bluuebunny/crossref_metadata_2025 huggingface dataset:
Taking Stock of the Century‐long Utilization of the Case Method in Management Education
Authors: Mesny Anne
Published: March 2013

Over the last century, the case method has been a key teaching tool in management education. This article takes stock of the main characteristics of the case method, clarifies its learning goals, and exposes the relationships between these goals and supporting learning theories, in particular active‐learning theory and experiential learning. It then examines the multiple variations of the case method that have developed over the years and discusses arguments against the case method. Finally, four proposals are made in view of strengthening the case method's value: extend case variety, moderate the case method's ambition to foster experiential learning, conduct empirical research about the case method's learning impacts, and emphasize the close relationship between case research and case teaching. Copyright © 2013 ASAC. Published by John Wiley & Sons, Ltd.
Electrical Plasticity and Cardioprotection in Myocardial Ischemia—Role of Selective Sodium Channel Blockers
Authors: Madonna Rosalinda , Cevik Cihan , Nasser Maher
Published: March 2013

The concept of electrical protection of the ischemic myocardium is in constant evolution and has recently been supported by experimental and clinical studies. Historically, antiplatelet agents, angiotensin‐converting enzyme inhibitors, β‐blockers, and statins have been all proposed as drugs conferring anti‐ischemic cardioprotection. This was supported by the evidence consistently indicating that all these drugs were capable of reducing mortality and the risk of repeat myocardial infarction. The electrical plasticity paradigm is, however, a novel concept that depicts the benefits of improved sodium channel blockade with drugs such as ranolazine and cariporide. Although it has been hypothesized that the protective role of ranolazine depends on decreased fatty acid β‐oxidation affecting preconditioning, we speculate against such a hypothesis, because inhibition of β‐oxidation requires higher concentrations of the drug, above the therapeutic range. Rather, we discuss the key role of calcium overload reduction through inhibition of the late sodium current (INa). Mechanisms driving cardioprotection involve the block of a cascade of complex ionic exchanges that can result in intracellular acidosis, excess cytosolic calcium, myocardial cellular dysfunction, and eventually cell injury and death. In this review we discuss the studies that demonstrate how electrical plasticity through sodium channel blockers can promote cardioprotection against ischemia in coronary heart disease.
Genetic variations in regulator of G‐protein signaling (RGS) confer risk of bladder cancer
Authors: Lee Eugene K. , Ye Yuanquing , Kamat Ashish M. , Wu Xifeng
Published: March 2013

BACKGROUND:

Alterations in the regulator of G‐protein signaling (RGS) pathway have been implicated in several cancers; therefore, the authors investigated the role of such alterations in overall bladder cancer risk, recurrence, progression, and survival.

METHODS:

In this case‐control series, 803 patients with bladder cancer were frequency‐matched with a control cohort of 803 healthy individuals. Ninety‐five single‐nucleotide polymorphisms (SNPs) in 17 RGS genes were investigated for an association with overall bladder cancer risk, recurrence, and progression in patients who had nonmuscle‐invasive bladder cancer (NMIBC) and for an association with death in patients who had muscle‐invasive bladder cancer (MIBC). Cumulative effects and classification and regression tree analyses were performed for SNPs that were associated with overall bladder cancer risk. Kaplan‐Meier plots were created to evaluate differences in the survival of patients with MIBC.

RESULTS:

Reference SNP 10759 (rs10759) on the RGS4 gene demonstrated the greatest association with overall bladder cancer risk, conferring a 0.77‐fold reduced risk with an increasing number of variant alleles (P < .001). A cumulative effects analysis that included all 5 significant SNPs demonstrated an increasing risk with the number of unfavorable genotypes (odds ratio, 4.13; 95% confidence interval, 2.14‐7.98). In patients with NMIBC, 11 SNPs were identified that had an association with disease recurrence, and 13 SNPs were associated with disease progression. Of the 10 SNPs that were associated with death in patients with MIBC, rs2344673 in an additive model was the most significant and was associated with a decreased median survival of 13.3 months compared with 81.9 months in individuals without a variant allele.

CONCLUSIONS:

Genetic variations in the RGS pathway were associated with the overall risk of bladder cancer, recurrence, and progression in patients with NMIBC and with the risk of death in patients with MIBC. Cancer 2013. © 2013 American Cancer Society.
Ion‐Acoustic Waves Instability in a Three Components Magneto‐Plasma with Nonthermal Electrons
Authors: Haider M. M.
Published: March 2013

A theoretical investigation has been made on obliquely propagating ion‐acoustic (IA) solitary structures in a three components magneto‐plasma containing cold inertial ions, Boltzmann distributed positrons, and hot non‐thermal electrons. The Zakharov‐Kuznetsov equation has been derived by the reductive perturbation method, and its solitary wave solution has been analyzed. Multi‐dimensional instability has also studied by the small‐k (long wave‐length plane wave) perturbation expansion technique, which is found to exist in such a plasma. The effects of the external magnetic field, nonthermal electrons, obliqueness and temperature ratio have significantly modified the basic properties of small but finite‐amplitude IA solitary waves, such as amplitude, width, instability criterion and the growth rate. The present investigation contributes to the physics of the nonlinear IA waves in space and laboratory electron‐positron‐ion magneto‐plasmas in which wave damping produces an electron tail. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A Hybrid Structure/Pharmacophore‐Based Virtual Screening Approach to Design Potential Leads: A Computer‐Aided Design of South African HIV‐1 Subtype C Protease Inhibitors
Authors: Soliman Mahmoud E. S.
Published: March 2013

