bluuebunny/crossref_metadata_2025 huggingface dataset:
Toronto’s Health Department in Action: Influenza in 1918 and SARS in 2003
Authors: MacDougall Heather
Published: October 2006

This article compares the Toronto Health Department’s role in controlling the 1918 influenza epidemic with its activities during the SARS outbreak in 2003 and concludes that local health departments are the foundation for successful disease containment, provided that there is effective coordination, communication, and capacity. In 1918, Toronto’s MOH Charles Hastings was the acknowledged leader of efforts to contain the disease, care for the sick, and develop an effective vaccine, because neither a federal health department nor an international body like WHO existed. During the SARS outbreak, Hastings’s successor, Sheela Basrur, discovered that nearly a decade of underfunding and new policy foci such as health promotion had left the department vulnerable when faced with a potential epidemic. Lack of cooperation by provincial and federal authorities added further difficulties to the challenge of organizing contact tracing, quarantine, and isolation for suspected and probable cases and providing information and reassurance to the multi-ethnic population. With growing concern about a flu pandemic, the lessons of the past provide a foundation for future communicable disease control activities.
Sin1 binds to both ATF‐2 and p38 and enhances ATF‐2‐dependent transcription in an SAPK signaling pathway
Authors: Makino Chieko , Sano Yuji , Shinagawa Toshie , Millar Jonathan B. A. , Ishii Shunsuke
Published: October 2006

Yeast Sin1 binds to the Sty1 kinase, a member of the stress‐activated kinases (SAPKs), and is required for stress‐induced phosphorylation and activation of the transcription factor Atf1, a homolog of the vertebrate‐activating transcription factor‐2 (ATF‐2). Here we report that mammalian Sin1 plays an important role in the SAPK signaling pathway by binding to both ATF‐2 and p38. In response to stress, ATF‐2, a member of the ATF/cAMP response element‐binding protein family, is phosphorylated by p38/Jun NH2‐terminal protein kinase and activates the transcription of apoptosis‐related genes. In contrast, in response to serum stimulation, ATF‐2 is phosphorylated via the Ras effector pathway and leads to the induction of growth‐related genes. We found that Sin1 binds directly to both ATF‐2 and p38. Sin1 over‐expression enhanced osmotic stress‐induced phosphorylation of ATF‐2 and ATF‐2‐mediated transcription, whereas knockdown of Sin1 expression by siRNA suppressed these responses. Moreover, a reduction in Sin1 expression suppressed osmotic stress‐induced apoptosis and the expression of Gadd45β, one of the ATF‐2 target genes that is correlated with apoptosis. Decreased Sin1 expression, however, did not affect the serum stimulation‐induced phosphorylation of ATF‐2. Sin1 may contribute to ATF‐2 signaling specificity by acting as a nuclear scaffold.
Endogenous interleukin‐18 is involved in immunity to Leishmania donovani but its absence does not adversely influence the therapeutic activity of sodium stibogluconate
Authors: Mullen Alexander B. , Lawrence Catherine E. , McFarlane Emma , Wei Xiao‐Quing , Carter Katharine C.
Published: October 2006

Immunity to Leishmania donovani is associated with an interleukin (IL)‐12 driven T helper 1 (Th1) response. In addition, the ability to respond to chemotherapy with sodium stibogluconate (SSG) requires a fully competent immune response and both Th1 and Th2 responses have been shown to positively influence the outcome of drug treatment. In the present study, the influence of IL‐18, which can modulate both interferon (IFN)‐γ and IL‐4 production, on the outcome of primary L. donovani infection and SSG therapy following infection was assessed using BALB/c IL‐18‐deficient and wild type mice. IL‐18 deficiency was associated with an increased susceptibility to L. donovani infection, evident by day 40 post infection, resulting in higher parasite burdens in the spleen, liver, and bone marrow compared with wild type control animals. Infected IL‐18‐deficient mice had significantly lower splenocyte concanavalin A (ConA) induced IFN‐γ production as well as lower serum IL‐12 and IFN‐γ levels, indicating a reduced Th1 response. However, drug treatment was equally effective in both mouse strains and restored serum IL‐12 and IFN‐γ levels, and IFN‐γ production by ConA stimulated splenocytes of IL‐18‐deficient mice, to levels equivalent to similarly treated wild type mice.
Gap disturbance triggers the recolonization of the clonal plant Ambrosia tenuifolia in a flooding grassland of Argentina
Authors: INSAUSTI PEDRO , GRIMOLDI AGUSTÍN A.
Published: October 2006

