Heat capacity measurements on the equiatomic compounds in Ni-X (X = Al, In, Si, Ge and Bi) and M-Sb (with M = Ni, Co and Fe) systems

Molar heat capacities of the binary compounds NiAl, NiIn, NiSi, NiGe, NiBi, NiSb, CoSb and FeSb were determined every 10 K by differential scanning calorimetry in the temperature range 310-1080 K. The experimental results have been fitted versus temperature according to C-p = a + b . T + c . T-2 + d . T-2. Results are given, discussed and compared to estimations found in the literature. Two compounds, NiBi and FeSb, are subject to transformations between 460 and 500 K. (C) 1999 Elsevier Science Ltd. All rights reserved.

Topographic forcing of flow partition and flow structures at river bifurcations

This paper presents the predicted flow dynamics from the application of a Reynolds-averaged NavierStokes model to a series of bifurcation geometries with morphologies measured during previous flume experiments. The topography of the bifurcations consists of either plane or bedform-dominated beds which may or may not possess discordance between the two bifurcation distributaries. Numerical predictions are compared with experimental results to assess the ability of the numerical model to reproduce the division of flow into the bifurcation distributaries. The hydrodynamic model predicts: (1) diverting fluxes in the upstream channel which direct water into the distributaries; (2) super-elevation of the free surface induced at the bifurcation edge by pressure differences; and (3) counter-rotating secondary circulation cells which develop upstream of the apex of the bifurcation and move into the downstream channels, with water converging at the surface and diverging at the bed. When bedforms are not present, weak transversal fluxes characterize the upstream channel for almost its entire length, associated with clearly distinguishable secondary circulation cells, although these may be under-estimated by the turbulence model used in the solution. In the bedform dominated case, the same hydrodynamic conditions were not observed, with the bifurcation influence restricted and depth scale secondary circulation cells not forming. The results also demonstrate the dominant effect bed discordance has upon flow division between the two distributaries. Finally, results indicate that in bedform dominated rivers. Consequently, we suggest that sand-bed river bifurcations are more likely to have an influence that extends much further upstream and have a greater impact upon water distribution. This may contribute to observed morphological differences between sand-bedded and gravel-bedded braided river networks. Copyright (C) 2012 John Wiley & Sons, Ltd.

ZHARP: three-dimensional motion tracking from a single image plane.

Three-dimensional imaging and quantification of myocardial function are essential steps in the evaluation of cardiac disease. We propose a tagged magnetic resonance imaging methodology called zHARP that encodes and automatically tracks myocardial displacement in three dimensions. Unlike other motion encoding techniques, zHARP encodes both in-plane and through-plane motion in a single image plane without affecting the acquisition speed. Postprocessing unravels this encoding in order to directly track the 3-D displacement of every point within the image plane throughout an entire image sequence. Experimental results include a phantom validation experiment, which compares zHARP to phase contrast imaging, and an in vivo study of a normal human volunteer. Results demonstrate that the simultaneous extraction of in-plane and through-plane displacements from tagged images is feasible.

Molecular pathways: emerging pathways mediating growth, invasion, and metastasis of tumors progressing in an irradiated microenvironment.

Radiotherapy is a well-established therapeutic modality in oncology. It provides survival benefits in several different cancer types. However, cancers relapsing after radiotherapy often develop into more aggressive conditions that are difficult to treat and are associated with poor prognosis. Cumulative experimental evidence indicates that the irradiated tumor bed contributes to such aggressive behavior. The involved mechanisms have for long remained elusive. Recent progress in the field revealed previously unrecognized cellular and molecular events promoting growth, invasion, and metastasis of tumors progressing in an irradiated microenvironment. Cellular mechanisms include inhibition of sprouting angiogenesis, formation of hypoxia, activation and differentiation of stromal cells, and recruitment of bone marrow-derived cells with vasculogenic and prometastatic activities. Identified pathways include TGF-β/ALK5, CXCL12/CXCR4, KITL/KIT, and CYR61/αVβ5 integrin. The availability of pharmacologic inhibitors impinging on these pathways opens novel opportunities for translational and clinical studies. These experimental results and ongoing work highlight the importance of the irradiated microenvironment in modulating the tumor response to radiotherapy and open new opportunities for the development of novel therapeutic strategies for patients with cancer who relapse after radiotherapy. Here, we review and discuss recent advances in the field and their translational and therapeutic implications to human cancer treatment.

