Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin

Glycoprotein 330 (gp330) is a member of a family of endocytic receptors related to the low density lipoprotein receptor. gp330 has previously been shown to bind a number of ligands in common with its family member, the low density lipoprotein receptor-related protein (LRP). To identify ligands specific for gp330 and relevant to its localization on epithelia such as in the mammary gland, gp330-Sepharose affinity chromatography was performed. As a result, a 70-kDa protein was selected from human milk and identified by protein sequencing to be apolipoprotein J/clusterin (apoJ). Solid-phase binding assays confirmed that gp330 bound to apoJ with high affinity (Kd = 14.2 nM). Similarly, gp330 bound to apoJ transferred to nitrocellulose after SDS-polyacrylamide gel electrophoresis. LRP, however, showed no binding to apoJ in either type of assay. The binding of gp330 to apoJ could be competitively inhibited with excess apoJ as well as with the gp330 ligands apolipoprotein E, lipoprotein lipase, and the receptor-associated protein, a 39-kDa protein that acts to antagonize binding of all known ligands for gp330 and LRP. Several cultured cell lines that express gp330 and ones that do not express the receptor were examined for their ability to bind and internalize 125I-apoJ. Only cells that expressed gp330 endocytosed and degraded radiolabeled apoJ. Furthermore, F9 cells treated with retinoic acid and dibutyryl cyclic AMP to increase expression levels of gp330 displayed an increased capacity to internalize and degrade apoJ. Cellular internalization and degradation of radiolabeled apoJ could be inhibited with unlabeled apoJ, receptor-associated protein, and gp330 antibodies. The results indicate that gp330 but not LRP can bind to apoJ in vitro and that gp330 expressed by cells can mediate apoJ endocytosis leading to lysosomal degradation.     

Analytical, numerical and experimental investigations of transverse fracture propagation from horizontal wells

This paper presents results of a comprehensive study involving analytical, numerical and experimental investigations into transverse fracture propagation from horizontal wells. The propagation of transverse hydraulic fractures from horizontal wells is simulated and investigated in the laboratory using carefully designed experimental setups. Closed-form analytical theories for Mode I (opening) stress intensity factors for idealized fracture geometries are reviewed, and a boundary element-based model is used herein to investigate non-planar propagation of fractures. Using the mixed mode fracture propagation criterion of the model, a reasonable agreement is found with respect to fracture geometry, net fracture pressures and fracture propagation paths between the modeled fractures and the laboratory tested fractures. These results suggest that the propagation of multiple fractures requires higher net pressures than a single fracture, the underlying reason of which is theoretically justified on the basis of local stress distribution.     

Swift and Selective Reduction of Nitroaromatics to Aromatic Amines with Ni–Boride–Silica Catalysts System at Low Temperature

Various nitroaromatics are successfully reduced to amines with 100% conversion and selectivity in methanol at low temperature (≈5 °C), by using versatile system of 5% Ni–SiO₂ catalyst and NaBH₄ and in situ generation of Ni boride. The catalytic efficiency of Ni loading (5%, 10% and 15%) with silica or titania as support materials is investigated for reduction of nitrobenzene. The Ni–titania/NaBH₄ system recorded lower conversion and selectivity. The IR studies indicate that silica support does not have free –OH group on its surface. Thus the nickel boride is anchored to the silica to facilitate the catalytic process.     

Multilevel optimization applied to hull girder design using three panel forms

A multilevel design scheme for ship's hull girders (longitudinal members between two adjacent transverse frames) is presented in this paper. This design scheme handles, very conveniently, the complexity of using an optimization algorithm for such complex design problems having a large number of design variables, nonlinear constraints dealing with different failure modes and interactions among substructures, and nonlinear design objectives. The conventional multilevel design technique is modified by introducing an approach called constraint coordination to increase the probability of achieving the overall optimum very efficiently.The scheme is demonstrated by application to the structural design of hull girders with simple structural modelling to represent inland waterway ships on which there was a special emphasis in the original research project (Rahman 1991). Three possible panel (consisting of one stiffener and its attached plating) forms; tee stiffened, flat-bar stiffened and corrugated, are optimized to synthesize the hull girder in order to achieve the most efficient structure. The effect of price-structure (labour rate to material price ratio) on the design is also investigated.     

Cyclobutanones as markers for irradiated samples of Brie and Camembert cheese

The feasibility of applying a chemical method based on the formation of 2-alkylcyclobutanone to samples of irradiated soft cheese (Brie and Camembert) was investigated. Significant quantities of 2-dodecylcyclobutanone (DCB) and 2-tetradecylcyclobutanone (TCB) were detected in both types of irradiated cheese and are proposed as qualitative markers. Other members of the cyclobutanone family (decyl- and tetradecenyl-) are also thought to be present but could not be substantiated due to a lack of authentic standards. These compounds were absent from the unirradiated samples. Results also show a significant linear relationship between the irradiation dose (1 to 8 kGy) and the amount of DCB and TCB detected in the cheese.     

