bluuebunny/crossref_metadata_2025 huggingface dataset:
Instabilities of Tubular Beams Simultaneously Subjected to Internal and External Axial Flows
Authors: Hannoyer M. J. , Pai¨doussis M. P.
Published: November 2010

This paper examines the dynamics and stability of cylindrical tubular beams conveying fluid and simultaneously subjected to axial external flow. In deriving the equation of small motions, inviscid hydrodynamic forces are obtained by slender-body theory, modified to account for the boundary-layer thickness of the external flow; internal dissipation and gravity effects are also taken into account. Solutions are obtained by means of a method similar to Galerkin’s, with the eigenfunctions approximated by Fourier series. Calculations are presented for tubular beams either clamped at both ends or cantilevered. It is shown that for sufficiently high flow velocities, either internal or external, the system, is subject to divergence and/or flutter. In the case of clamped-clamped tubular beams the effect of the two flows (internal and external) on stability is additive, so that if either flow is just below the corresponding critical value for instability, an increase in the other flow precipitates instability. This is not always the case for cantilevered beams; if the system is just below the threshold of instability due to either flow, instability may be eliminated if the other flow is increased. Experiments conducted with moulded rubber tubular beams in a vertical water tunnel corroborate the theoretically predicted behavior.
The Rigidity and Performance of a Helicopter Gearbox With a Cantilevered Housing and Two Taper Roller Bearings
Authors: Taha M. M. A. , Ettles C. M. McC. , MacPherson P. B.
Published: November 2010

A theoretical study has been made to determine the rigidity and performance of a helicopter gearbox with a cantilevered housing and two taper roller bearings. Due to the interaction of the deflection of all component parts such as gears, shafts, bearings, casings, spacers, etc., it was necessary to consider these in combination rather than individually. A computer program has been developed for analyzing a typical helicopter type input pinion assembly in which the pinion is supported by a pair of taper roller bearings. This program is suitable for determining the influence that various factors exert on the rigidity of the pinion and the performance of the bearings and which would be difficult to consider by other means. Typically the influence of endfloat or preload, misalignment of the races, casing and shaft deflection, wall thickness of the casing and the hollow shaft, and the spacing between bearings are all considered. The program is now being used as a basis for design optimization in terms of bearing lives and pinion stiffness.
On the Determination of the Fundamental Frequency of Vibration of Clamped Rectangular Plates of Variable Thickness
Authors: Laura P. A. A. , Luisoni L. E.
Published: November 2010

It is shown that use of polynomial approximations and a variational approach allows for a very simple determination of the fundamental frequency of vibration in two cases of practical interest and results are obtained for several values of width to length ratios.
Thermal Response of Slabs Subjected to Non-Symmetric Convective Heat Transfer
Authors: Fasiczka R. G. , Westermann E. L.
Published: November 2010

This paper presents a general solution of the transient response of an infinite plate (0 < x < l; y & z = ± ∞) to a step change in the surrounding temperatures. Each face of the plate is subjected to independent boundary conditions in terms of temperature and convective heat transfer coefficient. The results are presented in chart form as a function of dimensionless time with the two surface Biot numbers as the parameters. Results include surface temperatures, average temperature, and the first moment of the temperature distribution. The results are quite useful for the solution of a wide range of transient thermal problems. This includes heat flux determinations and thermal transient stresses in nuclear power piping.
A New Interpretation for the Dynamic Phenomena Associated with Geneva Mechanisms
Authors: Taat M. , Tesar D.
Published: November 2010

The basic Geneva Mechanism is one of the most widely used intermittent motion mechanisms. The classification of its dynamic characteristics is established in this paper to make feasible, meaningful comparisons with all other available mechanisms for the same task. Further, the coupling in series of two Genevas or another mechanism and a Geneva is considered and recommendations are made in terms of several dynamic criteria. A large collection of reference charts and a tabulation of numerical classification data are provided for comparative design by the engineer.
Generalized Force Curve Shapes for Structural Synthesis of Joint Torque Systems to Produce a Desired Dynamic Motion Time Response of a 4R-4Bar
Authors: Carson W. L. , Haney R. S.
Published: November 2010

Synthesis of a force system which will drive a linkage to have a desired dynamic motion-time response is basically a task of curve fitting the generalized force curve equation, GFS, of a force system to the generalized force, DGF, required to drive the mechanism. This design, synthesis task can be broken into two phases: 1) structural synthesis and 2) dimensional synthesis. This paper deals primarily with Phase 1; selecting which type, number of each, and between which links to attach each force device. The hypotheses upon which this paper is based are: 1) that specific linkage-force system configurations have “characteristically” shaped GFS curves, and 2) their shape must in general be similar to the DGF curve shape to obtain “satisfactory” results in dimensional synthesis. The paper presents a summary of characteristic curve shapes for joint torque in a 4R-4Bar crank-rocker mechanism, the influence of parameters on these curves, and an illustrative example of structural synthesis.
Game Theory Approach in Multicriteria Optimization of Function Generating Mechanisms
Authors: Rao S. S. , Hati S. K.
Published: November 2010

