bluuebunny/crossref_metadata_2025 huggingface dataset:
Considerations for Second-Line Therapy of Non-Small Cell Lung Cancer
Authors: Stinchcombe Thomas E. , Socinski Mark A.
Published: February 2008

For patients with advanced non-small cell lung cancer and a good functional status, platinum-based first-line chemotherapy improves quality of life, reduces disease-related symptoms, and improves survival. The addition of bevacizumab to carboplatin and paclitaxel in the first-line setting has been shown to produce a higher response rate and longer progression-free survival and overall survival times than with carboplatin and paclitaxel. Despite these therapies, all patients inevitably experience disease progression. There are currently three agents approved for treating patients who progress after one prior regimen: docetaxel, pemetrexed, and erlotinib. Erlotinib is also indicated for patients who progress after two prior regimens. These agents appear to have similar efficacies in terms of response and overall survival, but have significantly different toxicity profiles. Currently, the choice of agent depends on a number of factors, including the patient's comorbidities, toxicity from previous treatments, the risk for neutropenia, smoking history, and patient preference. A better understanding of prognostic factors in the second-line setting may allow clinicians to better select patients for second-line therapy, and lead to better-designed second-line trials. Patients with a good performance status in second-line trials have a median survival duration of approximately 9 months, and may receive two second-line therapies during the course of their treatment. Several new agents have shown activity in phase II trials, and may be integrated into second-line therapy as single agents or in combination with current agents in the future.
Systemic Chemotherapy for Advanced Non-Small Cell Lung Cancer: Recent Advances and Future Directions
Authors: Ramalingam Suresh , Belani Chandra
Published: February 2008

Systemic therapy improves the survival and quality of life of patients with advanced stage non-small cell lung cancer (NSCLC). Several new therapeutic options have emerged for advanced NSCLC, incorporating novel cytotoxic agents (taxanes, gemcitabine, pemetrexed) and molecular-targeted agents (erlotinib, bevacizumab). Efforts to improve the outcome of first-line therapy for advanced and metastatic NSCLC have primarily focused on the addition of targeted agents to platinum-based two-drug regimens. Bevacizumab, an antibody against vascular endothelial growth factor, is the first drug to demonstrate superior outcomes when added to systemic chemotherapy in advanced disease. Evaluation of the role of maintenance therapy following four to six cycles of first-line combination chemotherapy is ongoing. Both cytotoxic agents and targeted agents are suitable for evaluation in the maintenance setting. Promising results have been noted with single-agent paclitaxel as maintenance therapy following four cycles of combination therapy with carboplatin and paclitaxel. Phase III studies are now under way to evaluate the roles of gemcitabine, pemetrexed, and erlotinib as maintenance therapies for patients who experience a response or disease stabilization after four cycles of combination chemotherapy. Whether this approach will be successful in extending the survival of a select group of patients remains to be seen.
Accounting and Machiavellianism
Authors: Wakefield Robin L.
Published: February 2008

Research exploring the Machiavellian personality trait shows it is often a significant variable influencing career choice and behavior in the workplace. This study proposes a number of research questions examining the relationships between the Machiavellian trait and accountants' demographic characteristics, job satisfaction, career satisfaction and ethical ideology. Findings indicate that, in general, accountants participating in this study are significantly less Machiavellian than vocational groups participating in previous studies. However, accountants higher in the trait appear to be less satisfied with accounting as a career and tend toward a relativistic ethical stance. Findings suggest that Machiavellian behavior is not required to achieve success in the accounting profession, and the promulgation of ethical standards should sustain a high level of integrity in a profession characterized by idealism.
Accounting Firm Culture and Governance: A Research Synthesis
Authors: Jenkins J. Gregory , Deis Donald R. , Bedard Jean C. , Curtis Mary B.
Published: February 2008

This paper summarizes research related to accounting firm culture and governance. While perennially important, this topic has immediacy due to the intention of the Public Company Accounting Oversight Board (PCAOB) to consider revisions of the current U.S. interim auditing standards on quality control. Our purposes are to bring together several disparate lines of research on this broad topic in order to identify specific areas of insufficient research. We review literature related to the roles of culture and subcultures within audit firms, and the relation between culture and audit quality. We also consider governance and control mechanisms, including policies related to consultation, independent monitoring boards, ethics training, and acculturation. Throughout the paper, we offer suggestions for future research based on the current status of the literature and the recent environmental changes in the auditing profession.
Disclosure versus Recognition of Stock Option Compensation: Effect on the Credit Decisions of Loan Officers
Authors: Viger Chantal , Belzile Réjean , Anandarajan Asokan A.
Published: February 2008

We examine if different stock option reporting formats affect bank loan officers' judgments and decisions. Three formats were used: (1) descriptive note of stock options plan only, (2) descriptive note that included a pro forma disclosure showing the impact of expensing the cost of stock options on net income, and (3) recognition of the stock options cost in the income statement. Our results show that loan officers estimated a higher risk rating and a more pessimistic trend rating, were less inclined to grant the loan, and charged a higher risk premium when the stock option expense was recognized in the income statement. Judgments and decisions did not significantly differ for the two methods of footnote disclosure, suggesting that loan officers are functionally fixated on reported earnings. Overall, our results support the FASB's claim that “disclosure is not an adequate substitute for recording.”
Developing an Operating Budget for Extended Family, Inc.: A Not-for-Profit Human Service Organization
Authors: Mammano Karyl A. , Tyson Thomas N.
Published: February 2008

