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Stepper motors have been used to drive mechanical systems for many decades. Stepper motors require a current-limited multiphase driver, and techniques have evolved from simple resistive drivers to complex high efficiency, high-performance switching devices. The first high-efficiency switching designs were patented over 30 years ago and have become widely used throughout industry. This has caused a shift in driver technology from a quad-drive system to an H-bridge system, and a change in motor design from four windings to two. There are a great many older systems with the earlier motor technology still in use. Retrofitting such systems can take one of several paths: (1) Replacing the entire mechanical drive motor system, its driver, and reworking all the associated communications protocol between the driver and the outside world; (2) Choosing a high-efficiency “H”-bridge driver, reworking its communications protocol and raising the drive voltages to hazardous levels to get the older-technology motor to perform adequately; (3) Designing a high-efficiency, high-performance motor driver system that will work with older-technology motors and existing communications protocols. This paper presents a high-efficiency, high-performance stepper motor driver and that provides all the advantages of a modern motor driver, yet works with existing older-technology stepper motors. It also solves a well-known failure mode of the standard “H” bridge drive system, and will pay for itself in decreased electrical energy costs compared to an old-technology resistive driver. An application-specific communications controller and motor driver will be described to create a drop-in replacement for an existing controller-driver system.

A novel failure mechanism of the high-voltage (HV) product during the negative-current-triggered (NCT) latch-up test is found. From the failure analysis and simulation results, the failure is identified as the unexpected parasitic-bipolar transistors turn-on induced the regulator malfunction to result in the low-voltage (LV) component damage.

The pharmacokinetics of several proteins were investigated using two different assays. A 23kDa recombinant protein fragment of bactericidal/permeability-increasing protein (rBPI 23 ) was radiolabeled with 125 I using Iodo-beads® and administered to rats. Plasma samples were collected and assayed for 125 I-rBPI 23 by radioactivity. In a separate experiment, rBPI 23 was administered to rats and plasma samples were assayed for rBPI 23 by ELISA. The clearance determined from plasma concentrations of 125 I-rBPI 23 measured by radioactivity was about 2.5-fold lower than that of rBPI 23 determined by ELISA. In addition, the steady state volumes of distribution and mean residence times of 125 I-rBPI 23 measured by radioactivity were four-fold and 10-fold greater, respectively, compared to those measured by the ELISA method. By studying several proteins with a range of molecular weights, we found that the pharmacokinetics of proteins below about 60kDa were different when assayed by radioactivity or ELISA, but those of proteins with molecular weights of at least 80kDA revealed only minor differences. To determine which assay method yielded the correct plasma pharmacokinetic profile, rBPI 23 was metabolically labeled with 35 S-methionine and administered to rats, and plasma samples were assayed by radioactivity. The concentration-time profile assessed by this method was very close to that determined by ELISA. Exposing rBPI 23 to chloramine-T (the oxidant used in the iodination process) and measuring its plasma concentration by ELISA revealed pharmacokinetics similar to those of the iodinated protein measured by radioactivity. In contrast, radiolabeling rBPI 23 using iodinated Bolton-Hunter reagent (which avoids exposing the protein to oxidant), and measuring 125 I-rBPI 23 by radioactivity, yielded pharmacokinetics that were similar, although not identical, to the pharmacokinetics of rBPI 23 measured by ELISA. Thus, our data suggest that directly iodinating low-molecular-weight proteins by oxidation procedures alters their clearance from the blood, preventing reliable determination of pharmacokinetic parameters.

Study Objective. To evaluate the cost-effectiveness of laparoscopic versus abdominal Burch procedures in women with urinary stress incontinence (USI). Design. A historical cohort with a minimum follow-up of 1 year. Setting. Two tertiary, university-affiliated referral centers. Patients. Women with USI who had either a laparoscopic Burch (31 women) or an abdominal Burch procedure (31). They were matched for the type of procedure as well as any concurrent procedures. Measurements and Main Results. The primary outcome was cure, defined as the absence of USI subjectively as described by the patient, and objectively as confirmed by urodynamic and stress tests. Cost data were extracted from hospital charts and office records. To calculate costs we assessed professional fees (physicians, nurses, nursing assistants), investigations (laboratory tests, radiology, urodynamics), drugs, capital equipment, disposable equipment, and length of stay. The cure rates were 97% and 90%, respectively. The mean duration of follow-up was 1.2 years (range 1–2.5 yrs) for a laparoscopic Burch and 2.7 years (range 1–9 yrs) for an abdominalBurch. Preliminary results showed a significant difference in cost effectiveness between the procedures. The average cost for a laparoscopic Burch was $2938.35 and for an abdominal Burch $5692.30. The higher costs for abdominal Burch were due to increased hospital stay. The cost-effectiveness ratios (cost/cure) were $3029.23 and $6324.78, respectively. Sensitivity analysis was performed to assess for robustness. Conclusions. The preliminary results show that a laparoscopic Burch is more cost-effective than the abdominal Burch in treating women with USI.

Parke-Davis Pharmaceutical Research, Ann Arbor, Michigan 48105 (J.WH.); Miles, Inc., Elkhart, Indiana 46515 (K.G.H.); USFDA, Rockville, Maryland 20852 (M.A.S., J.A.C.); California Regional Primate Research Center, Davis, California 95616 (A.G.H.); Hoffman-LaRoche, Inc., Nutley, New Jersey 07110 (N.D.A.); Skyline Technology Consulting Group, Znc., San Francisco, California 94133 (A.H.C.K.); and Genentech, Znc., South San Francisco, California 94080 (J.M.)

