bluuebunny/crossref_metadata_2025 huggingface dataset:
Dorsorostral Snout Muscles in the Rat Subserve Coordinated Movement for Whisking and Sniffing
Authors: Haidarliu Sebastian , Golomb David , Kleinfeld David , Ahissar Ehud
Published: May 2012

Histochemical examination of the dorsorostral quadrant of the rat snout revealed superficial and deep muscles that are involved in whisking, sniffing, and airflow control. The part of M. nasolabialis profundus that acts as an intrinsic (follicular) muscle to facilitate protraction and translation of the vibrissae is described. An intraturbinate and selected rostral‐most nasal muscles that can influence major routs of inspiratory airflow and rhinarial touch through their control of nostril configuration, atrioturbinate and rhinarium position, were revealed. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.
The free‐radical theory of ageing – older, wiser and still alive
Authors: Kirkwood Thomas B. L. , Kowald Axel
Published: May 2012

The continuing viability of the free‐radical theory of ageing has been questioned following apparently incompatible recent results. We show by modelling positional effects of the generation and primary targets of reactive oxygen species that many of the apparently negative results are likely to be misleading. We conclude that there is instead a need to look more closely at the mechanisms by which free radicals contribute to age‐related dysfunction in living systems. There also needs to be deeper understanding of the dynamics of accumulation and removal of the various kinds of molecular damage, in particular mtDNA mutations. Finally, the expectation that free‐radical damage on its own might cause ageing needs to be relinquished in favour of the recognition that the free‐radical theory is just one of the multiple mechanisms driving the ageing process.
Dose–response relationship from longitudinal data with response‐dependent dose modification using likelihood methods
Authors: Funatogawa Ikuko , Funatogawa Takashi
Published: May 2012

In some clinical trials or clinical practice, the therapeutic agent is administered repeatedly, and doses are adjusted in each patient based on repeatedly measured continuous responses, to maintain the response levels in a target range. Because a lower dose tends to be selected for patients with a better outcome, simple summarizations may wrongly show a better outcome for the lower dose, producing an incorrect dose–response relationship. In this study, we consider the dose–response relationship under these situations. We show that maximum‐likelihood estimates are consistent without modeling the dose‐modification mechanisms when the selection of the dose as a time‐dependent covariate is based only on observed, but not on unobserved, responses, and measurements are generated based on administered doses. We confirmed this property by performing simulation studies under several dose‐modification mechanisms. We examined an autoregressive linear mixed effects model. The model represents profiles approaching each patient's asymptote when identical doses are repeatedly administered. The model takes into account the previous dose history and provides a dose–response relationship of the asymptote as a summary measure. We also examined a linear mixed effects model assuming all responses are measured at steady state. In the simulation studies, the estimates of both the models were unbiased under the dose modification based on observed responses, but biased under the dose modification based on unobserved responses. In conclusion, the maximum‐likelihood estimates of the dose–response relationship are consistent under the dose modification based only on observed responses.
On ROC analysis with nonbinary reference standard
Authors: Shiu Shang-Ying , Gatsonis Constantine
Published: May 2012

Statistical methods for the evaluation of the accuracy of diagnostic tests usually assume a binary true disease status. However, this assumption may not be realistic in practical settings in which “disease” is defined by dichotomizing continuous or ordinal categorical measures using a pre‐specified threshold value. In this paper, we focus on the analysis of studies in which both the diagnostic test and the reference standard are reported as continuous measures. We propose a semiparametric model for estimating the sensitivity, specificity, and the ROC curve as functions of reference standard thresholds. Under suitable order restrictions on the mean of the test result variable, fitting is done via two alternative approaches: isotonic regression and monotone smoothing splines. The model provides the basis to assess the effect of varying reference standard threshold on the performance of a diagnostic test. An example to evaluate the ability of the maximal SUV‐lean (standardized uptake value normalized to lean body mass) in predicting axillary node involvement in women diagnosed with breast cancer is presented.
State‐of‐the‐art in downstream processing of monoclonal antibodies: Process trends in design and validation
Authors: Marichal‐Gallardo P. A. , Álvarez M. M.
Published: May 2012

Monoclonal antibodies (mAbs) are the most important family of biopharmaceutical compounds in terms of market share. At present, 30 mAbs have been approved and are now commercialized for therapeutic purposes. mAbs are typically produced by mammalian cell culture in bioreactors that range in scale of 1–20 m3. Regardless of scale, from laboratory to commercial settings, the recovery and purification of mAbs present important challenges. Depending on the scale, the particular product, and the type of production process (bioreactor operation, process time, complexity of the culture media, cell density, etc.), many possible downstream configurations are possible and have been used. In this contribution, we review each type of unit operation that forms a downstream train for mAb production. We provide information regarding typical operation settings and critical variables for centrifugation, ultrafiltration, affinity chromatography, ion exchange chromatography, and viral removal operations. In addition, we discuss some important considerations required for the formulation of drugs based on mAbs. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 28: 899–916, 2012
Decisional tool to assess current and future process robustness in an antibody purification facility
Authors: Stonier Adam , Simaria Ana Sofia , Smith Martin , Farid Suzanne S.
Published: May 2012