In this case, you will develop an operating budget for Extended Family, Inc., a not-for-profit (NFP) human service organization. Completing this budget successfully requires a high level of decision making, as you must determine the number of cost pools and allocation bases upon which common costs are to be allocated to the organization's three revenue-generating programs. This case will expose you to many real-world issues that NFP financial managers confront when they prepare operating budgets. These issues include: (1) allocating revenue among programs; (2) distinguishing among program, administrative, and fundraising costs; (3) properly treating temporarily restricted contributions; and (4) facing an array of ongoing financial challenges connected with NFPs.
Implementing a Required Ethics Class for Students in Accounting: The Texas Experience
Authors: Hurtt R. Kathy , Thomas C. William
Published: February 2008

This paper describes a triangulated case study of the experiences and attitudes of educators in Texas regarding recent implementation of a three-semester-hour course in ethics as a prerequisite education requirement for CPA examination candidates. We present the results of (1) examining syllabi of courses on the Texas State Board of Public Accountancy (TSBPA)'s approved list as of January 2006; (2) two follow-up surveys of course instructors; and (3) unstructured interviews of selected members and staff of the TSBPA. The purpose of this descriptive study is to gather information concerning the content and pedagogy in college and university ethics courses for CPA exam candidates in Texas. In addition, we report impressions of course instructors and TSBPA staff as to their course and implementation experiences. The results of this study may be useful to educators elsewhere who are attempting to design and implement future courses in ethics for accounting students. In addition, our findings might prove insightful to policy makers and regulators as well as to practitioners who both hire the graduates and serve on state boards and other policy-making groups.
The Unintended Consequences of Sarbanes-Oxley on Technology Innovation and Supply Chain Integration
Authors: Arnold Vicky , Benford Tanya S. , Canada Joseph , Kuhn John R. , Sutton Steve G.
Published: February 2008

This paper reports the results of a series of case studies conducted to explore the impact of the Sarbanes-Oxley Act of 2002 on the performance of small and medium-sized enterprises (SMEs). This issue is critical as the SEC and the PCAOB continue to defend the requirement that SMEs adhere to the internal control reporting requirements of Section 404 in the Act, albeit at a revised level of expectation focusing on more of a top-down risk-based approach. Cross-sectional case study data is used to explore the impacts of SOX on SMEs adopting organizational theories as a lens for observing behavior and outcomes. The results of the study confirm that there are both benefits and costs associated with SOX compliance. All of the organizations studied experienced substantial improvements in enterprise risk management approaches. However, the level of difficulty experienced by the various organizations in implementing SOX requirements was highly variable and could be traced back to the underlying factors in structural inertia theory: size, complexity, experience with change, experience with strict controls, and adaptability. Perhaps the most important finding is that SOX does impact organizational flexibility to various degrees as predicted by theory; and this impact can in turn affect production cycle times, information technology investment, supply chain performance, and ultimately, market competitiveness.
Confidence in the Implementation Process of a New Information System
Authors: Dow Kevin E. , Leitch Robert A.
Published: February 2008

The perceived likelihood that a new system will be able to support the transaction processing and decision-making needs of an organization can enhance the confidence in an information system. The objective of this paper is to examine antecedent constructs (training, communication, top management support, and change management) that can enhance or diminish a user's confidence in a new information system for a large financial services organization, as it is phased in over time. Using structural equation modeling techniques, the relationships of these antecedents to confidence are analyzed. The structural model fits the data well and the model explains approximately 80 percent of the variance of confidence. In general, these antecedents affect confidence in the new system. We further find that change management, during the implementation process, partially mediates the effect of the other three antecedents and that this mediating effect changes significantly between groups of implementers.
The Potential Impact of More Frequent Financial Reporting and Assurance: User, Preparer, and Auditor Assessments (Retracted)
Authors: Hunton James E. , Wright Arnold M. , Wright Sally
Published: February 2008

The purpose of this study is to examine some of the potential impacts of more frequent financial reporting and concurrent assurance, as assessed by members of the assurer, preparer, and investor communities. Two hundred and fifteen participants (84 auditors, 30 controllers, 80 investors, as surrogated by MBA students, and 21 sell-side analysts) took part in an experiment where they received a case situation involving a company that was planning to voluntarily change from quarterly to monthly (daily) external financial statement reporting, without (with) assurance. After reading the case materials, the participants assessed the likely effects of such changes on the decision usefulness of financial statements, quality of earnings, financial reporting behavior, stock market price volatility, analysts' consensus forecasts, and cost of capital.

