bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase 2 trial results with the novel neurokinin‐1 receptor antagonist casopitant in combination with ondansetron and dexamethasone for the prevention of chemotherapy‐induced nausea and vomiting in cancer patients receiving moderately emetogenic chemotherapy
Authors: Arpornwirat Wichit , Albert Istvan , Hansen Vincent L. , Levin Jeremey , Bandekar Rajesh R. , Grunberg Steven M.
Published: October 2009

BACKGROUND:

This randomized, double‐blind, dose‐ranging, placebo‐controlled, phase 2 trial evaluated the neurokinin‐1 receptor antagonist casopitant mesylate in combination with ondansetron/dexamethasone (ond/dex) for the prevention of chemotherapy‐induced nausea and vomiting (CINV) related to moderately emetogenic chemotherapy (MEC).

METHODS:

Chemotherapy‐naive patients who were receiving MEC (N = 723) were randomized to receive either oral placebo or casopitant at doses of 50 mg, 100 mg, or 150 mg daily (on Days 1‐3) plus ondansetron (on Days 1‐3) and dexamethasone (Day 1). Two exploratory arms evaluated single‐dose casopitant (150 mg) plus ond/dex and a 3‐day casopitant regimen with once‐daily ondansetron and dexamethasone. Primary endpoints were rates of complete response (CR) (no vomiting, retching, rescue therapy, or premature discontinuation) and significant nausea (SN) (≥25 mm on a visual analog scale) over the first 120 hours after Cycle 1 of MEC. Secondary endpoints included acute and delayed CR and SN rates, rates of nausea, vomiting, and safety.

RESULTS:

All casopitant doses that were tested significantly increased the proportion of patients with CR: The CR rates were 80.8% with casopitant 50 mg, 78.5% with casopitant 100 mg, and 84.2% with casopitant 150 mg compared with 69.4% in the control group (P = .0127); casopitant 150 mg was identified as the minimally effective dose. In exploratory analyses, single‐dose casopitant demonstrated a 79.2% CR rate, and once‐daily ondansetron plus casopitant produced an 83.5% CR rate. Vomiting rates in the first 5 days after MEC were reduced with casopitant‐containing regimens (from 23% to 10%‐16%). Rates of SN did not differ among treatment arms (range, 28%‐29%). Casopitant appeared to be well tolerated with no notable differences in overall adverse event frequency.

CONCLUSIONS:

Casopitant plus ond/dex was more effective than ond/dex alone for the prevention of CINV. Cancer 2009. © 2009 American Cancer Society.
Impact of radiation and chemotherapy on risk of dental abnormalities
Authors: Kaste Sue C. , Goodman Pamela , Leisenring Wendy , Stovall Marilyn , Hayashi Robert J. , Yeazel Mark , Beiraghi Soraya , Hudson Melissa M. , Sklar Charles A. , Robison Leslie L. , Baker K. Scott
Published: October 2009

BACKGROUND:

The current study was performed to describe frequencies and risk factors of altered oral health and odontogenesis in childhood cancer survivors.

METHODS:

In total, 9308 survivors who were diagnosed between 1970 and 1986 and 2951 siblings from the Childhood Cancer Survivor Study completed a survey that contained oral‐dental health information. The authors analyzed treatment impact, socioeconomic data, and patient demographics on dental outcomes using univariate and multivariate logistic regression models to estimate odds ratios (ORs).

RESULTS:

In multivariate analysis, survivors were more likely to report microdontia (OR, 3.0; 95% confidence interval [95% CI], 2.4‐3.8), hypodontia (OR, 1.7; 95% CI, 1.4‐2.0), root abnormalities (OR, 3.0; 95% CI, 2.2‐4.0), abnormal enamel (OR, 2.4; 95% CI, 2.0‐2.9), teeth loss ≥6 (OR, 2.6; 95% CI, 1.9‐3.6), severe gingivitis (OR, 1.2; 95% CI, 1.0‐1.5), and xerostomia (OR, 9.7; 95% CI, 4.8‐19.7). Controlling for chemotherapy and socioeconomic factors, radiation exposure of ≥20 Gray to dentition was associated significantly with an increased risk of ≥1 dental abnormality. Dose‐dependent alkylating agent therapy significantly increased the risk of ≥1 anatomic/developmental dental abnormalities in survivors who were diagnosed at age <5 years (OR, 1.7, 2.7, and 3.3 for alkylating agent scores of 1, 2, and 3, respectively).

CONCLUSIONS:

Radiation and chemotherapy were independent risk factors for adverse oral‐dental sequelae among childhood cancer survivors. The authors concluded that patients who received receiving alkylating agents at age <5 years should be closely monitored. Cancer 2009. © 2009 American Cancer Society.
Effect of allopurinol versus urate oxidase on methotrexate pharmacokinetics in children with newly diagnosed acute lymphoblastic leukemia
Authors: Crews Kristine R. , Zhou Yinmei , Pauley Jennifer L. , Howard Scott C. , Jeha Sima , Relling Mary V. , Pui Ching‐Hon
Published: October 2009

BACKGROUND:

Allopurinol and urate oxidase are both effective in preventing or treating hyperuricemia during remission induction therapy for lymphoid malignancies, but to the authors' knowledge, their effects on concomitant anticancer drug therapy have not been compared.