Abstract  Flooding provokes the death of many dicotyledonous species in grazed grasslands of the Flooding Pampa in Argentina, including the clonal plant Ambrosia tenuifolia, which produce the opening of numerous gaps. The objective of this study was to investigate the recolonization of grassland by A. tenuifolia after this species disappeared due to the occurrence of prolonged flooding events. To this end, responses of seed germination to environmental factors associated with gaps, such as light quality and temperature regime, conditions related to seedling survival, and clonal growth of ramets outside the gaps were studied in two different experiments in the field. Environmental factors related to gaps promoted the recruitment of new genets. The combined effect of alternating temperatures and the high red : far‐red ratio set off germination from the soil seed bank; germination also was enhanced when signals were generated artificially under the intact canopy in the field. Higher resource availabilities and maximum seedling survival were recorded in canopy gaps, which were the focus of invasion. Grassland recolonization outside the gaps continued rapidly by clonal growth, from small gaps and large ones, even within the dense surrounding canopy. This provoked an intense competition with the other species. Gap opening by disturbances, seed germination in gaps and clonal growth were decisive for the recolonization of A. tenuifolia populations. This sequence of events triggered the recolonization of the plant community by this species, in sites where it had been eliminated by prolonged flooding. This process represents one of the most significant fluctuations in the vegetation dynamics of the Flooding Pampa Grasslands.
Diet of four rock‐dwelling macropods in the Australian monsoon tropics
Authors: TELFER WENDY R. , BOWMAN DAVID M. J. S.
Published: October 2006

Abstract  An unusually high diversity of macropods inhabit the rocky areas in the monsoon tropics of the Northern Territory, Australia, yet the mechanisms that allow their niche separation are not clear. Previous studies suggest that the nabarlek, Petrogale concinna, may have a more grazing diet than the short‐eared rock‐wallaby, Petrogale brachyotis, with whom it coexists. Thus, diet may be an important mechanism of niche separation between these species. We examined the diet of the four sympatric species (the black wallaroo Macropus bernardus, common wallaroo Macropus robustus, P. brachyotis and P. concinna) to determine whether there are differences in the dominant plant groups eaten by the species across the landscape and with season. Diets were determined with a macroscopic analysis of the seed and fruit content of scats and an analysis of the 12C to 13C isotope ratios of scats using mass spectrometry. In the dry season the rock‐wallaby species predominantly consumed browse and/or forbs, and the larger wallaroos predominantly consumed grass. However, there was large variation across the landscape in the dry season diets of P. brachyotis, M. bernardus and M. robustus; including high proportions of grass eaten at some sites and high proportions of browse at other sites. In the wet season, greater proportions of grass were eaten by P. brachyotis and M. bernardus than in the dry season. Generally, there was little evidence to support the previous suggestion that P. concinna is more of a grazer than P. brachyotis, but there was some evidence than M. bernardus consumes greater amounts of browse and/or forbs than M. robustus.
Comparative analysis of leaf angle and sclerophylly of Aspidosperma quebracho‐blanco on a water deficit gradient
Authors: BARCHUK ALICIA H. , VALIENTE‐BANUET ALFONSO
Published: October 2006

Abstract  Aspidosperma quebracho‐blanco is found throughout the Chaco (17°−33°S) in Argentina, and it is the dominant tree species in the arid Chaco. Under the hypothesis that morpho‐physiological features of A. quebracho‐blanco change as a function of its geographical position on a water deficit gradient, it was predicted that with increasing water stress, leaf angles (specifically horizontal) would be greater and mean values of the leaf mass per area would increase. These leaf characteristics were compared at three points on a water deficit gradient extending from the humid Chaco through semi‐arid Chaco to the arid Chaco of Argentina (south‐west to north‐east rainfall gradient, from 350 to 1200 mm annual mean precipitation). Twig and leaf positions were modified and water potentials were measured at the highest heating hour of the day at a site of the arid Chaco. Daily and seasonal water potential variations of untreated twigs were also observed. Leaf angle modification towards horizontal produced more negative twig water potentials with respect to those of leaves in non‐horizontal positions. The comparison of the three sites along the gradient showed contrasting patterns of leaf‐angle frequency distribution of adults. In Chancaní (mean annual temperature: 18–24°C, mean annual precipitation: 450 mm, arid) there was a higher frequency of angles near 90° for non‐pendulous and about 270° for pendulous trees. Leaf angles in Copo (semi‐arid) and Chaco National Park (mean annual temperature: 20–23°C, mean annual precipitation: 1300 mm humid) were widely distributed with higher frequency towards the angles near 0° and 180°. This sclerophyllous tree species showed plasticity in its leaf traits along the precipitation gradient. Plasticity in leaf mass per area and leaf position enables plants to develop efficiently in contrasting environmental conditions of humidity and aridity.
Growth curves of the fetal prostate based on three‐dimensional reconstructions: a correlation with gestational age and maternal testosterone levels
Authors: Lunacek Andreas , Oswald Josef , Schwentner Christian , Schlenck Barbara , Horninger Wolfgang , Fritsch Helga , Longato Stefano , Sergi Consolato , Bartsch Georg , Radmayr Christian
Published: October 2006

There are two papers in this section this month. The first, by authors from Austria, concerns growth curves of the fetal prostate, correlating gestational age and maternal testosterone using three‐dimensional reconstructions. The second, from the UK, investigated testicular microlithiasis, and found no convincing evidence that alone it is a premalignant condition.

OBJECTIVE

To create a nomogram of the fetal growth of the human prostate corresponding to gestational age, and to investigate the relationship between the expansive growth of the fetal prostate and the maternal testosterone surge during pregnancy.

MATERIALS AND METHODS

In all, 27 fetal prostates at 11–40 weeks of gestation, and seven neonatal specimens at 1–20 weeks after birth, were analysed. Serial sections of prostates were immunostained and examined using light microscopy. After modular image acquisition the volumes were calculated using three‐dimensional reconstruction. The prostate volumes were correlated with gestational age, and related to reference testosterone levels during pregnancy.

