cssi/SciSciGPT-SciSciNet huggingface dataset:
One Cold Autumn Day

Behavioral change is at the heart of effective primary care, but when patients don’t change, how do we account for our days? In this personal essay, I relate an encounter with a patient who wants to quit smoking, lose weight, and control her diabetes. I am discouraged when she deflects my recommendations, but a colleague’s comment encourages a deeper inquiry. Knowing the patient’s story and deepening the conversation, however, do not guarantee change. The experience reminds me why patience, humility, and faith are core values of the primary care physician.
Effective Hf-Pd Co-doped β-NiAl(Cr) coatings for single-crystal superalloys

Abstract Cyclic oxidation behavior of β NiAlCr coatings was investigated at 1150 °C with emphasis on effective Pd + Hf and Pt + Hf co-doping composition and the concomitant phase transformations and interdiffusion of Pd and Pt into the substrate. Coatings with compositions in the range of Ni–(33–39)Al–5Cr–(2–5)Pd/Pt were deposited on Rene N5 single-crystal substrates and subjected to long-term cyclic oxidation. The Pt + Hf- and Pd + Hf-modified overlay coatings exhibited comparable oxidation kinetics and matched the range of oxidation behavior exhibited by the standard Pt-aluminide coating. In particular, additions of about (2–5)Pd+(0.15–0.3)Hf and (2–5)Pt+(0.15–0.3)Hf among the studied composition range exhibited long lifetimes of >2000 oxidation cycles. A positive synergistic effect between Pd–Hf and Pt–Hf was clearly observed when comparing the lifetimes of β NiAlCr-Pd and β NiAlCr-Pt quaternary coatings with the quinary coatings. Transformations from β → 3R + 7R-martensites at low temperature and β → γ′ → γ + γ′ at high temperature occurred in both Pd- and Pt-modified coatings due to Al depletion to substrate and surface oxide. A greater depletion of Pd to the substrate compared to Pt was observed at 1150 °C compared to 1100 °C; the interdiffusion coefficients were consistent with those measured in NiAl–NiAl + Pt/Pd diffusion couples. These results are very encouraging in supporting the exploration of Pd-modified coating supplanting the currently used, expensive Pt-based coatings.
Between-measure consistency in social-skills assessment

The purpose of the present study was to assess the between-measure consistency of general and specific social-skills assessment strategies. Nineteen mentally retarded adults were assessed using both common and newly devised measures of social skills: (1) specific (molecular) behavior ratings from role-play assessments, (2) general (molar) ratings based on the role plays, staff (3) molar and (4) molecular predictions of client social skills use in the described role-play situations, (5) peer sociometric ratings, and molecular in vivoobservations conducted in (6) cafeteria and (7) party settings. For all molecular measures, the subjects were assessed on eye contact, response relevance, response latency, voice volume, and appropriate affect, which allowed for direct comparisons to be made between each of these assessment modalities. In addition, the role-play assessment was conducted under two distinct conditions to determine whether role-play performance varied between standard and reinforced administrations; however, multivariate analyses (MANOVA) revealed no differences between the two assessments. Correlations between the molar and the molecular measures suggested a substantial overlap between the measures, with staff ratings having the highest consistency with the other measures. Furthermore, MANOVAs calculated between role-play ratings and those of staff revealed little difference between the two. The limitations on and practical significance of these findings are discussed.
Most Nursing Home Social Service Directors Lack Training in Working With Lesbian, Gay, and Bisexual Residents

The purpose of this descriptive study is to report findings from a nationally representative mail-in survey of nursing home social service directors (n = 1,071) who were asked if they had received at least one hour of training in six different areas of cultural competency in the past five years. Of the six areas, the lowest percentage of directors reported having training in homophobia. Three-fourths of the sample had not received even one hour of homophobia training over the past five years. Directors who were more recently educated were more likely to report having received homophobia training, as were directors with a college degree, and those who worked in nursing homes located in the West and South regions of the United States. Directors with the most experience were less likely to report having received training. Findings call for immediate development and dissemination of heterosexism and homophobia training of social service staff, policy changes within the nursing home, and policy advocacy priorities for social workers.
Idiopathic Gingival Hyperplasia: A Case Report with a 17-Year Followup

This is a case report of a patient with idiopathic gingival hyperplasia and an undiagnosed genetic disorder that demonstrated static encephalopathy, mental retardation, developmental delay, seizures, hypotonia, and severe gingival hypertrophy. The clinical dental management and attempts to obtain a genetic diagnosis are described.
Identification of Residues of Spinach Thioredoxin f That Influence Interactions with Target Enzymes

