bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel COL4A1 mutations associated with HANAC syndrome: A role for the triple helical CB3[IV] domain
Authors: Plaisier Emmanuelle , Chen Zhiyong , Gekeler Florian , Benhassine Safa , Dahan Karine , Marro Béatrice , Alamowitch Sonia , Paques Michel , Ronco Pierre
Published: September 2010

The COL4A1 gene encodes the α1‐chain of type IV collagen, which is ubiquitously expressed in basement membranes. Mutations in COL4A1 have been reported in autosomal‐dominant porencephaly and in patients with symptomatic small vessel brain disease, inconstantly associated with eye defects. We have previously reported three COL4A1 mutations associated with a systemic phenotype that we called HANAC (Hereditary Angiopathy, Nephropathy, Aneurysms, and Cramps). We carried out a clinical and genetic study of three families presenting with characteristic features of HANAC syndrome. Common systemic signs included arterial retinal tortuosity and muscle cramps, with a variable combination of small vessel brain disease, Raynaud phenomena, and kidney defects. Three novel COL4A1 missense substitutions are described, which affect highly conserved glycine residues within the collagenous domain of the protein. All six known mutations associated with the HANAC phenotype are localized within the CB3[IV] fragment of COL4A1, which encompasses major integrin‐binding sites. Our results confirm that HANAC syndrome is a distinct clinical entity within the COL4A1‐related disorders, which is characterized by systemic involvement and usually asymptomatic brain disease. The restricted distribution of COL4A1 mutations within the CB3[IV] region is a characteristic of the reports of patients with HANAC, which suggests that abnormal cell‐type IV collagen interactions may underlie the systemic defects observed in this syndrome. © 2010 Wiley‐Liss, Inc.
Likelihood inference for a two‐stage design with treatment selection
Authors: Bebu Ionut , Luta George , Dragalin Vladimir
Published: September 2010

A conditional likelihood‐based approach is proposed to construct confidence intervals for the parameters of interest in a two‐stage design with treatment selection after the first stage. Both a Wald confidence interval and a confidence interval based on inverting the likelihood ratio test are proposed. The operating characteristics of these confidence intervals: the coverage probabilities and average confidence interval lengths, as well as the average bias and mean‐square error of the corresponding point estimates, compare favorably with other available techniques. Possible extensions and an alternative unconditional approach based on the likelihood with missing at random mechanism are also briefly described.
Planar Chiral P,O‐Compounds Derived from Ferrocenyl Aryl Ethers
Authors: Schaarschmidt Dieter , Lang Heinrich
Published: September 2010

The ortho‐directed lithiation of FcOC6H4‐4‐tBu (1) [Fc = (η5‐C5H4)(η5‐C5H5)Fe] with nBuLi/tmeda is reported (tmeda = tetramethylethylenediamine). In this reaction, multimetalation occurs to yield novel 1,2‐functionalized P,O‐derivatives that contain up to four phosphanyl moieties as determined by NMR spectroscopic studies and single‐crystal X‐ray diffraction analysis. Thus available planar chiral P,O‐ferrocenes can successfully be applied in the palladium‐catalyzed Suzuki coupling of diverse aryl halides and aryl boronic acids. The aforementioned systems allow the activation of carbon–chlorine bonds in an efficient way and tolerate catalyst loadings as low as 10 ppm. Noteworthy is their remarkable ability to economically generate hindered biaryls under mild reaction conditions.
The use of ablation‐dominated medial moraines as samplers for 10Be‐derived erosion rates of glacier valley walls, Kichatna Mountains, AK
Authors: Ward Dylan J. , Anderson Robert S.
Published: September 2010

We use cosmogenic 10Be concentrations in amalgamated rock samples from active, ice‐cored medial moraines to constrain glacial valley sidewall backwearing rates in the Kichatna Mountains, Alaska Range, Alaska. This dramatic landscape is carved into a small ∼65 Ma granitic pluton about 100 km west of Denali, where kilometer‐tall rock walls and ‘cathedral’ spires tower over a radial array of over a dozen valley glaciers. These supraglacial landforms erode primarily by rockfall, but erosion rates are difficult to determine. We use cosmogenic 10Be to measure rockwall backwearing rates on timescales of 103–104 years, with a straightforward sampling strategy that exploits ablation‐dominated medial moraines.

A medial moraine and its associated englacial debris serve as a conveyor system, bringing supraglacial rockfall debris from accumulation‐zone valley walls to the moraine crest in the ablation zone. We discuss quantitatively several factors that complicate interpretation of cosmogenic concentrations in this material, including the complex scaling of production rates in very steep terrain, the stochastic nature of the rockfall erosion process, the unmixed nature of the moraine sediment, and additional cosmogenic accumulation during transport of the sediment.