The multicriteria optimization of function generating mechanisms is considered using game theory. Specifically the design of spherical four-revolute function generating mechanisms, with the objective of minimizing structural error, mechanical error and a measure of manufacturing cost, is considered. Both the side and behavior constraints are included in the formulation of the probabilistic model of the system. The solution concepts of game theory are translated in finding an optimal trade-off between the three objectives. A method of obtaining the desired Pareto-optimal solution, which maximizes a specified supercriterion, is discussed. The proposed method of synthesis is illustrated by considering the generation of the function y = sin x.
Technology Transfer in Biokinematics of the Human Spine
Authors: Patwardhan A. G. , Soni A. H. , Sullivan J. A.
Published: November 2010

The present paper examines the role of theoretical kinematics of rigid body motion in solving some of the basic research problems in the study of intervertebral motion in human spine. The paper presents an extensive literature search in the bio-kinematics of human spine and discusses the opportunities for technology transfer in theoretical kinematics to study the mechanics of human spine.
Finite Element Analysis of Mindlin Plates
Authors: Bapu Rao M. N. , Kumaran K. S. S.
Published: November 2010

A finite element displacement formulation with the shear deformation capability for the axisymmetric bending analysis of circular plates is presented. The displacement field is expressed in terms of interpolation functions which are exact solutions to Mindlin’s governing plate equations. Numerical results for some representative example problems are also presented to demonstrate the accuracy of the proposed method.
Reliability Analysis and Design of Epicyclic Gear Trains
Authors: Rao S. S.
Published: November 2010

The concepts of system reliability are applied for the structural reliability analysis and design of epicyclic gear trains. The reliability analysis is based on the representation of an epicyclic gear train as a series-parallel network. The power transmitted, the speed of the input shaft, the center distance between the gear pairs and the permissible stresses are assumed to be random variables following normal distribution. The layout of the gears and the speed ratios are assumed to be known. The face widths of the gears are taken as random design parameters. The design criterion is that the reliability of the gear train either in bending or surface wear failure mode at any of the output speeds must be equal to a specified value. The design of an epicyclic transmission system which gives four forward speeds and one reverse speed is considered for illustration. The results of the reliability-based design of the gear train are compared with those of the conventional deterministic design.
A Microprocessor-Controlled Test System Utilizing Relevant Component Duty Cycles
Authors: King R. K. , Decker R. L.
Published: November 2010

The need for meaningful fatigue tests of hydraulic and mechanical components is ever-increasing. Such tests are often performed in the laboratory. Previous investigations have shown that laboratory test lives will be different than field duty lives if laboratory test cycles used have either a different load or “time at load” than the field duty cycle. Field duty cycles often consist of complex shapes. The closer that the laboratory test cycles approximate the field duty cycle, the better the correlation that can be drawn between laboratory and field lives. This paper presents a technique for predicting field endurance life from laboratory test results which capitalizes on the OSU material failure number theory. It describes a microprocessor-controlled test system which provides an inexpensive, reliable means of producing test cycles which approximate the shape of the field duty cycle. An example application is presented.
Interrelationships Between Mechanical Properties and the Significance of Defects
Authors: Nichols R. W.
Published: November 2010

This paper reviews some of the recent developments in the use of fracture mechanics to define the acceptable sizes and shapes of flaws in single-wall steel pressure vessels. The results of such appraisals are being incorporated in standard specifications and codes, for example in ASME and UK proposals. These steps make towards a worthwhile improvement in assessed reliability, and put in perspective particularly the considerable tolerance for porosity and slag inclusion flaws. Even so, for cracklike defects there are uncertainties still left after making such an analysis: these can be reduced by devoting sufficient attention to quality control of material fracture toughness, fabrication routes and inspection methods. The choice of materials of high intrinsic fracture toughness and low sensitivity to fabrication and process is of great importance. From the nondestructive examination side, reliability and certainty of reporting are more important than sensitivity, putting the emphasis on automated recording techniques and on overall inspection tools such as acoustic emission. Attention to these aspects must be given when considering permissible design stresses and permissible stress concentration levels.
Inelastic, Nonlinear Analysis of Stiffened Shells of Revolution by Numerical Integration
Authors: Levine H. S. , Svalbonas V.
Published: November 2010

This paper describes the latest addition to the STARS system of computer programs, STARS-2P, for the plastic, large deflection analysis of axisymmetrically loaded shells of revolution. The STARS system uses a numerical integration scheme to solve the governing differential equations. Several unique features for shell of revolution programs that are included in the STARS-2P program are described. These include orthotropic nonlinear kinematic hardening theory, a variety of shell wall cross sections and discrete ring stiffeners, cyclic and nonproportional mechanical and thermal loading capability, the coupled axisymmetric large deflection elasto-plastic torsion problem, an extensive restart option, arbitrary branching capability, and the provision for the inelastic treatment of smeared stiffeners, isogrid, and waffle wall constructions. To affirm the validity of the results, comparisons with available theoretical and experimental data are presented.
Formulas for Canister and Pipe Design in Underground Nuclear Emplacement
Authors: Blake A.
Published: November 2010

In this paper, pressure vessel theory and practice are applied to the analysis and design of long emplacement strings and canister hardware used in a complex environment of underground nuclear tests. Design formulas are given for the collapse pressure of canisters and piping under external soil pressure and for the axial response of gussetted flanges supported by the theoretical and experimental results. The paper is intended primarily as a practical treatment of a complex problem of structural response with the aid of user-oriented, closed-form solutions.
On the Dynamic Analysis of Curved and Twisted Cylinders Transporting Fluids
Authors: Doll R. W. , Mote C. D.
Published: November 2010

