Synthesis of Long-Chain β-Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria

In the quest for new antibacterial agents, a series of novel long- and medium-chain mono- and disubstituted β-lactones was developed. Their activity against three pathogenic mycobacteria—M. abscessus, M. marinum, and M. tuberculosis—was assessed by the resazurin microtiter assay (REMA). Among the 16 β-lactones synthesized, only 3-hexadecyloxetan-2-one (VM005) exhibited promising activity against M. abscessus, whereas most of the β-lactones showed interesting activities against M. marinum, similar to that of the classical antibiotic, isoniazid. Regarding M. tuberculosis, six compounds were found to be active against this mycobacterium, with β-lactone VM008 [trans-(Z)-3-(hexadec-7-en-1-yl)-4-propyloxetan-2-one] being the best growth inhibitor. The promising antibacterial activities of the best compounds in this series suggest that these molecules may serve as leads for the development of much more efficient antimycobacterial agents.     

Analogue switch for very low-voltage applications

A new analogue switch suitable for operation at very low-voltage supply in a standard CMOS technology is presented. The proposed switch is based on 'quasi-floating-gate' transistors and has a simple and compact structure. For illustrative purposes, two sample-and-hold circuits operating from a single supply voltage close to the threshold voltage of a transistor, and using the proposed technique, are presented. Experimental results obtained from prototypes in a 1.5 /spl mu/m CMOS technology are provided.     

Room-temperature laser emission of GaInNAs-GaAs quantum wells grown on GaAs (111)B

In this work, we present room-temperature laser emission at 1.206 /spl mu/m from GaInNAs-GaAs quantum-well (QW) laser diodes (LDs) grown on misoriented GaAs (111)B substrates for the first time. Details of the structure and the molecular beam epitaxial growth of the lasers are discussed. We found that the postgrowth rapid thermal annealing increased the optimum emission, while the in situ self annealing effect in these QWs is almost negligible. The optimum annealing cycle (30 s at 850/spl deg/C) is comparable to that found for the cladding-free GaInNAs single QW samples grown on GaAs (111)B. Finally, the optical and electrical characterization of these LD devices is presented. The LDs show a room-temperature threshold current density of 2.15 kA/cm/sup 2/, with a differential quantum efficiency of 37%, under pulsed conditions.     

Stable neurovisual servoing for robot manipulators

In this paper, we propose a stable neurovisual servoing algorithm for set-point control of planar robot manipulators in a fixed-camera configuration an show that all the closed-loop signals are uniformly ultimately bounded (UUB) and converge exponentially to a small compact set. We assume that the gravity term and Jacobian matrix are unknown. Radial basis function neural networks (RBFNNs) with online real-time learning are proposed for compensating both gravitational forces and errors in the robot Jacobian matrix. The learning rule for updating the neural network weights, similar to a back propagation algorithm, is obtained from a Lyapunov stability analysis. Experimental results on a two degrees of freedom manipulator are presented to evaluate the proposed controller.     

Apoptosis in the failing human heart

BACKGROUND: Loss of myocytes is an important mechanism in the development of cardiac failure of either ischemic or nonischemic origin. However, whether programmed cell death (apoptosis) is implicated in the terminal stages of heart failure is not known. We therefore studied the magnitude of myocyte apoptosis in patients with intractable congestive heart failure. METHODS: Myocardial samples were obtained from the hearts of 36 patients who underwent cardiac transplantation and from the hearts of 3 patients who died soon after myocardial infarction. Samples from 11 normal hearts were used as controls. Apoptosis was evaluated histochemically, biochemically, and by a combination of histochemical analysis and confocal microscopy. The expression of two proto-oncogenes that influence apoptosis, BCL2 and BAX, was also determined. RESULTS: Heart failure was characterized morphologically by a 232-fold increase in myocyte apoptosis and biochemically by DNA laddering (an indicator of apoptosis). The histochemical demonstration of DNA-strand breaks in myocyte nuclei was coupled with the documentation of chromatin condensation and fragmentation by confocal microscopy. All these findings reflect apoptosis of myocytes. The percentage of myocytes labeled with BCL2 (which protects cells against apoptosis) was 1.8 times as high in the hearts of patients with cardiac failure as in the normal hearts, whereas labeling with BAX (which promotes apoptosis) remained constant. The near doubling of the expression of BCL2 in the cardiac tissue of patients with heart failure was confirmed by Western blotting. CONCLUSIONS: Programmed death of myocytes occurs in the decompensated human heart in spite of the enhanced expression of BCL2; this phenomenon may contribute to the progression of cardiac dysfunction.     