We sampled medial moraines on each of three glaciers of different sizes and topographic aspects. All three moraines are sourced in areas with identical rock and similar sidewall relief of ∼1 km. Each sample was amalgamated from 25 to 35 clasts collected over a 1‐km longitudinal transect of each moraine. Two of the glaciers yield similar 10Be concentrations (∼1·6–2·2 × 104 at/g) and minimum sidewall slope‐normal erosion rates (∼0·5–0·7 mm/yr). The lowest 10Be concentrations (8 × 103 at/g) and the highest erosion rates (1·3 mm/yr) come from the largest glacier in the range with the lowest late‐summer snowline. These rates are reasonable in an alpine glacial setting, and are much faster than long‐term exhumation rates of the western Alaska Range as determined by thermochronometric studies. Copyright © 2010 John Wiley & Sons, Ltd.
Gross erosion, net erosion and gross deposition of dust by wind: field data from 17 desert surfaces
Authors: Goossens Dirk , Buck Brenda
Published: September 2010

Wind erosion measurements were carried out in Nellis Dunes Recreation Area, southern Nevada, USA. Gross erosion (the total mass of sediment effectively blown away from a surface), gross deposition (the total mass of sediment effectively depositing on a surface) and net erosion (the difference in sediment mass before and after an event) were measured for 1 year, on 17 different types of surfaces developed on loose dune sand, compacted sand, loose silt, compacted and/or aggregated silt, rock‐covered sands and silts, mixtures of sand, silt and clay, exposed petrocalcic horizons, gravelly substrata and bedrock. Results showed that net erosion, which is the type of erosion measured in field and laboratory experiments, strongly differs from gross erosion. Activity on a surface is much higher than classic net erosion measurements suggest. Future studies on wind erosion should better acknowledge the distinction between the two types of process. Also, a grain diameter of maximum susceptibility to wind erosion (‘optimum deflation diameter’) near 70 µm as proposed by the aeolian literature only exists for net wind erosion. No such optimum diameter was found for gross wind erosion within the particle range 0–100 µm delineating the transport modes of suspension and modified saltation. In addition, desert surfaces predominantly composed of sand did not show an optimum deflation diameter (for net erosion) around 70 µm. Instead, there was a preferential grain size around 15 µm at which particles were most vulnerable to net emission. Desert surfaces poor in sand showed the classic value of 70 µm. This suggests that interactions exist between the type of surface and the susceptibility of particles to wind erosion. This study is solely based on field data. Although results are supported by two previous wind tunnel studies, more wind tunnel experiments documenting the interactions between gross erosion and gross deposition are necessary. Copyright © 2010 John Wiley & Sons, Ltd.
A parallel fully coupled algebraic multilevel preconditioner applied to multiphysics PDE applications: Drift‐diffusion, flow/transport/reaction, resistive MHD
Authors: Lin Paul T. , Shadid John N. , Tuminaro Raymond S. , Sala Marzio , Hennigan Gary L. , Pawlowski Roger P.
Published: September 2010

This study considers the performance of a fully coupled algebraic multilevel preconditioner for Newton–Krylov solution methods. The performance of the preconditioner is demonstrated on a set of challenging multiphysics partial differential equation (PDE) applications: a drift‐diffusion approximation for semiconductor devices; a low Mach number formulation for the simulation of coupled flow, transport and non‐equilibrium chemical reactions; and a low Mach number formulation for visco‐resistive magnetohydrodynamics (MHD) systems. These systems contain multiple physical mechanisms that are strongly coupled, highly nonlinear, non‐symmetric and produce solutions with multiple length‐ and time‐scales. In the context of this study the governing PDEs for these systems are discretized in space by a stabilized finite element (FE) method that collocates all unknowns at each node of the FE mesh. The algebraic multilevel preconditioner is based on an aggressive‐coarsening graph‐partitioning of the non‐zero block structure of the Jacobian matrix. The performance of the algebraic multilevel preconditioner is compared with a standard variable overlap additive Schwarz domain decomposition preconditioner. Representative performance and parallel scaling results are presented for a set of direct‐to‐steady‐state and fully implicit transient solutions. The performance studies include parallel weak scaling studies on up to 4096 cores and also includes the solution of systems as large as two billion unknowns carried out on 24000 cores of a Cray XT3/4. In general, the results of this study indicate that on this reasonably diverse set of challenging multiphysics applications the algebraic multilevel preconditioner performs very well. Copyright © 2010 John Wiley & Sons, Ltd.
A remedy for numerical oscillations in weakly compressible smoothed particle hydrodynamics
Authors: Fatehi R. , Manzari M. T.
Published: September 2010

Weakly Compressible Smoothed Particle Hydrodynamics (WCSPH) can lead to non‐physical oscillations in the pressure and density fields when simulating incompressible flow problems. This in turn may result in tensile instability and sometimes divergence. In this paper, it is shown that this difficulty originates from the specific form of spatial discretization used for the pressure term when solving the mass conservation equation. After describing the pressure–velocity decoupling problem associated with the so‐called colocated grid methods, a modified approach is presented that overcomes this problem using a different discretization scheme for the second derivative of pressure. The modified scheme is employed for solving a number of benchmark problems including both single‐phase and two‐phase test cases. Copyright © 2010 John Wiley & Sons, Ltd.
Numerical and analytical solutions of an Oldroyd 8‐constant MHD fluid with nonlinear slip conditions
Authors: Hameed M. , Ellahi R.
Published: September 2010

The flow of an Oldroyd 8‐constant non‐Newtonian MHD fluid is investigated analytically and numerically. The governing equations for the flow field are derived for a steady one‐dimensional flow. The effect of constant applied magnetic field is included and its influence on the flow field is studied. The nonlinear governing equation along with nonlinear boundary conditions is solved analytically and the solution is obtained in an elegant way. Numerical solutions are also obtained using higher order Chebyshev spectral methods. The influence of various non‐Newtonian parameters and applied magnetic field is investigated. Results showing the effect of various physical parameters of the flow are presented and investigated. Copyright © 2010 John Wiley & Sons, Ltd.
Polysomnographic diagnosis of idiopathic REM sleep behavior disorder
Authors: Montplaisir Jacques , Gagnon Jean‐Francois , Fantini Maria Livia , Postuma Ronald B. , Dauvilliers Yves , Desautels Alex , Rompré Sylvie , Paquet Jean
Published: September 2010

