פרסומים

It has been suggested that the very low incidence of atherosclerosis in glycogen storage disease type Ia (GSD Ia) subjects might be attributed to elevated levels of uric acid, one of the potent low molecular- weight antioxidants found in plasma. The present communication describes a use of two analytical methods-cyclic voltammetry and ferric reducing ability of plasma-and also two chemiluminescence methods to evaluate the total oxidant-scavenging capacities (TOSC) of plasma from GSD Ia patients. Our results verified the elevation of TOSC in GSD Ia patients and we propose the inclusion of luminescence and cyclic voltammetry assays as reliable methods for estimating TOSC in a variety of clinical disorders. Our findings with the cyclic voltammetry method add support to the assumption that the elevated uric acid levels might be the main contributor to plasma antioxidant capacity and possible protection against atherosclerosis.

Flash-flood warning models can save lives and protect various kinds of infrastructure. In dry climate regions, rainfall is highly variable and can be of high-intensity. Since rain gauge networks in such areas are sparse, rainfall information derived from weather radar systems can provide useful input for flash- flood models. This paper presents a flash-flood warning model which utilizes radar rainfall data and applies it to two catchments that drain into the dry Dead Sea region. Radar-based quantitative precipita- tion estimates (QPEs) were derived using a rain gauge adjustment approach, either on a daily basis (allowing the adjustment factor to change over time, assuming available real-time gauge data) or using a constant factor value (derived from rain gauge data) over the entire period of the analysis. The QPEs served as input for a continuous hydrological model that represents the main hydrological processes in the region, namely infiltration, flow routing and transmission losses. The infiltration function is applied in a distributed mode while the routing and transmission loss functions are applied in a lumped mode. Model parameters were found by calibration based on the 5 years of data for one of the catchments. Val- idation was performed for a subsequent 5-year period for the same catchment and then for an entire 10- year record for the second catchment. The probability of detection and false alarm rates for the validation cases were reasonable. Probabilistic flash-flood prediction is presented applying Monte Carlo simulations with an uncertainty range for the QPEs and model parameters. With low probability thresholds, one can maintain more than 70% detection with no more than 30% false alarms. The study demonstrates that a flash-flood warning model is feasible for catchments in the area studied.

Natural proteins often partake in several highly specific protein-protein interactions. They are thus subject to multiple opposing forces during evolutionary selection. To be functional, such multispecific proteins need to be stable in complex with each interaction partner, and, at the same time, to maintain affinity toward all partners. How is this multispecificity acquired through natural evolution? To answer this compelling question, we study a prototypical multispecific protein, calmodulin (CaM), which has evolved to interact with hundreds of target proteins. Starting from high-resolution structures of sixteen CaM-target complexes, we employ state-of-the-art computational methods to predict a hundred CaM sequences best suited for interaction with each individual CaM target. Then, we design CaM sequences most compatible with each possible combination of two, three, and all sixteen targets simultaneously, producing almost 70,000 low energy CaM sequences. By comparing these sequences and their energies, we gain insight into how nature has managed to find the compromise between the need for favorable interaction energies and the need for multispecificity. We observe that designing for more partners simultaneously yields CaM sequences that better match natural sequence profiles, thus emphasizing the importance of such strategies in nature. Furthermore, we show that the CaM binding interface can be nicely partitioned into positions that are critical for the affinity of all CaM-target complexes and those that are molded to provide interaction specificity. We reveal several basic categories of sequence-level tradeoffs that enable the compromise necessary for the promiscuity of this protein. We also thoroughly quantify the tradeoff between interaction energetics and multispecificity and find that facilitating seemingly competing interactions requires only a small deviation from optimal energies. We conclude that multispecific proteins have been subjected to a rigorous optimization process that has fine-tuned their sequences for interactions with a precise set of targets, thus conferring their multiple cellular functions.