Analytical and numerical analysis of phase and amplitude errors in the performance of arrayed waveguide gratings

The closed expression of the mean power transfer function for an arrayed waveguide grating (AWG), taking into account fabrication errors, is presented. Comparison with numerical simulations using a previous Fourier optics modeling show good agreement. The procedure to predict the AWG floor level using the numerical modeling is presented and checked against the analytical derived expressions.     

Behavioral model synthesis with Cones

The Cones synthesis system for automatic generation of VLSI implementations is discussed. Named for the cones in sequential logic, Cones takes behavioral models written in C and produces gate-level implementations in technologies such as standard cells and programmable logic arrays or programmable logic devices. The overall design is produced faster, more efficiently, and with fewer errors. Designers are free to concentrate on functions, instead of on the details of the implementation technology     

A multiple-switch high-voltage DC-DC converter

Series connection of power devices has evolved into a mature technique and is widely applied in HV DC power systems. Static and dynamic voltage balance is ensured by shunting individual devices with dissipative snubbers. The snubber losses become pronounced for increased operating frequencies and adversely affect power density. Capacitive snubbers do not exhibit these disadvantages, but they require a zero-voltage switching mode. Super-resonant power converters facilitate the principle of zero-voltage switching. A high-voltage DC-DC power converter with multiple series-connected devices is proposed. It allows the application of nondissipating snubbers to assist the voltage sharing between the multiple series-connected devices and lowers turnoff losses. Simulation results obtained with a circuit simulator are validated in an experimental power converter operating with two series-connected devices. The behavior of the series connection is examined for MOSFETs and IGBTs by both experimental work with a 2 kW prototype and computer simulation. Applications can be found in traction and heavy industry, where the soft-switching power converter is directly powered from a high-voltage source     

The Effects of Insulin-Like Growth Factor I and BTP-2 on Acute Lung Injury

Acute lung injury (ALI) afflicts approximately 200,000 patients annually and has a 40% mortality rate. The COVID-19 pandemic has massively increased the rate of ALI incidence. The pathogenesis of ALI involves tissue damage from invading microbes and, in severe cases, the overexpression of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). This study aimed to develop a therapy to normalize the excess production of inflammatory cytokines and promote tissue repair in the lipopolysaccharide (LPS)-induced ALI. Based on our previous studies, we tested the insulin-like growth factor I (IGF-I) and BTP-2 therapies. IGF-I was selected, because we and others have shown that elevated inflammatory cytokines suppress the expression of growth hormone receptors in the liver, leading to a decrease in the circulating IGF-I. IGF-I is a growth factor that increases vascular protection, enhances tissue repair, and decreases pro-inflammatory cytokines. It is also required to produce anti-inflammatory 1,25-dihydroxyvitamin D. BTP-2, an inhibitor of cytosolic calcium, was used to suppress the LPS-induced increase in cytosolic calcium, which otherwise leads to an increase in proinflammatory cytokines. We showed that LPS increased the expression of the primary inflammatory mediators such as toll like receptor-4 (TLR-4), IL-1β, interleukin-17 (IL-17), TNF-α, and interferon-γ (IFN-γ), which were normalized by the IGF-I + BTP-2 dual therapy in the lungs, along with improved vascular gene expression markers. The histologic lung injury score was markedly elevated by LPS and reduced to normal by the combination therapy. In conclusion, the LPS-induced increases in inflammatory cytokines, vascular injuries, and lung injuries were all improved by IGF-I + BTP-2 combination therapy.