Effect of acute increases in filtered HCO3- on renal hydrogen transporters: II. H(+)-ATPase

Adaptive increases in renal bicarbonate reabsorption occur in response to acute increases in filtered bicarbonate (FLHCO3). In a previous study, we showed that an increase in FLHCO3 induced by plasma volume expansion increased the Vmax for Na+/H+ exchange activity in renal cortical brush border membrane vesicles (BBMV), providing a potential mechanism for the adaptive increase in HCO3- reabsorption. The present studies were undertaken to determine whether the increase in FLHCO3 induced by plasma expansion also stimulates the other major H+ transporter in cortical BBMV, the H(+)-ATPase. H(+)-ATPase activity was assessed in BBMV obtained from hydropenic and plasma expanded Munich-Wistar rats, using a NADH-linked ATPase assay. H(+)-ATPase activity was measured as the ouabain and oligomycin-insensitive, bafilomycin A1-sensitive component of total ATPase activity. Acute plasma expansion doubled single nephron FLHCO3, and this change was associated with a 64% increase in the Vmax for H(+)-ATPase activity, with no change in apparent Km. The Vmax for H(+)-ATPase activity correlated directly with whole kidney GFR and FLHCO3 (r = 0.68 and 0.72, respectively), and with single nephron GFR and FLHCO3 (r = 0.76 and 0.80, respectively). Thus, the mechanism for the adaptive increase in proximal tubular HCO3- reabsorption that occurs in response to acute increases in FLHCO3 appears to be related to increased activity of both H(+)-ATPase and Na+/H+ exchange in the apical membrane of the proximal tubule epithelium.     

Scientific and artistic investigation of multi-dimensional fractals on the AT & T pixel machine

The pipelined architecture and parallel organization of the AT&T Pixel Machine image computer are described and demonstrated with applications for the visualization of multidimensional fractals, particularly linear fractals and quaternion/ stacked Julia sets. Techniques for pushing the Pixel Machine to its peak abilities are described and apply to more recent parallel image computers as well.     

Robust crossfeed design for hovering rotorcraft

Control law design for rotorcraft fly-by-wire systems normally attempts to decouple the angular responses using fixed-gain crossfeeds. This approach can lead to poor decoupling over the frequency range of pilot inputs and increase the load on the feedback loops. In order to improve the decoupling performance, dynamic crossfeeds should be adopted. Moreover, because of the large changes that occur in the aircraft dynamics due to small changes about the nominal design condition, especially for near-hovering flight, the crossfeed design must be ‘robust’. A new low-order matching method is presented here to design robust crossfeed compensators for multi-input, multi-output (MIMO) systems. The technique minimizes cross-coupling given an anticipated set of parameter variations for the range of flight conditions of concern. Results are presented in this paper of an analysis of the pitch/roll coupling of the UH-60 Black Hawk helicopter in near-hovering flight. A robust crossfeed is designed that shows significant improvement in decoupling perfomance and robustness over the fixed-gain or single point dynamic compensators. The design method and results are presented in an easily used graphical format that lends significant physical insight to the design procedure. This plant precompensation technique is an appropriate preliminary step to the design of robust feedback control laws for rotorcraft.     

ENHANCING THE CREATIVITY OF REENGINEERING Techniques for Making IS More Creative

Industries in the US continue to lose ground in international competition. If IS is to help change that trend, it will have to become more creative. Creativity improvement programs are being introduced in other areas of the company— now is the time for IS organizations to follow suit.     

Effects of the glucocorticoid agonist, RU28362, and the antagonist RU486 on lung phosphatidylcholine and antioxidant enzyme development in the genetically obese Zucker rat

The biochemical maturation of the lung in late gestation and in the young animal is regulated by glucocorticoids. The present study was aimed at dissociating the different glucocorticoid receptor sites involved in these regulatory functions. The obese Zucker rat was selected as a model for this study as it exhibits hypersensitivity to glucocorticoid hormone action by virtue of its elevated receptor numbers and activity. Two synthetic steroid analogues were administered to obese animals; RU28362, a specific type II receptor agonist, and the type II antagonist RU486. RU28362 promoted a strong catabolic effect, which was associated with reduced food intake and the abolition of growth in the rats. The agonist, RU28362, attenuated developmental increases in antioxidant enzyme activities, and altered the growth of the tissue. At the age studied, development of the lung phosphatidylcholine (PC) system was almost complete, but RU28362 increased disaturated PC 16:0/16:0 concentrations by almost 2-fold, and altered the molecular composition of total pulmonary PC. RU486 attenuated the growth of the rats and reduced their food intake. Treatment with the type II antagonist attenuated lung growth and increased the activities of pulmonary copper zinc (Cu/Zn) and manganese (Mn) superoxide dismutases. RU486 had no effect on lung PC concentrations and molecular composition. The data suggest a role for type I glucocorticoid receptors in the regulation of the antioxidant enzyme system in the lung, as type II antagonism will channel endogenous glucocorticoid binding to the type I site. Type II receptor binding would appear to play a role in regulating the lung PC content.     

Problems in monitoring dust levels within mines

The collection of dust samples in mines is a multifaceted problem. Initially, one must define the situation being sampled and the purpose of the sampling in order to establish an appropriate sampling plan, including specification of the type of mining process (surface vs. underground, metal vs. nonmetal vs. coal) as well as the mining system employed (equipment). The next step is to decide the nature of the hazard being monitored (i.e., dust depositing in alveolar air spaces entails use of respirable dust sampling, upper airways entails thoracic-fraction sampler, and systemic effects call for an inhalable-fraction sampler) in order to select the appropriate sampler. Deciding on a particular sampling strategy is a complex issue involving federal regulations as well as compliance.     

Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7

Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease.     

On the formation and stability of dislocation patterns—I: One-dimensional considerations

By distinguishing among mobile and immobile dislocations and operating within the framework of continuum mechanics it is possible to derive a set of partial differential equations of the diffusion-reaction type for the evolution of dislocation species. On examining the competition between gradient dependent terms modelling the motion of dislocations and nonlinear terms modelling their interactions, it is shown that stable solutions are possible. The wavelength turns out to be a material property in agreement with observations. The discussion is limited to one dimension, that is to glide of straight dislocations in the slip direction, and the model corresponds physically to the ladder-like structure of persistent slip bands.