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The Christian Medical and Dental Associations (CMDA) was founded in 1931 and is made up of the Christian Medical Association (CMA) and the Christian Dental Association (CDA) CMDA has a current membership of over 19,000 physicians, dentists, and other allied health professionals During and in direct response to the pressing urgencies of the COVID-19 universal pandemic of 2020 the President of CMDA commissioned a special task force to provide current and future Christian reflection and guidance on triage and resource allocation policies during pandemics and other forms of crisis surge medical conditions (e g , mass casualty situations) This is a condensed version of the CMDA special task force position statement © 2020 Center for Health in Mission All rights reserved

OBJECTIVE To investigate the relationship between Krebs von den Lungen 6 (KL-6) and CCL18 levels and the severity and progression of systemic sclerosis (SSc)-related interstitial lung disease (ILD). METHODS Patients enrolled in the Scleroderma Lung Study II (cyclophosphamide [CYC] versus mycophenolate mofetil [MMF]) were included. Baseline and 12-month plasma samples were analyzed by enzyme-linked immunosorbent assay to assess CCL18 and KL-6 levels. The forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLco) were measured every 3 months. Joint models were created to investigate the relationship between baseline CCL18 and KL-6 levels and the course of the FVC and DLco over 1 year according to treatment arm. RESULTS Baseline KL-6 and CCL18 levels each correlated with the extent of radiographic fibrosis. Levels of both CCL18 and KL-6 declined significantly at 1 year. In both treatment arms (n = 71 for CYC, n = 62 for MMF), a higher baseline KL-6 level predicted progression of ILD based on the course of FVC (P = 0.024 for CYC; P = 0.005 for MMF) and DLco (P < 0.001 for CYC; P = 0.004 for MMF) over 1 year. A higher baseline CCL18 level predicted progression of ILD based on the course of the FVC (P < 0.001 for CYC; P = 0.007 for MMF) and DLco (P = 0.001 for CYC; P < 0.001 for MMF) over 1 year, as well as mortality (P = 0.0008 for CYC arm only). CONCLUSION In a rigorously conducted clinical trial for SSc-related ILD, KL-6 and CCL18 levels correlated with ILD severity and declined with immunosuppression. Patients with higher baseline KL-6 and CCL18 levels were more likely to experience disease progression despite treatment. KL-6 and CCL18 levels could be used to identify patients with a progressive ILD phenotype who may benefit from a more aggressive initial treatment approach.

Rationale: FVC percent predicted (FVC%) is the primary outcome measure in clinical trials of systemic sclerosis interstitial lung disease. For interpretation of change in the FVC% over time, it is important to define whether these changes are clinically meaningful. Objectives:: To assess the reliability and the minimal clinically important differences (MCID) for FVC% in the Scleroderma Lung Study I and II (SLS-I and -II). Methods: Using data from SLS-I and -II (N = 300), we evaluated the test-retest reliability for FVC% (screening vs. baseline) using intraclass correlation. MCID estimates at 12 months were calculated in the pooled cohort (SLS-I and -II) using two anchors: Transition Dyspnea Index (≥change of 1.5 units for improvement and worsening, respectively) and the Medical Outcomes Short Form-36 Health Transition question (“Compared with one year ago, how would you rate your health in general now”?), where “somewhat better” or “somewhat worse” were defined as the MCID estimates. We next assessed the association of MCID estimates for improvement and worsening of FVC% with patient-reported outcomes (PROs) and computer-assisted quantitation of extent of fibrosis (QLF) and of total interstitial lung disease (QILD) on high-resolution computed tomography. Student’s t test was used to compare the mean difference in outcomes between the MCID improvement/worsening and the “no change” group. Measurements and Main Results: Reliability of FVC%, assessed at a mean of 34 days, intraclass correlation was 0.93 for the pooled cohort. The MCID estimates for the pooled cohort at 12 months for FVC% improvement ranged from 3.0% to 5.3% and for worsening from −3.0% to −3.3%. FVC% improvement by greater than or equal to MCID was associated with either statistically significant or numerical improvements in some PROs, QILD, and QLF, whereas FVC% worsening greater than or equal to MCID was associated with statistically significant or numerical worsening of PROs, QILD, and QLF. Conclusions: FVC% has acceptable test-retest reliability, and we have provided the MCID estimates for FVC% in systemic sclerosis interstitial lung disease–based changes at 12 months from baseline in two clinical trials. Clinical trial registered with www.clinicaltrials.gov (NCT00004563 for SLS-I and NCT00883129 for SLS-II).

