bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporating a mucosal environment in a dynamic gut model results in a more representative colonization by lactobacilli
Authors: Van den Abbeele Pieter , Roos Stefan , Eeckhaut Venessa , MacKenzie Donald A. , Derde Melanie , Verstraete Willy , Marzorati Massimo , Possemiers Sam , Vanhoecke Barbara , Van Immerseel Filip , Van de Wiele Tom
Published: October 2011

To avoid detrimental interactions with intestinal microbes, the human epithelium is covered with a protective mucus layer that traps host defence molecules. Microbial properties such as adhesion to mucus further result in a unique mucosal microbiota with a great potential to interact with the host. As mucosal microbes are difficult to study in vivo, we incorporated mucin‐covered microcosms in a dynamic in vitro gut model, the simulator of the human intestinal microbial ecosystem (SHIME). We assessed the importance of the mucosal environment in this M‐SHIME (mucosal‐SHIME) for the colonization of lactobacilli, a group for which the mucus binding domain was recently discovered. Whereas the two dominant resident Lactobacilli, Lactobacillus mucosae and Pediococcus acidilactici, were both present in the lumen, L. mucosae was strongly enriched in mucus. As a possible explanation, the gene encoding a mucus binding (mub) protein was detected by PCR in L. mucosae. Also the strongly adherent Lactobacillus rhamnosus GG (LGG) specifically colonized mucus upon inoculation. Short‐term assays confirmed the strong mucin‐binding of both L. mucosae and LGG compared with P. acidilactici. The mucosal environment also increased long‐term colonization of L. mucosae and enhanced its stability upon antibiotic treatment (tetracycline, amoxicillin and ciprofloxacin). Incorporating a mucosal environment thus allowed colonization of specific microbes such as L. mucosae and LGG, in correspondence with the in vivo situation. This may lead to more in vivo‐like microbial communities in such dynamic, long‐term in vitro simulations and allow the study of the unique mucosal microbiota in health and disease.
Importance of computed tomography imaging features for the diagnosis of autoimmune acute liver failure
Authors: Yasui Shin , Fujiwara Keiichi , Okitsu Koichiro , Yonemitsu Yutaka , Ito Hisao , Yokosuka Osamu
Published: October 2011

Aim:  The diagnosis of acute liver failure due to autoimmune hepatitis is often difficult because of atypical clinicopathological features. Patients with autoimmune acute liver failure are sometimes resistant to immunosuppressive therapy and have poor prognosis. Although their survival rates are especially poor (5–20%) without liver transplantation in Japan, their clinicopathological features have remained uncertain. A major problem is that there is no gold standard for making the diagnosis of acute onset autoimmune hepatitis. If there are diagnosing tools supporting clinicopathological features, they are of benefit to the patients. We examined computed tomography (CT) imaging features of autoimmune acute liver failure to clarify the usefulness of imaging for the diagnosis.

Methods:  A retrospective analysis of 129 unenhanced CT scans of 68 patients with acute hepatitis, consisting of 23 with autoimmune acute liver failure (ALF) (group 1), 25 with early admission‐viral ALF (group 2) and 20 with late admission‐viral ALF (group 3), was performed.

Results:  Autoimmune acute liver failure showed heterogeneous hypoattenuating areas and viral ALF diffuse ones (P < 0.001). The diffuse hypoattenuating areas were present in none of group 1, 15 (60%) of group 2, and 7 (30%) of group 3. The heterogeneous hypoattenuating areas were present in 15 (65%) of group 1, none of group 2 and 1 (5%) of group 3.

Conclusions:  Heterogeneous hypoattenuation on unenhanced CT was a characteristic CT imaging feature of autoimmune acute liver failure compared with viral ALF. This finding could be one of the tools for diagnosing autoimmune acute liver failure in combination with clinicopathological features.
Fulminant hepatitis: Who survives without liver transplantation?
Authors: Miyake Yasuhiro , Yasunaka Tetsuya , Ikeda Fusao , Takaki Akinobu , Nouso Kazuhiro , Yamamoto Kazuhide
Published: October 2011

Aim:  In order to rescue more patients with fulminant hepatitis (FH) in a setting of the shortage of liver grafts, it is important not only to determine the suitable timing for liver transplantation (LT) but also to reduce avoidable operations for patients surviving without LT. This study aimed to identify prognostic parameters for survival without LT in FH patients.

Methods:  In 96 FH patients who did not receive LT, we examined prognostic parameters at the time of the diagnosis of FH, which were associated with patient's survival.

Results:  Fifty‐three patients (55%) were female. The median age was 48 years. At the time of the diagnosis of FH, hepatic coma grade was II in 63 patients (66%), III in 22 (23%) and IV in 11 (11%). Forty‐six patients (48%) were in a state of systemic inflammatory response syndrome (SIRS). Four parameters of age (<45 years), SIRS (no), direct bilirubin/total bilirubin ratio (>0.65), and total bilirubin (<12.0 mg/dL) were associated with patient's survival. Overall survival rate of eight patients ulfilling all four parameters were 88%. In 17 patients fulfilling any three parameters, 2‐week, 4‐week and overall survival rates were 82%, 77% and 71%, respectively. On the other hand, overall survival rate of 38 patients fulfilling any one parameter or none was less than 10%.

