bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemic dynamics of two coexisting hepatitis C virus subtypes
Authors: Jiménez-Hernández Nuria , Torres-Puente Manuela , Bracho Maria Alma , García-Robles Inmaculada , Ortega Enrique , del Olmo Juan , Carnicer Fernando , González-Candelas Fernando , Moya Andrés
Published: December 2006

Hepatitis C virus (HCV) infection affects about 3 % of the human population. Phylogenetic analyses have grouped its variants into six major genotypes, which have a star-like distribution and several minor subtypes. The most abundant genotype in Europe is the so-called genotype 1, with two prevalent subtypes, 1a and 1b. In order to explain the higher prevalence of subtype 1b over 1a, a large-scale sequence analysis (100 virus clones) has been carried out over 25 patients of both subtypes in two regions of the HCV genome: one comprising hypervariable region 1 and another including the interferon sensitivity-determining region. Neither polymorphism analysis nor molecular variance analysis (attending to intra- and intersubtype differences, age, sex and previous history of antiviral treatment) was able to show any particular difference between subtypes that might account for their different prevalence. Only the demographic history of the populations carrying both subtypes and analysis of molecular variance (AMOVA) for risk practice suggested that the route of transmission may be the most important factor to explain the observed difference.
Comparison of ovine herpesvirus 2 genomes isolated from domestic sheep (Ovis aries) and a clinically affected cow (Bos bovis)
Authors: Taus Naomi S. , Herndon David R. , Traul Donald L. , Stewart James P. , Ackermann Mathias , Li Hong , Knowles Donald P. , Lewis Gregory S. , Brayton Kelly A.
Published: December 2006

The rhadinovirus Ovine herpesvirus 2 (OvHV-2) is the causative agent of sheep-associated malignant catarrhal fever. OvHV-2 primarily affects ruminants and has a worldwide distribution. In this study, a composite sequence of OvHV-2 genomic DNA isolated from nasal secretions of sheep experiencing virus-shedding episodes was determined and compared with the sequence of OvHV-2 DNA isolated from a lymphoblastoid cell line derived from a clinically affected cow. The study confirmed the OvHV-2 sequence information determined for the cell line-isolated DNA and showed no apparently significant changes in the OvHV-2 genome during passage through a clinically susceptible species with subsequent maintenance in vitro. Amino acid identity between the predicted open reading frames (ORFs) of the two genomes was 94–100 %, except for ORF73, which had an identity of 83 %. Polymorphism in ORF73 was due primarily to variability in the G/E-rich repetitive central region of the ORF.
Annexin 2-mediated enhancement of cytomegalovirus infection opposes inhibition by annexin 1 or annexin 5
Authors: Derry Mélanie C. , Sutherland Michael R. , Restall Christina M. , Waisman David M. , Pryzdial Edward L. G.
Published: December 2006

Biochemical studies have suggested that annexin 2 (A2) may participate in cytomegalovirus (CMV) infection. In the current work, effects of A2 monomer (p36) and heterotetramer (A2t; p362p112) were investigated. Demonstrating a role for endogenous A2, the four stages of infection that were followed were each inhibited by anti-p36 or anti-p11 at 37 °C. Immuno-inhibition was attenuated when the virus and cells were pre-incubated at 4 °C to coordinate virus entry initiated afterwards at 37 °C, reconciling controversy in the literature. As an explanation, CMV-induced phosphorylation of p36 was prevented by the 4 °C treatment. Supporting these immuno-inhibition data, purified A2t or p11 increased CMV infectious-progeny generation and CMV gene expression. A specific role for A2t was indicated by purified p36 having no effect. Unlike other steps, primary plaque formation was not enhanced by purified A2t or p11, possibly because of undetectable phosphorylation. As annexins 1 (A1) and 5 (A5) interact with A2, their effect on CMV was also tested. Both purified proteins inhibited CMV infection. In each experiment, the concentration of A1 required for half-maximal inhibition was five- to 10-fold lower than that of A5. Addition of A2 opposed A1- or A5-mediated inhibition of CMV, as did certain A2-specific antibodies that had no effect in the absence of added A1 or A5. Transfection of the p36-deficient cell line HepG2 increased CMV infection and was required for inhibition by the other annexins. These data suggest that CMV exploits A2t at physiological temperature to oppose the protection of cells conferred by A1 or A5.
Apple chlorotic leaf spot virus 50 kDa movement protein acts as a suppressor of systemic silencing without interfering with local silencing in Nicotiana benthamiana
Authors: Yaegashi Hajime , Takahashi Tsubasa , Isogai Masamichi , Kobori Takashi , Ohki Satoshi , Yoshikawa Nobu
Published: December 2006

