A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion

Direct allorecognition is the earliest and most potent immune response against a kidney allograft. Currently, it is thought that passenger donor professional antigen-presenting cells (APCs) are responsible. Further, many studies support that graft ischemia-reperfusion injury increases the probability of acute rejection. We evaluated the possible role of primary human proximal renal tubular epithelial cells (RPTECs) in direct allorecognition by CD4+ T-cells and the effect of anoxia-reoxygenation. In cell culture, we detected that RPTECs express all the required molecules for CD4+ T-cell activation (HLA-DR, CD80, and ICAM-1). Anoxia-reoxygenation decreased HLA-DR and CD80 but increased ICAM-1. Following this, RPTECs were co-cultured with alloreactive CD4+ T-cells. In T-cells, zeta chain phosphorylation and c-Myc increased, indicating activation of T-cell receptor and co-stimulation signal transduction pathways, respectively. T-cell proliferation assessed with bromodeoxyuridine assay and with the marker Ki-67 increased. Previous culture of RPTECs under anoxia raised all the above parameters in T-cells. FOXP3 remained unaffected in all cases, signifying that proliferating T-cells were not differentiated towards a regulatory phenotype. Our results support that direct allorecognition may be mediated by RPTECs even in the absence of donor-derived professional APCs. Also, ischemia-reperfusion injury of the graft may enhance the above capacity of RPTECs, increasing the possibility of acute rejection.     

Diffusion-weighted echo planar MR imaging of the neck at 3 T using integrated shimming: comparison of MR sequence techniques for reducing artifacts caused by magnetic-field inhomogeneities

Objective

Our objective was to compare available techniques reducing artifacts in echo planar imaging (EPI)-based diffusion-weighed magnetic resonance imaging MRI (DWI) of the neck at 3 Tesla caused by B0-field inhomogeneities.

Materials and methods

A cylindrical fat–water phantom was equipped with a Maxwell coil allowing for additional linear B0-field variations in z-direction. The effect of increasing strength of this superimposed gradient on image quality was observed using a standard single-shot EPI-based DWI sequence (sEPI), a zoomed single-shot EPI sequence (zEPI), a readout-segmented EPI sequence (rsEPI), and an sEPI sequence with integrated dynamic shimming (intEPI) on a 3-Tesla system. Additionally, ten volunteers were examined over the neck region using these techniques. Image quality was assessed by two radiologists. Scan durations were recorded.

Results

With increasing strength of the external gradient, marked distortions, signal loss, and failure of fat suppression were observed using sEPI, zEPI, and rsEPI. These artifacts were markedly reduced using intEPI. Significantly better in vivo image quality was also observed using intEPI compared with the other techniques. Scan time of intEPI was similar to sEPI and zEPI and shorter than rsEPI.

Conclusion

The use of integrated 2D shim and frequency adjustment for EPI-based DWI results in a significant improvement in image quality of the head/neck region at 3 Tesla. Combining integrated shimming with rsEPI or zEPI can be expected to provide additional improvements.

     

Modeling heterogeneous bacterial populations exposed to antibiotics: The logistic‐dynamics case

In typical in vitro tests for clinical use or development of antibiotics, samples from a bacterial population are exposed to an antibiotic at various concentrations. The resulting data can then be used to build a mathematical model suitable for dosing regimen design or for further development. For bacterial populations that include resistant subpopulations—an issue that has reached alarming proportions—building such a model is challenging. In prior work, we developed a related modeling framework for such heterogeneous bacterial populations following linear dynamics when exposed to an antibiotic. We extend this framework to the case of logistic dynamics, common among strongly resistant bacterial strains. Explicit formulas are developed that can be easily used in parameter estimation and subsequent dosing regimen design under realistic pharmacokinetic conditions. A case study using experimental data from the effect of an antibiotic on a gram‐negative bacterial population exemplifies the usefulness of the proposed approach. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2385–2393, 2015     

HPLC separation,NMR and QTOF/MS/MS structure elucidation of a prominent nitric oxide donor agent based on an isomeric composition of a nitrosyl ruthenium complex

A new and promising nitrosyl ruthenium complex, [Ru(NO)(bdqi-COOH)(terpy)](PF₆)₃, bdqi-COOH is 3,4-diiminebenzoic acid and terpy is 2,2′-terpyridine, has been synthesized as a NO donor agent. The procedure used for [Ru(NO)(bdqi-COOH)(terpy)](PF₆)₃ synthesis has, apparently, yielded the formation of two isomers in which the ligand bdqi-COOH appears to be coordinated in its reduced form (bdcat-COOH), which could have differences in their pharmacological properties. Therefore, it was intended to separate the two possible isomers by high-performance liquid chromatography (HPLC) and to characterize them by high resolution mass spectrometry (QTOF MS) and by magnetic nuclear resonance spectroscopy (NMR). The results obtained by MS showed that the ESI-MS mass spectra of both HPLC column fractions, e.g. peak 1 and peak 2, are essentially equal, showing that both isomers display nearly identical gas-phase behavior with clusters of isotopologue ions centered at m/z 573, m/z 543 and m/z 513. Regarding the NMR analysis, the results showed that the positional isomerism is located in the bdqi-COOH ligand. From the observed results it can be concluded that the synthesis procedure that has been used results in the formation of two [Ru(terpy)(bdqi-COOH)NO](PF₆)₃ isomers.     

