bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of pegylated interferon and ribavirin on morbidity and mortality in patients with chronic hepatitis C and normal aminotransferases in France #
Authors: Deuffic-Burban Sylvie , Babany Gérard , Lonjon-Domanec Isabelle , Deltenre Pierre , Canva-Delcambre Valérie , Dharancy Sébastien , Louvet Alexandre , Roudot-Thoraval Françoise , Mathurin Philippe
Published: July 2009

Clinicians continue to raise questions concerning the necessity of treating chronic hepatitis C virus (HCV)-infected patients with normal alanine aminotransferase (N-ALT), in light of their slower progression to cirrhosis than patients with elevated alanine aminotraferase (E-ALT). This study was undertaken to predict the impact of pegylated interferon (IFN) and ribavirin on HCV-related morbidity and mortality in patients with N-ALT. A previous Markov model was adapted to separately simulate patients with N-ALT (30%) and those with E-ALT (70%). The model estimates fibrosis progression rates according to age, sex, and whether ALT levels are normal or elevated, assuming that patients with E-ALT have a 2.6 times higher progression than those with N-ALT. It takes into account improvement in HCV screening and treatment and competitive mortality. We assumed that N-ALT patients were treated 80% less frequently between 2002 and 2004 and 70% less frequently from 2005 on, as obtained in real life from three multicentric cohorts (Hepatys, Adequation, Persee). Antiviral treatment of HCV-infected populations might reduce 2008-2025 HCV-related morbidity and mortality by 34,200 cases of cirrhosis (36%, 33,000-35,000), 22,400 complications (28%, 21,000-23,000) and 17,500 deaths (25%, 17,000-18,000), including 3000 cases of cirrhosis (22%, 2000-5000), 1200 complications (15%, 1000-1700), and 1000 deaths (14%, 900-1300) in the N-ALT population, despite a probability of receiving treatment that is three to five times less in this population. If N-ALT patients are treated at the same proportions as those with E-ALT, morbidity and mortality could be further reduced by 1400 cases of cirrhosis (13%, 1200-2200), 600 complications (9%, 600-1000), and 500 deaths (9%, 500-800). Conclusion: Treatment of N-ALT patients would decrease HCV morbidity and mortality. These patients should be considered candidates for treatment just as others are. (Hepatology 2009.)
A model for employee performance trend analysis of distribution centers
Authors: Wu Yu‐Jen , Hou Jiang‐Liang
Published: July 2009

To enhance the operational efficiency of a distribution center (DC), the DC managers have to identify the variations of employee performance with time and use the appropriate management strategies for employee rewards and training. However, the DC managers usually lack a systematic approach for analyzing the employee performance trend to determine the employees to be rewarded or trained. To solve the issue, this research develops a model for analysis of employee performance trend based on an employee performance estimation model. The proposed model consists of two main modules—namely, Derivation of Performance Control Limits (DPCL) and Appraisal of Performance Trend (APT). In the DPCL module, the employee performance can be estimated and the upper and lower control limits of employee performance can be determined. After that, by application of the APT module, the indices of employee performance trend can be derived and can be represented visually for efficient decision of DC managers. On the basis of the proposed model, this research also establishes a Web‐based system for employee performance trend analysis (namely, EPTA platform). Furthermore, a real‐world case was used to evaluate the applicability of the proposed model and platform. By application of the improved analysis diagram generated by the EPTA platform, the uncertain variations of performance trend can be removed to enhance the accuracy of performance trend analysis. As a result, the DC managers can efficiently determine whether the performance trends of employees indicate significant performance increases or decreases by using the proposed model and system. © 2009 Wiley Periodicals, Inc.
Serum IL‐6 levels and the risk for hepatocarcinogenesis in chronic hepatitis C patients: An analysis based on gender differences
Authors: Nakagawa Hayato , Maeda Shin , Yoshida Haruhiko , Tateishi Ryosuke , Masuzaki Ryota , Ohki Takamasa , Hayakawa Yoku , Kinoshita Hiroto , Yamakado Minoru , Kato Naoya , Shiina Shuichiro , Omata Masao
Published: July 2009

Interleukin‐6 (IL‐6) may play a role in the pathogenesis of hepatocellular carcinoma (HCC). Recently, it was reported in mouse models that estrogen‐mediated inhibition of IL‐6 production explains the gender disparity in HCC. We conducted a retrospective cohort study to examine whether this hypothesis is applicable to human HCC. We enrolled 330 patients with chronic hepatitis C whose serum samples were collected between January 1994 and December 2002. Serum IL‐6 concentrations were measured and patients were divided into three groups according to IL‐6 levels: low, middle, and high. We evaluated the association between serum IL‐6 levels and the risk of subsequent HCC development, including subgroup analysis on each gender. During the follow‐up period (mean 9.0 yr), HCC developed in 126 patients. The incidence rates differed significantly among the three groups (p = 0.015), increasing in accordance with serum IL‐6 levels. However, unexpectedly, this tendency was significant only in female patients. In a multivariate analysis, higher serum IL‐6 level was an independent risk factor for HCC development in female patients, with a hazard ratio of 1.61. Although female patients showed a weak negative correlation between serum IL‐6 levels and estradiol levels, the lower risk of HCC in female patients cannot be fully explained by estrogen‐mediated inhibition of IL‐6 production. In conclusion, higher serum IL‐6 level was an independent risk factor for HCC development in female but not male chronic hepatitis C patients. Measurement of serum IL‐6 levels may provide useful information for predicting future HCC development in female chronic hepatitis C patients. © 2009 UICC
Relationships between critical period of estrogen exposure and circulating levels of insulin‐like growth factor‐I (IGF‐I) in breast cancer: evidence from a case‐control study
Authors: Wu Mei‐Hsuan , Chou Yu‐Ching , Chou Wan‐Yun , Hsu Giu‐Cheng , Chu Chi‐Hong , Yu Cheng‐Ping , Yu Jyh‐Cherng , Sun Chien‐An
Published: July 2009