This study compares outcomes of kidney transplantation with two distinct induction protocols Basiliximab (Simulect) versus Muromonab (OTK 3) in the setting of cyclosporine (Neoral)-based immunosuppression. Postinduction protocols included either total prednisone avoidance or prednisone sparing versus standard prednisone dosing. Two hundred forty five adult patients receiving kidney transplantation between 1995 and 2000 were included in the study. Treatment in group 1 was OKT 3 + Neoral + adjunct + standard prednisone; group 2, Simulect + Neoral + adjunct + steroid sparing; group 3, Simulect + Neoral + adjunct + no prednisone. The demographics between all groups were similar. The mean (+/- SD) trough cyclosporine levels at 1 month were 276 +/- 128 versus 291 +/- 180 versus 398 +/- 365 (P=.020); at 3 months were 261 +/- 120 versus 280 +/- 152 versus 399 +/- 408 (P=.32); at 12 month were 235 +/- 144 versus 245 +/- 154 versus 234 +/- 132 (P=.96). Creatinine clearance at 1 month was 59 +/- 24 versus 58 +/- 18 versus 47 +/- 23 mL/min (P=.004); at 3 months was 66 +/- 28 versus 62 +/- 22 versus 53 +/- 25 mL/min (P=.007); at 12 months was 68 +/- 38 versus 65 +/- 22 versus 64 +/- 29 mL/min (P=.556). Serum creatinine at 1 month was 1.8 +/- 0.9 versus 1.6 +/- 1.2 versus 2.8 +/- 2.21 mg/dL (P=.005); at 3 months was 1.7 +/- 0.6 versus 1.9 +/- 1.0 versus 2.3 +/- 1.3 mg/dL (P=.007); at 12 months was 1.9 +/- 1.3 versus 2.1 +/- 1.0 versus 2.3 +/- 1.7 mg/dL (P=.179). The incidence of acute rejection within 1 year in the respective groups were 28% versus 15% versus 16%. Therefore, we conclude that using Simulect in transplant recipients results in long-term patient and graft survival similar to those achieved with OKT 3. The use of Simulect resulted in significant reduction in clinical rejection incidence within the first year regardless of steroid use. Thus, the use of Simulect allows complete steroid avoidance in Neoral-based immunosuppression regimen.

A summary of the current understanding of the lean NOx reduction reaction on various metal oxides, particularly Cu-ZrO2, is presented. Whenever appropriate, a comparison with the behavior of the corresponding ZSM-5-based catalysts is made. It is concluded that there are many mechanistic similarities between metal oxide-based and zeolite-based catalysts. Thus, the catalytic properties are determined more by the nature of the active centers than by the nature of the support. Potential advantages offered by metal oxides should make them attractive candidates for practical applications.

The reduction of NOx with propene or propane in the presence of 1 or 4% O2 was studied at low conversions over a 7.4 wt% Cu-ZrO2 and a 3.2 wt% Cu-ZSM-5 catalyst. The rates of N2 production were compared in experiments using only NO or a mixture of NO and NO2 in the feed. They were also compared with the rates of NO2 reduction to NO under the same conditions, and of NO oxidation to NO2 in the absence of hydrocarbon. It was found that the reduction of NO2 to NO was very fast, consistent with literature data. The data were best explained by a reaction scheme in which the hydrocarbon was activated primarily by reaction with adsorbed NO2 to form an adsorbed oxidized N-containing hydrocarbon intermediate, the reaction of which with NO was the principal route to produce N2 under lean NOx conditions.

Fusion proteins between cell-targeting domains and cytotoxic proteins should be particularly effective therapeutic reagents. We constructed a family of immunofusion proteins linking humanized Fab, F(ab')2, or single chain antibody forms of the H65 antibody (which recognizes the CD5 antigen on the surface of human T cells) with the plant ribosome-inactivating protein gelonin. We reasoned that such an immunofusion would kill human target cells as efficiently as the previously described chemical conjugates of H65 and gelonin (Better M., Bernhard, S. L., Fishwild, D. M., Nolan, P. A., Bauer, R. J., Kung, A. H. C., and Carroll, S. F. (1994) J. Biol. Chem. 269, 9644-9650) if both the recognition and catalytic domains remained active, and a proper linkage between domains could be found. Immunofusion proteins were produced in Escherichia coli as secreted proteins and were recovered directly from the bacterial culture supernatant in an active form. All of the immunofusion proteins were purified by a common process and were tested for cytotoxicity toward antigen-positive human cells. A 20-60-fold range of cytotoxic activity was seen among the fusion family members, and several fusion proteins were identified which are approximately as active as effective chemical conjugates. Based on these constructs, immunofusion avidity and potency can be controlled by appropriate selection of antibody domains and ribosome-inactivating protein.

Because of suggestions that thyroid hormones modulate serum lipoprotein(a) [Lp(a)] concentration, we evaluated prospectively the serial changes of serum Lp(a), measured as apolipoprotein(a) [apo(a)], and other lipoproteins in 40 subjects with hyperthyroidism treated with radioactive iodine (RAI) therapy. Hyperthyroid patients had lower (P < 0.001) concentrations of apo(a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apo B, but higher apo A-I concentrations compared with age-matched controls [geometric mean (range)]; apo(a) 81 (17-614) vs 187 (17-1808 IU/L): TC 4.07 +/- 0.8 vs 5.22 +/- 1.00 mmol/L (mean +/- SD); LDL-C 2.47 +/- 0.89 vs 3.40 +/- 0.88 mmol/L; HDL-C 1.05 +/- 0.33 vs 1.24 +/- 0.34 mmol/L; apo B 0.66 +/- 0.23 vs 1.13 +/- 0.34 g/L, and apo A-I 2.07 +/- 0.42 vs 1.46 +/- 0.28 g/L, respectively. Euthyroidism was associated with normalization of serum TC, LDL-C, and apo B within 1 month of treatment. However, apo(a) required 4 months to normalize, and HDL-C and apo A-I were still abnormal 6 months after RAI. Serum apo(a), TC, LDL-C, and apo B were negatively correlated with serum thyroxine (T4), free thyroxine index, and triiodothyronine (T3) and positively correlated with thyrotropin during the transitional period from hyperthyroidism to euthyroidism. Parallel changes of these lipoproteins and thyroid hormones were also observed after treatment of hyperthyroidism. In conclusion, thyroid hormones do modulate lipoproteins, particularly Lp(a). The delay in normalization of apo(a) but not LDL suggests an effect on apo(a) production rather than on LDL removal.