The results indicate that monthly reporting without assurance would significantly enhance the decision usefulness of financial statements, improve the quality of earnings, and reduce managements' aggressiveness with respect to discretionary accounting accruals, estimates, and principles; further, the findings suggest stock price volatility would be lower, analyst consensus of future earnings estimates would increase, and cost of capital would decrease. Assessments of daily reporting were consistent with monthly reporting, yet significantly stronger. The inclusion of concurrent auditor assurance resulted in directionally consistent yet significantly pronounced results in both monthly and daily reporting conditions on all measures. Additionally, participants agreed that providing monthly reports would be technically and economically feasible at this time, while daily reporting would not be feasible.
Altman's 1968 Bankruptcy Prediction Model Revisited via Genetic Programming: New Wine from an Old Bottle or a Better Fermentation Process?
Authors: McKee Thomas E.
Published: February 2008

Prior research raised questions about the information value of some of the variables included in Altman's 1968 seminal bankruptcy prediction model. Answering these questions is of great importance since the original Altman model and variations on it are still used to provide bankruptcy risk signals in accounting and audit practice.

This study applied genetic programming to Altman's original data set in order to examine the issue of variable significance. Two parsimonious models employing either one or two variables were developed that equaled the accuracy rate of Altman's five variable model when tested on Altman's original data set. The two variable model also equaled or exceeded the Altman model both when error rates were compared based on prior probabilities of bankruptcy and when relative misclassification costs were considered. The accuracy levels and parsimony of the two genetic programming models supports prior research and confirms that some of the variables in the original model were an artifact of discriminant analysis.
Group-based Aerobic Interval Training in Patients With Chronic Heart Failure: Norwegian Ullevaal Model
Authors: Nilsson Birgitta Blakstad , Hellesnes Brit , Westheim Arne , Risberg May Arna
Published: February 2008

Background and Purpose

The purpose of this case report is to describe the responses of 4 patients with chronic heart failure (CHF) to a novel rehabilitation program: a group-based, high-intensity, interval-training program that includes aerobic, resistance, flexibility, and balance activities.

Case Descriptions

Four patients (55–71 years of age) with CHF (New York Heart Association class III) participated in the rehabilitation program twice per week for 16 weeks. Outcome measures included a 6-minute walk test (6MWT), a cycle ergometer test (aerobic capacity), and a quality-of-life questionnaire.

Outcomes

Patients 1, 2, and 3 increased their aerobic capacity (17%, 25%, and 52%, respectively). Patient 4 did not complete the cycle ergometer test because of limitations associated with his pacemaker. All patients increased their 6MWT distance (117, 66, 135, and 143 m for patients 1, 2, 3, and 4, respectively). No adverse events were reported.

Discussion

The Norwegian Ullevaal Model of cardiac rehabilitation is a novel high-intensity, interval-training program. The 4 patients with CHF in this case series who participated in this program experienced improvements in physical capacity and quality of life and had no adverse events. These results are consistent with recent evidence supporting the efficacy of high-intensity interval training in people with CHF. Randomized clinical trials are needed to evaluate the clinical efficacy of this group-based, high-intensity, aerobic interval-training program for patients with CHF.
Identifying Chromosomal Targets of DNA‐Binding Proteins by Sequence Tag Analysis of Genomic Enrichment (STAGE)
Authors: Kim Jonghwan , Iyer Vishwanath R.
Published: February 2008

Sequence Tag Analysis of Genomic Enrichment (STAGE) is a method for experimentally identifying the in vivo chromosomal targets of DNA‐binding proteins in any sequenced genome. STAGE generates 21‐bp tags derived from DNA isolated by chromatin immunoprecipitation (ChIP; UNIT 21.3). Concatamers of tags are cloned and sequenced to yield a STAGE library. Tags in the library represent DNA fragments that were occupied by the DNA‐binding protein, and mapping these tag sequences to the genome identifies the binding loci of the DNA‐binding protein in vivo. STAGE can be applied to any sequenced genome to identify targets of DNA‐binding proteins without requiring extensive microarray resources.
Childhood antecedents of serious violence in adult male offenders
Authors: Hill Jonathan , Nathan Rajan
Published: February 2008

Prospective longitudinal studies have shown strong predictions from conduct disorders (CDs) in childhood to antisocial personality disorder (ASPD) and violence in adults. However, little is known of the childhood antecedents of serious violence nor whether these may vary depending on the context in which the violence occurs.

In this study, 54 men aged 21–40 years serving prison sentences for violent crime were assessed. Standardized interviews of ASPD and violence were conducted independently of interviews covering retrospective recall of childhood psychiatric disorders and adverse experiences. Analyses of the predictors of overall violence suggested a pathway involving childhood CD and adult ASPD associated with interparental discord, and an additional pathway associated with experiencing interparental violence in childhood. Different results were however obtained when account was taken of the context of the violence. The CD–ASPD pathway was associated with social violence, but not with partner violence. Partner violence was predicted by retrospective reports of having been exposed to interparental violence during childhood but not by reports of childhood CD or adult ASPD. Thus developmental pathways to serious violence may be different depending on the social domain in which the violence occurs. Aggr. Behav. 34:329–338, 2008. © 2008 Wiley‐Liss, Inc.
New Enantioselective Synthesis of Monofluorinated Pyridines Designed for the Preparation of Chemical Libraries
Authors: Blayo Anne‐Laure , Le Meur Stéphanie , Grée Danielle , Grée René
Published: February 2008