Epidemiological observations suggest that insulin‐like growth factor‐I (IGF‐I), a potent mitogenic and anti‐apoptotic peptide, plays a role in the etiology of breast cancer. Estrogen, which is crucial in breast carcinogenesis, both regulates and is influenced by IGF‐I family. A case‐control study was conducted to assess the role of IGF‐I as a biomarker for breast cancer and to evaluate the potential joint effect of circulating IGF‐I and critical period of estrogen exposure, as estimated by the interval between age at menarche and age at first full‐term pregnancy on the risk of breast cancer. Questionnaire information and blood samples were taken before treatment from 297 incident cases with breast cancer and 593 controls admitted for health examination at the Tri‐Service General Hospital, Taipei between 2004 and 2006. Plasma levels of IGF‐I and IGFBP‐3 were measured by immunoradiometric assay. Conditional logistic regression was used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Our case‐control data indicate that breast cancer risk related to IGF‐I differs according to menopausal status. High circulating levels of IGF‐I increased risk of pre‐ but not postmenopausal breast cancer (top vs. bottom tertile, adjusted OR, 1.86; 95% CI, 1.01–3.44). Furthermore, elevated IGF‐I concentrations in conjunction with prolonged interval of critical period of estrogen exposure were associated with significantly increased risk of breast cancer, particularly among estrogen‐positive cases (adjusted OR, 2.42, 95% CI, 1.33–4.38). These results suggest that the joint effect of IGF‐I and estrogens may provide novel methods of breast cancer risk reduction among women.
Relationship between dietary and supplemental intake of folate, methionine, vitamin B6 and folate receptor α expression in ovarian tumors
Authors: Kotsopoulos Joanne , Hecht Jonathan L. , Marotti Jonathan D. , Kelemen Linda E. , Tworoger Shelley S.
Published: July 2009

Because folate receptor α (FRα) is frequently over‐expressed in epithelial ovarian tumors, we hypothesized that its association with folate may differ by FRα expression or by the timing of intake. We examined the association between folate and other cofactors in 152 ovarian cancers evaluated for FRα expression from the Nurses' Health Study. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. FRα expression was higher in serous invasive and advanced stage ovarian tumors. Recent dietary folate intake ≥ 300 μg/day compared to < 300 μg/day was associated with decreased risk of developing ovarian cancer (OR = 0.62; 95%CI 0.40–0.96). There was suggestion of an increased risk with total folate (dietary and supplemental) (OR=1.42; 95%CI 0.94–2.14 for past and OR = 1.53; 95%CI 0.99–2.37 for recent intake). These results did not vary by FRα status of the tumor. Methyl group score, a marker of high dietary folate and methionine intake but low alcohol consumption, was inversely associated with risk of ovarian cancer (OR = 0.44; 95%CI 0.23–0.84 for past and OR=0.46; 95%CI 0.24–0.88 for recent intake). There were no clear individual associations between methionine, vitamin B6, or multivitamin use and ovarian cancer risk overall or by FRα tumor status. Our data do not support the hypothesis that the relationship between factors involved in one‐carbon metabolism and ovarian cancer risk differs by FRα status of the tumor.
Mitochondrial ATP‐independent chaperones
Authors: Petrakis Nikos , Alcock Felicity , Tokatlidis Kostas
Published: July 2009

Mitochondria possess a dedicated‐chaperone system in the intermembrane space, the small Tims that are ubiquitous in all eukaryotes from yeast to man. They escort membrane proteins to the outer or the inner membrane for proper insertion. These mitochondrial chaperones do not require external energy to perform their function and have structural similarities to other ATP‐independent chaperones. Here, we discuss their structural properties and how these relate to their chaperoning function in the mitochondrial intermembrane space. © 2009 IUBMB IUBMB Life 61(9): 909–914, 2009
Controlling biological interfaces on the nanometer length scale
Authors: Schmidt Ray C. , Healy Kevin E.
Published: July 2009

A number of techniques currently exist that allow researchers to generate spatially resolved patterns of chemistry and topography on the nanometer length scale. Both chemically and topographically nanopatterned surfaces can be generated to more accurately mimic the natural extracellular environment. Chemically patterned surfaces can also be used to study tightly controlled and highly specific cell–cell and cell‐substrate interactions or to create increasingly densely packed biosensors. From a biological standpoint, these methods enable fabrication of elaborate interfaces to mechanistically study the effects of cell adhesion ligand density, spacing, clustering, and spatial distribution on cell fate and function. The most commonly used nanopatterning techniques in the biomaterials arena are reviewed here, including scanning probe, electron beam, colloidal, and imprint lithographies, critically examining the resolution available and the scalability of the technique for generating the number of surfaces necessary for statistically relevant cell culture studies. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Cell confinement in patterned nanoliter droplets in a microwell array by wiping
Authors: Kang Lifeng , Hancock Matthew J. , Brigham Mark D. , Khademhosseini Ali
Published: July 2009