The necessity for two types of thioredoxins (Trx f and m) within chloroplasts of higher plants that mediate the same redox chemistry with various target enzymes is not well understood. To approach this complex issue, we have applied site-directed mutagenesis to the identification of residues of Trx f that affect its binding to and selectivity for target enzymes. Based upon amino acid sequence alignments and the three-dimensional structure of Escherichia coli thioredoxin, putative key residues of Trx f were replaced with residues found at corresponding positions of Trx m to generate the mutants K58E, Q75D, N74D, and deletion mutants ΔAsn-74 and ΔAsn-77. Kinetics of activation of oxidized recombinant sorghum leaf NADP-dependent malate dehydrogenase and oxidized spinach chloroplastic fructose-1,6-bisphosphatase by wild-type Trx f, wild-type Trx m, and Trx f mutants were compared. All of the mutants are less efficient than wild-type Trx f in the activation of fructose-1,6-bisphosphatase and are altered in both S0.5 and Vmax. In contrast to literature reports, the activation of NADP-dependent malate dehydrogenase does not display rate saturation kinetics with respect to the concentration of Trx f, thereby signifying very weak interactions between the two proteins. The mutants of Trx f likewise interact only weakly with NADP-dependent malate dehydrogenase, but the apparent second-order rate constants for activation are increased compared to that with wild-type Trx f. Thus, Lys-58, Asn-74, Gln-75, and Asn-77 of Trx f contribute to its interaction with target enzymes and influence target protein selectivity.
On the maximum stoichiometry of energy-linked Ca++ accumulation during electron transport in rat liver mitochondria.

Abstract Several recent investigations have shown that approximately 1.7 – 2.0 molecules of divalent cation (Ca++, Sr++, or Mn++) may be accumulated by isolated mitochondria coupled to the passage of a pair of electrons through each energy-conserving site of the respiratory chain ( Rossi and Lehninger, 1963 , Rossi and Lehninger, 1964 ; Chappell, Cohn, and Greville, 1963 ; Carafoli, Weiland, and Lehninger, 1965 ; Carafoli, 1965 ; Chance, 1963 , Chance, 1965 ). Most reported measurements of the Ca++:∼ stoichiometry have been carried out with inorganic phosphate in the medium; under such conditions phosphate is also accumulated. However, limited amounts of divalent cations may also be accumulated in the absence of phosphate, with apparently similar stoichiometry with oxygen uptake ( Rossi and Lehninger, 1964 ; Chappell et al. , 1963 ; Carafoli, 1965 ). This communication describes two sets of conditions under which Ca++:∼ accumulation ratios over twice as high as those previously reported may be observed. When the concentration of certain neutral salts in the medium, such as NaCl or KCl, is increased to 240 mM or higher, with pH held constant at 7.4, the Ca++:∼ ratio increases to values exceeding 4.0. When the pH is raised from 7.0 to 8.0, with the NaCl concentration held constant at 80 mM, the Ca++:∼ ratio increases to as high as 7.0. In the presence of phosphate, however, the Ca++:∼ ratio remains at 2.0, regardless of pH or salt concentration.
Comparison of in Vivo and in vitro Hahn T2 measurements in rat lung

We compared in vivo and in vitro Hahn echo T2 measurements in rat lungs in both imaging and nonimaging modes. All measurements could be characterized by multiexponential functions consisting of either two or three exponentials. Essentially the same values of the time constants were observed for spontaneously breathing rats and for excised lungs. © 1991 Academic Press, Inc.
Robust machines accept easy sets

Abstract A robust machine is a machine that maintains some computational property for every oracle. In this paper we study robustly complementary, robustly categorical, robustly ∑ ∗ -accepting, and robustly ∑ ∗ -spanning machines. We prove that robust machines squander their powerful nondeterministic oracle access in all relativizations—relative to any oracle A , their languages and properties can be computed in P NP A .
Developmentally regulated expression of Sp1 in the mouse cornea.

Purpose To examine the expression of transcription factor Sp1 in the cornea of the mouse eye throughout developmental stages. The environmental effect of light on Sp1 expression was also assessed. Methods C57BL/6 mice were set up for timed mating. Embryos on embryonic day (E)10.5, E12.5, E15.5, and E18.5 and eyes from mice on postnatal day (P)0, P7, P11, P15, P30, and P60 were collected for immunohistochemical staining and in situ hybridization. One group of mice was bred strictly in the dark between E18.5 and P15, and the eyes were collected at P0, P7, P11, and P15 time points. Results Sp1 expression was observed in the ectoderm and lens vesicle as early as E10.5. Both Sp1 protein and mRNA were abundant in the corneal basal epithelium and keratocytes until P11. Their levels were markedly reduced at P15, right after eyelid opening, and declined further between P15 and P60. In those mice bred in the dark, Sp1 was evident in the cornea at P0. The Sp1 level gradually increased until P11 and was decreased at P15. This expression pattern was nearly identical in mice bred either in a light/dark cycle or in the dark. The Sp1 level in the central lens epithelium was much lower than that in the cornea from E15.5 to late stages. Conclusions The present study indicates that Sp1 expression is developmentally regulated, providing a basis for further investigations on the regulation of the Sp1 gene during the course of corneal development and in diseases such as keratoconus.
Anticancer activity and cellular repression of c-MYC by the G-quadruplex-stabilizing 11-piperazinylquindoline is not dependent on direct targeting of the G-quadruplex in the c-MYC promoter.