Chiral pyridines with a fluorine atom in the benzylic position are easily accessible from optically active propargylic fluorides by using the Bohlmann–Rahtz reaction. Such pyridines, possessing four points of molecular diversity, are useful scaffolds for the preparation of chemical libraries.
Linear QSPRs for predicting pure compound properties in homologous series
Authors: Brauner Neima , St. Cholakov Georgi , Kahrs Olaf , Stateva Roumiana P. , Shacham Mordechai
Published: February 2008

Linear QSPRs, containing 1 through 4 descriptors, are developed for predicting the normal boiling temperature, melting point temperature, and critical properties for the n‐alkane, 1‐alkene, n‐alkylbenzene, 1‐alcohol, and alkanoic monocarboxylic acid homologous series. It has been shown that property values for which experimental data are available can be predicted within experimental error level (with very few and very small exceptions), irrespective of whether interpolation or extrapolation is involved. Property values for which predicted literature data are available can be matched within the reported “reliability” level, even when extrapolation is carried out from very small training sets containing experimental data. Thus, the linear QSPRs developed represent well the nonlinear variation of the particular property with the carbon number, and increase the confidence in the values predicted when extrapolation is involved. © 2008 American Institute of Chemical Engineers AIChE J, 54: 978–990, 2008
Absence of cutaneous neurofibromas in an NF1 patient with an atypical deletion partially overlapping the common 1.4 Mb microdeleted region
Authors: Kehrer‐Sawatzki Hildegard , Schmid Eva , Fünsterer Carsten , Kluwe Lan , Mautner Victor‐Felix
Published: February 2008

The majority of neurofibromatosis type 1 (NF1) microdeletions in 17q11.2 span ∼1.4 Mb and have breakpoints that lie within the proximal and distal NF1‐low copy repeats, termed NF1‐REPs. Less frequent are patients with atypical deletions and non‐recurring breakpoints. NF1 patients with gross deletions have been reported to manifest a more severe clinical phenotype than NF1 patients with intragenic mutations, and display early onset and extensive growth of neurofibromas. It has been suggested that the deletion of a neighboring gene or genes in addition to the NF1 gene may modify the expression of the disease, particularly with regard to the high burden of cutaneous neurofibromas. Thus, atypical deletions partially overlapping with the common 1.4 Mb microdeletion interval could prove useful in identifying possible genetic modifiers in the NF1 gene region whose haploinsufficiency might promote neurofibroma growth. Here we report a 20‐year‐old female who has an atypical deletion with a proximal breakpoint in NF1 intron 21 and a distal deletion breakpoint in the ACCN1 gene. The deletion spans 2.7 Mb and was mediated by an intrachromosomal non‐homology‐driven mechanism, for example, non‐homologous end‐joining (NHEJ). Remarkably, this patient did not exhibit cutaneous neurofibromas. However, genotype–phenotype comparisons in this and other previously reported patients with atypical deletions partially overlapping the commonly deleted 1.4 Mb interval do not identify a specific deleted region that is associated with increased neurofibroma growth. © 2008 Wiley‐Liss, Inc.
Test Equality and Sample Size Calculation Based on Risk Difference in a Randomized Clinical Trial with Noncompliance and Missing Outcomes
Authors: Lui Kung‐Jong , Chang Kuang‐Chao
Published: February 2008

In a randomized clinical trial (RCT), noncompliance with an assigned treatment can occur due to serious side effects, while missing outcomes on patients may happen due to patients' withdrawal or loss to follow up. To avoid the possible loss of power to detect a given risk difference (RD) of interest between two treatments, it is essentially important to incorporate the information on noncompliance and missing outcomes into sample size calculation. Under the compound exclusion restriction model proposed elsewhere, we first derive the maximum likelihood estimator (MLE) of the RD among compliers between two treatments for a RCT with noncompliance and missing outcomes and its asymptotic variance in closed form. Based on the MLE with tanh–1(x) transformation, we develop an asymptotic test procedure for testing equality of two treatment effects among compliers. We further derive a sample size calculation formula accounting for both noncompliance and missing outcomes for a desired power 1 – β at a nominal α‐level. To evaluate the performance of the test procedure and the accuracy of the sample size calculation formula, we employ Monte Carlo simulation to calculate the estimated Type I error and power of the proposed test procedure corresponding to the resulting sample size in a variety of situations. We find that both the test procedure and the sample size formula developed here can perform well. Finally, we include a discussion on the effects of various parameters, including the proportion of compliers, the probability of non‐missing outcomes, and the ratio of sample size allocation, on the minimum required sample size. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Targeted protein accumulation promoted by autoassembly and its recovery from plant cells
Authors: Noizet Mildred , Harrabi Faouzi , Vijayalakshmi Mookambeswaran , Galbraith David , Thomas Daniel , Thomasset Brigitte
Published: February 2008