RESULTS

There was exponential growth of the fetal prostate with gestational age. The increasing volume of the prostate during the fetal period corresponded with maternal testosterone levels. In the second trimester there was a significant increase in prostate volume in relation to the bladder. In infants, macroscopically there was an inverse proportion between bladder size and prostate volume.

CONCLUSIONS

Starting from the second trimester there is distinct growth of the fetal prostate, obviously triggered by the maternal testosterone surge. In neonates there is an inversion of the dimensions between bladder and prostate. These results indicating exponential growth of the fetal prostate provide evidence of a gender‐related transient infravesical obstruction in human fetuses.
Could a rural lifestyle decrease the prevalence of erectile dysfunction?
Authors: De Almeida Claro Joaquim , Kaufmann Oskar Grau , Alarcon Gustavo , Aguiar Wilson , Nadozza Archimedes , Ortiz Valdemar , Srougi Miguel
Published: October 2006

OBJECTIVE

To determine the prevalence of erectile dysfunction (ED) in a specific population and explore potential correlates with lifestyle.

SUBJECTS AND METHODS

This prospective observational study, covering a population of a very small rural town, included 2000 men aged ≥ 20 years from a total population of 121 831 (51% female and 49% male). The International Index of Erectile Function was completed by each of the 2000 men at their homes over a 1‐year period. Another questionnaire assessing socio‐economic status and health‐related determinants of ED were also completed.

RESULTS

All 2000 men completed the questionnaires; overall, only 34 reported ED (1.7%). The frequency of mild, mild to moderate, moderate and severe ED was 12%, 29%, 20% and 38%, respectively. Significantly more men aged > 51 years had ED than those aged <41 years (0.05% and 0.45%, respectively; P < 0.001). There was no difference in ED with salary levels.

CONCLUSION

The prevalence of ED in this particular rural population of Brazil was very low, at only 1.7%. Although ED increases with age, this association was not apparent for all age groups. It seems that several others factors, e.g. lifestyle, culture and diet, could be important for the onset of ED.
Development of a cell‐isolation method for human prostatic smooth muscle cells based on cell type‐specific activation of the SM22 gene promoter
Authors: Wang Chun‐Yu , Shi Jian‐Dang , Yan Chun‐He , Wu Quan , Klocker Helmut , Park Irwin , Lee Chung , Zhang Ju
Published: October 2006

OBJECTIVE

To separate smooth muscle cells (SMCs) from fibroblasts in cultured human prostatic stromal cells (PrSCs) by characterizing the SM22 promoter as a prostatic SMC‐specific gene promoter, and to investigate its use for a promoter‐based cell‐sorting method, as SMCs are critical for stromal function and the pathological changes in the development of benign prostatic hyperplasia.

MATERIALS AND METHODS

Human PrSCs were cultured in SMC‐selective medium or standard medium, respectively, to obtain typical cultures of SMCs and fibroblasts. SM22 promoter activity and specificity were analysed by luciferase reporter‐gene assay. A dual‐colour vector was constructed with the expression of the red fluorescent protein (RFP) under the control of the 1.4 kb SMC‐specific SM22 promoter, and the expression of the green fluorescent protein (GFP) under cytomegalovirus promoter. Fluorescence‐activated cell sorting (FACS) was used to isolate and enrich GFP+/RFP+ and GFP+/RFP– cells. Cell phenotype was confirmed by reverse transcription‐polymerase chain reaction and immunofluorescence.

RESULTS

The 1.4 kb SM22 promoter activity was much higher in PrSCs cultured in SMC‐selective medium. Immunofluorescence staining and merged fluorescence microscopy ensured that SM22 promoter‐driven GFP positive cells were SMCs. After transfection of the dual‐colour vector into PrSCs, GFP+/RFP+ cells (SMCs) and GFP+/RFP– cells (fibroblasts) were isolated by FACS. The phenotype of FACS‐enriched SMCs and fibroblasts was confirmed.

CONCLUSION

These results indicate that the 1.4 kb SM22 promoter is specific for prostatic SMCs. This dual‐colour vector could be a useful tool for separating living SMCs from fibroblasts using FACS.
Australia's switch to international financial reporting standards: a perspective from account preparers
Authors: Jones Stewart , Higgins Alison D.
Published: October 2006

This study reports the findings of a structured telephone survey on adoption of international financial reporting standards (IFRS) from 60 firms drawn from among Australia's top 200 corporations. Although we find evidence of strong systematic variation in survey responses with factors such as firm size, industry background and expected impacts on financial performance, the general results indicate that many respondents have not been well prepared for the transition and are generally very sceptical about the claimed benefits of IFRS as enunciated in the government's Corporate Law Economic Reform Program. The results have implications to other international reporting jurisdictions, particularly the European Union, where adoption of IFRS is already underway.
OPTIMAL INTERNATIONAL ASSET ALLOCATION WITH TIME‐VARYING RISK
Authors: Flavin Thomas J. , Wickens Michael R.
Published: October 2006