METHODS:

The authors compared plasma methotrexate pharmacokinetics in pediatric patients with newly diagnosed acute lymphoblastic leukemia who received concomitant allopurinol (n = 20) versus those treated with nonrecombinant or recombinant urate oxidase (n = 96) during high‐dose methotrexate administration before conventional remission induction therapy.

RESULTS:

The minimum plasma concentration of uric acid was significantly (P < .0001) lower after urate oxidase treatment than the concentration after allopurinol treatment. Methotrexate clearance was significantly higher (median, 117.1 mL/minute/m2 vs 91.1 mL/minute/m2; P = .019) in patients who received urate oxidase. A higher proportion of patients in the allopurinol group had elevated methotrexate plasma concentrations (36% vs 7%; P = .003) and experienced mucositis (45% vs 16%; P = .003) after methotrexate treatment compared with the urate oxidase group.

CONCLUSIONS:

The lower rate of methotrexate clearance in patients who received allopurinol likely reflected a less potent hypouricemic effect of allopurinol, leading to precipitation of uric acid in renal tubules. Hence, during remission induction therapy for lymphoid malignancies, the authors concluded that renally excreted drugs should be monitored closely, especially in patients who are receiving allopurinol. Cancer 2010. © 2010 American Cancer Society.
Analysis and modeling of the semantically associated network on the Web
Authors: Chen Xue , Luo Xiangfeng , Zhang Shun Xiang , Xu Zheng
Published: October 2009

The semantically associated network on the Web is a Semantic Link Network built by mining the associated relation between Web pages. The associated link from page A to page B indicates that users who have browsed page A is likely to also browse page B. This paper explores the statistical properties of the associated network on the Web. Web pages of a specific domain are automatically downloaded by a Web crawler to build an associated network. We analyze the associated network at different domain thresholds and classify the topology into three states, that is, the original state, the kernel state and the final state. A mathematical model is built to study the in‐degree distribution, the out‐degree distribution and the total‐degree distribution for both the kernel state and the final state. By tuning the model parameters to reasonable values, we obtain the distinct power‐law forms for the three degree distributions with exponents that agree well with the statistical data. The proposed model can not only describe the evolving processes of the associated network on the Web, but also provides theory basis for complex applications such as semantic community discovery, intelligent browsing and recommendation. Copyright © 2009 John Wiley & Sons, Ltd.
A novel imaging‐based high‐throughput screening approach to anti‐angiogenic drug discovery
Authors: Evensen Lasse , Micklem David R. , Link Wolfgang , Lorens James B.
Published: October 2009

The successful progression to the clinic of angiogenesis inhibitors for cancer treatment has spurred interest in developing new classes of anti‐angiogenic compounds. The resulting surge in available candidate therapeutics highlights the need for robust, high‐throughput angiogenesis screening systems that adequately capture the complexity of new vessel formation while providing quantitative evaluation of the potency of these agents. Available in vitro angiogenesis assays are either cumbersome, impeding adaptation to high‐throughput screening formats, or inadequately model the complex multistep process of new vessel formation. We therefore developed an organotypic endothelial‐mural cell co‐culture assay system that reflects several facets of angiogenesis while remaining compatible with high‐throughput/high‐content image screening. Co‐culture of primary human endothelial cells (EC) and vascular smooth muscle cells (vSMC) results in assembly of a network of tubular endothelial structures enveloped with vascular basement membrane proteins, thus, comprising the three main components of blood vessels. Initially, EC are dependent on vSMC‐derived VEGF and sensitive to clinical anti‐angiogenic therapeutics. A subsequent phenotypic VEGF‐switch renders EC networks resistant to anti‐VEGF therapeutics, demarcating a mature vascular phenotype. Conversely, mature EC networks remain sensitive to vascular disrupting agents. Therefore, candidate anti‐angiogenic compounds can be interrogated for their relative potency on immature and mature networks and classified as either vascular normalizing or vascular disrupting agents. Here, we demonstrate that the EC‐vSMC co‐culture assay represents a robust high‐content imaging high‐throughput screening system for identification of novel anti‐angiogenic agents. A pilot high‐throughput screening campaign was used to define informative imaging parameters and develop a follow‐up dose‐response scheme for hit characterization. High‐throughput screening using the EC‐vSMC co‐culture assay establishes a new platform to screen for novel anti‐angiogenic compounds for cancer therapy. © 2009 International Society for Advancement of Cytometry
Differential expression of TrkB isoforms switches climbing fiber‐Purkinje cell synaptogenesis to selective synapse elimination
Authors: Sherrard Rachel M. , Dixon Kirsty J. , Bakouche Joëlle , Rodger Jenny , Lemaigre‐Dubreuil Yolande , Mariani Jean
Published: October 2009