The expression of a fusion protein formed between the avian infectious bronchitis virus M protein and the bacterial enzyme β‐glucuronidase (GUS) in plants promotes the formation of new organization of the endoplasmic reticulum in tobacco plants. This unusual organization of the membranes, never present in nontransformed plants, has been explained by the oligomerization of the GUS domains of the IBVM‐GUS fusion proteins. These specific organized membranes could have broad implications for biotechnology since their formation could be used as a mechanism for retaining and accumulating resident proteins in specific and discrete membrane compartments. In this study, we have shown that the unusual organization of native membranes due to overexpression of the IBVM‐GUS fusion gene in tobacco transgenic plants and calli is present at higher levels in plant cell suspensions than in plant tissues. In these cell suspensions, IBVM‐GUS protein was continuously synthesized and accumulated throughout the cell culture. An enrichment of the chimeric IBVM‐GUS protein corresponding to a five‐fold increase in the microsomal fractions was achieved and the GUS enzyme did not show any modification on enzyme kinetics. However, the GUS activity could be differentially distributed in the fractions eluted at different pH suggesting differences in the surface topography of histidine residues for this recombinant GUS.
Drosophila female sterile (1) homeotic is a multifunctional transcriptional regulator that is modulated by Ras signaling
Authors: Florence Brian L. , Faller Douglas V.
Published: February 2008

The Drosophila (fs(1)h) gene encodes small (Fs(1)hS) and large (Fs(1)hL) chromatin‐binding BET protein transcription factor isoforms. Zygotic mutations cause either lethality or female sterility, whereas maternal mutations cause segmental deletions and thoracic homeotic transformations. Here, we describe novel fs(1)h embryonic phenotypes: homeosis of the head in zygotic mutants and deletion of head and tail regions in maternal mutants, similar to those caused by dominant torso (torD) alleles. tor activates transcription of tailless (tll) and hückebein (hkb) by means of a canonical Ras pathway, through inactivation of Groucho (Gro), Capicua (Cic) and, possibly, Grainy‐head (Grh) repressors. Expression of both tailless and hückebein are de‐repressed in fs(1)h maternal mutants, as in torD, gro, grh, and cic mutant animals, indicating fs(1)h is also necessary for tll and hkb repression. These data link Ras signaling with modulation of a chromatin‐binding transcription factor, Fs(1)h, suggesting a novel mechanism by which Ras can modulate gene expression. Developmental Dynamics 237:554–564, 2008. © 2008 Wiley‐Liss, Inc.
Molecular evolution and expression of zebrafish St8SiaIII, an alpha‐2,8‐sialyltransferase involved in myotome development
Authors: Bentrop Joachim , Marx Monika , Schattschneider Sebastian , Rivera‐Milla Eric , Bastmeyer Martin
Published: February 2008

Enzymes of the St8Sia family, a subgroup of the glycosyltransferases, mediate the transfer of sialic acid to glycoproteins or glycolipids. Here, we describe the cloning of the zebrafish St8SiaIII gene and study its developmental activity. A conserved synteny relationship among vertebrate chromosome regions containing St8SiaIII loci underscores an ancient duplication of this gene in the teleost fish lineage and a specific secondary loss of one paralog in the zebrafish. The single zebrafish St8SiaIII enzyme, which is expected to function as an oligosialyltransferase, lacks maternal activity, is weakly expressed during nervous system development, and shows a highly dynamic expression pattern in somites and somite‐derived structures. Morpholino knock‐down of St8SiaIII leads to anomalous somite morphologies, including defects in segment boundary formation and myotendious‐junction integrity. These phenotypes hint for a basic activity of zebrafish St8SiaIII during segmentation and somite formation, providing novel evidence for a non‐neuronal function of sialyltransferases during vertebrate development. Developmental Dynamics 237:808–818, 2008. © 2008 Wiley‐Liss, Inc.
Activin/nodal signaling modulates XPAPC expression during Xenopus gastrulation
Authors: Lou Xin , Li Shuangwei , Wang Jinhu , Ding Xiaoyan
Published: February 2008

Gastrulation is the first obligatory morphogenesis during vertebrate development, by which the body plan is established. Nodal signaling is a key player in many developmental processes, including gastrulation. XPAPC has been found to exert its biological function through modifying the adhesion property of cells and interacting with other several important molecules in embryos. In this report, we show that nodal signaling is necessary and sufficient for XPAPC expression during Xenopus gastrulation. Furthermore, we isolated 4.8 kb upstream DNA sequence of Xenopus XPAPC, and proved that this 4.8‐kb genomic contig is sufficient to recapitulate the expression pattern of XPAPC from gastrula to tail bud stage. Transgene and ChIP assays indicate that Activin/nodal signaling participates in regulation of XPAPC expression through a Smad binding element within the XPAPC promoter. Concomitant investigation suggests that the canonical Wnt pathway‐activated XPAPC expression requires nodal signaling. Developmental Dynamics 237:683–691, 2008. © 2008 Wiley‐Liss, Inc.
Dynamics of zebrafish somitogenesis
Authors: Schröter Christian , Herrgen Leah , Cardona Albert , Brouhard Gary J. , Feldman Benjamin , Oates Andrew C.
Published: February 2008

Vertebrate somitogenesis is a rhythmically repeated morphogenetic process. The dependence of somitogenesis dynamics on axial position and temperature has not been investigated systematically in any species. Here we use multiple embryo time‐lapse imaging to precisely estimate somitogenesis period and somite length under various conditions in the zebrafish embryo. Somites form at a constant period along the trunk, but the period gradually increases in the tail. Somite length varies along the axis in a stereotypical manner, with tail somites decreasing in size. Therefore, our measurements prompt important modifications to the steady‐state Clock and Wavefront model: somitogenesis period, somite length, and wavefront velocity all change with axial position. Finally, we show that somitogenesis period changes more than threefold across the standard developmental temperature range, whereas the axial somite length distribution is temperature invariant. This finding indicates that the temperature‐induced change in somitogenesis period exactly compensates for altered axial growth. Developmental Dynamics 237:545–553, 2008. © 2008 Wiley‐Liss, Inc.
Characterization and comparative expression of zebrafish calpain system genes during early development
Authors: Lepage Stephanie E. , Bruce Ashley E.E.
Published: February 2008