This paper examines the optimal allocation each period of an internationally diversified portfolio from the different points of view of a UK and a US investor. We find that investor location affects optimal asset allocation. The presence of exchange rate risk causes the markets to appear not fully integrated and creates a preference for home assets. Domestic equity is the dominant asset in the optimal portfolio for both investors, but the US investor bears less risk than the UK investor, and holds less foreign equity – 20% compared with 25%. Survey evidence indicates actual shares are 6% and 18%, respectively, making the home‐bias puzzle more acute for US than UK investors. There would seem to be more potential gains from increased international diversification for the US than the UK investor.
On modeling panels of time series*
Authors: Franses Philip Hans
Published: October 2006

This paper reviews research issues in modeling panels of time series. Examples of this type of data are annually observed macroeconomic indicators for all countries in the world, daily returns on the individual stocks listed in the S&P500, and the sales records of all items in a retail store. A panel of time series concerns the case where the cross‐sectional dimension and the time dimension are large. Often, there is noa priorireason to select a few series or to aggregate the series over the cross‐sectional dimension. The use of, for example, a vector autoregression or other types of multivariate models then becomes cumbersome. Panel models and associated estimation techniques are more useful. Due to the large time dimension, one should however incorporate the time‐series features. And, the models should not have too many parameters to facilitate interpretation. This paper discusses representation, estimation and inference of relevant models and discusses recently proposed modeling approaches that explicitly aim to meet these requirements. The paper concludes with some reflections on the usefulness of large data sets. These concern sample selection issues and the notion that more detail also requires more complex models.
World Englishes and the multilingual history of English
Authors: MESTHRIE RAJEND
Published: October 2006

ABSTRACT: Traditional histories of English (e.g.,Baugh and Cable, 1993) present a mostly unilinear account of the language that privileges the standard in Britain and to a lesser extent, the US. Most other varieties (e.g., in Australia, Nigeria or India) are treated as appendages to this history, of interest mainly for their lexical innovations. At the same time, studies of New Englishes (e.g.,Plattet al., 1984) have also promulgated this separateness in history. This paper attempts to unify the history of Englishes by highlighting a thread that is downplayed in traditional accounts: that the language hasalwaysexisted amidst a multilingual ethos in which language contact has been ever‐present.
Emerging South‐East Asian Englishes and intelligibility
Authors: DETERDING DAVID , KIRKPATRICK ANDY
Published: October 2006

ABSTRACT:  An English lingua franca seems to be emerging in the ten ASEAN countries, and this paper investigates features of the pronunciation of this lingua franca. Twenty speakers, two from each of the ASEAN countries, were recorded while they were conversing in groups of three or four people, all from a different country. The speech that they used is analysed to identify shared features of pronunciation, especially to evaluate the effect that these features have on intelligibility, and it is argued that some of their shared non‐standard features actually enhance intelligibility. Finally, some of the misunderstandings that occurred are analysed to determine the extent to which pronunciation played a part, and it is found that only those features of pronunciation not shared by speakers from other ASEAN countries resulted in a break‐down in communication.
Globalization and English in Chinese higher education
Authors: CHANG JUNYUE
Published: October 2006

ABSTRACT:  This paper sets China's education of English majors within the changing global and national context. It examines the impact of accelerating globalisation and the rise of global English, the adjustment of China's English language policy, the growth of the education of English majors and the challenges faced by this sector of education. To adapt to the changes, efforts have been made to change the training models, revise the national curriculum and update textbooks. The introduction of six new training models is significant: “English major plus courses in other specialisms”, “English major plus an orientation towards other disciplines”, “English major plus a minor”, “A major plus English language”, “English language plus another foreign language”, and “Dual degree: BA degree of English language and literature plus another BA degree”. Turning out ‘composite‐type’ graduates has become a training objective of the curriculum for English majors, with consequent implications for the future development of this sector of education in China.
Global optimization of feature weights and the number of neighbors that combine in a case‐based reasoning system
Authors: Ahn Hyunchul , Kim Kyoung‐jae , Han Ingoo
Published: October 2006

Abstract:Case‐based reasoning (CBR) often shows significant promise for improving the effectiveness of complex and unstructured decision‐making. Consequently, it has been applied to various problem‐solving areas including manufacturing, finance and marketing. However, the design of appropriate case indexing and retrieval mechanisms to improve the performance of CBR is still a challenging issue. Most previous studies on improving the effectiveness of CBR have focused on the similarity function aspect or optimization of case features and their weights. However, according to some of the prior research, finding the optimal k parameter for the k‐nearest neighbor is also crucial for improving the performance of the CBR system. Nonetheless, there have been few attempts to optimize the number of neighbors, especially using artificial intelligence techniques. In this study, we introduce a genetic algorithm to optimize the number of neighbors that combine, as well as the weight of each feature. The new model is applied to the real‐world case of a major telecommunication company in Korea in order to build a prediction model for customer profitability level. Experimental results show that our genetic‐algorithm‐optimized CBR approach outperforms other artificial intelligence techniques for this multi‐class classification problem.
Revisiting the Turkish Revolution, 1923–1938: Secular Reform and Religious “Reaction”1
Authors: Brockett Gavin D.
Published: October 2006

