Role of newly synthesized cholesterol or its metabolites on the regulation of bile acid biosynthesis after short-term biliary diversion in the rat

Cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the bile acid biosynthetic pathway, is thought to be regulated by hydrophobic bile acids through negative feedback control. The role of cholesterol in the regulation of cholesterol 7 alpha-hydroxylase is more controversial, in part because of incomplete understanding of the relationship between the pathways of cholesterol synthesis and degradation. The main objective of this study was to define the interaction between these two pathways in an experimental model in which the supply of newly synthesized cholesterol was interrupted by sustained infusion of mevinolin (lovastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) or accelerated by a continuous infusion of mevalonate, a cholesterol precursor. The study was carried out in rats subjected to short-term bile fistula. In one set of experiments, rats were treated postoperatively with mevinolin (5 mg/kg loading dose followed by 2 mg/kg/hr infusion), mevalonate (180 mumol/hr infusion) or both for up to 96 hr. In a separate set of experiments, rats were infused intraduodenally with taurocholate (36 mumol/100 gm/hr for up to 96 hr). We determined cholesterol 7 alpha-hydroxylase- and HMG-CoA reductase specific activities at those time intervals, whereas bile acid synthesis rates were determined throughout the study. Compared with rats not subjected to surgery, rats with short-term biliary diversion had increases in cholesterol 7 alpha-hydroxylase activity of 259% and 827% at 48 and 96 hr, respectively. The increase in bile acid biosynthesis was less pronounced. Continuous infusion of mevinolin completely prevented increases in cholesterol 7 alpha-hydroxylase specific activity and bile acid biosynthesis at both time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-wavelength infrared photoinduced switching of a resonanttunneling diode using the intersubband transition

Voltage switching induced by long-wavelength infrared light from a CO₂ laser was observed using a double-barrier resonant tunneling diode (RTD) biased in the bistable region and the intersubband transition (IT) between the quantum confined states. Possible optoelectronic and all-optical switching applications involving hysteresis are proposed and discussed     

The late results of the surgical treatment of patients with a pathologically mobile kidney

Long-term (1-10 years) results of wandering kidney surgery were followed-up for 118 patients. The outcomes were found dependent on the duration of the disease, variety and severity of the lesion, age of the patients. The response appeared better in younger patients, in those with shorter duration of the disease and with unessential changes in the kidney. Recommendations are provided on the regimens, jobs, outpatient and inpatient follow-up for the subjects treated surgically for wandering kidney to reinforce the correction results achieved.     

Investigation of the mechanism underlying the inhibitory effect of heterologous ras genes in plant cells

The ras genes from yeast and mammalian cells were fused to plant expression promoters, and introduced into plant cells via Agrobacterium, to study their effect on cell growth and development. All introduced ras genes had a strong inhibitory effect on callus and shoot regeneration from plant tissues. This is consistent with earlier findings that heterologous ras genes were highly lethal to protoplasts following direct DNA uptake. These effects could not be reversed by increasing exogenous or endogenous cytokinin levels. These effects were also independent of the v-Ha-ras mutations in functionally important regions of Ras proteins such as effector-binding and membrane-binding sites. Similarly, co-transformation with the genes encoding the Ras-negative regulators, GTPase-activating protein and neurofibromin did not affect the ras inhibitory effect, indicating that the mechanism of ras inhibition of plant cells is not related to normal ras cellular functions. This conclusion was supported by further studies in which ras gene expression was modified using various promoters and antisense constructs. The introduced ras sequences remained fully inhibitory regardless of which promoters (inducible or tissue-specific) or which orientations (sense or antisense) were tested. This strongly suggests that the ras DNA sequence itself, rather than the Ras protein or ras mRNA, is directly involved in the inhibitory effect. The mechanism underlying this novel phenomenon remains unknown. Introduced ras genes may inhibit plant cell growth by inducing co-suppression of unknown endogenous ras or ras-related genes, thereby leading to the arrest of cell growth.     

Importance of the Arg-Gly-Asp triplet in human thrombin for maintenance of structure and function