This G-rich region of the c-MYC promoter has been shown to form a G-quadruplex structure that acts as a silencer element for c-MYC transcriptional control. In the present work, we have synthesized a series of 11-substituted quindoline analogues as c-MYC G-quadruplex–stabilizing compounds, and the cell-free and in vitro activity of these compounds were evaluated. Two lead compounds (4 and 12) demonstrated good cell-free profiles, and compound 4 (2-(4-(10H-indolo[3,2-b]quinolin-11-yl)piperazin-1-yl)-N,N-dimethylethanamine) significantly down-regulated c-MYC expression. However, despite the good cell-free activity and the effect of these compounds on c-MYC gene expression, we have demonstrated, using a cellular assay in a Burkitt’s lymphoma cell line (CA46-specific), that these effects were not mediated through targeting of the c-MYC G-quadruplex. Thus, caution should be used in assigning the effects of G-quadruplex-interactive compounds that lower c-MYC to direct targeting of these promoter elements unless ...
A role for Orai in TRPC-mediated Ca2+ entry suggests that a TRPC:Orai complex may mediate store and receptor operated Ca2+ entry

TRPC and Orai proteins have both been proposed to form Ca2+-selective, store-operated calcium entry (SOCE) channels that are activated by store-depletion with Ca2+ chelators or calcium pump inhibitors. In contrast, only TRPC proteins have been proposed to form nonselective receptor-operated calcium entry (ROCE) cation channels that are activated by Gq/Gi-PLCβ signaling, which is the physiological stimulus for store depletion. We reported previously that a dominant negative Orai1 mutant, R91W, inhibits Ca2+ entry through both SOCE and ROCE channels, implicating Orai participation in both channel complexes. However, the argument for Orai participating in ROCE independently of store depletion is tenuous because store depletion is an integral component of the ROCE response, which includes formation of IP3, a store-depleting agent. Here we show that the R91W mutant also blocks diacylglycerol (DAG)-activated Ca2+ entry into cells that stably, or transiently, express DAG-responsive TRPC proteins. This strongly suggests that Orai and TRPC proteins form complexes that participate in Ca2+ entry with or without activation of store depletion. To integrate these results with recent data linking SOCE with recruitment of Orai and TRPCs to lipid rafts by STIM, we develop the hypothesis that Orai:TRPC complexes recruited to lipid rafts mediate SOCE, whereas the same complexes mediate ROCE when they are outside of lipid rafts. It remains to be determined whether the molecules forming the permeation pathway are the same when Orai:TRPC complexes mediate ROCE or SOCE.
Orbital measurement and verification of the Chandra X-ray Observatory's PSF

The recently launched Chandra x-ray Observatory (CXO) was designed to have the sharpest angular resolution yet of any x-ray telescope. Detailed modeling and metrology of the optics followed by extensive testing at the X-ray Calibration Facility at the Marshall p Space Flight Center in Huntsville, Alabama, indicated that the optics were performing exceedingly well, within our ability to account for distortion of the mirrors due to gravity, and the effects of finite distance and size of the x-ray generator. Thus it was only on-orbit that we expected to directly observe the specified half arcsecond performance. We present here results of the on-orbit calibration of the point spread function (PSF), comparing it with our predictions. We discuss how the PSF varies with source location in the telescope field of view, as well as with the spectral energy distribution of the source.
Influence of hydrocortisone acetate on pancreas and mucosal weight, amylase and disaccharidase activities in 14-day-old pigs

Abstract 1. 1. One litter of 12 pigs was used to evaluate the effects of hydrocortisone acetate injection on organ weight and carbohydrase activities. 2. 2. Pigs were injected with hydrocortisone acetate or an equal volume of saline at 7 days of age and killed at 14 days, and tissues were collected, weighed, and analyzed for carbohydrase activities. 3. 3. Hydrocortisone had no effect (P >O.40) on daily gain, liver weight, spleen weight, or small intestinal length. 4. 4. Hydrocortisone increased pancreatic weight by 29% and total pancreatic α-amylase content by 38%. 5. 5. Hydrocortisone increased duodenal mucosal weight by 23%, duodenal lactase activity by 44%, duodenal maltase activity by 163%, and duodenal sucrase activity by 214%.
Impact of Age and Comorbidity on Treatment and Outcomes in Elderly Cancer Patients

Cancer is a prevalent disease in elderly patients, who are also more likely to have comorbid illnesses than younger patients. Both increasing age and comorbidities are associated with a lower use of aggressive cancer therapies—including surgery, chemotherapy, and radiation therapy—but age is often the stronger determinant. A large proportion of elderly but otherwise healthy cancer patients do not receive aggressive treatments. Although there is an underrepresentation of elderly patients in clinical trials, the available evidence suggests that elderly patients can derive similar survival benefits from aggressive treatments as younger patients. For certain cancers and treatments, elderly patients may experience higher rates of toxicity and therefore require closer monitoring. Patients with comorbid illnesses have worse health-related quality of life at baseline but experience a similar health-related quality of life decline from treatment as healthier patients. However, patients with significant comorbidities are less likely to derive benefit from aggressive treatments. There is a need for studies to better identify, at baseline, patients who are likely to benefit from and tolerate aggressive treatment. A systematic use of sophisticated assessments, such as the geriatric assessment, may allow physicians to select appropriate patients and reduce underutilization of aggressive treatments in elderly cancer patients.
Combining constructed wetlands and aquatic and soil filters for reclamation and reuse of water