This article explores the common notion that the secular reforms introduced by Turkey's founding President, Mustafa Kemal Atatürk, met with constant opposition in the form of Islamic “reaction.” It explores the genealogy of this concept and its place in the historical literature concerning Turkey. The argument is that the idea of Islamic “reaction” results in the misrepresentation of Turkish history and is based on a fundamentally flawed view of religion and society.
A Mutant Chaperone Converts a Wild-Type Protein into a Tumor-Specific Antigen
Authors: Schietinger Andrea , Philip Mary , Yoshida Barbara A. , Azadi Parastoo , Liu Hui , Meredith Stephen C. , Schreiber Hans
Published: October 2006

Monoclonal antibodies have become important therapeutic agents against certain cancers. Many tumor-specific antigens are mutant proteins that are predominantly intracellular and thus not readily accessible to monoclonal antibodies. We found that a wild-type transmembrane protein could be transformed into a tumor-specific antigen. A somatic mutation in the chaperone gene
Cosmc
abolished function of a glycosyltransferase, disrupting O-glycan Core 1 synthesis and creating a tumor-specific glycopeptidic neo-epitope consisting of a monosaccharide and a specific wild-type protein sequence. This epitope induced a high-affinity, highly specific, syngeneic monoclonal antibody with antitumor activity. Such tumor-specific glycopeptidic neo-epitopes represent potential targets for monoclonal antibody therapy.
Cellular and Subcellular Structure of Neoproterozoic Animal Embryos
Authors: Hagadorn James W. , Xiao Shuhai , Donoghue Philip C. J. , Bengtson Stefan , Gostling Neil J. , Pawlowska Maria , Raff Elizabeth C. , Raff Rudolf A. , Turner F. Rudolf , Chongyu Yin , Zhou Chuanming , Yuan Xunlai , McFeely Matthew B. , Stampanoni Marco , Nealson Kenneth H.
Published: October 2006

Stereoblastic embryos from the Doushantuo Formation of China exhibit occasional asynchronous cell division, with diminishing blastomere volume as cleavage proceeded. Asynchronous cell division is common in modern embryos, implying that sophisticated mechanisms for differential cell division timing and embryonic cell lineage differentiation evolved before 551 million years ago. Subcellular structures akin to organelles, coated yolk granules, or lipid vesicles occur in these embryos. Paired reniform structures within embryo cells may represent fossil evidence of cells about to undergo division. Embryos exhibit no evidence of epithelial organization, even in embryos composed of â¼1000 cells. Many of these features are compatible with metazoans, but the absence of epithelialization is consistent only with a stem-metazoan affinity for Doushantuo embryos.
Eccentric overload training in patients with chronic Achilles tendinopathy: a systematic review
Authors: Kingma J J , de Knikker R , Wittink H M , Takken T
Published: October 2006

Background:Eccentric overload training seems to be a promising conservative intervention in patients with chronic Achilles tendinopathy. The efficacy of eccentric overload training on the outcome measures of pain and physical functioning are not exactly clear.

Study design:Systematic review of the literature.

Methods:Electronic databases were searched for randomised clinical trials concerning eccentric overload training in patients with chronic Achilles tendinopathy. The Delphi list was used to assess the methodological quality of the studies.

Results:Nine clinical trials were included. Only one study had sufficient methodological quality. The included trials showed an improvement in pain after eccentric overload training. Because of the methodological shortcomings of the trials, no definite conclusion can be drawn concerning the effects of eccentric overload training in patients with chronic Achilles tendinopathy.

Conclusion:The effects of eccentric exercise training in patients with chronic Achilles tendinopathy on pain are promising; however, the magnitude of the effects cannot be determined. Large, methodologically sound studies from multiple sites in which functional outcome measures are included are warranted.
BOOSTING-BASED FRAMEWORK FOR PORTFOLIO STRATEGY DISCOVERY AND OPTIMIZATION
Authors: GAVRISHCHAKA VALERIY V.
Published: October 2006

Increasing availability of the multi-scale market data exposes limitations of the existing quantitative models such as low accuracy of the simplified analytical and statistical frameworks as well as insufficient interpretability and stability of the best machine learning algorithms. Boosting was recently proposed as a simple and robust framework for intelligent combination of the clarity and stability of the analytical and parsimonious statistical models with the accuracy of the adaptive data-driven models. Encouraging results of the boosting application to symbolic volatility forecasting have also been reported. However, accurate forecasting does not always warrant optimal decision making that leads to acceptable performance of the portfolio strategy. In this work, a boosting-based framework for a direct trading strategy and portfolio optimization is introduced. Due to inherent adaptive control of the parameter space dimensionality, this technique can work with very large pools of base strategies and financial instruments that are usually prohibitive for other portfolio optimization frameworks. Unlike existing approaches, this framework can be effectively used for the coupled optimization of the portfolio capital/asset allocation and dynamic trading strategies. Generated portfolios of trading strategies not only exhibit stable and robust performance but also remain interpretable. Encouraging preliminary results based on real market data are presented and discussed.
The Multiple Endocrine Neoplasia Syndromes
Authors: Lakhani Vipul T. , You Y. Nancy , Wells Samuel A.
Published: October 2006