Correct neural function depends on precisely organized connectivity, which is refined from broader projections through synaptic/collateral elimination. In the rat, olivocerebellar topography is refined by regression of multiple climbing fiber (CF) innervation of Purkinje cells (PC) during the first two postnatal weeks. The molecules that initiate this regression are not fully understood. We assessed the role of cerebellar neurotrophins by examining tropomycin receptor kinase (Trk) receptor expression in the inferior olive and cerebellum between postnatal days (P)3‐7, when CF‐PC innervation changes from synapse formation to selective synapse elimination, and in a denervation‐reinnervation model when synaptogenesis is delayed. Trks A, B, and C are expressed in olivary neurons; although TrkA was not transported to the cerebellum and TrkC was unchanged during innervation and reinnervation, suggesting that neither receptor is involved in CF‐PC synaptogenesis. In contrast, both total and truncated TrkB (TrkB.T) increased in the olive and cerebellum from P4, whereas full‐length and activated phosphorylated TrkB (phospho‐TrkB) decreased from P4‐5. This reveals less TrkB signaling at the onset of CF regression. This expression pattern was reproduced during CF‐PC reinnervation: in the denervated hemicerebellum phospho‐TrkB decreased as CF terminals degenerated, then increased in parallel with the delayed neosynaptogenesis as new CFs reinnervated the denervated hemicerebellum. In the absence of this signaling, CF reinnervation did not develop. Our data reveal that olivocerebellar TrkB activity parallels CF‐PC synaptic formation and stabilization and is required for neosynaptogenesis. Furthermore, TrkB.T expression rises to reduce TrkB signaling and permit synapse elimination. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009
MHD peristaltic flow of a third order fluid in an asymmetric channel
Authors: Ali N. , Hayat T. , Wang Y.
Published: October 2009

This study is concerned with peristaltic flow of a magnetohydrodynamic (MHD) fluid in an asymmetric channel. Asymmetry in the flow is induced by waves on the channel walls having different amplitudes and phase. A systematic approach based on an expansion of Deborah number is used for the solution series. Analytic expressions have been developed for the stream function, axial velocity and axial pressure gradient. The pressure rise over a wavelength has been addressed through numerical integration. Particular attention has been given to the effects of Hartman number and Deborah number on the pressure rise over a wavelength and the trapping phenomenon. Several limiting solutions of interest are obtained as the special cases of the presented analysis by taking the appropriate parameter(s) to be zero. Copyright © 2009 John Wiley & Sons, Ltd.
A note on compressive limiting for two‐material flows
Authors: Banks J. W.
Published: October 2009

In this short note we describe a simple extension to the multi‐material shock‐capturing algorithm presented in (J. Comput. Phys. 2007; 223:262–297) that can be used to maintain sharp material interfaces. The method takes the form of an artificial compression which is designed so that the material indicator jumps across only a few cells but which does not excite physical instabilities in the flow. The advantages of the approach include its simplicity and flexibility in that it provides a parameter that effectively determines the captured interface thickness. Copyright © 2009 John Wiley & Sons, Ltd.
Neurological signs and late‐life depressive symptoms in a community population: the ESPRIT study
Authors: Soremekun Mishael , Stewart Robert , Portet Florence , Artero Sylvaine , Ancelin Marie‐Laure , Ritchie Karen
Published: October 2009

Objective

Depression in the elderly is common and often resistant to treatment. It has been suggested that late‐life depression may be related to underlying neurobiological changes. However, these observations are derived from diverse clinical samples and as yet have not been confirmed in a more representative population study. Our aim was to investigate associations between neurological signs as markers of underlying brain dysfunction and caseness for depression in an elderly community sample, controlling for physical health and comorbid/past neurological disorders.

Method

A cross‐sectional analysis of 2102 older people without dementia from the ESPRIT project. Depressive symptomatology was ascertained using the CES‐D and abnormal neurological signs/comorbidity from a full neurological examination according to ICD‐10 criteria.

Results

Pyramidal, extrapyramidal, cranial nerve and sensory deficit signs were significantly associated with case‐level depressive symptoms. However, all odds ratios were close to null values in participants who did not have previous neurological disorder.

Conclusions

We confirmed previous findings of an association between neurological signs and case‐level depressive symptoms in late life. However, this association may simply reflect the impact of more severe comorbid neurological disorder. Copyright © 2009 John Wiley & Sons, Ltd.
Nursing home structure and association with agitation and use of psychotropic drugs in nursing home residents in three countries: Norway, Austria and England
Authors: Testad I. , Auer S. , Mittelman M. , Ballard C. , Fossey J. , Donabauer Y. , Aarsland D.
Published: October 2009

Background

Understanding the underlying mechanisms and risk factors leading to agitation is crucial to reduce the severity of agitation and increase quality of life. International comparative studies offer special advantages in elucidating environmental risk factors by providing a wider diversity of environmental exposures such as nursing home structures, health care systems and genetic diversity.

Methods

Baseline data for three different intervention studies in Austria (n = 38), England (n = 302) and Norway (n = 163) were combined posthoc. Patients were grouped according to their dementia severity using the global deterioration scale (GDS), functional assessment staging (FAST) and clinical dementia rating (CDR) scales. For the measurement of agitation, the Cohen‐Mansfield Agitation Inventory (CMAI) was used. Data analysis was performed using one‐way ANOVA, multivariate and linear regression analysis.

Results

CMAI scores were available for 503 subjects with dementia. There were significant differences between the nursing home residents in the three countries regarding age, gender and dementia severity (all p values < 0.001). In the multivariate analyses, the level of agitation differed with higher mean scores in the Austrian (mean (SD) score 51.9(21.8)) compared to UK (43.3(16.1)) and Norwegian (41.6(13.2)) nursing homes (p = 0.002). Similarly, the use of psychotropic drugs differed significantly, with a higher proportion of neuroleptics in UK (48%, p < 0.001) and Austrian (52.6%; p = 0.001) compared to Norwegian (19%) nursing homes.

