A methodology for optimally designing console panels for use by a single operator

A seven-step methodology is presented to determine a dimensionally correct optimal layout of a console panel for a single operator. This methodology integrates the steps in the layout design process and uses a mathematical optimization model from facility design to obtain the optimal panel layout. A major difference in this methodology from previous work is that the mathematical optimization model incorporates factors that are only partially included in previous mathematical models. In addition, it includes the areas of the panel components as a new factor. This methodology is illustrated by the design of a nuclear power plant console panel.     

Heating of cryogenic targets in a light ion fusion cavity

Survivability of cryogenic targets in single-shot and reactor cavity environments is an essential prerequisite for high gain (>25) target experimentation, target development, and power production. Heat sources in a gas-filled light ion beam cavity include radiative, convective, and viscous heating by the cavity fill gas, heating due to laser radiation used to initiate low-density plasma channels for beam propagation, and heating due to ohmic dissipation of channel currents near the target. Prior to injection of the target into the cavity, tritium decay and target acceleration are the sources of heat. In this paper the parametric dependence, time scale, and magnitude of each of these thermal sources are discussed. Potential thermal protection techniques which may be applicable to long (>0.1 s), intermediate ( ms), and short-duration ( μs) heat loads are described, and remaining concerns are noted.     

Nephrotoxicity studies of the immunosuppressants tacrolimus (FK506) and ascomycin in rat models

The nephrotoxic potential of ascomycin, the C21-ethyl analogue of FK506, was defined and ways explored to enhance its detection. After 14-day dosing in the Fischer-344 rat, FK506 and ascomycin reduced creatinine clearance by >50% at doses of 1 and 3 mg/kg, i.p., respectively. Ascomycin also had a 3-fold lower immunosuppressive potency in a popliteal lymph node hyperplasia assay, resulting in an equivalent therapeutic index consistent with a common mechanistic dependence on calcineurin inhibition. Renal impairment with different routes of administration was correlated with pharmacokinetics. Sensitivity of detection was not adequate with shorter dosing durations in rats with unilateral nephrectomy or in mice using a cytochrome P-450 inhibitor, SKF-525A. In 14-day studies, nephrotoxicity was not induced by continuous i.p. infusion of ascomycin at 10 mg/kg/day or daily oral administration (up to 50 mg/kg/day) in rats on a normal diet, nor by continuous i.v. infusion (up to 6 mg/kg/day) in rats on a low salt diet to enhance susceptibility. The lack of toxicity at high oral doses of FK506 or ascomycin, and the finding of non-linear oral pharmacokinetics of ascomycin show that this drug class has an oral absorption ceiling. The negative results with continuous infusion suggest that ascomycin nephrotoxicity is governed by peak drug levels. In addition to defining ways to meaningfully compare the nephrotoxic potential of FK506 derivatives, these results have implications for overall safety assessment and improved clinical use.     

Diagnosis of pregnancy with a radioreceptor assay for hCG

To date a number of cases of nephrologic syndrome, linked with a recently passed pregnancy or with the use of oral contraceptives, have been described in the literature. Microscopic analyses of the pathological basis of this syndrome are examined, centering on the infarctic nature of the nerve bundles. There is some disagreement on the type of differential treatment indicated. Treatment, which is generally heparin, must depend on the state of advancement of the syndrome. The syndrome is not well understood yet, but should not be considered completely alien.     

The DNA recognition subunit of the type IB restriction-modification enzyme EcoAI tolerates circular permutions of its polypeptide chain

The DNA specificity subunit (HsdS) of type I restriction-modification enzymes is composed of two independent target recognition domains and several regions whose amino acid sequence is conserved within an enzyme family. The conserved regions participate in intersubunit interactions with two modification subunits (HsdM) and two restriction subunits (HsdR) to form the complete endonuclease. It has been proposed that the domains of the HsdS subunit have a circular organisation providing the required symmetry for their interaction with the other subunits and with the bipartite DNA target. To test this model, we circularly permuted the HsdS subunit of the type IB R-M enzyme EcoAI at the DNA level by direct linkage of codons for original termini and introduction of new termini elsewhere along the N-terminal and central conserved regions. By analysing the activity of mutant enzymes, two circularly permuted variants of HsdS that had termini located at equivalent positions in the N-terminal and central repeats, respectively, were found to fold into a functional DNA recognition subunit with wild-type specificity, suggesting a close proximity of the N and C termini in the native protein. The wild-type HsdS subunit was purified to homogeneity and shown to form a stable trimeric complex with HsdM, M2S1, which was fully active as a DNA methyltransferase. Gel electrophoretic mobility shift assays revealed that the HsdS protein alone was not able to form a specific complex with a 30-mer oligoduplex containing a single EcoAI recognition site. However, addition of stoichiometric amounts of HsdM to HsdS led to efficient specific DNA binding. Our data provide evidence for the circular organisation of domains of the HsdS subunit. In addition, they suggest a possible role of HsdM subunits in the formation of this structure.     

Powder formation by atmospheric spray-freeze-drying

Freeze-drying (lyophilization) has been one of the most useful methods for producing high quality powder from thermosensitive drugs. However, lyophilization has high capital and process costs. A new method for manufacturing powder has been developed in this work, with the aim of reducing drying time and increasing collection efficiency. Compared with other published atmospheric spray-freeze-drying technologies, the new technology combines the spray-freezing step and fluidization conveying of frozen powder using co-current flow to convey the frozen powder to the exit filter. This overcomes the difficulty of fluidizing and elutriating cohesive frozen powder from a substrate. In this process, a powder cake with uniform thickness builds up on the exit filter. Freeze-drying was then performed by continuously flowing a dry gas stream through the packed powder bed at a temperature below the eutectic point of water. The pressure in the chamber was monitored and the residual moisture of the powder was also measured vs time in the drying process. After the completion of drying, a loose powder cake was generated and a free-flowing powder was readily collected. Compared to lyophilization, the experiment indicates the content of α-helix of heat-sensitive protein (samples of bovine serum albumin) was essentially unchanged after drying (96.7% in 2.5 mM NaHCO₃ solution and 102.9% in 2.5 mM NaHCO₃ with trehalose protection (BSA:trehalose = 2:1)) and the powders show good aerosol dispersion for inhalation drug delivery (fine particle fraction FPF_< 5.6 μm was 62.1% ± 2.9% for a mannitol/ciprofloxacin powder). In addition, viability of bacteria (Bordetella pertussis avirulent strain) subjected to this powder processing method was more than 90% after drying, showing that this process has excellent potential for production of powdered biologics. The present process also offers greatly reduced process times i.e. drying was completed in 1-2 h vs 1-2 d with conventional lyophilization in a vacuum.