Increases in cell culture titers in existing facilities have prompted efforts to identify strategies that alleviate purification bottlenecks while controlling costs. This article describes the application of a database‐driven dynamic simulation tool to identify optimal purification sizing strategies and visualize their robustness to future titer increases. The tool harnessed the benefits of MySQL to capture the process, business, and risk features of multiple purification options and better manage the large datasets required for uncertainty analysis and optimization. The database was linked to a discrete‐event simulation engine so as to model the dynamic features of biopharmaceutical manufacture and impact of resource constraints. For a given titer, the tool performed brute force optimization so as to identify optimal purification sizing strategies that minimized the batch material cost while maintaining the schedule. The tool was applied to industrial case studies based on a platform monoclonal antibody purification process in a multisuite clinical scale manufacturing facility. The case studies assessed the robustness of optimal strategies to batch‐to‐batch titer variability and extended this to assess the long‐term fit of the platform process as titers increase from 1 to 10 g/L, given a range of equipment sizes available to enable scale intensification efforts. Novel visualization plots consisting of multiple Pareto frontiers with tie‐lines connecting the position of optimal configurations over a given titer range were constructed. These enabled rapid identification of robust purification configurations given titer fluctuations and the facility limit that the purification suites could handle in terms of the maximum titer and hence harvest load. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 28: 1019–1028, 2012
Guanidines: Highly Nucleophilic Organocatalysts
Authors: Maji Biplab , Stephenson David S. , Mayr Herbert
Published: May 2012

The nucleophile‐specific parameters N and sN, as defined by log k20 °C=sN(N+E) have been derived for the guanidines 1 a–h from the second‐order rate constants of their reactions with diarylcarbenium tetrafluoroborates in CH2Cl2 at 20 °C. The applicability of these parameters for predicting rate constants of the reactions of guanidines with ordinary Michael acceptors has been demonstrated. Comparison with other organocatalysts shows that 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene, the strongest nucleophile of this series, exceeds the nucleophilicity of diazabicyclononene and 4‐(dimethylamino)pyridine by factors of 3 to 7.
FimH Antagonists: Structure–Activity and Structure–Property Relationships for Biphenyl α‐D‐Mannopyranosides
Authors: Pang Lijuan , Kleeb Simon , Lemme Katrin , Rabbani Said , Scharenberg Meike , Zalewski Adam , Schädler Florentina , Schwardt Oliver , Ernst Beat
Published: May 2012

Urinary tract infections (UTIs) are caused primarily by uropathogenic Escherichia coli (UPEC), which encode filamentous surface‐adhesive organelles called type 1 pili. FimH is located at the tips of these pili. The initial attachment of UPEC to host cells is mediated by the interaction of the carbohydrate recognition domain (CRD) of FimH with oligomannosides on urothelial cells. Blocking these lectins with carbohydrates or analogues thereof prevents bacterial adhesion to host cells and therefore offers a potential therapeutic approach for prevention and/or treatment of UTIs. Although numerous FimH antagonists have been developed so far, few of them meet the requirement for clinical application due to poor pharmacokinetics. Additionally, the binding mode of an antagonist to the CRD of FimH can switch from an in‐docking mode to an out‐docking mode, depending on the structure of the antagonist. In this communication, biphenyl α‐D‐mannosides were modified to improve their binding affinity, to explore their binding mode, and to optimize their pharmacokinetic properties. The inhibitory potential of the FimH antagonists was measured in a cell‐free competitive binding assay, a cell‐based flow cytometry assay, and by isothermal titration calorimetry. Furthermore, pharmacokinetic properties such as log D, solubility, and membrane permeation were analyzed. As a result, a structure–activity and structure–property relationships were established for a series of biphenyl α‐D‐mannosides.
Pupil and salivary indicators of autonomic dysfunction in autism spectrum disorder
Authors: Anderson Christa J. , Colombo John , Unruh Kathryn E.
Published: May 2012

Dysregulated tonic pupil size has been reported in autism spectrum disorder (ASD). Among the possible sources of this dysregulation are disruptions in the feedback loop between norepinephrine (NE) and hypothalamic systems. In the current study, we examined afternoon levels of salivary alpha‐amylase (sAA, a putative correlate of NE) and cortisol (used to assess stress‐based responses) in two independent samples of children with ASD. We found a larger pupil size and lower sAA levels in ASD, compared to typical and clinical age‐matched controls. This was substantiated at the individual level, as sAA levels were strongly correlated with tonic pupil size. Relatively little diurnal variation in sAA taken in the home environment in the ASD group was also observed, while typical controls showed a significant linear increase throughout the day. Results are discussed in terms of potential early biomarkers and the elucidation of underlying neural dysfunction in ASD. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 465–482, 2013
Total Syntheses of (–)‐α‐Kainic Acid
Authors: Stathakis Christos I. , Yioti Efthymia G. , Gallos John K.
Published: May 2012

Kainoid amino acids are a unique group of non‐proteinogenic pyrrolidinedicarboxylic acids. The parent member, (–)‐α‐kainic acid (originally known as digenic acid), has attracted considerable interest, largely because of its neuroexcitatory properties, as well as its pronounced insecticidal and anthelmitic activities. Because these activities are strongly due to its stereochemistry, (–)‐α‐kainic acid represents a considerable synthetic challenge, and many groups have therefore reported syntheses of kainic acids, as well as of kainoid analogues. This article is intended to review the total synthesis of kainic acid from 1996 until the end of 2011.
An Efficient Suzuki–Miyaura Coupling of Aryl Sulfamates and Boronic Acids Catalyzed by NiCl2(dppp)
Authors: Chen Guo‐Jun , Han Fu‐She
Published: May 2012

