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.     

Mathematical and Scientific Foundations for an Integrative Engineering Curriculum

All fields of engineering, whether chemical, civil, electrical, materials, mechanical, etc., encompass a common body of essential mathematics and science. In the freshman year of Drexels E⁴ program, this common mathematical and scientific foundation is cultivated in the Mathematical and Scientific Foundations of Engineering I, II and III (MSFE I, MSFE II, MSFE III). In an integrated fashion, MSFE I presents the essential calculus, physics and engineering mechanics vital to the freshman engineering student. In the first two quarters, MSFE II presents chemistry with clearly defined engineering applications and significance: in the third quarter, MSFE II presents living systems with the same thrust. Also in the third quarter, MSFE III presents basic circuits and circuit elements, and a brief introduction to electromagnetic theory.     

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.     

Anomalous Defects and Dynamic Failure of Armor Ceramics

The ballistic performance of state-of-the-art silicon carbide armor material can exhibit a fairly wide variability in certain test configurations, which, it is proposed, may be due to the presence of large (>0.1 mm), rare defects, termed, herein, "anomalous" defects. SiC rubble resulting from ballistic tests was examined, as were quasi-static test samples. Ballistic fragment fracture surfaces revealed large carbonaceous defects that seemed to affect fracture path and mode. Low-strength biaxial flexure samples demonstrated similar defects (>0.1 mm) as failure origins. Carbonaceous defects similar in appearance but smaller in size were also found at the fracture origins of SiC bend bars. Frequently, alumina inclusions were found within the carbonaceous discontinuities. These alumina inclusions may cause the graphitic regions to form during sintering. The random distribution of such large, rare carbonaceous discontinuities from sample-to-sample, as well as batch-to-batch variability, may explain high ballistic variability for SiC armor ceramics.