Succinate and malate improve development of hamster eight-cell embryos in vitro: confirmation of viability by embryo transfer

The in vitro development of hamster preimplantation embryos is supported by non-glucose energy substrates. To investigate the importance of embryonic metabolism, influence of succinate and malate on the development of hamster 8-cell embryos to blastocysts was examined using a chemically defined protein-free modified hamster embryo culture medium-2 (HECM-2m). There was a dose-dependent influence of succinate on blastocyst development; 0.5 mM succinate was optimal (85.1% +/- 3.9 vs. 54.5% +/- 3.5). In succinate-supplemented HECM-2m, blastocyst development was reduced by omission of lactate (68.5% +/- 7.2), but not pyruvate (85.8% +/- 6.2) or glutamine (84.1% +/- 2.1). Succinate along with either glutamine or lactate or pyruvate poorly supported blastocyst development (28%-58%). Malate also stimulated blastocyst development; 0.01 mM malate was optimal (86.3% +/- 2.8). Supplementation of both succinate and malate to HECM-2m supported maximal (100%) blastocyst development, which was inhibited 4-fold by the addition of glucose/phosphate. The mean cell numbers (MCN) of blastocysts cultured in succinate-supplemented HECM-2m was higher (28.3 +/- 1.1) than it was for those cultured in the absence of glutamine or pyruvate (range 20-24). The MCN was the highest (33.4 +/- 1.6) for blastocysts cultured in succinate-malate-supplemented HECM-2m followed by those in succinate (28.3 +/- 1.1) or malate (24.7 +/- 0.5) supplemented HECM-2m. Embryo transfer experiments showed that 29.8% (+/- 4.5) of transferred blastocysts cultured in succinate-malate-supplemented HECM-2m produced live births, similar (P > 0.1) to the control transfers of freshly recovered 8-cells (33.5% +/- 2.0) or blastocysts (28.9% +/- 3.0). These data show that supplementation of succinate and malate to HECM-2m supports 100% development of hamster 8-cell embryos to high quality viable blastocysts and that non-glucose oxidizable energy substrates are the most preferred components in hamster embryo culture medium.     

Accommodation without feedback suggests directional signals specify ocular focus

Accommodation was monitored continuously under open-loop conditions while subjects viewed a sinusoidally oscillating sine-wave grating (0.2 Hz; +/- 1 D; 2.7 c/d; 0.56 contrast) in a Badal optometer. The target was illuminated by monochromatic light (590 nm) or white light (3000 K) with longitudinal chromatic aberration (LCA) normal, doubled, neutralized and reversed. Subjects (12) accommodated well in white light with LCA normal and doubled (mean gains = 0.85 and 0.94), gain was reduced in the neutralized condition (0.54), in monochromatic light (0.43), and especially when LCA was reversed (0.30). The results suggest that accommodation responds to changes in the relative contrast of spectral components of the retinal image and perhaps to the vergence of light.     

Ex vivo cytotoxic drug evaluation by DiSC assay to expedite identification of clinical targets: results with 8-chloro-cAMP

There is a pressing need to reduce the time and cost of developing new cytotoxic agents and to accurately identify clinically active agents at an early stage. In this study, the differential staining cytotoxicity (DiSC) assay was used to assess the efficacy of the novel antitumour cAMP analogue, 8-chloro-cAMP (8-Cl-cAMP) (and its metabolite 8-Cl-adenosine) against 107 fresh specimens of human neoplastic and normal cells. Diagnoses included chronic and acute leukaemias, myeloma, non-Hodgkin's lymphoma (NHL) and miscellaneous solid tumours. The aim was to identify targets for subsequent phase I, II and III trials. 8-Cl-cAMP was tested at 4-985 microM, along with standard chemotherapeutic drugs. 8-Cl-cAMP and its metabolite caused no morphologically observable cell differentiation but induced dose-dependent cytotoxicity. Compared with untreated patients, previously treated chronic lymphocytic leukaemia (CLL) patients showed no increase in ex vivo resistance to 8-Cl-cAMP (P = 0.878); minimal cross-resistance with other cytotoxic drugs was detected. Compared with normal cells (mean LC90 = 1803 microM), 8-Cl-cAMP showed significant ex vivo activity against CLL (117.0 microM; P < 0.0001) and NHL (140.0 microM; P < 0.0001), of which eight were mantle cell NHL (84.7 microM), and greatest activity against cells from patients with acute myeloid leukaemia (AML; mean LC90 = 24.3 microM; in vitro therapeutic index 74-fold, P < 0.0001). Solid tumour specimens were comparatively resistant to 8-Cl-cAMP. The results highlight the clinical potential of 8-Cl-cAMP, point to several new phase I, II and III trial possibilities and provide a rationale for the inclusion of ex vivo cytotoxic drug evaluation in the drug development process.     

Availability modeling of energy management systems

Energy management system (EMS) computer architectures have changed significantly over the recent past increasing the difficulty and the need for a priori assessment of system performance and dependability. The old practice based on measurements is no longer acceptable because of the flexibility accrued with the deployment of the new distributed computer-based systems. The number of “what if” questions increased since EMS systems are now implemented using multiple workstations that can be interconnected in various different ways.In this paper we show how alternative configurations can be modeled and analyzed, before proposing and purchasing any equipment, with the assistance of Markov reward models. We review the concept of Markov reward models and show how they can be applied in the availability analysis of SCADA/EMS computer systems. The paper also presents a software tool that facilitates automatic generation and solution of large Markov reward models. The input language of this modeling tool uses a variation of stochastic Petri nets called stochastic reward nets, which are also reviewed. We believe this is the first time a detailed quantitative model of a SCADA/EMS computer system is proposed and solved in the general literature.     