Cell patterning is useful for a variety of biological applications such as tissue engineering and drug discovery. In particular, the ability to localize cells within distinct fluids is beneficial for a variety of applications ranging from microencapsulation to high‐throughput analysis. However, despite much progress, cell immobilization and maintenance within patterned microscale droplets remains a challenge. In particular, no method currently exists to rapidly seed cells into microwell arrays in a controllable and reliable manner. In this study, we present a simple wiping technique to localize cells within arrays of polymeric microwells. This robust method produces cell seeding densities that vary consistently with microwell geometry and cell concentration. Moreover, we develop a simple theoretical model to accurately predict cell seeding density and seeding efficiency in terms of the design parameters of the microwell array and the cell density. This short‐term cell patterning approach is an enabling tool to develop new high‐throughput screening technologies that utilize microwell arrays containing cells for screening applications. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Defining critical inflammatory parameters for endotoxin impurity in manufactured alginate microcapsules
Authors: Breger Joyce C. , Lyle Daniel B. , Shallcross Jonathan C. , Langone John J. , Wang Nam Sun
Published: July 2009

Since current purification methods cannot completely remove all traces of endotoxin in biomaterials intended for use in implantable or blood‐contacting devices, acceptable levels of endotoxin contamination that will not cause a significant inflammatory reaction need to be defined. Inflammatory reactions to biomaterials may include production of high concentrations of potentially harmful nitric oxide (NO) generated by macrophages. Nitrite accumulation was measured from RAW264.7 cells treated with either lipopolysaccharide (LPS) free in solution or defined quantities of LPS incorporated into alginate in the absence or presence of murine interferon‐γ (mrIFN‐γ). In the absence of IFN‐γ, significant NO production by RAW 264.7 cells occurred for LPS levels down to 0.018 EU/mL. In the presence of mrIFN‐γ, the lowest concentration of LPS tested in solution (0.006 EU/mL) elicited a significant increase in NO production. In the absence or presence of mrIFN‐γ, five times the concentration of LPS incorporated into alginate as compared to LPS free in solution was necessary to elicit a similar NO response by RAW264.7. These results demonstrate that very low concentrations of endotoxin can elicit significant NO responses from macrophages, particularly when inflammatory cytokines are present. Biomaterials may sequester endotoxin, resulting in lower inflammatory reactions that otherwise might be expected. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Dynamic changes in chromatin structure through post‐translational modifications of histone H3 during replication origin activation
Authors: Rampakakis E. , Di Paola D. , Chan M.K. , Zannis‐Hadjopoulos M.
Published: July 2009

Genome duplication relies on the timely activation of multiple replication origins throughout the genome during S phase. Each origin is marked by the assembly of a multiprotein pre‐replication complex (pre‐RC) and the recruitment of the replicative machinery, which can gain access to replication origins on the DNA through the barrier of specific chromatin structures. Inheritance of the genetic information is further accompanied by maintenance and inheritance of the epigenetic marks, which are accomplished by the activity of histone and DNA modifying enzymes traveling with the replisome. Here, we studied the changes in the chromatin structure at the loci of three replication origins, the early activated human lamin B2 (LB2) and monkey Ors8 (mOrs8) origins and the late‐activated human homologue of the latter (hOrs8), during their activation, by measuring the abundance of post‐translationally modified histone H3. The data show that dynamic changes in the levels of acetylated, methylated and phosphorylated histone H3 occur during the initiation of DNA replication at these three origin loci, which differ between early‐ and late‐firing origins as well as between human‐ and monkey‐derived cell lines. These results suggest that specific histone modifications are associated with origin firing, temporal activation and replication fork progression and underscore the importance of species specificity. J. Cell. Biochem. 108: 400–407, 2009. © 2009 Wiley‐Liss, Inc.
Modulatory effect of rRNA synthesis and ppUL83 nucleolar compartmentalization on human cytomegalovirus gene expression in vitro
Authors: Arcangeletti Maria‐Cristina , Rodighiero Isabella , De Conto Flora , Gatti Rita , Orlandini Guido , Ferraglia Francesca , Motta Federica , Covan Silvia , Razin Sergey V. , Dettori Giuseppe , Chezzi Carlo
Published: July 2009

The nucleolus is a nuclear domain involved in the biogenesis of ribosomes, as well as in many other important cellular regulatory activities, such as cell cycle control and mRNA processing. Many viruses, including herpesviruses, are known to exploit the nucleolar compartment during their replication cycle. In a previous study, we demonstrated the preferential targeting and accumulation of the human cytomegalovirus (HCMV) UL83 phosphoprotein (pp65) to the nucleolar compartment and, in particular, to the nucleolar matrix of lytically infected fibroblasts; such targeting was already evident at very early times after infection. Here we have investigated the possible effects of rRNA synthesis inhibition upon the development of HCMV lytic infection, by using either actinomycin D or cisplatin at low concentrations, that are known to selectively inhibit RNA polymerase I activity, whilst leaving RNA polymerase II function unaffected. Following the inhibition of rRNA synthesis by either of the agents used, we observed a significant redistribution of nucleolar proteins within the nucleoplasm and a simultaneous depletion of viral pp65 from the nucleolus; this effect was highly evident in both unextracted cells and in nuclear matrices in situ. Of particular interest, even a brief suppression of rRNA synthesis resulted in a very strong inhibition of the progression of HCMV infection, as was concluded from the absence of accumulation of HCMV major immediate‐early proteins within the nucleus of infected cells. These data suggest that a functional relationship might exist between rRNA synthesis, pp65 localization to the nucleolar matrix and the normal development of HCMV lytic infection. J. Cell. Biochem. 108: 415–423, 2009. © 2009 Wiley‐Liss, Inc.
Dys‐regulated activation of a Src tyroine kinase Hck at the Golgi disturbs N‐glycosylation of a cytokine receptor Fms
Authors: Hassan Ranya , Suzu Shinya , Hiyoshi Masateru , Takahashi‐Makise Naoko , Ueno Takamasa , Agatsuma Tsutomu , Akari Hirofumi , Komano Jun , Takebe Yutaka , Motoyoshi Kazuo , Okada Seiji
Published: July 2009

