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.     

DiGeorge anomaly with renal agenesis in infants of mothers with diabetes

We report on 2 infants with the DiGeorge anomaly born to diabetic mothers treated with insulin. Both infants had unilateral renal agenesis. One of the mothers has manifestations suggestive of velo-cardio-facial syndrome (VCFS). Cytogenetic studies on both patients and the mother with apparent VCFS were normal. Molecular studies utilizing probes from the DiGeorge critical region did not demonstrate a 22q11 microdeletion in either patient or the mother with apparent VCFS. We conclude that maternal diabetes is a pathogenetic factor in the DiGeorge anomaly, and infants of diabetic mothers who have this anomaly should also be screened for renal agenesis.     

Structure of interleukin 16 resembles a PDZ domain with an occluded peptide binding site

BACKGROUND: Cervical lymphadenectomy to remove metastatic disease in level II encompasses lymph nodes associated with the upper third of the internal jugular vein and the adjacent spinal accessory nerve (SAN). Conservative neck dissection (ND) preserves these structures but requires manipulation of the SAN to remove tissue located in the posterosuperior aspect of level II. Limiting the dissection to the nodal group anterior to the SAN may reduce operating time and limit injury to it without compromising the removal of lymph nodes at risk for involvement with cancer. METHODS: Seventy-one patients with squamous cell carcinoma of the head and neck treated with cervical lymphadenectomy at two separate institutions were prospectively evaluated. One hundred two neck dissection specimens were histologically analyzed for number of lymph nodes present and number involved with cancer. At the time of surgery, level II was separated into the supraspinal accessory nerve component (IIa) and the component anterior to the SAN (IIb). Nodal involvement in level II was analyzed according to characteristics of the cancer at the primary site as well as nodal involvement of other levels. RESULTS: Neck dissections were most commonly done for cancer of the oral cavity (n = 33), followed in frequency by the larynx (n = 17), oropharynx (n = 7), skin of face (n = 4), unknown primary (n = 4), and other sites (n = 6). Eighty NDs were selective and 22 were either radical or modified radical NDs. Pathologic staging of the neck specimen was most commonly N0 (n = 61), followed in frequency by N1 (n= 17), N2 (n= 11), and N3 (n= 11). Data were unclear for two specimens. Level IIb contained an average of 6.9 nodes and the IIa component contained an average of 4.2 nodes. Level II contained metastatic disease in 31 of 39 node positive specimens (79%). Level IIa was involved with cancer in four cases, all of which were preoperatively staged N2 or greater. CONCLUSIONS: The additional time required and morbidity associated with dissection of the supraspinal accessory nerve component of level II may not be necessary when performing elective ND. More research with larger numbers of patients, long-term follow-up, and meticulous tissue analysis is needed to permit conclusions as to where to draw the line in determining extent of cervical lymphadenectomy.     

Immortalization of osteoclast precursors by targeting Bcl -XL and Simian virus 40 large T antigen to the osteoclast lineage in transgenic mice

Cellular and molecular characterization of osteoclasts (OCL) has been extremely difficult since OCL are rare cells, and are difficult to isolate in large numbers. We used the tartrate-resistant acid phosphatase promoter to target the bcl-XL and/or Simian Virus 40 large T antigen (Tag) genes to cells in the OCL lineage in transgenic mice as a means of immortalizing OCL precursors. Immunocytochemical studies confirmed that we had targeted Bcl-XL and/or Tag to OCL, and transformed and mitotic OCL were readily apparent in bones from both Tag and bcl-XL/Tag mice. OCL formation in primary bone marrow cultures from bcl-XL, Tag, or bcl-XL/Tag mice was twofold greater compared with that of nontransgenic littermates. Bone marrow cells from bcl-XL/Tag mice, but not from singly transgenic bcl-XL or Tag mice, have survived in continuous culture for more than a year. These cells form high numbers of bone-resorbing OCL when cultured using standard conditions for inducing OCL formation, with approximately 50% of the mononuclear cells incorporated into OCL. The OCL that form express calcitonin receptors and contract in response to calcitonin. Studies examining the proliferative capacity and the resistance of OCL precursors from these transgenic mice to apoptosis demonstrated that the increased numbers of OCL precursors in marrow from bcl-XL/Tag mice was due to their increased survival rather than an increased proliferative capacity compared with Tag, bcl-XL, or normal mice. Histomorphometric studies of bones from bcl-XL/Tag mice also confirmed that there were increased numbers of OCL precursors (TRAP + mononuclear cells) present in vivo. These data demonstrate that by targeting both bcl-XL and Tag to cells in the OCL lineage, we have immortalized OCL precursors that form bone-resorbing OCL with an efficiency that is 300-500 times greater than that of normal marrow.     