Conclusions:  Patients fulfilling all four parameters will be successfully treated without LT. In patients fulfilling any three parameters, intensive care including artificial liver support in expectation of hepatic regeneration during a few weeks may be possible.
Randomized, Placebo Controlled Study of the Effect of Propentofylline on Survival Time and Quality of Life of Cats with Feline Infectious Peritonitis
Authors: Fischer Y. , Ritz S. , Weber K. , Sauter‐Louis C. , Hartmann K.
Published: October 2011

Background

Currently there is no drug proven to effectively treat cats with feline infectious peritonitis (FIP).

Hypothesis

Propentofylline (PPF) can decrease vasculitis, and therefore prolong survival time in cats withFIP, and increase their quality of life.

Animals

Twenty‐three privately owned cats withFIP.

Methods

Placebo‐controlled double‐blind trial.FIPwas confirmed by histology or immunostaining of feline coronavirus (FCoV) antigen in effusion or tissue macrophages or both. The cats were randomly selected for treatment with eitherPPFor placebo. All cats received additional treatment with glucocorticoids, antibiotics, and low molecular weight heparin according to methods.

Results

There was no statistically significant difference in the survival time of cats treated with PPF (8 days, 95% CI 5.4–10.6) versus placebo (7.5 days, 95% CI 4.4–9.6). The median survival time of all cats was 8 days (4–36 days). There was neither a difference in quality of life (day 7,P = .892), in the amount of effusion (day 7,P = .710), the tumor necrosis factor‐alpha (TNF‐α) concentration (day 7,P = .355), nor in any other variable investigated in this study, including a complete blood count, and a small animal biochemistry profile.

Conclusions and Clinical Importance

This study did not detect an effect ofPPFon the survival time, the quality of life, or any clinical or laboratory parameter in cats withFIP. Therefore,PPFdoes not appear to be an effective treatment option in cats with a late stage of the diseaseFIP.
Murderball in the Classroom
Authors: Barrett Ron
Published: October 2011

Film reviewed in this issue.

Murderball
. (2005) 88 minutes. Directed by Henry Dubin and Dana Shapiro.
Expression of wild‐type and mutant S20G hIAPP in physiologic knock‐in mouse models fails to induce islet amyloid formation, but induces mild glucose intolerance
Authors: Hiddinga Henry J , Sakagashira Setsuya , Ishigame Masayuki , Madde Pranathi , Sanke Tokio , Nanjo Kishio , Kudva Yogish C , Lee James J , van Deursen Jan , Eberhardt Norman L
Published: October 2011

Aims/Introduction:  Human islet polypeptide S20G mutation (hIAPPS20G) is associated with earlier onset type 2 diabetes and increased amyloidogenicity and cytotoxicity in vitro vs wild‐type hIAPP (hIAPPWT), suggesting that amyloidogenesis may be pathogenic for type 2 diabetes. We compared the contributions of hIAPPS20G and hIAPPWT toward intra islet amyloid formation and development of type 2 diabetes in a unique physiologic knock‐in mouse model.

Materials and Methods:  We replaced the mouse IAPP gene (M allele) with hIAPPWT (W allele) and hIAPPS20G (G allele) via homologous recombination and backbred transgenic mice against C57Bl/6 strain 5 generations to minimize genetic variation. Mice (3 month old) were maintained on control (CD) or high fat diet (HFD) for 15 months and studied at 3 month intervals by oral glucose tolerance testing (OGTT) and pancreas histology to assess glucose homeostastis, amyloidogeneisis, islet mass, β cell replication, and apoptosis.

Results:  IAPP blood levels were indistinguishable in all mice. WW and GW mice maintained on both diets lacked intraislet amyloid at all ages. On both diets relative to MM controls WW and GW mice exhibit glucose intolerance (P < 0.008) with no differences in insulin secretion. However, GW mice secreted significantly more insulin (P < 0.03 that WW mice on both diets throughout the study. By 12 months on the high fat diet all mice increased their β cell mass about 3‐fold and were indistinguishable.

Conclusions:  Physiologic expression of hIAPPWT and hIAPPS20G in C57Bl/6 mice produces mild glucose intolerance with inappropriately normal insulin secretion that is independent of intraislet amyloid formation. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00166.x, 2011)
Estimation of HbA1c response to sitagliptin by change in glycated albumin level for 2 weeks
Authors: Hamaguchi Tomoya , Koga Masafumi , Murai Jun , Saito Hiroshi , Tamada Daisuke , Kurebayashi Shogo , Katsuno Tomoyuki , Miyagawa Jun‐ichiro , Namba Mitsuyoshi
Published: October 2011

Aims/Introduction:  Since glycated albumin (GA) reflects shorter‐term (about 2 weeks) control of plasma glucose levels compared with HbA1c, GA is thought to be a useful glycemic control indicator for the early period following commencement of the treatment of diabetes. In this study, we attempted to estimate HbA1c using the change in GA level before and after the first 2 weeks (ΔGA2w) of administration of sitagliptin, a dipeptidyl peptidase‐4 (DPP‐4) inhibitor.

Materials and Methods:  The study included 28 patients with type 2 diabetes who were administered sitagliptin at a dose of 50 mg/day for 12 weeks.