The classic calpain system has been implicated in regulating a variety of cellular processes including cell adhesion, migration, and intracellular signaling; however, little is known regarding the function of this system in vivo. Two heterodimeric Ca2+‐dependent cysteine proteases, μ‐calpain (CAPN1) and m‐calpain (CAPN2), and the endogenous inhibitor calpastatin (CAST) comprise the classic/ubiquitous calpain system in mammals. Recently, knockout of two murine classic calpain genes, Capn2 and Capn4/Capns1, revealed that components of the classic system are indispensable for preimplantation development. We identified four classic calpain catalytic subunit genes (capn1a, 1b, 2a, 2b), two regulatory subunit genes (capns1a, 1b), and calpastatin (cast) from the zebrafish. Our data suggest that the components of the classic mammalian system are both conserved and expanded in the teleost lineage. In contrast to the classic/ubiquitous mammalian system, zebrafish calpain system genes acquire unique, tissue‐specific patterns of expression within the first 2 days of development. Developmental Dynamics 237:819–829, 2008. © 2008 Wiley‐Liss, Inc.
Cardiac malformations and myocardial abnormalities in podoplanin knockout mouse embryos: Correlation with abnormal epicardial development
Authors: Mahtab Edris A.F. , Wijffels Maurits C.E.F. , Van Den Akker Nynke M.S. , Hahurij Nathan D. , Lie‐Venema Heleen , Wisse Lambertus J. , DeRuiter Marco C. , Uhrin Pavel , Zaujec Jan , Binder Bernd R. , Schalij Martin J. , Poelmann Robert E. , Gittenberger‐De Groot Adriana C.
Published: February 2008

Epicardium and epicardium‐derived cells have been shown to be necessary for myocardial differentiation. To elucidate the function of podoplanin in epicardial development and myocardial differentiation, we analyzed podoplanin knockout mouse embryos between embryonic day (E) 9.5 and E15.5 using immunohistochemical differentiation markers, morphometry, and three‐dimensional reconstructions. Podoplanin null mice have an increased embryonic lethality, possibly of cardiac origin. Our study reveals impairment in the development of the proepicardial organ, epicardial adhesion, and spreading and migration of the epicardium‐derived cells. Mutant embryos show a hypoplastic and perforated compact and septal myocardium, hypoplastic atrioventricular cushions resulting in atrioventricular valve abnormalities, as well as coronary artery abnormalities. The epicardial pathology is correlated with reduced epithelial–mesenchymal transformation caused by up‐regulation of E‐cadherin, normally down‐regulated by podoplanin. Our results demonstrate a role for podoplanin in normal cardiac development based on epicardial–myocardial interaction. Abnormal epicardial differentiation and reduced epithelial–mesenchymal transformation result in deficient epicardium‐derived cells leading to myocardial pathology and cardiac anomalies. Developmental Dynamics 237:847–857, 2008. © 2008 Wiley‐Liss, Inc.
mTOR signaling contributes to chondrocyte differentiation
Authors: Phornphutkul Chanika , Wu Ke‐Ying , Auyeung Valerie , Chen Qian , Gruppuso Philip A.
Published: February 2008

The mammalian Target Of Rapamycin (mTOR) is a nutrient‐sensing protein kinase that regulates numerous cellular processes. Fetal rat metatarsal explants were used as a physiological model to study the effect of mTOR inhibition on chondrogenesis. Insulin significantly enhanced their growth. Rapamycin significantly diminished this response to insulin through a selective effect on the hypertrophic zone. Cell proliferation (bromodeoxyuridine incorporation) was unaffected by rapamycin. Similar observations were made when rapamycin was injected to embryonic day (E) 19 fetal rats in situ. In the ATDC5 chondrogenic cell line, rapamycin inhibited proteoglycan accumulation and collagen X expression. Rapamycin decreased content of Indian Hedgehog (Ihh), a regulator of chondrocyte differentiation. Addition of Ihh to culture medium reversed the effect of rapamycin. We conclude that modulation of mTOR signaling contributes to chondrocyte differentiation, perhaps through its ability to regulate Ihh. Our findings support the hypothesis that nutrients, acting through mTOR, directly influence chondrocyte differentiation and long bone growth. Developmental Dynamics 237:702–712, 2008. © 2008 Wiley‐Liss, Inc.
Nanocomposites: From Fabrications to Electrochemical Bioapplications
Authors: Xiao Yinghong , Li Chang Ming
Published: February 2008