HIV‐1 Nef accelerates the progression to AIDS by binding with and activating a Src kinase Hck, but underlying molecular basis is not understood. We revealed that Nef disturbed N‐glycosylation/trafficking of a cytokine receptor Fms in an Hck‐dependent manner, a possible trigger to worsen uncontrolled immune system. Here, we provide direct evidence that dys‐regulated activation of Hck pre‐localized to the Golgi apparatus causes this Fms maturation arrest. A striking change in Hck induced by Nef other than activation was its skewed localization to the Golgi due to predominant Golgi‐localization of Nef. Studies with different Nef alleles and their mutants showed a clear correlation among higher Nef‐Hck affinity, stronger Hck activation, severe Golgi‐localization of Hck and severe Fms maturation arrest. Studies with a newly discovered Nef‐Hck binding blocker 2c more clearly showed that skewed Golgi‐localization of active Hck was indeed the cause of Fms maturation arrest. 2c blocked Nef‐induced skewed Golgi‐localization of an active form of Hck (Hck‐P2A) and Fms maturation arrest by Nef/Hck‐P2A, but showed no inhibition on Hck‐P2A kinase activity. Our finding establishes an intriguing link between the pathogenesis of Nef and a newly emerging concept that the Golgi‐localized Src kinases regulate the Golgi function. J. Cell. Physiol. 221: 458–468, 2009. © 2009 Wiley‐Liss, Inc.
Synthesis of novel pyrazole‐linked norcantharidin derivatives of substituted aromatic amines with efficient 1,3‐dipolar cycloaddition
Authors: Deng Liping , Tao Weifeng , Lv Jianguo , Wang Wei
Published: July 2009

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Highly efficient, practical and convenient synthesis of twelve compounds by the [3+2] 1, 3‐dipolar cycloaddition reaction of norcantharidin derivatives of substituted aromatic amines with two hydrazines in the presence of chloramine‐T. J. Heterocyclic Chem., (2009).
Hafnium (IV) bis(perfluorooctanesulfonyl)amide‐catalyzed one‐pot synthesis of substituted quinolines in fluorous media
Authors: Shen Ming‐Gui , Cai Chun , Yi Wen‐Bin
Published: July 2009

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Hafnium (IV) bis(perfluorooctanesulfonyl)amide (Hf(NPf)4) catalyzed the one‐pot synthesis of substituted quinolines in fluorous media. By simple phase separation, the fluorous phase containing the catalyst can be used several times. J. Heterocyclic Chem., (2009).
Estimation of clear‐sky effective erythema radiation from broadband solar radiation (300–3000 nm) data in an arid climate
Authors: Sabziparvar Ali A.
Published: July 2009

This study reports the first observations of effective erythema radiation (EER) from an arid region of Iran. The hourly and daily measured clear‐sky global solar radiation (G) and biologically important EER incident on a horizontal surface at Esfahan, Iran, during 2002–2004 are used. The EER irradiation was recorded by a spectrophotometer Brewer type MK IV mounted on the roof of the Esfahan site. The total daily broadband radiation was measured using an Eppley Pyranometer (Kipp & Zonen CM) at the same site. Using the mentioned experimental data, a linear relationship (EER = β × G + α) is established between daily integrated totals of EER and the daily totals of broadband global solar radiation (300–3000 nm). At statistically significant levels (p < 0.05 and R2 > 0.92) a good linear correlation between the daily G and EER was found. The observed (G) data is a routine meteorological measurement at many meteorological stations and such a relationship would enable estimates of the daily EER to be made from accessible records. The seasonal variability of EER/G is also discussed. The effect of the annual cycles of solar zenith angle (SZA) and total column ozone (TCO) on the ratios (EER/G) is presented and the correction factors are determined for the inclusion of the ozone cycle. Copyright © 2009 Royal Meteorological Society
Electrical Modes in Scanning Probe Microscopy
Authors: Berger Rüdiger , Butt Hans‐Jürgen , Retschke Maria B. , Weber Stefan A. L.
Published: July 2009

Scanning probe microscopy methods allow the investigation of a variety of sample surface properties on a nanometer scale, even down to single molecules. As molecular electronics advance, the characterization of electrical properties becomes more and more important. In both research and industry, films made from composite materials and lithographically structured elements have already reached structure sizes down to a few nanometers. Here, we review the major scanning probe microscopy modes that are used for electrical characterization of thin films, that is, scanning conductive force microscopy, Kelvin probe force microscopy and scanning electric field microscopy. To demonstrate the possibilities and capabilities of these modes, reference samples were fabricated by means of focused ion beam deposition and analyzed using the described methods. Furthermore, two upcoming modes are presented that are based on: i) local current measurements while the SPM‐cantilever is excited into torsional vibrations, and, ii) changes in a backscattered microwave that was coupled into a scanning probe microscopy‐cantilever. The scanning‐probe‐based electrical modes are applicable for studies of functional layers used in soft matter electronic devices under realistic environmental conditions.

