Synthesis of a technetium-99m-labeled thymidine analog: a potential HSV1-TK substrate for non-invasive reporter gene expression imaging

{2-[5-(2′-Fluoro-2′-deoxyuridin-5-yl)pent-4(E)-enyl] [2-(2-mercaptoethyl)aminoethyl]aminoethanethiolato(3)-N,N′,S,S′}oxo-[^99mTc]technetium(V), a potential viral thymidine kinase substrate, was synthesized by coupling 2′-fluoro-2′-deoxyuridine analog with a N2S2 radiometal chelator, followed by [Tc-99m]technetium conjugation. The chemical structure of the radioactive probe was characterized by ¹H NMR and high resolution MS using Re-188 conjugated mimics. The radiochemical purity and yield were identified as 98% and 42%, respectively.     

Adaptive Remodeling in the Elastase-Induced Rabbit Aneurysms

Background

Rupture of brain aneurysms is associated with high fatality and morbidity rates. Through remodeling of the collagen matrix, many aneurysms can remain unruptured for decades, despite an enlarging and evolving geometry.

Objective

Our objective was to explore this adaptive remodeling for the first time in an elastase induced aneurysm model in rabbits.

Methods

Saccular aneurysms were created in 22 New Zealand white rabbits and remodeling was assessed in tissue harvested 2, 4, 8 and 12 weeks after creation.

Results

The intramural principal stress ratio doubled after aneurysm creation due to increased longitudinal loads, triggering a remodeling response. A distinct wall layer with multi-directional collagen fibers developed between the media and adventitia as early as 2 weeks, and in all cases by 4 weeks with an average thickness of 50.6?±?14.3 μm. Collagen fibers in this layer were multi-directional (AI?=?0.56?±?0.15) with low tortuosity (1.08?±?0.02) compared with adjacent circumferentially aligned medial fibers (AI?=?0.78?±?0.12) and highly tortuous adventitial fibers (1.22?±?0.03). A second phase of remodeling replaced circumferentially aligned fibers in the inner media with longitudinal fibers. A structurally motivated constitutive model with both remodeling modes was introduced along with methodology for determining material parameters from mechanical testing and multiphoton imaging.

Conclusions

A new mechanism was identified by which aneurysm walls can rapidly adapt to changes in load, ensuring the structural integrity of the aneurysm until a slower process of medial reorganization occurs. The rabbit model can be used to evaluate therapies to increase aneurysm wall stability.

     

Two approaches to optimal routing and admission control in systems with real-time traffic

This paper addresses the problem of routing and admission control of real-time traffic in a queueing system where customers must begin service within given deadlines (or complete service within given deadlines), otherwise they are considered lost. Performance in such systems is measured by the probability a customer is lost. For a system ofK parallel servers with a probabilistic routing and admission control scheme, the problem of the optimal routing and admission control is considered and two approaches are presented. Assuming the availability of a closed-form expression for the probability of loss at each server, the problem is solved under general conditions and properties of the optimal flow allocation are given. However, such closed-form expressions are often unavailable. This motivates a second approach, which involves a gradient-based stochastic optimization algorithm with on-line gradient estimation. The gradient estimation problem for loss probabilities is solved through a recently-developed smoothed perturbation analysis (SPA) technique. The effectiveness of on-line stochastic optimization using this type of gradient estimator is demonstrated by combining the SPA algorithm with a sampling-controlled stochastic optimization algorithm for the aforementioned routing and admission control problem.This work was supported in part by the Office of Naval Research under Contract N00014-87-K-0304, by the Rome Air Development Center under Contract F30602-88-D-0027, by NASA under Contract NAG 2-595, and by the National Science Foundation under Grant EID-92-12122.The authors are grateful to Don Towsley for several contributions to Section 2 and to an anonymous reviewer for pointing out a redundant assumption in the proof of Lemma 2.1.     

Smoothed perturbation analysis algorithms for estimating the derivatives of occupancy-related functions in serial queueing networks

We present unbiased Smoothed Perturbation Analysis (SPA) estimators for the derivatives of occupancy-related performance functions in serial networks ofG/G/1 queues with respect to parameters of the distributions of service times at the queues. The sample functions for these performance measures are piecewise constant, and established Infinitesimal Perturbation Analysis (IPA) methods typically fail to provide unbiased estimators in this case. The performance measures considered in this paper are: the average network occupancy as seen by an arrival, the average occupancy of a specific queue as seen by an arrival to it, the probability that a customer is blocked at a specific queue, and the probability that a customer leaves a queue idle. The SPA estimators derived are quite simple and flexible, and they lend themselves to straightforward analysis. Unlike most of the established SPA algorithms, ours are not based on the comparison of hazard rates, and the proofs of their unbiasedness do not require the boundedness of such hazard rates.Supported in part by the National Science Foundation under Grant ECS-8801912, by the Office of Naval Research under Contract N00014-87-K-0304, and by NASA under Contract NAG 2-595.