The Role of the CD4 Receptor versus HIV Coreceptors in Envelope-Mediated Apoptosis in Peripheral Blood Mononuclear Cells

AbstractWe examined the role of CD4, CXCR4, and CCR5 in HIV envelope-mediated apoptosis by measuring the response of activated PBMCs to recombinant envelope proteins derived from CXCR4- and CCR5-utilizing viruses. Apoptosis of T cells was assessed by annexin-V staining and TdT-mediated dUTP-biotin nick-end labeling. Treatment of CCR5Δ32 homozygote PBMCs with a CCR5-specific envelope induced apoptosis in T cells, demonstrating that envelope–CD4 interactions are sufficient to induce apoptosis. However, a CXCR4-specific envelope induced higher levels of apoptosis than a CCR5-specific envelope, suggesting that envelope-mediated apoptosis can be enhanced by envelope–CXCR4 interactions. We conclude that envelope can induce apoptosis in T cells independently of the coreceptor specificity of a given envelope, or the expression profile of CXCR4 or CCR5 on a target cell. However, envelope–coreceptor interactions, and in particular, envelope–CXCR4 interactions, can contribute to this process

Is type II diabetes mellitus (NIDDM) a surgical disease?

Since February 1, 1980, 515 morbidly obese patients have undergone the Greenville gastric bypass (GGB) operation. Of these, 212 (41.2%) were euglycemic, 288 (55.9%) were either diabetic or had glucose intolerance, and 15 (2.9%) were unable to complete the evaluation. After the operation, only 30 (5.8%) patients remained diabetic (and 20 of these improved), 457 (88.7%) became and have remained euglycemic, and inadequate data prevented classification of the other 28 (5.4%). The patients who failed to return to normal glucose values were older and their diabetes was of longer duration than those who did. The effect of the GGB was not only limited to the correction of abnormal glucose levels. The GGB also corrected the abnormal levels of fasting insulin and glycosylated hemoglobin in a cohort of 52 consecutive severely obese patients with non-insulin-dependent diabetes. The GGB effectively controls weight. If morbid obesity is defined as 100 pounds over ideal body weight, 89% of the patients are no longer "morbidly" obese within 2 years. In most patients, the control of the weight has been well maintained during the 11 years of follow-up; most of the upward creep in weight of 20.8% between 24 and 132 months was from the 49 (9.5%) patients who had staple line breakdowns between the large and small gastric pouches. Non-insulin-dependent diabetes, previously considered a chronic unrelenting disease, can be controlled in the severely obese by the gastric bypass. Whether the correction of glucose metabolism affects the complications of diabetes is unknown. Whether the gastric bypass should be considered for patients with advanced non-insulin-dependent diabetes but who are not severely obese deserves consideration. The GGB has an unacceptably high rate of staple line failure. Accordingly, the authors have recently changed their procedure to one that divides the stomach rather than partitions it with staples. Originally published Annals of Surgery, Vol. 215, No. 6, June 199

Entropy estimates of small data sets

Estimating entropies from limited data series is known to be a non-trivial task. Naive estimations are plagued with both systematic (bias) and statistical errors. Here, we present a new 'balanced estimator' for entropy functionals Shannon, R\'enyi and Tsallis) specially devised to provide a compromise between low bias and small statistical errors, for short data series. This new estimator out-performs other currently available ones when the data sets are small and the probabilities of the possible outputs of the random variable are not close to zero. Otherwise, other well-known estimators remain a better choice. The potential range of applicability of this estimator is quite broad specially for biological and digital data series.Comment: 11 pages, 2 figure

Performance Analysis and Functional Verification of the Stop-and-Wait Protocol in HOL

Real-time systems usually involve a subtle interaction of a number of distributed components and have a high degree of parallelism, which makes their performance analysis quite complex. Thus, traditional techniques, such as simulation, or the state-based formal methods usually fail to produce reasonable results. In this paper, we propose to use higher-order-logic (HOL) theorem proving for the performance analysis of real-time systems. The idea is to formalize the real-time system as a logical conjunction of HOL predicates, whereas each one of these predicates define an autonomous component or process of the given real-time system. The random or unpredictable behavior found in these components is modeled as random variables. This formal specification can then be used in a HOL theorem prover to reason about both functional and performance related properties of the given real-time system. In order to illustrate the practical effectiveness of our approach, we present the analysis of the Stop-and-Wait protocol, which is a classical example of real-time systems. The functional correctness of the protocol is verified by proving that the protocol ensures reliable data transfers. Whereas, the average message delay relation is verified in HOL for the sake of performance analysis. The paper includes the protocol’s formalization details along with the HOL proof sketches for the major theorems