Preclinical Research

Virtual screening is the computational mirror image of high‐throughput screening and refers to the in silico evaluation of the biological activity of different molecular entities. Various virtual screening strategies and workflows have been adopted to enhance the process of identification of potential hits. Structure‐based scoring relies solely on the interactions between the ligand and the target protein. Conversely, pharmacophore‐based scoring relies on the shape complementation of each ligand candidate to a three‐dimensional reference ligand. Herewith, we report a systematic integrated hybrid approach, along with the use of well‐defined physicochemical and biological filters, to enhance high‐ranking hit structures complementing the binding site architecture while also mimicking the three‐dimensional features of known active ligands.

With a lack of experimental data on the South African HIV protease enzyme (C‐SA HIV PR), very limited research has been conducted to design inhibitors against this enzyme variant. In this paper, a focused integrated structure‐ and pharmacophore‐based virtual screening protocol is introduced to identify potential leads to assist toward designing potent inhibitors against the C‐SA PR variant. This rapid and systematic approach can potentially be implemented for the design and discovery of inhibitors against a wide range of biological targets.
Dominant negative mutations of caenorhabditis elegans daf‐7 confer a novel developmental phenotype
Authors: Crook Matt , Grant Warwick N.
Published: March 2013

Background: TGF‐β signaling pathways are involved in the control of development in every member of the animal kingdom. As such, TGF‐β ligands are widely divergent yet retain a set of core conserved features, specifically, a pre‐protein cleavage site and several conserved ligand domain residues, the disruption of which produces a dominant negative phenotype. Results: We have extended these observations into an invertebrate system by creating a series of loss‐of‐function Caenorhabditis elegans daf‐7 transgenes. When we tested these mutant transgenes in a daf‐7/+ background, we saw a molting and excretory canal phenotype. Members of both pathways downstream of daf‐4 were required for this phenotype. Conclusions: Our results show that the basic mechanisms of TGF‐β function are conserved across the animal kingdom. A subset of our daf‐7 mutations also produced an unexpected and novel phenotype. Epistasis experiments demonstrated that both daf‐3/‐5 and sma‐4/‐9 were downstream of our mutant daf‐7 transgenes, which suggests not only a role for DAF‐7 in the control of molting and the development of the excretory system but also that daf‐7 and dbl‐1 signaling may converge downstream of their shared Type II receptor, daf‐4. Our approach may unveil new roles in development for other invertebrate TGF‐β ligands. Developmental Dynamics 242:654–664, 2013. © 2013 Wiley Periodicals, Inc.
Jagged1 is the major regulator of notch‐dependent cell fate in proximal airways
Authors: Zhang Shubing , Loch Amanda J. , Radtke Freddy , Egan Sean E. , Xu Keli
Published: March 2013

Background: The Notch signaling pathway plays complex roles in developing lungs, including regulation of proximodistal fates, airway cell specification and differentiation. However, the specific Notch‐mediated signals involved in lung development remain unclear. Results: Here we report that Jagged1 is expressed in a subset of bronchial and bronchiolar epithelial cells, where it controls proximal airway cell fate and differentiation. In agreement with previous studies involving disruption of all Notch signaling, we found that deletion of Jagged1 in airway epithelium increased the number of ciliated cells at the expense of Clara cells, a phenotype associated with downregulation of Hes1. Deletion of Jagged1 also led to an increased number of pulmonary neuroendocrine cells (PNEC), suggesting that Jagged1/Notch signaling inhibits PNEC cell fate. As expected, Jagged1 deletion did not affect alveolar cell differentiation, although alveolar septation was impaired, likely an indirect effect of proximal airway defects. Finally, in the postnatal lung, Jagged1 deletion induced mucous metaplasia, accompanied by downregulation of Hes1 and Hes5. Conclusions: Our results demonstrate that Jagged1‐mediated Notch signaling regulates multiple cell fate decisions as well as differentiation in the respiratory system to coordinate lung development and to maintain a balance of airway cell types in adult life. Developmental Dynamics 242:678–686, 2013. © 2013 Wiley Periodicals, Inc.
On the relation between soil moisture dynamics and the geographical distribution of Culicoides imicola
Authors: Peters Jan , Conte Annamaria , Van doninck Jasper , Verhoest Niko E. C. , De Clercq Eva , Goffredo Maria , De Baets Bernard , Hendrickx Guy , Ducheyne Els
Published: March 2013