A substantial increase in device performance and operational stability in solution processed inverted bulk heterojunction (BHJ) organic photovoltaic devices (OPV) is demonstrated by introducing a zinc oxide (ZnO) interlayer between the electron collecting bottom electrode and the photoactive blend of poly(3-hexylthiophene) (P3HT) and phenyl-C61-butyric acid methyl ester (PCBM). The structure and morphology of the dense, planar ZnO layers were controlled either by electro-deposition or spray pyrolysis techniques. Metal oxide sandwich OPV devices based on the photoactive blend on an electro-deposited ZnO interlayer with a (100) preferential crystal orientation, and using a tungsten oxide (WOx) interlayer on the opposite electrode, resulted in a remarkable increase in power conversion efficiency with a value of 4.91% under AM1.5 illumination and an external quantum efficiency of 74%. Electro-deposition of the ZnO at low temperature proved to be the most promising method for forming the ZnO interlayers, allowing the highest control of film structure and morphology, as well as leading to significantly improved device efficiency and stability.

The adsorption of hydrogen on single-walled carbon nanotubes was measured using micro-gravimetric nitrogen and hydrogen adsorption isotherms at 77 K for gas pressures of up to 1 bar (nitrogen) and 12 bar (hydrogen). Results show that surface area and hydrogen uptake depend on the concentration of the iron catalyst used for making the nanotubes. Langmuir fits to the hydrogen uptake curves clearly show two adsorption energies for each sample which we attribute to the groove site for the higher adsorption energy and to the convex tube surface for the lower energy. We also present calculations of the binding energy of hydrogen on these same sites on SWCNTs and confirm that the groove site has a significantly higher (radius-dependent) binding energy than the surface site, consistent with the experimental values. This suggests that the use of the Langmuir model is appropriate to the adsorption of H2 on activated carbons for the temperature and pressure range investigated and could be used as a rapid way of estimating the average tube radius in the sample.

TiO2 nanotubes (8–20 nm outer diameter and 3–5 nm inner diameter) grown via alkaline hydrothermal synthesis are characterised and compared to 6 nm diameter TiO2 (anatase) nanoparticles. Zeta potential, voltammetric, and titration experiments reveal that, in contrast to anatase nanoparticles (p.z.c. ca. 6), TiO2 nanotubes carry a stronger negative surface charge (p.z.c. ca. 3, acidic protons ca. 2 × 10−3 mol g−1, electrostatic cation adsorption sites in neutral solution ca. 7 × 10−5 mol g−1) and, under neutral conditions, offer electrostatic binding sites for cations.When immobilised onto an inert boron-doped diamond substrate, TiO2 nanotubes show electrochemical reactivity due to reversible Ti(IV) reduction, which is very similar to that observed for anatase nanoparticles. Three cationic redox systems, Meldola’s blue, Ni2+, and cytochrome c, are immobilised on the TiO2 nanotube surface; the binding ability and the number of binding sites are quantified voltammetrically. Redox proteins, such as cytochrome c, adsorb readily and irreversibly. Well-defined voltammetric signals for the immobilised protein are observed in an aqueous buffer. TiO2 nanotubes are shown to be novel, inert substrates for both inorganic and biological electrocatalysts. Keywords: TiO2, Nanotubes, Catalysis, Cytochrome c, Ethanol, Meldola’s blue, Sensors

Langmuir–Schaefer (LS) films of poly(ortho-anisidine) (POAS) were fabricated by utilizing water and water acidified HCl as subphases, respectively. The uniformity of the films formation and the doping with Nafion were verified by UV–Vis spectroscopy. The morphology and the thickness of the POAS, HCl post-doping POAS and Nafion post-doping POAS LS films were investigated using atomic force microscopy. The electrochemical properties of POAS LS films, HCl post-doping POAS and Nafion post-doping POAS were investigated and compared with our previously published work. The electrochemical switching time of HCl post-doping POAS and Nafion post-doping POAS LS films were also estimated. Keywords: Poly(ortho-anisidine), Nafion, Langmuir–Schaefer, Conducting polymers, Electrochemistry

The voltage dependence of light emission from illuminated porous silicon samples immersed in solutions containing persulfate anions was studied. It is reported that the signal obtained is not simply the sum of the individual photoluminescence and electroluminescence signals. The ‘cross-talk’ observed is discussed in terms of a previously proposed mechanism of photoluminescence and electroluminescence potential tuning. It is shown that a mechanism involving radiative quenching by an Auger process is consistent with the results obtained. Keywords: Porous silicon, Electroluminescence, Photoluminescence, Potential tuning

In this paper we examine the claim that the power law distribution of burst lifetimes in the AE index is evidence that the magnetosphere is a Self-Organized Critical (SOC) system. To do this we compare the burst lifetime distributions of the AU and |AL| indices with those of the υBs and e solar wind input functions. We show for the first time that both the υBs and e burst lifetime distributions are of power law form with an exponential cut-off, consistent with the solar wind being an SOC system. Furthermore, the power law of the e burst lifetime distribution is not significantly different to that of the AU and |AL| indices, indicating that this scale-free property of the AE indices could arise from the solar wind input and may not be an intrinsic property of the magnetospheric system. We discuss the implications of this result for SOC theories of the magnetosphere.