Thiourea drugs have been postulated to possess radioprotective property. We studied the effect of adjunctive antithyroid drugs (ATD) and L-thyroxine (L-T4) on the result of radioiodine (RAI) 131I therapy and determined the incidence of hypothyroidism and relapse of hyperthyroidism. One hundred and fifty-nine patients with Graves' disease were randomized prospectively to receive either RAI alone or adjunctive ATD in a form of block-replacement regimen of methimazole (MMI) plus L-T4 for 6 months. The patients were observed for a mean period of 4.6 (range 2-10) years. The incidence of permanent hypothyroidism was studied and the effect of ATD on iodine kinetics was analyzed. The cumulative incidence of hypothyroidism in the ATD group was significantly lower than the RAI group (p = 0.0009), and the difference is accounted by a reduction of early hypothyroidism within 12 months from 20.2 to 3.7% (p = 0.003). The incidence of late hypothyroidism was similar between the two groups. Treatment with ATD did not affect the one dose cure rate with RAI (61.2 vs 55.5%, p = NS), but the time to achieve euthyroidism was significantly earlier with adjunctive ATD (2 vs 8 weeks, p0.02). The incidence of relapse within the first year after one dose was also similar between the two groups (38.7 vs 44.5%, p = NS). Comparing the kinetics of the therapeutic dose with a tracer dose, patients receiving MMI were found to be underdosed by 22% (p = 0.003) and the biological half-life was significantly shortened. We conclude that ATD rendered euthyroidism earlier without compromising the one dose cure rate of RAI.(ABSTRACT TRUNCATED AT 250 WORDS)

A recombinant 23-kDa amino-terminal fragment of human bactericidal/permeability-increasing protein (rBPI23), a potent lipopolysaccharide (LPS)-binding/neutralizing protein, was used as a probe to assess the role of endotoxin in the acute inflammatory responses elicited by gram-negative bacteria in rat subcutaneous air pouches. In initial experiments, rBPI23 prevented the Escherichia coli O111:B4 LPS-induced accumulation of polymorphonuclear leukocytes (PMN), tumor necrosis factor alpha (TNF-alpha), and nitrite (a stable end product of nitric oxide formation) in exudate fluids. Significant inhibition of TNF-alpha production was still evident when rBPI23 treatment was delayed for 30 min after LPS instillation. In subsequent experiments, rBPI23 also prevented the nitrite and early (2-h) TNF-alpha accumulation induced by three different strains of formaldehyde-killed gram-negative bacteria (E. coli O7:K1, E. coli O111:B4, and Pseudomonas aeruginosa 12.4.4) but did not inhibit the PMN or late (6-h) TNF-alpha accumulation induced by these bacteria. As with LPS challenge, a significant inhibition of early TNF-alpha production was still evident when rBPI23 treatment was delayed for 30 to 60 min after instillation of killed bacteria. The results indicate that in this experimental model the NO and early TNF-alpha responses to gram-negative bacterial challenge are mediated predominantly by endotoxin, whereas the PMN and late TNF-alpha responses may be mediated by other bacterial components. Moreover, the results indicate that rBPI23 can inhibit the bacterially induced production of certain potentially harmful mediators (TNF-alpha and NO) without entirely blocking the host defense, i.e., PMN response, against the bacteria.

A facile route that combines co-assembly and photothermal reduction was developed to synthesize free-standing, flexible FeF(3)-graphene papers. The papers contain well-dispersed FeF(3) nanoparticles and open diffusion channels in a porous, electrically conducting network of graphene sheets, and demonstrate promising applications as cathodes in high-energy density Li-ion batteries.

A Useful Cover-Up Many industrial catalysts that consist of metal nanoparticles adsorbed on metal oxide supports undergo deactivation after prolonged use. Organic reactants can decompose and cover the metal with carbon (“coking”), and other processes can push the size distribution to fewer but larger particles that have less overall surface area available for reaction (“sintering”). Lu et al. (p. 1205 ) used atomic-layer deposition to apply a uniform overlayer of alumina onto supported palladium nanoparticles. This coating greatly increased the resistance of the nanoparticles to coking and sintering during the oxidative dehydration of ethane to ethylene.

Effects of an N-terminal fragment of bactericidal/permeability increasing protein (rBPI21) on bacterial infections were determined. Intravenous (i.v.) rBPI21 increased survival and reduced bacteremia in rats after an iv injection of Escherichia coli O7:K1 bacteria. rBPI21 inhibited the rise in tumor necrosis factor-alpha resulting from challenge with 2 strains of E. coli. Intraperitoneal (ip) injection of rBPI21 increased survival of mice after ip injection of E. coli O7:K1 and Pseudomonas aeruginosa and reduced bacteria in peritoneal lavage fluid and blood and inhibited cytokine production in response to E. coli. rBPI21 alone did not protect mice challenged with E. coli O111:B4 but was protective and reduced bacterial counts when administered in combination with the antibiotic cefamandole. The data show that protection with rBPI21 is associated with reductions in bacterial counts and is enhanced by antibiotics. Bactericidal activity, in addition to antiendotoxin activity, is involved in the efficacy of rBPI21 in models of gram-negative infection.

BACKGROUND Platelets play an important role in the pathogenesis of cardiovascular diseases. It is also noticed that on one hand, regular exercise can reduce the risk of cardiovascular diseases, and on the other hand, vigorous exercise provokes sudden cardiac death. We therefore hypothesize that various intensities of exercise may affect platelet function differently. METHODS AND RESULTS Strenuous and moderate exercise (about 50% to 55% of peak oxygen consumption, VO2peak) on a bicycle ergometer in 10 sedentary and 10 physically active healthy young men was executed on two separate occasions. Blood samples were collected before and immediately after exercise. A newly designed tapered parallel plate chamber was used to assess platelet adhesiveness. Platelet aggregation induced by ADP was evaluated by the percentage of reduction in single platelet count. beta-Thromboglobulin (beta-TG) and platelet factor 4 (PF4) were measured by ELISA. In addition, a similar study on 5 patients with stable angina were also conducted. Our results showed that (1) in the sedentary healthy group, platelet adhesiveness and aggregation were increased by strenuous exercise and depressed by moderate exercise; (2) in the active healthy group, platelet adhesiveness and aggregation were enhanced by severe exercise, whereas only aggregation was decreased by moderate exercise; (3) in the patients with stable angina, platelet adhesiveness and aggregation were enhanced by strenuous exercise and adhesiveness was suppressed by moderate exercise; (4) the degree of hemoconcentration induced by acute exercise tended to be related to the severity of exercise in all subjects; and (5) although severe exercise elevated beta-TG and PF4, there were no significant changes in beta-TG, PF4, and the ratio of beta-TG to PF4 in healthy subjects after exercise. CONCLUSIONS It is concluded that platelet adhesiveness and aggregability may be sensitized by strenuous exercise in both healthy subjects and patients with stable angina. In contrast, platelet function can be suppressed significantly by moderate exercise in the healthy and tends to be depressed in patients with stable angina. The former may increase the risk of cardiac arrest and the latter may protect us from cardiovascular diseases. In addition, the effects of acute exercise tend to be more pronounced in the sedentary than in the active.