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Elliptical field‐of‐view PROPELLER imaging
Authors: Devaraj Ajit , Pipe James G.
Published: July 2009

Traditionally two‐dimensional scans are designed to support an isotropic field‐of‐view (iFOV). When imaging elongated objects, significant savings in scan time can potentially be achieved by supporting an elliptical field‐of‐view (eFOV). This work presents an empirical closed‐form solution to adapt the PROPELLER trajectory for an eFOV. The proposed solution is built on the geometry of the PROPELLER trajectory permitting the scan prescription and data reconstruction to remain largely similar to standard PROPELLER. The achieved FOV is experimentally validated by the point spread function (PSF) of a phantom scan. The details of potential savings in scan time and the signal‐to‐noise ratio (SNR) performance in comparison to iFOV scans for both phantom and in‐vivo images are also described. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Towards automatic patient positioning and scan planning using continuously moving table MR imaging
Authors: Koken Peter , Dries Sebastian P.M. , Keupp Jochen , Bystrov Daniel , Pekar Vladimir , Börnert Peter
Published: July 2009

A concept is proposed to simplify patient positioning and scan planning to improve ease of use and workflow in MR. After patient preparation in front of the scanner the operator selects the anatomy of interest by a single push‐button action. Subsequently, the patient table is moved automatically into the scanner, while real‐time 3D isotropic low‐resolution continuously moving table scout scanning is performed using patient‐independent MR system settings. With a real‐time organ identification process running in parallel and steering the scanner, the target anatomy can be positioned fully automatically in the scanner's sensitive volume. The desired diagnostic examination of the anatomy of interest can be planned and continued immediately using the geometric information derived from the acquired 3D data. The concept was implemented and successfully tested in vivo in 12 healthy volunteers, focusing on the liver as the target anatomy. The positioning accuracy achieved was on the order of several millimeters, which turned out to be sufficient for initial planning purposes. Furthermore, the impact of nonoptimal system settings on the positioning performance, the signal‐to‐noise ratio (SNR), and contrast‐to‐noise ratio (CNR) was investigated. The present work proved the basic concept of the proposed approach as an element of future scan automation. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
School‐wide healthy weight behaviors: Promoting Universal Longevity via School–family Ecologies (PULSE)
Authors: Anderson Laura M. , Phelps LeAdelle
Published: July 2009

Rates of childhood obesity have more than tripled in the last 40 years, resulting in a challenge from the public sector and various governmental institutions for the development of effective prevention/early intervention programming. Based on an extensive review of the literature, an evidence‐based, school‐wide curriculum is proposed. Promoting Universal Longevity via School–family Ecologies (PULSE) is intended to change weight imbalance behaviors via proactive and long‐term interventions directed toward all children and their families (universal prevention model) via the school setting. The authors provide a review of the literature and outline the conceptual model of PULSE. © 2009 Wiley Periodicals, Inc.
Cell cycle regulator cdk2ap1 inhibits prostate cancer cell growth and modifies androgen‐responsive pathway function
Authors: Zolochevska Olga , Figueiredo Marxa L.
Published: July 2009

BACKGROUND

We evaluated the effect of expressing the cell cycle regulator cdk2ap1, downregulated in prostate cancer cell lines, in inhibiting prostate cancer cell growth.

METHODS

Expression of cdk2ap1 using a tet‐inducible lentiviral system modified growth rate, induced cell cycle arrest and apoptosis and reduced the invasive ability of prostate cancer cell lines, as assayed by cell viability, cell cycle profiling, Caspase 3/7 detection, and matrigel invasion assays. We examined the effect of expressing cdk2ap1 on gene expression profiles of cytokine, invasion, apoptotic, and androgen response pathways using quantitative real‐time PCR, and used androgen‐responsive reporter gene assays, and methylation‐sensitive PCR to examine the mechanism of cdk2ap1 interaction with androgen‐responsive pathways.

RESULTS

The expression of cdk2ap1 correlated with a reduction in cellular growth, irrespective of inhibition or stimulation of androgen receptor (AR) signaling pathways. Cell cycle arrest, increased apoptosis, and a reduction in invasiveness phenotypes were observed upon cdk2ap1 expression. Enhanced demethylation at the AR promoter, AR expression increases, and enhanced AR transcriptional activity correlated with cdk2ap1 expression.