The presence of either excessive tonic chin EMG activity during REM sleep, or excessive phasic submental or limb EMG twitching is required to diagnose REM sleep behavior disorder (RBD). The aim was to identify cut‐off values and to assess the sensitivity and specificity of these values taken separately or combined to diagnose idiopathic RBD patients. Eighty patients presenting with a clinical diagnosis of idiopathic RBD and 80 age‐ and gender‐matched normal controls were studied in the sleep laboratory. Receiver operating characteristic curves were drawn to find optimal cut‐off values for three REM sleep EMG parameters. Tonic and phasic EMG activity were measured in the chin, but not in the limbs. Videos were examined during the recording but were not systematically reviewed by the authors. Total correct classification of 81.9% was found for tonic chin EMG density ≥30%; 83.8% for phasic chin EMG density ≥15% and 75.6% for ≥24 leg movements per hour of REM sleep. Five patients did not fulfill any of these three polysomnographic (PSG) criteria. Conversely, one subject of the control group met the PSG criteria for RBD. This study estimates the diagnostic value of a visual scoring method for the diagnosis of idiopathic RBD and establishes cut‐off values to be used in clinical and research set‐ups. For the five RBD patients who did not show chin EMG abnormalities, it cannot be excluded that they had increased phasic EMG activity in the upper limbs and presented visible motor activity. © 2010 Movement Disorder Society
Grasping premanifest Huntington's disease – shaping new endpoints for new trials
Authors: Reilmann Ralf , Bohlen Stefan , Klopstock Thomas , Bender Andreas , Weindl Adolf , Saemann Philipp , Auer Dorothee P. , Ringelstein Erich B. , Lange Herwig W.
Published: September 2010

Future clinical trials in subjects with premanifest Huntington's disease (preHD) may depend on the availability of biomarkers. It was previously shown in symptomatic HD that, the grip force variability coefficient‐of‐variation (GFV‐C) in a grasping paradigm was correlated to the Unified‐Huntington's‐Disease‐Rating‐Scale‐Total‐Motor‐Score (UHDRS‐TMS) and increased in a 3 year follow‐up study. To further elucidate its potential as a biomarker, we investigated whether GFV‐C is able to detect a motor phenotype in preHD and is correlated to the genotype assessed by a disease‐burden‐score. The ability of preHD (n = 15) and symptomatic HD subjects (n = 20) to maintain stable grip forces, while holding an object (250 g and 500 g), was measured and compared with the controls (n = 19). GFV‐C was increased in preHD at 500 g, in symptomatic subjects at both weights and was correlated to the disease‐burden‐score and UHDRS‐TMS. GFV‐C may be a useful objective and quantitative marker of motor dysfunction across genetically diagnosed premanifest and symptomatic HD subjects. © 2010 Movement Disorder Society
Brain stem pathology in Parkinson's disease: An evaluation of the Braak staging model
Authors: Kingsbury Ann E. , Bandopadhyay Rina , Silveira‐Moriyama Laura , Ayling Hilary , Kallis Constantinos , Sterlacci William , Maeir Hans , Poewe Werner , Lees Andrew J.
Published: September 2010

The lower brain stem of 25 pathologically‐confirmed Parkinson's disease (PD) cases was examined by alpha synuclein immunohistochemistry to characterize pathological accumulation of alpha synuclein (Lewy‐type α‐synucleinopathy, LTS) in the medulla oblongata, to examine differences between affected regions and test a proposed model of staging of pathology in PD. All cases had LTS in the medulla, including the dorsal motor nucleus of the vagus (dmX), when present. The distribution followed a consistent pattern and appeared to be concentrated in a tyrosine hydroxylase (TH) immunoreactive region, probably representing the dorsal IX/X nuclear complex and the intermediate reticular zone. LTS density was greatest in the dmX. A similar distribution pattern to PD was seen in 14 incidental Lewy body disease (ILBD) cases, five derived from the Queen Square Brain Bank tissue collection and nine identified in separate series of 60 neurologically‐normal individuals, and in three cases with the G2019S mutation of LRRK2. Semiquantitative assessment showed that severity of pathology in the dmX was not correlated with the severity of cortical pathology. Semiquantitative assay of TH and ChAT peptide expression in the medulla showed that TH expression in PD and ILBD did not differ from controls. These findings broadly support the Braak hypothesis of caudo‐rostral development but indicate that the extent of the disease in the cortex and the severity of pathology in the medulla were independent of one another. © 2010 Movement Disorder Society
Impaired postural stability as a marker of premanifest Huntington's disease
Authors: Salomonczyk Danielle , Panzera Robert , Pirogovosky Eva , Goldstein Jody , Corey‐Bloom Jody , Simmons Roger , Gilbert Paul E.
Published: September 2010

