cssi/SciSciGPT-SciSciNet huggingface dataset:
Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

We propose that postmortem tissue is an underutilized substrate that may be used to translate genetic and/or preclinical studies, particularly for neuropsychiatric illnesses with complex etiologies. Postmortem brain tissues from subjects with schizophrenia have been extensively studied, and thus serve as a useful vehicle for illustrating the challenges associated with this biological substrate. Schizophrenia is likely caused by a combination of genetic risk and environmental factors that combine to create a disease phenotype that is typically not apparent until late adolescence. The complexity of this illness creates challenges for hypothesis testing aimed at understanding the pathophysiology of the illness, as postmortem brain tissues collected from individuals with schizophrenia reflect neuroplastic changes from a lifetime of severe mental illness, as well as treatment with antipsychotic medications. While there are significant challenges with studying postmortem brain, such as the postmortem interval, it confers a translational element that is difficult to recapitulate in animal models. On the other hand, data derived from animal models typically provide specific mechanistic and behavioral measures that cannot be generated using human subjects. Convergence of these two approaches has led to important insights for understanding molecular deficits and their causes in this illness. In this review, we discuss the problem of schizophrenia, review the common challenges related to postmortem studies, discuss the application of biochemical approaches to this substrate, and present examples of postmortem schizophrenia studies that illustrate the role of the postmortem approach for generating important new leads for understanding the pathophysiology of severe mental illness.
THE TRANSMISSION OF CRITHIDIA FASCICULATA LEGER 1902 IN CULISETA INCIDENS (THOMSON).

SYNOPSIS. It has been shown that larva-to-larva transmission effected by means of free-living Crithidia can account for the incidence of this flagellate in natural populations of adult mosquitoes. Larval infections lost at molting were reacquired early in subsequent instars. Infections of pupae came about by contamination of the midgut of the prepupa with nectomonads while the peritrophic membrane was being shed prior to pupation. By the time pupation was completed the flagellates had become immotile and continued to multiply in the pupal midgut; they again became motile in the midgut of the newly emerged adult. Adult-to-larva transmission was effected through water contaminated by adult mosquitoes infected with flagellates.
Rathke's pouch grafts in adult brain sites.

Donor tissue containing Rathke's pouch (RP) with its associated mesenchyme and neural lobe was isolated from 15-day fetal rats and stereotaxically transplanted either to hypothalamic hypophysiotropic sites or to cerebral cortex of adult females for 30 days. Hosts either were intact or had been hypophysectomized 2–4 weeks prior to transplantation of Rathke's pouch. Grafts in the hypothalamus of either intact or hypophysectomized hosts were pleomorphic and large, often as wide as 1–2 mm, and occasionally larger. Grafts in the cortex of either intact or hypophysectomized hosts were nodular and occasionally projected upward in association with the meninges (cortex/meninges grafts). Certain features were characteristic of the grafts in all experimental groups, i.e., development of histotypic pars distalis with cell cords and fenestrated capillaries. In all experimental groups gonadotrophs and somatotrophs, when present, were localized at the graft margin adjacent to the connective-tissue interface; mammotrophs, when present, were distributed throughout the graft. Features specific to each experimental group also were apparent. Grafts in the hypothalamus of both intact and hypophysectomized hosts typically were encapsulated by a labyrinthine meshwork of cell processes, whereas cortex/meninges grafts directly abutted dense connective tissue or neural tissue. In hypothalamic grafts in intact hosts, moderately differentiated mammotrophs, gonadotrophs, and somatotrophs could be identified by their cytological features and immunopositivity for prolactin, luteinizing hormone, and growth hormone, respectively. In hypothalamic grafts in hypophysectomized hosts, mammotrophs were absent, and gonadotrophs and somatotrophs were poorly granulated and not abundant. Grafts in the cortex of intact hosts contained numerous, well-differentiated mammotrophs, gonadotrophs, and somatotrophs. Many of the mammotrophs in these grafts were hypertrophied, and profiles of exocytosis were common. In grafts in the cortex of hypophysectomized hosts, mammotrophs were either absent or very few, whereas gonadotrophs and somatotrophs were numerous. Gonadotrophs in these grafts were dramatically hypertrophied, although exocytosis was rare. The results indicate that development of histotypic pars distalis may occur in hypophysiotropic and nonhypophysiotropic brain sites and that the hormonal state of the host as well as implantation site modulate cytodifferentiation of specific pars distalis cell types.
Serum lipoprotein and apoprotein concentrations in 4-(4-chlorophenyl)-2-hydroxytetronic acid and clofibrate-treated cholesterol and cholic acid-fed rats