Poly(arylene ether) main-chain phosphonium ionomers were successfully synthesized and characterized. The reaction scheme involved first preparing the poly(arylene ether phosphine oxide) by a nucleophilic step or condensation polymerization of bisphenolates on activated aryl halides, wherein phenyl phosphine oxide was the activating group. High-molecular-weight, tough, film-forming polymers were produced with glass transition temperatures of 200°C or higher. The resulting materials were successfully reduced using phenylsilane in refluxing chlorobenzene. The derived phosphine or phosphine/phosphine oxide copolymer was reacted with alkyl halides to produce the phosphonium salts. The resulting materials showed enhanced hydrophilicity and in some cases could be successfully dispersed in water. In addition, chromophores such as Methyl Orange and Methyl Red were combined with the backbone ionomer to produce new film-forming, ionically linked species. The materials are of general interest for situations where water-dispersible intermediates, e.g. coatings, fiber sizings etc. are required. The phosphonium salts can be converted back to the phosphine oxide in fairly high yields by simple thermal methods and in quantitative yield by chemical methods (e.g. the Wittig reaction). © 1998 John Wiley & Sons, Ltd.

Hydrolytically stable phosphorus-containing monomers, such as 4,4'-bis(fluorophenyl)methylphosphine oxide (BFPMPO), 4,4'-bis(hydroxyphenyl)methylphosphine oxide (BOHPMPO), and 4,4-bis(hydroxyphenyl)phenylphosphine oxide (BOHPPO), were synthesized and used in nucleophilic aromatic substitution polycondensation to prepare poly(arylene ether phosphine oxide) engineering thermoplastics. The synthesis and characterization of these novel polymers are described. It was determined that by incorporating the phosphine oxide moiety into the polymer backbone, certain properties of the resulting poly(arylene ether) were substantially improved, such as an increase in T g , thermal stability in air, modulus, and char yield compared with control poly(arylene ether sulfone)s. The high char yields obtained for these polymers in air along with observed intumescence indicates that these materials have improved fire resistance. Preliminary cone calorimetry measurements support this conclusion.

The phenomena of electron injection occurring during anodic dissolution of Si are studied in a dual-electrolyte transistor-like geometry: variations in the population of minority carriers of a p-Si wafer resulting from injection are detected by a second liquid junction on the back side of the electrode. Investigations in acidic fluoride media show that electrons injected during porous silicon formation undergo ready surface recombination. A significant back current is detected in the electropolishing regime, indicating that important injection processes occur even under the latter conditions. Analogous investigations at p-Si in 2 M KOH show electron injection in correspondence to the oxidation peak leading to passivation. Results are compared with literature data and discussed with reference to current models of silicon dissolution.

A novel and convenient method of monitoring the internal surface area of porous silicon layers grown on either n-type or p-type silicon is described. The method involves measurement of the interfacial capacitance under conditions where electrons accumulate at the electrode surface. The technique has been used to study the growth and leaching of porous silicon layers in hydrofluoric acid/ethanol. The changes in the interfacial capacitance have been related to the development of photoluminescence.

Voltage-dependent tuning of photoluminescence (PL) and electroluminescence (EL) spectra of porous silicon layers grown on n+ and n− substrates has been studied using electrolyte contacts. It has been demonstrated that PL and EL tuning occur under accumulation conditions. A mechanism that explains both PL and EL tuning is proposed on the basis of a kinetic; “scheme of squares” that considers incremental electron injection into quantum-confined particles, leading to Auger quenching of photoexcited or electrochemically generated electron-hole pairs. The tuning effects are predicted to occur as a consequence of the dependence of electron accumulation on the energy of the conduction band, which is turn related to particles size. PL and EL spectra have been simulated for an ensemble of particles of different sizes, and it is shown that the model correctly predicts all the experimentally observed characteristics of the voltage tuning.

