The discovery and structure-activity relationships of nonpeptide, low molecular weight antagonists selective for the endothelin ET(B) receptor

The systematic modification of the ETA selective N-(5-isoxazolyl)benzene-sulfonamide endothelin antagonists to give ETB selective antagonists is reported. The reversal in selectivity was brought about by substitution of the 4-position with aryl and substituted aryl groups. Of all the aromatic substituents studied, the para-tolyl group gave rise to the most active and selective ETB antagonist. Larger substituents caused a decrease in both ETB activity and selectivity. A similar trend was observed by substitution at the 5-position of the N-(5-isoxazolyl)-2-thiophenesulfonamide ETA receptor antagonists. The para-tolyl group was again found to be optimal for the ETB activity and selectivity. The structural features that were found to be favorable for binding to the ETB receptor, that is, the presence of a linear, conjugated pi-system of definite shape and size, have been successfully incorporated into the design of ETB selective polycyclic aromatic sulfonamides antagonists.     

A new equation for estimating [η] from single-viscosity measurement in dilute solution

The use of a linear two-parameter approximation for determining limiting viscosity number, [η], of a polymer in the state of infinite dilution requires considerable amount of time, effort, and materials. Several workers who attempted to estimate [η] directly from single-viscosity measurement also proposed equations for this purpose. Such equations are tested and found to have good applicability to practical data within specified limits of concentration or specific viscosity. A new equation has been derived and tested for polymers of high and low molecular weights in various solvents and at different temperatures. The introduction of a constant in this equation makes it applicable over a wider range of specific viscosity. It is found to serve better for determination of [η] from a single-viscosity measurement.     

Binding of tsHMG, a mouse testis-specific HMG-domain protein, to cisplatin-DNA adducts

The anticancer drug cisplatin is particularly effective against testicular tumors. Although the clinical consequences of cisplatin chemotherapy are well-known, the precise mechanism of action remains elusive. Specific recognition of cisplatin-damaged DNA by a class of proteins containing the high-mobility group (HMG) domain DNA-binding motif could play a role in mediating the cytotoxicity of the drug. This study presents a quantitative investigation of binding of the murine testis-specific high-mobility group protein tsHMG to DNA modified by cisplatin. The binding affinity and specificity of this protein to a site-specific 1,2-d(GpG) cisplatin-DNA intrastrand cross-link in a 20 bp probe were determined. A value for the apparent dissociation constant, Kd(app), of 24 +/- 5 nM was obtained by gel mobility shift assays. Binding competition assays with the corresponding unmodified 20 bp probe gave a ratio (rho) of nonspecific to specific Kd(app) values of 230. A polypeptide containing tsHMG domain A (residues 1-82) was expressed and purified to homogeneity. This domain alone was sufficient for specific recognition of cisplatin-modified DNA with a Kd(app) of 300 +/- 50 nM and a rho of 20, a comparatively high discrimination factor. DNase I interference analysis of the adduct-containing strand revealed that tsHMG binding extends over 14 nucleotides, centered around the platinated bases. The domain A polypeptide protection pattern covers a slightly smaller area of 13 nucleotides. The binding affinity and specificity of tsHMG for cisplatin-modified DNA are exceptional compared to those of other HMG-domain proteins studied previously. The possible relevance of these findings to the mechanism of action of cisplatin is discussed.     

Microwave remote sensing of soil moisture: elimination of textureeffect

In view of the influence of soil texture on microwave radiation, an attempt is made to eliminate the textural effects on the microwave reflectivity/emission. To determine the appropriate soil moisture parameter that minimizes the textural influences on microwave radiation from soils, soil moisture is expressed in terms of gravimetric and volumetric units and percentage of field capacity (M_fc ) and is plotted individually against the microwave reflectivity of soils. Only when soil moisture is in volumetric units are the textural influences significantly reduced. Therefore, a parameter, termed the critical water content (W_c), that takes into account the bound-water content of soils is used. An empirical relation between the interpolated values of W_c and the wilting point of soils has been developed. The soil water content above the W_c of each soil is considered as effective water M_eff     

Identification of factors that lead to perceived learning improvements for female students