Buffer losses vs. deadline violations for ABR traffic in an ATM switch: A computational approach

The B‐ISDN will carry a variety of traffic types: the Variable Bit Rate traffic (VBR), of which compressed video is an example, Continuous Bit Rate traffic (CBR), of which telemetry is an example, Data traffic, and Available Bit Rate traffic (ABR) that represents aggregate data traffic with very limited guarantees on quality. Of these, VBR and CBR have timing constraints and need synchronous bandwidth; data traffic is relatively delay insensitive. In this paper, we consider the VBR, Data and ABR traffic types and obtain the cumulative distribution function (cdf) of the queueing delay experienced by a burst of ABR traffic in the output buffer of an ATM switch. The cdf is used to trade off buffer loss probabilities against deadline violation probabilities through adjusting the buffer size and (delay) deadline values. Large buffers result in low losses but queueing delays can become excessive and cause a high level of deadline violations. Both losses and violations are detrimental and an operating point must be chosen to achieve a balance. In this paper we study the nature of the trade off. We develop a stochastic Petri net model assuming periodic burst arrivals for VBR and Poisson arrival processes for the Data and ABR traffic types at the burst level, and solve the model analytically (numerically) using a decomposition approach. This decomposition, along with the inherent decomposability of the tagged customer approach for obtaining the cdf opens up a possibility of carrying out fast computations using a parallel machine for selecting the operating point each time that a call is admitted. This revised version was published online in June 2006 with corrections to the Cover Date.     

Chronic myelogenous leukemia

Chronic myelogenous leukemia is a clonal hematopoietic malignancy characterized by a balanced translocation between chromosomes 9 and 22 that results in the generation of an abnormal bcr/abl fusion protein with increased tyrosine kinase activity. This abnormal fusion protein has transforming activity for hematopoietic cells in vitro and causes chronic myelogenous leukemia-like myelopoiesis in mice. Chronic myelogenous leukemia progenitor cells display abnormalities in their interactions with bone marrow stroma, perhaps due to defective adhesion molecule function. Conventional therapies for chronic myelogenous leukemia include hydroxyurea, busulfan, or interferon. Treatment with interferon may prolong overall survival, especially in patients who achieve a cytogenetic response. Related donor marrow transplantation can result in long-term survival in more than 65% of patients treated early in the course of disease. For patients without an available matched sibling donor, unrelated donor marrow transplantation or autologous marrow transplantation are alternative therapeutic options.     

A new silver sulfadiazine water soluble gel

Silver sulfadiazine is the most commonly used topical antibacterial agent for the treatment of burn wounds. It has many clinical advantages, including a broad spectrum of antimicrobial activity, low toxicity, and minimal pain on application. The current formulation of silver sulfadiazine contains a lipid soluble carrier, polypropylene glycol, that has certain disadvantages, including pseudo-eschar formation and the need for twice daily application. The purpose of this investigation was to describe a new formulation of silver sulfadiazine in a water soluble gel, poloxamer 188. The antibacterial activity of this new gel has been compared to that of the commercially available silver sulfadiazine cream by in vitro and in vivo testing. The results of the in vitro antibacterial testing of these two different agents demonstrated the superiority of the new gel formulation. In experimental wounds, the antibacterial activity of the gel and the commercially available silver sulfadiazine cream were not significantly different when applied once a day. The antibacterial activity of the gel when applied once a day was comparable to that encountered by twice daily applications of the silver sulfadiazine cream by experimental wounds. The major advantage of this gel was its ease of application and removal that is attributed to its water solubility.     

Lane Change Intent Analysis Using Robust Operators and Sparse Bayesian Learning

In this paper, we demonstrate a driver intent inference system that is based on lane positional information, vehicle parameters, and driver head motion. We present robust computer vision methods for identifying and tracking freeway lanes and driver head motion. These algorithms are then applied and evaluated on real-world data that are collected in a modular intelligent vehicle test bed. Analysis of the data for lane change intent is performed using a sparse Bayesian learning methodology. Finally, the system as a whole is evaluated using a novel metric and real-world data of vehicle parameters, lane position, and driver head motion.     

Occupant posture analysis with stereo and thermal infrared video: algorithms and experimental evaluation

Dynamic analysis of vehicle occupant posture is a key requirement in designing "smart airbag" systems. Vision-based technology could enable the use of precise information about the occupant's size, posture, and, in particular, position in making airbag-deployment decisions. Novel sensory systems and algorithms need to be developed for capture, analysis, and classification of dynamic video-based information for a new generation of safe airbags. This paper presents a systematic investigation in which stereo and thermal long-wavelength infrared video-based real-time vision systems are developed and systematically evaluated. It also includes the design of several test beds, including instrumented vehicles for systematic experimental studies for the evaluation of independent and comparative evaluation in automobiles. Results of extensive experimental trials suggest basic feasibility of stereo and thermal long-wavelength infrared video-based occupant position and posture-analysis system.     

Modeling of solidification microstructures in concentrated solutions and intermetallic systems

Most of the theoretical models for the predictions of solidification microstructure and solute segregation are based on the assumption mat the solute distribution coefficient,k, is independent of temperature. For concentrated alloys and for alloys near intermetallic compounds,k may vary significantly with temperature. A theoretical analysis which shows the necessary modifications in the theoretical models which must be made ifk varies with temperature is developed. It is shown that for phase diagrams with linear liquidus and solidus segments, many of the results derived with constantk can be used if the solute distribution coefficientk is replaced by a modified parameterk* which includesk as well as the derivative ofk with composition. The application of the model to concentrated alloys and to compositions near intermetallic phases is discussed. It is shown that the variation ink with temperature can significantly alter the composition dependence of dendritic microstructural scales and change the solute segregation profiles in solidified alloys.