Loss of heterozygosity and overexpression of the p53 gene in ovarian carcinoma

Eight anticonvulsant drugs-including clonazepam, diazepam and phenobarbital-were tested for their effects on GABA-stimulated chloride uptake in rat cerebral cortical microsacs (unfiltered synaptoneurosomes). "Mid" and "high" therapeutic concentrations were screened, and, if significant enhancement was found, full concentration-response tests were done. In the initial screens, enhancement of GABA-stimulated uptake was found only with phenobarbital, clonazepam and diazepam. In subsequent concentration-response tests, the effects of phenobarbital were found to occur throughout the range of normal, anticonvulsant concentrations, whereas the effects of clonazepam and diazepam were observed only above the concentrations normally used for the chronic control of seizures or anxiety. These data suggest that phenobarbital's anticonvulsant effects are mediated via the GABAA receptor complex, but that the low-dose effects of the benzodiazepines may be mediated via some other mechanism.     

On knowledge networks in science: collaboration among equals

Knowledge is produced from labor and existing knowledge as embodied in documents and persons. Through knowledge networks, researchers can utilize knowledge inputs from other scientists. This paper examines institutions for knowledge exchange and attempts a formal analysis of scientific exchange in passive and active collaboration.I am indebted to Professors Tawada, Sakai, Ohta and John Roy for helpful comments and corrections.This paper was presented in draft form at an International Workshop on Trade, Knowledge and the Network Economy, held in December 1992 in Mallacoota, Australia.     

A criterion for plane strain,fully plastic,quasi-steady crack growth

Plane strain fracture by hole growth in ordinary-sized parts of low-to-medium strength steels is essentially rigid-plastic, and may be approximated as non-hardening. Quasi-steady crack growth for such materials is predicted for crack-tip fields approximated by a pair of slip lines, such as unequally grooved specimens in tension and deep singly-face-cracked specimens under combined bending and tension. The crack growth increment a is given in terms of material parameters, far-field geometry, and loadings and their increments.For the rigid-plastic, non-hardening approximation, stress and strain increment fields for growing cracks are identical to those for stationary cracks. For fields with a pair of symmetric slip-lines, the flanks of the decohering zone turn out to be rigid, and the decohering zone does not affect the crack-tip opening angle (CTOA), which then depends only on the micromechanisms of hole nucleation, growth and linkage by flow localization or fine cracking. These mechanisms are in turn approximately controlled by the near-field plasticity parameters: the angle of the slip plane _s, and the normal stress and displacement increment across the slip plane _s and u_s. Note the three-parameter characterization of the near-tip fields, in contrast to the one- or two-parameter characterization in elastic or nonlinear elastic fracture mechanics.A sliding off and shear-cracking model for a growing crack, based on a hole growth equation, gives an approximate CTOA in terms of _s, _s, and material parameters. When hole nucleation strain is negligible, the estimated CTOA exhibits an inverse exponential dependence on _s and a higher order parabolic dependence on _s. For a given material, a series of fully plastic crack growth experiments is suggested to determine the approximate material parameters needed to characterize the dependence of CTOA on _s and _s, or from kinematics, of the shear strain behind the slip plane, _f, on _s.     

How can I help you? Design principles for task-oriented speech dialog systems in customer service

Organizations are increasingly delegating customer inquiries to speech dialog systems (SDSs) to save personnel resources. However, customers often report frustration when interacting with SDSs due to poorly designed solutions. Despite these issues, design knowledge for SDSs in customer service remains elusive. To address this research gap, we employ the design science approach and devise a design theory for SDSs in customer service. The design theory, including 14 requirements and five design principles, draws on the principles of dialog theory and undergoes validation in three iterations using five hypotheses. A summative evaluation comprising a two-phase experiment with 205 participants yields positive results regarding the user experience of the artifact. This study contributes to design knowledge for SDSs in customer service and supports practitioners striving to implement similar systems in their organizations.

     

Two-stage stochastic master production scheduling under demand uncertainty in a rolling planning environment

This paper proposes a scenario-based two-stage stochastic programming model with recourse for master production scheduling under demand uncertainty. We integrate the model into a hierarchical production planning and control system that is common in industrial practice. To reduce the problem of the disaggregation of the master production schedule, we use a relatively low aggregation level (compared to other work on stochastic programming for production planning). Consequently, we must consider many more scenarios to model demand uncertainty. Additionally, we modify standard modelling approaches for stochastic programming because they lead to the occurrence of many infeasible problems due to rolling planning horizons and interdependencies between master production scheduling and successive planning levels. To evaluate the performance of the proposed models, we generate a customer order arrival process, execute production planning in a rolling horizon environment and simulate the realisation of the planning results. In our experiments, the tardiness of customer orders can be nearly eliminated by the use of the proposed stochastic programming model at the cost of increasing inventory levels and using additional capacity.     

