Magnetic resonance water proton relaxation in protein solutions and tissue: T(1rho) dispersion characterization.

BACKGROUND: Image contrast in clinical MRI is often determined by differences in tissue water proton relaxation behavior. However, many aspects of water proton relaxation in complex biological media, such as protein solutions and tissue are not well understood, perhaps due to the limited empirical data. PRINCIPAL FINDINGS: Water proton T(1), T(2), and T(1rho) of protein solutions and tissue were measured systematically under multiple conditions. Crosslinking or aggregation of protein decreased T(2) and T(1rho), but did not change high-field T(1). T(1rho) dispersion profiles were similar for crosslinked protein solutions, myocardial tissue, and cartilage, and exhibited power law behavior with T(1rho)(0) values that closely approximated T(2). The T(1rho) dispersion of mobile protein solutions was flat above 5 kHz, but showed a steep curve below 5 kHz that was sensitive to changes in pH. The T(1rho) dispersion of crosslinked BSA and cartilage in DMSO solvent closely resembled that of water solvent above 5 kHz but showed decreased dispersion below 5 kHz. CONCLUSIONS: Proton exchange is a minor pathway for tissue T(1) and T(1rho) relaxation above 5 kHz. Potential models for relaxation are discussed, however the same molecular mechanism appears to be responsible across 5 decades of frequencies from T(1rho) to T(1).

Antibiotic resistance-the need for global solutions.

The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.

Clinical Research Environment in India: Challenges and Proposed Solutions.

India has compelling need and keen aspirations for indigenous clinical research. Notwithstanding this need and previously reported growth the expected expansion of Indian clinical research has not materialized. We reviewed the scientific literature, lay press reports, and ClinicalTrials.gov data for information and commentary on projections, progress, and impediments associated with clinical trials in India. We also propose targeted solutions to identified challenges. The Indian clinical trial sector grew by (+) 20.3% CAGR (compound annual growth rate) between 2005 and 2010 and contracted by (-) 14.6% CAGR between 2010 and 2013. Phase-1 trials grew by (+) 43.5% CAGR from 2005-2013, phase-2 trials grew by (+) 19.8% CAGR from 2005-2009 and contracted by (-) 12.6% CAGR from 2009-2013, and phase-3 trials grew by (+) 13.0% CAGR from 2005-2010 and contracted by (-) 28.8% CAGR from 2010-2013. This was associated with a slowing of the regulatory approval process, increased media coverage and activist engagement, and accelerated development of regulatory guidelines and recuperative initiatives. We propose the following as potential targets for restorative interventions: Regulatory overhaul (leadership and enforcement of regulations, resolution of ambiguity in regulations, staffing, training, guidelines, and ethical principles [e.g., compensation]).Education and training of research professionals, clinicians, and regulators.Public awareness and empowerment. After a peak in 2009-2010, the clinical research sector in India appears to be experiencing a contraction. There are indications of challenges in regulatory enforcement of guidelines; training of clinical research professionals; and awareness, participation, partnership, and the general image amongst the non-professional media and public. Preventative and corrective principles and interventions are outlined with the goal of realizing the clinical research potential in India.

Phenotypic characteristics of human type II alveolar epithelial cells suitable for antigen presentation to T lymphocytes.

Type II alveolar epithelial cells (AECII) are well known for their role in the innate immune system. More recently, it was proposed that they could play a role in the antigen presentation to T lymphocytes but contradictory results have been published both concerning their surface expressed molecules and the T lymphocyte responses in mixed lymphocyte cultures. The use of either AECII cell line or fresh cells could explain the observed discrepancies. Thus, this study aimed at defining the most relevant model of accessory antigen presenting cells by carefully comparing the two models for their expression of surface molecules necessary for efficient antigen presentation.

Identifying Barriers and Practical Solutions to Conducting Site-Based Research in North America: Exploring Acute Heart Failure Trials As a Case Study.