Apple chlorotic leaf spot virus (ACLSV) is the type species of the genus Trichovirus and its single-stranded, plus-sense RNA genome encodes a 216 kDa protein (P216) involved in replication, a 50 kDa movement protein (P50) and a 21 kDa coat protein (CP). In this study, it was investigated whether these proteins might have RNA silencing-suppressor activities by Agrobacterium-mediated transient assay in the green fluorescent protein-expressing Nicotiana benthamiana line 16c. The results indicated that none of these proteins could suppress local silencing in infiltrated leaves. However, systemic silencing in upper leaves induced by both single- and double-stranded RNA could be suppressed by P50, but not by a frame-shift mutant of P50, P216 or CP. Moreover, when P50 was expressed separately from where silencing signals were generated in a leaf, systemic silencing in upper leaves was inhibited. Collectively, our data indicate that P50 acts as a suppressor of systemic silencing without interfering with local silencing, probably by inhibiting the movement of silencing signals.
Re‐evaluation and functional classification of non‐synonymous single nucleotide polymorphisms of the human ATP‐binding cassette transporter ABCG2
Authors: Tamura Ai , Wakabayashi Kanako , Onishi Yuko , Takeda Misako , Ikegami Yoji , Sawada Seigo , Tsuji Masahisa , Matsuda Yoichi , Ishikawa Toshihisa
Published: December 2006

Impacts of genetic polymorphisms of the ATP‐binding cassette (ABC) transporter BCRP/MXR1/ABCP (ABCG2) on drug response have been implicated; however, the hitherto reported data involve some inconsistencies. To re‐evaluate the effect of single nucleotide polymorphisms (SNP) of ABCG2 in vitro, we created a total of seven variant cDNAs (V12M, Q141K, F208S, S248P, F431L, S441N and F489L) by site‐directed mutagenesis and stably expressed each of them in Flp‐In‐293 cells using the Flp recombinase system. Multicolor fluorescence in situ hybridization mapping analysis revealed that one single copy of ABCG2 cDNA was incorporated into the telomeric region of chromosome 12p. It was proven that mRNAs of those integrated ABCG2 variants were expressed evenly in Flp‐In‐293 cells. However, the protein expression levels varied among those variants. In particular, expression of the F208S and S441N variants was markedly low, suggesting the instability of these variant proteins. Drug resistance profiles of Flp‐In‐293 cells expressing two major SNP variants (V12M and Q141K) toward the drug SN‐38 demonstrated that the IC50 value (drug concentrations producing a 50% reduction of cell growth) for Q141K was approximately 50% of that for wild type. The contributions of the minor SNP variants (F208S, S248P, F431L, S441N and F489L) to drug resistance toward SN‐38, mitoxantrone, doxorubicin, daunorubicin or etoposide were significantly lower than wild type. Based on our functional validation, the above‐mentioned non‐synonymous polymorphisms as well as acquired mutants (R482G and R482T) of ABCG2 were classified into four groups. Furthermore, new camptothecin analogs synthesized by our research group had potent effects in circumventing ABCG2‐mediated drug resistance without any influence from major non‐synonymous polymorphisms. (Cancer Sci 2007; 98: 231–239)
Colorectal serrated adenocarcinoma
Authors: Mäkinen M J
Published: December 2006

Colorectal cancer (CRC) ranks among the three most common cancers in terms of both cancer incidence and cancer‐related deaths in most Western countries. Serrated adenocarcinoma is a recently described, distinct variant of CRC, accounting for about 7.5% of all CRCs and up to 17.5% of most proximal CRCs. It has been postulated that about 10–15% of sporadic CRCs would have their origin in serrated polyps that harbour a significant malignant potential. These lesions include hyperplastic‐type aberrant crypt foci, hyperplastic polyps, sessile serrated adenomas, admixed polyps and serrated adenomas, and constitute the so‐called ‘serrated pathway’, which is distinct from both the conventional adenoma–carcinoma pathway and the mutator pathway of hereditary non‐polyposis CRC and is characterized by early involvement of oncogenic BRAF mutations, excess CpG island methylation (CIM) and subsequent low‐ or high‐level DNA microsatellite instability (MSI). Methylation of hMLH1 is likely to explain the increased frequency of high‐level MSI (16%) and methylation of MGMT is postulated to explain the low‐level MSI (29%) in serrated adenocarcinomas. Reproducible histopathological criteria for serrated adenocarcinoma have recently been established and they have been qualified by DNA expression analysis for 7928 genes, showing clustering of serrated adenocarcinomas into a molecular entity apart from conventional adenocarcinoma, and representing with distinct down‐regulation of EPHB2, PTCH and up‐regulation of HIF1α.
Application of the focused ion beam technique in aerosol science: detailed investigation of selected, airborne particles
Authors: KAEGI R. , GASSER PH.
Published: December 2006

The focused ion beam technique was used to fabricate transmission electron microscope lamellas of selected, micrometre‐sized airborne particles. Particles were sampled from ambient air on Nuclepore polycarbonate filters and analysed with an environmental scanning electron microscope. A large number of particles between 0.6 and 10 µm in diameter (projected optical equivalent diameter) were detected and analysed using computer‐controlled scanning electron microscopy. From the resulting dataset, where the chemistry, morphology and position of each individual particle are stored, two particles were selected for a more detailed investigation. For that purpose, the particle‐loaded filter was transferred from the environmental scanning electron microscope to the focused ion beam, where lamellas of the selected particles were fabricated. The definition of a custom coordinate system enabled the relocation of the particles after the transfer. The lamellas were finally analysed with an analytical transmission electron microscope. Internal structure and elemental distribution maps of the interior of the particles provided additional information about the particles, which helped to assign the particles to their sources. The combination of computer‐controlled scanning electron microscopy, focused ion beam and transmission electron microscopy offers new possibilities for characterizing airborne particles in great detail, eventually enabling a detailed source apportionment of specific particles. The particle of interest can be selected from a large dataset (e.g. based on chemistry and/or morphology) and then investigated in more detail in the transmission electron microscope.
Determination of mean free path for energy loss and surface oxide film thickness using convergent beam electron diffraction and thickness mapping: a case study using Si and P91 steel
Authors: MITCHELL D. R. G.
Published: December 2006