Results:  At 2 weeks after administration of sitagliptin, GA markedly decreased, while HbA1c had only slightly decreased. A significant positive correlation was observed between the ΔGA2w and the change in HbA1c before and after the first 12 weeks of administration of sitagliptin (ΔHbA1c12w) (R = 0.793, P < 0.0001). The latter was about 0.6 times the former. The estimated HbA1c after 12 weeks of therapy was calculated by adding ΔGA2w × 0.6 to the baseline HbA1c. A significant positive correlation was observed between the estimated HbA1c and the measured HbA1c after 12 weeks (R = 0.735, P < 0.0001) and both were similar levels.

Conclusions:  HbA1c in the first 12 weeks after administration of sitagliptin could be estimated from the formula using the ΔGA2w. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00167.x, 2011)
Dynamic in-situ eutectic formation for topical drug delivery
Authors: Fiala Sarah , Brown Marc B , Jones Stuart A
Published: October 2011

Objectives

The relationship between the solution-state chemistry of eutectic systems and their transmembrane transport characteristics is difficult to define as these mixtures are sensitive to delivery vehicle-induced penetration enhancement. Through in-situ formation of a molten eutectic mixture using highly evaporative sprays this study aimed to gain an understanding of solution-state thermodynamic and chemical properties of eutectic combinations pertinent to transmembrane transport in the absence of a delivery vehicle.

Methods

In-situ molten lidocaine–prilocaine eutectics were formed using a hydroflouroalkane (HFA) propellant. Transport through silicone membranes and human skin in upright Franz diffusion cells was determined using in-house manufactured creams as controls.

Key findings

The application of the two drugs in an HFA spray produced a molten oil even when the melting point of the drug mixture was above the experimental temperature at the membrane surface. In the absence of vehicle effects, molecule presentation to the membrane interface was most effective using a lidocaine-rich mixture of 0.7% w/w lidocaine:prilocaine – 1985.06 ± 128.87 µg/h/cm2.

Conclusions

There appeared to be no link between melting point and transmembrane transport of lidocaine:prilocaine from a eutectic mixture. The rate of drug presentation to the membrane interface, which was highest in drug-rich, high-activity molten eutectic mixtures, was the driver for transmembrane transport in the absence of significant barrier interactions.
Hemin-coupled iron(III)-hydroxide nanoparticles show increased uptake in Caco-2 cells
Authors: Jahn Markus Richard , Shukoor Ibrahim , Tremel Wolfgang , Wolfrum Uwe , Kolb Ute , Nawroth Thomas , Langguth Peter
Published: October 2011

Objectives

The absorption of commonly used ferrous iron salts from intestinal segments at neutral to slightly alkaline pH is low, mainly because soluble ferrous iron is easily oxidized to poorly soluble ferric iron and ferrous iron but not ferric iron is carried by the divalent metal transporter DMT-1. Moreover, ferrous iron frequently causes gastrointestinal side effects. In iron(III)-hydroxide nanoparticles hundreds of ferric iron atoms are safely packed in nanoscaled cores surrounded by a solubilising carbohydrate shell, yet bioavailability from such particles is insufficient when compared with ferrous salts. To increase their intestinal uptake iron(III)-hydroxide nanoparticles were coupled in this study with the protoporphyrin hemin, which undergoes carrier-mediated uptake in the intestine.

Methods

Uptake of iron(III)-hydroxide nanoparticles with hemin covalently coupled by DCC reaction was measured in Caco-2 cells with a colorimetric assay and visualized by transmission electron microscopy.

Key findings

Nanoparticles were taken up by carrier-mediated transport, since uptake was temperature-dependent and increased with an increasing hemin substitution grade. Furthermore, uptake decreased with an increasing concentration of free hemin, due to competition for carrier-mediated uptake.

Conclusions

Hemin-coupled iron(III)-hydroxide nanoparticles were carried by a heme specific transport system, probably via receptor mediated endocytosis. It can be expected that this system shows improved absorption of iron compared with uncoupled iron(III)-hydroxide nanoparticles, which exist on the market today.
Discursive psychology and feminism
Authors: Weatherall Ann
Published: October 2011

This appraisal highlights the productive engagement between feminism and discursive psychology (DP). It discusses some of the confluence and tensions between DP and feminism. The two share critical perspectives on science and psychology, a concern with prejudice, and have ideas in common about the constructed nature of social categories, such as gender. One difficulty arises from the relativism associated with the post‐structural theoretical underpinnings of DP, which can be understood as politically paralyzing. Another problem comes from an endorsement of a conversation analytic mentality, where identity categories such as gender can only be legitimately used in an analysis when participants’ orient to their relevance. The high‐profile debates and literature in DP shows it has made a notable contribution to social psychology and its influence can also be found in other areas. A particular influence of DP highlighted in the present appraisal is on gender and language research.
The day after an electoral defeat: Counterfactuals and collective action
Authors: Milesi Patrizia , Catellani Patrizia
Published: October 2011

An intriguing question for scholars of collective action is how participants of unsuccessful actions become re‐engaged in future collective activities. At an individual level, previous research has shown that after negative outcomes counterfactual thoughts (‘if only … ’) may serve to prepare for future action. In the current research, we investigated whether counterfactuals may also prepare for future action at a collective level. After a defeat of their party at the regional elections, 163 political activists rated their agreement with abstract (as opposed to concrete) and party‐focused (as opposed to other‐focused) counterfactuals about how the elections outcome might have been better. Results showed that abstract counterfactuals, dealing with the core elements of the elections, supported collective action intention better than concrete ones. Consistent with the recent developments of dual‐pathway models of collective action, counterfactuals predicted collective action intention through the mediation of group efficacy and group identification. In particular, while both party‐ and other‐focused abstract counterfactuals increased group efficacy, only other‐focused abstract counterfactuals increased group identification. Discussion focuses on how the investigation of counterfactuals can enlarge our knowledge of the socio‐cognitive antecedents of collective action.
The Half-Space Under Pressure Distributed Over an Elliptical Portion of Its Plane Boundary
Authors: Deresiewicz H.
Published: October 2011