Although the prognosis of ambulatory heart failure (HF) has improved dramatically there have been few advances in the management of acute HF (AHF). Despite regional differences in patient characteristics, background therapy, and event rates, AHF clinical trial enrollment has transitioned from North America and Western Europe to Eastern Europe, South America, and Asia-Pacific where regulatory burden and cost of conducting research may be less prohibitive. It is unclear if the results of clinical trials conducted outside of North America are generalizable to US patient populations. This article uses AHF as a paradigm and identifies barriers and practical solutions to successfully conducting site-based research in North America.

Resolution beyond the diffraction limit for regularized object restoration

We propose a new formulation of Miller's regularization theory, which is particularly suitable for object restoration problems. By means of simple geometrical arguments, we obtain upper and lower bounds for the errors on regularized solutions. This leads to distinguish between ' Holder continuity ' which is quite good for practical computations and ` logarithmic continuity ' which is very poor. However, in the latter case, one can reconstruct local weighted averages of the solution. This procedure allows for precise valuations of the resolution attainable in a given problem. Numerical computations, made for object restoration beyond the diffraction limit in Fourier optics, show that, when logarithmic continuity holds, the resolution is practically independent of the data noise level. © 1980 Taylor & Francis Group, LLC.

Positive regularised solutions in electromagnetic inverse scattering

Fredholm integral equations of the first kind are the mathematical model common to several electromagnetic, optical and acoustical inverse scattering problems. In most of these problems the solution must be positive in order to satisfy physical plausibility. We consider ill-posed deconvolution problems and investigate several linear regularization algorithms which provide positive approximate solutions at least in the absence of errors on the data.

Linear inverse problems with discrete data: II. Stability and regularization

For pt.I. see ibid. vol.1, p.301 (1985). In the first part of this work a general definition of an inverse problem with discrete data has been given and an analysis in terms of singular systems has been performed. The problem of the numerical stability of the solution, which in that paper was only briefly discussed, is the main topic of this second part. When the condition number of the problem is too large, a small error on the data can produce an extremely large error on the generalised solution, which therefore has no physical meaning. The authors review most of the methods which have been developed for overcoming this difficulty, including numerical filtering, Tikhonov regularisation, iterative methods, the Backus-Gilbert method and so on. Regularisation methods for the stable approximation of generalised solutions obtained through minimisation of suitable seminorms (C-generalised solutions), such as the method of Phillips (1962), are also considered.

Culture-bound technological solutions: An artificial theoretic insight

Sometimes, technological solutions to practical problems are devised that conspicuously take into account the constraints to which a given culture is subjecting the particular task or the manner in which it is carried out. The culture may be a professional culture (e.g., the practice of law), or an ethnic-cum-professional culture (e.g., dance in given ethnic cultures from South-East Asia), or, again, a denominational culture prescribing an orthopraxy impinging on everyday life through, for example, prescribed abstinence from given categories of workday activities, or dietary laws. Massimo Negrotti's Theory of the artificial is a convenient framework for discussing some of these techniques. We discuss a few examples, but focus on the contrast of two that are taken from the same cultural background, namely, technological applications in compliance with Jewish Law orthopraxy. •Soya-, mycoprotein- or otherwise derived meat surrogates are an example ofnaturoid; they emulate the flavours and olfactory properties, as well as the texture and the outer and inner appearance, of the meat product (its kind, cut, form) they set out to emulate (including amenability to cooking in the usual manner for the model), while satisfying cultural dietary prohibitions. •In contrast, the Sabbath Notebook, a writing surrogate we describe in this paper, is atechnoid: it emulates a technique (writing to store alphanumeric information), while satisfying the prohibition of writing at particular times of the liturgical calendar (the Sabbath and the major holidays).

Moment decay rates of solutions of stochastic differential equations

The objective of this paper is to investigate the p-ίh moment asymptotic stability decay rates for certain finite-dimensional Itό stochastic differential equations. Motivated by some practical examples, the point of our analysis is a special consideration of general decay speeds, which contain as a special case the usual exponential or polynomial type one, to meet various situations. Sufficient conditions for stochastic differential equations (with variable delays or not) are obtained to ensure their asymptotic properties. Several examples are studied to illustrate our theory.