Determining transmission electron microscope specimen thickness is an essential prerequisite for carrying out quantitative microscopy. The convergent beam electron diffraction method is highly accurate but provides information only on the small region being probed and is only applicable to crystalline phases. Thickness mapping with an energy filter is rapid, maps an entire field of view and can be applied to both crystalline and amorphous phases. However, the thickness map is defined in terms of the mean free path for energy loss (λ), which must be known in order to determine the thickness. Convergent beam electron diffraction and thickness mapping methods were used to determine λ for two materials, Si and P91 steel. These represent best‐ and worst‐case scenario materials, respectively, for this type of investigation, owing to their radically different microstructures. The effects of collection angle and the importance of dynamical diffraction contrast are also examined. By minimizing diffraction contrast effects in thickness maps, reasonably accurate (±15%) values of λ were obtained for P91 and accuracies of ±5% were obtained for Si. The correlation between the convergent beam electron diffraction‐derived thickness and the log intensity ratios from thickness maps also permits estimation of the thickness of amorphous layers on the upper and lower surfaces of transmission electron microscope specimens. These estimates were evaluated for both Si and P91 using cross‐sectional transmission electron microscopy and were found to be quite accurate.
Proximal tubule endocytic apparatus as the specific renal uptake mechanism for vitamin D‐binding protein/25‐(OH)D3 complex (Review Article)
Authors: NEGRI ARMANDO LUIS
Published: December 2006

SUMMARY:  The renal proximal tubule exhibits a very extensive apical endocytic apparatus that is involved in the reabsorption of molecules filtered in the glomeruli. Several key receptors appear to be involved in this function, which serves not only to conserve protein but also to reabsorb different vitamins in complex with their binding proteins. Recent research has established megalin as probably the most important receptor in this endocytosis process. Cubilin is another receptor identified in the proximal tubule endocytic apparatus. Because cubilin lacks transmembrane or cytoplasmic domains required for endocytosis, this receptor associates with megalin to recycle and internalize its ligands. Recent studies have shown that vitamin D‐binding protein (DBP)/25‐(OH)D3 complex is one of the megalin/cubilin ligands. Megalin knockout mice develop vitamin D deficiency and bone disease owing to an inability of the proximal tubules to capture the DBP/25‐(OH)D3 complexes from the glomerular filtrate. In the same way, kidney‐specific megalin knockout mice have severe plasma vitamin D deficiency, hypocalcaemia and serious bone disease, like the complete megalin knockout mice. Anti‐cubilin antibodies inhibit cellular uptake of DBP/25‐(OH)D3 by up to 70%. Anti‐megalin antibodies produced a similar reduction in DBP/25‐(OH)D3 endocytosis. When both antibodies were applied, impairment of DBP/25‐(OH)D3 was only slightly more impaired (around 80%), suggesting that cubilin and megalin function through the same endocytic pathway. Specific forms of renal Fanconi syndrome are associated with endocytic pathway dysfunction with disruption of megalin‐mediated uptake DBP/25‐(OH)D3 complex, producing metabolic bone disease in affected individuals as a prominent clinical finding.
Does complementary resource use enhance ecosystem functioning? A model of light competition in plant communities
Authors: Yachi Shigeo , Loreau Michel
Published: December 2006

Recent experiments on grassland ecosystems have shown that biodiversity can enhance ecosystem processes such as plant biomass production. Functional complementarity is generally regarded as the main class of mechanisms generating these effects of biodiversity on ecosystem functioning. Although intuitively appealing and supported by some data, the complementarity hypothesis has been little explored theoretically using mechanistic approaches. Here, we present a simple dynamical model for a light‐limited terrestrial ecosystem to assess the effects of species diversity on light competition and total biomass in plant communities. Our model shows that competitive relaxation (reduction in average light competition intensity) due to differences in foliar architecture among species enhances total plant biomass in mixtures, but that competitive imbalance (generated by the variance of the average light competition intensity experienced by different species) can either reinforce the effect of competitive relaxation or counteract it and contribute to reducing total plant biomass. Thus, complementary resource use is not enough to increase total plant biomass in species‐rich communities; competitive balance among species also plays an important role. We propose an operational measure of light‐use complementarity using empirical field data on light absorption to test the presence of complementarity in natural plant communities.
Sensitivity analysis of transient population dynamics
Authors: Caswell Hal
Published: December 2006