Influence of clofibrate and an aci-reductone, 4-(4-chlorophenyl)-2-hydroxytetronic acid (CHTA) on lipoproteins and apoproteins was studied in cholesterol- plus cholic acid-fed rats. CHTA (0.4 mmol/kg body wt, twice daily) significantly lowered serum total cholesterol and triglyceride concentrations at both 10 and 16 days, whereas clofibrate at the same dose did not alter serum cholesterol levels, but elevated serum triglyceride concentrations at 16 days. The abnormal cholesterol-rich very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and low density lipoproteins (LDL) produced by cholesterol plus cholic acid were significantly reduced in their cholesterol content by treatment with CHTA, a compound having an oxidation reduction potential. Conversely, clofibrate administration increased VLDL-cholesterol with concomitant decreases in IDL- and LDL-cholesterol concentrations. Administration of CHTA to cholesterol- plus cholic acid-fed rats significantly increased concentrations of VLDL and IDL, but had no effect on HDL protein. Both CHTA and clofibrate administration to cholesterol- plus cholic acid-fed rats significantly lowered IDL protein concentrations. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) studies of apoproteins revealed that clofibrate treatment significantly reduced apoC-III and C-II in VLDL, C-II in IDL, and apoA-IV and A-I in HDL. Rats treated with CHTA significantly raised apoC-II and C-III in HDL. Isoelectric focusing (IEF) of VLDL apoproteins showed a significant decrease in apoC-II, C-III-0 and apoC-III-3 in clofibrate-treated animals. Thus, the mechanism for antilipidemic action of the oxidation reduction compound, CHTA, which differs markedly from the prototype drug, clofibrate, is independent from major apoprotein modification.
Monoclonal antibody studies of ferredoxin:NADP+ oxidoreductase

Eleven independent monoclonal antibodies, all IgG's, have been raised against the ferredoxin:NADP+ oxidoreductase of spinach leaves. All 11 monoclonal antibodies were able to produce substantial inhibition of the NADPH to 2,6-dichlorophenol indophenol (DCPIP) diaphorase activity of the enzyme, but none of the antibodies produced any significant inhibition of electron flow from NADPH to ferredoxin catalyzed by the enzyme. Spectral perturbation assays were used to demonstrate that antibody interaction with NADP+ reductase did not interfere significantly with the binding of either ferredoxin or NADP+ to the enzyme. Ultrafiltration binding assays were used to confirm that the monoclonal antibodies did not interfere with complex formation between ferredoxin and the enzyme. These results have been interpreted in terms of the likely presence of one or more highly antigenic epitopes at the site where the nonphysiological electron acceptor, DCPIP, binds to the enzyme. Furthermore, the results suggest that the site where DCPIP is reduced differs from both of the two separate sites at which the two physiological substrates, ferredoxin and NADP+/NADPH, are bound.
Electrical characteristics of high performance Au/n-GaN Schottky diodes