Conclusion

We found differences in agitation and antipsychotic drug use which are likely related to structural and cultural differences in nursing homes in three European countries. These findings suggest that structural changes can improve quality of care and quality of life for nursing home residents. Copyright © 2009 John Wiley & Sons, Ltd.
Being liked activates primary reward and midline self‐related brain regions
Authors: Davey Christopher G. , Allen Nicholas B. , Harrison Ben J. , Dwyer Dominic B. , Yücel Murat
Published: October 2009

The experience of being liked is a key social event and fundamental to motivating human behavior, though little is known about its neural underpinnings. In this study, we examined the experience of being liked in a group of 15‐ to 24‐year‐old: a cohort for whom forming friendships has a great degree of salience, and for whom the explicit representation of relationships is familiar from their frequent use of social networking technologies. Study participants (n = 19) were led to believe that other participants had formed an opinion on their likability based on their appearance in a photograph, and during fMRI scanning viewed the photographs of people who had purportedly responded favorably to them (alongside photographs of control participants). Results indicated that being liked activated primary reward‐ and self‐related regions, including the nucleus accumbens, midbrain (in an area corresponding to the ventral tegmentum), ventromedial prefrontal cortex, posterior cingulate cortex (including retrosplenial cortex), amygdala, and insula/opercular cortex. Participants showed greater activation of ventromedial prefrontal cortex and amygdala in response to being liked by people that they regarded highly compared to those they regarded less so. Finally, being liked by the opposite compared to the same gender activated the right caudal orbitofrontal cortex and right anterior insula: areas important for the representation of primary somatic rewards. This study demonstrates that neural response to being liked has features that are consistent with response to other rewarding events, but it has additional features that reflect its intrinsically interpersonal character. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.
TL1A produced by lamina propria macrophages induces Th1 and Th17 immune responses in cooperation with IL-23 in patients with Crohn's disease
Authors: Kamada Nobuhiko , Hisamatsu Tadakazu , Honda Haruki , Kobayashi Taku , Chinen Hiroshi , Takayama Tetsuro , Kitazume Mina T. , Okamoto Susumu , Koganei Kazutaka , Sugita Akira , Kanai Takanori , Hibi Toshifumi
Published: October 2009

Background

Tumor necrosis factor (TNF)-like protein 1A (TL1A) is a member of the TNF superfamily and contributes to the pathogenesis of Crohn's disease (CD) by stimulating T-helper (Th) 1 cells. In addition to Th1, recent studies have focused on the role of Th17 cells in the pathogenesis of CD. Here we tried to clarify the role of TL1A in Th1 and Th17 immunity in CD.

Methods

TL1A expression was assessed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) in lamina propria (LP) macrophages (LP-MΦs) from normal controls (NC) and patients with CD or ulcerative colitis (UC). Purified LP CD4+ T cells were stimulated with TL1A and/or IL-23 and interferon gamma (IFN-γ) and interleukin (IL)-17 levels were analyzed. We also examined the effect of TL1A on naïve CD4+ T-cell differentiation.

Results

We found that LP-MΦs are a major producer of TL1A. TL1A expression was markedly enhanced in LP-MΦs from CD patients compared with NC or UC patients. IL-23, in addition to TL1A, was induced in LP-MΦs by commensal bacteria stimulation. TL1A and IL-23 synergistically promoted the production of IFN-γ and IL-17 by LP T cells, while TL1A alone did not induce cytokine production. Furthermore, TL1A promoted Th17 differentiation from naïve T cells by LP-MΦs; however, IL-23 did not show any synergistic effects on Th17 differentiation.

Conclusions

TL1A expressed in LP-MΦs might play an important role in the pathogenesis of CD by inducing Th1 and Th17 immunity. IL-23 differentially regulated these functions of TL1A on memory and naïve T cells. Inflamm Bowel Dis 2009
Antitumor effects of a recombinant pseudotype baculovirus expressing Apoptin in vitro and in vivo
Authors: Pan Yongfei , Fang Liurong , Fan Huiying , Luo Rui , Zhao Qian , Chen Huanchun , Xiao Shaobo
Published: October 2009

Apoptin, a chicken anemia virus‐derived, p53‐independent, bcl‐2‐insenstive apoptotic protein with the ability to specifically induce apoptosis in tumor or transformed cells, is a promising tool for cancer gene therapy. In this study, pseudotype baculovirus, a recently developed alternative gene delivery system, was used as a vector to express Apoptin. The resultant recombinant baculovirus (BV‐Apoptin) efficiently expressed the Apoptin protein and induced apoptosis in HepG2 and H22 cells. Studies in vivo showed that intratumoral injection of BV‐Apoptin into a xenogeneic tumor (derived from H22 murine hepatoma cells in C57BL/6 mice) significantly suppressed tumor growth, and significantly prolonged the survival of tumor‐bearing mice compared to a control pseudotype baculovirus that expressed EGFP. Taken together, these results suggest that Apoptin, expressed from the pseudotype baculovirus vector, has the potential to become a therapeutic agent for the treatment of solid tumors.
Distinct mechanisms are utilized to induce stress sensorgadd45bby different stress stimuli
Authors: Zumbrun Steven D. , Hoffman Barbara , Liebermann Dan A.
Published: October 2009