Short‐term, transient population dynamics can differ in important ways from long‐term asymptotic dynamics. Just as perturbation analysis (sensitivity and elasticity) of the asymptotic growth rate reveals the effects of the vital rates on long‐term growth, the perturbation analysis of transient dynamics can reveal the determinants of short‐term patterns. In this article, I present a completely new approach to transient sensitivity and elasticity analysis, using methods from matrix calculus. Unlike previous methods, this approach applies not only to linear time‐invariant models but also to time‐varying, subsidized, stochastic, nonlinear and spatial models. It is computationally simple, and does not require calculation of eigenvalues or eigenvectors. The method is presented along with applications to plant and animal populations.
Synergistic and antagonistic effects of viral lysis and protistan grazing on bacterial biomass, production and diversity
Authors: Weinbauer Markus G. , Hornák Karel , Jezbera Jan , Nedoma Jiři , Dolan John R. , Šimek Karel
Published: December 2006

In a mesotrophic reservoir, we examined the effects on the bacterioplankton of distinct consumers of bacteria, viruses and heterotrophic nanoflagellates, both alone and combined in an experiment using natural populations and in situ incubations in dialysis bags. Ribosomal RNA‐targeted probes were employed as well as 16S RNA gene based PCR denaturing gradient gel electrophoresis (DGGE) to enumerate bacterial groups and assess bacterial community composition. We employed probes for Actinobacteria (HGC69a probe), Cytophaga‐Flavobacterium‐Bacteroidetes bacteria (CF319a probe), BET42a probe (Betaproteobacteria) and a subgroup‐Betaproteobacteria (R‐BT065 probe). We found consumer‐specific effects on bacterial activity and diversity (against a background of CF and BET dominating all treatments) suggesting distinct vulnerabilities to the two sources of mortality. For example, growth rate of Actinobacteria was only positive in the presence of flagellates, while towards the end of the experiment (T72−96 h) growth rate of R‐BT was only positive in the viruses only treatment. More specific data on how viruses and flagellates influenced Flectobacillus are shown in the companion paper. Highest richness (number of DGGE bands) was found in the virus only treatment and lowest when both consumers were present. In addition, we found suggestions of both antagonistic and synergistic interactions between the two sources of bacterial mortality. Notably, bactivory by flagellates was associated with reductions in bacterial diversity and increases in viral production.
Grazer and virus‐induced mortality of bacterioplankton accelerates development of Flectobacillus populations in a freshwater community
Authors: Šimek Karel , Weinbauer Markus G. , Hornák Karel , Jezbera Jan , Nedoma Jiři , Dolan John R.
Published: December 2006

We present a detailed analysis of the effects of distinct bacterial mortality factors, viral lysis and heterotrophic nanoflagellates (HNF) bacterivory, associated with the development of filamentous Flectobacillus populations. Reservoir bacterioplankton communities were subjected to additions of both HNF and viruses together, or HNF alone, and then incubated in situ in dialyses bags. For distinct bacterial groups, mortality or growth stimulation was analysed by examining bacterial prey ingested in HNF food vacuoles with fluorescence in situ hybridization (FISH) and via FISH with microautoradiography (MAR‐FISH). We also developed a semi‐quantitative MAR‐FISH‐based estimation of relative activities of Flectobacillus populations (targeted by the R‐FL615 probe). Bacterial groups vulnerable to HNF predation (mainly clusters of Betaproteobacteria), or discriminated against (Actinobacteria), were detected. Bacterial lineages most vulnerable to virus‐lysis (mainly the Betaproteobacteria not targeted by the R‐BT065 probe, of the Polynucleobacter cluster) were identified by comparing treatments with HNF alone to HNF and viruses together. Filaments affiliated with the Flectobacillus cluster appeared in both treatments, but were about twice as abundant, long and active as in incubations with viruses and HNF as compared with HNF alone. Viruses appeared to selectively suppress several bacterial groups, perhaps enhancing substrate availability thus stimulating growth and activity of filamentous Flectobacillus.
QUANTIFYING MARKET POWER IN THE GERMAN WHOLESALE ELECTRICITY MARKET USING A DYNAMIC MULTI‐REGIONAL DISPATCH MODEL*
Authors: MÜSGENS FELIX
Published: December 2006

This paper quantifies the degree of market power in the German wholesale electricity market. A dispatch model simulates competitive marginal costs. In addition to common input factors like plant capacities, fuel prices and load structures, the model also incorporates international power exchange and dynamic effects like start‐up costs and hydro storage plant dispatch. The simulated prices are subsequently used as a benchmark for observed electricity prices. The analysis reveals significant market power in the German electricity market, mainly exhibited during peak periods. Producer surplus is also increased significantly due to strategic behavior.
New Institutionalism and Sexuality at Work in Local Government
Authors: Monro Surya
Published: December 2006