Multiple endocrine neoplasia (MEN) type 1 and type 2 exhibit an autosomal dominant pattern of inheritance. In the past two decades the germline mutations that cause these inherited syndromes have been identified. The large majority of patients with MEN1 have mutations in the menin gene. Mutations in the REarranged during Transfection (RET) gene cause MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC). Specific codon mutations within RET correlate with disease phenotype and severity. Also, children from families with MEN2A, MEN2B, or FMTC, who are found to have inherited a mutated RET allele, can be managed by prophylactic thyroidectomy, thus preventing the development of medullary thyroid carcinoma (MTC), the dominant endocrinopathy in patients with these hereditary syndromes. New insights into the molecular pathway of RET signal transduction are leading to novel targeted therapies in patients with locally advanced or metastatic hereditary MTC.
Stochastic Simulation of Chemical Kinetics
Authors: Gillespie Daniel T.
Published: October 2006

Stochastic chemical kinetics describes the time evolution of a well-stirred chemically reacting system in a way that takes into account the fact that molecules come in whole numbers and exhibit some degree of randomness in their dynamical behavior. Researchers are increasingly using this approach to chemical kinetics in the analysis of cellular systems in biology, where the small molecular populations of only a few reactant species can lead to deviations from the predictions of the deterministic differential equations of classical chemical kinetics. After reviewing the supporting theory of stochastic chemical kinetics, I discuss some recent advances in methods for using that theory to make numerical simulations. These include improvements to the exact stochastic simulation algorithm (SSA) and the approximate explicit tau-leaping procedure, as well as the development of two approximate strategies for simulating systems that are dynamically stiff: implicit tau-leaping and the slow-scale SSA.
Kinetics of integrated electron transfer in the mitochondrial respiratory chain: random collisions vs. solid state electron channeling
Authors: Lenaz Giorgio , Genova Maria Luisa
Published: October 2006

Recent evidence, mainly based on native electrophoresis, has suggested that the mitochondrial respiratory chain is organized in the form of supercomplexes, due to the aggregation of the main respiratory chain enzymatic complexes. This evidence strongly contrasts the previously accepted model, the Random Diffusion Model, largely based on kinetic studies, stating that the complexes are randomly distributed in the lipid bilayer of the inner membrane and functionally connected by lateral diffusion of small redox molecules, i.e., coenzyme Q and cytochrome c. This review critically examines the experimental evidence, both structural and functional, pertaining to the two models and attempts to provide an updated view of the organization of the respiratory chain and of its kinetic consequences. The conclusion that structural respiratory assemblies exist is overwhelming, whereas the expected functional consequence of substrate channeling between the assembled enzymes is controversial. Examination of the available evidence suggests that, although the supercomplexes are structurally stable, their kinetic competence in substrate channeling is more labile and may depend on the system under investigation and the assay conditions.
Role of Na+-K+-Cl− cotransport and Na+/Ca2+ exchange in mitochondrial dysfunction in astrocytes following in vitro ischemia
Authors: Kintner Douglas B. , Luo Jing , Gerdts Josiah , Ballard Andy J. , Shull Gary E. , Sun Dandan
Published: October 2006

Na+-K+-Cl− cotransporter isoform 1 (NKCC1) and reverse mode operation of the Na+/Ca2+ exchanger (NCX) contribute to intracellular Na+ and Ca2+ overload in astrocytes following oxygen-glucose deprivation (OGD) and reoxygenation (REOX). Here, we further investigated whether NKCC1 and NCX play a role in mitochondrial Ca2+ (Cam2+) overload and dysfunction. OGD/REOX caused a doubling of mitochondrial-releasable Ca2+ ( P < 0.05). When NKCC1 was inhibited with bumetanide, the mitochondrial-releasable Ca2+ was reduced by ∼42% ( P < 0.05). Genetic ablation of NKCC1 also reduced Cam2+ accumulation. Moreover, OGD/REOX in NKCC1+/+ astrocytes caused dissipation of the mitochondrial membrane potential (Ψm) to 42 ± 3% of controls. In contrast, when NKCC1 was inhibited with bumetanide, depolarization of Ψm was attenuated significantly (66 ± 10% of controls, P < 0.05). Cells were also subjected to severe in vitro hypoxia by superfusion with a hypoxic, acidic, ion-shifted Ringer buffer (HAIR). HAIR/REOX triggered a secondary, sustained rise in intracellular Ca2+ that was attenuated by reversal NCX inhibitor KB-R7943. The hypoxia-mediated increase in Cam2+ was accompanied by loss of Ψm and cytochrome c release in NKCC1+/+ astrocytes. Bumetanide or genetic ablation of NKCC1 attenuated mitochondrial dysfunction and astrocyte death following ischemia. Our study suggests that NKCC1 acting in concert with NCX causes a perturbation of Cam2+ homeostasis and mitochondrial dysfunction and cell death following in vitro ischemia.
Mechanisms of endothelial cell protection by blockade of the JAK2 pathway
Authors: Neria Fernando , Caramelo Carlos , Peinado Héctor , González-Pacheco Francisco R. , Deudero Juan JP. , de Solis Alain J. , Fernández-Sánchez Ruth , Peñate Silvia , Cano Amparo , Castilla Mª Ángeles
Published: October 2006

