Ladder‐Type Oligo‐p‐phenylene‐Cored Chromophores
Authors: Zheng Qingdong , Gupta Sandesh K. , He Guang S. , Tan Loon‐Seng , Prasad Paras N.
Published: July 2008

This paper reports on the two‐photon absorption (TPA) and related up‐converted emission properties of a novel series of chromophores containing ladder‐type oligo‐p‐phenylenes with various π‐conjugation lengths. The design and synthesis of these ladder‐type two‐photon chromophores are first discussed. An increase in the π‐conjugated length of the ladder‐type oligo‐p‐phenylene for these chromophores leads to an increase in TPA cross‐section together with an increased fluorescence quantum yield. These chromophores exhibit high fluorescence quantum yields because of the rigid planar structure of the ladder‐type oligomers. The chromophore with an enhanced TPA cross‐section together with an increased fluorescence quantum yield would provide significant benefits for two‐photon excited fluorescence based applications. An improved optical limiting behavior was also demonstrated using the ladder‐type pentaphenylene cored chromophore.
Postthaw survival of rhesus macaque sperm: variation in the response of individual males to different freezing protocols
Authors: Gagliardi Christine , Myers Leann , Kubisch H. Michael
Published: July 2008

This study was designed to assess the effects of various cryopreservation protocols on the postthaw survival of rhesus macaque sperm. Multiple ejaculates of five mature males were collected and frozen by each of four different methods. Cryopreservation significantly reduced motility in all samples, regardless of the method, and the response of different ejaculates of the same male to each method proved to be consistent. The freezing method was a significant factor in determining the immediate postthaw motility, although this effect disappeared after 4 hr. Moreover, there was a significant interaction between individual males and freezing method suggesting that developing a single freezing protocol that is universally suitable may be difficult. Am. J. Primatol. 70:1093–1096, 2008. © 2008 Wiley‐Liss, Inc.
Investigations of the Growth Kinetics of Capped CdSe and CdS Nanocrystals by a Combined Use of Small Angle X‐ray Scattering and Other Techniques
Authors: Varghese Neenu , Biswas Kanishka , Rao C. N. R.
Published: July 2008

The growth of capped CdSe and CdS nanocrystals formed by the reaction of selenium or sulfur with cadmium stearate in toluene solution in the presence of dodecanethiol or trioctylphosphine oxide and tetralin, has been investigated by a variety of techniques to obtain reliable data. Whereas small angle X‐ray scattering has provided statistically satisfactory data on the variation of size distribution with time, TEM has been used as a direct probe of the particle size, although with a limited sampling size. UV/Vis and photoluminescence spectroscopies have also provided information about the time evolution of the average diameter (D) of the nanocrystals. By employing all these techniques, we have obtained the D(t) data and fitted then to various growth models. Although certain qualitative observations suggest growth of the nanocrystals to be controlled by diffusion‐limited Ostwald ripening, we have found it is necessary to include the surface reaction term in the growth equation. Thus, the growth of CdSe and CdS nanocrystals has contributions from both diffusion and surface reaction, with a D3+D2 type behavior, independent of the capping agent.
Solphos: A New Family of Efficient Biaryl Diphosphine Ligands
Authors: Kesselgruber Martin , Lotz Matthias , Martin Pierre , Melone Gianpietro , Müller Markus , Pugin Benoît , Naud Frédéric , Spindler Felix , Thommen Marc , Zbinden Paul , Blaser Hans‐Ulrich
Published: July 2008

Solphos (7,7′‐bis(diarylphosphino)‐3,3′,4,4′‐tetrahydro‐4,4′‐dimethyl‐8,8′‐bis‐2H‐1,4‐benzoxazine) is a new modular atropisomeric biaryl ligand with a very attractive activity profile. A technically feasible synthesis is described allowing the synthesis of various derivatives of enantiopure ligand on a technical scale. Very good catalytic performances have been demonstrated for the following transformations: Ru‐catalyzed hydrogenation of various β‐keto esters (95–99 % ee, s/c up to 100 000), of acetyl acetone (>99 % ee, dl/meso>98:2), and of an exocyclic α,β‐unsaturated acid (98.6 % ee, s/c 250). In several cases, the nature of the PAr2 moiety had a significant effect on the enantioselectivity. Furthermore, Rh and Ir Solphos complexes achieved high enantioselectivities for a novel synthesis of 3,3‐disubstituted phthalides and the reductive coupling of alkynes with N‐sulfonyl imines, respectively.
Stereoselective Synthesis of Cyclopropanes Based on a 1,2‐Chirality Transfer
Authors: Muehling Olaf , Wessig Pablo
Published: July 2008

A stereoselective route to enantiomerically enriched bicyclic cyclopropane derivatives 13 is described which is based on a conceptually novel 1,2‐chirality transfer approach. The hyperconjugative interaction of an electronically excited carbonyl group with the σ* orbital of an adjacent CX bond in the transition state of a hydrogen abstraction causes the preference of a certain conformation and consequently the differentiation between two diastereotopic methylene groups. The 1,2‐chirality transfer is completed by a subsequent HX elimination which destroys the only stereogenic center in the reactants 12. Furthermore, it was found that contrary enthalpic and entropic influences result in the existence of an inversion temperature T0. Upon crossing T0 the stereoselectivity is reversed. Considering this temperature dependency, chirality transfer efficiencies of up to 83 % could be achieved. The absolute configuration of most products could be unambiguously determined by VCD spectroscopy combined with DFT calculations.
Case–control study of oral and oropharyngeal cancer in whites and genetic variation in eight metabolic enzymes
Authors: Buch Shama C. , Nazar‐Stewart Valle , Weissfeld Joel L. , Romkes Marjorie
Published: July 2008

Background.