In determining the safety of foundations the assumption is usually made that the pressure distribution on the ground, in general unknown, is closely approximated by a constant one. Mathematically, the problem is thereby reduced to finding the components of stress and displacement in a half-space due to a uniform pressure on a portion of its plane boundary. The present paper contains an investigation of this problem for the case of loading over an area bounded by an ellipse. Two of the results are: (a) On the normal to the loading area through its center, the two principal stresses in planes parallel to the undeformed surface, compressive on and near the surface, become tensile within a depth smaller than the length of the corresponding principal axis of the loading area; (b) the normal deflection of the surface is greater at the extremity of the minor axis of the loading area than at the extremity of the major axis, the difference between the two values increasing with the ellipticity of the bounding curve.
Axially Symmetric Waves in Elastic Rods
Authors: Mindlin R. D. , McNiven H. D.
Published: October 2011

A system of approximate, one-dimensional equations is derived for axially symmetric motions of an elastic rod of circular cross section. The equations take into account the coupling between longitudinal, axial shear, and radial modes. The spectrum of frequencies for real, imaginary, and complex wave numbers in an infinite rod is explored in detail and compared with the analogous solution of the three-dimensional equations.
Plane-Stress Unloading Waves Emanating From a Suddenly Punched Hole in a Stretched Elastic Plate
Authors: Miklowitz Julius
Published: October 2011

The present paper points out that Kromm’s [1] plane-stress solution, for compressional waves in an infinite elastic plate subjected to radial pressure in a circular hole at its center, has application to still another problem of interest. This is the problem of a stretched elastic plate in which a circular hole is suddenly punched. The plane-stress solution for the tensile circumferential stresses, generated by the unloading mechanism in punching, is given here. This solution is derived independently of Kromm’s work in which a rather special Laplace-transform technique was used. The derivation given here also makes use of the Laplace transform but in a more direct manner, employing the inversion integral and a contour integration. It is also shown that the present inversion technique offers important simplifying features over that used by Selberg [3] in the closely related plane-strain problem. The numerical results presented are of interest in fragmentation studies. It is shown that the dynamic circumferential stress field in the vicinity of the punched hole is quite severe; which would be important to the creation and propagation of radial cracks.
The Melting of Finite Slabs
Authors: Goodman Theodore R. , Shea John J.
Published: October 2011

An approximate method, known as the heat-balance integral, is used to determine the melting rate of a finite slab which is initially at a uniform temperature below the melting point. The slab is acted upon by a constant heat input at one face and has its other face either insulated or kept at its initial temperature. The first three terms of series solutions in an intrinsically small parameter are obtained for the time histories of melting and the temperature distribution in the slab.
The Motion and Loading of a Hinged Ramp Which Supports a Sliding Mass
Authors: Saelman B.
Published: October 2011

Equations of motion of a hinged ramp supporting a sliding mass, which moves at constant velocity, are derived; these are shown to have no closed solution when the ramp is spring supported or when the cylinder force is proportional to the square of the velocity. For small velocities of the sliding mass the Coriolis term may be neglected and a good approximation to the solution of the equations is obtained by means of the Madelung transformation. The solutions by special methods are compared to the solutions obtained by standard numerical methods.
Relaxation of a Cylinder on a Rigid Shaft
Authors: Davis E. A.
Published: October 2011

Equations are developed for the radial and tangential stresses in a cylinder that has been shrunk on a rigid shaft. The analysis is made for a material having elastic properties and behaving according to a power-function speed-effect law.
Plastic Stress Concentration at a Circular Hole in an Infinite Sheet Subjected to Equal Biaxial Tension
Authors: Budiansky Bernard , Mangasarian O. L.
Published: October 2011

With the use of J2 deformation theory, the stress-concentration factor at a circular hole in an infinite sheet of strain-hardening material subjected to equal biaxial tension at infinity is found for a variety of representative materials. The analysis exploits a transformation which permits the calculation of the stress-concentration factor without determining the stress distribution in the sheet. Subsequent calculations reveal that, for a monotonically increasing applied stress, the stress history at all points in the sheet is nearly radial.
Effect of the Wall on Two-Phase Turbulent Motion
Authors: Soo S. L. , Tien C. L.
Published: October 2011

Stationary solution on the effect of a wall on two-phase (solid particles in gas) turbulent motion shows that the intensity of motion of solid particles is affected by the presence of the wall and the distribution of turbulent intensity of the stream near the wall. The intensity of motion of solid particles can be significantly higher than the turbulence intensity of the mean stream. These modifications are consequences of Bernoulli force acting between the wall and the particle.
On a Dynamical Saint Venant Principle
Authors: Boley B. A.
Published: October 2011