Inhibition of the JAK2/STAT pathway has been implicated recently in cytoprotective mechanisms in both vascular smooth muscle cells and astrocytes. The advent of JAK2-specific inhibitors provides a practical tool for the study of this pathway in different cellular types. An interest in finding methods to improve endothelial cell (EC) resistance to injury led us to examine the effect of JAK2/STAT inhibition on EC protection. Furthermore, the signaling pathways involved in JAK2/STAT inhibition-related actions were examined. Our results reveal, for the first time, that blockade of JAK2 with the tyrosine kinase inhibitor AG490 strongly protects cultured EC against cell detachment-dependent death and serum deprivation and increases reseeding efficiency. Confirmation of the specificity of the effects of JAK2 inhibition was attained by finding protective effects on transfection with a dominant negative JAK2. Furthermore, AG490 blocked serum deprivation-induced phosphorylation of JAK2. In terms of mechanism, treatment with AG490 induces several relevant responses, both in monolayer and detached cells. These mechanisms include the following: 1) Increase and nuclear translocation of the active, dephosphorylated form of β-catenin. In functional terms, this translocation is transcriptionally active, and its protective effect is further supported by the stimulation of EC cytoprotection by transfectionally induced excess of β-catenin. 2) Increase of platelet endothelial cell adhesion molecule (PECAM)/CD31 levels. 3) Increase in total and phosphorylated AKT. 4) Increase in phosphorylated glycogen synthase kinase (GSK)3α/β. The present findings imply potential practical applications of JAK2 inhibition on EC. These applications affect not only EC in the monolayer but also circulating detached cells and involve mechanistic interactions not previously described.
Partial Reconstruction of Muscle Activity From a Pruned Network of Diverse Motor Cortex Neurons
Authors: Schieber Marc H. , Rivlis Gil
Published: October 2006

Primary motor cortex (M1) neurons traditionally have been viewed as “upper motor neurons” that directly drive spinal motoneuron pools, particularly during finger movements. We used spike-triggered averages (SpikeTAs) of electromyographic (EMG) activity to select M1 neurons whose spikes signaled the arrival of input in motoneuron pools, and examined the degree of similarity between the activity patterns of these M1 neurons and their target muscles during 12 individuated finger and wrist movements. Neuron–EMG similarity generally was low. Similarity was unrelated to the strength of the SpikeTA effect, to whether the effect was pure versus synchrony, or to the number of muscles influenced by the neuron. Nevertheless, the sum of M1 neuron activity patterns, each weighted by the sign and strength of its SpikeTA effect, could be more similar to the EMG than the average similarity of individual neurons. Significant correlations between the weighted sum of M1 neuron activity patterns and EMG were obtained in six of 17 muscles, but showed R2 values ranging from only 0.26 to 0.42. These observations suggest that additional factors—including inputs from sources other than M1 and nonlinear summation of inputs to motoneuron pools—also contributed substantially to EMG activity patterns. Furthermore, although each of these M1 neurons produced SpikeTA effects with a significant peak or trough 6–16 ms after the triggering spike, shifting the weighted sum of neuron activity to lead the EMG by 40–60 ms increased their similarity, suggesting that the influence of M1 neurons that produce SpikeTA effects includes substantial synaptic integration that in part may reach the motoneuron pools over less-direct pathways.
Interest and Self-Sustained Learning as Catalysts of Development: A Learning Ecology Perspective
Authors: Barron Brigid
Published: October 2006

Adolescents often pursue learning opportunities both in and outside school once they become interested in a topic. In this paper, a learning ecology framework and an associated empirical research agenda are described. This framework highlights the need to better understand how learning outside school relates to learning within schools or other formal organizations, and how learning in school can lead to learning activities outside school. Three portraits of adolescent learners are shared to illustrate different pathways to interest development. Five types of self-initiated learning processes are identified across these case portraits. These include the seeking out of text-based informational sources, the creation of new interactive activity contexts such as projects, the pursuit of structured learning opportunities such as courses, the exploration of media, and the development of mentoring or knowledge-sharing relationships. Implications for theories of human development and ideas for research are discussed.
Cutaneous Manifestations of Diabetes Mellitus
Authors: Al-Mutairi Nawaf , Zaki Amr , Sharma Ashok Kumar , Al-Sheltawi Mazen
Published: October 2006

Objective: To study the prevalence of cutaneous disorders in patients with diabetes mellitus. Subjects and Methods: All diabetic patients attending the Department of Dermatology, Al-Farwaniya Hospital, Kuwait, and diabetic in-patients with skin disorders were examined over a period of 18 months from March 2004 to August 2005. A total of 106 diabetic patients displaying 1 or more dermatological manifestations were identified and thoroughly examined for any skin disorder. The diabetic profile of the patients was obtained from medical records. Results: Of the 106 patients, 69 had only 1 cutaneous manifestation, 27 had 2, 6 had 3 and 4 had 4. Infections (68.0%) were the major cutaneous manifestations with fungal infection occurring in 41 patients followed by bacteria in 27. The second most common presenting symptom was pruritus. Hypertension (74%) was the most common systemic complication, and most of the diabetic patients who developed cutaneous manifestations were in the 40- to 60-year age group. Conclusions: The data show that infections were the most common cutaneous manifestation and hypertension the most common systemic complication.
Competition between Plasmid-Bearing and Plasmid-Free Organisms in the Host: Population Dynamics and Antibiotic Resistance
Authors: Song Hui-Xing , Peng Yuan-Ying , Zhu Zhi-Fu
Published: October 2006