The Suzuki–Miyaura cross‐coupling of aryl sulfamates and boronic acids was investigated by using [1,3‐bis(diphenylphosphanyl)propane]nickel(II) chloride {NiCl2(dppp)} as the catalyst. The results showed that NiCl2(dppp) is a highly active and general catalyst that allows effective Suzuki–Miyaura cross‐coupling of aryl sulfamates with a slight excess amount of the boronic acid (1.2 equiv.) in the presence of a low catalyst loading (generally 1.0–1.5 mol‐%). The method also displays broad generality not only to various aryl sulfamates, but also to an array of boronic acids. Furthermore, various functional groups are tolerated. These apparent advantages make NiCl2(dppp) a practical and reliable catalyst system for the Suzuki–Miyaura coupling of aryl sulfamates.
Evaluating competing hypotheses for the origin and dynamics of river anastomosis
Authors: Kleinhans M. G. , de Haas T. , Lavooi E. , Makaske B.
Published: May 2012

Anastomosing rivers have multiple interconnected channels that enclose flood basins. Various theories potentially explain this pattern, including an increased discharge conveyance and sediment transport capacity of multiple channels, deltaic branching, avulsion forced by base‐level rise, or a tendency to avulse due to upstream sediment overloading. The former two imply a stable anabranching channel pattern, whereas the latter two imply disequilibrium and evolution towards a single‐channel pattern in the absence of avulsion. Our objective is to test these hypotheses on morphodynamic scenario modelling and data of a well‐documented case study: the upper Columbia River.

Proportions of channel and floodplain sediments along the river valley were derived from surface mapping. Initial and boundary conditions for the modelling were derived from field data. A 1D network model was built based on gradually varied flow equations, sediment transport prediction, mass conservation, transverse slope and spiral meander flow effects at the bifurcations.

The number of channels and crevasse splays decreases in a downstream direction. Also, measured sediment transport is higher at the upstream boundary than downstream. These observations concur with bed sediment overloading from upstream, which can have caused channel aggradation above the surrounding floodplain and subsequent avulsion. The modelling also indicates that avulsion was likely caused by upstream overloading.

In the model, multi‐channel systems inevitably evolve towards single‐channel systems within centuries. The reasons are that symmetric channel bifurcations are inherently unstable, while confluenced channels have relatively less friction than two parallel channels, so that more discharge is conveyed through the path with more confluences and less friction. Furthermore, the present longitudinal profile curvature of the valley could only be reproduced in the model by temporary overfeeding.

We conclude that this anastomosing pattern is the result of time‐varying sediment overloading and is not an equilibrium pattern feature, and suggest this is valid for many anastomosing rivers. Copyright © 2012 John Wiley & Sons, Ltd.
The Intraday and Overnight Behavior of SPY Options and Adjusted Delta Hedging
Authors: Simon David P.
Published: May 2012

This study examines the intraday and overnight performance of S&P 500 exchange traded fund (SPY) put options from May 2005 through April 2010. The basic findings indicate that deviations of put option price changes from projections based on Black–Scholes–Merton (BSM) deltas are often substantial and can be explained mostly by the negative relation between implied volatility and SPY returns. The study then examines the impact of adjusting deltas with out of sample estimates of the relationship between implied volatility and SPY returns on the profitability of intraday and overnight delta hedged short SPY put option positions. The findings indicate that these adjustments lower P&L volatility and improve measures of downside risk relative to both BSM deltas and deltas adjusted with the volatility skew. © 2012 Wiley Periodicals, Inc. Jrl Fut Mark 33:443‐468, 2013
PI3K/Akt pathway mediates high glucose‐induced lipid accumulation in human renal proximal tubular cells via spliced XBP‐1
Authors: Zhao Song , Zhu Lin , Duan Huijun , Liu Shuxia , Liu Qingjuan , Liu Wei , Hao Jun
Published: May 2012

In the present study, we investigated the effect of X‐box‐binding protein‐1 (XBP‐1) splicing on lipogenesis in high glucose‐stimulated human renal proximal tubular cell line (HKC). The results revealed that high glucose promoted the splicing of XBP‐1, concomitant with up‐regulation of lipogenic genes including fatty acid synthase, acetyl‐CoA carboxylase, adipocyte differentiation‐related protein, and cellular triglyceride. Again, silence of XBP‐1 with shRNA vector inhibited high glucose‐caused increased lipogenesis. Furthermore, we confirmed that the inhibition of phosphotidyl inositol 3‐kinase (PI3K)/Akt pathway with LY294002 or Akt shRNA vector blocked the effect of high glucose on XBP‐1 splicing and cellular triglyceride. These above data suggest that spliced XBP‐1 mediates high glucose‐induced lipid accumulation in HKC cells and PI3K/Akt pathway may be involved in high glucose‐caused XBP‐1 splicing. J. Cell. Biochem. 113: 3288–3298, 2012. © 2012 Wiley Periodicals, Inc.
Hypoxia modulation of peroxisome proliferator‐activated receptors (PPARs) in human glioblastoma stem cells. Implications for therapy
Authors: Galzio Renato , Cristiano Loredana , Fidoamore Alessia , Cifone Maria Grazia , Benedetti Elisabetta , Cinque Benedetta , Menghini Paola , Raysi Dehcordi Sohelia , Ippoliti Rodolfo , Giordano Antonio , Cimini Annamaria
Published: May 2012