Culicoides imicola is the main biological vector in the transmission of the Bluetongue virus in the Mediterranean basin. Its geographical range is constrained by environmental characteristics, and soil moisture has been proposed as an important constraint because of its effect on C. imicola breeding habitat. The few field studies on breeding habitat of C. imicola indicate the favourability of (semi‐)moist habitat that is not flooded. Data on C. imicola in Calabria revealed the presence of C. imicola at the eastern Ionian coastal area and the absence at the greater part of the western Tyrrhenian coastal area. A spatially distributed soil moisture model was applied to obtain daily soil moisture estimates for Calabria and to assess the relationship between soil moisture and the particular C. imicola distribution at the study region. The temporal soil moisture pattern was not significantly different between locations of contrasting C. imicola occurrence. The monthly average volumetric soil moisture content, however, was found to differ substantially. Soil moisture conditions of the topsoil at locations of C. imicola presence were consistently wetter. Particularly in August, at the onset of the season of high C. imicola abundance, soil moisture was significantly higher at the presence sites and sustained the larval stages of the C. imicola life cycle. This study provides evidence that soil moisture imposes an important constraint on the geographical distribution of C. imicola. Soil moisture may therefore be considered as a key environmental variable for the delineation of suitable C. imicola habitat. Copyright © 2013 John Wiley & Sons, Ltd.
Robotized method for the quantification of fatty acids by gas–liquid chromatography
Authors: Beggio Maurizio , Giuffrida Francesca , Golay Pierre‐Alain , Nagy Kornél , Destaillats Frédéric
Published: March 2013

Analysis of fatty acid profile in fats and oils is conventionally performed by gas–liquid chromatography (GLC) as their fatty acid methyl ester (FAME) derivatives. Accurate quantification can be achieved by adding internal standard(s) prior to the derivatization step and calibration of the system using certified FAME mixture. GLC instruments equipped with online sample preparation units became recently commercially available and in theory can be used to improve laboratory productivity and safety. However, studies showing that this type of approach can be used to obtain reliable results are scarce. In the present study, we developed a method suitable for quantitative analysis of fatty acids in fats and oils by robotic preparation and online GLC analysis of FAME using methanolic potassium hydroxide as transmethylation reagent. The method has been validated on different fats and oils including milk fat, palm kernel, rapeseed and long‐chain polyunsaturated fatty acids containing oil samples. Method performance has been compared to the corresponding manual procedure and results show good repeatability [CV(r)<5%] and good intermediate reproducibility [CV(iR)<5%] in accordance with FDA guidelines. The results obtained show that transmethylation and GLC analysis of fats and oils can be robotized while remaining accurate and providing fatty acid data expressed as g of fatty acid per 100 g of sample. Compared to conventional methods, the volume of reagent and solvent is three times lower per sample analyzed with the robotized version which contributes to the reduction of waste and chemical risk exposure.
Aryl Bromides and Aryl Chlorides for the Direct Arylation of Benzylic Amines Mediated by Ruthenium(II)
Authors: Dastbaravardeh Navid , Schnürch Michael , Mihovilovic Marko D.
Published: March 2013

The ruthenium(II)‐catalyzed sp3 C–H bond arylation of benzylic amines with aryl halides is reported. In the present method, aryl iodides and, more importantly, also the cheaper aryl bromides and aryl chlorides can be applied as aryl sources. Additionally, the method does not require elaborate manipulations in a glove box and can be carried out in simple screw cap vials. Potassium pivalate proved to be beneficial for the transformation with aryl bromides or iodides as aryl source, but was not required for aryl chlorides. In the latter case, the addition of PPh3 led to high conversion. 3‐Methyl and 3‐phenyl pyridine were established as directing groups, and the substituent in the 3‐position represents a key structural feature for high conversion. The directing group can be cleaved after the transformation, which allows access to diarylmethylamines. Mechanistic studies were carried out and critically compared to mechanistic reports of related transformations.
Two‐dimensional nonlinear diffusive numerical simulation of geomorphic modifications to cinder cones
Authors: de' Michieli Vitturi Mattia , Arrowsmith J Ramón
Published: March 2013

The temporal evolution of simple landforms such as cinder cones by nonlinear diffusive processes is studied through the use of a new 2D numerical model using well‐established and accurate numerical mathematics and high‐resolution digital elevation models (DEMs). Extending 1D (profile) nonlinear diffusion analyses used in cinder cone, hillslope and fault scarp evolution studies, we have implemented a 2D numerical model with a spatially and temporally varying sediment transport rate coefficient scaled nonlinearly by the ratio of local slope to critical slope. The high accuracy and efficient numerical implementation are documented in the paper and the MATLAB toolkit developed is used to solve for the developmentof an initial 2D cone form. First, we examine the nonlinear transport rule and suggest a refinement that accounts explicitly for flux at threshold slopes. We find that the maximum diffusion (necessarily introduced in the numerical model to avoid infinite rates) at the critical slope controls the final morphology, especially approaching steady state. Secondly, solving the landscape evolution problem in 2D enables a natural accounting for sediment flux convergence or divergence in the profile. Thirdly, the boundary behavior of a given landscape element controls much of what happens in that domain and so we allow for arbitrary flux magnitude or elevation boundary conditions. Fourthly, landscapes are heterogeneous in their surface cover and so we allow for spatially and temporally varying transport rate k and we permit an arbitrary vertical displacement field within the model domain. To test the new formulation for the nonlinear term, the effect of variable diffusivity k and the numerical schemes implemented, we apply the model to cinder cones built on the flanks of Mount Etna in 2001 and 2002–2003. We explore the effects of DEM resolution with data from the 2001 cone and the utility of spatially variable diffusivity to explain the variation in erosion measured by differencing repeat light detection and ranging (LIDAR) surveys gathered in 2004 and 2007 over the 2002–2003 cone complex. Copyright © 2013 John Wiley & Sons, Ltd.
Exploring geochemical controls on weathering and erosion of convex hillslopes: beyond the empirical regolith production function
Authors: Lebedeva Marina I. , Brantley Susan L.
Published: March 2013