CONCLUSIONS

Our findings support a novel concept by which cell cycle inhibitor genes can impact prostate cancer phenotypes by restoring a tumor suppressive function to androgen‐responsive pathways and this function may involve modulation of a subset of functions of the AR. Prostate 69: 1586–1597, 2009. © 2009 Wiley‐Liss, Inc.
Large‐scale analysis of secondary structure changes in proteins suggests a role for disorder‐to‐order transitions in nucleotide binding proteins
Authors: Dan Adi , Ofran Yanay , Kliger Yossef
Published: July 2009

Conformational changes in proteins often involve secondary structure transitions. Such transitions can be divided into two types: disorder‐to‐order changes, in which a disordered segment acquires an ordered secondary structure (e.g., disorder to α‐helix, disorder to β‐strand), and order‐to‐order changes, where a segment switches from one ordered secondary structure to another (e.g., α‐helix to β‐strand, α‐helix to turn). In this study, we explore the distribution of these transitions in the proteome. Using a comprehensive, yet highly conservative method, we compared solved three‐dimensional structures of identical protein sequences, looking for differences in the secondary structures with which they were assigned. Protein chains in which such secondary structure transitions were detected, were classified into two sets according to the type of transition that is involved (disorder‐to‐order or order‐to‐order), allowing us to characterize each set by examining enrichment of gene ontology terms. The results reveal that the disorder‐to‐order set is significantly enriched with nucleotide binding proteins, whereas the order‐to‐order set is more diverse. Remarkably, further examination reveals that >22% of the purine nucleotide binding proteins include segments which undergo disorder‐to‐order transitions, suggesting that such transitions play an important role in this process. Proteins 2010. © 2009 Wiley‐Liss, Inc.
How and when does complex reasoning occur? Empirically driven development of a learning progression focused on complex reasoning about biodiversity
Authors: Songer Nancy Butler , Kelcey Ben , Gotwals Amelia Wenk
Published: July 2009

In order to compete in a global economy, students are going to need resources and curricula focusing on critical thinking and reasoning in science. Despite awareness for the need for complex reasoning, American students perform poorly relative to peers on international standardized tests measuring complex thinking in science. Research focusing on learning progressions is one effort to provide more coherent science curricular sequences and assessments that can be focused on complex thinking about focal science topics. This article describes an empirically driven, five‐step process to develop a 3‐year learning progression focusing on complex thinking about biodiversity. Our efforts resulted in empirical results and work products including: (1) a revised definition of learning progressions, (2) empirically driven, 3‐year progressions for complex thinking about biodiversity, (3) an application of statistical approaches for the analysis of learning progression products, (4) Hierarchical Linear Modeling results demonstrating significant student achievement on complex thinking about biodiversity, and (5) Growth Model results demonstrating strengths and weaknesses of the first version of our curricular units. The empirical studies present information to inform both curriculum and assessment development. For curriculum development, the role of learning progressions as templates for the development of organized sequences of curricular units focused on complex science is discussed. For assessment development, learning progression‐guided assessments provide a greater range and amount of information that can more reliably discriminate between students of differing abilities than a contrasting standardized assessment measure that was also focused on biodiversity content. © 2009 Wiley Periodicals, Inc. J Res Sci Teach 46: 610–631, 2009
Measuring progressions: Assessment structures underlying a learning progression
Authors: Wilson Mark
Published: July 2009

This article describes some of the underlying conceptualizations that have gone into the work of the BEAR Center in the development of learning progressions. The core of all of these developments has been the construct map, which is the first building block in the BEAR Assessment System (BAS). After introducing the concept of a learning progression, the article summarizes the elements of the BAS, emphasizing the central concept of a construct map. The article then describes a series of several different ways to see the relationship between the idea of a construct map and the idea of a progression (which I call the “assessment structure”), and also gives illustrative examples from recent BEAR projects. The article then discusses some strengths and limitations of these conceptualizations, focusing on both educational and measurement issues. The article concludes with some general reflections. © 2009 Wiley Periodicals, Inc. J Res Sci Teach 46: 716–730, 2009
An analytic formula for the delta of variance swap
Authors: Coulombe Benoit , Marini Alexander , Yesayan Ararat
Published: July 2009

The purpose of this short article is to derive an analytic formula for a variance swap delta. It shows that the delta is determined by the volatility skew and the vega of vanilla options only. Copyright © 2009 Wilmott Magazine Ltd
Property derivatives and the subprime crisis
Authors: Syz Juerg M. , Vanini Paolo
Published: July 2009

The recent real estate bubble was fuelled by non‐risk‐adjusted lending policies, low interest rates, and complex finance vehicles. Mortgage‐backed securities (MBS) played a crucial role in the crisis. These vehicles were praised as liquid capital market instruments that allowed mortgage lenders to replenish their funds, which could then be used for additional origination activities. However, in some forms, securitized mortgage pools are highly complex and hard to price. It turned out that MBS were not able to deal with the risks of the real estate market appropriately. The painful burst of the real estate bubble highlights the urgent need for instru‐ments that provide more transparency and allow better mitigating of both house price and commercial property risk. Property derivatives, currently emerging in the US and the UK, address real estate prices directly and make them more transparent. Thus, they facilitate a more efficient risk allocation. We illustrate the possibilities and limitations of property derivatives with respect to the current subprime crisis. Copyright © 2009 Wilmott Magazine Ltd
Barrier options and lumpy dividends
Authors: Vitalis Siven Johannes , Suchanecki Michael , Poulsen Rolf
Published: July 2009

We study the pricing of barrier options on stocks with lumpy dividends. By extending the European option methodology presented in Haug, Haug, and Lewis (2003), we show that in the Black–Scholes model with a single dividend payment, barrier option prices can be expressed in terms of well‐behaved one‐dimensional integrals that can be evaluated very rapidly. With multiple dividend payments, the price integrals are more involved, but we show that for the down‐and‐out call option a simple approximation method gives accurate results. Copyright © 2009 Wilmott Magazine Ltd
A note on hedging: restricted but optimal delta hedging, mean, variance, jumps, stochastic volatility, and costs
Authors: Ahn Hyungsok , Wilmott Paul
Published: July 2009