Au/n-GaN Schottky diodes with the Au electrode deposited at low temperature (LT=77K) have been studied. In comparison, the same chip of GaN epitaxial layer was also used for room temperature Schottky diodes. The low temperature Schottky diodes exhibit excellent performance. Leakage current density as low as 2.55×10−11 A·cm−2 at −2.5 V was obtained in the LT Schottky diodes. The linear region in the current-voltage curve at forward bias extends more than eight orders in current magnitude. Current-voltage-temperature measurements were carried out to study the characteristics of the LT Schottky diodes. A typical barrier height of about 1.32 eV for the LT diode, which is the highest value ever reported, was obtained. The obvious enhancement in electrical performance makes the LT processing a very promising technique for GaN device application although the detailed mechanisms for the LT Au/n-GaN Schottky diodes are still under investigation.
Estimation of developmental parameters for adult emergence of Gonatocerus morgani, a novel egg parasitoid of the glassy-winged sharpshooter, and development of a degree-day model

Abstract The effects of temperature on the development (egg–adult emergence) of Gonatocerus morgani Triapitsyn, a newly-described parasitoid of Homalodisca vitripennis (Germar), were determined at 14.8, 18.7, 23.5, 26.9, 28.7, 30.4, 32.8, and 33.8 °C in the laboratory. Survival rate (percent adult emergence from parasitized host eggs) varied significantly among the experimental temperatures, with the highest (59%) and lowest (0%) occurring at 30.4 and 33.8 °C, respectively. The survival rates (%) were fitted with a polynomial model to describe a temperature-dependent pattern. Developmental rates (1/d) across seven temperatures were fitted with the nonlinear Briere model, which estimated the lower threshold to be 8.06 °C, the optimal temperature to be 29.22 °C, and the upper threshold to be 33.49 °C. A linear model fitted to developmental rates at 14.8–28.7 °C indicated that 189.75 degree-days above the lower threshold of 9.71 °C were required to complete development. A simulation model of G. morgani adult emergence was constructed to predict daily counts over the entire range of constant temperatures by incorporating the survival rate model, the Briere model, and the Weibull model. In outdoor validation, a degree-day model for predicting adult emergence showed ⩽2 d differences between prediction and observation. Based on the observed temperature requirement, the insect could complete thirteen to sixteen generations per year in southern California, depending on weather and location.
Interaction of periclase and corundum refractories with iron and iron-manganese melts

The authors have experimentally investigated the reaction of periclase and corundum refractories with iron and iron-manganese melts. They propose a physicochemical scheme of the reaction, taking account of the characteristics of the composition and structure of the specimens. They show the influence of manganese and of the composition of the primary oxide phase on the character of the reaction. The coefficients of diffusion of the primary oxide phase in periclase grains have been determined.
Silicon carbide nanowires as an electrode material for high temperature supercapacitors

Supercapacitors have attracted much attention for energy storage applications, owing to their long cycle life and high power densities. We report on the growth of silicon carbide (SiC) nanowires (NW) and the evaluation of their performance as electrode material for micro-supercapacitors. Their specific capacitance has been studied as a function of their morphology (size, diameter) and the optimal growth conditions have lead to a capacitance comparable to the state of the art. They exhibit an exceptional stability, with a lifetime exceeding 106 charge/discharge cycles. An excellent thermal stability is expected for SiC NWs, opening the way to the fabrication of high temperature micro-supercapacitors.
Plasma adiponectin concentrations and risk of incident breast cancer.