Subtle changes in fine motor control have been observed in individuals who carry the Huntington's disease (HD) mutation but have not yet manifested symptoms, referred to as premanifest HD (preHD). However, few studies have examined gross motor impairments in this population. This study sought to examine the role of sensory involvement in maintaining postural stability during the premanifest and manifest stages of HD using computerized dynamic posturography. Eleven HD participants, 22 preHD subdivided into “preHD Near” (<5 years from estimated clinical onset) and “preHD Far” (>5 years from estimated clinical onset), and 17 nongene carriers (NGC) completed a sensory organization test (SOT) to assess postural control when vestibular, visual, and somatosensory information was systematically degraded. The HD group demonstrated greater postural sway than the NGC and preHD Far groups on all conditions including baseline, and greater postural sway than the preHD Near group when sensory information was manipulated. The preHD Near group showed significantly greater postural sway than the preHD Far group when visual and somatosensory information was degraded and only vestibular information was available and reliable for maintaining postural stability. The results of this study highlight subtle postural deficits in the face of changing sensory conditions in preHD up to 5 years before estimated disease onset. The findings suggest that the SOT may be a highly sensitive indicator of early motor impairment and subsequent phenoconversion to manifest HD in preHD. © 2010 Movement Disorder Society
Clinical course of the first Asian family with Parkinsonism related to SNCA triplication
Authors: Sekine Takeshi , Kagaya Hajime , Funayama Manabu , Li Yuanzhe , Yoshino Hiroyo , Tomiyama Hiroyuki , Hattori Nobutaka
Published: September 2010

Triplication of SNCA is a rare cause of familial Parkinson's disease compared with duplication. Its clinical course is believed to be more robust than duplication, though it is uncertain. Marked as the first among the Asian population, we identified a Japanese family (paternal grandfather, father, and son) with SNCA triplication based on genetic and clinical analyses. The proband had a completely triplicated region including SNCA. This allele did not share any common haplotypes with those of previously reported Japanese families with SNCA duplication. Clinical analysis indicated early onset, rapidly progressive parkinsonism with mild levodopa response. Further studies are needed to clarify the gene dose effect of SNCA. © 2010 Movement Disorder Society
Spinocerebellar ataxia type 10: Frequency of epilepsy in a large sample of Brazilian patients
Authors: Teive Hélio A.G. , Munhoz Renato P. , Raskin Salmo , Arruda Walter O. , de Paola Luciano , Werneck Lineu C. , Ashizawa Tetsuo
Published: September 2010

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder caused by an ATTCT repeat intronic expansion in the SCA10 gene. SCA 10 has been reported in Mexican, Brazilian, Argentinean and Venezuelan families. Its phenotype is overall characterized by cerebellar ataxia and epilepsy. Interestingly, Brazilian patients reported so far showed pure cerebellar ataxia, without epilepsy. Here, authors provide a systematic analysis of the presence, frequency and electroencephalographic presentation of epilepsy among 80 SCA10 patients from 10 Brazilian families. Overall, the frequency of epilepsy was considered rare, been found in 3.75 % of the cases while this finding in populations from other geographic areas reaches 60% of SCA10 cases. © 2010 Movement Disorder Society
Olfactory heterogeneity in LRRK2 related Parkinsonism
Authors: Silveira‐Moriyama Laura , Munhoz Renato Pupi , de J. Carvalho Margarete , Raskin Salmo , Rogaeva Ekaterina , de C. Aguiar Patricia , Bressan Rodrigo A. , Felicio Andre C. , Barsottini Orlando G.P. , Andrade Luiz Augusto F. , Chien Hsin F. , Bonifati Vincenzo , Barbosa Egberto R. , Teive Helio A. , Lees Andrew J.
Published: September 2010

LRRK2 mutations can cause familial and sporadic Parkinson's disease (PD) with Lewy‐body pathology at post‐mortem. Studies of olfaction in LRRK2 are sparse and incongruent. We applied a previously validated translation of the 16 item smell identification test from Sniffin' Sticks (SS‐16) to 14 parkinsonian carriers of heterozygous G2019S LRRK2 mutation and compared with 106 PD patients and 118 healthy controls. The mean SS‐16 score in LRRK2 was higher than in PD (p < 0.001, 95% CI for β = −4.7 to −1.7) and lower than in controls (p = 0.007, 95% CI for β = +0.6 to +3.6). In the LRRK2 group, subjects with low scores had significantly more dyskinesia. They also had younger age of onset, longer disease duration, and reported less frequently a family history of PD, but none of these other differences reached significance. Odor identification is diminished in LRRK2 parkinsonism but not to the same extent as in idiopathic PD. © 2010 Movement Disorder Society
How well do caregivers detect mild cognitive change in Parkinson's disease?
Authors: Naismith Sharon L. , Pereira Marilia , Shine James M. , Lewis Simon J.G.
Published: September 2010

Using the Cambridge Behavior Inventory‐Revised, this study evaluated the relationship between caregiver ratings of cognitive change and neuropsychological performance. In sixty‐one nondemented patients with Parkinson's Disease (PD; mean age = 64.5 years, MMSE = 28.7), 62% met criteria for mild cognitive impairment. This group were rated as having more overall change as well as memory and behavior change. Caregiver ratings were related to poorer psychomotor speed, learning/memory, language, and executive functioning. The capacity for caregivers to rate mild cognitive change in PD may be useful to assist in early screening and intervention approaches. © 2010 Movement Disorder Society
Partial cranial trephination by means of Hippocrates' trypanon from 5th century BC Himera (Sicily, Italy)
Authors: Fabbri P. F. , Lonoce N. , Masieri M. , Caramella D. , Valentino M. , Vassallo S.
Published: September 2010