Landscape curvature evolves in response to physical, chemical, and biological influences that cannot yet be quantified in models. Nonetheless, the simplest models predict the existence of equilibrium hillslope profiles. Here, we develop a model describing steady‐state regolith production caused by mineral dissolution on hillslopes which have attained an equilibrium parabolic profile. When the hillslope lowers at a constant rate, the rate of chemical weathering is highest at the ridgetop where curvature is highest and the ridge develops the thickest regolith. This result derives from inclusion of all the terms in the mathematical definition of curvature. Including these terms shows that the curvature of a parabolic hillslope profile varies with distance from the ridge. The hillslope model (meter‐scale) is similar to models of weathering rind formation (centimeter‐scale) where curvature‐driven solute transport causes development of the thickest rinds at highly curved clast corners. At the clast scale, models fit observations.

Here, we similarly explore model predictions of the effect of curvature at the hillslope scale. The hillslope model shows that when erosion rates are small and vertical porefluid infiltration is moderate, the hill weathers at both ridge and valley in the erosive transport‐limited regime. For this regime, the reacting mineral is weathered away before it reaches the land surface: in other words, the model predicts completely developed element‐depth profiles at both ridge and valley. In contrast, when the erosion rate increases or porefluid velocity decreases, denudation occurs in the weathering‐limited regime. In this regime, the reacting mineral does not weather away before it reaches the land surface and simulations predict incompletely developed profiles at both ridge and valley. These predictions are broadly consistent with observations of completely developed element‐depth profiles along hillslopes denuding under erosive transport‐limitation but incompletely developed profiles along hillslopes denuding under weathering limitation in some field settings. Copyright © 2013 John Wiley & Sons, Ltd.
Assessment of the genotoxic potential of essential oil constituents by the Drosophila wing spot test
Authors: Mademtzoglou Despoina , Pavlidou Theodora , Bazioti Maria‐Georgia , Koutsonikou Chrysoula , Lioulia Elisavet , Akmoutsou Paraskevi , Drosopoulou Elena , Vokou Despoina , Mavragani‐Tsipidou Penelope
Published: March 2013

The genotoxic activity of 15 essential oil constituents used as flavouring agents or cosmetic ingredients was assessed at four concentrations (2.5, 5.0, 7.5 and 10 µl/ml) using the Drosophila melanogaster (Meigen) somatic mutation and recombination test, also known as the wing spot test. Ten of the compounds tested here, namely d‐neomenthol, nerol, 1‐octen‐3‐ol, α‐terpineol, neryl acetate, terpinyl acetate, p‐cymene, α‐pinene, β‐pinene, α‐terpinene were found free of mutagenic or recombinogenic activity, at the applied concentrations. On the other hand, for (1R)‐(−)‐myrtenol and linalyl acetate, weak positive effects were exhibited even at the lowest concentration. For myrtenyl acetate, weakly positive effects were recorded at the high but not at the low concentrations. The two hydrocarbons, γ‐terpinene and terpinolene, showed no genotoxic activity at the low concentrations, but at the high ones they significantly increased the frequency of mutant clones. Results clearly demonstrate differences in activity of positional isomers such as α‐ and γ‐terpinene and terpinolene. Our data suggest the need for re‐evaluating the safety of suspect compounds with cross‐checked genotoxicity studies and at a range of different concentrations. Copyright © 2013 John Wiley & Sons, Ltd.
About the formulation, verification and validation of the hypersonic flow solver Eilmer
Authors: Gollan R.J. , Jacobs P.A.
Published: March 2013

We describe the formulation of the gas dynamics and high‐temperature thermochemical modules of the Eilmer code, an open‐source Navier–Stokes solver for transient compressible flow in two and three dimensions. The core gas dynamics formulation is based on finite‐volume cells, and the thermochemical effects are handled with specialised updating schemes that are coupled into the overall time‐stepping scheme. Verification of the code is explored via a number of case studies that use analytic and semi‐analytic solutions as comparison. These include both smooth and shocked flows and are used to demonstrate the order of spatial accuracy of the code. Cases include manufactured solutions for rather abstract inviscid and viscous flow, an idealised detonation wave supported by a curved body, and the transient flow of an idealised but high‐performance shock tube. Validation of the inviscid gas dynamics and thermochemical models is then explored using data from a selection of experimental studies. These studies include ballistic range experiments with chemically‐inert noble gases and high‐temperature chemically‐reacting air. These comparisons show that the code performs well and they provide a lesson in considering a range of experimental data rather than relying upon isolated data points for validation. These verification and validation cases are described in full detail and will be useful for other code developers of high‐temperature compressible flow solvers. Copyright © 2013 John Wiley & Sons, Ltd.
A Geometric Framework for Evaluating Rare Variant Tests of Association
Authors: Liu Keli , Fast Shannon , Zawistowski Matthew , Tintle Nathan L.
Published: March 2013