Abstract Reclamation and reuse of water and nutrients at their source provide the opportunity to use simple, less costly technologies and lessens potentials for catastrophic effects due to centralized treatment system failures. The combination of multiple treatment environments within constructed wetlands can provide water quality suitable for reuse. A current project in rural Chatham County, NC, uses simple, aesthetically pleasing treatment components constructed both outdoors and indoors to reclaim domestic sewage for toilet flushing, landscape irrigation and aesthetic water features. A courtyard containing constructed wetlands and a solarium with modular soil filter components and aquatic chambers are designed to treat sewage from within a small business facility and to provide recreational space for its 60 employees. The combination of vertical flow and horizontal flow constructed wetlands with fill and draw controls provides the necessary environments for nitrification–denitrification, removal of organic materials and phosphorus adsorption reactions. The system is designed to treat and reuse 4500 l day −1 (1200 gal day −1 ) of domestic sewage from the business. Some of the plants used are selectively bred or genetically engineered to maximize their water reclamation potential. Utilization of simple treatment and reuse technology has permitted the business owner to renovate an abandoned and deteriorating school building into a home for two thriving and internationally based businesses and to protect the water quality of a nearby reservoir.
Fermi resonance in solid CO2 under pressure.

The symmetric-stretching fundamental (ν1) and the bending first overtone (2ν2) of CO2, which are accidentally degenerate with the same symmetry, undergo a Fermi resonance and give rise to two Raman bands with a frequency difference of 107 cm−1 and an intensity ratio of 2.1. Both the frequency difference and intensity ratio can be varied by pressure applied to CO2 in condensed phases, which has been utilized as a spectroscopic geobarometer for minerals with CO2 inclusion. This study calculates the pressure dependence of the Fermi dyad frequency difference and intensity ratio by combining the embedded-fragment second-order Moller–Plesset perturbation calculations of harmonic frequencies of solid CO2 under pressure and the coupled-cluster singles and doubles with noniterative triples and vibrational configuration-interaction calculations of anharmonic frequencies of molecular CO2. It reproduces frequency difference quantitatively and intensity ratio qualitatively up to 10 GPa. The analysis of the results is shown to render strong support for one particular order of unperturbed frequencies, ν1 > 2ν2, in both the gas and solid phases, which has been a matter of controversy for decades.
Sexual Health Counselor Preferences of African American and European American Women: A Brief Report

African American women (n = 42) and European American women (n = 46) were queried regarding their comfort level discussing various sexual health topics with hypothetical counselors who were varied by race (African American vs. European American) or counseling value (culturally sensitive vs. knowledgeable). Contrary to hypotheses, European American participants were more comfortable with the knowledgeable African American counselor and the culturally sensitive European American counselor, while African American women showed no preference. Implications are discussed for improving sexual health counseling services for African American and European American women with consideration of client sexual attitude and race of counselor in order to reduce disparities in sexual health.
Model calculation on DNA-protein interaction

As a model for DNA-protein interaction we have performed an STO-3G calculation on the hydrogen bonded methylguanidium + dihydrogen-orthophosphate − composite system and its constituent ions. The analysis of the change in the charge distribution due to the interaction shows that the calculated −2.55 eV interaction energy is nearly purely electrostatic.
Atrial natriuretic peptide: an essential physiological regulator of transvascular fluid, protein transport, and plasma volume

Atrial natriuretic peptide (ANP) acts acutely to reduce plasma volume by at least 3 mechanisms: increased renal excretion of salt and water, vasodilation, and increased vascular permeability. Authors of a study in this issue of the JCI performed a knockout of the receptor for ANP in vascular endothelia in order to distinguish the effects of ANP-dependent increases in vascular permeability from those of other endocrine actions of ANP in the regulation of plasma volume. The knockout mice exhibited reduced vascular permeability to plasma protein, resulting in chronically increased plasma volume, arterial hypertension, and cardiac hypertrophy. Renal excretion and vasodilation did not account for these changes. Thus ANP-induced increases in endothelial permeability may be critical to the ability of ANP to lower arterial blood pressure.
Perturbationless calibration of pulse transit time to blood pressure

Pulse transit time (PTT) often shows strong correlation with blood pressure (BP) and may therefore represent a means for achieving continuous, non-invasive, and cuff-less BP monitoring. However, construction of the subject-specific curve needed to calibrate PTT to BP conventionally requires simultaneous measurements of PTT and BP during an experimental perturbation that varies BP over a significant range. We propose a technique for perturbationless calibration of PTT to BP. This technique constructs the calibration curve from central and peripheral BP waveforms by exploiting the natural pulsatile variation in the waveforms via a nonlinear tube-load model. We conducted initial testing of the technique in animals by applying it to the waveforms during a baseline period and then predicting mean BP during subsequent major hemodynamic interventions via PTT calibrated with the resulting curve. The bias in the mean BP error was 4.9 mmHg, while the precision in this error was 7.6 mmHg.
Anisotropy gradients from QL surface waves: Evidence for vertically coherent deformation in the Tibet region