Long-term survival data and prognostic factors of a complete response to chemotherapy in patients with head and neck cancer treated with platinum-based induction chemotherapy: a Hellenic Co-operative oncology Group study

Sudden infant death syndrome (SIDS) is the most common cause of postneonatal infant death in developed countries. The causes of SIDS remain unknown. The principal hypothesis appears abnormality of cardiorespiratory control, sleep-wake regulation. Also in our personal date the autopsy have not been of sufficient specificity and sensitivity to explain the disease.     

A self-adaptive service provisioning framework for 3G+/4G mobile applications

In light of the increasing acceptance of the notion of next generation networks (NGN), which results from the convergence of the fixed and mobile telecommunications, Internet, and entertainment sectors, there is a need for the realization of next-generation service delivery platforms to allow seamless and adaptive provisioning of multimedia information and communication services to mobile users. This means that in such an NGN environment different end systems, access networks, and service platforms have to be integrated. For this highly heterogeneous communications and services environment, we propose a self-adaptive service provisioning middleware framework (ASPF), which, by interoperating with existing wireless and wireline service delivery platforms, aims to enable seamless omnipresent service provisioning to mobile users anywhere, anytime, and in any context. The ASPF is intended to "liberate" applications from space and time limitations, networks, platforms, and device dependences, minimize time-to-market constraints, and eliminate major hurdles that hinder the rapid deployment of new mobile services and applications. Key to this goal is interworking/integration with current SDPs, such as IN/CAMEL, OSA/Parlay, and the emerging IMS.     

Viscous and Aeroelastic Effects on Wind Turbine Blades. The VISCEL project. Part I: 3D Navier–Stokes Rotor simulations

Aerodynamic modelling of HAWT rotors by means of “engineering methods” has reached a saddle point, where no further development can be expected without a breakthrough in understanding the physics of unsteady, rotating three‐dimensional flows. However, such a breakthrough becomes ever more necessary, as the size of the wind turbines increases. With the experimental work in that direction being mostly limited to observing the phenomena and interpreting the associated mechanisms, and its increased cost, alternatives are being sought. The use of CFD techniques and state‐of‐the‐art Navier–Stokes solvers is considered a very serious contender, a belief shared by the members of the present consortium, which has worked on the VISCEL JOR3‐CT98‐0208 Joule III project. This project's goal was to determine the aerodynamic characteristics as well as the aeroelastic behaviour of wind turbine blades across their broad range of operational conditions, from attached to highly separated flow regimes. The work programme included specific tasks for the validation and assessment of existing 3D solvers, for the parametric study of 3D flow around realistic blades and for the investigation of aeroelastic stability, at the blade section level. Copyright © 2003 John Wiley & Sons, Ltd.     

Integrating mental health services within primary care. A Canadian program

The increasingly prominent role of the family physician in delivering mental health care can be enhanced if productive and collaborative relationships can be established with local mental health services. This paper describes a Canadian program that has achieved this by bringing mental health counselors and psychiatrists into the offices of 87 family physicians in 35 practices in a community in Southern Ontario. The paper describes the program, the activities of counselors and psychiatrists within the practices, and the administrative structures set up to coordinate these activities. Data is presented from the evaluation of the first year of the program's operation (13 practices and 45 family physicians) during which time 3085 referrals were received. The program made mental health care more available and accessible, increased continuity of care, provided additional support for the family physician, offered new opportunities for continuing education, and led to a reduced and more efficient use of other mental health services. The components of the program can be adapted to most communities.     

Automated reference-free detection of motion artifacts in magnetic resonance images

Objectives

Our objectives were to provide an automated method for spatially resolved detection and quantification of motion artifacts in MR images of the head and abdomen as well as a quality control of the trained architecture.

Materials and methods

T1-weighted MR images of the head and the upper abdomen were acquired in 16 healthy volunteers under rest and under motion. Images were divided into overlapping patches of different sizes achieving spatial separation. Using these patches as input data, a convolutional neural network (CNN) was trained to derive probability maps for the presence of motion artifacts. A deep visualization offers a human-interpretable quality control of the trained CNN. Results were visually assessed on probability maps and as classification accuracy on a per-patch, per-slice and per-volunteer basis.

Results

On visual assessment, a clear difference of probability maps was observed between data sets with and without motion. The overall accuracy of motion detection on a per-patch/per-volunteer basis reached 97%/100% in the head and 75%/100% in the abdomen, respectively.

Conclusion

Automated detection of motion artifacts in MRI is feasible with good accuracy in the head and abdomen. The proposed method provides quantification and localization of artifacts as well as a visualization of the learned content. It may be extended to other anatomic areas and used for quality assurance of MR images.