Pseudo-spectral solutions for fluid flow and heat transfer in electro-metallurgical applications

The pseudo-spectral solution method offers a flexible and fast alternative to the more usual finite element/volume/difference methods, particularly when the long-time transient behaviour of a system is of interest. Since the exact solution is obtained at the grid collocation points superior accuracy can be achieved on modest grid resolution. Furthermore, the grid can be freely adapted with time and in space, to particular flow conditions or geometric variations. This is especially advantageous where strongly coupled, time-dependent, multi-physics solutions are investigated. Examples include metallurgical applications involving the interaction of electromagnetic fields and conducting liquids with a free sutface. The electromagnetic field then determines the instantaneous liquid volume shape and the liquid shape affects in turn the electromagnetic field. In AC applications a thin "skin effect" region results on the free surface that dominates grid requirements. Infinitesimally thin boundary cells can be introduced using Chebyshev polynomial expansions without detriment to the numerical accuracy. This paper presents a general methodology of the pseudo-spectral approach and outlines the solution procedures used. Several instructive example applications are given: the aluminium electrolysis MHD problem, induction melting and stirring and the dynamics of magnetically levitated droplets in AC and DC fields. Comparisons to available analytical solutions and to experimental measurements will be discussed.

A study of user requirements for COTS: computer off the shelf software solutions

[This abstract is based on the authors' abstract.]Three new standards to be applied when adopting commercial computer off-the-shelf (COTS) software solutions are discussed. The first standard is for a COTS software life cycle, the second for a software solution user requirements life cycle, and the third is a checklist to help in completing the requirements. The standards are based on recent major COTS software solution implementations.

Pseudo-spectral solutions for fluid flow and heat transfer in electro-metallurgical applications

The pseudo-spectral solution method offers a flexible and fast alternative to the more usual finite element and volume methods, particularly when the long-time transient behaviour of a system is of interest. The exact solution is obtained at grid collocation points leading to superior accuracy on modest grids. Furthermore, the grid can be freely adapted in time and space to particular flow conditions or geometric variations, especially useful where strongly coupled, time-dependent, multi-physics solutions are investigated. Examples include metallurgical applications involving the interaction of electromagnetic fields and conducting liquids with a free surface. The electromagnetic field determines the instantaneous liquid volume shape, which then affects the electromagnetic field. A general methodology of the pseudo-spectral approach is presented, with several instructive example applications: the aluminium electrolysis MHD problem, induction melting in a cold crucible and the dynamics of AC/DC magnetically levitated droplets. Finally, comparisons with available analytical solutions and to experimental measurements are discussed.

A hybrid Laplace transform/finite difference boundary element method for diffusion problems

The solution process for diffusion problems usually involves the time development separately from the space solution. A finite difference algorithm in time requires a sequential time development in which all previous values must be determined prior to the current value. The Stehfest Laplace transform algorithm, however, allows time solutions without the knowledge of prior values. It is of interest to be able to develop a time-domain decomposition suitable for implementation in a parallel environment. One such possibility is to use the Laplace transform to develop coarse-grained solutions which act as the initial values for a set of fine-grained solutions. The independence of the Laplace transform solutions means that we do indeed have a time-domain decomposition process. Any suitable time solver can be used for the fine-grained solution. To illustrate the technique we shall use an Euler solver in time together with the dual reciprocity boundary element method for the space solution

Rapid solutions for application specific IGBT module design

The electric car, the all electric aircraft and requirements for renewable energy are prime examples of potential technologies needing to be addressed in the world problem of global warming/carbon emission etc. Power electronics are fundamental for the underpinning of these technologies and with the diverse requirements for electrical configurations and the range of environmental conditions, time to market is paramount for module manufacturers and systems designers alike. This paper presents a 'virtual' design methodology together with theoretical and experimental results that demonstrate enhanced product design with improved reliability, performance and cost value within competitive schemes.