Gliobastoma (GB), the most common adult brain tumor, infiltrates normal brain area rendering impossible the complete surgical resection, resulting in a poor median survival (14–15 months), despite the aggressive multimodality treatments post‐surgery, such as radiation and chemo‐therapy. GB is characterized by hypoxic and necrotic regions due to a poorly organized tumor vascularization, leading to inadequate blood supply and consequently to hypoxic and necrotic areas. We have previously shown that, under hypoxia GB primary cells increased the expression of stemness markers as well as the expression of the nuclear receptor peroxisome proliferator‐activated receptor α (PPARα) and also the crucial role played by PPARs in mouse neural stem cells maintenance and differentiation. Due to the importance of lipid signaling in cell proliferation and differentiation, in this work, we analyzed the expression of PPARs in GB neurospheres both in normoxic and hypoxic conditions. The results obtained suggest a differential regulation of the three PPARs by hypoxia, thus indicating a possible therapeutic strategy to counteract GB recurrencies. J. Cell. Biochem. 113: 3342–3352, 2012. © 2012 Wiley Periodicals, Inc.
Interleukin‐11 Increases Cell Motility and Up‐Regulates Intercellular Adhesion Molecule‐1 Expression in Human Chondrosarcoma Cells
Authors: Li Te‐Mao , Wu Chi‐Ming , Huang Hsin‐Chih , Chou Pei‐Chi , Fong Yi‐Chin , Tang Chih‐Hsin
Published: May 2012

Interleukin‐11 (IL‐11) was originally identified as the cytokine that could induce the proliferation of human cells. Recent studies have shown that IL‐11 plays a critical role in tumor growth, angiogenesis, and metastasis. Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. However, the effects of IL‐11 on human chondrosarcoma cells are largely unknown. Here, we found that IL‐11 increased the migration and expression of intercellular adhesion molecule‐1 (ICAM)‐1 in human chondrosarcoma cells. We also found that human chondrosarcoma tissues had significant expression of the IL‐11 which was higher than that in primary chondrocytes. The phosphatidylinositol 3‐kinase (PI3K), Akt, and NF‐κB pathways were activated by IL‐11 treatment, and the IL‐11‐induced expression of ICAM‐1 and migration activity were inhibited by the specific inhibitors and mutant forms of PI3K, Akt, and NF‐κB cascades. Taken together, our results indicate that IL‐11 enhanced the migration of the chondrosarcoma cells by increasing ICAM‐1 expression through the IL‐11Rα receptor, PI3K, Akt, and NF‐κB signal transduction pathway. J. Cell. Biochem. 113: 3353–3362, 2012. © 2012 Wiley Periodicals, Inc.
Mesenchymal stem cell‐derived interleukin‐6 and vascular endothelial growth factor promote breast cancer cell migration
Authors: De Luca Antonella , Lamura Luana , Gallo Marianna , Maffia Veronica , Normanno Nicola
Published: May 2012

Several different cytokines and growth factors secreted by mesenchymal stem cells (MSCs) have been hypothesized to play a role in breast cancer progression. By using a small panel of breast cancer cell lines (MCF‐7, T47D, and SK‐Br‐3 cells), we analyzed the role of interleukin‐6 (IL‐6) and vascular endothelial growth factor A (VEGF) in the cross‐talk between MSCs and breast cancer cells. We performed migration assays in which breast cancer cells were allowed to migrate in response to conditioned medium from MSCs (MSCs‐CM), in absence or in presence of the anti‐VEGF antibody bevacizumab or an anti‐IL‐6 antibody, alone or in combination. We found that anti‐VEGF and anti‐IL‐6 antibodies inhibited the migration of breast cancer cells and that the combination had an higher inhibitory effect. We next evaluated the effects of recombinant VEGF and IL‐6 proteins on breast cancer cell growth and migration. IL‐6 and VEGF had not significant effects on the proliferation of breast carcinoma cells. In contrast, both VEGF and IL‐6 significantly increased the ability to migrate of MCF‐7, T47D and SK‐Br‐3 cells, with the combination showing a greater effect as compared with treatment with a single protein. The combination of VEGF and IL‐6 produced in breast cancer cells a more significant and more persistent activation of MAPK, AKT, and p38MAPK intracellular signaling pathways. These results suggest that MSC‐secreted IL‐6 and VEGF may act as paracrine factors to sustain breast cancer cell migration. J. Cell. Biochem. 113: 3363–3370, 2012. © 2012 Wiley Periodicals, Inc.
Synthesis of Oximes with NH2OH.HCl/DOWEX(R)50WX4 System
Authors: Setamdideh Davood , Khezri Behrooz , Esmaeilzadeh Seyran
Published: May 2012