Introduction: Previous retrospective case-control studies suggest that adiponectin, an obesity-related hormone, is inversely associated with breast cancer risk, particularly in postmenopausal women; however, no prospective studies exist. Therefore, we conducted a prospective case-control study nested within the Nurses’ Health Study (NHS) and NHSII cohorts examining the association between plasma adiponectin concentrations and breast cancer risk. Materials and Methods: Blood samples were collected from 1989 through 1990 (NHS) and 1996 through 1999 (NHSII); adiponectin was measured by RIA. The analysis included 1477 breast cancer cases diagnosed after blood collection and before June 2000 (NHS) or June 2003 (NHSII) who had one or two controls (n 2196) matched on age, menopausal status, postmenopausal hormone (PMH) use, fasting, and time of day and month of blood collection. We adjusted for body mass index at age 18, weight change from age 18 to blood draw, family history of breast cancer, history of benign breast disease, duration of PMH use, ages at menarche and first birth, and parity. Results: Although we observed no association between adiponectin and breast cancer risk overall, there was a nearly significant interaction by menopausalstatus(P0.08),witharelativerisk,topvs.bottomquartile of 0.73 (95% confidence interval, 0.55–0.98; P trend 0.08) among postmenopausal women and 1.30 (95% confidence interval, 0.80–2.10; P trend 0.09) for premenopausal women. Among postmenopausal women, adiponectin appeared more strongly inversely associated in women who never used PMH (P heterogeneity 0.05) and women with low circulating estradiol levels (P heterogeneity 0.05). Discussion: Our results suggest that adiponectin may be inversely associated with postmenopausal breast cancer risk, particularly in a low-estrogen environment. (J Clin Endocrinol Metab 92: 1510–1516, 2007)
Ligand-dependent Linkage of the ATP Site to Inhibition Gate Closure in the KATP Channel

Major advances have been made on the inhibition gate and ATP site of the Kir6.2 subunit of the KATP channel, but little is known about conformational coupling between the two. ATP site mutations dramatically disrupt ATP-dependent gating without effect on ligand-independent gating, observed as interconversions between active burst and inactive interburst conformations in the absence of ATP. This suggests that linkage between site and gate is conditionally dependent on ATP occupancy. We studied all substitutions at position 334 of the ATP site in Kir6.2ΔC26 that express in Xenopus oocytes. All substitutions disrupted ATP-dependent gating by 10-fold or more. Only positive-charged arginine or lysine at 334, however, slowed ligand-independent gating from the burst, and this was in some but not all patches. Moreover, the polycationic peptide protamine reversed the slowed gating from the burst of 334R mutant channels, and speeded the slow gating from the burst of wild-type SUR1/Kir6.2 in the absence of ATP. Our results support a two-step ligand-dependent linkage mechanism for Kir6.2 channels in which ATP-occupied sites function to electrostatically dissociate COOH-terminal domains from the membrane, then as in all Kir channels, free COOH-terminal domains and inner M2 helices transit to a lower energy state for gate closure.
Effects of Second Intracellular Loop Mutations on Signal Transduction and Internalization of the Gonadotropin-releasing Hormone Receptor

The gonadotropin-releasing hormone (GnRH) receptor belongs to the superfamily of heptahelical G protein coupled receptors, most of which have a highly conserved DRYXXV/IXXPL sequence in the second intracellular (2i) loop that has been implicated in G protein coupling. The predicted 2i loop of the GnRH receptor contains serine rather than tyrosine in the DRY sequence but retains the conserved hydrophobic Leu residue, which is required for G protein coupling and internalization of muscarinic receptors. The present study examined the effects of mutating the unique Ser140 to the conserved Tyr, and the conserved Leu147 to Ala or Asp, on agonist binding, internalization, and signal transduction. The S140Y mutant showed a 100% increase in agonist binding affinity, and its internalization was increased by 60% above that of the wild-type receptor. The binding characteristics of the Leu147 mutants were indistinguishable from those of the wild-type receptor, but their internalization was reduced by about 50%. The L147A and L147D mutants also showed significant impairment of GnRH-stimulated inositol phosphate production. These findings demonstrate that substitution of Ser140 by Tyr does not affect G protein coupling but significantly increases receptor affinity and internalization rate. In contrast, replacement of a conserved aliphatic residue (Leu147) impairs both G protein coupling and agonist-induced receptor internalization.
The TREM receptor family and signal integration

TREM proteins are a family of cell surface receptors that participate in diverse cell processes, including inflammation, bone homeostasis, neurological development and coagulation. TREM-1, the first to be identified, acts to amplify inflammation. Other TREM proteins regulate the differentiation and function of macrophages, microglia, dendritic cells, osteoclasts and platelets. Here we discuss the state of the field, putative ligands of TREM proteins and the challenges that remain in understanding TREM biology.
GENERALIZED EDEMA RELATED TO SENSITIVITY TO FOODS