The M(r) = 94,000 heavy chain of bovine factor Va contains 10 cysteine residues which are distributed in the 2 A domains which make up this portion of the factor V molecule. The A1 domain contains four cysteines while the A2 domain contains six cysteines. The locations of disulfide bridges and free cysteines in bovine factor Va heavy chain were analyzed using iodo[14C]acetamide-labeled factor Va heavy chain digested with trypsin, plasmin, V-8 protease, and cyanogen bromide. Following HPLC separation of the resulting peptides, free cysteines were identified by the incorporation of radioactivity while disulfide-containing peptides were detected using an SBD-F fluorometric assay after reduction. All cysteine-containing peptides were analyzed by amino acid sequence analysis. The four cysteines in the A1 domain are associated with two disulfide bonds, Cys139-Cys165 and Cys220-Cys301. One disulfide bond was explicitly identified in the A2 domain; Cys471-Cys497, and a free cysteine was found in the A2 domain at Cys538. Significant difficulties were encountered in preparing identifiable or soluble peptides which would permit the explicit identification of the three remaining cysteines in the A2 domain. On the basis of homology, it is likely that Cys589 is a free SH while a disulfide bridge exists between Cys579 and Cys660. Thus, three major disulfide bonding patterns, characterized as "alpha", "beta", and "gamma" loops, are found in factor V. Each A domain contains a 26 residue "alpha loop at positions 139-165, 471-497, and 1684-1710. The A1 and A2 domains each contain 81 amino acid residue "beta" loops at 220-301 and 579-660.(ABSTRACT TRUNCATED AT 250 WORDS)

A new method of increasing manoeuvring target tracking performance is presented. The target manoeuvring is modelled as process white gaussian noise so that the system equations to which optimal filtering theory applies can be obtained. A multi-model adaptive Kalman filter is developed to estimate the target positions, based on process noise covariance matching and multi-model measurement noise. In the conventional adaptive filter, only one of process noise and measurement noise covariance matching can be done in a program. In this algorithm, the tracking filter estimates the covariance of process noise and measurement noise simultaneously to increase the accuracy of the conventional real-time tracking filter. Finally, an illustrative numerical example is included.

The formation of a chromium-carbide conversion coating on SiC was achieved using the pack-cementation technique. The conversion coating is intended to improve the corrosion resistance of SiC and its derivatives, such as SiC-base continuous fibers and composites, by forming a protective Cr2O3 scale upon exposure to high-temperature corrosive environments. Different pack chemistry and processing parameters were evaluated in the laboratory. Results indicated that the coating morphologies and compositions achieved were significantly affected by variation of these processing factors. In this paper, the conversion coating obtained from one of the systems investigated is reported. The coating consists of a multilayered structure with each of the sublayers containing a high-Cr concentration. In addition, the coating surface is relatively dense and pore free compared to the underlying SiC substrate material. A dense and pore-free morphology is highly desirable for coating applications, especially on porous substrates. The multilayered coating structure consists of the following sublayers: Cr23C6/Cr7C3/Cr7C3+Cr3Si/Cr5Si3Cx/SiC substrate.

The immunoconjugate, XomaZyme-CD5 Plus, consists of a murine immunoglobulin IgGl monoclonal antibody directed against the CD5 antigen present on mature human T lymphocytes and ricin A chain (RTA), a potent ribosomal inhibitory protein. XomaZyme-CD5 Plus, administered as an 1-hour infusion, has shown efficacy in patients with steroid-resistant acute graft versus host disease. An animal model was developed to study the toxicity profile of XomaZyme-CD5 Plus when administered by continuous intravenous infusion in the rat and to support the delivery of the drug by this method in human clinical trials. This animal model involved the continuous i.v. infusion of XomaZyme-CD5 Plus in conscious rats for 10 consecutive days via catheterization of the external jugular vein and surgical attachment of the animals to a tether/swivel system leading to a syringe pump. In addition, a comparison study was conducted with XomaZyme-CD5 Plus administered to rats at the same daily dose by bolus i.v. injection for 10 days. Qualitatively similar toxicity profiles were observed for XomaZyme-CD5 Plus given by bolus injection and by continuous infusion in rats. Comparing equivalent dose levels, 0.5 mg/kg/day, XomaZyme-CD5 Plus given by continuous i.v. infusion was similar in toxicity as given by bolus injection. The anti-immunoconjugate (XomaZyme-CD5 Plus) antibody response occurred later and titers were lower after infusion in comparison to bolus injection. We have demonstrated that the rat continuous i.v. infusion model can be successfully used to deliver protein therapeutics at accurate dosages to study standard acute to subchronic toxicity profiles.

Cu-Zr-O catalyst is active and selective in the NO reduction by propene in an oxidizing atmosphere. This is due to the inertness of ZrO2 in hydrocarbon oxidation and its ability to disperse Cu. Other transition metal-zirconium mixed oxides were also tested for NO reduction by hydrocarbons in an oxidizing atmosphere. When propene is used as a reductant, Cu, Ni and Co supported on zirconia are active and selective catalysts. When propane is used as a reductant NO conversion decreases for all of the catalysts. The decrease is mild for Ni and Co but is very severe for Cu.