Activation of 5-HT2 receptors facilitates depolarization of neocortical neurons by N-methyl-D-aspartate

We prospectively studied 63 children with transient hyperglycemia to determine their risk of acquiring insulin-dependent diabetes mellitus (IDDM) and to evaluate the predictive value of immunologic markers of prediabetes and of the intravenous glucose tolerance test. Children with transient hyperglycemia were identified by a prospective systematic review of the laboratory reports of a large children's hospital and an office-based pediatric practice and by referral from pediatricians. Transient hyperglycemia occurred in 0.46% of children seen in the children's hospital and in 0.013% of children attending a pediatric office practice. Insulin-dependent diabetes mellitus developed within 18 months of identification in 32% of children in whom transient hyperglycemia was discovered in the absence of a serious illness, compared with 2.3% of children identified during a serious illness (relative risk, 13.9; 95% confidence interval, 1.56 to 123.5). Islet cell antibodies and competitive insulin autoantibodies each had a 100% positive predictive value for IDDM; the negative predictive value of islet cell antibodies and competitive insulin autoantibodies was 96% and 98%, respectively. The stimulated insulin release during an intravenous glucose tolerance test, adjusted for age, had the highest overall accuracy of prediction. All children less than 6 years of age with stimulated insulin release levels < 85 pmol/L (12 microU/ml) subsequently had IDDM, as did an 11-year-old child whose stimulated insulin release level was below the 1st percentile of 170 pmol/L (24 microU/ml). To date, no child whose stimulated insulin release level was above the 5th percentile has had IDDM. We conclude that when transient hyperglycemia occurs during a serious intercurrent illness, the risk of progression to IDDM is low. In contrast, one third of children in whom transient hyperglycemia is identified without a serious illness can be expected to have IDDM within 1 year. A combination of islet cell antibodies, competitive insulin autoantibodies, and stimulated insulin release levels during an intravenous glucose tolerance test can accurately distinguish children with prediabetes from those with presumed benign transient increases in plasma glucose concentrations.     

Circulating angiotensin II and renal sodium handling in man: a dose-response study

1. Animal studies have shown that angiotensin II has a biphasic effect on urinary sodium excretion. To examine whether this is also true in man, we studied seven salt-replete male subjects in a single-blind placebo-controlled manner. 2. While undergoing maximum diuresis, subjects were infused with 0, 1, 2, 5 or 10 ng of angiotensin II min-1 kg-1 over 80 min. Subjects were studied while seated, and stood every 20 min for urine collection. 3. Angiotensin II produced a dose-dependent antidiuretic effect. The urine flow rate, in ml/min expressed as the change from baseline with increasing dose of angiotensin, was: +3.4 +/- 1.77, -1.26 +/- 0.49 (P < 0.05), -2.75 +/- 1.23 (P < 0.05), -4.21 +/- 0.82 (P < 0.05) and -6.51 +/- 1.07 (P < 0.01). 4. In contrast, the effect of angiotensin II on sodium excretion showed a flat dose-response curve beyond 5 ng min-1 kg-1. The urinary sodium excretion, in mumol/min expressed as the change from baseline with increasing dose of angiotensin, was: 9.5 +/- 21.2, -18.9 +/- 29.6, -37.0 +/- 11.6 (P < 0.05), -67.7 +/- 19.6 (P < 0.01) and -63.8 +/- 14.3 (P < 0.01). 5. The fractional distal reabsorption of sodium, determined by using the lithium clearance technique, showed a rise with all doses of angiotensin II used and reached statistical significance with the top two doses. 6. Unlike antidiuresis, antinatriuresis after graded doses of angiotensin II in human subjects showed a flat dose-response curve beyond 5 ng min-1 kg-1. Pressor doses of angiotensin II also have a significant effect on the distal tubule in promoting sodium reabsorption.     

Simulation and experimental analyses of electromagnetic transients behaviors of lightning surge on vertical conductors

Simulation of very fast surge phenomena in a three-dimensional (3-D) structure requires a method based on Maxwell's equations, such as the finite-difference time-domain (FDTD) method or the method of moments, because circuit-equation-based methods cannot handle the phenomena. This paper uses a method of thin-wire representation of the vertical conductor system for the FDTD method which is suitable for the 3-D surge simulation. The thin-wire representation is indispensable to simulate electromagnetic surges on wires or steel frames in which the radius is smaller than a discretized space step used in the FDTD simulation. In this paper, a general surge analysis program named the virtual surge test lab based on the Maxwell's equations formulated by the FDTD method, is used to simulate the surge phenomena of a vertical conductor, including the effects of horizontal wave incidence and vertical wave incidence. Experimental results on the reduced scale model have been presented in order to compare among the simulation results by the FDTD method and the results using numerical electromagnetic code based on the MoM.     

The functional reanimation of paralyzed limbs.

The functional reanimation of paralyzed limbs has been a longstanding goal of neural prosthetic research, but clinically successful applications have been elusive. Natural voluntary limb movement requires four major elements: actuators (i.e., motor units), sensors (i.e., somatosensory afferents), commands (i.e., cerebral cortical activity), and control (i.e., integration of the previous three elements at various levels of the neuraxis). Prosthetic equivalents of each of these elements are, as yet, primitive and often cumbersome to deploy, but new technologies promise substantial improvements for all. This article focuses on one such technology, bionic neuon (BION) modular microimplants, and its relationship to alternative and complementary technologies. The challenge remains to select and integrate them into systems that can be tailored efficiently to the widely disparate needs of patients with various patterns of weakness and paralysis.