Azaaurones as Potent Antimycobacterial Agents Active against MDR- and XDR-TB

Herein we report the screening of a small library of aurones and their isosteric counterparts, azaaurones and N-acetylazaaurones, against Mycobacterium tuberculosis. Aurones were found to be inactive at 20 μm , whereas azaaurones and N-acetylazaaurones emerged as the most potent compounds, with nine derivatives displaying MIC₉₉ values ranging from 0.4 to 2.0 μm . In addition, several N-acetylazaaurones were found to be active against multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical M. tuberculosis isolates. The antimycobacterial mechanism of action of these compounds remains to be determined; however, a preliminary mechanistic study confirmed that they do not inhibit the mycobacterial cytochrome bc1 complex. Additionally, microsomal metabolic stability and metabolite identification studies revealed that N-acetylazaaurones are deacetylated to their azaaurone counterparts. Overall, these results demonstrate that azaaurones and their N-acetyl counterparts represent a new entry in the toolbox of chemotypes capable of inhibiting M. tuberculosis growth.     

Biocompatibility considerations at the electrode-neural interface

Abstract

Parameters for the design of neural prostheses are discussed.     

Synaptic transmission and hippocampal long-term potentiation in olfactory cyclic nucleotide-gated channel type 1 null mouse

Field potential recording was used to investigate properties of synaptic transmission and long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in both hippocampal slices of mutant mice in which the alpha-subunit of the olfactory cyclic nucleotide-gated channel (alpha3/OCNC)1 was rendered null and also in slices prepared from their wild-type (Wt) littermates. Several measures of basal synaptic transmission were unaltered in the OCNC1 knockout (KO), including maximum field excitatory postsynaptic potential (fEPSP) slope, maximum fEPSP and fiber volley amplitude, and the function relating fiber volley amplitude to fEPSP slope and paired-pulse facilitation. When a high-frequency stimulation protocol was used to induce LTP, similar responses were seen in both groups [KO: 1 min, 299 +/- 50% (mean +/- SE), 60 min, 123 +/- 10%; Wt: 1 min, 287 +/- 63%; 60 min, 132 +/- 19%). However, on theta-burst stimulation, the initial amplitude of LTP was smaller (1 min after induction, 147 +/- 16% of baseline) and the response decayed faster in the OCNC1 KO (60 min, 127 +/- 18%) than in Wt (1 min, 200 +/- 14%; 60 min, 169 +/- 19%). Analysis of waveforms evoked by LTP-inducing tetanic stimuli revealed a similar difference between groups. The development of potentiation throughout the tetanic stimulus was similar in OCNC1 KO and Wt mice when high-frequency stimulation was used, but OCNC1 KO mice showed a significant decrease when compared with Wt mice receiving theta-burst stimulation. These results suggest that activation of cyclic nucleotide-gated channels may contribute to the induction of LTP by weaker, more physiological stimuli, possibly via Ca2+ influx.     

Hydrodynamic analysis of calenderable PVC and ABS compounds

Calendering of rigid and semirigid PVC (and ABS) compounds require an understanding of compound rheology and critical processing parameters. Compound rheology is modified with processing aids and lubricants. The choice of processing aid can be critical to achieving the desired rheology needed for calendering. This paper will focus on defining calendering rheology parameters as a function of a super high molecular weight MMA/SAN copolymer processing aid. These rheology parameters will be defined in terms of mill roll gap pressure, adhesive force (compound roll release) melt temperature, and shear rate. The ability to measure these parameters via a computerized two roll mill and relate this data to the actual calendering line will also be discussed.     

How to make great sludge cake: When utilized properly, pressure filters bolster operating efficiencies in wastewater treatment, saving time and money

Pressure filters can produce high-quality sludge cake from a wastewater system's treatment process sludge stream in one to three hours. In order to do this, they need to be operated in a batch-process technique, with a feed that has been properly concentrated, conditioned, and fed at system-designed pressure rates.

Run on a proactive basis by experienced operators; you will minimize the need for adding units. If you already have multiple units and you adjust your techniques accordingly, you will have presses standing empty, unneeded. And you can forget about pricing a new one—it just won't be required.

Get your cycle times down, way down. Make thebest of your current capital equipment and save time and money.     

Carbon monoxide: an endogenous modulator of the nitric oxide-cyclic GMP signaling system

Carbon monoxide (CO) is an activator of soluble guanylyl cyclase and is implicated as a neuronal messenger. CO production, nitric oxide synthase (NOS) activity, and guanosine 3',5'-monophosphate (cGMP) levels were quantitated in cerebellar granule cell cultures. Metabolic labeling experiments enabled the direct measurement of neuronal CO production in vitro. CO production is significant, and peaked during early stages of culture. NOS activity and cGMP levels synchronously increased as cells matured. Whereas inhibition of NOS depleted cGMP in mature cultures, inhibitors of CO production potentiated the nitric oxide (NO)-mediated cGMP increase. Exogenous CO at similar concentrations to endogenous levels blocked the NO-mediated cGMP increase. These results directly demonstrate that endogenous neuronal CO production is high and indicate that while NO is the major regulator of cGMP in these neurons, CO may modulate the NO-cGMP signaling system.     

Clinical and ethical issues in the treatment of a Jehovah's Witness with acute myeloblastic leukemia

We report the first documented case of the use of peripheral blood stem cell autografting in the treatment of a Jehovah's Witness with acute myeloblastic leukemia. This case illustrates the complex ethical and clinical issues that arise in the treatment of such patients.     

Nearly resonant third-order optical non-linearity in c60 cast films

We have carried out measurements of the third-order optical non-linearityX⁽³⁾ of C₆₀ cast films using the z-scan technique. The measurements have shown that two-photon absorption is the dominant non-linear process around the 3.76 eV absorption region. The real and imaginary parts of X⁽³⁾ of C₆₀ films have been measured at 665 nm are found to be 2.8 × 10^?8 and ?3.2 × 10^?8 esu respectively.     

An examination of the stability of regional lumber demand in the contiguous United States, 1950–1985

Public policy limits the quantity of timber which is cut from federal forest land in order to avoid a timber shortage. This policy has led the U.S. Department of Agriculture to employ forecasts of future demand for forest products, including lumber. Lumber demand has been estimated regionally, but demand parameters have been assumed stable so that fixed coefficient methods are employed in official forecasts. In this paper, we test the hypothesis that regional lumber demand parameters are stochastic. We find the demand for lumber in all regions except the Southeast to be fairly stable.The authors thank Darius Adams, John Angle, Brian Berry, Theodore Bos, Richard Haynes, Jan Palmer, and Vishwa Shukla for helpful comments and suggestions. The authors alone are responsible for errors.