Basic fibroblast growth factor (bFGF) is a potent endothelial cell mitogen found in a variety of normal and tumor tissues. bFGF lacks a classical amino-terminal signal sequence and is not readily detectable in plasma from normal subjects. In earlier studies we showed increased bFGF-like mitogenic activity for parathyroid-derived endothelial cells and (increased) bFGF immunoreactivity (0.24-1.28 ng/mL) in plasma of subjects with multiple endocrine neoplasia type 1 (MEN-1). In the present study we examined the proliferative activity of MEN-1 and normal plasmas (applied to protein-A columns) in calf pulmonary artery endothelial cells. Protein-A-eluted activity in plasma from MEN-1 prolactinoma plasma exceeded activity from normal and MEN-1 nonprolactinoma plasma in three of eight MEN-1 subjects with untreated or recurrent prolactinoma. Protein-A-eluted active fractions from MEN-1 prolactinoma plasma had several properties of an immunoglobulin G, including affinity for antihuman immunoglobulin G (IgG) agarose, sensitivity to thiols, and (prepared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions) apparent mol wt corresponding to those of the heavy and light chains of IgG. The IgG fraction of MEN-1 prolactinoma plasma had far more activity in endothelial cells than did optimal concentrations of known growth factors or conditioned medium from prolactinoma cells. Endothelial cell bioactivity in protein-A-eluted fractions from MEN-1 prolactinoma plasma was neutralized 70% by rabbit antibodies to intact bFGF. These results imply novel growth stimulatory bFGF-like autoantibodies in a subset of MEN-1 patients with prolactinoma.

The extension of spectrofluorimetric hydrodynamic voltammetry for the study of heterogeneous reactions occurring at solid/liquid interfaces is described. In particular the rate of migration of the cationic species H+ and K+ within a thin organic film containing the fluorescent probe N-(5-fluoresceinthiocarbamoyl)-1,2-dihexadecanoyl-sn-glycero-3- phosphoethanolamine (F362) as the triethylammonium salt dispersed in a large excess of 1-trimethylammonium 2,3-di [C14-C18 acyloxy] propane chloride (HEQCl) may be followed through the quenching of the F362 fluorescence by the cation. Two different types of experiment are described. In the first the organic film is supported on the silica wall of a channel flow cell, and the migration of H+ cations into the film, induced through their stepwise formation at an electrode located upstream of the organic layer. In the second the film is coated onto the channel electrode surface, and migration of K+ ions induced by changes in the electrode potential. In each case the diffusion coefficient of the cation within the membrane may be inferred from the fluorescence transient. © 1994 American Chemical Society.

Computational thermodynamics using density functional theory ab initio codes is a powerful tool for calculating phase diagrams. The method is usually applied at the standard pressure of p = 1 bar and where the Gibbs energy is assumed to be equal to the Helmholtz energy. In this work, we have calculated the Gibbs energy in order to study the release temperature and phase modifications of MgH(2) at high pressures up to 10 GPa (100 kbar). The isotopic substitution of hydrogen with deuterium (or tritium) does not bring about any strong effects on the phase diagram. These considerations are of extreme importance for (i) the synthesis of novel substitutional magnesium based materials at high pressure and (ii) the determination of the correct reference states for the calculation of phase diagrams at high pressure. The calculated results are compared with experimental data obtained with an in situ neutron diffraction measurement.

The transient electron paramagnetic resonance spectrum of pre-reduced, perdeuterated cells of the photosynthetic bacterium Rhodospirillum rubrum is analysed using a quantum mechanical description of the spin dynamics. The spectrum, of the reduced secondary electron acceptor (a ubisemiquinone anion, Q−), displays anisotropic electron spin polarization, which is seen to arise principally from a combination of three interactions: the dipolar coupling of Q− to the reduced primary electron acceptor (a bacteriopheophytin anion, I−), the g-tensor anisotropy of Q− and the electronic exchange interaction between I− and the oxidised form of the primary electron donor (a bacteriochlorophyll dimer cation, P+). Using parameter values for Rhodobacter sphaeroides, it emerges that the P+I− exchange interaction JPI must be positive to account for the phase of the polarization, that is, the singlet state of the primary radical pair P+I− must lie higher in energy than the triplet. This finding puts restrictions on the permissible values of the energy gap between P∗ (the excited singlet state of P) and P+B−A (where BA is the accessory chlorophyll) and gives information on the mechanism of primary charge separation, P∗I → P+I−.