The wave of next‐generation sequencing data has arrived. However, many questions still remain about how to best analyze sequence data, particularly the contribution of rare genetic variants to human disease. Numerous statistical methods have been proposed to aggregate association signals across multiple rare variant sites in an effort to increase statistical power; however, the precise relation between the tests is often not well understood. We present a geometric representation for rare variant data in which rare allele counts in case and control samples are treated as vectors in Euclidean space. The geometric framework facilitates a rigorous classification of existing rare variant tests into two broad categories: tests for a difference in the lengths of the case and control vectors, and joint tests for a difference in either the lengths or angles of the two vectors. We demonstrate that genetic architecture of a trait, including the number and frequency of risk alleles, directly relates to the behavior of the length and joint tests. Hence, the geometric framework allows prediction of which tests will perform best under different disease models. Furthermore, the structure of the geometric framework immediately suggests additional classes and types of rare variant tests. We consider two general classes of tests which show robustness to noncausal and protective variants. The geometric framework introduces a novel and unique method to assess current rare variant methodology and provides guidelines for both applied and theoretical researchers.
Association between depressive symptoms and metabolic syndrome in Japanese community‐dwelling older people: a cross‐sectional analysis from the baseline results of the Fujiwara‐kyo prospective cohort study
Authors: Morikawa Masayuki , Okamoto Nozomi , Kiuchi Kuniaki , Tomioka Kimiko , Iwamoto Junko , Harano Akihiro , Saeki Keigo , Fukusumi Masami , Hashimoto Kazumichi , Amano Nobuko , Hazaki Kan , Yanagi Motokazu , Iki Masayuki , Yamada Fumio , Kishimoto Toshifumi , Kurumatani Norio
Published: March 2013

Objective

Metabolic syndrome contains many risks for medical diseases such as cardiovascular disease and diabetes, which might precipitate depressive symptoms in the older people. However, the association between depressive symptoms and metabolic syndrome in Japanese community‐dwelling older people is unclear. This study was performed to answer this important question.

Methods

Cross‐sectional analyses were performed on 3796 community‐dwelling independent older people (≥65 years, 1911 men and 1885 women) from the 2007–2008 baseline examination of the Fujiwara‐kyo study, a prospective cohort study on successful aging. Depressive symptoms were assessed using the 15‐item short form of the Geriatric Depression Scale and metabolic syndrome was defined according to the 2005 International Diabetes Federation. Covariates were social supports, negative life events, health behavior, education, cognitive function, anthropometric status, and others. Multiple logistic regression analyses were performed to determine the relationships between depressive symptoms and these variables.

Results

The prevalence of depressive symptoms (Geriatric Depression Scale‐15 ≥6) and metabolic syndrome were 14.8% and 16.6%, respectively. Significant protective factors against depressive symptoms were higher education, more opportunity for drinking of alcohol, better social supports, and more walking daily. Metabolic syndrome was statistically associated with depressive symptoms (adjusted odds ratio = 1.32, 95% confidence interval = 1.03–1.68). Other risk factors significantly associated with depressive symptoms were sleep disturbance, visual or hearing impairment, and negative life events.

Conclusions

The present study showed an association between metabolic syndrome and depressive symptoms in ambulatory Japanese older people, as in western countries.
Revisiting the hysteresis effect in surface energy budgets
Authors: Sun Ting , Wang Zhi‐Hua , Ni Guang‐Heng
Published: March 2013

The hysteresis effect in diurnal cycles of net radiation Rn and ground heat flux G0 has been observed in many studies, while the governing mechanism remains vague. In this study, we link the phenomenology of hysteresis loops to the wave phase difference between the diurnal evolutions of various terms in the surface energy balance. Rn and G0 are parameterized with the incoming solar radiation and the surface temperature as two control parameters of the surface energy partitioning. The theoretical analysis shows that the vertical water flux W and the scaled ratio (net shortwave radiation to outgoing longwave radiation) play crucial roles in shaping hysteresis loops of Rn and G0. Comparisons to field measurements indicate that hysteresis loops for different land covers can be well captured by the theoretical model, which is also consistent with Camuffo‐Bernadi formula. This study provides insight into the surface partitioning and temporal evolution of the energy budget at the land surface.
Sensitivity of summer precipitation to tropical sea surface temperatures over East Asia in the GRIMs GMP
Authors: Chang Eun‐Chul , Yeh Sang‐Wook , Hong Song‐You , Wu Renguang
Published: March 2013

In this study, uncoupled atmospheric general circulation model experiments are conducted to examine the sensitivity of tropical Ocean basins from the Indian Ocean to the tropical Pacific Ocean on the summer precipitation variability over East Asia. It is remarkable that the Indian Ocean basin sea surface temperature (SST) and the tropical Pacific basin SST act on summer precipitation variability over Northeast Asia and southern China quite differently. That is, SST warming in the Indian Ocean largely contributes to the increase in the amount of summer precipitation over East Asia, which is in contrast to the warming of the western tropical Pacific Ocean. Our further analysis indicates that an altered large‐scale atmospheric circulation over the western tropical Pacific contributes to contrasting atmospheric motion over East Asia due to the tropics‐East Asia teleconnections, which results in changes in the amount of summer precipitation due to the warming of the Indian and western tropical Pacific Oceans.
High time resolution observations of HF cross‐modulation within the D region ionosphere
Authors: Langston J. , Moore R. C.
Published: March 2013