Cisplatin, cis-[Pt(NH(3))(2)Cl(2)], is an effective anticancer agent in wide clinical use whose efficacy is affected by cellular interactions with sulfur-containing nucleophiles. These interactions can potentially enhance the efficacy of the drug by mediating its delivery to nuclear DNA or inactivate the drug by binding to it irreversibly or by labilizing the NH(3) ligands. Despite the potential importance of trans-labilization reactions in the mechanism of action of the drug, few detailed studies on trans labilization of the ammines have been conducted. We used 2D NMR to show that some trans labilization occurs in proliferating cells and that aqueous extracts of cancer cells labilized 20% of the amine ligands of cis-[PtCl(2)((13)CH(3)NH(2))(2)] after a 12-h incubation. Both low molecular mass nucleophiles (less than 3 kDa) and high molecular mass nucleophiles (more than 3 kDa) labilize the amines with similar efficiency. Studies with model compounds show that thiols and thioethers bind to platinum(II) at similar rates, but thioethers are significantly more efficient at labilizing the am(m)ine at lower pH. N-Acetylcysteine is a more efficient trans-labilizer than glutathione, suggesting that the displacement of the amine proceeds through an associative mechanism. The lag time, the time that elapses from the formation of the Pt-S bond till the release of the amine trans to the sulfur, depends on the pH (for thiols), increasing at lower pH. Quantification of the platinum adducts obtained from incubation of cisplatin with cell extracts indicates that two thirds of the platinum is bound to cellular components with molecular mass greater than 3 kDa.

An electrooptical channel waveguide array was constructed in potassium lithium tantalate niobate substrate by the implantation of He+ ions at high energies. The array was fabricated by two successive implantation sessions at 1.6 MeV and 1.2 MeV through a comb-like stopping mask that limited the implanted ions to penetrate the substrate in 1 ?m wide stripes periodically distributed at 3.5 ?m intervals. This generated a grating of amorphized stripes with reduced refractive index. This was followed by a uniform implantation of He+ ions at 1.8 MeV which created a bottom cladding layer below the array. Wave propagation in the array was studied by focusing a light beam at 636 nm into the central channel, and observing the wavefront it created at the output plane of the array. It was found that applying an electric field across the array strongly affects the coupling between adjacent channels and governs the width of the wavefront at the output plane.

Published in: Chronique d’Egypte, 84, pp. 136–152.This work of Jean Winand’s aims at providing an account of Tense and Aspect (or rather Aspect and Tense) systems in Egyptian: this (notwithstanding the focus on Old and Middle Egyptian, with Late Egyptian rather thinly treated, and Demotic and Coptic virtually absent) is a staggeringly ambitious undertaking. It implies a confidence in our comprehension of Egyptian, synchronic and diachronic, which this reviewer must admire, but cannot share. And yet, it is almost a blessing that the Later Egyptian systems are only lightly touched upon, for this renders the in-depth treatment of OE and ME virtually monographic, which would be hardly feasible for the whole of Egyptian history — all the more so, since the joints or seams between “successive” phases are fictive and indeed fallacious. On the other hand, one would wish for an extended application of the author’s hypotheses to LE (and Demotic), for the cryptic nature of the earlier phases of Egyptian renders any judgement made regarding their imponderables both subjective and irrefutable. It is easy to pass speculation on O/ME as descriptive statement, which would never do in the more “transparent” later phases. Be that as it may, the reader gets occasionally the eerie, unsettling feeling that it is a transcendental, panchronic (or panoramic) Egyptian that is here under typological scrutiny. (I cannot see, for instance, the soundness of a combined statement [p. 197] on the Stative and sḏm.n.f forms on the basis of Sinuhe and the Late Ramesside Letters).Uploading this article to the Internet Archive is done with the author’s permission and by his request.

It has been argued that increased life expectancy raises the rate of return on education, causing a rise in the investment in education followed by an increase in lifetime labor supply. Empirical evidence of these relations is rather weak. Building on a lifecycle model with uncertain longevity, this paper shows that increased life expectancy does not suffice to warrant the above hypotheses. We provide assumptions about the change in survival probabilities, specifically about the age dependence of hazard rates, which determine individuals' behavioral response w.r.t. education, work and age of retirement. Comparison is made between the case when individuals have access to a competitive annuity market and the case of no insurance.