Poly(arylene ether) main-chain phosphonium ionomers were successfully synthesized and characterized. The reaction scheme involved first preparing the poly(arylene ether phosphine oxide) by a nucleophilic step or condensation polymerization of bisphenolates on activated aryl halides, wherein phenyl phosphine oxide was the activating group. High-molecular-weight, tough, film-forming polymers were produced with glass transition temperatures of 200°C or higher. The resulting materials were successfully reduced using phenylsilane in refluxing chlorobenzene. The derived phosphine or phosphine/phosphine oxide copolymer was reacted with alkyl halides to produce the phosphonium salts. The resulting materials showed enhanced hydrophilicity and in some cases could be successfully dispersed in water. In addition, chromophores such as Methyl Orange and Methyl Red were combined with the backbone ionomer to produce new film-forming, ionically linked species. The materials are of general interest for situations where water-dispersible intermediates, e.g. coatings, fiber sizings etc. are required. The phosphonium salts can be converted back to the phosphine oxide in fairly high yields by simple thermal methods and in quantitative yield by chemical methods (e.g. the Wittig reaction). © 1998 John Wiley & Sons, Ltd.

The formation of amorphous silicon in crystalline silicon by bombardment with light (Si) and heavy (Xe) ions has been investigated by transmission electron microscopy with in situ ion irradiation. Experiments have been carried out at room temperature and low temperature (50 K) and the results are compared to a simple numerical model for amorphization. The results indicate that the amorphization mechanisms for both irradiations are heterogeneous in nature and that numerous overlaps of the collision cascade are generally required to render the crystal amorphous. Following from this, the nature of the material within the confines of collision cascades will be discussed and it will be shown that the individual cascade volume is not necessarily amorphous as previously described in the scientific literature but contains varying degrees of damage depending on the energy deposited within the cascade.

The electrochemical oxidation of Langmuir-Blodgett films of n-doxyl-stearates (n = 5, 7, 12, 16; present as their cadmium salts) on indium tin oxide electrodes has been studied. The n = 12 species gives cyclic voltammograms (CVs) that reveal split peaks consistent with the formation of an ordered partially oxidized layer with a structure controlled by interactions of longer range than nearest neighbor.

We have shown that administration of the antifibrotic agent cis-4-hydroxy-L-proline (cHyp) to rats at the onset of exposure to hypoxia prevents collagen accumulation in pulmonary arteries and the rise in pulmonary blood pressure. In this experiment, we tested whether cHyp is effective when administered after hypertension was already established. Rats were exposed to hypoxia (10% O2) for 21 days. Groups were hypoxic animals treated with cHyp (200 mg/kg sc twice daily) on days 10-21 (hypoxic cHyp) and saline-injected hypoxic animals (hypoxic). On day 21, we measured mean right ventricular pressure, hematocrit, collagen content of main and intrapulmonary arteries, and wall thickness of arterioles. Treatment reduced right ventricular pressure from 21 +/- 1 to 17 +/- 1 mmHg (P less than 0.05), hematocrit from 66 +/- 1 to 56 +/- 1% (P less than 0.05), hydroxyproline content of intrapulmonary arteries from 30 +/- 3 to 11 +/- 2 micrograms/vessel (P less than 0.05), and wall thickness from 27 +/- 3 to 16 +/- 2 microns (P less than 0.05). These results show that vascular collagen content is increased in established pulmonary hypertension and that cHyp treatment is effective in partially preventing the hemodynamic, structural, and biochemical changes if started after pulmonary hypertension is established. cHyp may also affect the rheological properties of blood.

A novel and convenient method of monitoring the internal surface area of a porous silicon layer formed on an n‐type substrate has been developed. The technique has been employed during electrochemical growth and subsequent chemical leaching of porous silicon layers in hydrofluoric acid/ethanol. The method involves periodic interruption of the anodization current to allow in situ measurement of the interfacial capacitance under forward bias using a triangular voltage wave form. The observed evolution of the internal surface area is related to the development of photoluminescence.

We calculate the probability density functions P of burst energy e, duration T, and interburst interval tau for a known turbulent system in nature. Bursts in the Earth-Sun component of the Poynting flux at 1 AU in the solar wind were measured using the MFI and SWE experiments on the NASA WIND spacecraft. We find P(e) and P(T) to be power laws, consistent with self-organized criticality (SOC). We find also a power-law form for P(tau) that distinguishes this turbulent cascade from the exponential P(tau) of ideal SOC, but not from some other SOC-like sandpile models. We discuss the implications for the relation between SOC and turbulence.