Site-directed mutagenesis was employed to assess the importance of the Arg-Gly-Asp triplet that comprises residues 197 to 199 in the B-chain of thrombin. Properties of the R197E and the D199E variants were compared with those of zeta-thrombin and the inactive S205A variant wherein the active site Ser is replaced by Ala. Relative to zeta-thrombin, the R197E thrombin variant under the assay conditions used exhibits 26% activity toward a small chromogenic substrate, 13% activity in the activation of protein C in the presence of thrombomodulin, < 3% activity in processing fibrinogen, and 1% activity in inducing platelet activation. Thus, the substrate specificity of thrombin was altered by the R197-->E replacement. The D199E variant was essentially inactive. It exhibited only 0.02% of the activity of thrombin toward the chromogenic substrate and its reactivity toward the active site-directed alkylating agent D-Phe-Pro-Arg-CH2Cl was 10,000-fold lower than that of thrombin. Like the inactive S205A thrombin variant, the D199E variant antagonized the interactions of thrombin with hirudin and thrombomodulin, but was a less effective antagonist. The dependence of the antagonism of the thrombin-thrombomodulin interaction on the concentration of D199E thrombin variant provided evidence suggesting the presence of two or more domains in thrombin that independently interact with their counterparts in thrombomodulin. Although the S205A thrombin variant antagonized the action of thrombin on platelets no such activity could be demonstrated for the D199E variant in the concentration range studied (< 800 nm). Comparison of the circular dichroism spectra of zeta-thrombin, the D199E, R197E, and S205A variants indicated that subtle differences in conformation exist between the D199E variant and the other thrombins. These differences in conformation might well account for the altered behavior of the D199E variant with respect to its interactions toward thrombomodulin, hirudin, and platelets.     

Information systems in modeling interactive computations on granules

In this paper, we discuss the importance of information systems in modeling interactive computations performed on (complex) granules and we propose a formal approach to interactive computations based on generalized information systems and rough sets which can be combined with other soft computing paradigms such as fuzzy sets or evolutionary computing, but also with machine learning and data mining techniques. Information systems are treated as dynamic granules used for representing the results of the interaction of attributes with the environment. Two kinds of attributes are distinguished, namely, the perception attributes, including sensory attributes, and the action attributes. Sensory attributes are the basic perception attributes, other perception attributes are constructed on the basis of the sensory ones. Actions are activated when their guards, being often complex and vague concepts, are satisfied to a satisfactory degree. The guards can be approximated on the basis of measurements performed by sensory attributes rather than defined exactly. Satisfiability degrees for guards are results of reasoning called the adaptive judgment. The approximations are induced using hierarchical modeling. We show that information systems can be used for modeling more advanced forms of interactions in hierarchical modeling. The role of hierarchical interactions is emphasized in the modeling of interactive computations. Some illustrative examples of interactions used in the ACT-R 6.0 system are reported. ACT-R 6.0 is based on a cognitive architecture and can be treated as an example of a highly interactive complex granule which can be involved in hierarchical interactions. For modeling of interactive computations, we propose much more general information systems than the studied dynamic information systems (see, e.g., Ciucci (2010) [8] and Pa?asiński and Pancerz (2010) [32]). For example, the dynamic information systems are making it possible to consider incremental changes in information systems. However, they do not contain the perception and action attributes necessary for modeling interactive computations, in particular for modeling intrastep interactions.     

Terahertz Semiconductor Quantum Well Devices

For eventually providing terahertz science with compact and convenient devices,terahertz (1～10THz) quantum-well photodetectors and quantum-cascade lasers are investigated. The design and projected detector performance are presented together with experimental results for several test devices,all working at photon energies below and around optical phonons. Background limited infrared performance (BLIP) operations are observed for all samples (three in total) ,designed for different wavelengths. BLIP temperatures of 17,13, and 12K are achieved for peak detection frequencies of 9.7THz(31μm) ,5.4THz(56μm) ,and 3.2THz(93μm) ,respectively. A set of THz quantum-cascade lasers with identical device parameters except for doping concentration is studied. The δ-doping density for each period varies from 3.2 × 1010 to 4. 8 × 1010cm-2. We observe that the lasing threshold current density increases monotonically with doping concentration. Moreover, the measurements for devices with different cavity lengths provide evidence that the free carrier absorption causes the waveguide loss also to increase monotonically. Interestingly the observed maximum lasing temperature is best at a doping density of 3.6 × 1010cm-2.     

Coacervates as a Modern Delivery System of Hand Dishwashing Liquids

Hand dishwashing liquids can be produced in a coacervate form. Such a delivery system can be readily mixed with water and, in the initial dilution stage, may exhibit a high viscosity. This makes it feasible to formulate concentrated products which can be diluted by consumers. The surfactant concentration in the starting formulation is found to affect the possibility of producing hand dishwashing liquids in coacervate form. Hand dishwashing liquids in coacervate form are produced by the separation of the upper phase under the effect of sodium chloride, whose concentration is a key parameter. An increase in the concentration of anionic surfactants in the starting formulation, requires a slight increase in the concentration of sodium chloride to start coacervation and this results in an increase in coacervate volume. The properties of the coacervate, i.e. viscosity, washability, emulsifying power and foamability, are reported and found to be similar to those of typical commercial products.