The longitudinal, torsional and 2-transverse equations of motion are formulated for the titled problem through application of Hamilton’s Principle. Curvature-torsion conditions under which linear oscillation in a plane can exist are identified. The finite element method with isoparametric elements is used for discretization prior to spectra analysis. Natural frequency calculations over a range of mass transport velocities and cylinder end conditions were carried out for comparison with constant and variable curvature analyses and experiment. These results support the application of the constant curvature, inextensible centerline model for curved cylinder vibration analysis.
Creep-Fatigue Crack Propagation in Austenitic Stainless Steel
Authors: Shahinian P.
Published: November 2010

The inclusion of tensile hold periods during cyclic loading did not detrimentally affect rate of crack propagation in solution-annealed type 304 steel and 20 percent cold-worked type 316 steel at 427 C (800 F). But at 593 C (1100 F), increases in hold time caused higher crack growth rates (da/dN), for a given stress intensity factor range (ΔK), for both steels. In terms of da/dt, hold periods decreased growth rates for the type 304 steel. The number of cycles to failure of the type 304 steel decreased and the time to failure increased with increasing hold times; but the trends were not the same for the type 316 steel. Hold periods caused a shift in cracking mode from transgranular to intergranular.
Thermoelastic Analysis of Nonaxisymmetrically Heated Thick Cylindrical Shells
Authors: Gupta G. D. , Rao M. S. M. , Narayanan T. V. , Gangadharan A. C.
Published: November 2010

The thermoelastic problem of a thick cylinder subjected to nonaxisymmetric temperature distribution is considered. The temperature distribution may be harmonic or non-harmonic. The problem is formulated in terms of the in-plane displacements u and v and a solution is obtained by using Fourier series method. Two examples corresponding to a steady state and transient thermal distributions are solved. The steady-state case is compared to an exact solution and the transient problem is compared to a finite element solution. The transient problem considered is that of a solar superheater during startup after the departure of a cloud cover. The problem has applications in the conventional fossil-fired steam generators as well.
Nonshrinking Heat and Acid-Resistant Hydrothermal Cements for Use in Oil and Gas Wells
Authors: Mallow W. A. , Dean J. K.
Published: November 2010

Novel hydrothermal cements have been developed for use in the recovery of energy sources from hot and deep wells ranging in temperatures from 150°F to over 1000°F.
Pressure Losses Inside Tool Joints Can Alter Drilling Hydraulics
Authors: Denison E. B.
Published: November 2010

Pressure losses associated with small-throated (internal upset) tool joints have been measured. Computations show that these losses may contribute significantly to the overall loss in a mud circulating system. This can limit the hydraulic horsepower available at the bit and/or the annular velocity in the borehole.
Normal Mode Solution of Fluid-Coupled Concentric Cylindrical Vessels
Authors: Stokey W. F. , Scavuzzo R. J.
Published: November 2010

A normal mode solution is developed for concentric cylinders coupled by fluid between them and subjected to foundation input motion. Both time-history and spectral inputs can be specified. Example problems are presented.
Failure Analysis of Steam Generator Tubes With Dented and Wastage Configurations
Authors: Reich M. , Prachuktam S. , Chang T. Y.
Published: November 2010

The occurrence of PWR steam generator tube cracking, denting, and wastage has been reported in the recent literature [1–5]. As indicated by its title, this paper concerns itself with the inelastic structural response of the tubes that result from various assumed monotonic as well as cyclic loading conditions, which ultimately could lead to the tube failure.
The Estimation of Aquifer Properties From Reservoir Performance in Water-Drive Fields
Authors: Chatas A. T.
Published: November 2010

The purpose of this paper is to indicate a method for estimating values of specified aquifer parameters from an investigation of the reservoir performance of an associated oilfield. To achieve this objective an analysis was made of the simultaneous solution of the material-balance and diffusivity equations, followed by an application of the method of least squares. Three analytical functions evolved, which in dimensionless form were numerically evaluated by computer and tabulated herein. Application of the proffered method requires the simultaneous solution of the three normal equations developed in the paper.
Finite Element Static Analysis of Axisymmetric Solids With Material and Geometric Nonlinearities
Authors: Hartzman M.
Published: November 2010

The application of the finite-element method to the analysis of various axisymmetric solids subjected to axisymmetric static loads is described. The analysis accounts for geometric nonlinear effects due to assumed large displacements and rotations and to elastic-plastic deformation. The solutions are obtained by applying an incremental-iterative numerical algorithm. Results are shown for the problem of an internally pressurized thick cylinder where considerable deformation occurred. Comparison with an alternate numerical solution indicates reasonable agreement. Additional numerical examples include the calculation of the collapse load of a built-in spherical dome and the instability load of a flat plate subjected to transverse pressure.
An Energy-Based Fatigue and Creep-Fatigue Damage Parameter
Authors: Leis B. N.
Published: November 2010