Measurement of vascular cell proliferation in animal models of hypertension is currently accomplished by demonstrating [(3)H]-thymidine ([(3)H]-dT) incorporation into DNA using autoradiography. This method, however, is labor intensive, requires radioactivity, and is limited by the inherent difficulty in discriminating labeled and unlabeled cells. To address these limitations, a flow cytometric-based method is described utilizing incorporation of 5-bromo-2'-deoxyuridine (BrdU) into DNA of nuclei isolated from blood vessels.Pulmonary hypertension was induced in rats by exposure to 10% O(2) (hypoxia) for varying periods of time. Pulmonary arteries and aorta from rats injected with BrdU prior to sacrifice were isolated, fixed with 10% formalin, and digested with Protease XIV. The intact nuclei liberated by this treatment were successively treated with HCl/Triton X-100 and sodium borate. Processed nuclei were probed with a BrdU-specific fluorescein-conjugated antibody, and the percentage of BrdU staining cells was determined using flow cytometry.An approximately 20-fold increase in BrdU-positive cells at 3 days of hypoxia in pulmonary arteries (relative to control) with no change in aorta was observed. These results were similar to previous studies using [(3)H]-dT labeling.Flow cytometric determination of cell proliferation in blood vessels is a simple, objective technique that may facilitate measurement of cell proliferation in animal models of vascular disease.

The role of genomic imprinting in the development of tumors with defective retinoblastoma protein function remains debatable. Disruption of either parental allele of the murine retinoblastoma (Rb) gene is sufficient for spontaneous melanotroph carcinogenesis to occur in almost all Rb+/- mice. Nevertheless, mice with a disrupted paternal Rb allele succumb to tumors faster. In these animals, the first foci of proliferating atypical Rb-negative cells appear and progress to overtly malignant tumors earlier. In addition, more foci of early atypical proliferation are observed. In Rb+/- mice, however, parental origin influences neither Rb expression nor proliferation of melanotrophs. Accordingly, Rb-/- mice rescued by the human RB transgene transmitted either paternally or maternally have similar survival rates. Taken together, the data point to the existence of an imprinted gene in an Rb-linked locus. The function of this gene affects the onset of melanotroph carcinogenesis, likely by controlling preferential survival of the cells with secondary loss of the Rb maternal allele. Rb+/- mice may serve as useful models to identify and characterize genomic imprinting mechanisms influencing carcinogenesis associated with Rb loss of function.

Recent studies have shown that extremely dilute HCl mixtures can offer considerable cost savings and improved particle performance relative to traditional SC2 formulations. This work indicates, however, that extreme levels of dilution are not necessary to secure many of the benefits suggested for dilute HCI. Significant benefit can be attained by pursuing moderate concentration and temperature alterations. In this study, an intermediate dilution and temperature reduction are evaluated to assess potential production advantage. Comparison of a 1:1:20 formulation at 60 C is made to a more traditional 1:1:6 mixture at 85 C. The impact of the chemistry and temperature alteration on peroxide decomposition rate is shown to be dramatic. While initial pour-up ratios suggest that the dilute recipe could require 1/3 as much peroxide as the traditional chemistry, chemical savings are significantly more dramatic due to the ability of the solution to maintain concentration over time. An additional benefit associated with the alternative pour-up is a marked reduction in particle levels on silicon surfaces; particle levels on thermal oxide wafers have not shown the same trend. VPD-ICPMS measurements are used in this study to illustrate that the recipe change results in comparable metallic removal efficiency.

Nutritional impairment can adversely affect the respiratory system. The structure of the lung is altered by severe calorie-protein restriction in rodents producing an emphysema-like lesion after several weeks of severe caloric restriction. Biochemical and morphological evidence suggests destruction of collagen and elastin in nutritional emphysema. Impaired lung growth may explain the biochemical changes in growing animals. Although the molecular basis of nutritional emphysema is not known, altered gene expression by nutrients affects several metabolic pathways, and examples of the effects of nutrients on gene expression are given. Nutritional emphysema in animals may be relevant to humans because malnutrition may accelerate the progression of the disease in patients with advanced emphysema.

We have constructed several rat tropoelastin minigene recombinants encoding the complete sequence of rat tropoelastin, two isoforms of rat tropoelastin and a truncated tropoelastin lacking the domains encoded by exons 19-31 of the rat gene. Coding and non-coding domains in all these recombinants were placed under the transcriptional control of 3 kb of the promoter domain of the rat tropoelastin gene. These minigenes were used to prepare a total of 28 separate founder lines of transgenic mice. A species-specific reverse-transcriptase polymerase chain reaction (RT-PCR) assay was established to demonstrate the synthesis of rat and mouse tropoelastin mRNA in several tissues obtained from both neonatal and adult transgenic mice. Thermolytic digestion of insoluble elastin isolated from several neonatal mouse tissues revealed the presence of rat tropoelastin peptides in progeny from all those founder mice in which detectable levels of rat tropoelastin mRNA were noted. Phenotypic and histopathological assessment of transgenic and non-transgenic animals revealed the development of two diverse elastic tissue disorders. The progeny of two separate founder lines overexpressing the rat tropoelastin isoform lacking exon 33, developed an emphysematous phenotype in early adulthood. In contrast, transgenic mice, in which expression of the truncated rat tropoelastin minigene lacking exons 19-31 had been observed, died of a ruptured ascending aortic aneurysm. Tropoelastin gene mutations, therefore, will result in heritable disorders of elastic tissue. Moreover, different mutations in the tropoelastin gene will be responsible for very different abnormalities in elastic tissue function.