The oximation of a variety of carbonyl compounds was efficiently carried out with DOWEX(R)50WX4/NH2OH·HCl system. The reactions were performed in ethanol to give Z‐aldoximation isomers of aldehydes and E‐oximaton of acetophenone derivatives in a perfect selectively. The oximation of compounds with two carbonyl groups was carried out selectively on one carbonyl moiety. Also, the oximation of aldehydes over ketones has been accomplished successfully by this system.
Differential Pulse Anodic Stripping Voltammetric Determination of Bismuth(III) with 1‐(2‐Pyridylazo)‐2‐naphthol and Ionic Liquid Modified Carbon Paste Electrode
Authors: Ruan Chengxiang , Li Tongtong , Ju Xiaomei , Liu Hejian , Lou Jin , Sun Wei
Published: May 2012

In this paper 1‐(2‐pyridylazo)‐2‐naphthol (PAN) and ionic liquid 1‐ethyl‐3‐methylimidazolium tetrafluoroborate (EMIMBF4) were mixed with graphite powder to get a modified carbon paste electrode (PAN‐IL‐CPE), which was further used for the sensitive determination of bismuth(III). By the co‐contribution of the formation of PAN‐Bi complex and the accumulation effect of IL, more bismuth(III) was electrodeposited on the surface of the PAN‐IL‐CPE. Then the reduced Bi was oxidized and detected by differential pulse anodic stripping voltammetry (DPASV) with the oxidation peak appeared at 0.17 V (vs. SCE). Under the optimal conditions the oxidation peak current was proportional to the bismuth(III) concentration in the range from 0.04 to 7.5 μmol L−1 with the detection limit as 3.9 nmol L−1. The proposed method was successfully applied to the stomach medicine sample detection with good recovery.
Detachments of Amalgamated 3‐Uniform Hypergraphs Factorization Consequences
Authors: Bahmanian M. Amin
Published: May 2012

A is a hypergraph obtained from by splitting some or all of its vertices into more than one vertex. Amalgamating a hypergraph can be thought of as taking , partitioning its vertices, then for each element of the partition squashing the vertices to form a single vertex in the amalgamated hypergraph . In this paper, we use Nash‐Williams lemma on laminar families to prove a detachment theorem for amalgamated 3‐uniform hypergraphs, which yields a substantial generalization of previous amalgamation theorems by Hilton, Rodger, and Nash‐Williams.

To demonstrate the power of our detachment theorem, we show that the complete 3‐uniform n‐partite multihypergraph can be expressed as the union of k edge‐disjoint factors, where for , is ‐regular, if and only if:

for all ,

for each i, , and

.
A Two‐Year Prospective Study of Psychache and its Relationship to Suicidality Among High‐Risk Undergraduates
Authors: Troister Talia , Holden Ronald R.
Published: May 2012

Objectives

Edwin Shneidman's theory of suicide was tested by examining the relationships of depression, hopelessness, and psychache with suicide ideation, longitudinally.

Design

Forty‐one high‐risk students who were suicide ideators completed questionnaires measuring depression, hopelessness, psychache, and suicide ideation at baseline and 2 years later.

Results

Regression analyses showed that at baseline and at follow‐up, psychache was the only unique contributor to the statistical prediction of suicide ideation. When examining change over time, change in psychache was the only factor that added significant unique variance to the prediction of change in suicide ideation.

Conclusions

Results support Shneidman's assertion that other psychological factors, such as depression and hopelessness, are only important to suicide insofar as their relationship with psychache, and that psychache and suicide ideation co‐vary over time.
Cyclical Parthenogenesis and Viviparity in Aphids as Evolutionary Novelties
Authors: DAVIS GREGORY K.
Published: May 2012

Evolutionary novelties represent challenges to biologists, particularly those who would like to understand the developmental and genetic changes responsible for their appearance. Most modern aphids possess two apparent evolutionary novelties: cyclical parthenogenesis (a life cycle with both sexual and asexual phases) and viviparity (internal development and live birth of progeny) in their asexual phase. Here I discuss the evolution of these apparent novelties from a developmental standpoint. Although a full understanding of the evolution of cyclical parthenogenesis and viviparity in aphids can seem a daunting task, these complex transitions can at least be broken down into a handful of steps. I argue that these should include the following: a differentiation of two developmentally distinct oocytes; de novo synthesis of centrosomes and modification of meiosis during asexual oogenesis; a loss or bypass of any cell cycle arrest and changes in key developmental events during viviparous oogenesis; and a change in how mothers specify the sexual vs. asexual fates of their progeny. Grappling with the nature of such steps and the order in which they occurred ought to increase our understanding and reduce the apparent novelty of complex evolutionary transitions. J. Exp. Zool. (Mol. Dev. Evol.) 318B:448–459, 2012. © 2012 Wiley Periodicals, Inc.
Testing Inferences in Developmental Evolution: The Forensic Evidence Principle
Authors: LARSSON HANS C. E. , WAGNER GÜNTER P.
Published: May 2012

