Androgen regulation of hypothalamic neurons containing gonadotropin-releasing hormone in a cichlid fish: integration with social cues

Reproduction in vertebrates is regulated by internal signals such as hormone levels and by external signals such as social interactions. In an African cichlid fish, Haplochromis burtoni, the effect of social interactions is evident in the hypothalamo-pituitary-gonadal (HPG) axis of males. Territorial males, characterized by aggressive and reproductive activity, have significantly larger hypothalamic gonadotropin-releasing hormone (GnRH)-containing neurons and larger testes than nonterritorial males. Furthermore, a switch in the social status of an adult male causes a corresponding change in GnRH neuron size and testis size. Here we show that the GnRH-containing neurons in the hypothalamus of adult territorial males are also influenced by gonadal hormones. Castration of territorial males caused GnRH neurons to increase in size. This neuronal hypertrophy in castrated animals was prevented either by testosterone (T) or 11-ketotestosterone (KT) treatment. Estradiol (E2) treatment did not reduce GnRH cell size in castrated animals. These results suggest that androgens reduce the size of GnRH cells through negative feedback. Since E2 had no effect, androgen influence on GnRH cell size appears to be independent of aromatization. These data are consistent with the hypothesis that the setpoint for hypothalamic GnRH cell size is determined by social cues and that this setpoint is maintained by negative feedback from gonadal androgens.     

A knowledge-based approach to the evaluation of fault trees

A list of critical components is useful for determining the potential problems of a complex system. However, to find this list through evaluating the fault trees is expensive and time consuming. This paper intends to propose an integrated software program which consists of a fault tree constructor, a knowledge base, and an efficient algorithm for evaluating minimal cut sets of a large fault tree. The proposed algorithm uses the approaches of top-down heuristic searching and the probability-based truncation. That makes the evaluation of fault trees obviously efficient and provides critical components for solving the potential problems in complex systems. Finally, some practical fault trees are included to illustrate the results.     

Processing of chimeric antisense oligonucleotides by human vascular smooth muscle cells and human atherosclerotic plaque. Implications for antisense therapy of restenosis after angioplasty

BACKGROUND: Antisense oligonucleotides have been used in animals to inhibit the accumulation of vascular smooth muscle cells (VSMCs) after arterial injury. This has raised prospects for an oligonucleotide-mediated approach to prevent restenosis in patients undergoing angioplasty. However, little is known about the processing of oligonucleotides by human VSMCs or their bioavailability in human atherosclerotic tissue. METHODS AND RESULTS: Oligonucleotides were synthesized with a mixture of unmodified and sulfur-modified linkages (S-chimeric oligonucleotides). These were more stable than unmodified oligonucleotides and could be recovered from within human VSMCs after 36 hours. Oligonucleotide antisense to human proliferating cell nuclear antigen mRNA specifically reduced DNA synthesis (P < .01) and proliferating cell nuclear antigen protein content (P < .05) in human VSMCs. Confocal microscopy of both live and fixed cells showed modest oligonucleotide uptake that was primarily nuclear. Surprisingly, cationic liposomes did not enhance nuclear uptake but led to extensive, punctated cytoplasmic loading without an enhanced antisense effect. Oligonucleotides incubated with human coronary atherosclerosis fragments associated with cells within 1 hour, despite the presence of abundant extracellular matrix. CONCLUSIONS: S-chimeric oligonucleotides are stable and can specifically inhibit gene expression in human VSMCs. Nuclear transport is a feature of oligonucleotide processing by human VSMCs, indicating a potential influence at the nuclear level rather than with cytoplasmic mRNA. Cationic liposomes increased oligonucleotide uptake but not intracellular bioavailability, and S-chimeric oligonucleotides can be incorporated into cells within human atherosclerotic plaque, despite the presence of a dense extracellular matrix.     

An in vitro diffusion model for the study of calcification of bovine pericardium tissue

Bovine pericardium (BP) is extensively used for the production of heart valve bioprostheses. BP has excellent mechanical properties but a limited lifespan because of intrinsic subsurface calcification in vivo. In this study, the in vitro mineralization of BP was investigated by a novel diffusion cell model. In two sets of experiments, glutaraldehyde-treated BP membranes were placed between two compartments, both of which contained calcium phosphate solutions made by equilibration of octacalcium phosphate (Exp I) or dicalcium phosphate dihydrate (Exp II) in phosphoric acid. The movement of calcium (Ca), phosphate (P), and protons through the BP membrane was followed throughout the diffusion process. Histology, scanning electron microscopy, wet chemical analysis, and energy dispersive X-ray analyses provided good evidence of subsurface mineralization of BP that resembled in vivo mineral deposition. Energy dispersive x-ray microanalyses found a Ca/P heterogeneity of the early subsurface mineral that formed in the membrane. The use of a diffusion cell to model BP calcification under well-characterized conditions has led to in vitro mineralization that more closely matches that observed in vivo. The results suggest that this in vitro diffusion model can be used to study the mechanism of pathological mineralization. This model has the potential to provide rapid, inexpensive, basic information about the mineralization process.     