Anecdotal reports have described association of cyclic edema with sensitivity to specific foods. Although it occurs in children, this study was carried out in 4 women, ages 23-48 yr. Fasting 4 days on distilled water resulted in wt loss (avg 3.9Kg) and elimination of edema. Individual food challenges, 4 daily, were then performed for 10 days. Measurements of wt. and urine output were obtained on constant fluid intake. Urine volumes were collected 4 hr after ingestion of foods and for each 24 hr period. Serum and urine osmolality, electrolytes and aldosterone and serum cortisol, C3, and immunoglobulins G, A, M, and E were measured serially. The decreased wt and loss of edema were maintained throughout the study period except for transient fluid retention after ingestion of particular foods. Specific foods caused decrease in 4 hr urine output to amounts less than 1 S.D. from mean 4 hr urine volume. Fifteen foods were found to produce fluid retention. Reactions were reproducible. Four patients had high serum IgE and 3 and 4 elevated IgM levels. During positive tests, urine output decreased within one hr unassociated with increased urine osmolality. A direct vascular effect with decreased renal blood flow is a likely explanation. Elimination of test positive foods resulted in good control of edema in all patients.
Engaging homeless young people in HCI research

Jill Palzkill Woelfer discusses vulnerability, susceptibility, and more than six years of research with homeless young people. In the US government and international organization documents, vulnerability has been assigned to groups as diverse as pregnant women, children, prisoners, students, employees, members of the armed forces or police, nursing home residents, people receiving welfare benefits or social assistance, other poor people, the unemployed, patients, some ethnic and racial minority groups, homeless persons, nomads, refugees, politically powerless individuals, and people unfamiliar with modern medical concepts. Identifying all these groups as vulnerable may help to frame research that is less likely to cause harm to participants. Once homeless, a young person may be further harmed by persistent negative experiences with institutions such as police and the court system, by violence, or by the situational exacerbation of mental illness or substance abuse, and so on. Harm may also arise through societal factors such as stigmatization and stereotyping. Language: en
Experimental Study Of Sweep-Out In Hydrogenated Amorphous Silicon

We present experimental results on the transient response of i/n/i hydrogenated amorphous silicon (a-Si:H) structures as a function of voltage. Comparison with M/i/n devices and results from a novel double-pulse experiment show that the transient current is initially space-charge limited and later limited by emission from deep states in the injecting n layer. Theoretical analysis of these results suggests the existence of a peak in the density of states of As-doped a-Si:H located within 0.3 eV of the conduction-band mobility edge.
A pH-sensitive RNA tertiary interaction affects self-cleavage activity of the HDV ribozymes in the absence of added divalent metal ion

Self-cleavage of the genomic and antigenomic ribozymes from hepatitis delta virus (HDV) requires divalent cation for optimal activity. Recently, the HDV genomic ribozyme has been shown to be active in NaCl in the absence of added divalent metal ion at low pH (apparent pKa 5.7). However, we find that the antigenomic ribozyme is 100 to 1000-fold less active under similar conditions. With deletion of a three-nucleotide sequence (C41-A42-A43) unique to the genomic ribozyme, the rate constant for cleavage decreased substantially, while activity of the antigenomic ribozyme was enhanced by introducing a CAA sequence. From the crystal structure, it has been proposed that C41 in this sequence is protonated. To investigate a possible connection between activity at low pH and protonation of C41, mutations were made that were predicted to either eliminate protonation or alter the nature of the tertiary interaction upon protonation. In the absence of added Mg2+, these mutations reduced activity and eliminated the observed pH-rate dependence. Thermal denaturation studies revealed a pH-sensitive structural feature in the genomic ribozyme, while unfolding of the mutant ribozymes was pH-independent. We propose that, in the absence of added Mg2+, protonation of C41 contributes to enhanced activity of the HDV genomic ribozyme at low pH.
Interaction Between an Anionic and an Amphoteric Surfactant. Part I: Monomer–Micelle Equilibrium