Developmental evolution (DE) examines the influence of developmental mechanisms on biological evolution. Here we consider the question: “what is the evidence that allows us to decide whether a certain developmental scenario for an evolutionary change is in fact “correct” or at least falsifiable?” We argue that the comparative method linked with what we call the “forensic evidence principle” (FEP) is sufficient to conduct rigorous tests ofDEscenarios. TheFEPstates that different genetically mediated developmental causes of an evolutionary transformation will leave different signatures in the development of thederivedcharacter. Although similar inference rules have been used in practically every empirical science, we expand this approach here in two ways: (1) we justify the validity of this principle with reference to a well‐known result from mathematical physics, known as the symmetry principle, and (2) propose a specific form of theFEPforDE: given two or more developmental explanations for a certain evolutionary event, say an evolutionary novelty, then the evidence discriminating between these hypotheses will be found in the most proximal internal drivers of the derived character. Hence, a detailed description of the ancestral and derived states, and their most proximal developmental drivers are necessary to discriminate between various evolutionary developmental hypotheses. We discuss how this stepwise order of testing is necessary, establishes a formal test, and how skipping this order of examination may violate a more accurate examination ofDE. We illustrate the approach with an example from avian digit evolution. J. Exp. Zool. (Mol. Dev. Evol.) 318B:489–500, 2012. © 2012 Wiley Periodicals, Inc.
Towards water compatible MIPs for sensing in aqueous media
Authors: Horemans F. , Weustenraed A. , Spivak D. , Cleij T. J.
Published: May 2012

When synthesizing molecularly imprinted polymers (MIPs), a few fundamental principles should be kept in mind. There is a strong correlation between porogen polarity, MIP microenvironment polarity and the imprinting effect itself. The combination of these parameters eventually determines the overall binding behavior of a MIP in a given solvent. In addition, it is shown that MIP binding is strongly influenced by the polarity of the rebinding solvent. Because the use of MIPs in biomedical environments is of considerable interest, it is important that these MIPs perform well in aqueous media. In this article, various approaches are explored towards a water compatible MIP for the target molecule l‐nicotine. To this end, the imprinting effect together with the MIP matrix polarity is fine‐tuned during MIP synthesis. The binding behavior of the resulting MIPs is evaluated by performing batch rebinding experiments that makes it possible to select the most suitable MIP/non‐imprinted polymer couple for future application in aqueous environments. One method to achieve improved compatibility with water is referred to as porogen tuning, in which porogens of varying polarities are used. It is demonstrated that, especially when multiple porogens are mixed, this approach can lead to superior performance in aqueous environments. Another method involves the incorporation of polar or non‐polar comonomers in the MIP matrix. It is shown that by carefully selecting these monomers, it is also possible to obtain MIPs, which can selectively bind their target in water. Copyright © 2012 John Wiley & Sons, Ltd.
Wear resistant performance of highly cross‐linked and annealed ultra‐high molecular weight polyethylene against ceramic heads in total hip arthroplasty
Authors: Sato Taishi , Nakashima Yasuharu , Akiyama Mio , Yamamoto Takuaki , Mawatari Taro , Itokawa Takashi , Ohishi Masanobu , Motomura Goro , Hirata Masanobu , Iwamoto Yukihide
Published: May 2012

The purpose of this study was to examine the effects of ceramic femoral head material, size, and implantation periods on the wear of annealed, cross‐linked ultra‐high molecular weight polyethylene (UHMWPE) (XLPE) in total hip arthroplasty compared to non‐cross‐linked conventional UHMWPE (CPE). XLPE was fabricated by cross‐linking with 60 kGy irradiation and annealing. Femoral heads made from zirconia and alumina ceramics and cobalt–chrome (CoCr) of 22 or 26 mm diameter were used. In this retrospective cohort study, the femoral head penetration into the cup was measured digitally on radiographs of 367 hips with XLPE and 64 hips with CPE. The average follow‐up periods were 6.3 and 11.9 years, respectively. Both XLPE creep and wear rates were significantly lower than those of CPE (0.19 mm vs. 0.44 mm, 0.0001 mm/year vs. 0.09 mm/year, respectively). Zirconia displayed increased wear rates compared to alumina in CPE; however, there was no difference among head materials in XLPE (0.0008, 0.00007, and −0.009 mm/year for zirconia, alumina, and CoCr, respectively). Neither head size or implantation period impacted XLPE wear. In contrast to CPE, XLPE displayed low wear rates surpassing the effects of varying femoral head material, size, implantation period, and patient demographics. Further follow‐up is required to determine the long‐term clinical performance of the annealed XLPE. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:2031–2037, 2012
Implications of goat eradication on the survivorship of the Galapagos hawk
Authors: Rivera‐Parra Jose L. , Levenstein Kenneth M. , Bednarz James C. , Vargas F. Hernan , Carrion Victor , Parker Patricia G.
Published: May 2012

Non‐native mammals cause ecological disasters in island ecosystems and their eradication is usually considered beneficial to native biodiversity. Goats (Capra hircus) were introduced to Santiago Island, Galapagos, Ecuador, in the early 1800s, and their numbers increased to about 100,000 by 1970. A goat eradication campaign initiated in 2002 was successful, eliminating the last individuals in 2006. To evaluate the effects of goat eradication, between 1998 and 2010 we studied the Galapagos hawk (Buteo galapagoensis) population on Santiago Island before, during, and after eradication. We used a 12‐year data set in a capture–mark–recapture analysis to estimate the apparent survivorship of territorial adults in 33 breeding territories, and a 5‐year data set to estimate the population sizes of the floater (non‐territorial) fraction of the population. Juvenile floaters showed a drastic decline starting in 2006 and continuing in 2007, 2008, and 2010, which we attribute to the completion of goat eradication in 2006, and subsequent habitat changes. We found a significant decline in adult survivorship after the goat eradication program. Additionally, group size positively affected adult survivorship in this cooperatively polyandrous raptor, presumably reflecting the benefit of shared defense and offspring provisioning during harsher conditions. The changes in the hawk population after goat eradication are an example of unforeseen consequences of a restoration program, and we hypothesize that these changes are adjustments towards a new equilibrium under the current ecosystem characteristics and capacity. © 2012 The Wildlife Society.
fMRI evaluation of cochlear implant candidacy in diffuse cortical cytomegalovirus disease
Authors: Weiss Joshua P. , Bernal Byron , Balkany Thomas J. , Altman Nolan , Jethanamest Dan , Andersson Erin
Published: May 2012