The crystal structure of the recombinant calmodulin from Paramecium tetraurelia (rPCaM, M(r) = 16 700, 148 residues) has been determined at 1.68 A resolution. X-ray intensity data were collected at 263 K using a Siemens-Nicolet area detector and Cu Kalpha radiation from a rotating-anode source. A total of 35 936 observations were processed with XENGEN1.3 and scaled to yield 16 255 unique reflections with R(symm)(I) of 4.1%. The crystals are triclinic, with unit-cell dimensions a = 29.89, b = 53.42, c = 25.35 A, alpha = 93.67, beta = 96.88, gamma = 89.24 degrees, space group P1, with one molecule in the unit cell. The atomic coordinates of the wild-type Paramecium calmodulin (PCaM) studied in our laboratory provided the starting model. Refinement of the structure by X-PLOR and refitting it into omit maps yielded an R value of 0.194 for 15 965 reflections greater than 3sigma(F) in the 6.0-1.68 A resolution range. The final model contained 1165 protein atoms for all of the 148 residues, four Ca(2+) ions, and 172 water molecules. The dumbbell structure has seven alpha-helices including a long 7.8 turn central helix connecting the two terminal domains each containing two EF-hand (helix-loop-helix motif) calcium-binding sites. The loops within each pair of EF-hand motifs in the N- and C-terminal domains are brought into juxtaposition to form a pair of hydrogen-bonded antiparallel beta-sheets which are extended at either ends by water bridges. The four calcium-binding EF-hands are superposable with r.m.s. deviations of 0.31-0.79 A. The best agreement is between site 1 and site 3 and the worst agreement is between site 1 and 4. The largest differences are in the ninth and tenth residues of the calcium-binding loops probably because of their involvement in the mini beta-sheets. The calcium coordination distances vary between 2.04 and 2.69 A, average 2.34 A. The rPCaM and wild-type PCaM have an r.m.s. deviation of 0.36 A for equivalent C(alpha) atoms. The side chains of Lys13 and Lys115 are more extended in rPCaM compared to the wild type where the post-translational modified di- and tri-methylated lysine residues are more folded. The sequence of PCaM differs from those of mammalian (MCaM) and Drosophila calmodulin (DCaM), but the overall structures are very similar, with r.m.s,. deviations of 0.44 and 1.68 A for equivalent C(alpha) atoms, respectively. However, in rPCaM, the first four N-terminal residues stretch out and make intermolecular crystal contacts, in contrast to those in recombinant Drosophila calmodulin (rDCaM), they stretch out in the opposite direction and towards the second calcium-binding site (see note below), while in MCaM and wild-type PCaM, the N-terminal residues are not visible. The central helix in rPCaM has all its backbone hydrogen bonds intact with no unusually long separation between the carbonyl and amide groups as found in MCaM and rDCaM.

The energetics characteristics of the observed and simulated general circulation are analyzed using three-dimensional normal mode expansions. The data sets involved are the Goddard Laboratory for Atmospheres (GLA) analysis and simulation data and the Geophysical Fluid Dynamics Laboratory (GFDL) analysis data. The spectral energy properties of the Rossby and gravity modes and energy transformations are presented. Significant influences of model characteristics and the assimilation techniques are observed in the barotropic energy spectrum, particularly for the gravity mode. Energy transformations of the zonal mean field in the GLA analysis and simulation are similar, but distinctly different from that in the GFDL analysis. However, overall, the energy generation in the baroclinic mode is largely balanced by the sink in the barotropic mode. The present study may demonstrate utilities of the three-dimensional normal mode energetics in the analysis of the general circulation. DOI: 10.1111/j.1600-0870.1986.tb00474.x

The unique combination of high surface area, high electrical conductivity and robust mechanical integrity has attracted great interest in the use of graphene sheets for future electronics applications. Their potential applications for high-power energy storage devices, however, are restricted by the accessible volume, which may be only a fraction of the physical volume, a consequence of the compact geometry of the stack and the ion mobility. Here we demonstrated that remarkably enhanced power delivery can be realized in graphene papers for the use in Li-ion batteries by controlled generation of in-plane porosity via a mechanical cavitation-chemical oxidation approach. These flexible, holey graphene papers, created via facile microscopic engineering, possess abundant ion binding sites, enhanced ion diffusion kinetics, and excellent high-rate lithium-ion storage capabilities, and are suitable for high-performance energy storage devices.

Serum osteoprotegerin (OPG) level is a key biomarker for numerous traits of clinical importance like diabetes, coronary artery disease, blood pressure, lipid profile, and cancers, but its genetic basis remains poorly understood. We estimated the heritability (h(2)) of serum OPG level in 1442 southern Chinese subjects from 306 families. The h(2) for unadjusted OPG was 0.62 for females and 0.17 for males; and for age-adjusted OPG, 0.75 for females and 0.37 for males. Adjustment for lifestyle factors including calcium and phytoestrogen intake, exercise, smoking, and alcohol consumption exerted only a modest effect on the h(2). In conclusion, we confirmed that circulating OPG is a heritable trait and there is a significant difference in heritability between sexes.

New IQ demodulator, which will be used in the reflectometry system, was developed for the Alcator C-Mod experiments. Because the demodulator itself is a 4 mm × 4 mm integrated circuit chip and has very wide operational bandwidth (0.7 GHz – GHz), it can be mounted on a circuit board with its low frequency IQ outputs connecting directly to gain control and dc offset adjustment circuits. This whole circuitry is realized on a 4′×2.5″ printed circuit board and can be well tailored to meet the requirements for any type of data collection system. Since the RF and LO ports are operated at very narrow bandwidth in this application, single stub match circuits are designed to improve the ports matching as well as serve as a single pole filter.

