BID: a novel BH3 domain-only death agonist

The BCL-2 family of proteins consists of both antagonists (e.g., BCL-2) and agonists (e.g., BAX) that regulate apoptosis and compete through dimerization. The BH1 and BH2 domains of BCL-2 are required to heterodimerize with BAX and to repress cell death; conversely, the BH3 domain of BAX is required to heterodimerize with BCL-2 and to promote cell death. To extend this pathway, we used interactive cloning to identify Bid, which encodes a novel death agonist that heterodimerizes with either agonists (BAX) or antagonists (BCL-2). BID possesses only the BH3 domain, lacks a carboxy-terminal signal-anchor segment, and is found in both cytosolic and membrane locations. BID counters the protective effect of BCL-2. Moreover, expression of BID, without another death stimulus, induces ICE-like proteases and apoptosis. Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. A BH3 mutant of BID that still heterodimerized with BCL-2 failed to promote apoptosis, dissociating these activities. In contrast, the only BID BH3 mutant that retained death promoting activity interacted with BAX, but not BCL-2. This BH3-only molecule supports BH3 as a death domain and favors a model in which BID represents a death ligand for the membrane-bound receptor BAX.     

Early and intensive physiotherapy accelerates recovery postarthroscopic meniscectomy: results of a randomized controlled study

The efficacy of an early, intensive, supervised rehabilitation program to accelerate knee strength recovery in the first 3 weeks postmeniscectomy by arthroscopy was evaluated using a randomized controlled trial design. The maximal voluntary isokinetic strength of 31 men, randomly allocated to either a treatment (EXP) or a control (CTL) group, was measured twice by a blind rater: preoperatively (pretest) and 3 weeks postsurgery (posttest), using a computer-controlled Kin-Com dynamometer (Chattecx Corporation, Chattanooga, TN). Strength deficits of the operated leg at the pretest and posttest were established in percent of the values obtained for the sound leg at the pretest. In the interval between the surgery and the posttest, the patients of the EXP group (n = 15) received nine supervised treatments combined to home exercises whereas patients of the control group (n = 16) had no specific physiotherapy treatment but were given instructions in postsurgical management and prescribed exercises by the orthopedic surgeons. Patients of the EXP group had better knee extensor strength recovery than patients of the CTL group (ANCOVA, p < 0.001). The size of the strength difference (3 weeks postsurgery) between EXP and CTL subgroups (n = 8) matched according to preoperative deficits was as large as 26% and the residual deficits of the untreated patients were two to three times larger than those of the treated patients. The results of this study highlight the importance of instituting an early intensive and supervised rehabilitation program, especially for workers returning to a strenuous job requiring good knee extensor muscle function.     

CTLA4 mediates antigen-specific apoptosis of human T cells

The regulation of T cell-mediated immune responses requires a balance between amplification and generation of effector function and subsequent selective termination by clonal deletion. Although apoptosis of previously activated T cells can be induced by signaling of the tumor necrosis factor receptor family, these molecules do not appear to regulate T-cell clonal deletion in an antigen-specific fashion. We demonstrate that cross-linking of the inducible T-cell surface molecule CTLA4 can mediate apoptosis of previously activated human T lymphocytes. This function appears to be antigen-restricted, since a concomitant signal T-cell receptor signal is required. Regulation of this pathway may provide a novel therapeutic strategy to delete antigen-specific activated T cells.     

A kernel-based framework for image collection exploration

While search engines have been a successful tool to search text information, image search systems still face challenges. The keyword-based query paradigm used to search in image collection systems, which has been successful in text retrieval, may not be useful in scenarios where the user does not have the precise way to express a visual query. Image collection exploration is a new paradigm where users interact with the image collection to discover useful and relevant pictures. This paper proposes a framework for the construction of an image collection exploration system based on kernel methods, which offers a mathematically strong basis to address each stage of an image collection exploration system: image representation, summarization, visualization and interaction. In particular, our approach emphasizes a semantic representation of images using kernel functions, which can be seamlessly harnessed across all system components. Experiments were conducted with real users to verify the effectiveness and efficiency of the proposed strategy.     