Nanostructured materials including nanoparticles, nanowires, nanobands and carbon nanotubes (CNT) have been intensively investigated due to their fantastic ‘size effect’ and superior chemical and physical properties and functions. Nanocomposites can be fabricated not only with different nanostructured materials, but also with various biomolecules and conducting polymers to possess unique hybrid properties characteristic of neither the incorporated components nor the host matrices. The nanocomposites may be confined in nanoscale domains in one, two, or three dimensions for the unusual size‐dependent behavior. The synergistic effects of the components lead to broad bioapplications of the nanocomposites such as biosensors, drug delivery systems and biofuel cells. A review of studies on nanocomposites from design, fabrication to their biocompatibility and electrochemical bioapplications is presented.
Assessment of chromosomal gains as compared to DNA content changes is more useful to detect dysplasia in Barrett's esophagus brush cytology specimens
Authors: Rygiel Agnieszka M. , Milano Francesca , ten Kate Febo J. , de Groot John G. , Peppelenbosch Maikel P. , Bergman Jacques J. G. H. M. , Krishnadath Kauslillia K.
Published: February 2008

Abnormal DNA ploidy status has been suggested as a prognostic factor for Barrett's esophagus progression into esophageal adenocarcinoma (EAC). The aim of the study was to compare image cytometry DNA analysis (ICDA) and fluorescent in situ hybridization (FISH) in the assessment of DNA ploidy status in Barrett's esophagus (BE), and to determine the value of these abnormalities as an adjunct to conventional cytology in detection of dysplasia and EAC. Brush cytology specimens of 90 BE patients were examined using ICDA and FISH with peri‐centromeric probes for chromosomes 7 and 17. The results of ICDA and FISH were compared with each other, and with dysplasia grade or EAC as determined by histology and cytology. FISH and ICDA detected abnormalities in 41% (37/90) and 22% (19/90) of the BE cases, respectively. Gains of chromosome 7 and/or 17 were present in 13% of nondysplasia cases, which further increased with dysplasia stage, while overall DNA content aneuploidy was detected predominantly in high grade dysplasia (HGD) and EAC. Using FISH results combined with cytology, we were able to identify IND/LGD (indefinite/ low grade dysplasia) with a sensitivity and specificity of 75 and 76%, respectively. FISH alone detected HGD/EAC with a high sensitivity and specificity of 85 and 84%, which was superior to that of cytology alone. Thus, FISH is more sensitive than ICDA to detect chromosomal abnormalities in BE brush cytology specimens. FISH detects chromosomal gains in early stages of BE and represents a valuable adjunct to conventional cytology to detect dysplasia or EAC. © 2008 Wiley‐Liss, Inc.
Desert Dust over Europe
Authors: Heintzenberg Jost
Published: February 2008

From Morocco to Europe: Scientists are studying the pathway and weather effects of a five‐kilometre‐high cloud of Saharan dust in a large‐scale experiment
Our Word of the Year
Authors: Kleiner Matthias
Published: February 2008

The Excellence Initiative is a great boost for the German scientific community and will also benefit the country and German society as a whole
Times of Change in Omani Oases
Authors: Bürkert Andreas , Hammer Karl , Schlecht Eva , Häser Jutta , Al Khanjari Sulaiman
Published: February 2008

For millennia, highly developed oasis farming, alongside fishing, has formed the basis of life for the sedentary people of Oman. Researchers take a deeper look at the changing land use strategies in remote mountain oasis settlements
Estimating production costs in the economic evaluation of health‐care programs
Authors: Herrero Carmen , Moreno‐Ternero Juan D.
Published: February 2008

We propose a method for calculating the production costs of an intervention in a manner that accounts for differences in productive ‘effort.’ This method could be used within a cost‐effectiveness analysis framework in the evaluation of new medical technologies, pharmaceuticals, treatment programs, or public health interventions. We apply it to show evidence in favor of implementing a newborn screening program to detect congenital hearing impairment. Copyright © 2008 John Wiley & Sons, Ltd.
Thermal pollution of streams by runoff from paved surfaces
Authors: Herb William R. , Janke Ben , Mohseni Omid , Stefan Heinz G.
Published: February 2008

Urban development dramatically alters a drainage system by landscaping, changes in surface cover, and addition of stormwater handling systems. Increased and warmer runoff from impervious surfaces into streams can lead to a degradation of habitat for coldwater fish. For the projection of thermal impacts of new land development projects, hydro‐thermal simulation models have been developed. With measured climate as input, these deterministic models can be used to predict the thermal impact of individual storm events. Surface runoff and runoff temperature were simulated for an asphalt parking lot using 6 years of climate data from Minnesota, USA, with 282 individual rainfall events. The thermal loading from each rainfall event was quantified by three parameters: runoff temperature ( °C), rate of heat export (W/m2) and total (integral) heat export (J/m2). Many storm events were found to have little thermal impact, but a few events per year have high thermal impact, either due to large rainfall amounts at a high dew point temperature or due to high land surface temperature combined with moderate rainfall amounts. The amount of heat added to the runoff is highly dependent on both the characteristics of the rainfall event and the weather conditions prior to the storm event. Runoff temperatures from asphalt were found to be well correlated to a linear combination of three parameters: average dew point temperature during the storm, air temperature prior to the storm, and solar radiation prior to the storm. The study results imply that stormwater thermal pollution is more severe when (1) atmospheric air and dew point temperatures are higher than stream temperature, e.g. for streams that are fed by groundwater that is colder than the ambient air, (2) rainfall events are short, intense and preceded by full or partial sun, and (3) watersheds have a high percentage of impervious, particular paved, surfaces. Copyright © 2008 John Wiley & Sons, Ltd.
Transient receptor potential vanilloid 4 deficiency suppresses unloading‐induced bone loss
Authors: Mizoguchi Fumitaka , Mizuno Atsuko , Hayata Tadayoshi , Nakashima Kazuhisa , Heller Stefan , Ushida Takashi , Sokabe Masahiro , Miyasaka Nobuyuki , Suzuki Makoto , Ezura Yoichi , Noda Masaki
Published: February 2008