Recent statutory and policy changes have raised the profile of lesbian, gay and bisexual equalities initiatives in the local government arena. These initiatives are increasingly developed and delivered via inter‐agency partnerships. This article applies concepts from the sociological branch of new institutionalism to the field of sexualities equalities partnership work in local government, drawing on findings from a large empirical project. Notions of norms, ritual, templates and isomorphism all have purchase in this sensitive, value‐laden field, providing insight into the organizational dynamics associated with inter‐agency and partnership working. The article introduces the notion of institutional hybridization as a means of understanding the collaborative, and sometimes conflicting, processes associated with governance in the field of sexualities equalities work.
Gender‐specific Effects at Work: An Empirical Study of Four Countries
Authors: Gunkel Marjaana , Lusk Edward J. , Wolff Birgitta , Li Fang
Published: December 2006

Using a questionnaire based upon the work of Geert Hofstede, we examined the effects of gender on the following three work‐related dimensions: the importance of work‐related goals, the preference for performance rewards and the preference for management styles. The study was conducted for a multinational corporation headquartered in Germany with branches in China, Japan and the USA. Even though some inter‐country differences in the importance of work‐related matters are identified and intra‐country gender differences exist in work goal evaluation, overall we find that men and women exhibit similar preferences concerning performance rewards and managerial styles. Finally, for the three dimensions studied, our data do not confirm the stereotypical work‐related gender differences often reported in the literature and popular press.
A contingency approach to resource‐creation processes
Authors: Bowman Cliff , Collier Nardine
Published: December 2006

The resource‐based view has provided valuable insights into sources of competitive advantage, but little attention has been paid to the processes of resource creation. To address this shortcoming, this paper reviews the strategy process literature, explaining the theoretical positions and assumptions that underpin different types of process. It then examines the mechanisms by which resources have been found to be created; luck, resource picking, internal development and alliances. Next, a series of resource‐creation pathways that illustrate the different routes firm inputs might take on the way to becoming unique and valuable resources is developed. These pathways are also discussed in terms of the strategy processes through which they are developed, and the appropriate resource‐creation processes. The review is then extended with the introduction of two contingent variables − task complexity and environmental stability – and the resource‐creation processes that are congruent with different combinations of these variables are explored. From this review, one is able to identify the combination of complex task and stable environment likely to be the most conducive to resource creation. Finally, the paper explores opportunities that firms might have to engineer stability and complexity in some parts of their operations with the aim of developing a resource‐based advantage.
Recapitulation of cell signaling events associated with astrogliosis using the brain slice preparation
Authors: Damiani Candice L. , O’Callaghan James P.
Published: December 2006

Astroglial activation constitutes a dominant response to all types of injuries of the CNS. Despite the ubiquitous nature of this cellular reaction to neural injury, a little is known concerning the signaling mechanisms that initiate it. Recently, we demonstrated that astrocytic hypertrophy and enhanced expression of glial fibrillary acidic protein resulting from toxicant‐induced neurodegeneration are linked to activation of the janus kinase (JAK)‐signal transducer and activator of transcription‐3 (STAT3) pathway. These observations implicate ligands at the gp130 receptor as potential upstream effectors of astrogliosis. Here we used the brain slice preparation to examine potential activators of the JAK‐STAT3 pathway. Following incubation of freshly cut striatal slices in phosphate‐free oxygenated buffer for up to 75 min, we found that slicing the striatum itself was a sufficient stimulus to initiate a rapid activation of the JAK‐STAT3 pathway as assessed with immunoblots of pSTAT3(tyr705) using phospho‐state specific antibodies. The mRNA for the gp130 cytokines, leukemia inhibitory factor, interleukin‐6 and oncostatin M or the β‐chemokine, monocyte chemoattractive protein (CCl2) also were up‐regulated in the slice. Moreover, we could enhance the activation of STAT3(tyr705) by adding exogenous cytokines to the slice and we could inhibit phosphorylation of STAT3(tyr705) by addition of tyrosine kinase inhibitors (Lav A and AG490) or neutralizing antibodies directed against leukemia inhibitory factor or oncostatin M. These data suggest that STAT3 activation is an early event in slice‐induced glial activation and establishes the brain slice preparation method as a reliable model to examine the signaling mechanisms that underlie glial activation.
Reduced Frontal Lobe Activity in Subjects With High Impulsivity and Alcoholism
Authors: Chen Andrew C. H. , Porjesz Bernice , Rangaswamy Madhavi , Kamarajan Chella , Tang Yongqiang , Jones Kevin A. , Chorlian David B. , Stimus Arthur T. , Begleiter Henri
Published: December 2006

Objective: Impulsivity is an important characteristic of many psychiatric disorders, including substance‐related disorders. These disinhibitory disorders have a similar underlying genetic diathesis, with each disorder representing a different expression of the same underlying genetic liability. This study assessed whether there is a relationship between impulsivity and alcohol dependence, and their correlations with P3 (P300) amplitude, a proposed endophenotype of alcoholism.

Methods: Healthy control subjects (n=58) and subjects with DSM‐IV diagnosis of alcohol dependence (n=57) were assessed with a visual oddball task. Event‐Related Potentials (ERPs) were recorded from 61 scalp electrodes and P3 amplitudes measured. Barratt Impulsiveness Scale (BIS), version 11, was used to evaluate impulsivity. Source localization of P3 was computed using low‐resolution brain electromagnetic tomography (LORETA).