Frequency domain regularization of d-dimensional structure tensor-based directional fields

The present work is intended to address two of the major difficulties that can be found when tackling the estimation of the local orientation of the data in a scene, a task which is usually accomplished by means of the computation of the structure tensor-based directional field. On one hand, the orientation information only exists in the non-homogeneous regions of the dataset, while it is zero in the areas where the gradient (i.e. the first-order intensity variation) remains constant. Due to this lack of information, there are many cases in which the overall shape of the represented objects cannot be precisely inferred from the directional field. On the other hand, the orientation estimation is highly dependent on the particular choice of the averaging window used for its computation (since a collection of neighboring gradient vectors is needed to obtain a dominant orientation), typically resulting in vector fields which vary from very irregular (thus yielding a noisy estimation) to very uniform (but at the expense of a loss of angular resolution). The proposed solution to both drawbacks is the regularization of the directional field; this process extends smoothly the previously computed vectors to the whole dataset while preserving the angular information of relevant structures. With this purpose, the paper introduces a suitable mathematical framework and deals with the d-dimensional variational formulation which is derived from it. The proposed formulation is finally translated into the frequency domain in order to obtain an increase of insight on the regularization problem, which can be understood as a low-pass filtering of the directional field. The frequency domain point of view also allows for an efficient implementation of the resulting iterative algorithm. Simulation experiments involving datasets of different dimensionality prove the validity of the theoretical approach.     

IP Squared: Internet Standards and Intellectual Property

Standards-development organizations (SDOs) comprise participants from large and small companies, academia, and the open source community. The participants come with varying backgrounds with regard to copyright and patents in the areas that are being standardized, and the SDOs must deal with these issues in ways that both satisfy the participants (and their employers) and result in useful standards. Each SDO — including the IEEE — has its own intellectual property (IP) policy. This issue, we look at how the IETF handles IP, in an overview cowritten by an attorney who has represented the IETF for some years and the current IETF Chair.     

Using Similarity Analyses to Scale Out Research Findings Across Andean Watershed Basins

Abstract

Strategic research in agriculture and natural resources carried out by international research centers is deemed a public good and should, sooner or later, be put into the hands of development, governmental and non-governmental organizations. However, this research is usually done at specific pilot sites; there is a greater need to know how representative those sites are in relation to the diversity of contexts in other locations. Such is the case with the Challenge Program on Water and Food (CPWF), a global initiative in water research promoted by the Consultative Group on International Agricultural Research (CGIAR), which is developing and implementing strategic research in nine basins located in the tropics of Africa, Asia and South America. Given that resources are not available to collect data from the whole of the region, pilot sites are needed. It is hoped that research outputs obtained in the selected pilot sites can be the basis for scaling out solutions to similar situations in neighbouring or adjacent areas in same or different basins.

In order to contribute to the scaling-out process, different classification methodologies were applied to determine how specific watershed basins are representative of larger areas. The Andean eco-region served as a case study but the methods can easily be applied in other regions. The spatial diversity of biophysical and social conditions across the Andes requires careful site selection. Two methods, a combination of Weight of Evidence (WofE) and Logistic Regression (LR) methods and Fast Cluster analysis, were used to determine the similarity of selected sites with those excluded. A 1-km study resolution covering most of the Andes eco-region included annual rainfall, elevation, length of growing period, land cover, roads and population density as the key variables. Results showed complementarities between the two methods in presenting a probability surface of similarity across the Andes and a clustering of similar sites inside and outside the pilot basins. The output information forms a strong basis for devising plans to scale out research findings from the pilot basins to the whole region.     

Replacing dichromate with hydrogen peroxide in the chemical oxygen demand (COD) test

The widely used standard method for chemical oxygen demand (COD) involves hazardous chromium species, and its two-hour heating protocol entails a substantial amount of energy expenditure. In the present work we report a proof of concept for a major modification of this method in the range 10-800 mgCOD/L, whereby H2O2 is proposed as a replacement oxidizer. This modification not only reduces the use of unsafe chromium species but also allows for the use of milder conditions that decrease the total energy outlay. The results are comparable with those obtained either with the standard method or with a commercial Hach? kit.