Objective: To clarify the effects of antibiotic exposure on bacterial antibiotic resistance. Materials and Methods: A competitive population dynamics model for plasmid-bearing organisms and plasmid-free organisms in the host was established. The Poincaré-Bendixson theorem was used for analysis. Results: All possible results of the competition dependent on biologically meaningful parameters were obtained, which can be classified into eight categories. With the outcomes of the plasmid model, we discussed the sterilizing effect if an antibiotic was added to the host. Conclusion: When antibiotic-resistant bacteria existed in a host, a higher dosage of antibiotics was needed with an increased risk of survival of plasmid-bearing organisms and greater danger of resistance to antibiotics.
The Use of Surgery in Displaced Scapular Neck Fractures
Authors: Khallaf F. , Mikami A. , Al-Akkad M.
Published: October 2006

Objectives: To evaluate the use of surgical management in displaced scapular neck fractures. Subjects and Methods: 14 adult male patients (average age 34 years, range 19–44) with displaced scapular neck fractures were treated by open reduction and internal fixation in Al-Jahra Hospital, Kuwait from April 2000 to January 2004. Patients’ clinical and radiological results were analyzed retrospectively. Results: The average follow-up was 20 months (range 6–30 months). Anatomical or near-anatomical reduction of the fracture with excellent clinical function was obtained in 12 patients (86%) and with good functional outcome in 2 patients (14%). One patient with associated head injury developed heterotopic ossification connected to the lateral border of the scapula. Conclusion: The results of this report show that open reduction and internal fixation of grossly displaced scapular neck fractures are the treatment of choice for these injuries to restore the normal biomechanics of both glenohumeral and scapulothoracic joints and allow favorable clinical outcome.
Induction of Apoptosis in HaCaT Cells by Photodynamic Therapy with Chlorin e6 or Pheophorbide a
Authors: Radestock A. , Elsner P. , Gitter B. , Hipler U.-C.
Published: October 2006

The two photosensitizers, chlorin e6 and pheophorbide a, were tested in an in vitro model of topical photodynamic therapy (PDT). Both dyes accumulate in HaCaT keratinocytes as verified by fluorescence measurement but pheophorbide a is enriched fivefold more strongly than chlorin e6 after 24 h. HaCaT cells are susceptible to PDT with both dyes. The phototoxicity measured by ATP bioluminescence is caused by necrosis and apoptosis depending on the photosensitizer used and the treatment modality. Chlorin e6 shows higher toxic potential because it elicits nearly 90% cell mortality 24 h after PDT comparable to pheophorbide a but with a fivefold lower rate of accumulation. These results implicate caution with topical PDT of oncologic diseases due to the risk of serious side effects on healthy skin in the course of topical photodynamic treatment. But the lack of dark toxicity and the time-dependent enrichment of both dyes in HaCaT cells are arguments for the application of these sensitizers in topical PDT of non-malign skin disorders. Further studies are necessary to discover appropriate lower doses and mechanisms of action of topical PDT with both compounds.
In vitro Percutaneous Absorption and in vivo Stratum Corneum Distribution of an Organic and a Mineral Sunscreen
Authors: Mavon A. , Miquel C. , Lejeune O. , Payre B. , Moretto P.
Published: October 2006

Sunscreens, whose main function is to protect the skin against the harmful effects of solar irradiation, should remain at the skin surface or impregnate the first layers of the stratum corneum only and not penetrate into the underlying living tissue. The goal of this work was to assess the penetration of titanium dioxide (TiO2) and methylene bis-benzotriazoyl tetramethylbutylphenol (MBBT), included in a broad-spectrum sunscreen formulation, into human skin in vivo, using the tape stripping method, and in vitro, using a compartmental approach. An additional objective was to propose an easy and minimally invasive approach to determining the percutaneous uptake of sunscreens following topical application. TiO2 and MBBT were quantified using colorimetric assay and HPLC analysis, respectively. The transmission electron microscopy and particle-induced X-ray emission techniques were used to localize the TiO2 in skin sections.More than 90% of both sunscreens was recovered in the first 15 tape strippings. In addition we have shown that the remaining 10% did not penetrate the viable tissue, but was localized in the furrows and in the opened infundibulum. Less than 0.1% of MBBT was detected in the receptor medium, and no TiO2 was detected in the follicle, viable epidermis or dermis. Thus, this in vivo and in vitro penetration study showed an absence of TiO2 penetration into the viable skin layers through either transcorneal or transfollicular pathways and negligible transcutaneous absorption of MBBT. However, differences in distribution within the stratum corneum reinforced the need for a complementary approach, using minimally invasive in vivo methodology and in vitro compartmental analysis.This combination represents a well-adapted method for testing the safety of topically applied sunscreen formulations in real-life conditions.