A general damage parameter for fatigue and creep-fatigue applications based on the hypothesis that damage is dependent on the internal total octahedral strain energy is derived. This general parameter is valid for isothermal mechanical cycling and inherently accounts for multiaxiality and mean stress for both nonviscous and viscous deformation response, including hold times. Forms of the parameter which correspond to laboratory test conditions under generalized states of stress and strain with nonzero mean stress are derived. The ability of these specific forms to affect data consolidation is examined using experimental fatigue and creep-fatigue life data for the corresponding conditions. It is shown that these specific forms of the general parameter affect a high degree of data consolidation.
Loading Mechanisms in Thawed Permafrost Around Arctic Wells
Authors: Goodman M. A.
Published: November 2010

Four permafrost thaw-subsidence loading mechanisms are described for inducing casing strain. Phase change contraction in ice rich soil and consolidation with fluid flow are more likely to occur in surface and near surface soils. Stiffness reduction and pore pressure reduction are important in deep permafrost and generate body force-type loads. The equations for stiffness reduction loading are presented in terms of an elastic model. The effects of lithology and thaw variations on casing loads are examined in the context of the four mechanisms.
Approximate Analysis of Intersecting Equal Diameter Cylindrical Shells Under Internal Pressure
Authors: Updike D. P. , Kalnins A.
Published: November 2010

Stresses in the vicinity of the crotch of a pressurized, crossed cylinder pipe connection and a tee connection with equal diameter and thickness branches are determined by two different methods. In the first the structure is reduced to an equivalent, axisymmetric shell, while in the second, ovaling deformations are taken into account. The results agree well with each other and with published experimental results.
Metallurgical and Mechanical Considerations in Selection of a Fracture-Safe Explosives Containment Vessel
Authors: Puzak P. P. , Loss F. J.
Published: November 2010

Public safety agencies in many large metroplitan cities need a mobile system which is capable of safely transporting “terrorist-type” bombs from a discovery point to a disposal area. In view of the requirement of such a system by the Government of the District of Columbia, Metropolitan Police Department (DC-MPD), the Naval Research Laboratory has provided a solution to this problem by designing and fabricating a prototype explosives containment system. The system capability was successfully demonstrated by proof tests using dynamite. The critical elements of the system are an ultrahigh-strength, highly fracture-resistant steel pressure vessel held in a specially fabricated support base made of similar steel. Materials for the system were selected and evaluated on the basis of advanced metals characterization procedures to ensure fracture-safe performance in this unique application. A duplicate system has been donated to the DC-MPD. This system is considered to be the most reliable, highest-strength and lightest-weight mobile explosives containment system available to any metropolitan public safety organization.
VALIDITY OF NAKAMURA–KUDO SCALING OF CHARGED PARTICLE PSEUDORAPIDITY DISTRIBUTION IN RELATIVISTIC HIGH-ENERGY h–A INTERACTIONS
Authors: GHOSH DIPAK , DEB ARGHA , PAL SITARAM , DAS RUPA , LAHIRI MADHUMITA BANERJEE
Published: November 2010

Nakamura and Kudo proposed a scaling form for charged particle pseudorapidity distributions on the basis of scaling in the mean hypothesis. This scaling form was tested primarily for hadron–hadron interaction data. But no attempt was made to verify this for hadron–nucleus interaction which offers unique opportunity to learn about the space–time structure of a strongly interacting process. In view of this we report an analysis of p–AgBr interaction data at 400 GeV/c and 200 GeV/c, π-–AgBr interaction data at 200 GeV/c and 350 GeV/c to test its (Nakamura–Kudo scaling) validity in hadron–nucleus interaction. In all cases the data show a remarkable agreement with the scaling behavior of Nakamura and Kudo.
PREDICTION OF THE EXPOSURE STATUS OF TRANSMEMBRANE BETA BARREL RESIDUES FROM PROTEIN SEQUENCE
Authors: HAYAT SIKANDER , WALTER PETER , PARK YUNGKI , HELMS VOLKHARD
Published: November 2010

We present BTMX (Beta barrel TransMembrane eXposure), a computational method to predict the exposure status (i.e. exposed to the bilayer or hidden in the protein structure) of transmembrane residues in transmembrane beta barrel proteins (TMBs). BTMX predicts the exposure status of known TM residues with an accuracy of 84.2% over 2,225 residues and provides a confidence score for all predictions. Predictions made are in concert with the fact that hydrophobic residues tend to be more exposed to the bilayer. The biological relevance of the input parameters is also discussed. The highest prediction accuracy is obtained when a sliding window comprising three residues with similar Cα- Cβvector orientations is employed. The prediction accuracy of the BTMX method on a separate unseen non-redundant test dataset is 78.1%. By employing out-pointing residues that are exposed to the bilayer, we have identified various physico-chemical properties that show statistically significant differences between the beta strands located at the oligomeric interfaces compared to the non-oligomeric strands. The BTMX web server generates colored, annotated snake-plots as part of the prediction results and is available under the BTMX tab at . Exposure status prediction of TMB residues may be useful in 3D structure prediction of TMBs.
PREDICTING PROTEIN FOLDING RATE FROM AMINO ACID SEQUENCE
Authors: GUO JIANXIU , RAO NINI
Published: November 2010