The dynamic behavior of a simple mechanical model composed of two Timoshenko beams connected by springs is studied. The accuracy of a quasi-static solution and of Saint Venant’s principle is studied for various rates of load application.
Possible Similarity Solutions for Laminar Free Convection on Vertical Plates and Cylinders
Authors: Yang Kwang-Tzu
Published: October 2011

In this paper, a study is made of the unsteady laminar boundary-layer equations for free convection on vertical plates and cylinders to establish necessary and sufficient conditions under which similarity solutions are possible. On the basis of these conditions, all possible cases are derived, including those for unsteady conditions. And it is found that the available similarity solutions in the literature have essentially covered all steady cases, except that the present analysis shows that somewhat more general conditions may also be taken in account.
Normal Modes of Nonlinear Dual-Mode Systems
Authors: Rosenberg R. M.
Published: October 2011

A system consisting of two unequal masses, interconnected by a coupling spring, and each connected to an anchor spring, is examined. The springs may all be unequal and nonlinear, but each resists being compressed to the same degree as being stretched. The concept of normal modes is rigorously defined, and methods of finding them are given. A knowledge of these modes reduces the coupled system to two uncoupled ones which can always be integrated in quadrature. There exists an infinity of systems, of which the linear is one, which can be integrated in closed form. This approach yields, even for the linear system, new results of great simplicity.
On the Optimum Design of Shells
Authors: Shield R. T.
Published: October 2011

A procedure is developed for obtaining the design of an elastic, perfectly plastic shell or structure which will support prescribed loads and which is the optimum design for a given criterion. The action of body forces is included in the analysis. Some problems in the minimum volume design of a circular cylindrical sandwich shell are solved to illustrate the method, and it is found that only for relatively short shells does the minimum volume design effect an appreciable saving over the membrane design.
On the Indeterminateness of the Boundary Conditions for the Mixing of Two Parallel Streams
Authors: Yen K. T.
Published: October 2011

Results obtained from a study of the indeterminateness of the boundary conditions for laminar “free” mixing of two parallel streams under constant pressure are presented in this paper. A method is given for the determination of the interface velocity, the location of the interface in the mixing region, and the transverse force acting on the dividing wall as a consequence of the mixing. Based on available numerical data, calculations have been made for two free-stream velocity ratios, 0.5 and 0. It is shown that values of interface velocity obtained here differ appreciably from those obtained using other proposed boundary conditions (the third condition). In addition, for a free-stream velocity ratio of 0.5 the interface deflects toward the higher velocity stream, while for a zero free-stream velocity ratio it deflects toward the zero (lower) velocity stream.
Hydrodynamic Entrance Lengths for Incompressible Laminar Flow in Rectangular Ducts
Authors: Han L. S.
Published: October 2011

The problem of determining the hydrodynamic entrance length in a rectangular channel is solved by the method of linearizing the Navier-Stokes equation. The resulting equation is regarded as an equation to generate a mathematical expression for the axial velocity in the entire region, making smooth transition from a uniform profile to the fully developed one. From this expression, the entrance length, defined as where 99 per cent of the fully developed center-line velocity is attained, is calculated for channels of six aspect ratios. The pressure drops are also calculated and presented herein. A comparison is made with the limited amount of experimental and theoretical data.
On Saint Venant’s Principle: Elastic Shells and Plates
Authors: Naghdi P. M.
Published: October 2011

This investigation is concerned with an examination of the validity of Saint Venant’s principle in the theory of thin elastic shells and plates. With the aid of an integral formula derived for the displacements and their relevant partial derivatives of all orders at a fixed point of the shell middle surface, the conclusions reached may be roughly stated as follows: If the loads acting on the shell maintained in equilibrium are purely edge loads, then the orders of magnitude of the displacements and stresses are in accord with the traditional statement of Saint Venant’s principle. On the other hand, if the loads on the shell are purely surface loads, then the conclusions concerning the orders of magnitude of the displacements and stresses are the same as those of the modified Saint Venant principle.
The Contact Problem for Viscoelastic Bodies
Authors: Lee E. H. , Radok J. R. M.
Published: October 2011

The contact problem in viscoelasticity is one in which different types of boundary conditions are prescribed depending on whether boundary points inside or outside the region of contact are considered. Since, in general, the contact region varies with time, this lends to a problem which cannot be treated directly by application of the Laplace transform, which has formed the basis for most published viscoelastic stress-distribution solutions. It is shown that the solution of the viscoelastic counterpart of the Hertz problem in elasticity can, however, be deduced from the elastic solution. A particular example is presented, and the marked effect of viscoelastic behavior on the pressure distribution in the contact region is illustrated. The problem also illustrates the tentative nature of the method of approach and the need for a separate confirmation of the solution. The solution is presented for general linear viscoelastic operators and offers the possibility of determining these from a contact test.
Shear Buckling of Bars
Authors: Herrmann G. , Armena`kas A. E.
Published: October 2011

It is shown that a perfectly straight bar, subjected to a state of uniform shear stress, will buckle, in a manner similar to a column under compression, if the shear stress exceeds a certain critical value. The buckling equations are obtained by the Newtonian approach and also by the application of the principle of minimum potential energy. In order to provide additional insight into this buckling mechanism, a simple model is introduced and analyzed.
Transient and Residual Thermal Stresses in an Elastic-Plastic Cylinder
Authors: Landau H. G. , Zwicky E. E.
Published: October 2011

