Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis

Retinol and retinyl esters are converted with time to slowly increasing amounts of all-trans retinoic acid (RA) in cultured human keratinocytes. Exogenous RA has been shown to limit retinol oxidation and to increase retinol esterification. Because significant amounts of retinol are present in biologic systems, we examined whether RA and all-trans-retinoyl-beta-D-glucuronide (RAG) interact with retinol in exhibiting their activities on HaCaT keratinocytes maintained in a retinoid-free culture system. RA was more potent than RAG and retinol in inducing ultrastructural changes attributed to retinoids, inhibiting cell proliferation as well as enhancing keratin 19 expression. In addition, retinoids were able to induce cellular retinoic acid-binding protein II mRNA levels in the cultures, whereas early RA and late RAG activity was detected. The described biologic effects of RA and RAG were diminished by simultaneous cell exposure to retinol. HaCaT cells quickly metabolized retinol to retinyl esters and consequently to low amounts of RA. RA treatment led to an early high peak of cellular RA followed by reduction to trace amounts. Treatment with RAG resulted in constantly high cellular RAG and low RA levels. Under the combined RA and retinol treatment retinyl esters were increased and RA was reduced in HaCaT cells, whereas extracellular RA levels were similar to those obtained by RA alone. On the other hand, the combination of RAG and retinol resulted in higher extracellular RAG, similar cellular RAG, and lower cellular RA levels than those obtained by RAG alone without any change in retinyl esters. This study demonstrates that retinoid signaling by RA and RAG is attenuated by simultaneous exposure of HaCaT keratinocytes in vitro to retinol. The presence of retinol in the medium alters the rate of RA or RAG metabolism and thus cellular RA concentrations. The intensity of retinoid signal is probably dependent on cellular RA levels. The resulting "antagonism" among retinoids is consistent with the presence of an auto-regulatory mechanism in human keratinocytes offering protection against excessive accumulation of cellular RA.     

Leading Psychology Forward: Staying the Course in Uncertain Times.

Like everyone in the country, those in organized psychology have functioned recently in a climate marked by threats of terrorism, uncertainty, and a declining economy. In such challenging times, it might seem logical for the profession to wonder how it needs to change to respond to current circumstances. Yet at such times, staying the course already charted is likely a far more effective strategy. For psychology, this means continuing to press for mental health parity, educating decision makers about the important role of psychological services in preventive care, helping to integrate psychological and physical health services, continuing to hold managed care companies accountable, and increasing the profession's political giving. Psychologists must also be prepared to ensure that psychological services are treated as an integral part of any health reform plan that emerges. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Narrowband to broadband conversions of land surface albedo: II. Validation

In the first paper of this series, we developed narrowband to broadband albedo conversion formulae for a series of sensors. These formulae were determined based on extensive radiative transfer simulations under different surface and atmospheric conditions. However, it is important to validate the simulation results using independent measurement data. In this paper, the validation results for three broadband albedos (total-shortwave, -visible and -near-IR albedos) using ground measurement of several cover types on five different days at Beltsville, MD are presented. Results show that the conversion formulae in the previous paper are very accurate and the average residual standard errors of the resulting broadband albedos for most sensors are around 0.02, which meets the required accuracy for land surface modeling.     

A straightforward Rojas still riles some practitioners: California's top court endorses mediation law,but ADR professionals remain split about the decision

Two articles sort out this summer's biggest ADR‐related case, the California Supreme Court's Rojas decision. First, Alternatives discusses the holding and the fallout. Then, full‐time neutral Jeff Kichaven, of Los Angeles, who worked on an amicus filing in the case, discusses why he believes the opinion, which backs an almost total ban on litigation discoverability of mediation materials, will hurt the profession.     

Antigen processing: where tumor-specific T-cell responses begin

It is well established that tumor-specific CD8+ T cells have the capacity to prevent and cure malignancies in animals under experimental conditions. This has raised expectations that it will prove possible to achieve similar successes with human cancers. CD8+ T cells recognize peptides of 8-10 residues derived from cytosolic proteins that are bound to the class I molecules of the major histocompatibility complex. To most effectively manipulate the T-cell response to tumor cells, it is essential to understand the means by which the peptide-class I complex is created in cells. An overview of this process is provided with an emphasis toward the recent findings made by our laboratory.     