Osteoporosis is a serious worldwide epidemic. Increased risk of fractures is the hallmark of the disease and is associated with increased morbidity, mortality and economic burden. FRAX® is a web-based tool developed by the Sheffield WHO Collaborating Center team, that integrates clinical risk factors, femoral neck BMD, country specific mortality and fracture data and calculates the 10 year fracture probability in order to help health care professionals identify patients who need treatment. However, only 31 countries have a FRAX® calculator at the time paper was accepted for publication. In the absence of a FRAX® model for a particular country, it has been suggested to use a surrogate country for which the epidemiology of osteoporosis most closely approximates the index country. More specific recommendations for clinicians in these countries are not available. In North America, concerns have also been raised regarding the assumptions used to construct the US ethnic specific FRAX® calculators with respect to the correction factors applied to derive fracture probabilities in Blacks, Asians and Hispanics in comparison to Whites. In addition, questions were raised about calculating fracture risk in other ethnic groups e.g., Native Americans and First Canadians. In order to provide additional guidance to clinicians, a FRAX® International Task Force was formed to address specific questions raised by physicians in countries without FRAX® calculators and seeking to integrate FRAX® into their clinical practice. The main questions that the task force tried to answer were the following: The Task Force members conducted appropriate literature reviews and developed preliminary statements that were discussed and graded by a panel of experts at the ISCD-IOF joint conference. The statements approved by the panel of experts are discussed in the current paper.

Heart failure occurs in 6% of hyperthyroid patients. Nonetheless, only half of those with hyperthyroidism-related heart failure have impaired left ventricular (LV) systolic function. Thus, diastolic dysfunction may play an important role in the pathogenesis.We performed serial echocardiographic examinations in 70 consecutive patients with hyperthyroidism (39 ± 2 years, 47 women) to determine their diastolic function and repeated the examinations 6 months after achieving a euthyroid state. All patients had normal LV systolic function, but diastolic dysfunction was detected in 22 cases (mild: 3, moderate: 15 and severe: 4). The prevalence of diastolic dysfunction increased with age from 17·9 % in patients40 years to 100% in those60 years. Increasing age was the only independent predictor for diastolic dysfunction in hyperthyroid patients. After achievement of a euthyroid state, most patients (16/22, 72%) had completely normalized diastolic function: 100% of patients40 years, 33·3 % of those ≥ 60 years. Further analyses revealed significant age-related differences in the cardiovascular response to hyperthyroidism. Among patients40 years, hyperthyroidism resulted in a marked reduction in total peripheral vascular resistance, increased cardiac output and enhanced diastolic function as determined by E'. No such significant change in total peripheral vascular resistance or cardiac output was observed in hyperthyroid patients ≥ 40 years. In addition, hyperthyroidism was associated with reduced E', signifying diastolic dysfunction in older hyperthyroid patients.Hyperthyroidism is associated with diastolic dysfunction, particularly in older patients. It is partly reversible following achievement of a euthyroid state.

The single‐feed, end‐grounded straps of the NSTX 12‐strap HHFW antenna array have been replaced with double‐feed, center‐grounded straps to reduce the voltages in the vicinity of the Faraday shield (FS) for a given strap current. The strap spacings to the FS and to the back plate were increased by 3 mm to decrease the electric fields for a given voltage. The electric fields near the FS have been roughly halved for the same strap currents, permitting a direct examination of the roles that internal fields play in determining antenna power limits in plasmas. Extensive RF/plasma conditioning of the antenna was required to remove enough of the evaporated Li deposits from prior wall conditioning to permit coupling in excess of 4 MW to L‐ and H‐mode plasmas in 2009. Most arcs were associated with expulsion of Li from the FS/antenna frame surfaces. The center‐grounded straps were less susceptible to arcing during ELMing H‐mode plasmas. Reliable operation above 2 MW was difficult after the installation of the Liqu...

The relative contributions of CD5+ and CD5- B-cells in production of rheumatoid factors (RF) was evaluated in polyclonally activated B-cells from patients with IgA nephropathy (IgAN), rheumatoid arthritis (RA) and Graves' disease (GD). In IgAN and RA, diseases in which RFs are believed to be involved in pathogenesis, there were 10- and 4-fold decreases respectively in CD5+ IgG-RF-secreting B-cells compared with controls. Furthermore, the number of CD5- IgG-RF- and IgA-RF-secreting B-cells were increased 12- and 14-fold in IgAN and 9- and 4-fold in RA. Such abnormalities were not apparent in GD, in which RFs have not been implicated in pathogenesis. These findings are compatible with the concept of CD5+ RF-secreting B-cells normally acting to prevent production of potentially pathogenic RFs by CD5- B-cells. When IgAN or RA patients' B-cells were activated in the presence of control instead of autologous CD4+ cells, numbers of RF-secreting CD5- B-cells were reduced to the levels seen with control B-cells plus control T-helper cells. Presumably lymphokine secretion profiles of T-helper cells would be important in determining whether CD5+ or CD5- B-cells are activated to secrete RFs, and perhaps therapeutic manipulation of these profiles could restore normal activity of CD5+ B-cells in IgAN and RA.

Untreated acromegaly is associated with an increased cardiovascular morbidity and mortality. The contribution of altered lipid metabolism remains unclear. We investigated the relationship between serum apolipoprotein(a) (apo(a)) and growth hormone (GH) levels in 15 patients with acromegaly before and during treatment with octreotide, a long-acting somatostatin analogue, 288–600 μg/day s.c., for 6 months. Before treatment serum apo(a) was significantly elevated in acromegalic patients (geometric mean being 323 U/1 vs. 142 U/1 in controls (n = 92; P < 0.01)). Octreotide treatment resulted in significant reductions in serum apo(a) concentration (F= 7.22; P < 0.01; geometric mean being 232 U/1 and 248 U/1 at 3 months and 6 months respectively) and apo(a) concentrations on treatment were not significantly different from control values. There were significant reductions in serum GH (F= 7.30; P < 0.01), insulin growth factor 1 (IGF1) (F=31.4, P < 0.001) and insulin (F=4.57; P < 0.05) concentrations. Plasma glycosylated haemoglobin levels were unchanged. Apo(a) levels correlated with serum GH (r = 0.450; P < 0.01) but showed no correlation with basal insulin concentrations. Serum HDL cholesterol increased on treatment (F= 4.29; P < 0.05). Triglycerides were reduced only in the 12 patients without diabetes mellitus (F= 4.75; P < 0.05). No significant change in LDL cholesterol occurred. Our findings suggest that apo(a) may constitute another cardiovascular risk factor in untreated acromegaly and that GH may be involved in the regulation of circulating apo(a) concentration.