Predicting protein folding rate from amino acid sequence is an important challenge in computational and molecular biology. Over the past few years, many methods have been developed to reflect the correlation between the folding rates and protein structures and sequences. In this paper, we present an effective method, a combined neural network — genetic algorithm approach, to predict protein folding rates only from amino acid sequences, without any explicit structural information. The originality of this paper is that, for the first time, it tackles the effect of sequence order. The proposed method provides a good correlation between the predicted and experimental folding rates. The correlation coefficient is 0.80 and the standard error is 2.65 for 93 proteins, the largest such databases of proteins yet studied, when evaluated with leave-one-out jackknife test. The comparative results demonstrate that this correlation is better than most of other methods, and suggest the important contribution of sequence order information to the determination of protein folding rates.
A peer-to-peer architecture for networked virtual environments
Authors: Varvello Matteo
Published: November 2010

A Networked Virtual Environment (NVE) is a synthetic world where human-controlled avatars can interact. Multiplayer on-line games such as Quake and World of Warcraft are the most popular applications for NVEs. In early 2003, Second Life (SL), a NVE where avatars can invent a new social life, was launched. The main innovative feature of SL is user-generated content: avatars participate in the development of the virtual environment by creating objects such as cars, trees, and buildings. SL rapidly became the most popular NVE, reaching more than 16 million registered users in September 2009.
The osmopressor response to water drinking
Authors: May Marcus , Jordan Jens
Published: November 2010

Water drinking elicits profound pressor responses in patients with impaired baroreflex function and in sinoaortic-denervated mice. Healthy subjects show more subtle changes in heart rate and blood pressure with water drinking. The water-induced pressor response appears to be mediated through sympathetic nervous system activation at the spinal level. Indeed, water drinking raises resting energy expenditure in normal weight and obese subjects. The stimulus setting off the response is hypoosmolarity rather than water temperature or gastrointestinal stretch. Studies in mice suggest that this osmopressor response may involve transient receptor potential vanniloid 4 (Trpv4) receptors. However, the (nerve) cell population serving as peripheral osmosensors and the exact transduction mechanisms are still unknown. The osmopressor response can be exploited in the treatment of orthostatic and postprandial hypotension in patients with severe autonomic failure. Furthermore, the osmopressor response acutely improves orthostatic tolerance in healthy subjects and in patients with neurally mediated syncope. The phenomenon should be recognized as an important confounder in cardiovascular and metabolic studies.
Phase II Study of Everolimus (RAD001) in Previously Treated Small Cell Lung Cancer
Authors: Tarhini Ahmad , Kotsakis Athanasios , Gooding William , Shuai Yongli , Petro Daniel , Friedland David , Belani Chandra P. , Dacic Sanja , Argiris Athanassios
Published: November 2010

Purpose: Mammalian target of rapamycin (mTOR) is a promising target in small cell lung cancer (SCLC). We designed a phase II study of everolimus, an mTOR inhibitor, in previously treated, relapsed SCLC.

Experimental Design: Patients were treated with everolimus 10 mg orally daily until disease progression. The primary endpoint was disease control rate (DCR) at 6 weeks. PI3K/Akt signaling pathway biomarkers were evaluated on baseline tumor tissue.

Results: A total of 40 patients were treated: 23 had 1 prior regimen/sensitive relapse, 4 had 1 prior regimen/refractory, and 13 had 2 prior regimens. Twenty-eight patients received 2 or more cycles of everolimus, 7 received 1 cycle, and 5 did not complete the first cycle. Best response in 35 evaluable patients: 1 (3%) partial response (in sensitive relapse), 8 (23%) stable disease, and 26 (74%) progression; DCR at 6 weeks was 26% (95% CI = 11–40). Median survival was 6.7 months and median time to progression was 1.3 months. Grade 3 toxicities included thrombocytopenia (n = 2), neutropenia (n = 2), infection (n = 2), pneumonitis (n = 1), fatigue (n = 1), elevated transaminases (n = 1), diarrhea (n = 2), and acute renal failure (n = 1). High phosphorylated AKT expression was modestly associated with overall survival (HR = 2.07; 95% CI = 0.97–4.43). Baseline S6 kinase protein expression was significantly higher in patients with disease control versus patients with progression (P = 0.0093).

Conclusions: Everolimus was well tolerated but had limited single-agent antitumor activity in unselected previously treated patients with relapsed SCLC. Further evaluation in combination regimens for patients with sensitive relapse may be considered. Clin Cancer Res; 16(23); 5900–7. ©2010 AACR.
Comparative Analysis by Chromosome Painting of the Sex Chromosomes in Arvicolid Rodents
Authors: Acosta M.J. , Romero-Fernández I. , Sánchez A. , Marchal J.A.
Published: November 2010

Sex chromosome evolution in mammals has been extensively investigated through chromosome-painting analyses. In some rodent species from the subfamily Arvicolinae the sex chromosomes contain remarkable features such as giant size, a consequence of heterochromatic enlargement, or asynaptic behaviour during male meiosis. Here, we have made a comparative study of the sex chromosomes in 6 arvicolid species using different probes from the X and Y chromosomes of 3 species, in order to gain knowledge about intra- or interspecific preservation of euchromatic regions. Our results clearly reveal poor conservation of the euchromatic region of the Y chromosome within these species, while the euchromatin on the X chromosome is extremely well preserved. Furthermore, we detected no clear correlation between the synaptic/asynaptic behaviour of the sex chromosomes, and the presence or absence of sequence homology within their euchromatic regions. Notably, our study has shown a new relationship between the giant sex chromosomes of 2 species, Microtus agrestis and Microtus cabrerae, that is, both X and Y share a novel region of common sequences in the euchromatin that is not present in the other species analysed. This interspecific euchromatic conservation, limited to the giant sex chromosomes, could point towards a common evolutionary origin for the heterochromatic enlargement process that has characterized the evolution of the sex chromosomes in some arvicolid species.
Oligoarray (105K) CGH Analysis of Chromosome Microdeletions within 10q22.1q24.32
Authors: Reddy K.S. , Mardach R. , Bass H.
Published: November 2010