Congenital cytomegalovirus infection is the most frequent nongenetic cause of pediatric hearing loss in the United States, affecting approximately 8,000 children each year. Due in part to variable cytomegalic involvement of the auditory cortex, cochlear implantation outcomes have varied widely. Functional magnetic resonance imaging (fMRI) has the potential to assist in determining candidacy for cochlear implantation through the detection of intact auditory pathways including the cortex. We report a case of a 21‐month‐old girl with cytomegalovirus‐related deafness and diffuse white matter involvement in which fMRI was a determining factor for cochlear implantation and side selection.
Balance disorders in the elderly: Epidemiology and functional impact
Authors: Lin Harrison W. , Bhattacharyya Neil
Published: May 2012

Objectives/Hypothesis:

To quantify the prevalence and determine the impact of dizziness and balance disorders in the elderly.

Study Design:

Cross‐sectional analysis of a national database.

Methods:

The balance problems survey module of the 2008 National Health Interview Survey was examined, and cases of reported dizziness or balance problems in persons ≥65 years old were identified. The prevalence of balance disorders and associated symptoms and their impacts on self‐reported functional limitations were determined. The related impact on daily activities for elderly persons with balance problems was quantified. Sex‐based differences in balance problems were determined.

Results:

Among 37.3 ± 0.9 million elderly persons (mean age, 74.4 ± 0.1 years; 56.9% ± 0.9% female), 7.0 ± 0.2 million persons (19.6% ± 0.7%) reported a problem with dizziness or balance in the preceding 12 months. Balance problems included difficulty with unsteadiness (68.0%), walking on uneven surfaces (54.8%), vertigo (30.1%), and faintness (29.6%). Prescription medication triggered the balance problem in 18.7%. Among the 50.0% of elderly persons with balance problems who sought care, 85.6%, 30.3%, 23.9%, and 16.8% saw a general practitioner, internist, neurologist, or otolaryngologist, respectively. Of this group, 27.4% reported that balance problems specifically prevented them from participating in activities including exercise (61.2%), social events (45.8%), and driving (47.1%). Females were more likely to experience balance problems than males (21.0% vs. 17.7%, P = .025).

Conclusions:

Approximately one in five elderly persons experiences annual problems with dizziness or balance. Given the significant prevalence and negative effect of balance problems on daily activities in the elderly, balance disorders merit special attention, particularly in the face of an aging population.
Weather and Language
Authors: Eriksen Pål K. , Kittilä Seppo , Kolehmainen Leena
Published: May 2012

This paper summarizes current findings in the cross‐linguistic study of meteorological constructions. It provides both a typology of weather events and a typology of encoding formats used for the expression of weather in and across languages. The discussion shows that there is a correlation between these two parameters: there are clear tendencies in the distribution of the various encoding types across the various event types. This gives rise to a typology of languages which explains linguistic variation in the encoding of meteorological events.
Indian English: Features and Sociolinguistic Aspects
Authors: Sailaja Pingali
Published: May 2012

Indian English has been the subject of study since colonial times, with several works written over the years describing its linguistic features. Considerable attention has been paid to the lexis, morphology and syntactic constructions, as also the sound system. Yet, the investigation is far from over, nor is there agreement on issues. Recent work has moved in the direction of corpus‐based studies, enabling the establishment of tendencies and grammaticalised forms in a quantified manner. Acoustic phonetic studies are increasingly the norm. These empirically verified conclusions either negate or confirm earlier intuition‐based and impressionistic descriptions. Together, these works help to establish what makes up the national variety, the standard and variation. Two theoretical debates emerge in this scenario. The first is the nature and extent of substrate influence and its intersection with L2 universals. The second is a debate on the phase to which Indian English belongs in Schneider’s dynamic model of evolution for New Englishes: phase 3 of nativisation or phase 4 of endonormative stabilisation.
Two‐Way Shape Changes of a Shape‐Memory Poly(ester urethane)
Authors: Bothe Martin , Pretsch Thorsten
Published: May 2012

Phase‐segregated PEU exhibits two‐way shape changes under various constant stresses. Most distinct actuation (expansion on cooling and contraction on heating) can be detected between +60 and −20 °C when the maximum stress applied during a thermo‐mechanical pretreatment approached the point where deformation‐induced crystallization of the PBA soft segment sets in. The driving forces for the strain‐related two‐way shape changes consist of PBA crystallization and PBA melting‐induced entropy elasticity. At low constant stresses (<1.5 MPa), entropy elasticity also contributes to specimen expansion on cooling. The results of multiple‐ cycling experiments imply that PEU is an appropriate candidate for the fabrication of thermoresponsive actuators working under constant stress conditions.
Induced Charge Effect by Co(II) Complexation on the Conformation of a Copolymer Containing a Bidentate 2‐(1,2,3‐Triazol‐4‐yl)pyridine Chelating Unit
Authors: Happ Bobby , Pavlov Georges M. , Perevyazko Igor , Hager Martin D. , Winter Andreas , Schubert Ulrich S.
Published: May 2012