The GADD45 family of proteins consists of three small proteins, GADD45A, GADD45B, and GADD45G, implicated in modulating the cellular response to genotoxic/physiological stressors. Despite similarities in sequence, structure and function, each gadd45 gene is induced differentially by different stress stimuli. Studies on stress‐mediated induction of the gadd45 genes have predominantly focused on gadd45a, with knowledge of gadd45b and gadd45g regulation lacking. To generate a more complete understanding of the regulation of gadd45 genes, a comprehensive analysis of stress‐mediated induction of human gadd45b has been carried out using human RKO colorectal carcinoma cells as a model system. Novel data indicate that gadd45b induction in RKO cells is regulated by distinct mechanisms in a stress‐specific manner. Methylmethane sulfonate (MMS), a DNA alkylating agent, induces gadd45b transcription through a cohort of both constitutive and inducible bound factors, including NFY, Sp1 and Egr1. In contrast, in a hyperosmotic environment generated with sorbitol, gadd45b mRNA is induced exclusively by mRNA stabilization. These findings indicate that the stress‐mediated induction of gadd45b is largely distinct from gadd45a. Furthermore, data obtained provide a novel paradigm for stress–response gene induction, indicating that gadd45b induction by distinct stressors, in the same cell type and under the same experimental settings, is differentially regulated at the level of mRNA transcription or mRNA stability. Importantly, this study also provides the groundwork to further examine the regulation of gadd45b expression in in vivo settings using animal models and tissues obtained from normal individuals and cancer patients prior to and after chemotherapeutic intervention. J. Cell. Biochem. 108: 1220–1231, 2009. © 2009 Wiley‐Liss, Inc.
Investigations of the fragmentation pathways of benzylpyridinium ions under ESI/MS conditions
Authors: Zins Emilie‐Laure , Rondeau David , Karoyan Philippe , Fosse Céline , Rochut Sophie , Pepe Claude
Published: October 2009

Benzylpyridinium ions are often used as ‘thermometer ions’ in order to evaluate the internal energy distribution of the ions formed in sources of mass spectrometers. However, the detailed fragmentation pathways of these parent ions were not well established. In particular, fragmentation involving a rearrangement (RR) process may be influencing the simulated distribution curves. In a previous study, we suggested that such RR actually occurred under electrospray ionization/mass spectrometry (ESI/MS) and fast atom bombardment/mass spectrometry (FAB/MS) experiments. Here, we present a systematic study of different substituted benzylpyridinium ions. Theoretical calculations showed that RR fragmentation leading to substituted tropylium ions could occur under ‘soft ionization’ conditions, such as ESI or FAB. Experimental results obtained under gas‐phase reactivity conditions showed that some substituted benzylpiridinium compounds actually undergo RR fragmentations under ESI/MS conditions. Mass‐analyzed kinetic experiments were also carried out to gain information on the reaction pathways that actually occur, and these experimental results are in agreement with the reaction pathways theoretically proposed. Copyright © 2009 John Wiley & Sons, Ltd.
Individual and combined action of pancreatic lipase and pancreatic lipase‐related proteins 1 and 2 on native versus homogenized milk fat globules
Authors: Berton Amélie , Sebban‐Kreuzer Corinne , Rouvellac Stéphanie , Lopez Christelle , Crenon Isabelle
Published: October 2009

Pancreatic lipase (PL) and pancreatic lipase‐related proteins 1 and 2 (PLRP1 and PLRP2) display different functional properties, despite close structures. The aim of the study was to compare the kinetic properties of recombinant human PLRP1, PLRP2, and PL on a physiological substrate: the milk fat under native and homogenized structures. No lipolytic activity is measured for PLRP1. PLRP2 hydrolyses milk fat with a lower catalytic efficiency than that of PL. PLRP2 activity, higher on homogenized than on native milk fat, is differently influenced by fatty acids (FA) and colipase depending on a proteolytic cleavage in the lid domain. FA enhance the activity on both milks. A colipase positive effect on the non‐proteolyzed PLRP2 is observed on homogenized milk and with FA on native milk fat. Bile salts are necessary. An original observation is a synergic effect between PL and PLRP2 on the two milks. An inhibitory effect of PLRP1 on PL activity is also demonstrated. The combined action of pancreatic lipases on milk fat digestion proposes PLRPs as modulators of PL. Our study supports the hypothesis of a major role of PLRP2 in fat digestion in newborns and brings new insights to understand the physiological role of PLRPs.
Na+/K+ATPase regulates sperm capacitation through a mechanism involving kinases and redistribution of its testis‐specific isoform
Authors: Newton Larissa D. , Krishnakumar Sulochana , Menon Ajitkumar Gopinadha , Kastelic John P. , van der Hoorn Frans A. , Thundathil Jacob C.
Published: October 2009