Ondansetron for prevention of postoperative nausea and vomiting following minor oral surgery: a double-blind randomized study

The efficacy and safety of ondansetron in preventing postoperative nausea and vomiting following minor oral surgery was evaluated in a prospective randomized double-blind study. Of a total of seventy-seven patients, randomly 38 had 4 mg of ondansetron and 39 had normal saline as placebo intravenously immediately prior to induction of anaesthesia. A standard general anaesthetic with thiopentone, suxamethonium, fentanyl, nitrous oxide and isoflurane was employed. Postoperatively nausea was assessed verbally and on a visual analog scale at 1, 4 and 24 hours from the time of awakening. Episodes of vomiting were recorded. Eight patients (21.1%) in the ondansetron group compared to 19 (48.7%) in the placebo group had nausea (P < 0.05) and 1 (2.6%) in the ondansetron group compared with 9 (23.1%) in the placebo group vomited (P < 0.05). Patients who vomited twice or more and the number who required a rescue antiemetic were significantly fewer in the ondansetron group (P < 0.05). Cardiovascular parameters were stable and showed no significant difference in the two groups. There were no significant adverse effects that could be directly attributable to ondansetron.     

Automatic inspection planning within a feature-based CAD system

This paper describe a CIM system which incorporates automatic generation of inspection on plans for coordinate measuring machines (CMMs). Design is done in terms of form features. Associated with each feature are inspection plan fragments (IPFs) which are instances of inspection procedures. There are three basic types of plan fragments for CMMs: (1) fragments for checking the internal dimensions of a feature, (2) fragments for checking the relationships between features, and (3) modified fragments for use when the feature to be inspected intersects another feature. Using this approach, a list of suitable inspection points and approach vectors is generated. A path planner then combines the elements of the list to produce a valid inspection path for the CMM. The system is consistent with the accepted ANSI Y14.5M standard for dimensioning and tolerancing as well as with observed industrial practice.     

Projection of circuit performance distributions by multivariatestatistics

Production test data from process monitoring test structures were utilized in a circuit simulator that accounts for the correlations between circuit elements. This `correlated' simulation is based on a principal component analysis technique that requires the means, the standard deviations, and the correlation coefficients of all circuit elements. A voltage reference subcircuit consisting of five n-p-n transistors and five based-diffused resistors was chosen for this simulation study. The statistical parameters of these circuit elements were approximated by those from the process monitor test structures and extracted from the test patterns of 1000 production wafers. The distributions of the reference voltage from this simulation were compared to a Monte Carlo simulation, and to the production data     

位置参数的非线性函数的估计(英文)

本文研究位置参数的非线性函数的估计问题。应用均方误差直到三阶的渐近展开比较了通常使用的δ法、Jackknife法和Boatstrap法,并证明了,如果只考虑展开的前二阶,则这三种估计是相同的。这些估计的性质依赖于总体分布及非线性函数的具体形式。基于δ法,本文提出了一种新的估计,与已有估计相比,它具有较小的均方误差。     

The effect of substrate doping on the performance of anode-shortedn-channel lateral insulated-gate bipolar transistors

The performance of n-channel lateral-insulated-gate bipolar transistors (n-LIGBTs) with anode shorts on p^- epi/p⁺ substrates is compared to that of anode-shorted n-LIGBTs on p^- substrates, as well as to that of conventional n-LIGBTs on either substrate. It is shown that both forward-voltage drop and turn-off time are better for anode-shorted devices fabricated on p^- epi/p⁺ substrate than for those on p^- substrates, due to a larger percentage component of vertical bipolar current and a lower collector resistance. Forward-voltage drops of 3.05 and 3.3 V at 133 A/cm² and turn-off times of 400 and 750 ns have been measured for devices on p^- epi/p⁺ and p ^- substrates respectively. All the LIGBTs showed current limiting at two to four times the ON-state conduction current during dynamic switching