Equations are given for the stress rates in solid cylinders subject to transient temperature distributions, based on the assumption of an elastic, perfectly plastic material obeying a von Mises temperature-dependent yield condition. A numerical procedure for integrating the equations is developed and applied to a temperature distribution approximating a phase transformation and to a quenched cylinder. The effect of various factors on the residual stresses is noted.
On Strain-Hardened Circular Cylindrical Shells
Authors: Perrone Nicholas , Hodge P. G.
Published: October 2011

A consistent kinematic hardening theory termed complete hardening, based on a Tresca initial yield condition, has been applied to determine the general flow laws for rotationally symmetric shells. Representative “long” and “short” cylindrical shell problems with zero axial load are solved using complete hardening and a simpler but approximate kinematic hardening theory, termed direct hardening. The direct-hardening results compare favorably with the complete hardening ones.
The Elastoplastic Thick-Walled Sphere Subjected to a Radial Temperature Gradient
Authors: Cowper G. R.
Published: October 2011

An exact solution is obtained for the behavior of an ideal elasto plastic hollow sphere which is thermally stressed by a slowly increasing temperature difference between the inner and outer surfaces. An approximate analysis in which elastic strains are neglected is also presented. It is shown that the approximate analysis gives the asymptotic form of the exact solution at infinitely high temperatures.
Effect of Small Hub-Radius Change on Bending Frequencies of a Rotating Beam
Authors: Lo Hsu , Goldberg J. E. , Bogdanoff J. L.
Published: October 2011

By the method of perturbation, a simple relation is formulated for the determination of the change of bending frequencies of a rotating beam due to a small change of hub radius. The first-order solution shows that a frequency parameter γ is a linear function of the hub-radius change and the constant of proportionality is readily obtainable from known parameters. The frequency ω itself can also be represented by a linear function of the hub-radius change. This confirms the results previously obtained by Boyce by repeated solutions of the differential equations for a particular beam. Higher-order solutions are also established and shown to be convergent within the limitation imposed on the amount of the hub-radius change allowable.
Dynamical Response of an Elastic Half-Space to Tangential Surface Loadings
Authors: Chao Chi-Chang
Published: October 2011

Exact and closed-form solutions are obtained for both tangential and vertical surface displacements of a homogeneous isotropic elastic half-space due to the application, at a point on the surface, of a concentrated force tangential to the plane boundary and varying with time as the Heaviside unit function. Similar expressions for the displacements in the interior of the body along a line directly below the applied force are derived. Solutions are obtained by a semi-inverse method with the aid of Laplace and Hankel transforms. The reciprocal relation in the static case, between tangential displacement due to a vertical force and vertical displacement due to a tangential force, is preserved in the dynamic case.
On the Compressibility Effects of the Lubricant for Two-Dimensional Slider Bearings
Authors: Yen K. T.
Published: October 2011

An analytical study of the compressibility effects on the characteristics of two-dimensional slider bearings is made. By the variational method, it is shown that, for a given bearing length, no optimal film shape of the bearing can be found to yield a maximum total load. Analysis of the numerical results carried out for stepped films with a compressible lubricant under isothermal compression or expansion indicates that this anomaly is due to the nonlinear nature of the compressible problem. By considering a modified variational problem, it is further shown that stepped-film bearings with isothermal lubricant still yield the maximum total load for a given mass flow rate passing through the bearings, but the exact shape of the optimal stepped film is found to depend on the value of the maximum pressure.
Transient Conduction in Coaxial Cylinders With Relative Motion and Heat Generation
Authors: Arpaci V. S.
Published: October 2011

Transient temperatures in a coaxially moving tube and a stationary rod resulting from a step change in the rate of energy generation within the rod are obtained. For the small values of time, the use of finite Hankel transforms reduces the problem to the solution of an integrodifferential equation. In the solution of this equation, Laplace transforms have been used considering the convolutive property of the kernel involved. For the large values of time, this method is not convenient, and the asymptotic behavior of the temperature functions is given by means of the classical approach which requires the use of Laplace transforms. For a given time, it is found that the interface temperature gradient is inversely proportional to the axial distance.
Thermal Stresses Due to Disturbance of Uniform Heat Flow by an Insulated Ovaloid Hole
Authors: Florence A. L. , Goodier J. N.
Published: October 2011

The linear thermoelastic problem is solved for a uniform heat flow disturbed by a hole of ovaloid form, which includes the ellipse and circle as special cases. Results for stress and displacement are found in closed form, by reducing the problem to one of boundary loading solvable by a method of Muskhelishvili.
Forced Oscillations of a Semi-Infinite Rod Exhibiting Weak Bilinear Hysteresis
Authors: Caughey T. K.
Published: October 2011

A first-order nonlinear solution is presented for the problem of forced sinusoidal oscillations of a semi-infinite bar exhibiting weak bilinear hysteresis.
Free, Transverse Vibrations of a Solid Elastic Mass in an Infinitely Long, Rigid, Circular-Cylindrical Tank
Authors: Baltrukonis J. H.
Published: October 2011

Making use of the field equations of elasticity, the frequency equation is derived for the free, transverse vibrations of a solid elastic mass contained by an infinitely long, rigid, circular-cylindrical tank. This frequency equation relates the natural circular frequencies and Poisson’s ratio. This relationship is plotted revealing a very interesting steplike variation of the natural frequency with Poisson’s ratio. Displacement fields are plotted for two natural frequencies in each of the first three modes.
On the Response of an Elastic Half-Space to a Moving Blast Wave
Authors: Miles J. W.
Published: October 2011