Nitric oxide as a regulator of prostacyclin synthesis in cultured rat heart endothelial cells

The effects of nitric oxide (NO) and its second messenger cyclic guanosine monophosphate (cGMT) on prostacyclin (PGI2) synthesis were studied in cultured rat heart endothelial cells using three different non-enzymatic nitric oxide releasing substances as well as inhibitors of nitric oxide synthase and of soluble guanylate cyclase. Production of prostacyclin, measured as 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), was stimulated up to 1.7 fold in endothelial cells treated with the NO donors SIN-1 (3-morpholino sydnonimine), GEA 3162 (3-aryl-substituted oxatriazole imine) and GEA 3175 (3-aryl-substituted oxatriazole sulfonyl), chloride). In each case the synthesis of cGMP increase as much as 40-100 fold. An inhibitor of NO synthase, NG-nitro-L-arginine methyl ester (L-NAME), decreased the basal production of 6-keto-PGF1 alpha in non-stimulated endothelial cells, an effect that could be reversed by the NO donors SIN-1, GEA 3162 and GEA 3175. cGMP formation in the L-NAME treated endothelial cells was unaltered. The guanylate cyclase inhibitors, methylene blue (100 mumol/l) and LY83583 (100 mumol/l), caused a 1.5-10 fold increase in 6-keto-PGF1 alpha production while NO-donor-stimulated endothelial cGMP production was decreased by 10 to 90%. However, when SIN-1 was used as a stimulant, LY83583 had no significant effect on the production of cGMP. These findings support the hypothesis that NO stimulates prostacyclin production directly by activating cyclooxygenase. The results also suggest that NO could have an indirect effect on prostacyclin production via cGMP.     

Purification, characterization, and crystallization of Escherichia coli ribokinase

Ribokinase phosphorylates ribose to form ribose-5-phosphate in the presence of ATP and magnesium. The phosphorylated sugar can enter the pentose phosphate pathway or be used for the synthesis of nucleotides, histidine, and tryptophan. Ribokinase belongs to the PfkB family of carbohydrate kinases, for which no three-dimensional structure is currently known. We describe an improved purification protocol for Escherichia coli ribokinase and give evidence from light-scattering and gel filtration studies that the protein forms a dimer in solution. Several types of crystals are also described that have been obtained of apo ribokinase, ribokinase in the presence of ATP, and in a ternary complex with an ATP-analogue and ribose. The latter crystals give the best X-ray diffraction. A complete data set has been collected at the synchrotron source in Hamburg, to 2.6 A resolution using a frozen crystal. The crystals belong to space group P6(1)22 or P6(5)22 with cell parameters a = b = 95 A and c = 155 A.     

51Cr diffusion in α-Zr single crystals

The volume diffusion coefficients of the fast-diffusing solute ⁵¹Cr have been obtained in oriented α-Zr single crystals, in the directions parallel and perpendicular to the c axis. The dependence of these diffusion coefficients on temperature was also measured between 750°C and 848°C.Single crystals were grown by thermal cycling through the α α β transformation temperature (862°C). Diffusion coefficients were measured using the “ thin film” method. In some experiments non-Gaussian penetration profiles were obtained and this behaviour is also analyzed.The diffusion of ⁵¹Cr is faster in the c axis direction, with Q_∥(153 kj/mol) < Q_⊥ (163 kj/mol). The anisotropy factor $\text{f}{}_{\mathrm{a}}\text{=}\text{D}{}_{\mathrm{\parallel }}\text{D⊥}\text{≈ 3}$. This factor, the activation energies and frequency factors are discussed in comparison with those of other solutes.     

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.