Abstract The India–Eurasia continental collision has not only caused the high uplift of the Tibetan Plateau, but also created a broad diffuse deformation zone in Central Asia. We relate the well-constrained extent of crustal deformation in the Tibet region with underlying mantle deformation by interpreting the quasi-Love (QL) surface wave scattering in the legacy data of Tibet. QL waves are waveform anomalies generated from cross-mode coupling of Earth's free oscillations, mainly through azimuthal anisotropy. Over 50 events with QL observations are identified using recordings in Tibet. The predominant frequency content of the QL waves is near 10 mHz, and reflects peak sensitivity of anisotropy at 150 km depth in the mantle assuming horizontally-oriented symmetry axes. By calculating the delay times between the QL waves and the main Love waves, we back-project the scatterers to cluster in areas like SE Tibet, Sayan Mountain and Iran. Noticeably the spatial distribution of these scatterers borders the crustal deformation pattern quite well, especially at the deformation limits of Central Asia. This linkage suggests a vertically coherent boundary condition through the crust and the upper mantle for the India–Eurasia continental collision in Central Asia.
Glutathione Metabolism during Aging and in Alzheimer Disease

The concentration of glutathione (GSH), the most abundant intracellular nonprotein thiol and important antioxidant, declines with age and in some age-related diseases. The underlying mechanism, however, is not clear. The previous studies from our laboratory showed that the age-dependent decline in GSH content in Fisher 344 rats was associated with a downregulation of glutamate cysteine ligase (GCL), the rate-limiting enzyme in de novo GSH synthesis. Our recent studies further indicated that the activity and mRNA content of glutathione synthase (GS), which catalyzes the second reaction in de novo GSH synthesis, were also decreased with age in some tissues. No age-associated change was observed in glutathione reductase or gamma-glutamyl transpeptidase activities. Also, although GSH content declined with age in both male and female mice, male mice experienced more dramatic age-associated decline in many tissues/organs than female mice. Furthermore, we found that GSH content was significantly decreased in the red blood cells from male Alzheimer disease patients, which was associated with decreases in GCL and GS activities. Finally, we showed that estrogen increased GSH content, GS and GR activities, and GCL gene expression in the liver of both male and female mice. Taken together, our results suggest that (1) GCL plays a critical role in maintaining GSH homeostasis under both physiological and pathological conditions; (2) decreased GSH content may be involved in AD pathology in humans; and (3) estrogen increases GSH content in mice by multiple mechanisms.
Innovations in Career Counseling

The work world is now full of uncertainty and change as a result of forces such as globalization, downsizing, advancing technology, and increased diversity in the work force. Further, people cannot count on maintaining a job with one company, or even one career, throughout their work lives. In order to meet clients' needs, career counselors must utilize approaches that are compatible with these realities. We review a set of approaches for career counseling that should be effective for clients now and into the future. Specifically, we argue for a holistic approach to career counseling, use of the Personal Career Theory as a client-centered approach to counseling sessions, incorporating creative interventions that draw upon chance events and flexible decision-making, and an emphasis on building interpersonal skills and relationships. We conclude with a summary of recommendations for career counseling practice.
Determining the position of the cell division plane

Proper positioning of the cell division plane during mitosis is essential for determining the size and position of the two daughter cells--a critical step during development and cell differentiation. A bipolar microtubule array has been proposed to be a minimum requirement for furrow positioning in mammalian cells, with furrows forming at the site of microtubule plus-end overlap between the spindle poles. Observations in other species have suggested, however, that this may not be true. Here we show, by inducing mammalian tissue cells with monopolar spindles to enter anaphase, that furrow formation in cultured mammalian cells does not require a bipolar spindle. Unexpectedly, cytokinesis occurs at high frequency in monopolar cells. Division always occurs at a cortical position distal to the chromosomes. Analysis of microtubules during cytokinesis in cells with monopolar and bipolar spindles shows that a subpopulation of stable microtubules extends past chromosomes and binds to the cell cortex at the site of furrow formation. Our data are consistent with a model in which chromosomes supply microtubules with factors that promote microtubule stability and furrowing.
Impaired Developmental Expression of Lung Endothelial Nitric Oxide Synthase and Abnormal Alveolarization in the Fawn-Hooded Rat : Implications for the Risk of Developing Pulmonary Hypertension 1689

The fawn-hooded rat (FHR) strain is characterized by platelet abnormalities and systemic hypertension, and has been used to study genetic risk factors for pulmonary hypertension (PH). Unlike other strains, FHR develop progressive PH when exposed to slight decreases in alveolar PaO2. We hypothesized that developmental abnormalities in lung vasoreactivity or growth may predispose the FHR for PH. Since endogenous nitric oxide (NO) modulates pulmonary vasoreactivity and growth, we further hypothesized that early decreases in lung endothelial NO synthase (eNOS) content may contribute to the development of PH in FHR. We measured lung eNOS content and growth in FHR and control rat strains (Fischer and Sprague-Dawley (SDR)). Lungs were harvested from late fetal and postnatal ages (days 1 & 7) and eNOS protein content measured by western blot analysis. Immunostaining for eNOS was performed with paraffin sections and the eNOS monoclonal antibody. Histology was assessed after tracheal installation of formalin at constant pressure (10cm water) and radial alveolar counts performed. Lung to body weight ratios were reduced in fetal and newborn FHR by 20-46% compared to controls (p<0.05). In comparison with SDR, FHR lung eNOS protein was decreased to 69±8%, 56±8%, and 68±7% at fetal, and postnatal days 1 and 7, respectively (p<0.05 at each age). Immunostaining studies demonstrated selective staining for eNOS only in vascular endothelium and no difference in the pattern of eNOS expression between strains. Histology revealed striking changes in lung maturation and growth in FHR at all ages, including reduced alveolarization(FHR 58±2% of SDR at day 7, p<0.05). We conclude that in comparison with other rat strains, lung eNOS content is decreased in the FHR fetus and newborn. In addition, the FHR lung has decreased alveolarization and histologic signs of delayed lung maturation. We speculate that reduced vascular surface area and eNOS increase the risk for developing PH, and that decreased NO production may be associated with abnormal lung growth and development.
Hydrogen attack behavior of the heat affected zone of a 2.25Cr-1Mo steel weldment