A formal integral transform solution is obtained for the response of an elastic half-space to a radially symmetric pressure signature of variable pressure and variable velocity. An asymptotic approximation to this solution is developed and expressed in terms of the known solution for the response of a half-space to a two-dimensional pulse moving with constant velocity plus a correction that is important only if the blast-wave speed directly above the point of observation is close to the Rayleigh-wave speed.
Computational Methods for the Design and Prediction of Performance of Tidal Turbines
Authors: Kinnas Spyros A. , Xu Wei , Yu Yi-Hsiang , He Lei
Published: October 2011

A design method based on a lifting line model is developed to determine the optimum radial circulation distribution on a turbine blade, which will produce the maximum output power for a given tip speed ratio and a given number of blades. The resulting optimum circulation distribution is used in order to determine the preliminary shape of the turbine blade. The blade shape is then refined by using an analysis method, based on a vortex-lattice scheme, in combination with a nonlinear optimization method, which determines the blade geometry that will produce the highest output power. Finally, the effect of nonuniform current inflow on the performance of a turbine is also addressed by coupling the vortex-lattice method with a viscous flow solver.
Run-Up of Solitary Waves on Twin Conical Islands Using a Boussinesq Model
Authors: Liang Dongfang , Borthwick Alistair G. L. , Romer-Lee Jonathan K.
Published: October 2011

This paper investigates the interaction of solitary waves (representative of tsunamis) with idealized flat-topped conical islands. The investigation is based on simulations produced by a numerical model that solves the two-dimensional Boussinesq-type equations of Madsen and Sørensen using a total variation diminishing Lax–Wendroff scheme. After verification against published laboratory data on solitary wave run-up at a single island, the numerical model is applied to study the maximum run-up at a pair of identical conical islands located at different spacings apart for various angles of wave attack. The predicted results indicate that the maximum run-up can be attenuated or enhanced according to the position of the second island because of wave refraction, diffraction, and reflection. It is also observed that the local wave height and hence run-up can be amplified at certain gap spacing between the islands, owing to the interference between the incident waves and the reflected waves between islands.
A Rattle Bag of Science and the Art of Translation
Authors: Edelman Elazer R. , FitzGerald Garret A.
Published: October 2011

Science Translational Medicine
’s new Co–Chief Scientific Advisors define translational science and articulate their vision for the journal.
Diabetes Impairs Hematopoietic Stem Cell Mobilization by Altering Niche Function
Authors: Ferraro Francesca , Lymperi Stefania , Méndez-Ferrer Simón , Saez Borja , Spencer Joel A. , Yeap Beow Y. , Masselli Elena , Graiani Gallia , Prezioso Lucia , Rizzini Elisa Lodi , Mangoni Marcellina , Rizzoli Vittorio , Sykes Stephen M. , Lin Charles P. , Frenette Paul S. , Quaini Federico , Scadden David T.
Published: October 2011

Impaired mobilization of hematopoietic stem cells in diabetic mice is due to sympathetic nervous system dysregulation of CXCL12 distribution.
Molecular Clue to Disease Prognosis
Authors: Lin Richard J.
Published: October 2011

Genetic signatures may help to risk-stratify a heterogeneous precancerous blood disorder.
Complete Genome Sequence of Strain S85, a Novel Member of the Family Flavobacteriaceae
Authors: Oh Chulhong , Kwon Young-Kyung , Heo Soo-Jin , De Zoysa Mahanama , Affan Abu , Lee Youngdeuk , Lee Jehee , Choi Young-Ung , Park Heung-Sik , Jung Kyung-Hwan , Lee Hyeon-Yong , Kang Do-Hyung
Published: October 2011

An agar-degrading marine bacterium identified as a novel member of the family
Flavobacteriaceae
(strain S85) was isolated from seawater in Micronesia. The sequenced strain S85 genome is composed of 3,384,629 bp in a circular chromosome, which includes 2,883 complete open reading frames.
VPg-Primed RNA Synthesis of Norovirus RNA-Dependent RNA Polymerases by Using a Novel Cell-Based Assay
Authors: Subba-Reddy Chennareddy V. , Goodfellow Ian , Kao C. Cheng
Published: October 2011

Molecular studies of human noroviruses (NoV) have been hampered by the lack of a permissive cell culture system. We have developed a sensitive and reliable mammalian cell-based assay for the human NoV GII.4 strain RNA-dependent RNA polymerase (RdRp). The assay is based on the finding that RNAs synthesized by transiently expressed RdRp can stimulate retinoic acid-inducible gene I (RIG-I)-dependent reporter luciferase production via the beta interferon promoter. Comparable activities were observed for the murine norovirus (MNV) RdRp. RdRps with mutations at divalent metal ion binding residues did not activate RIG-I signaling. Furthermore, both NoV and MNV RdRp activities were stimulated by the coexpression of their respective VPg proteins, while mutations in the putative site of nucleotide linkage on VPg abolished most of their stimulatory effects. Sequencing of the RNAs linked to VPg revealed that the cellular
trans
-Golgi network protein 2 (TGOLN2) mRNA was the template for VPg-primed RNA synthesis. Small interfering RNA knockdown of RNase L abolished the enhancement of signaling that occurred in the presence of VPg. Finally, the coexpression of each of the other NoV proteins revealed that p48 (also known as NS1-2) and VP1 enhanced and that VP2 reduced the RdRp activity. The assay should be useful for the dissection of the requirements for NoV RNA synthesis as well as the identification of inhibitors of the NoV RdRp.
The Structure of an Unconventional HD-GYP Protein from
Bdellovibrio
Reveals the Roles of Conserved Residues in this Class of Cyclic-di-GMP Phosphodiesterases
Authors: Lovering Andrew L. , Capeness Michael J. , Lambert Carey , Hobley Laura , Sockett R. Elizabeth
Published: October 2011