A human peripheral blood lymphocyte-reconstituted severe combined immunodeficient (hu-PBL-SCID) mouse model was used to compare in vivo efficacy of immunoconjugates directed against the CD5 antigen present on human T-cells. Four anti-CD5 immunoconjugates were tested, composed of chimeric human-mouse (cH65) F(ab′) 2 or Fab′ fragments chemically linked to recombinant gelonin (rGEL) or the 30,000 M r glycoform of ricin A chain (RTA 30 ). Immunoconjugate treatment was initiated ≈3 weeks after PBL transplantation and consisted of five consecutive daily bolus i.v. injections. Efficacy was subsequently assessed by quantitation of human T-cells in spleens, blood and peritoneal lavage fluid using 3-color flow cytometry. cH65 F(ab′) 2 - and cH65 Fab′-rGEL conjugates were essentially equally effective at depleting human T-cells from SCID mouse tissues, suggesting that bivalent binding is not required for efficacy when rGEL is the cytotoxic moiety. Treatment with unconjugated F(ab′) 2 , unconjugated Fab′ or a Fab-rGEL immunoconjugate of irrelevant binding specificity did not result in a significant depletion of T-cells, demonstrating that the cytotoxic moiety and a relevant human T-cell binding moiety are both required for efficacy. In contrast to the results observed with the rGEL conjugates, cH65 Fab′ - RTA 30 was not as effective as cH65 F(ab′) 2 -RTA 30 in depleting human T-cells from SCID mouse tissues. This paralleled in vitro findings in a human PBMC cytotoxicity assay, which demonstrated that cH65 Fab′ - RTA 30 was 17-fold less potent than cH65 F(ab′) 2 -RTA 30 and ≈50-fold less potent than the rGEL conjugates. These results indicate that the hu-PBL-SCID mouse model can be used to evaluate potential differences in efficacy of cytotoxic agents directed against human T-cells and implicate anti-CD5 conjugates containing rGEL as potentially potent therapeutic agents.

Bactericidal/permeability-increasing protein (BPI), a cationic protein found in neutrophil granules, binds with high affinity to gram-negative bacterial lipopolysaccharide (LPS) and can inhibit its actions in vitro. The in vivo efficacy of a recombinant 23-kDa amino-terminal LPS-binding fragment of BPI (rBPI23) was assessed in a mouse model of lethal endotoxemia. Systemic administration of rBPI23 protected actinomycin D-sensitized mice from lethal LPS (Escherichia coli O111:B4) challenge in a dose-dependent manner, with almost complete protection at the highest dose (10 mg/kg; 93% survival vs. 13% in vehicle-treated controls). Surviving rBPI23-treated animals did not show histopathologic signs of tissue damage evident in control animals that had died after LPS challenge. rBPI23 also attenuated the LPS-induced elevation in serum levels of tumor necrosis factor-alpha and interleukin-1 alpha, mediators believed to be involved in the pathogenesis of endotoxemia and sepsis. Thus, rBPI23 may be a potential new therapeutic agent for the treatment of gram-negative bacterial infection and sepsis.

Eleven cobalt-tolerant mutants were found to belong to a single complementation group, cot2. In addition to cobalt, the cot2 mutants were found to tolerate increased levels of the divalent cations Zn2+, Mn2+, and Ni2+ as well. All of the cot2 mutants exhibited a wiener-shaped cellular morphology that was exacerbated by the carbon and nitrogen source but was unaffected by metals. The rate of glucose-dependent transport of cobalt into cells was reduced in strains that carry mutations in the COT2 gene. COT2 is not essential for growth. Strains that carry a COT2 allele conferring complete loss of function are viable and exhibit phenotypes similar to those of spontaneous cot2 mutations. The sequence of the COT2 gene shows that it is identical to GRR1, which encodes a protein required for glucose repression. The glucose dependence of the transport defect implies that cot2 mutations affect the link between glucose metabolism and divalent cation active transport.

The catalytic oxidation of ethane, propane, 2-methylpropane, butane, pentane, and cyclohexane has been studied over Mg3(VO4)2-MgO, Mg2V2O7, and (VO)2P2O7. These reactions produced a wide range of products ranging from alkenes, dienes, anhydrides, acids, and carbon oxides. Broadly speaking, the major products were dehydrogenation products over Mg3(VO4)2, combustion products over Mg2V2O7, and oxygen-containing organic products over (VO)2P2O7, although there are exceptions to this broad generalization. From the product selectivities, the moles of oxygen consumed per mole of alkane reacted could be calculated. These were the average oxygen stoichiometries for the reactions. They had values of about unity for ethane oxidation over VPO, about two when oxidative dehydrogenation was the predominant reaction, and about four for the other reactions studied. The selectivity patterns in terms of the formation of dehydrogenation products versus oxygen-containing products including carbon oxides were explained by assuming that there existed a selectivity-determining step, which could be the reaction of the surface alkyl species or the adsorbed alkene before its desorption. The formation of oxygen-containing products would be facilitated if the surface alkyl or adsorbed alkene could interact with the vanadium ions in two adjacent VOx units such that it could easily react with the reactive oxygen in the V-O-V bridge. The results of ethane oxidation, however, could not be explained simply by this model, and other factors needed to be considered.

The electronic structure of vanadium oxides and (VO${)}_{2}$${\mathrm{P}}_{2}$${\mathrm{O}}_{7}$ is investigated by electron-energy-loss spectroscopy. The O K pre-edge in (VO${)}_{2}$${\mathrm{P}}_{2}$${\mathrm{O}}_{7}$ is substantially different from that of vanadium oxides, whereas the profiles of V ${\mathit{L}}_{2}$/${\mathit{L}}_{3}$ transition show no significant differences between these materials. We attribute the change of the O K pre-edge to the change of local symmetry of oxygen atoms in (VO${)}_{2}$${\mathrm{P}}_{2}$${\mathrm{O}}_{7}$ and the change of hybridization from pure d-p hybridization in vanadium oxide to mixed d-p-\ensuremath{\sigma} hybridization in (VO${)}_{2}$${\mathrm{P}}_{2}$${\mathrm{O}}_{7}$. It is also inferred that the V ${\mathit{L}}_{2}$/${\mathit{L}}_{3}$ transition ratio of (VO${)}_{2}$${\mathrm{P}}_{2}$${\mathrm{O}}_{7}$ is more like that of ${\mathrm{V}}_{2}$${\mathrm{O}}_{3}$.