Poly(alkyl methacrylate) copolymers embedding bidentate trzpy chelating units as comonomer in the side chains are synthesized utilizing the controlled radical RAFT polymerization process. The free trzpy units are complexed by iron(II) and cobalt(II) ions, which results in characteristic UV‐Vis absorption bands and an increase of solution viscosity. The intramolecular complexation with Co(II) ions is studied by different analytical ultracentrifugation experiments. Following the addition of a small amount of Co(II) ions, a significant decrease of the intrinsic sedimentation coefficient is observed that can be explained by the elongation of the individual polymer coils due to the electrostatic repulsion of the coordinated Co(II) ions.
The double sign of a real division algebra of finite dimension greater than one
Authors: Darpö Erik , Dieterich Ernst
Published: May 2012

For any real division algebra A of finite dimension greater than one, the signs of the determinants of left multiplication and right multiplication by an element a ∈ A∖{0} are shown to form an invariant of A, called its double sign. For each n ∈ {2, 4, 8}, the double sign causes the category \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathbb {D}_n$\end{document} of all n‐dimensional real division algebras to decompose into four blocks. The structures of these blocks are closely related, and their relationship is made precise for a sample of full subcategories of \documentclass{article}\usepackage{amssymb,mathrsfs}\begin{document}\pagestyle{empty}$\mathscr {D}_n$\end{document}.
On nonlocal BVPs with nonlinear boundary conditions with asymptotically sublinear or superlinear growth
Authors: Goodrich C. S.
Published: May 2012

In this paper we deduce the existence of at least one positive solution to boundary value problems with nonlinear, nonlocal boundary conditions, which have either asymptotically sublinear or asymptotically superlinear growth. Our model problem is y″ = −λf(t, y(t)), 0 < t < 1, subject to y(0) = H(ϕ(y)) and y(1) = 0, where H is a continuous function, which captures the nonlinearity of the boundary condition at t = 0, and ϕ(y) is a linear functional, which captures the nonlocality of the boundary condition at t = 0. We argue that this problem has at least one positive solution by imposing only an asymptotic growth condition on the function H together with some additional hypotheses on ϕ.
Q‐matrices as pseudo‐differential operators with negative definite symbols
Authors: Evans Kristian , Jacob Niels
Published: May 2012

Operators induced by Q‐matrices on \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$l_p(\mathbb {Z}^m)$\end{document} are shown to satisfy the positive maximum principle and to have a representation as a pseudo‐differential operator with symbol \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$q:\mathbb {Z}^m\times T^m\rightarrow \mathbb {C}$\end{document} which is with respect to the co‐variable negative definite (in the sense of Schoenberg). This observation leads already towards a more geometric interpretation of the transition matrix of the associated Markov chain.
Furan in heat‐treated foods: Formation, exposure, toxicity, and aspects of risk assessment
Authors: Moro Sabrina , Chipman James Kevin , Wegener Jan‐Willem , Hamberger Carolin , Dekant Wolfgang , Mally Angela
Published: May 2012

Furan is formed in a variety of heat‐treated foods through thermal degradation of natural food constituents. Relatively high levels of furan contamination are found in ground roasted coffee, instant coffee, and processed baby foods. European exposure estimates suggest that mean dietary exposure to furan may be as high as 1.23 and 1.01 μg/kg bw/day for adults and 3‐ to 12‐month‐old infants, respectively. Furan is a potent hepatotoxin and hepatocarcinogen in rodents, causing hepatocellular adenomas and carcinomas in rats and mice, and high incidences of cholangiocarcinomas in rats at doses ≥2 mg/kg bw. There is therefore a relatively low margin of exposure between estimated human exposure and doses that cause a high tumor incidence in rodents. Since a genotoxic mode of action cannot be excluded for furan‐induced tumor formation, the present exposures may indicate a risk to human health and need for mitigation. This review summarizes the current knowledge on mechanisms of furan formation in food, human dietary exposure to furan, and furan toxicity, and highlights the need to establish the risk resulting from the genotoxic and carcinogenic properties of furan at doses lower than 2 mg/kg bw.
An improved nonintrusive global–local approach for sharp thermal gradients in a standard FEA platform
Authors: Plews J. , Duarte C.A. , Eason T.
Published: May 2012

Several classes of important engineering problems—in this case, problems exhibiting sharp thermal gradients—have solution features spanning multiple spatial scales and, therefore, necessitate advancedhpfinite element discretizations. Althoughhp‐FEM is unavailable off‐the‐shelf in many predominant commercial analysis software packages, the authors herein propose a novel method to introduce these capabilities via a generalized FEM nonintrusively in a standard finite element analysis (FEA) platform. The methodology is demonstrated on two verification problems as well as a representative, industrial‐scale problem. Numerical results show that the techniques utilized allow for accurate resolution of localized thermal features on structural‐scale meshes withouthp‐adaptivity or the ability to account for complex and very localized loads in the FEA code itself. This methodology enables the user to take advantage of all the benefits of bothhp‐FEM discretizations and the appealing features of many available computer‐aided engineering /FEA software packages to obtain optimal convergence for challenging multiscale problems. Copyright © 2012 John Wiley & Sons, Ltd.