The kinetics of hydrogen attack (HA) has been studied in the heat affected zone (HAZ) in a 2.25Cr-1Mo steel weld to determine the relative rates of attack and bubble nucleation in the HAZ, base metal, and weld metal. The HAZ was found to suffer hydrogen attack at nearly twice the rate of the base metal, but not as rapidly as the weld metal. Nucleation of bubbles does not occur during HA of the HAZ of a 2.25Cr-1Mo steel, on exposure to hydrogen pressure of 20.5 MPa or less, but does occur at higher pressures up to 31.5 MPa (4500 psi) at 550 °C, or up to 27.5 MPa (4000 psi) at 580 °C. Such nucleation results in enhancement of the HA rate by a factor of six. The weak dependence of nucleation effects on hydrogen pressure and the saturation of the nucleation effects in a short time suggest some thermally activated nucleation of fresh bubbles.
Phytoplankton abundance and Late Paleozoic extinctions: A reply

Abstract Factors affecting nutrient supply and utilization changed in the Mid Paleozoic to result in reduced phytoplankton populations. Among these were the rise of vascular plants which for the first time retained such nutrients in a large terrestrial biomass, both as living plants and detrital accumulations. Prior phytoplankton populations had been adapted to a higher rate of influx. Modern aquatic vascular plants and filamentous algae are successful competitors for limited nitrogen abundance, and their growth is inhibiting to phytoplankton. Abundant bacteria, suggested by other data to have characterized the Permian, also would have competed for dissolved phosphorus. Although Mid Paleozoic extinctions were in part balanced by newly evolved introductions, the nature of the particular deletions and replacements also is consistent with modern communities of low net production, the highest extinction rates affecting sessile suspensions feeders and the higher trophic levels, and lowest rates characterizing detritus feeders and active predators. Offshore communities of lowest productivity underwent rapid changes. Invertebrates evolved new methods of feeding or turned to new kinds of food, such as the organic aggregates produced from dissolved matter by bacterial action or adsorption on bubbles and mineral particles, in response to reduced phytoplankton productivity. The direction of evolution supports the evidence of low productivity in the Late Paleozoic presented by the fossil record. Phytoplankton and invertebrate abundance did not immediately follow continental emergence as the reduced numbers had involved extensive extinctions. The annual exponential growth of phytoplankton resulting in the spring “blooms” results from a pre-existing, although reduced, wintering population or the germination of encysted individuals. Renewal of entire communities by evolution of new taxa is less predictable and far slower even on a geologic scale.
Effect of Insulin on Farnesyltransferase Gene Transcription and mRNA Stability

Abstract Recently, we have shown that hyperinsulinemia increases the activity of farnesyltransferase (FTase) in vitro (1) and in hyperinsulinemic animals (2), stimulates the phosphorylation of the FTase α-subunit (3), increases the amounts of cellular farnesylated p21Ras (4), and potentiates the nuclear effects of other peptide growth factors, such as EGF, IGF-1 and PDGF (5). To further investigate the mechanism by which insulin stimulates FTase activity we tested the effect of insulin on the rate of FTase transcription, the rate of FTase mRNA degradation, and the amounts of FTase protein. Insulin increased the amounts of FTase α- and β-subunit mRNA in 3T3-L1 fibroblasts 2.5-fold to 4-fold after 6 h and 24 h incubation, respectively, but did not increase the rate of FTase transcription over a 24 h period. Insulin did, however, increase the stability of both α- and β-subunit mRNA. The half-life for both FTase α- and β-subunit mRNA was approximately 3 h and 6h in the absence and in the presence of insulin, respectively. Although insulin stabilized the α- and β-subunit mRNA of FTase, there was no increase in amounts of protein of either subunit. These data suggest that although insulin increases the stability of the FTase mRNA, it stimulates FTase enzymatic activity only at the post-translational level.
Properties of separating polynomials and separating uniformly analytic functions

We consider the properties of separating polynomials and uniformly analytic separating functions. We prove that the polynomial automorphism preserves a separating polynomial with positive-definite components. We also show that the composition of a uniformly analytic separating function and a linear mapping that does not decrease the norm is a uniformly analytic separating function.
The clinical significance of the bifid or "W" pattern reversal visual evoked potential.