Incubation of bovine sperm with ouabain, an endogenous cardiac glycoside that inhibits both the ubiquitous (ATP1A1) and testis‐specific α4 (ATP1A4) isoforms of Na+/K+ATPase, induces tyrosine phosphorylation and capacitation. The objectives of this study were to investigate: (1) fertilizing ability of bovine sperm capacitated by incubating with ouabain; (2) involvement of ATP1A4 in this process; and (3) signaling mechanisms involved in the regulation of sperm capacitation induced by inhibition of Na+/K+ATPase activity. Fresh sperm capacitated by incubating with ouabain (inhibits both ATP1A1 and ATP1A4) or with anti‐ATP1A4 immunoserum fertilized bovine oocytes in vitro. Capacitation was associated with relocalization of ATP1A4 from the entire sperm head to the post‐acrosomal region. To investigate signaling mechanisms involved in oubain‐induced regulation of sperm capacitation, sperm preparations were pre‐incubated with inhibitors of specific signaling molecules, followed by incubation with ouabain. The phosphotyrosine content of sperm preparations was determined by immunoblotting, and capacitation status of these sperm preparations were evaluated through an acrosome reaction assay. We inferred that Na+/K+ATPase was involved in the regulation of tyrosine phosphorylation in sperm proteins through receptor tyrosine kinase, nonreceptor type protein kinase, and protein kinases A and C. In conclusion, inhibition of Na+/K+ATPase induced tyrosine phosphorylation and capacitation through multiple signal transduction pathways, imparting fertilizing ability in bovine sperm. To our knowledge, this is the first report documenting both the involvement of ATP1A4 in the regulation of bovine sperm capacitation and that fresh bovine sperm capacitated by the inhibition of Na+/K+ATPase can fertilize oocytes in vitro. Mol. Reprod. Dev. 77: 136–148, 2010. © 2009 Wiley‐Liss, Inc.
Therapeutische Proteine durch E.‐coli‐Sekretionstechnik
Authors: Leonhartsberger Susanne
Published: October 2009

Ein Sekretionssystem liefert hochreine pharmazeutische Wirkstoffe im industriellen Maßstab. Es senkt im Vergleich zu anderen biotechnischen Verfahren die Prozesskosten und verbessert die Prozessabläufe.
Prediction of mill liner shape evolution and changing operational performance during the liner life cycle: Case study of a Hicom mill
Authors: Cleary Paul W. , Owen Phil , Hoyer David I. , Marshall Steve
Published: October 2009

The prediction of wear and performance change over the life cycle of the consumable liners used to protect grinding mills is an important element of their optimization. Poor wear behaviour can lead to higher replacement costs and production loss during liner replacement. Prediction of wear behaviour using discrete element method (DEM) can provide valuable information about the impact of the design on the life cycle of the liner. Here, the DEM method is extended to predict the evolution of the
shape of the liner throughout the life cycle. Using a Hicom 110 nutating mill as a case study, we demonstrate a process for constructing a wear model that is shown to be able to quantitatively predict the spatially varying wear rates over the surface of the liner. The functional dependence of wear rate on micro‐mechanical flow quantities is not currently understood; hence, two model variants for each of the normal impact damage and the shear abrasion damage are considered. This model is validated by comparison with the actual erosion depths of a real liner. It is then used in a multi‐step DEM simulation to predict the liner evolution and the operational changes in the mill performance over the full life cycle of the liner. For the Hicom mill, it is demonstrated that the wear is entirely dominated by abrasion and that the best measure of this was the shear energy dissipation of wall contacts. It was also to identify that the floor of the mill was constructed of a more abrasion resistance material. The life cycle analysis showed a 20% decline in power draw as the increasing grinding chamber volume and eroding lifters lead to less efficient operation of the mill. Copyright © 2009 John Wiley & Sons, Ltd.
Numerical and analytical method for the design of piezoelectric modal sensors/actuators for shell‐type structures
Authors: Donoso A. , Bellido J. C. , Chacón J. M.
Published: October 2009

In this paper we treat the problem of designing distributed piezoelectric modal sensors/actuators for cylindrically curved panels. The design problem is tackled as an optimization problem where the design variable is a function (the polarization profile of the electrode) that takes on three values only: −1 (negative polarization), 0 (zero polarization or no piezoelectric material), 1 (positive polarization), and the objective function is connected with the frequency response of the transducer. For the model described here, we analytically prove that the electrode patterns that make it possible to ideally isolate particular vibration modes must entirely cover the piezoelectric lamina with either positive or negative polarization. Further, we propose an accurate numerical method for systematically designing these polarization patterns and a novel algorithm for parameterizing and visualizing them in 3d. Copyright © 2009 John Wiley & Sons, Ltd.
Visual and radiographic assessment of dental caries by osteologists: a validity and reliability study
Authors: Liebe‐Harkort C. , Ástvaldsdóttir Á. , Tranæus S.
Published: October 2009

In the skeletal remains of earlier populations, the presence and severity of dental caries preserves evidence about general health and diet. The quality of the data collected on dental caries is highly dependent on the diagnostic skills of the examining osteologist. A major barrier to more detailed data is reliance on visual inspection only. The present study compared quantification of carious lesions by osteologists, using both visual and radiographic inspection. Four osteologists with varying experience of caries diagnosis registered the presence and extent of dental caries on the crown and root surfaces of 61 teeth sourced from three different samples: archaeological, anthropological and modern. The teeth were subsequently sectioned to provide a control or standard reference. The interobserver differences were calculated as sensitivity (observer correctness in identifying teeth with caries disease). The two observers with more experience of dental paleopathology showed higher agreement with the standard reference than the other two observers, i.e. they correctly diagnosed more carious lesions. The most pronounced interobserver difference was for radiographic inspection of root surfaces. The recordings by the two experienced observers conformed much more closely with the standard reference than those of the less experienced observers. The results confirm that experience has a major influence on practical observations in dental paleopathology. The quality of collected data on dental caries could be enhanced by improving osteologists' knowledge of the disease process and the application of uniform, unambiguous criteria for registration of carious lesions. Copyright © 2009 John Wiley & Sons, Ltd.
Life and death on a Barbadian sugar plantation: historic and bioarchaeological views of infection and mortality at Newton Plantation
Authors: Shuler K. A.
Published: October 2009