Mechanosensing is one of the crucial components of the biological events. In bone, as observed in unloading‐induced osteoporosis in bed ridden patients, mechanical stress determines the levels of bone mass. Many molecules have been suggested to be involved in sensing mechanical stress in bone, while the full pathways for this event has not yet been identified. We examined the role of TRPV4 in unloading‐induced bone loss. Hind limb unloading induced osteopenia in wild‐type mice. In contrast, TRPV4 deficiency suppressed such unloading‐induced bone loss. As underlying mechanism for such effects, TRPV4 deficiency suppressed unloading‐induced reduction in the levels of mineral apposition rate and bone formation rate. In these mice, unloading‐induced increase in the number of osteoclasts in the primary trabecular bone was suppressed by TRPV4 deficiency. Unloading‐induced reduction in the longitudinal length of primary trabecular bone was also suppressed by TRPV4 deficiency. TRPV4 protein is expressed in both osteoblasts and osteoclasts. These results indicated that TRPV4 plays a critical role in unloading‐induced bone loss. J. Cell. Physiol. 216: 47–53, 2008. © 2008 Wiley‐Liss, Inc.
Using dynamic tests to study the continuous mixing of xanthan gum solutions
Authors: Saeed Salwan , Ein‐Mozaffari Farhad
Published: February 2008

BACKGROUND:The current understanding and implementation of continuous mixing of non‐Newtonian fluids is insufficient to ensure good mixing in many cases. In this study, the dynamic response of the continuous mixing of xanthan gum solution, which is a pseudoplastic fluid with yield stress, was quantified using a dynamic model that incorporated non‐ideal flows within the mixing vessel. The model allowed for two parallel flow paths through the tank: (1) a channeling zone and (2) a mixing zone.

RESULTS:Dynamic tests were made using the frequency‐modulated random binary input of a brine solution with the feed to determine the magnitude of non‐ideal flows. The extent of flow bypassing the mixing zone and the effective mixed volume were determined from dynamic tests and used as mixing quality criteria. We explored the effect of impeller speed, impeller type, feed flow rate through the mixing tank, fluid rheology, and feed and exit location on the degree of channeling and the fraction of fully mixed volume. Tests show that when the surface of the cavern created by impeller approaches the tank wall, the bottom of the tank, and the surface of the fluid within the mixing vessel, the percentage of non‐ideal flow approached zero.

CONCLUSION:This study identifies important criteria for continuous mixing vessels that will improve mixing efficiency. By applying these findings, a reduction in the extent of non‐ideal flow can be achieved, which will improve the quality and control of the continuous mixing processes such as continuous high‐viscosity reactor, continuous fermenter, and continuous solid–liquid mixing. Copyright © 2008 Society of Chemical Industry
Effects of sodium chloride on the production of bioactive exopolysaccharides in submerged cultures of Phellinus linteus
Authors: Shu Chin‐Hang , Hsu Hui‐Ju
Published: February 2008

BACKGROUND: Polysaccharides isolated from medicinal mushrooms have been shown to exhibit antitumour bioactivity, but the quality and quantity of these polysaccharides are affected by variations in medium composition and operational conditions in the submerged culture. This study was conducted to elucidate quantitatively the effects of sodium chloride (NaCl) supplementation on the production and quality of exopolysaccharides from the medicinal mushroom Phellinus linteus.

RESULTS: Supplementation of NaCl to submerged cultures of P. linteus significantly affected the morphology, the exopolysaccharide (PLPS) production, its average molecular weight and its biological activity. Phellinus linteus grew in a filamentous form in NaCl‐free medium, but a pellet form became predominant as NaCl supplemention increased. The specific growth rate decreased monotonically from 0.18 to 0.01 day−1 as the NaCl concentration increased from 0.0 to 2.0 g dm−3 (34.22 mmol dm−3); however, the specific product yield increased monotonically from 3.9 to 98.4 mg g−1 (25.2‐fold enhancement). Both 14.3‐fold enhancement (from 23 to 329 mg dm−3) in the production of PLPS and 1.5‐fold enhancement (from 670 to 995 pg TNF‐α (tumour necrosis factor α) cm−3) in its biological activity were achieved as the NaCl concentration increased from 0.0 to 1.0 g dm−3 (17.11 mmol dm−3). The biological activity of PLPS was highly correlated with its average molecular weight (coefficient R2 = 0.90).

CONCLUSION: The average molecular weight of PLPS was key to its biological activity. Both the quantity and bioactivity of PLPS could be significantly enhanced by appropriate NaCl supplementation to the submerged culture of the medicinal mushroom. Copyright © 2008 Society of Chemical Industry