Vanadium phosphorus oxide (P/V = 1.1) was found to be active for NO reduction by butane to N2 at 766–816 K. The conversion increased with increasing butane concentration, increasing temperature, and decreasing NO concentration. The activity per surface vanadium ion compared favorably with other active catalytic systems, but was low in the absence of butane. Propane was also effective in reducing NO over this catalyst.

An IBM power series server ×3350 was tested by using the liquid cooling system developed by Yang et al. [3, 4, 5]. The performance of the heat pipe based direct air cooling system equipped in the original server was also tested for comparison. Both CPU core temperature and cooling system noise level were measured in the present test, he test results of liquid cooling and direct air cooling show that the maximum average core temperature to air temperature difference (at 100% CPU loading condition) is 46.5 °C for IBM original direct air cooling but only 24.8 °C for liquid cooling at heat sink fan speed of 2200 rpm. At which the noise level is 59.5 and 49.5 dB respectively. While reduced the heat sink fan speed of the liquid cooling system to 1080 rpm, the core to air temperature difference slightly increased to 28.4 °C, but the noise level reduced to 36.5 dB. The liquid cooling system required only 1/5 to 1/3.5 of power of the direct air cooling did. These results indicated that the liquid cooling system provides much higher cooling performance but lower noise and lower power consumption than the direct air cooling system for high power server.

This paper describes the development of a transmitter and receiver leveraging a combination of monolithic and hybrid integration for Datacenter applications to deliver 500Gbps over 2km on a single mode fiber. The transmitter encompasses 12 electro-absorptive modulated lasers (EMLs) with wavelength channels from 1270nm to 1380nm on a 10nm channel grid. The lasers are grouped in three (3) arrays with each array monolithically integrating four (4) EMLs operating at 43Gbps each. The three EML arrays are flip-chip bonded to a planar light-guide circuit (PLC), which serves as the mounting platform and provides the optical multiplexer function. The receiver couples the signal through an optical PLC-based de-multiplexer to twelve (12) high-speed PIN detectors with a 3dB bandwidth of more than 50GHz. The transmission tests were performed over 2km of SMF with each channel tested at 40Gbps. For the demonstration, a commercial semiconductor optical amplifier was used in front of the receiver to boost the signal. Each channel was tested to be error free to

We report compact and low-loss silicon photonic filter devices that are readily integrated with actives to enable high-aggregate bitrate WDM systems. Data is presented for a 100Gbps link over 10km.

The catalytic oxidation of ethane, propane, 2-methylpropane, butane, pentane, and cyclohexane has been studied over Mg3(VO4)2-MgO, Mg2V2O7, and (VO)2P2O7. These reactions produced a wide range of products ranging from alkenes, dienes, anhydrides, acids, and carbon oxides. Broadly speaking, the major products were dehydrogenation products over Mg3(VO4)2, combustion products over Mg2V2O7, and oxygen-containing organic products over (VO)2P2O7, although there are exceptions to this broad generalization. From the product selectivities, the moles of oxygen consumed per mole of alkane reacted could be calculated. These were the average oxygen stoichiometries for the reactions. They had values of about unity for ethane oxidation over VPO, about two when oxidative dehydrogenation was the predominant reaction, and about four for the other reactions studied. The selectivity patterns in terms of the formation of dehydrogenation products versus oxygen-containing products including carbon oxides were explained by assuming that there existed a selectivity-determining step, which could be the reaction of the surface alkyl species or the adsorbed alkene before its desorption. The formation of oxygen-containing products would be facilitated if the surface alkyl or adsorbed alkene could interact with the vanadium ions in two adjacent VOx units such that it could easily react with the reactive oxygen in the V-O-V bridge. The results of ethane oxidation, however, could not be explained simply by this model, and other factors needed to be considered.

(18)O isotope labelling studies of the CO oxidation-assisted epoxidation of propene, catalyzed by a mixture of Au/TiO(2) and TS-1, using a methanol-H(2)O solvent showed the O in the epoxide was exclusively from O(2) and not H(2)O or methanol.

The International Society for Clinical Densitometry (lSCD) is a nonprofit multidisciplinary international professional organization. The ISCD mission is to advance excellence in the assessment of skeletal health. To achieve this mission, the ISCD has conducted a number of Position Development Conferences over the past 10 yr, bringing together international experts to review and create evidence-based position statements guiding clinicians involved in the area. The Asia-Pacific (AP) Panel of the ISCD was formed to give regional input to the ISCD from the AP Region and to oversee ISCD education and certification programs in the region. An AP Panel consensus meeting recently reviewed the most current Official Positions of the ISCD in view of the different population characteristics and health standards in the region. The reviewed position statements included those for bone testing by central and peripheral devices but did not include ISCD Official Positions on Vertebral Fracture Assessment or pediatric bone mineral density.

Takayasu's arteritis is a granulomatous giant-cell arteritis of the aorta and its major branches. It primarily affects East Asian women in their second or third decade of life but is well known to affect all ethnicities across the world. Given its systemic nature, Takayasu's arteritis has multiorgan involvement, with the majority of disease morbidity related to the cardiovascular, central nervous, and renal systems. This report describes an unusual presentation of Takayasu's arteritis in a 2½-year-old boy. This is the first report in the literature describing the presence of both severe aortic regurgitation and diffuse coronary artery involvement in a patient so young.

Image transfer properties of interferometrically produced dielectric light guides are investigated. A general technique of analysis is developed. Computer calculations based on this approach are used to study the behavior of pulses traversing the guiding structures for various values of refractive index. Experimental results are obtained using photosensitized polymethyl methacrylate as the recording material. Computer results are compared with existing theory and found to be in close agreement.