High‐frequency cross‐modulation is employed to probe the D region ionosphere during HF heating experiments at the High‐frequency Active Auroral Research Program (HAARP) observatory. We have adapted Fejer's well‐known cross‐modulation probing method to determine the extent of ionospheric conductivity modification in the D region ionosphere with high (5 μsec) time resolution. We demonstrate that the method can be used to analyze D region conductivity changes produced by HF heating both during the initial stages of heating and under steady state conditions. The sequence of CW probe pulses used allow the separation of cross‐modulation effects that occur as the probe pulse propagates upward and downward through the heated region. We discuss how this probing technique can be applied to benefit ELF/VLF wave generation experiments and ionospheric irregularities experiments at higher altitudes. We demonstrate that large phase changes equivalent to Doppler shift velocities >60 km/s can be imposed on HF waves propagating through the heated D region ionosphere.
Quasi‐stationary North Equatorial Undercurrent jets across the tropical North Pacific Ocean
Authors: Qiu Bo , Rudnick Daniel L. , Chen Shuiming , Kashino Yuji
Published: March 2013

Subthermocline circulation in the tropical North Pacific Ocean (2°N–30°N) is investigated using profiling float temperature‐salinity data from the International Argo and the Origins of the Kuroshio and Mindanao Current (OKMC) projects. Three well‐defined eastward jets are detected beneath the wind‐driven, westward flowing North Equatorial Current. Dubbed the North Equatorial Undercurrent (NEUC) jets, these subthermocline jets have a typical core velocity of 2–5 cms−1 and are spatially coherent from the western boundary to about 120°W across the North Pacific basin. Centered around 9°N, 13°N, and 18°N in the western basin, the NEUC jet cores tend to migrate northward by ∼4° in the eastern basin. Vertically, the cores of the southern, central, and northern NEUC jets reside on the 26.9, 27.2, and 27.3 σθsurfaces, respectively, and they tend to shoal to lighter density surfaces, by about 0.2 σθ, as the jets progress eastward.
On the impact angle of Hurricane Sandy's New Jersey landfall
Authors: Hall Timothy M. , Sobel Adam H.
Published: March 2013

Hurricane Sandy's track crossed the New Jersey coastline at an angle closer to perpendicular than any previous hurricane in the historic record, one of the factors contributing to record‐setting peak‐water levels in parts of New Jersey and New York. To estimate the occurrence rate of Sandy‐like tracks, we use a stochastic model built on historical hurricane data from the entire North Atlantic to generate a large sample of synthetic hurricanes. From this synthetic set we calculate that under long‐term average climate conditions, a hurricane of Sandy's intensity or greater (category 1+) makes NJ landfall at an angle at least as close to perpendicular as Sandy's at an average annual rate of 0.0014 yr–1 (95% confidence range 0.0007 to 0.0023); i.e., a return period of 714 years (95% confidence range 435 to 1429).
Prevalence of strong bottom currents in the greater Agulhas system
Authors: Cronin Meghan F. , Tozuka Tomoki , Biastoch Arne , Durgadoo Jonathan V. , Beal Lisa M.
Published: March 2013

Deep current meter data and output from two high‐resolution global ocean circulation models are used to determine the prevalence and location of strong bottom currents in the greater Agulhas Current system. The two models and current meter data are remarkably consistent, showing that benthic storms, with bottom currents greater than 0.2 m s−1, occur throughout the Agulhas retroflection region south of Africa more than 20% of the time. Furthermore, beneath the mean Agulhas Current core and the retroflection front, bottom currents exceed 0.2 m s−1 more than 50% of the time, while away from strong surface currents, bottom currents rarely exceed 0.2 m s−1. Implications for sediment transport are discussed and the results are compared to atmospheric storms. Benthic storms of this strength (0.2 m s−1) are comparable to a 9 m s−1 (Beaufort 5) windstorm, but scaling shows that benthic storms may be less effective at lifting and transporting sediment than dust storms.
Inflammation-Induced Hepatocellular Carcinoma Is Dependent on Ccr5 in Mice
Authors: Barashi Neta , Weiss Ido D. , Wald Ori , Wald Hanna , Beider Katia , Abraham Michal , Klein Shiri , Goldenberg Daniel , Axelrod Jonathan , Pikarsky Eli , Abramovitch Rinat , Zeira Evelyne , Galun Eithan , Peled Amnon
Published: March 2013

Human hepatocellular carcinoma (HCC) is an inflammation-induced cancer, which is the third-leading cause of cancer mortality worldwide. We investigated the role of the chemokine receptors, CCR5 and CCR1, in regulating inflammation and tumorigenesis in an inflammation-induced HCC model in mice. Multidrug resistance 2 gene (Mdr2)-knockout (Mdr2-KO) mice spontaneously develop chronic cholestatic hepatitis and fibrosis that is eventually followed by HCC. We generated two new strains from the Mdr2-KO mouse, the Mdr2:CCR5 and the Mdr2:CCR1 double knockouts (DKOs), and set out to compare inflammation and tumorigenesis among these strains. We found that in Mdr2-KO mice lacking the chemokine receptor, CCR5 (Mdr2:CCR5 DKO mice), but not CCR1 (Mdr2:CCR1 DKO), macrophage recruitment and trafficking to the liver was significantly reduced. Furthermore, in the absence of CCR5, reduced inflammation was also associated with reduced periductal accumulation of CD24+ oval cells and abrogation of fibrosis. DKO mice for Mdr2 and CCR5 exhibited a significant decrease in tumor incidence and size. Conclusions: Our results indicate that CCR5 has a critical role in both the development and progression of liver cancer. Therefore, we propose that a CCR5 antagonist can serve for HCC cancer prevention and treatment. (Hepatology 2013;53:1021–1030)
Talent or Not? Employee Reactions to Talent Identification
Authors: Björkman Ingmar , Ehrnrooth Mats , Mäkelä Kristiina , Smale Adam , Sumelius Jennie
Published: March 2013