Results: Alcoholic subjects manifested reductions in target P3 amplitudes (p<0.0001). Using LORETA, significantly reduced activation was mapped in the cingulate, medial, and superior frontal regions in alcoholic subjects and highly impulsive subjects. Alcoholic subjects had significantly higher scores on the BIS (p<0.0001) than nonalcoholic individuals. There were significant negative correlations between total scores on BIS and P3 amplitude (r=−0.274, p=0.003, on Pz; r=−0.250, p=0.007, on Cz).

Conclusions: Our results demonstrate a strong frontal focus of reduced activation during processing of visual targets in alcoholic subjects and individuals with higher impulsivity. The findings suggest that impulsivity may be an important factor that underlies the pathogenesis of alcohol dependence. Studies are underway to examine the relationship between impulsivity and ERPs in offspring of alcoholic subjects, and to identify genes associated with the underlying predisposition involved in disinhibitory disorders.
Differential phospholipase gene expression by Candida albicans in artificial media and cultured human oral epithelium
Authors: SAMARANAYAKE Y. H. , DASSANAYAKE R. S. , CHEUNG B. P. K. , JAYATILAKE J. A. M. S. , YEUNG K. W. S. , YAU J. Y. Y. , SAMARANAYAKE L. P.
Published: December 2006

Phospholipases B1, B2, C and D of Candida albicans play a significant role in the host invasive process. Hence we evaluated the in vitro expression of PLB1, PLB2, PLC1 and PLD1 in phospholipase‐positive (PL+) and ‐deficient (PL−) C. albicans isolates in egg yolk agar (EYA), yeast peptone dextrose broth (YPD), and in a model of oral candidiasis based on reconstituted human oral epithelium (RHOE). The growth of Candida was then determined in YPD and its cellular invasion was investigated using the RHOE model. The PL+ group demonstrated PLB1, PLB2, PLC1 and PLD1 expression in both EYA and YPD, in contrast to the PL− group, which expressed only PLB2 and PLD1. Although PL+ isolates grew profusely in the RHOE model, they expressed only PLB2, PLC1 and PLD1, and not PLB1. Gene expression investigations could not be carried out with PL− isolates due to their inability to grow in the RHOE model. Significant growth differences in YPD medium were also observed within the PL+ and PL− groups. Taken together, these findings indicate that phospholipase gene expression in C. albicans is differentially affected by their growth milieu, and this in turn may modulate the disease outcomes in vivo.
Differentiating spitzoid melanomas from Spitz nevi through CD99 expression
Authors: King Mark S. , Porchia Sylvia J. , Hiatt Kim M.
Published: December 2006

Background:  A true diagnostic marker differentiating Spitz nevi (SN) from spitzoid melanoma (sMM) has been elusive. CD99, a transmembrane glycoprotein, believed to play a role in many neoplastic processes, has yet to be investigated in this regard. Recently, the expression of CD99 has been shown in 60% of primary melanomas. Other studies exploring the expression of CD99 in melanocytic lesions have not been performed. Here, we evaluate the presence of CD99 in these two histologically difficult to differentiate entities.

Methods:  Cases of sMM were selected based on the presence of key microscopic words: spitz, spindled and/or epitheliod. In addition, all the cases of SN over the past 7 years were retrieved. Each case was stained with anti‐human CD99 and analyzed for the presence of CD99 staining.

Results:  Fifteen of 27 cases (56%) of sMM expressed CD99 compared with only 3 of 58 cases (5%) of SN.

Conclusions:  This study shows 56% of sMM and only 5% of SN express CD99. Eight of the sMM showed strong diffuse staining, a pattern not seen in any of the SN. This study does not elucidate the role that CD99 plays in these melanocytic processes; however, it does show that CD99 can be a useful tool in distinguishing sMM from SN.
Melanophages reside in hypermelanotic, aberrantly glycosylated tumor areas and predict improved outcome in primary cutaneous malignant melanoma
Authors: Handerson Tamara , Berger Aaron , Harigopol Malini , Rimm David , Nishigori Chikako , Ueda Masato , Miyoshi Eiji , Taniguchi Naoyuki , Pawelek John
Published: December 2006

Background:  Previously, hypermelanotic regions of cutaneous malignant melanoma (CMM) were found to contain a mixture of highly melanized melanoma cells and melanophages. Both cell types produced β1,6‐branched oligosaccharides. These sugars are used for motility by myeloid cells and cancer cells alike and are associated with poor survival in carcinomas of the breast, colon and lung. This study further investigated associations between melanophages and β1,6‐branched oligosaccharides and their potential contributions to patient outcome.

Methods:  Individual archival melanomas and high‐throughput melanoma tissue microarrays were stained for melanophages with azure blue/S100 and for β1,6‐branched oligosaccharides with the lectin leukocytic phytohemagglutinin (LPHA, a selective marker for β1,6‐branched oligosaccharides).

Results:  In primary CMM, melanophages were highly enriched in hypermelanotic, LPHA‐positive tumor regions and correlated with improved outcome at 10‐ and 20‐year follow ups. While the combination of melanophages, LPHA positivity and high pigmentation indicated better outcome, a subset of LPHA‐positive cells not associated with melanophages indicated worse outcome.