Dynamic material properties of wood subjected to low-velocity impact

This article studied the effects of low-velocity impact on the failure stresses and stiffness using a pendulum test. The specimens were of variable depth (20, 30, and 40 mm), a width of 50 mm, length of 650 mm, and span-length of 480 mm. The smallest specimen depth was similar to specimen sizes tested in the literature used to create the duration of load curve, while the largest specimen depth are considered structural size specimens. The impact was predicted using a numerical approach with Euler–Bernoulli beam, as well as Timoshenko beam theory, with a plastic contact law. The models were validated for impact from a low release-angle (where the beam remained elastic), but could use improvement for the force prediction at a high incidence velocity. The measured force signals were used as forcing functions to obtain the dynamic failure stresses for all of the evaluated specimens, and the Timoshenko–Goens–Hearmon Method to derive the dynamic E. The resulting strain rates ranged from 9.11?×?10^?5 s^?1 for the quasi-static specimens up to 25 s^?1 for the greatest incidence velocity. The results from this study suggest different duration of load factors than the Madison Curve, influencing the design of structures subjected to dynamic loading.     

In vitro studies of PDR brachytherapy

BACKGROUND: Calculations on the basis of the LQ-model have been focussed on the possible radiobiological equivalence between common continuous low dose rate irradiation (CLDR) and a superfractionated irradiation (PDR = pulsed dose rate) provided that the same total dose will be prescribed in the same overall time as with the low doserate. A clinically usable fractionation scheme for brachytherapy was recommended by Brenner and Hall and should replace the classical CLDR brachytherapy with line sources with an afterloading technique using a stepping source. The hypothes is that LDR equivalency can be achieved by superfractionation was tested by means of in vitro experiments on V79 cells in monolayer and spheroid cultures as well as on HeLa monolayers. MATERIALS AND METHODS: Simulating the clinical situation in PDR brachytherapy, fractionation experiments were carried out in the dose rate gradient of afterloading sources. Different dose levels were produced with the same number of fractions in the same overall incubation time. The fractionation schedules which were to be compared with a CLDR reference curve were: 40 x 0.47 Gy, 20 x 0.94 Gy, 10 x 1.88 Gy, 5 x 3.76 Gy, 2 x 9.4 Gy given in a period of 20 h and 1 x 18.8 Gy as a "single dose" exposition. As measured by flow cytometry, the influence of the dose rate in the pulse on cell survival and on cell cycle distribution under superfractionation was examined on V79 cells. RESULTS: V79 spheroids as a model for a slowly growing tumor, reacted according to the radiobiological calculations, as a CLDR equivalency was achieved with increasing fractionation. Rapidly growing V79 monolayer cells showed an inverse fractionation effect. A superfractionated irradiation with pulses of 0.94 Gy/h respectively 0.47 Gy/0.5 h was significantly more effective than the CLDR irradiation. This inverse fractionation effect in log-phase V79 cells could be attributed to the accumulation of cycling cells in the radiosensitive G2/M phase (G2 block) during protected exposure which was drastically more pronounced for the pulsed scheme. HeLa cells were rather insensitive to changes of fractionation. Superfractionation as well as hypofractionation yielded CLDR equivalent survival curves. CONCLUSIONS: The fractionation scheme, derived from the PDR theory to achieve CLDR equivalent effects, is valid for many cell lines, however not for all. Proliferation and dose rate dependend cell cycle effects modify predictions derived from the sublethal damage recovery model and can influence acute irradiation effects significantly. Dose rate sensitivity and rapid proliferation favour cell cycle effects and substantiate, applied to the clinical situation, the possibility of a higher effectiveness of the pulsed irradiation on rapidly growing tumors.     

How can the success of a glaucoma operation be predicted?

PURPOSE: The effect of glaucoma surgery can simply be measured in terms of intraocular pressure (IOP) reduction. However, IOP reduction is not the final goal of glaucoma surgery, but rather long-term visual field preservation. Visual field preservation, on the other hand, can only be judged many years after surgery. Therefore, a formula that could be used to define the success of a pressure-lowering operation soon after surgery should take account of IOP reduction, but the correlation between "successful IOP reduction" and "long-term visual field preservation" should be as high as possible. METHODS: In an attempt to find such a formula, we examined the long-term course with reference to both IOP and visual field in 108 patients (mean follow-up 7.9 years). Several criteria were tested for their ability to predict the long-term visual field preservation. RESULT: The best correlation was obtained by a combined criterion specifying both an absolute upper limit and a relative IOP decrease (i.e. IOP postoperatively < 0.8*IOP preoperatively and IOP postoperatively < 21 mmHg). CONCLUSION: We recommend use of this criterion whenever the effect of a pressure-lowering operation has to be estimated shortly after surgery.     

Specification and refinement of networks of asynchronously communicating agents using the assumption/commitment paradigm

This paper presents an assumption/commitment specification technique and a refinement calculus for networks of agents communicating asynchronously via unbounded FIFO channels in the tradition of Kahn.

We define two types of assumption/commitment specifications, namely simple and general specifications.

It is shown that semantically, any deterministic agent can be uniquely characterized by a simple specification, and any nondeterministic agent can be uniquely characterized by a general specification.

We define two sets of refinement rules, one for simple specifications and one for general specifications. The rules are Hoare-logic inspired. In particular the feedback rules employ invariants in the style of a traditional while-rule.

Both sets of rules have been proved to be sound and also (semantic) relative complete.

Conversion rules allow the two logics to be combined. This means that general specifications and the rules for general specifications have to be introduced only at the point in a system development where they are really needed.