To populate the chromosome 10 genetic landscape with clinical correlations we describe 3 non-overlapping, nearly contiguous deletions within chromosome 10q22.1q24.32. Three cases were studied by oligoarray comparative genomic hybridization (CGH), cytogenetics, and/or fluorescence in situ hybridization. The array CGH showed de novo deletions: arr 10q22.1q22.2(74,115,795–77,077,025)×1dn, arr 10q22.3q23.2(81,437,039–89,144,374)×1dn and arr 10q23.33q24.32(94,894,780–103,144,781)×1dn. Developmental delay, speech impairment and growth retardation were observed in all 3 patients. Facial palsy and renal dysplasia were the other notable findings. The renal dysplasia was ascribed to the loss of a PAX2 gene in the 10q23.33q24.32 deletion patient (OMIM *167409). The facial palsy was seen in the case with a deletion of 10q22.1q22.2. One of three 10q22.3q23.2 deletions involved low copy repeats. We have described the phenotype specific to the chromosome region involved within 10q22.1–q24.32. The oligoarray analysis improved the clinical management of the patients and enabled counseling for deleted genes.
Nephrotoxicities Associated with the Use of Tyrosine Kinase Inhibitors: A Single-Center Experience and Review of the Literature
Authors: Jhaveri Kenar D. , Flombaum Carlos D. , Kroog Glenn , Glezerman Ilya G.
Published: November 2010

Background: Sunitinib is an oral multitargeted tyrosine kinase receptor inhibitor (MTKI) used for the treatment of renal cell carcinoma. These small-molecule agents inhibit signaling through receptor tyrosine kinases such as vascular endothelial growth factor receptor, platelet-derived growth factor receptor and cytokine stem cell factor receptor, among others. Although the development of these novel molecular-targeted agents represents a substantial advance in the treatment of metastatic cancer, the spectrum of their adverse effects may be broader than initially predicted. Method: We performed a retrospective chart review of patients who had received sunitinib and developed renal insufficiency. Results: We describe 4 patients with renal cell carcinoma and 1 patient with transitional cell carcinoma treated with sunitinib who experienced various degrees of nephrotoxicity including hypertension, proteinuria, thrombotic microangiopathy, and acute and chronic kidney injury which resolved upon cessation of MTKI. Conclusions: Nephrologists and oncologists should be aware of the potential for toxic renal effects, and we recommend guidelines for early recognition and treatment of these conditions in patients receiving MTKI.
X-Y Chromosome Synapsis and Recombination in 3 Vole Species of Asian Lineage of the Genus Microtus (Rodentia: Arvicolinae)
Authors: Borodin P.M. , Basheva E.A. , Dashkevich O.A. , Golenishchev F.N. , Kartavtseva I.V.
Published: November 2010

The pattern of X-Y chromosome pairing in male meiosis is an important taxonomic feature of grey voles of the genus Microtus. Asynaptic sex chromosomes have been found in the majority of species of the Palearctic phylogenetic lineage of this genus, while normal X-Y synapsis has been observed in the species of subgenus Pallasiinus belonging to the Asian phylogenetic lineage. We analyzed sex chromosome pairing and recombination in M. maximowiczii, M. mujanensis and M. fortis which also belong to the Asian phylogenetic lineage (subgenus Alexandromys). Using immunostaining for the proteins of the synaptonemal complex (SCP3) and recombination nodules (MLH1) we demonstrated that X and Y chromosomes of these species paired and recombined in a short subtelomeric region. This indicates that the sex chromosomes of these species retain an ancestral fully functional pseudoautosomal region, which has been lost or rearranged in the asynaptic species of the genus Microtus.
19p13.3 Aberrations Are Associated with Dysmorphic Features and Deviant Psychomotor Development
Authors: Siggberg L. , Olsén P. , Näntö-Salonen K. , Knuutila S.
Published: November 2010

Here, we describe 2 patients with de novo genomic imbalances of 19p13.3. Using high-resolution microarray analysis, we detected a 1.25-Mb deletion in one patient and a 0.81- Mb duplication in another. The resulting phenotypes are quite different; one is a 2-year-old boy with macrocephaly and normal growth, while the other is a 9-year-old boy with microcephaly and growth retardation since birth. Both have dysmorphic features and psychomotor developmental delay. This report gives evidence of the effect of small aberrations of chromosome 19 and describes the phenotypes arising from a duplication and deletion of the same location at 19p13.3.
Comparative Cytogenetics of Giant Trahiras Hoplias aimara and H. intermedius (Characiformes, Erythrinidae): Chromosomal Characteristics of Minor and Major Ribosomal DNA and Cross-Species Repetitive Centromeric Sequences Mapping Differ among Morphologically Identical Karyotypes
Authors: Blanco D.R. , Lui R.L. , Vicari M.R. , Bertollo L.A.C. , Moreira-Filho O.
Published: November 2010