Genetic variation in xenobiotic metabolizing enzymes may explain differing susceptibilities to the cancer causing effects of tobacco and alcohol.

Methods.

We compared 203 oral squamous cell carcinoma cases and 416 controls for single nucleotide polymorphisms (SNPs) in 8 genes (CYP1A1, CYP2E1, MPO, mEH, GSTM1, GSTT1, GSTP1, and NAT2). Except for NAT2, genotype frequencies were similar in the 2 groups. We classified subjects as fast or slow NAT2 acetylators genotyping 13 NAT2 SNPs.

Results.

Fast acetylators were overrepresented in cases (53.7%) compared with controls (43.9%; odds ratio (OR) 1.55, 95% confidence interval (CI) 1.08–2.20; p value = .03). Gene–gene interaction testing suggested several cancer‐NAT2 associations, with association strongest among persons without a CYP1A1 variant (*2C or *4) allele (OR 1.77, 95% CI 1.20–2.60, p value = .03) or with a variant MPO (463A) allele (OR 2.38, 95% CI 1.34–4.21, p value = .05).

Conclusion.

These results implicate fast NAT2 acetylation as a risk factor for oral cancer. © 2008 Wiley Periodicals, Inc. Head Neck 2008
Peroxynitrite damages U937 cell DNA via the intermediate formation of mitochondrial oxidants
Authors: Cantoni Orazio , Guidarelli Andrea
Published: July 2008

Eight years ago, we published in this journal the first evidence that peroxynitrite does not directly produce DNA single‐strand breakage in intact U937 cells (Guidarelli et al.,IUBMB Life, 50, 195–201). This event was rather attributed to the secondary reactive species produced at the mitochondrial level via a Ca2+‐dependent reaction, in which ubisemiquinone serves as an electron donor. Under these conditions, electrons are directly transferred to molecular oxygen and superoxide/H2O2, and the ensuing DNA damage can therefore be produced in a time‐ dependent manner for at least 30 min. Formation of H2O2and DNA single‐strand breaks was therefore dependent on interference with electron transport at the complex III level as well as on mitochondrial Ca2+accumulation. Further studies led to the demonstrations that peroxynitrite mobilizes Ca2+from the ryanodine receptor. Finally, in U937 cells, a pro‐monocytic cell line sharing with monocytes/macrophages the same signaling events to survive to peroxynitrite, mitochondrial H2O2promotes inhibition of survival via tyrosine phosphatase activation, leading to ERK1/2 dephosphorylation and thus to upstream inhibition of the survival signaling. © 2008 IUBMB IUBMB Life, 60(11): 753–756, 2008
Mapping nondominant voices into understanding stress‐coping mechanisms
Authors: Iwasaki Yoshitaka , Bartlett Judith , MacKay Kelly , Mactavish Jennifer , Ristock Janice
Published: July 2008

This study reports key findings from a research project, which examined the stress and coping mechanisms of several nondominant groups of individuals. The groups were based in Winnipeg, Manitoba, Canada and included (a) Aboriginal individuals with diabetes, (b) individuals with disabilities, and (c) gays and lesbians. Our analyses of personal narratives and life stories have led to develop an interpretive map of findings that depicts mechanisms of how stress and coping operate. Specifically, the interpretive map consists of personal and structuralstressors, meanings of stress, and personal and structuralresources, as well as of two constructs termedintersectionalityandsocial exclusion. Not only are nondominant voices and lived experiences recognized and incorporated into an emergent interpretive map, but this map also articulates the complex ways in which multiple identities intersect (i.e., intersectionality) and the realities of being excluded socioeconomically, culturally, and politically among nondominant groups (i.e., social exclusion). © 2008 Wiley Periodicals, Inc.
How do implementation efforts relate to program adherence? examining the role of organizational, implementer, and program factors
Authors: Dariotis Jacinda K. , Bumbarger Brian K. , Duncan Larissa G. , Greenberg Mark T.
Published: July 2008

Widespread replications of evidence‐based prevention programs (EBPPs) prompt prevention scientists to examine program implementation adherence in real world settings. Based on Chen's model (1990), we identified five key factors of the implementation system and assessed which characteristics related to program adherence. The sample included 32 EBPPs and results indicate that target recipient responsivity, program material quality, implementer prioritization, community collaborative system support, and parental support significantly relate to program adherence. Several differences reached statistical significance, thereby highlighting the importance of these variables and the need for future studies with larger sample sizes to identify factors related to program adherence adequately. © 2008 Wiley Periodicals, Inc.
Feasability of human endobronchial imaging with a linear‐array ultrasound catheter
Authors: Tranquart François , Palanchon Peggy , Cladé Odile , Bleuzen Aurore , Dinet Dominique , Magro Pascal , Diot Patrice
Published: July 2008

Purpose.