The paper deals with a new case of partial cranial trephination found in one of the necropolises of the Greek colony of Himera in Sicily. It is one of the very few cases of cranial trephination of Greek classical age. Macroscopic as well as radiological investigations prove that the operation was perimortal as no growth of new bone could be detected, SEM‐EDS microanalysis of the piece revealed the traces left by the tool used during trephination. The review of ancient Greek and Latin medical and surgical texts permitted us to establish that the tool used in Himera was a (trypanon) mentioned by Hippocrates and named terebra by Latin authors. Copyright © 2010 John Wiley & Sons, Ltd.
Formation and decomposition of N‐alkylnaphthalimides: experimental evidences and ab initio description of the reaction pathways
Authors: de Barros Teresa Cristina , Filho Pedro Berci , Loos Michel , Politi Mario José , Chaimovich Hernan , Cuccovia Iolanda Midea
Published: September 2010

The kinetics of hydrolysis of 1,8‐N‐butyl‐naphthalimide (1,8‐NBN) to 1,8‐N‐butyl‐naphthalamide (1,8‐NBAmide) and of 2,3‐N‐butyl‐naphthalimide (2,3‐NBN) to 2,3‐N‐butyl‐naphthalamide (2,3‐NBAmide), as well as the formation of the respective anhydrides from the amides were investigated in a wide acidity range. 1,8‐NBN equilibrates with 1,8‐NBAmide in mild alkali. Under the same conditions 2,3‐NBN quantitatively yields 2,3‐NBAmide. Over a wide range of acidities the reactions of the 1,8‐ and 2,3‐N‐butyl‐naphthalamides (or imides) yield similar products but with widely different rates and at distinct pH's. Anhydride formation in acid was demonstrated for 1,8‐NBAmide. The reactions mechanisms were rationalized in the manifold pathways of ab initio calculations. The differences in rates and pH ranges in the reactions of the 1,8‐ and 2,3‐N‐butyl‐naphthalamides were attributed to differences in the stability of the tetrahedral intermediates in alkali as well as the relative stabilities of the five and six‐membered ring intermediates. The rate of carboxylic acid assisted 1,8‐N‐Butyl‐naphthalamide hydrolysis is one of the largest described for amide hydrolysis models. Copyright © 2010 John Wiley & Sons, Ltd.
Geometrically centered region: A “wet” model of protein binding hot spots not excluding water molecules
Authors: Li Zhenhua , Li Jinyan
Published: September 2010

A protein interface can be as “wet” as a protein surface in terms of the number of immobilized water molecules. This important water information has not been explicitly taken by computational methods to model and identify protein binding hot spots, overlooking the water role in forming interface hydrogen bonds and in filing cavities. Hot spot residues are usually clustered at the core of the protein binding interfaces. However, traditional machine learning methods often identify the hot spot residues individually, breaking the cooperativity of the energetic contribution. Our idea in this work is to explore the role of immobilized water and meanwhile to capture two essential properties of hot spots: the compactness in contact and the far distance from bulk solvent. Our model is named geometrically centered region (GCR). The detection of GCRs is based on novel tripartite graphs, and atom burial levels which are a concept more intuitive than SASA. Applying to a data set containing 355 mutations, we achieved an F measure of 0.6414 when ΔΔG ≥ 1.0 kcal/mol was used to define hot spots. This performance is better than Robetta, a benchmark method in the field. We found that all but only one of the GCRs contain water to a certain degree, and most of the outstanding hot spot residues have water‐mediated contacts. If the water is excluded, the burial level values are poorly related to the ΔΔG, and the model loses its performance remarkably. We also presented a definition for the O‐ring of a GCR as the set of immediate neighbors of the residues in the GCR. Comparative analysis between the O‐rings and GCRs reveals that the newly defined O‐ring is indeed energetically less important than the GCR hot spot, confirming a long‐standing hypothesis. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Surface and electrochemical analysis for the understanding of TiO2 nanopores/nanotubes changes in post‐elaboration treatment
Authors: Manole Claudiu Constantin , Pirvu Cristian
Published: September 2010

The electrochemical stability of TiO2 nanoarchitecture fabricated in fluoride electrolyte presented in this paper is related to 2D and 3D geometries that present a shift from nanopores toward nanotubes. The fabrication conditions involve a 60 V applied voltage for 2 hours of anodizing in order to create the ordered structures, in a mixture of low‐water glycerol electrolyte and fluoride. With the use of different ultrasonication times, a variety of nanotubes/nanopores were observed. The surface interfacial aspects were investigated mainly by surface microscopy and hydrophilic/hydrophobic balance for the grown structures ultrasonicated at various periods of time. The electrochemical behavior of the nanotube‐structured surface was performed by potentiodynamic evaluation and electrochemical impedance spectroscopy in a simulated body fluid solution. As a most important result, all surface analysis and electrochemical data interpretation permitted the proposition of a model for elaboration of different nanostructures from nanopores to nanotubes. These different surface nanoarchitectures were obtained as a result of ultrasonication at various periods of time. Copyright © 2010 John Wiley & Sons, Ltd.
Effects of anodic spark oxidation by pulse power on titanium substrates
Authors: Park Il Song , Lee Min Ho
Published: September 2010