As knowledge of the genes and molecular events involved in specific kidney disorders expands, so do the potential applications for treating the disorders on fundamental levels. Progress in gene therapy for genetic diseases for which molecular events are simpler or better characterized has already been substantial. In addition, exciting first steps in targeting genes specifically to the kidney have emerged, although much work in defining kidney-specific genes and gene regulatory elements still needs to be done. To provide a framework for understanding the concepts and problems involved in gene therapy, we will discuss basic aspects of gene structure and regulation, gene delivery vectors, steps necessary to achieve tissue- and cell-specific expression of delivered genes, and some present and future applications of gene therapy in kidney diseases.

The retinoblastoma gene (RB) is the prototype of the tumor suppressor genes, which play critical roles in the genesis of cancer in humans. Mouse models created through gene knock-out and transgenic methods were established for exploring and manipulating RB in vivo. These models and several other pieces of evidence have shown that the retinoblastoma protein (Rb) plays dual roles in gating cell cycle progression and promoting cellular differentiation. The molecular mechanisms involved in these roles are becoming more obvious in some biological systems: Rb sequesters the transcription factor of E2F to regulate entry of cell cycle but enhances the activities of another class of the transcription factors, exemplified by NF-IL6, to initiate terminal cellular differentiation. Thus, the Rb protein can serve as a mediator for extracellular signals of growth or differentiation. The fundamental question of why only limited cell types are susceptible to tumor formation when Rb expression is lost, however, remains unanswered at present.

The retinoblastoma gene (RB) is a classical tumor suppressor. Several studies have shown that RB dosage is important in determining biological effects. To explore the effect of RB dosage on susceptibility to cancer, three groups of congenic C57BL/6 mice, each of which expresses a different amount of Rb protein from one, two, or three alleles, were treated at postnatal day 12 with a single 60-mg/kg body weight i.p. dose of the DNA-alkylating agent N-ethyl-N'-nitrosourea (ENU). Mice heterozygous for the RB gene developed characteristic pituitary tumors with nearly complete penetrance, whether or not they were treated with ENU. Tumors initiated earlier or progressed more rapidly, however, in ENU-treated mice. Furthermore, although mice treated with ENU had a higher incidence of several nonpituitary tumors compared with untreated controls, no significant differences in the incidence of these tumors were found between wild-type mice (mRB+/+), mice carrying only one normal RB allele and deficient in Rb protein expression (mRB+/-), and mice overexpressing Rb protein from two normal murine RB alleles and a human RB transgene (mRB+/+, hRB+/-). These studies underscore the tissue and mechanistic specificity of tumor predisposition caused by an inherited 50% reduction in RB dosage and indicate that most ENU-induced tumors occur independent of RB inactivation. Nonetheless, they suggest that certain point mutations induced by ENU may participate in the sequence of molecular steps involved in progression of tumor-prone, RB-deficient cells to the fully malignant state.

Progressive systolic dysfunction of the heart results in a broad array of physiologic compensatory mechanisms within the kidney. These mechanisms are primarily stimulated by diminution of the effective arterial blood volume and resultant activation of a biochemical cascade of neurohormonal responses, including activation of the renin-angiotensin-aldosterone system and enhanced release of norepinephrine, arginine vasopressin, prostaglandins, endothelin, and atrial natriuretic peptide. The interaction of these neurohormonal systems within the kidney is complex. Vasoconstriction induced by angiotensin II, arginine vasopressin, and catecholamines may decrease renal perfusion by both endocrine and neural actions. In contrast, systemic pressures may rise, which may facilitate perfusion.

Systolic dysfunction of the heart represents a state of "prerenal" azotemia, in which the excess of total body salt and water is redistributed to venous and interstitial fluid compartments. This results in a diminished effective circulating blood volume and thereby decreases tissue perfusion. The kidneys perceive the ineffective circulating volume and employ a complex series of interconnected hemodynamic and neurohumoral effector mechanisms to restore "adequate" perfusion. This is done by reclaiming a greater fraction of filtered sodium and water and elevating systemic vascular resistance to keep perfusion pressure to vital organs constant despite diminished cardiac output. Knowledge of the physiologic compensatory responses that occur in the kidneys of heart failure patients allows clinicians to develop a logical treatment plan. This knowledge should also help avoid a therapeutic misadventure by making it possible to exclude drugs known to adversely affect renal function in patients with a failing heart and poorly compensating kidneys.