Despite the rise in African Diaspora bioarchaeology, poor preservation and sampling bias has impeded Caribbean research. Paleodemography and infectious diseases are assessed here for 46 skeletons exhumed in 1997–98 from a slave cemetery at Newton Plantation (ca. 1660–1820). Life expectancy is closer to historic predictions than in earlier craniodental studies. High rates of periosteal infection were encountered but no evidence of specific skeletal diseases. Absence of sequelae does not support Newton as a healthy population relative to others. Rather, extreme stress, particularly for Newton females, is evidenced by the lowest relative mean age at death of any diaspora skeletal sample, and many mild to moderate lower limb infections in men, women and adolescents attest to injuries on the sugar gangs. Activity stress and abuse, coupled with disease and malnutrition, culminated in high mortality and replacement. This first comprehensive study of health on a Caribbean sugar plantation contributes to a growing biology of the African Diaspora and over three decades of Newton Plantation research. Specifically, it demonstrates the importance of systemic, multidisciplinary and comparative approaches to reconstructing the complex life stresses of slavery. Copyright © 2009 John Wiley & Sons, Ltd.
Capacity development for education service delivery in Pakistan: Top‐down devolution
Authors: Watson David , Khan Adnan Qadir
Published: October 2009

The historical, political, socio‐cultural and institutional context in the public service of Pakistan is not auspicious for the delivery of social services such as education. The then military regime introduced radical devolution reforms in 2001 that promised improvements in service delivery by enhancing accountabilities and capacities for change in local government. However the political economy of this top‐down devolution has proved contentious. It established new power structures and authorities over resources at local levels but without concurrent efforts to enhance service delivery capacities. This article examines capacity issues in two cases of capacity development in education service delivery in Pakistan's largest province. The Punjab Education Sector Reform Programme (PESRP) was managed by a provincial‐level implementation unit; the Strategic Policy Unit (SPU) of City District Government Faisalabad was a local government project supported by technical co‐operation. Both delivered major improvements in education delivery capacity in just 4 years, after decades of delivery stagnation and worsening education indicators. The sustainability of these initiatives is in doubt, as political economy factors remain a major impediment to devolved service delivery in Pakistan. Copyright © 2009 John Wiley & Sons, Ltd.
Condensation of alkoxysilanes in alcoholic media: I. Oligomerization of dimethyldiethoxysilane
Authors: Bennevault‐Celton Véronique , Maciejak Olek , Desmazières Bernard , Cheradame Hervé
Published: October 2009

In the context of the preservation of cultural heritage, the treatment of paper by an aminoalkylalkoxysilane, or its mixture with dimethyldiethoxysilane, has given encouraging results. Diluting the monomer bearing the amino function could contribute to obtaining a flexible network interpenetrating the fibre network. Due to the complexity of the system, the work presented here begins with a study of dimethyldiethoxysilane condensation under the conditions used for the paper deacidification (alcoholic medium, neutral condition, etc.). No detectable exchange reaction with ethanol was observed in anhydrous systems of dimethyldiethoxysilane for 24 h, but in the presence of water, hydrolysis and exchange were observed, the rate constant of the former being higher than that of the latter by one order of magnitude. In methanol, in the presence of water, condensation leading to dimerization was observed within less than three days, with polycondensation requiring a much longer time. From the rate constant measurements, in the presence of water, it appears that the condensation reaction is the slowest reaction. It can be concluded that with freshly prepared dimethyldiethoxysilane solutions in ethanol, this monomer cannot homopolymerize. The next step will be to determine to what extent it can be integrated into the network formed by the polycondensation of aminoalkylalkoxysilane. Copyright © 2009 Society of Chemical Industry
Synthesis and characterization of poly[acrylamide‐co‐(sodium 4‐styrenesulfonate)] via inverse microemulsion polymerization
Authors: Qiu Jianhua , Zhang Yanwu , Meng Xiaohong , Zhang Haoqin , Liu Jindun
Published: October 2009

An anionic polyelectrolyte based on acrylamide (Am) and sodium 4‐styrenesulfonate (SSS) was synthesized via the inverse microemulsion polymerization technique. The hydrophilic–lipophilic balance (HLB) values of the surfactant and the composition of the inverse microemulsion system were determined using pseudoternary phase diagrams. The reactivity ratios of Am and SSS in inverse microemulsion polymerization were calculated using the Kelen–Tüdös method. The optimum HLB value of the surfactant for the inverse microemulsion system was 8.58. The composition of the inverse microemulsion system was surfactants (25 wt%), cyclohexane (59 wt%) and aqueous solution of monomers (16 wt%). Am (r1) and SSS (r2) reactivity ratios were 0.61 and 1.99, respectively. Monomer reactivity ratios of Am and SSS determined in the present study differ from those reported for solution radical copolymerization. This indicates that the difference in microenvironment in solution and microemulsion plays an important role in governing the reactivity ratios of the monomers. Copyright © 2009 Society of Chemical Industry
Measuring elementary teacher stress and coping in the classroom: Validity evidence for the Classroom Appraisal of Resources and Demands
Authors: Lambert Richard G. , McCarthy Christopher , O'Donnell Megan , Wang Chuang
Published: October 2009