The characteristics of the oxide layer of titanium generated by anodic spark oxidation are affected significantly by the process variables. In this study, electrochemical treatments were performed while applying a direct current, a pulse current, and a reverse pulse current during anodic spark oxidation. A mixed solution of 0.015 M DL‐α‐GP (DL‐α‐glycerophosphate disodium salt) and 0.2 M CA (calcium acetate) was used as the electrolyte. The pore size generated after anodic spark oxidation was smallest in the group exposed to the reverse pulse current followed in order by the pulse current and direct current. Anatase was the major crystal phase of the TiO2 produced on the surfaces subjected to 280 V, and the rutile phase was additionally detected in the group subjected to 320 V. The crystals precipitated on the surface after the hydrothermal treatment were hydroxyapatite (HA) crystals that had a polygonal bar‐shaped needle structure. Good activity was observed in the 320‐V pulse treated group, in which very thin needle‐shaped crystals were observed after immersing the samples in Hanks' solution for 4 weeks. The cell viability was increased greatly by anodic spark oxidation, and the surface roughness was also increased. It is believed that the surface treated using a pulse current has excellent characteristics, making it suitable for applications in biomaterials. Copyright © 2010 John Wiley & Sons, Ltd.
Effects of elastic scattering and analyzer‐acceptance angle on the analysis of angle‐resolved X‐ray photoelectron spectroscopy data
Authors: Powell C. J. , Werner W. S. M. , Smekal W.
Published: September 2010

We have made calculations of N 1s, O 1s, Si(oxide) 2p, Hf 4f, and Si(substrate) 2p photoelectron intensities at selected emission angles for films of SiO1.6N0.4 and HfO1.9N0.1 of various thicknesses on silicon. These calculations were made with the National Institute of Standards and Technology (NIST) Database for Simulation of Electron Spectra for Surface Analysis (SESSA) to investigate effects of elastic scattering and analyzer‐acceptance angle that could be relevant in the analysis of angle‐resolved X‐ray photoelectron spectroscopy (ARXPS) experiments. The simulations were made for an XPS configuration with a fixed angle between the X‐ray source (i.e. for the sample‐tilting mode of ARXPS) and with Al and Cu Kα X‐ray sources. The no‐loss intensities changed appreciably as elastic scattering was switched ‘on’ and ‘off’, but changing the analyzer‐acceptance angle had a smaller effect. Ratios of intensities for each line from the overlayer film for the least realistic model condition (elastic scattering switched ‘off’, small analyzer‐acceptance angle) to those from the most realistic model condition (elastic scattering switched ‘on’, finite analyzer‐acceptance angle) changed relatively slowly with emission angle, but the corresponding intensity ratio for the Si(substrate) 2p line changed appreciably with emission angle. The latter changes, in particular, indicate that neglect of elastic‐scattering effects can lead to erroneous results in the analysis of measured ARXPS data. The elastic‐scattering effects were larger in HfO1.9N0.1 than in SiO1.6N0.4 (due to the larger average atomic number in the former compound) and were larger with the Al Kα X‐ray source than with the Cu Kα source because of the larger cross sections for elastic scattering at the lower photoelectron energies. Copyright © 2010 John Wiley & Sons, Ltd.
Studying clone evolution using incremental clone detection
Authors: Göde Nils , Koschke Rainer
Published: September 2010

Finding, understanding and managing software clones—passages of duplicated source code—is of large interest in research and practice. Analyzing the evolution of clones across multiple versions of a program adds value to both applications. Although there is an abundance of techniques to detect clones, current approaches are limited to a single version of a program. The current techniques to track clones utilize these single‐version approaches and map clones of consecutive versions retroactively. This causes an unnecessary overhead in runtime and may lead to an incorrect mapping due to ambiguity. In this paper, we present an incremental clone detection algorithm, which detects clones based on the results of the previous version's analysis. It creates a mapping between clones of consecutive versions along with the detection. We evaluated our incremental approach regarding its advantage in runtime as well as the usefulness of the mapping for studies on the clone evolution. Copyright © 2010 John Wiley & Sons, Ltd.
Selection and analysis of anti‐cancer antibodies for cancer therapy obtained from antibody phage library
Authors: Kurosawa Gene , Sumitomo Mariko , Ukai Yoshinori , Subere Juvy , Muramatsu Chiho , Eguchi Keiko , Tanaka‐Hashiba Miho , Sugiura Mai , Ando Misaki , Sato Noriko , Morita Miwa , Inaba Kazuki , Morigaki Satoko , Takasaki Akihiko , Akahori Yasushi , Miyakawa Shuichi , Uyama Ichiro , Maeda Koutarou , Shiroki Ryoichi , Hoshinaga Kiyotaka , Mizoguchi Yoshikazu , Hattori Yoshinobu , Sugioka Atsushi , Sugiura Mototaka , Kurosawa Yoshikazu
Published: September 2010