It is shown that electron spin polarization can be used to probe the anisotropy of singlet-triplet interconversion of radical pairs involved in photosynthetic charge separation. Anisotropic polarization may be observed with non-oriented reaction centres, provided an anisotropic interaction (e.g. zero-field splitting or g-tensor anisotropy) produces resolvable structure in the EPR spectrum of the reaction intermediates. Two examples, both for prereduced bacterial reaction centres, are discussed: (i) the triplet state of the primary donor (a bactenochlorophyll dimer) and (ii) the reduced secondary acceptor (a semiquinone). Computer simulations are used to understand the observed behaviour and yield information on the magnetic and electronic interactions involved in electron transport. © 1991 Springer.

We administered antifibrotic agent beta-aminopropionitrile (BAPN) to rats exposed to 10% O2-90% N2 for 3 wk to prevent excess vascular collagen accumulation. Groups of Sprague-Dawley rats studied were air breathing, hypoxic, and hypoxic treated with BAPN, 150 mg/kg twice daily intraperitoneally. After the 3-wk period, we measured mean right ventricular pressure (RVP), the ratio of weight of right ventricle to left ventricle plus septum (RV/LV + S), and hydroxyproline content of the main pulmonary artery (PA) trunk. Hypoxia increased RVP from 14 to 29 mmHg; RVP was 21 mmHg in hypoxic BAPN-treated animals. Hypoxia increased the RV/LV + S ratio from 0.28 to 0.41; the ratio was 0.32 in hypoxic BAPN-treated animals. Hypoxia increased PA hydroxyproline from 20 to 239 micrograms/artery; hydroxyproline was 179 micrograms/artery in hypoxic BAPN-treated animals. Thus BAPN prevented pulmonary hypertension, right ventricular hypertrophy, and excess vascular collagen produced by hypoxia. We conclude that vascular collagen contributes to the maintenance of chronic hypoxic pulmonary hypertension.

The effects of analgesic doses of morphine on ventilation, arterial blood gas tensions, chemical control of breathing, and the ventilatory response to exercise were studied in six normal subjects. After administration of 0.2 mg/kg morphine, resting ventilation decreased primarily because of a reduction of tidal volume. Ventilatory responses to carbon dioxide and hypoxia were significantly reduced to one-half and one-third of control, respectively. Ventilatory responses at any given level of exercise were significantly reduced after morphine. However, since oxygen consumption during exercise was similarly reduced after morphine, the relationship between ventilation and metabolic rate during steady-state exercise was not altered by the drug. In addition, morphine prolonged the attainment of steady-state ventilation in four of the six subjects, similar to that reported for chemodenervated subjects. The findings suggest that blunting of chemoreception for hypoxia and hypercapnia has no effect upon the link between metabolic rate and ventilation during steady-state exercise, but the hypoxia chemoreflex may be involved in determining the dynamic characteristics of the response.

Chronic hypoxic pulmonary hypertension in the rat is associated with increased collagen and elastin in the pulmonary artery. We investigated whether excess vascular collagen contributes to chronic hypoxic pulmonary hypertension by administering the proline analogue cis-4-hydroxy-L-proline (cHyp), an agent relatively specific for inhibiting collagen production, to rats exposed to chronic hypoxia. Sprague-Dawley rats (weighting 200 g) were exposed to air or hypoxia (10% O2-90% N2) for 3 wk. Groups studied were: air-exposed injected with saline, air-exposed injected with cHyp, hypoxic injected with saline, and hypoxic injected with cHyp. At the end of 3 wk, we measured mean right ventricular pressure (RVP) of animals breathing room air and hydroxyproline and desmosine contents of the main pulmonary artery trunk. Hypoxia increased RVP from 13 +/- 1 to 27 +/- 1 mm Hg (p less than 0.05); cHyp partially prevented this increase since RVP was 17 +/- 1 mm Hg (p less than 0.05). There was no effect of cHyp on cardiac output. Hypoxia increased collagen from 0.9 +/- 0.1 to 2.0 +/- 0.3 mg/artery (p less than 0.05); cHyp completely prevented this increase since collagen was 1.0 +/- 0.2 mg/artery (p less than 0.05). Hypoxia increased elastin from 1.1 +/- 0.1 to 2.4 +/- 0.2 mg/artery (p less than 0.05); cHyp had no apparent effect since elastin was 2.1 +/- 0.1 mg/artery. Also, cHyp did not affect RVP or vascular collagen or elastin in air-breathing animals. The cHyp treatment prevented luminal narrowing and thickening of arteriolar walls by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)