We consider the pricing of options when delta hedging only takes place at discrete intervals. We show how to include transaction costs, jumps and stochastic volatility while optimally, but discretely, dynamically hedging. Copyright © 2009 Wilmott Magazine Ltd
Within‐tree distribution of nest sites and foraging areas of ants on canopy trees in a tropical rainforest in Borneo
Authors: Tanaka Hiroshi O. , Yamane Seiki , Itioka Takao
Published: July 2009

It has been argued that canopy trees in tropical rainforests harbor species‐rich ant assemblages; however, how ants partition the space on trees has not been adequately elucidated. Therefore, we investigated within‐tree distributions of nest sites and foraging areas of individual ant colonies on canopy trees in a tropical lowland rainforest in Southeast Asia. The species diversity and colony abundance of ants were both significantly greater in crowns than on trunks. The concentration of ant species and colonies in the tree crown seemed to be associated with greater variation in nest cavity type in the crown, compared to the trunk. For ants nesting on canopy trees, the numbers of colonies and species were both higher for ants foraging only during the daytime than for those foraging at night. Similarly, for ants foraging on canopy trees, both values were higher for ants foraging only during the daytime than for those foraging at night. For most ant colonies nesting on canopy trees, foraging areas were limited to nearby nests and within the same type of microhabitat (within‐tree position). All ants foraging on canopy trees in the daytime nested on canopy trees, whereas some ants foraging on the canopy trees at night nested on the ground. These results suggest that spatial partitioning by ant assemblages on canopy trees in tropical rainforests is affected by microenvironmental heterogeneity generated by three‐dimensional structures (e.g., trees, epiphytes, lianas, and aerial soils) in the crowns of canopy trees. Furthermore, ant diversity appears to be enriched by both temporal (diel) and fine‐scale spatial partitioning of foraging activity.
Early meiosis in Rhynchospora pubera L. (Cyperaceae) is marked by uncommon ultrastructural features
Authors: San Martin Barrera Juca Abramo , de Andrade Jesus Tardeli Celia Guadalupe , Vanzela Laforga André Luís
Published: July 2009

The family Cyperaceae has an unusual microsporogenesis in which tetrad formation does not occur. In addition, other cytological features are important, such as the occurrence of holokinetic chromosomes and post‐reductional meiosis. We have examined the ultrastructural features of the pollen mother cell (PMC) of Rhynchospora pubera. Anthers of several sizes were analyzed using light and transmission electron microscopy. The PMC before meiosis presented a central nucleus and a regular profile of the nuclear envelope. During prophase I, the nucleus was in the abaxial region of the cell. This cellular polarization was accompanied by other marked ultrastructural features in the nuclear envelope. Morphological changes involved dilations of perinuclear cisterns and polarization of the nuclear pore complexes. The results show that polarization occurs in the initial phases of microsporogenesis in R. pubera, unlike other plant species.
Excessive O‐GlcNAcylation of proteins suppresses spontaneous cardiogenesis in ES cells
Authors: Kim Hoe-Suk , Park Sang Yoon , Choi Yu Rim , Kang Jeong Gu , Joo Hyun Jung , Moon Woo Kyung , Cho Jin Won
Published: July 2009

Increased modification of proteins with O‐linked N‐acetylglucosamine (O‐GlcNAc) has been implicated in the development of diabetic cardiomyopathy. We used the well‐characterized ES cells (Nkx2.5GFP knock‐in ES cells), to investigate the role of O‐GlcNAcylation in cardiomyocyte development. O‐GlcNAcylation decreased in differentiating ES cells, as did the expression of O‐GlcNAc transferase. Increasing O‐GlcNAcylation with glucosamine or by inhibiting N‐acetylglucosaminidase (streptozotocin or PUGNAc) decreased the number of cardiomyocyte precursors and cardiac‐specific gene expression. On the other hand, decreasing O‐GlcNAcylation with an inhibitor of glutamine fructose‐6‐phosphate amidotransferase (6‐diazo‐5‐oxo‐norleucine) increased cardiomyocyte precursors. These results suggest that excessive O‐GlcNAcylation impairs cardiac cell differentiation in ES cells.
Gesundheit zwischen Staat und Markt: Der Einfluss Europas
Authors: Gerlinger Thomas
Published: July 2009

Einleitung

Die deutsche Gesundheitspolitik wird heutzutage in wachsendem Maße von der Europäischen Union (EU) beeinflusst, obwohl der EG-Vertrag ausdrücklich vorsieht, dass „die Verantwortung der Mitgliedstaaten für die Organisation des Gesundheitswesens und die medizinische Versorgung in vollem Umfang gewahrt“ wird (Art. 152 Abs. 5 EGV). Der Beitrag beschreibt die Wege der direkten und indirekten Einflussnahme der europäischen Ebene auf die Gesundheitspolitik der Mitgliedsstaaten und die sich daraus ergebenden Konsequenzen.
Privates Kapital und staatliche Regulierung im Gesundheitsmarkt
Authors: Bührlen Bernhard
Published: July 2009