The search for effective antibodies (Ab) for curable cancer immunotherapy has been a quest of many research groups in order to find an effective target that exists on the cancer cell surface. So far there have been no conclusive answers to shed light on the search. This study therefore aimed to bridge the gap of cancer therapy. Screening against 49 kinds of cell lines belonging to 11 kinds of solids cancers was performed. Isolation and characterization for approximately 4200 monoclonal antibodies (mAb) was also performed thereafter. Of those mAb 488 clones that turned out to bind to 29 tumor‐associated antigens (TAA) were subjected to immunohistochemical (IHC) analyses. Selection of target antigens (Ag) and a potential antibody for cancer therapy was conducted prior to clinical examinations. In order to find predictably effective targets for therapeutic Ab against solid cancers, expression of the Ag on the surface of cancer and normal cells was extensively examined by IHC analyses using fresh cancer specimens resected from patients. In this study, the tendencies of all staining patterns and distribution of the Ab are reported. While all of the TAA appeared to be involved in tumorigenesis, their expression was not restricted to some specific tumor types but rather randomly distributed among various cancers. Some kinds of Ab including anti‐epidermal growth factor receptor (EGFR) and anti‐human epidermal growth factor receptor 2 (HER2) indicated the frequency of expression in normal cells was generally low. We concluded that identification of 488 mAb and the accumulated results of IHC analyses in this study could be the key for further therapeutic Ab against cancers. The targets that showed cancer‐specific expression are expected to be better for therapeutic Ab than the other Ab. Moreover, further investigation into the growth of cancer cell lines using full human IgG form of Ab shows available efficacy in specific cases. (Cancer Sci 2011; 102: 175–181)
Prospective randomized phase II study determines the clinical usefulness of genetic biomarkers for sensitivity to primary chemotherapy with paclitaxel in breast cancer
Authors: Ito Yoshinori , Nagasaki Koichi , Miki Yoshio , Iwase Takuji , Akiyama Futoshi , Matsuura Masaaki , Horii Rie , Makita Masujiro , Tokudome Nahomi , Ushijima Masaru , Yoshimoto Masataka , Takahashi Shunji , Noda Tetsuo , Hatake Kiyohiko
Published: September 2010

In patients with breast cancer, taxane as well as anthracycline play central roles in systemic chemotherapy. By evaluating the pathological response, we can gauge sensitivity to primary chemotherapy. However, biomarkers that would predict a response to taxane have not yet been established. We conducted a prospective randomized trial to evaluate whether selecting patients using sensitivity testing based on the gene expression of the tumor might enhance the probability of the pathological response. Five genes were identified as biomarkers derived from a microarray of DNA gene profiles from microdisected breast tumors. In the experimental arm (B1), 12 cycles of weekly paclitaxel, 80 mg/m2, were preoperatively given when the sensitivity test was positive and therefore judged to be sensitive to paclitaxel. When the test was negative, meaning insensitive to paclitaxel, four cycles of FEC100 were given (arm B2). In the control arm (A), paclitaxel was administered weekly without the use of the sensitivity test. A total of 92 patients were enrolled and 86 patients were analyzed. The pathological response rate (pRR) of each arm was 36.4% in B1 (expected sensitive to paclitaxel), 21.1% in A (control) and 12.5% in B2, respectively. Weekly paclitaxel‐treated patients selected by the sensitivity test did not enhance the pRR. The study failed to validate sensitivity testing using five gene expressions for primary chemotherapy with paclitaxel in patients with breast cancer. However, this study suggests that a randomized phase II study is a robust tool for obtaining a rapid conclusion on the usefulness of biomarkers and could be the foundation for further large clinical trials. (Cancer Sci 2011; 102: 130–136)
Interference competition at the landscape level: the effect of free‐ranging dogs on a native mesocarnivore
Authors: Vanak Abi Tamim , Gompper Matthew E.
Published: September 2010

1. Free‐ranging domestic dogs are the world’s most common carnivore and can negatively interact with native wildlife at multiple levels. Yet the intraguild competitive effects of dogs on the distribution and habitat use of native carnivores are poorly known, especially in areas of conservation concern.

2. We examined the spatial distribution of sympatric populations of radiocollared Indian foxes and free‐ranging dogs to determine if Indian foxes alter their habitat use in the presence of dogs. We tested the effects of landcover type, primary prey abundance (rodents) and the presence of dogs as predictors of Indian fox spatial distribution in a threatened grassland habitat in central India.

3. By counting rodent burrows, we determined that the relative abundance of rodents was higher in fallow land and agricultural land compared to natural grasslands. From radiotelemetry data, we determined that the presence of dogs was closely linked to human‐modified habitats, such as agricultural land and human settlements.

4. Top ranked models, based on Akaike’s Information Criterion corrected for small sample size, indicated that the negative effects of the presence of dogs and agricultural land, and the positive effects of the presence of grassland and fallow land habitats were the strongest predictors of Indian fox spatial distribution. Thus, the use of the landscape by Indian foxes was determined not only by habitat type, but also by the presence of a mid‐sized carnivore, the dog.

5. Synthesis and applications. Our results show that the presence of domestic dogs on the periphery of natural habitats can interfere with the spatial distribution of a sympatric carnivore. Vaccination and sterilization programmes, aimed at reducing population sizes and pathogen prevalence, do not restrict the free‐ranging behaviour of dogs. Therefore, in areas of conservation value, control of free‐ranging dogs would be required to fully mitigate the deleterious effects of dogs on native carnivores and other wildlife.
Nitrogen source interacts with ROP signalling in root hair tip‐growth
Authors: BLOCH DARIA , MONSHAUSEN GABRIELE , SINGER MEROMIT , GILROY SIMON , YALOVSKY SHAUL
Published: September 2010