A mixture of anionic and amphoteric surfactants is composed of three components at intermediate pH levels: anionic, cationic (protonated amphoteric), and zwitterionic (unprotonated amphoteric). Knowledge of the composition of each surfactant in both monomer and micellar forms (monomer–micelle equilibrium) is important in applications using this mixture. Hydrogen ion titration of the mixed surfactant solution as a function of surfactant composition is combined with the pseudophase separation model and regular solution theory for the three-surfactant mixture to calculate the concentration of each surfactant in monomer and in micelle forms at different pH levels. The specific systems studied here contain sodium dodecyl sulfate (SDS) and dimethyldodecylamine oxide (DDAO), which are used in a wide range of consumer products. The degree of protonation of monomeric DDAO is not affected by the presence of SDS, indicating an insignificant formation of ion pairs between these monomers. However, the presence of SDS in micelles shifts the micellar pK a of DDAO protonation significantly and the method used here allows the quantification of partial fugacities of each individual surfactant in micelle form. The composition in the monomer phase at each pH will aid in understanding and predicting solution compositions corresponding to anionic/amphoteric surfactant precipitation boundaries, which is the focus of the subsequent paper in this series.
Factors affecting the reproducibility and validity of colposcopy for product development: review of current literature.

Colposcopy has been adapted from cervical cytology screening as a tool to assess the tolerance of vaginal products in development for anti-infective and contraceptive indications. As the vagina is poorly enervated, symptoms do not correlate well with visual findings, which increases the importance of secondary assessment. Dysplasia screening has used biopsy liberally to verify the colposcopic diagnostic impression. The few studies that include correlative biopsy with colposcopy performed for product development are reviewed. A recent study of the reproducibility of two observations at a single visit by a single or two different physicians is discussed. The review points to magnification and experience of the observer as factors in improving the agreement between observations. Observers are more likely to agree on areas greater than I cm in diameter. Variation is reduced when fewer observers are used and they report findings as dichotomous or categorical data.
Anderson localization in strongly anisotropic metals

Conditions for Anderson localization are derived for three cases: (1) anisotropic three-dimensional metal, (2) quasi-two-dimensional metal, and (3) quasi-one-dimensional metal. For all these cases the conductivity at T=0 as well as the interference correction are calculated. The simplest models are used. From the estimate \ensuremath{\Delta}\ensuremath{\sigma}/\ensuremath{\sigma}\ensuremath{\sim}1, localization conditions are obtained. It is shown that localization takes place in all three cases but in cases (2) and (3) the critical value of the random potential is essentially reduced if the overlap integrals are small. In a two-dimensional metal this refers to the conductivity along the planes whereas for the conductivity perpendicular to the planes the three-dimensional condition applies, i.e., contrary to common wisdom localization in this direction is more difficult to reach than along the planes.
Androgens in Skin Surface Lipids

Sebum collected from thigh, scalp, back, and face skin of adult males was examined for the presence, in either free or conjugated state, of seven androgens. Estimates of the quantities present were made by gas chromatographic analysis after separation of free from conjugated steroids, solvolysis of the conjugates, preliminary purification by thin-layer chromatography, and formation of the trimethylsilyl derivatives of the hydroxysteroids. Losses during these procedures were estimated by measuring the recovery of 3H-labeled steroids added to the sebum before treatment. Suggestive evidence was found for the presence of androstanedione, androstenedione, dihydrotestosterone, androsterone, and dehydroepiandrosterone. The amounts obtained were much lower than values that have been reported previously and were insufficient for full characterization. Testosterone and etiocholanolone were not detected.
Adipocyte Lineage Cells Contribute to the Skin Stem Cell Niche to Drive Hair Cycling