To explore the feasability of imaging lung masses with a novel endobronchial linear‐array transducer.

Method.

We used a linear‐array transducer of 7 F (2.3 mm in diameter) operating at a center frequency of 10 MHz for endobronchial imaging. We used the probe in 20 subjects with suspected lung cancer to identify and measure the tumor; to asses the tumor's sonographic characteristics, bronchial wall invasion, and presence of lymph nodes; to guide a transbronchial needle aspiration (TBNA); and to evaluate potential side effects.

Results.

In all patients, the tumor was identified and the relationship with the bronchial wall correctly evaluated through the depiction of a 3‐layer wall pattern. Bronchial wall invasion was suspected in 5 patients, small adjacent lymph nodes were detected in 3 patients, and a small pleural effusion was observed close to the lung lesion in 2 patients. The linear‐array probe allowed the guidance of successful TBNA with no complications.

Conclusion.

This feasibility study shows that the prototype probe can be used to depict pulmonary lesions and to guide biopsy nodes. Larger series are needed to validate its usefulness in clinical work‐ups and patients management. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008
Development and validation of an HPLC method for the determination of benzodiazepines and tricyclic antidepressants in biological fluids after sequential SPE
Authors: Uddin Mohammad Nasir , Samanidou Victoria F. , Papadoyannis Ioannis N.
Published: July 2008

A novel method for the simultaneous determination of six benzodiazepines (BZDs) and four tricyclic antidepressants (TCAs) in biological fluids by HPLC with UV detection at 240 nm has been developed. After a deproteinization step biological fluids were analyzed by direct injection. SPE on Nexus cartridges was also applied. Since two compounds, namely imipramine and diazepam, were coeluting, a sequential SPE protocol has been developed. BZDs were eluted by a mixture of methanol/ACN (1:1), followed by the elution of TCAs with methanol. Separation was performed on a Kromasil C8 column (250×4 mm2 id, 5 μm) using a mobile phase of 0.05 M CH3COONH4/ACN/methanol (initial composition 55:15:30 v/v/v) at a flow rate of 1.0 mL/min delivered by a gradient program within 15 min. Colchicine was used as the internal standard (4 ng/μL). The method was linear for all analytes up to 20 ng/μL, with coefficients of regression between 0.996 and 0.99996. LODs and LOQs were 0.08–1.17 and 0.28–3.91 ng/μL, respectively. Recovery was in the range of 92.8–108.7% for within‐day and 91.9–109.9% for between‐day assays, with RSD values lower than 10.0% for all matrices.
Self‐Assembly of Rod‐Coil Block Copolymers for Photovoltaic Applications
Authors: Sary Nicolas , Rubatat Laurent , Brochon Cyril , Hadziioannou Georges , Mezzenga Raffaele
Published: July 2008

Summary: Two different approaches to obtain electron donor‐acceptor interfaces via self‐assembly of block copolymer systems are discussed, where the donor domains are formed by a π‐conjugated rod‐like polymer and the acceptor domains result from a coiled polymer modified by C60 fullerenes. In the first strategy, C60 is chemically grafted onto the coil polymer, typically a statistical copolymer of styrene and chloromethyl styrene. This has as major effect the increase in molecular weight and volume fraction of the coil block, which can markedly perturb the self‐assembled block copolymer final morphologies and eventually suppress any microseparated nanostructure in favour of fully isotropic homogeneous phases. We discuss how the presence of free homopolymer rods in the system can help recovering a microphase separated morphology suitable for photovoltaic applications. In the second approach we discuss the poly(diethylhexyl‐p‐phenylenevinylene‐b‐4‐vinylpyridine) (PPV‐P4VP) rod‐coil block copolymer system and we argue how supramolecular interactions among P4VP and free C60 can be exploited to blend rod‐coil block copolymers and C60 preserving the original lamellar phase.
Lead Sulfide Nanocrystal‐Polymer Composites for Optoelectronic Applications
Authors: Asunskis Daniel J. , Bolotin Igor L. , Wroble Amanda T. , Zachary Adam M. , Hanley Luke
Published: July 2008

Summary: Nanocomposite films were prepared by two methods in which lead sulfide (PbS) nanocrystals were contained in an organic matrix. One method used a wet chemical synthesis of the nanocrystals in the direct presence of a polymer, where the polymer controlled nanocrystal growth. The second method was gaseous deposition of nanocrystals into the organic phase. The two methods were similar in that the nanocrystals in the composites were free from surfactant capping layers that otherwise would add an interfacial region between the nanocrystal and the organic matrix. The gaseous deposition technique had several advantages over the wet chemical synthesis in that it allowed direct control over nanocrystal size and density, improved flexibility in the choice of organic phase, and was compatible with lithographic methods.