Conclusion:  This is the first report of an anti‐tumor role for the melanophage in melanoma biology. There appeared to be two classes of β1,6‐branched oligosaccharide‐producing melanoma cells with opposing effects on outcome: one that attracted melanophages (better) and another that did not (worse). The findings disclose new aspects of the immune system and aberrant glycosylation in CMM.
Delayed Access to Alcohol Accelerates Self‐Administration of Alcohol on a Progressive Ratio Schedule
Authors: Pickering Chris , Moreira Tiago , Liljequist Sture
Published: December 2006

Abstract:  In a previous report, we found that a 5‐min. delay in alcohol access increases ethanol intake in rats trained to self‐administer 5% ethanol. To assess the effects of this delay on the motivation to self‐administer ethanol, Wistar rats were trained on a progressive ratio schedule of reinforcement and presented with the 5‐min. delay. There was no change in break point (6 presses/delivery), active (125 presses/30 min.) or inactive (10 presses/30 min.) lever presses after the 5‐min. delay compared to baseline. However, response cessation occurred 10 min. earlier in this delay session compared to baseline indicating that consumption was accelerated by delayed access to alcohol.
DISENTANGLING THE RISKS: PARENT CRIMINAL JUSTICE INVOLVEMENT AND CHILDREN'S EXPOSURE TO FAMILY RISKS
Authors: PHILLIPS SUSAN D. , ERKANLI ALAATTIN , KEELER GORDON P. , COSTELLO E. JANE , ANGOLD ADRIAN
Published: December 2006

Research Summary:

The analyses reported in this article are based on data from a longitudinal epidmiologic study of youth from 11 rural counties in North Carolina—the Great Smoky Mountains Study. Nearly half (47.4%) of the children in the population represented in this study had a parent or other parent figure who had been arrested as an adult. Analyses showed that parent risk factors (i.e., substance abuse, mental illness, and lack of education) had a significant direct effect on children's exposure to family risks. These parent risk factors were also associated with greater odds of parental involvement in the criminal justice system (CJS), which in turn, had a significant association with children's likelihood of experiencing two types of family risks (i.e., economic strain and instability), net the effect of parent risk factors. Parent CJS involvement, however, was not significantly associated with family risks related to family structure or quality of care. Exposure to risks in these latter domains was better explained by the direct effect of parental substance abuse, mental health problems, and lack of education.

Policy Implications:

These findings provide empirical evidence that parent CJS involvement is significantly related to children's exposure to certain types of family risks independent of the possible confounding effect of parent risks. The fact that the two domains of family risks that were associated with CJS involvement were economic adversity and family stability is noteworthy as these mirror two of the ecological correlates of crime that are thought to be perpetuated by high levels of incarceration—poverty and population mobility. Second, these findings suggest that it is unrealistic to expect correctional programs that focus on inmates' relationships with their children to single‐handedly impact intergenerational incarceration. Programs of this nature may play an important role in offsetting some of the more immediate adverse effects parental incarceration might have on children, but these analyses suggest that they need to be coupled with rehabilitation efforts that target parental substance abuse, mental health problems, and inadequate education. This conclusion is made because although parent CJS involvement carries its own risks for children experiencing certain family risks (i.e., economic strain and instability), these parent problems are still significant predictors of the same as well as other family risks, which in turn, past research has linked to adverse youth outcomes such as substance abuse and delinquency.
VIOLENCE RISK SCREENING IN COMMUNITY CORRECTIONS*
Authors: DAVIES GARTH , DEDEL KELLY
Published: December 2006

Research Summary:

Issues of safety and screening for potential violence are particularly salient in community correctional settings. These contexts require a risk assessment mechanism that can both classify offenders according to their risk of violent recidivism and be administered quickly and effectively by nonclinicians. Existing assessment instruments such as the LSI‐R, PCL‐R‐2, VRAG, and HCR‐20 are of limited utility in relation to predicting violence in community corrections. This research describes the creation and validation of the Violence Risk Screening Instrument that better meets the requirements of community corrections. Violent recidivism among men was best predicted by a three‐item instrument consisting of Severe Violence, Domestic Violence, and Unstable Lifestyle.

Policy Implications:

Balancing the treatment and supervision needs of offenders with the task of ensuring public safety within a context of limited resources makes risk assessment and triage essential. Resource constraints mean that not all offenders can receive high levels of supervision; similarly, best practice research on responsivity suggests that only those offenders at higher risk will benefit from high levels of supervision (Andrews and Bonta, 1994). In the past two decades, the use of risk assessment instruments has brought greater objectivity to the process of classifying offenders into risk groups. However, a single risk assessment instrument cannot classify offenders according to all forms of risk. As supervision strategies become more precise and more focused on specific forms of risk, so too must the instruments that are used to derive the classification. The Violence Risk Screening Instrument proposed here is valuable insofar as it meets the requisite criteria for community corrections: It has demonstrable predictive utility, and it can be administered by line‐level personnel. Furthermore, it allows community corrections agencies to conserve limited resources for offenders determined to be at greatest risk of jeopardizing public safety.
Knowledge Diffusion and Networking in the Organic Production Sector: A Case Study
Authors: Morone Piergiuseppe , Sisto Roberta , Taylor Richard
Published: December 2006