In this article, we examine the effect of talent identification on employee attitudes. Building on social exchange theory, we analyze the association between employees' perceptions about whether or not they have been formally identified as “talent” and the following attitudinal outcomes: commitment to increasing performance demands, building skills, and supporting strategic priorities; identification with the unit and the multinational enterprise; and turnover intentions. Our analyses of 769 managers and professionals in nine Nordic multinational corporations reveal a number of differences between employees who perceive that they have been identified as “talent” and those who either perceive that they have not been identified or do not know whether they have been identified. We found only limited differences between the two latter categories.
Internal Commitment or External Collaboration? The Impact of Human Resource Management Systems on Firm Innovation and Performance
Authors: Zhou Yu , Hong Ying , Liu Jun
Published: March 2013

Complementing previous research that showed a positive effect of general human resource management (HRM) systems on general firm performance, this article undertakes an integrative approach to compare the main effects and examine the interaction effects of two particular HRM systems on influencing firm innovation and performance. Using data from 179 organizations in China, we found that both the commitment‐oriented system, which emphasized internal cohesiveness, and the collaboration‐oriented system, which was intended to build external connections, contributed to firm innovation and, subsequently, bottom‐line performance. We also found an attenuated interaction between the two HRM systems in predicting firm innovation. We employed a mediated‐moderation path model to extricate the relationships. Results suggested that organizations that implemented both HRM systems to promote innovation might face ambidexterity challenges. Ideas for future research and practical implications are discussed.
Colorectal cancers occurring after colonoscopy with polyp detection: Sites of polyps and sites of cancers
Authors: Brenner Hermann , Chang‐Claude Jenny , Jansen Lina , Seiler Christoph M. , Hoffmeister Michael
Published: March 2013

Colonoscopy with detection and removal of neoplasms strongly reduces risk of colorectal cancer (CRC). Nevertheless, CRCs occur after colonoscopic polypectomy. We assessed agreement beyond chance of location of polyps detected at colonoscopy and of subsequent CRCs to estimate the share of cancers that might be due to field effects or neoplasm recrudescence. In a population‐based case‐control study conducted in Germany (3,148 cases), detailed history and results of colonoscopies conducted within 10 years before cancer diagnosis were obtained by interview and from medical records. We determined the observed proportion of cancers for which a polyp had been detected at the same colorectal subsite at the preceding colonoscopy and compared it to the proportion expected by chance. A total of 155 cases with physician validated polyp detection at the preceding colonoscopy were identified. Among 148 cases with cancer restricted to a single subsite, 43 (29.1%) had a polyp detected in the same colorectal subsite at the preceding colonoscopy. Agreement of location of cancer occurrence and preceding polyp detection would have been expected by chance for 27 cases, and agreement beyond chance was estimated to account for 16 cases (10.8%, 95% confidence interval 2.7%–19.3%). Our study suggests that less than one of nine CRCs occurring within 10 years after colonoscopy with polyp detection may be due to field effects or polyp recrudescence.
Engraftment of low numbers of pediatric acute lymphoid and myeloid leukemias into NOD/SCID/IL2Rcγnull mice reflects individual leukemogenecity and highly correlates with clinical outcome
Authors: Woiterski Jeanette , Ebinger Martin , Witte Kai E. , Goecke Barbara , Heininger Vanessa , Philippek Martin , Bonin Michael , Schrauder Andre , Röttgers Silja , Herr Wolfgang , Lang Peter , Handgretinger Rupert , Hartwig Udo F. , André Maya C.
Published: March 2013

Although immortalized cell lines have been extensively used to optimize treatment strategies in cancer, the usefulness of such in vitro systems to recapitulate primary disease is limited. Therefore, the design of in vivo models ideally utilizing patient‐derived material is of critical importance. In this regard, NOD.Cg‐PrkdcscidIL2rgtmWjl/Sz (NSG) mice have been reported to provide superior engraftment rates. However, limited data exist on the validity of such a model to constitute a surrogate marker for clinical parameters. We studied primary and serial engraftment on more than 200 NSG mice with 54 primary pediatric B cell precursor acute lymphatic leukemia (B‐ALL), myeloid leukemia (AML) and T cell leukemia (T‐ALL) samples, characterized the leukemogenic profile and correlated engraftment kinetics with clinical outcome. Median time to engraftment was 7–10 weeks and 90% of the mice engrafted. Male recipients conferred significantly higher engraftment levels than female recipients (p ≤ 0.004). PCR‐based minimal residual disease marker expression and fluorescence in situ hybridization confirmed the presence of patient‐specific genetic aberrations in mice. Transcriptome cluster analysis of genes known to be important in the leukemogenesis of all three diseases revealed that well‐known tumor‐regulating genes were expressed to a comparable extent in mice and men. The extent of engraftment and overall survival of NSG mice highly correlated with the individual prognosis of B‐ALL, AML and T‐ALL patients. Thus, we propose an in vivo model that provides a valuable preclinical tool to explore the heterogeneity of leukemic disease and exploit patient‐tailored leukemia‐targeting strategies within multivariate analyses.
Shedding of endogenous MHC class I‐related chain molecules A and B from different human tumor entities: Heterogeneous involvement of the “a disintegrin and metalloproteases” 10 and 17
Authors: Chitadze Guranda , Lettau Marcus , Bhat Jaydeep , Wesch Daniela , Steinle Alexander , Fürst Daniel , Mytilineos Joannis , Kalthoff Holger , Janssen Ottmar , Oberg Hans‐Heinrich , Kabelitz Dieter
Published: March 2013