Patterns of gravity induced aggregate migration during casting of fluid concretes

In this paper, aggregate migration patterns during fluid concrete castings are studied through experiments, dimensionless approach and numerical modeling. The experimental results obtained on two beams show that gravity induced migration is primarily affecting the coarsest aggregates resulting in a decrease of coarse aggregates volume fraction with the horizontal distance from the pouring point and in a puzzling vertical multi-layer structure. The origin of this multi layer structure is discussed and analyzed with the help of numerical simulations of free surface flow. Our results suggest that it finds its origin in the non Newtonian nature of fresh concrete and that increasing casting rate shall decrease the magnitude of gravity induced particle migration. (C) 2012 Elsevier Ltd. All rights reserved.

Estimation of the noisy component of anatomical backgrounds.

The knowledge of the relationship that links radiation dose and image quality is a prerequisite to any optimization of medical diagnostic radiology. Image quality depends, on the one hand, on the physical parameters such as contrast, resolution, and noise, and on the other hand, on characteristics of the observer that assesses the image. While the role of contrast and resolution is precisely defined and recognized, the influence of image noise is not yet fully understood. Its measurement is often based on imaging uniform test objects, even though real images contain anatomical backgrounds whose statistical nature is much different from test objects used to assess system noise. The goal of this study was to demonstrate the importance of variations in background anatomy by quantifying its effect on a series of detection tasks. Several types of mammographic backgrounds and signals were examined by psychophysical experiments in a two-alternative forced-choice detection task. According to hypotheses concerning the strategy used by the human observers, their signal to noise ratio was determined. This variable was also computed for a mathematical model based on the statistical decision theory. By comparing theoretical model and experimental results, the way that anatomical structure is perceived has been analyzed. Experiments showed that the observer's behavior was highly dependent upon both system noise and the anatomical background. The anatomy partly acts as a signal recognizable as such and partly as a pure noise that disturbs the detection process. This dual nature of the anatomy is quantified. It is shown that its effect varies according to its amplitude and the profile of the object being detected. The importance of the noisy part of the anatomy is, in some situations, much greater than the system noise. Hence, reducing the system noise by increasing the dose will not improve task performance. This observation indicates that the tradeoff between dose and image quality might be optimized by accepting a higher system noise. This could lead to a better resolution, more contrast, or less dose.

From protein sequences to 3D-structures and beyond: the example of the UniProt knowledgebase.

With the dramatic increase in the volume of experimental results in every domain of life sciences, assembling pertinent data and combining information from different fields has become a challenge. Information is dispersed over numerous specialized databases and is presented in many different formats. Rapid access to experiment-based information about well-characterized proteins helps predict the function of uncharacterized proteins identified by large-scale sequencing. In this context, universal knowledgebases play essential roles in providing access to data from complementary types of experiments and serving as hubs with cross-references to many specialized databases. This review outlines how the value of experimental data is optimized by combining high-quality protein sequences with complementary experimental results, including information derived from protein 3D-structures, using as an example the UniProt knowledgebase (UniProtKB) and the tools and links provided on its website ( http://www.uniprot.org/ ). It also evokes precautions that are necessary for successful predictions and extrapolations.

Precision and scaling in morphogen gradient read-out.

Morphogen gradients infer cell fate as a function of cellular position. Experiments in Drosophila embryos have shown that the Bicoid (Bcd) gradient is precise and exhibits some degree of scaling. We present experimental results on the precision of Bcd target genes for embryos with a single, double or quadruple dose of bicoid demonstrating that precision is highest at mid-embryo and position dependent, rather than gene dependent. This confirms that the major contribution to precision is achieved already at the Bcd gradient formation. Modeling this dynamic process, we investigate precision for inter-embryo fluctuations in different parameters affecting gradient formation. Within our modeling framework, the observed precision can only be achieved by a transient Bcd profile. Studying different extensions of our modeling framework reveals that scaling is generally position dependent and decreases toward the posterior pole. Our measurements confirm this trend, indicating almost perfect scaling except for anterior most expression domains, which overcompensate fluctuations in embryo length.