Although the visual evoked potential (VEP) to an alternating checkerboard stimulus is usually recorded from the occipital midline as an N-P-N complex with a major positive deflection at 100 ms (P100), a wave form exhibiting a P-N-P or "W" morphology is occasionally encountered and its interpretation is the source of some controversy. A retrospective chart review identified 15 patients exhibiting the "W" VEP. This represented 7.6 percent of 197 VEP studies and 5.1 percent of 394 eyes. The response was encountered in 1.7 percent of 57 normal patients and 21.4 percent of 56 patients with definite, probable or possible multiple sclerosis (P less than .001). The "W" response was considered normal in only one patient. Of the remaining 14 cases, 13 had definite, probable or possible MS and one had ischemic optic neuropathy. It is concluded that the "W" VEP is an aberrant response that is rarely seen in normals and may have the same significance as a delayed P100 latency.
A computational/functional genomics approach for the enrichment of the retinal transcriptome and the identification of positional candidate retinopathy genes

Grouping genes by virtue of their sequence similarity, functional association, or spatiotemporal distribution is an important first step in investigating function. Given the recent identification of >30,000 human genes either by analyses of genomic sequence or by derivation/assembly of ESTs, automated means of discerning gene function and association with disease are critical for the efficient processing of this large volume of data. We have designed a series of computational tools to manipulate the EST sequence database (dbEST) to predict EST clusters likely representing genes expressed exclusively or preferentially in a specific tissue. We implemented this tool by extracting 40,000 human retinal ESTs and performing in silico subtraction against 1.4 million human ESTs. This process yielded 925 ESTs likely to be specifically or preferentially expressed in the retina. We mapped all retinal-specific/predominant sequences in the human genome and produced a web-based searchable map of the retina transcriptome, onto which we overlaid the positions of all mapped but uncloned retinopathy genes. This resource has provided positional candidates for 42 of 51 uncloned retinopathies and may expedite substantially the identification of disease-associated genes. More importantly, the ability to systematically group ESTs according to their predicted expression profile is likely to be an important resource for studying gene function in a wide range of tissues and physiological systems and to identify positional candidate genes for human disorders whose phenotypic manifestations are restricted to specific tissues/organs/cell types.
The 27 day solar UV response of stratospheric ozone: solar cycle 21 vs. solar cycle 22

Abstract A correlative study of ozone and the solar UV flux on the time scale of a solar rotation shows an anomalous response of ozone in the upper stratosphere during solar cycle 22. The study, which is based on the analysis of ozone and solar UV flux measured by the SBUV/2 spectrometer on NOAA 11 (January 1989–December 1990), shows a sharp transition from an in-phase relation between ozone and the solar UV flux below 2 mb to an almost out-of-phase relation above 1 mb. Such a phase change is not predicted by photochemical models and was not observed during solar cycle 21. The ozone measurements from the Nimbus-7 SBUV spectrometer from 1979 to 1984 showed an almost in-phase relation between ozone and the solar UV flux at these heights (in agreement with model predictions). Similar studies of ozone and temperature relations between 30 and 1 mb did not show significant changes from the solar cycle 21 to 22. The temperature oscillations appear to be primarily of dynamical origin, with no apparent correlation with solar UV flux.
Differences in illicit drug-use rates among Oklahoma and non-Oklahoma Indian youth

Demographic factors may serve as risk or protective factors for drug use in American Indian communities. The purpose of the present study was to compare drug-use rates among Oklahoma and Non-Oklahoma Indian youth, and test corresponding rates of preventative and protective community, family, and social-demographic factors. Participants' data included 1,928 Indian 7th-12th graders from non-Oklahoma schools and 1,938 Indian students from schools in Oklahoma, aggregated across 2-3 years from an ongoing survey study of substance use and prevention among Indian youth. As predicted, one-way analysis of variance tests indicated that Oklahoma youth showed lower rates of drug use, later ages of initiation of drug use, and greater levels of perceived harm from using drugs. These differences were reflected in the predicted protective factor differences, including higher levels of exposure to anti-drug campaigns in the community and schools, greater family involvement in drug-use prevention, and lower levels of peer drug associations. The strength of these protective factors is illustrated by the fact that drug-use rates were lower among Oklahoma youth despite the perception among Oklahoma youth that drugs were more available, compared with non-Oklahoma youth. Limitations and suggestions for future research are noted.
Genome-based pharmacogenetics and the pharmaceutical industry

Pharmacogenetic capabilities have changed markedly since The SNP Consortium made a dense single-nucleotide polymorphism (SNP) map freely available in 2001. For more than 40 years, pharmacokinetics and pharmacodynamics of drug-metabolizing molecules were the focus of practical applications. Today, it is possible to use SNP-mapping technologies to create a genetic profile of each individual that can be used to identify patterns of susceptibility genes for common diseases as well as genetic risk/efficacy factors that are related to the effects of drugs.
The FMN to heme electron transfer in cytochrome P450BM-3. Effect of chemical modification of cysteines engineered at the FMN-heme domain interaction site.