Einleitung

Bedingt durch den medizinisch-technischen Fortschritt, die alternde Bevölkerung, einen Rückgang informeller Pflege und steigende Preise nimmt der Kapitalbedarf für die Gesundheitsversorgung zu (OECD, 2006). Da gleichzeitig die Beiträge zur Gesetzlichen Krankenversicherung (GKV) begrenzt werden sollen, wird ein Teil der GKV-Ausgaben aus Steuermitteln ergänzt. Zunehmend werden Leistungen auch aus privaten Mitteln finanziert. Die Abstimmungsprozesse zwischen den Interessensgruppen müssen der veränderten Rolle der Nutzer angepasst werden.
Phylogenetic Analysis of the Neuraminidase Gene Reveals that the H5N1 Strains Prevalent in Chickens During 2006 Bird Flu Outbreaks in Two Regions of Maharashtra, India are Genetically Different
Authors: Danishuddin Mohd , Khan Asad U.
Published: July 2009

In February 2006, two outbreaks of highly pathogenic avian influenza A virus subtype H5N1 occurred in chickens in two neighboring districts (first in Nandurbar and second in Jalgaon) of Maharashtra, India, in a span of 12 days. In the present study, the neuraminidase (NA) gene of the two Indian H5N1 isolates was taken into consideration to find if the two strains are genetically similar. Phylogenetic analysis of the NA gene showed that the H5N1 strains isolated from the two outbreaks were not originated from the same source. The first Indian isolate (Nandubar/7972/06) was clustered closest to an isolate from chicken in Vietnam in 2004, whereas the second Indian isolate (Jalgaon/8824/06) showed resemblance to strains isolated from swan in Italy and Iran in 2006. Moreover, amino acid sequence analysis showed varying hot spots for substitutions between these two Indian isolates, and three substitutions were found at functional domain sites. Secondary structure changes due to these substitutions were also reported. This study reveals that the H5N1 strains isolated from chickens during 2006 bird flu outbreaks in two neighboring districts of Maharashtra, India are genetically different.
d-chiro-Inositol is absorbed but not synthesised in rodents
Authors: Lin Xiaobo , Ma Lina , Gopalan Chaya , Ostlund Richard E.
Published: July 2009

d-chiro-inositol (DCI) and pinitol (1d-3-O-methyl-chiro-inositol) are distinctive inositols reported to possess insulin-mimetic properties. DCI-containing compounds are abundant in common laboratory animal feed. By GC–MS of 6 m-HCl hydrolysates, Purina Laboratory Rodent Diet 5001 (diet 5001) contained 0·23 % total DCI by weight with most found in the lucerne and soya meal components. In contrast, only traces ofl-chiro-inositol were observed. The DCI moiety was present in a water-soluble non-ionic form of which most was shown to be pinitol. To measure the absorption of dietary inositols, rats were fed diet 5001 in a balance study or given purified pinitol or [2H6]DCI. More than 98 % of the total DCI fed to rats as diet 5001, purified pinitol or [2H6]DCI was absorbed from the gastrointestinal tract. Rats chronically on diet 5001 consumed 921 μmol total DCI/kg body weight per d but excreted less than 5·3 % in the stools and urine, suggesting that the bulk was metabolised. The levels of pinitol or DCI in plasma, stools or urine remained relatively stable in mice fed Purina PicoLab®Rodent Diet 20 5053 over a 5-week period, whereas these values declined to very low levels in mice fed a pinitol/DCI-deficient chemically defined diet. To test whether DCI was synthesised or converted frommyo-inositol, mice were treated with heavy water or [2H6]myo-inositol. DCI was neither synthesised endogenously from2H-labelled water nor converted from [2H6]myo-inositol. DCI and pinitol in rodents appear to be derived solely from the diet.
Morphology, biology and molecular characterizations of Opisthoteuthis calypso (Cephalopoda: Octopoda) from the Sardinian Channel (central western Mediterranean)
Authors: Cuccu Danila , Mereu Marco , Cannas Rita , Follesa Maria Cristina , Cau Angelo , Jereb Patrizia
Published: July 2009

Several aspects of the biology of Opisthoteuthis calypso were studied based on 38 individuals (23 males, 14 females and 1 indeterminate) retrieved from bottom trawls fished at 871 to 1420 m depth in the Sardinian Channel (central western Mediterranean). Data on full maturity of females are presented for the first time for this species. Information on the distribution, size, structure and fecundity for both sexes is provided, and the biological characteristics of the Sardinian samples are compared to those of other Mediterranean and Atlantic samples. Morphological variability and the peculiar structure of the shell and beak are reported and discussed. Molecular DNA sequences were obtained and compared with sequences available for the genus Opisthoteuthis.
A new marine flatworm (Plathelminthes: Rhabditophora: Otoplanidae) from the Ligurian coast
Authors: Lanfranchi A. , Melai M.
Published: July 2009

The morphology and taxonomy of a new species of otoplanid (Plathelminthes: Rhabditophora: Proseriata) is discussed. Otoplana proxima sp. nov., collected at Marina di Bibbona (Livorno), presents the typical morphological peculiarities of the subfamily Otoplaninae, but clearly differs from the previously described species with regard to the organization of the genital organs. The new flatworm appears more similar to Otoplana intermedia, but differs sharply in its body length and male copulatory organ made up of 23–24 pliable spines (42–70 μm long) characterized by a forked tip and a canaliculated proximal end.
Strindberg's illness
Authors: Anderson E. W.
Published: July 2009

SYNOPSIS

The nature of the episodes of severe mental disorder which Strindberg suffered after the age of 45 has led to considerable discussion, much of which must remain inconclusive until all the relevant documents, some still awaiting publication, can be assessed. On the basis of present evidence, the diagnosis of an affective, schizophrenic, or toxic state is considered, and the views of earlier psychiatrists are discussed.