Is it the grain size or the characteristic pore size that controls the induced polarization relaxation time of clean sands and sandstones?

There is a wide range of evidence to suggest that permeability can be constrained through of induced polarization measurements. For clean sands and sandstones, current mechanistic models of induced polarization predict a relationship between the low-frequency time constant inferred from induced polarization measurements and the grain diameter. A number of observations do, however, disagree with this and indicate that the observed relaxation behavior is rather governed by the so-called dynamic pore radius L. To test this hypothesis, we have developed a set of new scaling relationships, which allow the relaxation time to be computed from the pore size and the permeability to be computed from both the Cole-Cole time constant and the formation factor. Moreover, these new scaling relationships can be also used to predict the dependence of the Cole-Cole time constant as a function of the water saturation under unsaturated conditions. Comparative tests of the proposed new relationships with regard to various published experimental results for saturated clean sands and sandstones as well as for partially saturated clean sandstones, do indeed confirm that the dynamic pore radius L is a much more reliable indicator of the observed relaxation behavior than grain-size-based models.

In vivo distribution and ex vivo permeation of cyclosporine A prodrug aqueous formulations for ocular application.

Cyclosporine A is a poorly water-soluble, immunosuppressive drug used to treat a variety of ocular diseases. Its limited solubility makes challenging the development of a cyclosporine A-based eye drop for ocular topical application. Based on the prodrug strategy, the practically insoluble cyclosporine A was converted into a freely soluble prodrug. Such a water-soluble prodrug made it possible to develop water-based concentrated eye drops. The prodrug formulations were tested for their ex vivo permeation and in vivo distribution at three concentrations (equivalent to 0.05%, 0.50% and 2.00% w/v cyclosporine A). The ex vivo permeation experiments were performed on corneal and conjunctival epithelia. The in vivo distribution evaluated the total cyclosporine A present in the ocular structures as well as in serum, spleen and cervical lymphatic ganglions. Each prodrug formulation was compared to conventionally used cyclosporine A eye drops at an equivalent concentration. The experimental results showed that the tested eye drops behaved differently. The prodrug formulation was characterized by the following: i) preferential conjunctival penetration, ii) an interesting capacity to create large tissue deposits and iii) a lower risk of systemic complications and immunosuppression. The prodrug aqueous eye drop was demonstrated to be a patient-friendly option for the treatment of ocular diseases requiring high ocular levels of cyclosporine A, pushing the boundaries of the current therapeutic arsenal.

Large-scale clustering through functional embedding

We present a new framework for large-scale data clustering. The main idea is to modify functional dimensionality reduction techniques to directly optimize over discrete labels using stochastic gradient descent. Compared to methods like spectral clustering our approach solves a single optimization problem, rather than an ad-hoc two-stage optimization approach, does not require a matrix inversion, can easily encode prior knowledge in the set of implementable functions, and does not have an ?out-of-sample? problem. Experimental results on both artificial and real-world datasets show the usefulness of our approach.

Joint inversion of crosshole GPR and seismic traveltime data

Joint inversion of crosshole ground-penetrating radar and seismic data can improve model resolution and fidelity of the resultant individual models. Model coupling obtained by minimizing or penalizing some measure of structural dissimilarity between models appears to be the most versatile approach because only weak assumptions about petrophysical relationships are required. Nevertheless, experimental results and petrophysical arguments suggest that when porosity variations are weak in saturated unconsolidated environments, then radar wave speed is approximately linearly related to seismic wave speed. Under such circumstances, model coupling also can be achieved by incorporating cross-covariances in the model regularization. In two case studies, structural similarity is imposed by penalizing models for which the model cross-gradients are nonzero. A first case study demonstrates improvements in model resolution by comparing the resulting models with borehole information, whereas a second case study uses point-spread functions. Although radar seismic wavespeed crossplots are very similar for the two case studies, the models plot in different portions of the graph, suggesting variances in porosity. Both examples display a close, quasilinear relationship between radar seismic wave speed in unconsolidated environments that is described rather well by the corresponding lower Hashin-Shtrikman (HS) bounds. Combining crossplots of the joint inversion models with HS bounds can constrain porosity and pore structure better than individual inversion results can.