Karyotype and cytogenetic characteristics of 2 species of giant trahiras, Hopliasintermedius, São Francisco river basin, and Hopliasaimara, Arinos river (Amazon basin), were examined by conventional (C-banding, Ag-NOR, DAPI/CMA3 double-staining) and fluorescent in situ hybridization (FISH) with 5S, 18S rDNA probes and cross-species Cot-1 DNA probing. Both species invariably had diploid chromosome number 2n = 50 and identical karyotypes composed of 10 pairs of metacentric and 15 pairs of submetacentric chromosomes. On the other hand, staining with base-specific fluorochromes (CMA3, DAPI) and FISH mapping of repetitive DNA sequences showed extensive interspecific differences: while the genome of H. aimara had one submetacentric pair bearing CMA3-positive (DAPI-negative) sites, that of H. intermedius had 4 such pairs; while FISH with a 5S rDNA probe showed one (likely homologous) signal-bearing pair, that with 18S rDNA displayed one signal-bearing pair in H. intermedius and 2 such pairs in H. aimara. Cross-species FISH probing with Cot-1 DNA prepared from total DNA of both species showed no signals of Cot-1 DNA from H. aimara on chromosomes of H. intermedius but reciprocally (Cot-1 DNA from H. intermedius on chromosomes of H. aimara) displayed signals on at least 4 chromosome pairs. Present findings indicate (i) different composition of repetitive sequences around centromeres, (ii) different NOR phenotypes and (iii) distinct taxonomic status of both giant trahira species.
Conservation of shh cis-regulatory architecture of the coelacanth is consistent with its ancestral phylogenetic position
Authors: Lang Michael , Hadzhiev Yavor , Siegel Nicol , Amemiya Chris T , Parada Carolina , Strähle Uwe , Becker May-Britt , Müller Ferenc , Meyer Axel
Published: November 2010

Background

The modern coelacanth (Latimeria) is the extant taxon of a basal sarcopterygian lineage and sister group to tetrapods. Apart from certain apomorphic traits, its morphology is characterized by a high degree of retention of ancestral vertebrate structures and little morphological change. An insight into the molecular evolution that may explain the unchanged character of Latimeria morphology requires the analysis of the expression patterns of developmental regulator genes and their cis-regulatory modules (CRMs).

Results

We describe the comparative and functional analysis of the sonic hedgehog (shh) genomic region of Latimeria menadoensis. Several putative enhancers in the Latimeria shh locus have been identified by comparisons to sarcopterygian and actinopterygian extant species. Specific sequence conservation with all known actinopterygian enhancer elements has been detected. However, these elements are selectively missing in more recently diverged actinopterygian and sarcopterygian species. The functionality of the putative Latimeria enhancers was confirmed by reporter gene expression analysis in transient transgenic zebrafish and chick embryos.

Conclusions

Latimeria shh CRMs represent the ancestral set of enhancers that have emerged before the split of lobe-finned and ray-finned fishes. In contrast to lineage-specific losses and differentiations in more derived lineages, Latimeria shh enhancers reveal low levels of sequence diversification. High overall sequence conservation of shh conserved noncoding elements (CNE) is consistent with the general trend of high levels of conservation of noncoding DNA in the slowly evolving Latimeria genome.
Multilectin Assay for Detecting Fibrosis-Specific Glyco-Alteration by Means of Lectin Microarray
Authors: Kuno Atsushi , Ikehara Yuzuru , Tanaka Yasuhito , Angata Takashi , Unno Sachiko , Sogabe Maki , Ozaki Hidenori , Ito Kiyoaki , Hirabayashi Jun , Mizokami Masashi , Narimatsu Hisashi
Published: November 2010

BACKGROUND

Despite the progress made in understanding glyco-alterations of specific glycoproteins such as α1-acid glycoprotein (AGP) associated with liver fibrosis, there has been no useful diagnostic assay with a lectin recognizing the fibrosis-specific alteration and an antibody against the core protein. We therefore developed a compatible multiple lectin-antibody sandwich immunoassay on the basis of the results obtained by the lectin microarray analysis for monitoring fibrosis.

METHODS

AGP-enriched fractions derived from 0.5-μL sera of 125 patients with staging-determined fibrosis (26.4% F0–F1, 25.6% F2, 24% F3, and 23.2% F4) were subjected to systematic analysis by antibody-overlay lectin microarray. Data were analyzed to statistically relate to the degree of fibrosis progression. Additionally, we applied an optimal lectin signal set on the microarray to distinguish 45 patients with cirrhosis from 43 patients with chronic hepatitis.

RESULTS

Signal patterns of the 12 selected lectins reflected fibrosis-associated glyco-alteration of AGP. Among the 12 lectins, we found a specific lectin at each stage of fibrosis (i.e., significant fibrosis, severe fibrosis, and cirrhosis) (P < 0.0001). The test for the detection of cirrhosis showed that combinational use of 3 lectins (AOL, MAL, and DSA) on the array enhanced the diagnostic value for liver cirrhosis to 95% diagnostic sensitivity and 91% diagnostic specificity.