Past research has shown that females have more negative attitudes toward engineering and technology than do males. These negative attitudes may explain the decreasing number of females choosing technical careers. Past studies have shown that a change in learning environments and the methods by which learning takes place might foster a change in this situation. A multimedia case study incorporating a real-world engineering and technical problem faced by a power plant was developed in order to provide a new learning environment for engineering and business students. This research investigates whether the use of this material by female and male students led to differences in perceived higher level cognitive skills and, if so, seeks to identify the factors that cause the difference. The results suggest that when designing new learning environments, it is important for the female students to be challenged and have opportunities both to learn by themselves and to learn from others. These results have implications for teaching programs, such as the provision of opportunities for group learning, especially for female students.     

Concurrent design of manufacturing cell and control functions: A neural network approach

This paper presents a neural network based decision support system (DSS) for use in concurrently determining cell configuration, operation plans, and complexity requirements of cell control functions. Advanced simulators and neural network technology are used in developing the DSS. Simulation experiments were conducted with many possible combinations of design changes to generate training pairs for a neural network. Complexity of cell control functions required by each design option was assessed, based on operational requirements, and was used to train another neural net. Once both neural networks are properly trained, one network can be used to predict the cell design configuration given a set of desirable cell performance measures, while the other network can be used to identify complexity requirements of the cell control functions by using the output provided by the first network as input to the second neural net. An operation-driven cell design methodology was applied to sequentially predict requirements of both cell configuration and cell control functions from the trained neural networks. This innovative new design methodology was illustrated via a successful implementation exercise in acquiring a real automated manufacturing cell at industrial settings. The exercise proves that such a DSS serves well as an effective tool for cell designers and the management in determining appropriate cell configuration and cell control functions at the design stage.     

Effect of prior damage on the performance of cement based coatings on rebar: macrocell corrosion studies

The performance of any rebar coating system depends upon its resistance to corrosion in the presence of chloride contaminated concrete. It also mainly depends upon its tolerance towards damage that may occur during handling, transporting and concreting. The severe corrosion of epoxy coated reinforcing steel in long key bridge and other structures in Florida gave raise to the concern over the influence of damages in the coating system [R.J. Kessler, P.G. Powers, Interim report on corrosion evaluation of substructure in Long key bridge, Corrosion Report No. 87-9A, Florida Department of Transportation, Florida, 1987]. The performance of rebar coating such as galvanizing and epoxy based coating with prior surface damage has been evaluated and reported. [J. Hartley, Concrete Jan/Feb (1994) 12–15; A. Sagues, Performance of galvanized rebars in marine substructure service, Project ZE-418, Part I, October, 1994]. To date, the performance of cement based coatings with prior damages has not been widely studied and reported. In the present investigation the effect of prior damage produced during concrete pouring has been studied on inhibited cement slurry coating. To simulate the marine substructure environment, macrocell corrosion has been created via a chloride ion concentration gradient. Test conditions and method of macrocell current measurement as described in ASTM G 109-92 have been followed. The above investigation revealed that the cement based coating appears to have better tolerance towards defects in chloride contaminated concrete as compared to epoxy based coating system. The performance of the coating is independent of the height of concrete pouring.     

A high precision triangular plate bending element for the analysis of thick plates

A high precision triangular plate bending element for the analysis of thick plates is developed in thin paper. The element has three nodes and 12 degrees of freedom per node. Explicit expressions for stiffness coefficients are derived. The superiority of the element is demonstrated by the accuracy of the results obtained by applying it to some typical thick plate problems.     

Legal counselling system

Legal reasoning involves case analysis in statutory as well as real world perspectives. The impact of real world perspective on case analysis poses a serious challenge to knowledge engineers for building legal expert systems. A legal expert system intends to provide intelligent support to legal professionals. The proposed legal predictive system is an attempt to predict the most probable outcome of a case according to statutory as well as real world knowledge of the legal domain. The system accepts the current fact situation of a case and analyses it interactively with legal personnel. This work introduces a frame-like knowledge structure,lattice, with two-dimensional attributes. This paper contains a detailed discussion on artificial intelligence-based case analysis of theft cases in a real world perspective.