A new drug delivery system inhibits uveitis in an animal model after cataract surgery.

Cataract surgery is a common ocular surgical procedure consisting in the implantation of an artificial intraocular lens (IOL) to replace the ageing, dystrophic or damaged natural one. The management of postoperative ocular inflammation is a major challenge especially in the context of pre-existing uveitis. The association of the implanted IOL with a drug delivery system (DDS) allows the prolonged intraocular release of anti-inflammatory agents after surgery. Thus IOL-DDS represents an "all in one" strategy that simultaneously addresses both cataract and inflammation issues. Polymeric DDS loaded with two model anti-inflammatory drugs (triamcinolone acetonide (TA) and cyclosporine A (CsA)) were manufactured in a novel way and tested regarding their efficiency for the management of intraocular inflammation during the 3 months following surgery. The study involved an experimentally induced uveitis in rabbits. Experimental results showed that medicated DDS efficiently reduced ocular inflammation (decrease of protein concentration in aqueous humour, inflammatory cells in aqueous humour and clinical score). Additionally, more than 60% of the loading dose remained in the DDS at the end of the experiment, suggesting that the system could potentially cover longer inflammatory episodes. Thus, IOL-DDS were demonstrated to inhibit intraocular inflammation for at least 3 months after cataract surgery, representing a potential novel approach to cataract surgery in eyes with pre-existing uveitis.

Study of OSEM with different subsets in grating-based X-ray differential phase-contrast imaging.

Impressive developments in X-ray imaging are associated with X-ray phase contrast computed tomography based on grating interferometry, a technique that provides increased contrast compared with conventional absorption-based imaging. A new "single-step" method capable of separating phase information from other contributions has been recently proposed. This approach not only simplifies data-acquisition procedures, but, compared with the existing phase step approach, significantly reduces the dose delivered to a sample. However, the image reconstruction procedure is more demanding than for traditional methods and new algorithms have to be developed to take advantage of the "single-step" method. In the work discussed in this paper, a fast iterative image reconstruction method named OSEM (ordered subsets expectation maximization) was applied to experimental data to evaluate its performance and range of applicability. The OSEM algorithm with different subsets was also characterized by comparison of reconstruction image quality and convergence speed. Computer simulations and experimental results confirm the reliability of this new algorithm for phase-contrast computed tomography applications. Compared with the traditional filtered back projection algorithm, in particular in the presence of a noisy acquisition, it furnishes better images at a higher spatial resolution and with lower noise. We emphasize that the method is highly compatible with future X-ray phase contrast imaging clinical applications.

Binding free energy differences in a TCR-peptide-MHC complex induced by a peptide mutation: a simulation analysis.

Recognition by the T-cell receptor (TCR) of immunogenic peptides presented by class I major histocompatibility complexes (MHCs) is the determining event in the specific cellular immune response against virus-infected cells or tumor cells. It is of great interest, therefore, to elucidate the molecular principles upon which the selectivity of a TCR is based. These principles can in turn be used to design therapeutic approaches, such as peptide-based immunotherapies of cancer. In this study, free energy simulation methods are used to analyze the binding free energy difference of a particular TCR (A6) for a wild-type peptide (Tax) and a mutant peptide (Tax P6A), both presented in HLA A2. The computed free energy difference is 2.9 kcal/mol, in good agreement with the experimental value. This makes possible the use of the simulation results for obtaining an understanding of the origin of the free energy difference which was not available from the experimental results. A free energy component analysis makes possible the decomposition of the free energy difference between the binding of the wild-type and mutant peptide into its components. Of particular interest is the fact that better solvation of the mutant peptide when bound to the MHC molecule is an important contribution to the greater affinity of the TCR for the latter. The results make possible identification of the residues of the TCR which are important for the selectivity. This provides an understanding of the molecular principles that govern the recognition. The possibility of using free energy simulations in designing peptide derivatives for cancer immunotherapy is briefly discussed.