Knowledge Diffusion and Networking in the Organic Production Sector: A Case Study

Recent uncertainty throughout the food system has put pressure on European farmers, now facing economic globalisation, changing consumer preferences, and a new legal and regulatory framework. Under these new circumstances, policy‐makers must identify new strategies for developing food production systems in ways that benefit the whole of society, whilst minimising negative effects upon the environment. In this regard, the organic food sector, characterised by an ever more complex legislative framework and policy environment, presents an opportunity and a challenge for policy‐makers as well as for farms and firms. This article reports findings from a case study of knowledge diffusion in the organic sector in the province of Foggia, a developmentally backward area in Southern Italy. Our study shows that despite a cohesive‘network of interactions’ among organic producers, exchanges of knowledge are fairly marginal. This communication void is partially filled by local institutions that are shown to be effective in diffusing juridical and technical knowledge but less effective in providing commercial/market information. Further institutional efforts are required to cover these knowledge gaps. The study draws attention to some policy issues that can be shared by groups of organic producers elsewhere with characteristics similar to the Foggian case study, similarities that call for institutions to facilitate the creation, interpretation, and sharing of knowledge.
Developmental programming of obesity in mammals
Authors: Taylor P. D. , Poston L.
Published: December 2006

Converging lines of evidence from epidemiological studies and animal models now indicate that the origins of obesity and related metabolic disorders lie not only in the interaction between genes and traditional adult risk factors, such as unbalanced diet and physical inactivity, but also in the interplay between genes and the embryonic, fetal and early postnatal environment. Whilst studies in man initially focused on the relationship between low birth weight and risk of adult obesity and metabolic syndrome, evidence is also growing to suggest that increased birth weight and/or adiposity at birth can also lead to increased risk for childhood and adult obesity. Hence, there appears to be increased risk of obesity at both ends of the birth weight spectrum. Animal models, including both under‐ and overnutrition in pregnancy and lactation lend increasing support to the developmental origins of obesity. This review focuses upon the influence of the maternal nutritional and hormonal environment in pregnancy in permanently programming appetite and energy expenditure and the hormonal, neuronal and autocrine mechanisms that contribute to the maintenance of energy balance in the offspring. We discuss the potential maternal programming ‘vectors’ and the molecular mechanisms that may lead to persistent pathophysiological changes resulting in subsequent disease. The perinatal environment, which appears to programme subsequent obesity, provides a potential therapeutic target, and work in this field will readily translate into improved interventional strategies to stem the growing epidemic of obesity, a disease which, once manifest, has proven particularly resistant to treatment.
Axonal and somatic filtering of antidromically evoked cortical excitation by simulated deep brain stimulation in rat brain
Authors: Chomiak T. , Hu B.
Published: December 2006

Antidromic cortical excitation has been implicated as a contributing mechanism for high‐frequency deep brain stimulation (DBS). Here, we examined the reliability of antidromic responses of type 2 corticofugal fibres in rat over a stimulation frequency range compatible to the DBS used in humans. We activated antidromically individual layer V neurones by stimulating their two subcortical axonal branches. We found that antidromic cortical excitation is not as reliable as generally assumed. Whereas the fast conducting branches of a type 2 axon in the highly myelinated brainstem region follow high‐frequency stimulation, the slower conducting fibres in the poorly myelinated thalamic region function as low‐pass filters. These fibres fail to transmit consecutive antidromic spikes at the beginning of high‐frequency stimulation, but are able to maintain a steady low‐frequency (6–12 Hz) spike output during the stimulation. In addition, antidromic responses evoked from both branches are rarely present in cortical neurones with a more hyperpolarized membrane potential. Our data indicate that axon‐mediated antidromic excitation in the cortex is strongly influenced by the myelo‐architecture of the stimulation site and the excitability of individual cortical neurones.
Modeling of Spur and Helical Gear Planetary Drives With Flexible Ring Gears and Planet Carriers
Authors: Abousleiman V. , Velex P. , Becquerelle S.
Published: December 2006

A model is presented which enables the simulation of the three-dimensional static and dynamic behavior of planetary/epicyclic spur and helical gears with deformable parts. The contributions of the deflections of the ring gear and the carrier are introduced via substructures derived from 3D finite element models. Based on a modal condensation technique, internal gear elements are defined by connecting the ring-gear substructure and a planet lumped parameter model via elastic foundations which account for tooth contacts. Discrete mesh stiffness and equivalent normal deviations are introduced along the contact lines, and their values are recalculated as the mating flank positions vary with time. A constraint mode substructuring technique is used to simulate the planet carrier as a superelement which is connected to the planet center. Planetary/epicyclic gear models are completed by assembling lumped parameter sun gear/planet elements along with shaft elements, lumped stiffness, masses and inertias. The corresponding equations of motion are solved by combining a time-step integration scheme and a contact algorithm for all simultaneous meshes. Several quasistatic and dynamic results are given which illustrate the potential of the proposed hybrid model and the interest of taking into account ring gear and carrier deflections.