CONCLUSIONS

The multiple lectin-antibody sandwich immunoassay targeting AGP enables monitoring of disease progression in chronic hepatitis patients at risk of developing hepatocellular carcinoma.
Reelin Signals through Apolipoprotein E Receptor 2 and Cdc42 to Increase Growth Cone Motility and Filopodia Formation
Authors: Leemhuis Jost , Bouché Elisabeth , Frotscher Michael , Henle Frank , Hein Lutz , Herz Joachim , Meyer Dieter K. , Pichler Marina , Roth Günter , Schwan Carsten , Bock Hans H.
Published: November 2010

Lipoprotein receptor signaling regulates the positioning and differentiation of postmitotic neurons during development and modulates neuronal plasticity in the mature brain. Depending on the contextual situation, the lipoprotein receptor ligand Reelin can have opposing effects on cortical neurons. We show that Reelin increases growth cone motility and filopodia formation, and identify the underlying signaling cascade. Reelin activates the Rho GTPase Cdc42, known for its role in neuronal morphogenesis and directed migration, in an apolipoprotein E receptor 2-, Disabled-1-, and phosphatidylinositol 3-kinase-dependent manner. We demonstrate that neuronal vesicle trafficking, a Cdc42-controlled process, is increased after Reelin treatment and further provide evidence that the peptidergic VIP/PACAP38 system and Reelin can functionally interact to promote axonal branching. In conclusion, Reelin-induced activation of Cdc42 contributes to the regulation of the cytoskeleton of individual responsive neurons and converges with other signaling cascades to orchestrate Rho GTPase activity and promote neuronal development. Our data link the observation that defects in Rho GTPases and Reelin signaling are responsible for developmental defects leading to neurological and psychiatric disorders.
PHILOSOPHICAL LEGAL ETHICS AND PERSONAL INTEGRITY
Authors: Dare Tim
Published: November 2010

Alice Woolley's survey of contemporary legal ethics (UTLJ 60.4) discusses Daniel Markovits's A Modern Legal Ethics: Adversary Advocacy in a Democratic Age (Princeton University Press, 2008) and my The Counsel of Rogues? A Defence of the Standard Conception of the Lawyer's Role (Ashgate, 2009). Woolley argues that philosophical legal ethics has focused ‘too much on the ethical experience of the lawyer's life’ (???) and too little on ‘what, in a free and democratic society, the role of a lawyer should be’ (???). From that perspective, she finds my approach congenial. However, I do not entirely endorse the view that legal ethics should focus on one rather than the other of these sets of concerns. I discuss these issues in the first part of this response. In the second part, I contrast the accounts Markovits and I offer of integrity and roles. Markovits concludes that roles can underwrite integrity-preserving redescription only insofar as they are authoritatively insular, such that occupants ‘are not shaken by the fact others reject these concepts or even reject the role outright for themselves’ (225). Law, Markovits argues, is no longer insular in this way. I offer a different account of integrity, according to which whether a person has integrity turns upon whether they have engaged in a process of sincere and thorough reflection and displayed a readiness to accept the implications of such reflection. I argue that this is the better view of integrity, and that it allows the recognition of the authority of roles and so the possibility of integrity to lawyers.
INVESTING IN DEMOCRACY? POLITICAL PROCESS AND INTERNATIONAL INVESTMENT LAW
Authors: Schneiderman David
Published: November 2010

International investment law is rushing to stake out the high ground of democratic theory. It has been claimed that the interests of foreign investors ordinarily will not be represented within a host state's political processes and so investors deserve heightened protection from policy decisions that adversely affect investment interests. I argue in the present article that this smuggling of democratic theory and constitutional postulates into international investment law is inapt and, as an empirical matter, inaccurate. By looking to the us origins of political process doctrine, I argue that its invocation by international investment tribunals is inapposite given the doctrine's concern with relegating ordinary economic regulation to relaxed scrutiny. Nor is reference to the European experience all that helpful – representation reinforcement review has not been a hallmark of European jurisprudence. I claim that this worry over democratic processes masks an attempt at legitimating controversial review by investment tribunals of high public-policy matters. Moreover, as empirical studies suggest, this solicitude offered to investors by political process review is mostly unwarranted as foreign corporate actors can and do shape host domestic policy.
The Bluestockings and the Genealogy of the Modern Novel
Authors: Schellenberg Betty A.
Published: November 2010

Despite, or rather because of, their suspicion of the ‘novel’ and their relatively limited practice of the form, the eighteenth-century British intellectual women known as the Bluestockings serve as a useful indicator of their culture's gradual shift from resistance to sophisticated appreciation of the emerging novel genre. Their preference for generically mixed texts; their privileging of the active reading habits fostered by such materials; their elaboration of a novel theory emphasizing probability and ‘experiment’; and their increasing identification with stories of women's experience all worked to define the modern novel by the end of the century. I argue, indeed, that the novel the Bluestockings ultimately accepted, and that a second generation of Bluestocking writers such as Clara Reeve and Frances Burney adopted as its authorial specialty, was not the novel they initially resisted; rather, it was a deliberately constructed hybrid whose theory and practice had been shaped in part by their own priorities for, and understandings of, the operations of fiction.