Partial characterization of the human retinal endothelial cell tight and adherens junction complexes

PURPOSE: In diabetic retinopathy and macular edema, the blood-retinal barrier fails to function properly, and there is transvascular leakage of proteins and solutes. The tight junction protein occludin and the adherens junction protein cadherin-5 have been shown to be critical to maintaining the endothelial barrier and regulating paracellular transport of large vessel endothelia. However, the expression and distribution of these junction proteins in the retinal endothelium is not well characterized. METHODS: Human and bovine retinal endothelial cells were isolated as described previously. Western blot analysis and flow cytometry techniques were used to assay for the presence of occludin, zonula occludens-1 (ZO-1), cadherin-5, and beta-catenin. The subcellular localization of the proteins was visualized by immunohistochemistry performed on cultured human retinal endothelial cells and cryosections of bovine retina. RESULTS: Western blot analysis and flow cytometry techniques found occludin, ZO-1, cadherin-5, and beta-catenin in cultured human retinal endothelial cells. Immunofluorescence staining of cultured retinal endothelial cells and cryosections of bovine retina showed junctional localization of occludin, ZO-1, cadherin-5, and beta-catenin. CONCLUSIONS: This report demonstrates the expression of occludin and cadherin-5 in retinal endothelial cells and their localization to sites of cell-cell contact. Expression of their respective regulatory proteins, ZO-1 and beta-catenin, at sites of cell-cell contact suggests that occludin and cadherin-5 play a role in maintaining the retinal endothelial barrier.     

Architectural Options for the Next-Generation Networking Paradigm: Is Optical Internet the Answer?

Recent advances in optical networking technologies are setting the foundation for the next-generation data-centric networking paradigm, an “Optical Internet”. This work addresses one of the most challenging issues facing today's service providers and data vendors; how will the SONET/SDH-based legacy infrastructure currently in place make a graceful transition to the next generation networking paradigm?

A simplified, two-tiered architecture that requires two types of sub-systems will set the stage for a truly optical internet: service delivery platforms that enforce service policies; and transport platforms that intelligently deliver the necessary bandwidth to these service platforms. If IP can be mapped directly onto the WDM layer, some of the unnecessary network layers can be eliminated, opening up new possibilities for the potential of collapsing today's vertically layered network architecture into a horizontal model where all network elements work as peers to dynamically establish optical paths through the network. This paper presents a balanced view of the vision of the next-generation optical internet

The work presented here builds on the IETF multi-protocol lambda switching (MPλS) initiative and addresses the implementation issues of the path selection component of the traffic-engineering problem in a hybrid IP-centric DWDM-based optical network. An overview of the methodologies and associated algorithms for dynamic lightpath computation is presented. Specifically, we show how the complex problem of real-time provisioning of optical channels can be simplified by using a simple dynamic constraint-based routing and wavelength assignment (RWA) algorithm that compute solutions to three sub-problems: (a) routing; (b) constrained-based shortest-route selection; (c) wavelength assignment.

We present two different schemes for dynamic provisioning of the optical channels. The two schemes use the same dynamic lightpath computation approach proposed here, except that the third component, that is the wavelength assignment algorithm and its implementation, is different for each of the two schemes.

     

Noncoherent multiuser detection for nonlinear modulation over the Rayleigh-fading channel

The jointly optimum noncoherent multiuser detector is obtained for nonlinear nonorthogonal modulation over the frequency nonselective Rayleigh-fading multiple-access channel. Upper and lower bounds on the average bit-error probability are derived. While these bounds are numerically computable, they are too complicated to give insight into the relative influence of the system parameters on the essential behavior of the bit-error rate. Hence this paper develops an asymptotic analysis of the average bit-error probability. In particular, it is shown that the upper and lower bounds are asymptotically convergent. An exact formula for the asymptotic efficiency of the optimum noncoherent detector is derived. Interestingly, the asymptotic efficiency is found to be positive and independent of the signal strengths of the interfering users. In contrast, the noncoherent detector which would be optimal in a single-user channel (the "conventional detector"), when used over the multiuser channel, has an asymptotic efficiency that is identically equal to zero no matter what the powers of the interferers may be. While the performance analysis of the optimum detector provides the fundamental limit on achievable error rate, the implementational complexity of the optimum detector is exponential in the number of users. As a low-complexity alternative, a decorrelative energy detector is also proposed and analyzed in terms of error probability and asymptotic efficiency.