The interaction of the MHC class I‐related chain molecules A and B (MICA and MICB) with the corresponding natural killer group 2, member D (NKG2D) receptor triggers cytotoxic effector activity of natural killer cells and certain T‐cell subsets and provides a costimulatory signal for cytokine production. Thus, the presence of MICA/B on transformed cells contributes to tumor immunosurveillance. Consequently, the proteolytic cleavage of MICA/B is regarded as an important immune escape mechanism of various cancer cells. To investigate the molecular machinery responsible for the shedding of endogenous MICA/B, we analyzed different human tumor entities including mammary, pancreatic and prostate carcinomas. Flow cytometry and enzyme‐linked immunosorbent assay (ELISA) revealed that all tested tumor cells constitutively expressed MICA and MICB on the cell surface and also released NKG2D ligands into the supernatant. We demonstrate that the “a disintegrin and metalloproteases” (ADAMs) 10 and 17 are largely responsible for the generation of soluble MICA/B. Pharmacological inhibition of metalloproteases reduced the level of released MICA/B and increased cell surface expression. Studies using RNA interference not only revealed a prominent role of ADAM10 and ADAM17 in NKG2D ligand shedding but also a tumor cell‐specific role of ADAM10 and/or ADAM17 in shedding of MICA or MICB. Moreover, we report that in the prostate carcinoma cell line PC‐3, MICA was not shed at all but rather was secreted in exosomes. These data indicate that the release of NKG2D ligands from individual tumor entities is by far more complex than suggested in previously reported MICA/B transfection systems.
AGRICULTURAL/URBAN/ENVIRONMENTAL WATER SHARING IN THE WESTERN UNITED STATES: CAN ENGINEERS ENGAGE SOCIAL SCIENCE FOR SUCCESSFUL SOLUTIONS?
Authors: Smith Marylou M. , Smith Stephen W.
Published: March 2013

Throughout the world, demand exceeds supply when it comes to water for agriculture, urban needs and a healthy environment. In the western United States water is being permanently transferred from agriculture, putting food security and the viability of rural communities at risk. The authors of this paper are separately and jointly involved in projects and studies to determine how water might be shared between agricultural, urban, and environmental sectors in ways that effectively stretch supplies, with benefits to all.

Engineering solutions will be necessary. But legal and institutional changes and alternative approaches to achieve economic and other social benefits, must be addressed as well. Stakeholders from all sectors must be fully engaged at all levels.

The authors present a water‐sharing model under development in the South Platte River Basin of Colorado in the western United States. They discuss the convening in 2010 of western United States water leaders from agricultural, urban, and environmental sectors to develop recommendations for western governors for overcoming obstacles to multi‐sector water sharing. The authors draw from examples provided by international academics and practitioners to show that our greatest challenge in this water balance puzzle is not technological but sociological. Copyright © 2013 John Wiley & Sons, Ltd.
In vivo evaluation of resorbable bone graft substitutes in beagles: Histological properties
Authors: Shih Tsai‐Chin , Teng Nai‐Chia , Wang Peter‐D. , Lin Che‐Tong , Yang Jen‐Chang , Fong Sheng‐Wei , Lin Hsi‐Kuei , Chang Wei‐Jen
Published: March 2013

Calcium phosphate cement (CPC) is a promising material for use in minimally invasive surgery for bone defect repairs due to its bone‐like apatitic final setting product, biocompatibility, bioactivity, self‐setting characteristics, low setting temperature, adequate stiffness, and easy shaping into complicated geometrics. However, even though CPC is stable in vivo, the resorption rate of this bone cement is very slow and its long setting time poses difficulties for clinical use. Calcium sulfate dehydrate (CSD) has been used as a filler material and/or as a replacement for cancellous bone grafts due to its biocompatibility. However, it is resorbed too quickly to be optimal for bone regeneration. This study examines the invivo response of a hydroxyapatite (HA), [apatitic phase (AP)]/calcium sulfate (CSD) composite using different ratios in the mandibular premolar sockets of beagles. The HA (AP)/CSD composite materials were prepared in the ratios of 30/70, 50/50, and 70/30 and then implanted into the mandibular premolar sockets for terms of 5 and 10 weeks. The control socket was left empty. The study shows better new bone morphology and more new bone area in the histological and the histomorphometric study of the HA (AP)/CSD in the 50/50 ratio. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.