Cyclic-di-GMP is a near-ubiquitous bacterial second messenger that is important in localized signal transmission during the control of various processes, including virulence and switching between planktonic and biofilm-based lifestyles. Cyclic-di-GMP is synthesized by GGDEF diguanylate cyclases and hydrolyzed by EAL or HD-GYP phosphodiesterases, with each functional domain often appended to distinct sensory modules. HD-GYP domain proteins have resisted structural analysis, but here we present the first structural representative of this family (1.28 Å), obtained using the unusual Bd1817 HD-GYP protein from the predatory bacterium
Bdellovibrio bacteriovorus
. Bd1817 lacks the active-site tyrosine present in most HD-GYP family members yet remains an excellent model of their features, sharing 48% sequence similarity with the archetype RpfG. The protein structure is highly modular and thus provides a basis for delineating domain boundaries in other stimulus-dependent homologues. Conserved residues in the HD-GYP family cluster around a binuclear metal center, which is observed complexed to a molecule of phosphate, providing information on the mode of hydroxide ion attack on substrate. The fold and active site of the HD-GYP domain are different from those of EAL proteins, and restricted access to the active-site cleft is indicative of a different mode of activity regulation. The region encompassing the GYP motif has a novel conformation and is surface exposed and available for complexation with binding partners, including GGDEF proteins.

IMPORTANCE
It is becoming apparent that many bacteria use the signaling molecule cyclic-di-GMP to regulate a variety of processes, most notably, transitions between motility and sessility. Importantly, this regulation is central to several traits implicated in chronic disease (adhesion, biofilm formation, and virulence gene expression). The mechanisms of cyclic-di-GMP synthesis via GGDEF enzymes and hydrolysis via EAL enzymes have been suggested by the analysis of several crystal structures, but no information has been available to date for the unrelated HD-GYP class of hydrolases. Here we present the multidomain structure of an unusual member of the HD-GYP family from the predatory bacterium
Bdellovibrio bacteriovorus
and detail the features that distinguish it from the wider structural family of general HD fold hydrolases. The structure reveals how a binuclear iron center is formed from several conserved residues and provides a basis for understanding HD-GYP family sequence requirements for c-di-GMP hydrolysis.
Recombinase-Mediated Cassette Exchange as a Novel Method To Study Somatic Hypermutation in Ramos Cells
Authors: Baughn Linda B. , Kalis Susan L. , MacCarthy Thomas , Wei Lirong , Fan Manxia , Bergman Aviv , Scharff Matthew D.
Published: October 2011

Activation-induced cytidine deaminase (AID) mediates the somatic hypermutation (SHM) of immunoglobulin (Ig) variable (V) regions that is required for the generation of antibody diversity and for the affinity maturation of the antibody response against infectious agents and toxic substances. AID preferentially targets WRC (W = A/T, R = A/G) hot spot motifs, particularly WGCW motifs that create overlapping hot spots on both strands. In order to gain a better understanding of the generation of antibody diversity and to create a platform for thein vitrogeneration of affinity-matured antibodies, we have established a system involving recombinase-mediated cassette exchange (RMCE) to replace the V region and its flanking sequences. This makes it possible to easily manipulate the sequence of the Ig gene within the endogenous heavy chain of the Ramos human Burkitt’s lymphoma cell line. Here we show that the newly integrated wild-type (WT) VH regions introduced by RMCE undergo SHM similarly to non-RMCE-modified Ramos cells. Most importantly, we have shown that introducing a cluster of WGCW motifs into the complementary determining region 2 (CDR2) of the human heavy chain V region significantly raised the mutation frequency and number of mutations per sequence compared to WT controls. Thus, we have demonstrated a novel platform in Ramos cells whereby we can easily and quickly manipulate the endogenous human VH region to further explore the regulation and targeting of SHM. This platform will be useful for generating human antibodies with changes in affinity and specificityin vitro.

IMPORTANCEAn effective immune response requires a highly diverse repertoire of affinity-matured antibodies. Activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) of immunoglobulin (Ig) genes. Although a great deal has been learned about the regulation of AID, it remains unclear how it is preferentially targeted to particular motifs, to certain locations within the Ig gene and not to other highly expressed genes in the germinal center B cell. This is an important question because AID is highly mutagenic and is sometimes mistargeted to other highly expressed genes, including proto-oncogenes, leading to B cell lymphomas. Here we describe how we utilize recombinase-mediated cassette exchange (RMCE) to modify the sequence of the endogenous heavy chain locus in the Ramos Burkitt’s lymphoma cell line. This platform can be used to explore the regulation and targeting of SHM and to generate human antibodies with changes in affinity and specificityin vitro.