c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration.

The radical response of peripheral nerves to injury (Wallerian degeneration) is the cornerstone of nerve repair. We show that activation of the transcription factor c-Jun in Schwann cells is a global regulator of Wallerian degeneration. c-Jun governs major aspects of the injury response, determines the expression of trophic factors, adhesion molecules, the formation of regeneration tracks and myelin clearance and controls the distinctive regenerative potential of peripheral nerves. A key function of c-Jun is the activation of a repair program in Schwann cells and the creation of a cell specialized to support regeneration. We show that absence of c-Jun results in the formation of a dysfunctional repair cell, striking failure of functional recovery, and neuronal death. We conclude that a single glial transcription factor is essential for restoration of damaged nerves, acting to control the transdifferentiation of myelin and Remak Schwann cells to dedicated repair cells in damaged tissue

Asymptotic Expansions for Stationary Distributions of Perturbed Semi-Markov Processes

New algorithms for computing of asymptotic expansions for stationary distributions of nonlinearly perturbed semi-Markov processes are presented. The algorithms are based on special techniques of sequential phase space reduction, which can be applied to processes with asymptotically coupled and uncoupled finite phase spaces.Comment: 83 page

The ontological consequences of Copernicus: global being in the planetary world

This article argues that contemporary space exploration, in producing visual representations of the planetary Earth for terrestrial consumption, has engendered a shift in the way the Earth - as terra firma - is both experienced and conceived. The article goes on to suggest that this shift is a key, but still largely tacit presupposition, underlying contemporary discourses on globalization and cultural cosmopolitanization. However, a close reading of some of the texts that make up the canon of 20th-century European philosophy shows that this idea of a ‘deterritorialized’ planetary Earth challenges some basic presuppositions of that canon: especially its use of the pre-reflective experience of terra firma as a tropic site of intological and normative grounds. This article examines the way in which contemporary Western European philosophy - and intellectual culture generally - has responded to this challenge: and offers Deleuze and Guattari’s idea of the Earth as a ‘surface without territory’ as the most intellectually and ethically viable conception of the Earth in the age of ‘planetary deterritorialization’

Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes

<p>Abstract</p> <p>Background</p> <p>Development of a standardized platform for the rapid expansion of tumor-infiltrating lymphocytes (TILs) with anti-tumor function from patients with limited TIL numbers or tumor tissues challenges their clinical application.</p> <p>Methods</p> <p>To facilitate adoptive immunotherapy, we applied genetically-engineered K562 cell-based artificial antigen presenting cells (aAPCs) for the direct and rapid expansion of TILs isolated from primary cancer specimens.</p> <p>Results</p> <p>TILs outgrown in IL-2 undergo rapid, CD28-independent expansion in response to aAPC stimulation that requires provision of exogenous IL-2 cytokine support. aAPCs induce numerical expansion of TILs that is statistically similar to an established rapid expansion method at a 100-fold lower feeder cell to TIL ratio, and greater than those achievable using anti-CD3/CD28 activation beads or extended IL-2 culture. aAPC-expanded TILs undergo numerical expansion of tumor antigen-specific cells, remain amenable to secondary aAPC-based expansion, and have low CD4/CD8 ratios and FOXP3+ CD4+ cell frequencies. TILs can also be expanded directly from fresh enzyme-digested tumor specimens when pulsed with aAPCs. These "young" TILs are tumor-reactive, positively skewed in CD8+ lymphocyte composition, CD28 and CD27 expression, and contain fewer FOXP3+ T cells compared to parallel IL-2 cultures.</p> <p>Conclusion</p> <p>Genetically-enhanced aAPCs represent a standardized, "off-the-shelf" platform for the direct ex vivo expansion of TILs of suitable number, phenotype and function for use in adoptive immunotherapy.</p

Potential of a multiparametric optical sensor for determining in situ the maturity components of red and white vitis vinifera wine grapes