Root hairs elongate in a highly polarized manner known as tip growth. Overexpression of constitutively active Rho of Plant (ROP)/RAC GTPases mutants induces swelling of root hairs. Here, we demonstrate that Atrop11CA‐induced swelling of root hairs depends on the composition of the growth medium. Depletion of ammonium allowed normal root hair elongation in Atrop11CA plants, induced the development of longer root hairs in wild‐type plants and suppressed the effect of Atrop11CA expression on actin organization and reactive oxygen species distribution, whereas membrane localization of the protein was not affected. Ammonium at concentrations higher than 1 mM and the presence of nitrate were required for induction of swelling. Oscillations in wall and cytoplasmic pH are known to accompany tip growth in root hairs, and buffering of the growth medium decreased Atrop11CA‐induced swelling. Fluorescence ratio imaging experiments revealed that in wild‐type root hairs, the addition of NH4NO3 to the growth medium induced an increase in the amplitude of extracellular and intracellular pH oscillations and an overall decrease in cytoplasmic pH at the cell apex. Based on these results, we suggest a model in which ROP GTPases and nitrogen‐dependent pH oscillations function in parallel pathways, creating a positive feedback loop during root hair growth.
Circadian aspects of post‐operative morbidity and mortality
Authors: KVASLERUD T. , HANSEN M. V. , ROSENBERG J. , GÖGENUR I.
Published: September 2010

It has been well established that there exists a circadian concentration of cardiovascular, cerebrovascular and cardiopulmonary events. The aim was to describe aspects of circadian variation in relation to cardiovascular, cerebrovascular and thromboembolic diseases and to describe the literature concerning post‐operative circadian disturbances. We also present the literature concerning circadian variation in post‐operative morbidity and mortality. PubMed and the Cochrane database were searched for papers using a combination of ‘circadian,’‘surgery,’‘post‐operative,’‘mortality’ and ‘morbidity.’ Eleven relevant studies were found, and seven of these were excluded due to the use of time of surgery and not time of morbidity or mortality as the main variable. The results from the four articles showed a circadian distribution of morbidity and mortality that mimics the one seen without surgery. There is a peak incidence of myocardial ischemia, fatal thromboembolism and sudden unexpected death in the morning hours. A circadian variation exists in post‐operative morbidity and mortality. The observed circadian variation in post‐operative morbidity and mortality may warrant a chronopharmacological approach to patients in the perioperative period. The underlying pathophysiological mechanisms should be the focus for future studies.
Role of the Mesonephros as a Transient Haematopoietic Organ in the Bovine Embryo
Authors: Kritzenberger M. , Wrobel K.‐H.
Published: September 2010

With 7 figures and 2 tables

During vertebrate embryogenesis, haematopoietic stem cells (HSC) arise in the aorta‐gonads‐mesonephros (AGM) region. In the present study, we examined serial sections of 22–34 days post‐insemination (dpi) bovine embryos, a species with a well‐developed and functional mesonephros. We describe the temporo‐spatial distribution of presumptive c‐kit positive HSC and the occurrence of haematopoietic foci in the mesonephros and fetal liver using specific antibodies directed against haematopoietic cell markers and conventional electron microscopy. In the mesonephros, presumptive HSC were found at 23–24 dpi in the blood stream, in the endothelial lining of the filtering capillaries and in the septal stroma of the cranial part of the mesonephros, the mesonephric giant corpuscle (MGC), suggesting a colonalization via the blood stream from the haematopoietic clusters of the dorsal aorta. From 25 to 30 dpi, presumptive HSC predominate in the septal stroma of the MGC, were they first expand but then decline and disappear following 32 dpi. In parallel, we found ongoing erythropoiesis and myelopoiesis starting in the MGC at 24 dpi and extending during the complete observation period. In the embryonic liver, colonization with presumptive c‐kit positive HSC occurs slightly later, at 25 dpi. Active formation of blood cells in the liver increases following 30 dpi. In conclusion, the mesonephros of bovine embryos, in particular its MGC, functions as a primitive haematopoietic organ, temporarily intercalated between extraembryonic erythropoiesis and haematopoiesis within in the fetal liver, thus recapitulating for a short period a phylogenetically old site of blood formation.
Topical agents for idiopathic distal colitis and proctitis
Authors: Lawrance Ian Craig
Published: September 2010

Rectally administered topical agents have demonstrated efficacy in the maintenance of distal colitis (DC) and proctitis and as they are rarely associated with significant blood drug levels, side effects are infrequent. The topical 5‐aminosalicylic acid (5‐ASA) suppositories and enemas target different regions of the distal colon and are effective for proctitis and DC, respectively. They demonstrate clinical results that are better than oral 5‐ASAs and are preferred to topical steroids with better clinical, endoscopic and histological outcomes, without the risk of adrenal suppression. Disease resistant to topical agents, however, can be extremely difficult to manage. The addition of oral 5ASAs, steroids, immunosuppressants and the anti‐tumor necrosis factor‐α agents may be effective, but can result in significant side effects and not all patients will respond to the therapies. It is for these patients that new and novel therapies are required. Novel topical agents have been proposed for the management of resistant DC. These agents included butyrate, cyclosporine, and nicotine enemas, as well as tacrolimus suppositories, and tacrolimus, ecabet sodium, arsenic, lidocaine, bismuth, rebamipide and thromboxane enemas. While some of these agents appear to demonstrate impressive outcomes, the majority have only been examined in small open‐labeled studies. There is thus a desperate need for more randomized double‐blinded placebo controlled studies to investigate the clinical utility of these topical therapies. This review summarizes the efficacy of the established topical therapies, and explores the available data on the new and novel topical agents for the management of DC and proctitis.