Abstract The crystal structure of the complex between the heme and FMN-containing domains of Bacillus megaterium cytochrome P450BM-3 (Sevrioukova, I. F., Li, H., Zhang, H., Peterson, J. A., and Poulos, T. L. (1999)Proc. Natl. Acad. Sci. U. S. A. 96, 1863–1868) indicates that the proximal side of the heme domain molecule is the docking site for the FMN domain and that the Pro382—Gln387peptide may provide an electron transfer (ET) path from the FMN to the heme iron. In order to evaluate whether ET complexes formed in solution by the heme and FMN domains are structurally relevant to that seen in the crystal structure, we utilized site-directed mutagenesis to introduce Cys residues at positions 104 and 387, which are sites of close contact between the domains in the crystal structure and at position 372 as a control. Cys residues were modified with a bulky sulfhydryl reagent, 1-dimethylaminonaphthalene-5-sulfonate-l-cystine (dansylcystine (DC)), to prevent the FMN domain from binding at the site seen in the crystal structure. The DC modification of Cys372 and Cys387 resulted in a 2-fold decrease in the rates of interdomain ET in the reconstituted system consisting of the separate heme and FMN domains and had no effect on heme reduction in the intact heme/FMN-binding fragment of P450BM-3. DC modification of Cys104 caused a 10–20-fold decrease in the interdomain ET reaction rate in both the reconstituted system and the intact heme/FMN domain. This indicates that the proximal side of the heme domain molecule represents the FMN domain binding site in both the crystallized and solution complexes, with the area around residue 104 being the most critical for the redox partner docking.
Nondestructive and Nonintrusive Determination of Chemical and Isotopic Purity of Solvents by Near-Infrared Thermal Lens Spectrometry

A novel instrument which is based on the use of the thermal lens effect to facilitate the sensitive measurements of the absorption in the near-infrared region has been developed. In this instrument, the near-IR excitation light was provided by a solid-state, spectra-tunable (from 860 to 1060 nm) titanium:sapphire laser. The heat generated as a consequence of the sample absorption of the excitation beam was monitored in the visible region by a He-Ne laser. The data obtained were analyzed by multivariate calibration methods for the nondestructive, noninvasive determinations of chemical and isotopic impurities in solvents. Water in D2O and in tetrahydrofuran can be detected at levels as low as 0.006 and 0.3% (v/v). The method can also be used for the simultaneous determination of water and DMSO-h6 in DMSO-d6 and CD3OH in CD3OH, CD2HOH, and CDH2OH at levels as low as 10-3% (w/w).
Sociosexual behavior and the ovulatory cycle of ponies (Equus caballus) observed in harem groups.

Abstract Observations of sociosexual behavior of adult ponies, made on two harem groups (each comprised of one vasectomized male and three females), were correlated with follicular development and ovulation for a total of 15 cycles (minimum of 2 cycles per female). Mean cycle length (interovulatory interval) was found to be 19.7 days, with behavioral estrus lasting 7–8 days (5.5 days preovulatory; 2.3 days postovulatory). Estrous females typically showed increased frequencies of approaching and following the stallion, urinating, presenting, clitoral winking, and tail raising. Approaching and following the stallion appeared earlier and persisted longer than other estrous responses. Deviations from the modal estrous pattern included cycles with subestrus, continual estrus, behavioral estrus in the absence of ovulation, and displays of female mounting. Dominance tests revealed that a mare's status was unaffected by the phases of the estrous cycle. The presence of more than one estrous female affected the copulatory performance of both stallions, most notably in reduced latencies to first mount, intromission, and ejaculation, in spite of differences between the stallions in sexual vigor. Each stallion usually selected the dominant mare for copulation when there were multiple estrous females present, but mounts were not displayed exclusively to one female per test. The social testing situation made apparent the importance of use of space in sociosexual communication in this species, particularly in avoidance of the stallion by diestrous mares and standing alone or in proximity to him by estrous mares.
Prefibrotic myelofibrosis: is this diagnosis valid?

Wilkins and colleagues evaluate the utility of the World Health Organization (WHO) diagnostic criteria intended to separate cases previously classified as essential thrombocythemia (ET) into 2 groups: “true ET” and “prefibrotic myelofibrosis.” Focusing on bone marrow histology, the authors found substantial variation in classification of cases.
Thyroid physiology in the developing monkey fetus (Macaca mulatta).

A series of observations defining thyroid physiology in the developing monkey fetus (Macaca mulatta) were summarized in this paper. Follicle formation and colloid synthesis were apparent in the gland by conception age 50 days. They underwent vigorous proliferation and were progressively subdivided by interposing vessels and connective tissue. The total iodine content showed a fiftyfold increase between conception age 75 and 150 days yet gland weights increased only tenfold. The moieties, monoiodotyrosine (MIT), diiodotyrosine (DIT) and thyroxine (T4) were present in constant ratios. The 24-hour 131I uptake per milligram of thyroid tissue in fetuses was 8–12 times greater than in their mothers. The distribution of 131I among the various moieties was about the same in all fetal thyroid glands studied. The significant difference of T4 131I values observed between fetal and infant thyroid glands suggest that much less T4 is released from the gland in fetal life than after birth. BEI values in fetal glands were relatively low at the younger ages, however, they increased progressively and approached maternal values by conception age 150 days. By term maternal and fetal values are equal for this animal and man. However, when the data were expressed in term of the T4 concentration (molar) per milligram of protein nitrogen, the situation changed. The T4 (SA) values, observed through further elaborated studies in fetal thyroid glands coupled with data of placental and fetal tissue indicated clearly that the 131I-labeled T4 detected was of maternal origin. The fetal serum T4 values, observed from relatively long term maternal administration of large doses of 131I-labeled T4, showed little or no change from normal even though maternal values had exceeded normal by three times. There was also no indication of increased placental T4 transport to the fetus as a result of the high maternal T4 values.