A non-destructive fluorescence-based technique for evaluating Vitis vinifera L. grape maturity using a portable sensor (Multiplex ®) is presented. It provides indices of anthocyanins and chlorophyll in Cabernet Sauvignon, Merlot and Sangiovese red grapes and of flavonols and chlorophyll in Vermentino white grapes. The good exponential relationship between the anthocyanin index and the actual anthocyanin content determined by wet chemistry was used to estimate grape anthocyanins from in field sensor data during ripening. Marked differences were found in the kinetics and the amount of anthocyanins between cultivars and between seasons. A sensor-driven mapping of the anthocyanin content in the grapes, expressed as g/kg fresh weight, was performed on a 7-ha vineyard planted with Sangiovese. In the Vermentino, the flavonol index was favorably correlated to the actual content of berry skin flavonols determined by means of HPLC analysis of skin extracts. It was used to make a non-destructive estimate of the evolution in the flavonol concentration in grape berry samplings. The chlorophyll index was inversely correlated in linear manner to the total soluble solids (°Brix): it could, therefore, be used as a new index of technological maturity. The fluorescence sensor (Multiplex) possesses a high potential for representing an important innovative tool for controlling grape maturity in precision viticulture

How to handle mortality when investigating length of hospital stay and time to clinical stability

<p>Abstract</p> <p>Background</p> <p>Hospital length of stay (LOS) and time for a patient to reach clinical stability (TCS) have increasingly become important outcomes when investigating ways in which to combat Community Acquired Pneumonia (CAP). Difficulties arise when deciding how to handle in-hospital mortality. Ad-hoc approaches that are commonly used to handle time to event outcomes with mortality can give disparate results and provide conflicting conclusions based on the same data. To ensure compatibility among studies investigating these outcomes, this type of data should be handled in a consistent and appropriate fashion.</p> <p>Methods</p> <p>Using both simulated data and data from the international Community Acquired Pneumonia Organization (CAPO) database, we evaluate two ad-hoc approaches for handling mortality when estimating the probability of hospital discharge and clinical stability: 1) restricting analysis to those patients who lived, and 2) assigning individuals who die the "worst" outcome (right-censoring them at the longest recorded LOS or TCS). Estimated probability distributions based on these approaches are compared with right-censoring the individuals who died at time of death (the complement of the Kaplan-Meier (KM) estimator), and treating death as a competing risk (the cumulative incidence estimator). Tests for differences in probability distributions based on the four methods are also contrasted.</p> <p>Results</p> <p>The two ad-hoc approaches give different estimates of the probability of discharge and clinical stability. Analysis restricted to patients who survived is conceptually problematic, as estimation is conditioned on events that happen <it>at a future time</it>. Estimation based on assigning those patients who died the worst outcome (longest LOS and TCS) coincides with the complement of the KM estimator based on the subdistribution hazard, which has been previously shown to be equivalent to the cumulative incidence estimator. However, in either case the time to in-hospital mortality is ignored, preventing simultaneous assessment of patient mortality in addition to LOS and/or TCS. The power to detect differences in underlying hazards of discharge between patient populations differs for test statistics based on the four approaches, and depends on the underlying hazard ratio of mortality between the patient groups.</p> <p>Conclusions</p> <p>Treating death as a competing risk gives estimators which address the clinical questions of interest, and allows for simultaneous modelling of both in-hospital mortality and TCS / LOS. This article advocates treating mortality as a competing risk when investigating other time related outcomes.</p

Development Discourse and Practice: Alternatives and New Directions from Postcolonial Perspectives

Development and aid programs, such as those aimed at promoting economic growth and prosperity in ‘Third World’ nations and transition economies, often arise out of Western and neo-liberal policy ideologies and practices. These programs may, in some cases, provide useful guidelines for restructuring institutional structures and governance mechanisms in nations that have long struggled with poverty, economic instability, health crises, and social and political turmoil. However, a growing number of critical voices are raising concerns over the guiding assumptions and inclusiveness of these policies and programs in their aims to promote economic development and social well-being in non-Western nations. We join these critical perspectives by way of postcolonial frameworks to highlight some of the problematic assumptions and oversights of development programs, while offering new alternatives and directions. By doing so, we contribute to organizational theorizing in a global context, as postcolonial insights provide much needed engagement with international aid policies and programs, as well as development organizations and institutions. To accomplish this, we offer a historical perspective on development, present a critique of the policies and practices guiding many aid programs, and conclude with suggestions emanating from postcoloniality