The Classroom Appraisal of Resources and Demands (CARD, elementary version) was used to investigate teacher stress among a sample of elementary teachers (n = 521). The CARD measures teacher stress by examining the subjective experience of both classroom demands and resources provided by the school, and thereby attempts to capture the situationally specific nature of teacher stress. This study attempted to examine whether the CARD can provide reliable and valid information that addresses the call by experts in the field of teacher stress research for measures that consider each teacher's specific occupational circumstances. Specifically, the factor structure of the CARD was supported empirically. Further evidence was offered for the construct and concurrent validity by correlations between CARD scales scores and other measures theoretically relevant to teacher well‐being: general health, teacher efficacy, self‐critical attitudes, and burnout symptoms. © 2009 Wiley Periodicals, Inc.
A computational approach to inferring cellular protein‐binding affinities from quantitative fluorescence resonance energy transfer imaging
Authors: Mehta Khamir , Hoppe Adam D. , Kainkaryam Raghunandan , Woolf Peter J. , Linderman Jennifer J.
Published: October 2009

Fluorescence resonance energy transfer (FRET) microscopy can measure the spatial distribution of protein interactions inside live cells. Such experiments give rise to complex data sets with many images of single cells, motivating data reduction and abstraction. In particular, determination of the value of the equilibrium dissociation constant (Kd) will provide a quantitative measure of protein–protein interactions, which is essential to reconstructing cellular signaling networks. Here, we investigate the feasibility of using quantitative FRET imaging of live cells to estimate the local value of Kd for two interacting labeled molecules. An algorithm is developed to infer the values of Kd using the intensity of individual voxels of 3‐D FRET microscopy images. The performance of our algorithm is investigated using synthetic test data, both in the absence and in the presence of endogenous (unlabeled) proteins. The influence of optical blurring caused by the microscope (confocal or wide field) and detection noise on the accuracy of Kd inference is studied. We show that deconvolution of images followed by analysis of intensity data at local level can improve the estimate of Kd. Finally, the performance of this algorithm using cellular data on the interaction between yellow fluorescent protein‐Rac and cyan fluorescent protein‐PBD in mammalian cells is shown.
Native electrophoretic techniques to identify protein–protein interactions
Authors: Wittig Ilka , Schägger Hermann
Published: October 2009

Permanent protein–protein interactions are commonly identified by co‐purification of two or more protein components using techniques like co‐immunoprecipitation, tandem affinity purification and native electrophoresis. Here we focus on blue‐native electrophoresis, clear‐native electrophoresis, high‐resolution clear‐native electrophoresis and associated techniques to identify stable membrane protein complexes and detergent‐labile physiological supercomplexes. Hints for dynamic protein–protein interactions can be obtained using two‐hybrid techniques but not from native electrophoresis and other protein isolation techniques except after covalent cross‐linking of interacting proteins in vivo prior to protein separation.
Towards the mammalian interactome: Inference of a core mammalian interaction set in mouse
Authors: Shin Chang Jin , Davis Melissa J. , Ragan Mark A.
Published: October 2009

Protein–protein interactions (PPIs) underpin key biological processes in cells. Describing and interpreting this network of interactions is a key focus of computational systems biology. While mouse is commonly used as a model system for mammalian biology, the description of mouse PPIs available in public interaction databases is remarkably poor. Collectively, public resources such as BIND, IntACT and MINT contain only a few thousand mouse PPIs, far behind the many tens or hundreds of thousands likely to exist. To supplement this lack and to take advantage of other high‐throughput omic data sets in mouse, here we identify that portion of the human interactome with orthologs in mouse, and from that infer a mouse interolog network. By inferring interactions in mouse based on only the most closely related species with abundant PPI data (human), we create a view of mouse interactions enriched for shared mammalian biological processes. We also demonstrate that available methods for determining orthologs between even closely related species produce distinctly different results, and we propose an integrated view of mouse–human orthology from which to infer a broader interolog network.
Experimental and computational tools useful for (re)construction of dynamic kinase–substrate networks
Authors: Tan Chris Soon Heng , Linding Rune
Published: October 2009

The explosion of site‐ and context‐specific in vivo phosphorylation events presents a potentially rich source of biological knowledge and calls for novel data analysis and modeling paradigms. Perhaps the most immediate challenge is delineating detected phosphorylation sites to their effector kinases. This is important for (re)constructing transient kinase–substrate interaction networks that are essential for mechanistic understanding of cellular behaviors and therapeutic intervention, but has largely eluded high‐throughput protein‐interaction studies due to their transient nature and strong dependencies on cellular context. Here, we surveyed some of the computational approaches developed to dissect phosphorylation data detected in systematic proteomic experiments and reviewed some experimental and computational approaches used to map phosphorylation sites to their effector kinases in efforts aimed at reconstructing biological signaling networks.