In mammalian skin, multiple types of resident cells are required to create a functional tissue and support tissue homeostasis and regeneration. The cells that compose the epithelial stem cell niche for skin homeostasis and regeneration are not well defined. Here, we identify adipose precursor cells within the skin and demonstrate that their dynamic regeneration parallels the activation of skin stem cells. Functional analysis of adipocyte lineage cells in mice with defects in adipogenesis and in transplantation experiments revealed that intradermal adipocyte lineage cells are necessary and sufficient to drive follicular stem cell activation. Furthermore, we implicate PDGF expression by immature adipocyte cells in the regulation of follicular stem cell activity. These data highlight adipogenic cells as skin niche cells that positively regulate skin stem cell activity, and suggest that adipocyte lineage cells may alter epithelial stem cell function clinically.
Ion association of chloride and sulphate with sodium, potassium, magnesium and calcium in seawater at 25°C

Abstract Stoichiometric association constants, which have been measured for the ion pairs of Cl − and SO 4 −2 with Na + , K + , Mg 2+ , and Ca 2+ , were used to determine the speciation in an artificial sea water containing only these ions. The resulting distribution is quite different to that found in earlier models in which chloride ion association was ignored. The concentrations of chloride ion pairs with the cations are 4 to 5 times larger than the concentrations of the sulphate ion pairs with the same cations. The total activity coefficients of the neutral salts in sea water calculated from the model are in good agreement with the experimentally measured values. The concentration of MgSO 4 0 calculated to be present agrees with the amount determined from ultrasonic absorption data. The calculated solubility of gypsum is also in good agreement with the measured values.
1,25-Dihydroxyvitamin D3 Regulates the Expression of Low-Density Lipoprotein Receptor-Related Protein 5 via Deoxyribonucleic Acid Sequence Elements Located Downstream of the Start Site of Transcription

The skeleton is a direct target of vitamin D action, where the hormone modulates the proliferation of osteoblast precursors, their differentiation into mature osteoblasts, and their functional activity. Some of these effects of vitamin D are reminiscent of those orchestrated by the Wnt signaling pathway wherein stimulation of the membrane receptor Frizzled and its coreceptor LRP5 leads to activation of beta-catenin and subsequent transcription-mediated changes in osteoblast biology. Indeed, LRP5 is now known to play a particularly important role in bone formation such that the loss of this component results in a reduction in osteoblast number, a delay in mineralization, and a reduction in peak bone mineral density. Interestingly, we discovered during the course of a vitamin D receptor (VDR) chromatin immunoprecipitation/DNA microarray analysis that 1,25-(OH)2D3 could induce binding of the VDR to sites within the Lrp5 gene locus. VDR and retinoid X receptor binding was evident both in primary osteoblasts as well as in osteoblasts of cell line origin. Importantly, this interaction between 1,25-(OH)2D3-activated VDR and the Lrp5 gene led to both a modification in chromatin structure within the Lrp5 locus and the induction of Lrp5 mRNA transcripts in vivo as well as in vitro. One of these sites within the Lrp5 locus was discovered to confer vitamin D response to a heterologous promoter when introduced into osteoblastic cells, permitting both the identification and characterization of the vitamin D response element located within. Interestingly, additional studies revealed that whereas the regulatory region in the mouse Lrp5 gene was highly conserved in the human genome, the vitamin D response element was not. Our studies show that 1,25-(OH)2D3 can enhance the expression of a critical component of the Wnt signaling pathway that is known to impact osteogenesis.
Implications of U-Pb zircon ages for the tectonic settings of the Smartville and Slate Creek complexes, northern Sierra Nevada, California

U-Pb zircon ages combined with stratigraphic and structural data indicate that ca. 160 Ma arc rocks of the Smartville Complex were constructed across ca. 200 Ma arc rocks of the Slate Creek Complex, which were already juxtaposed against more easterly units in the northern Sierra Nevada. The Slate Creek Complex, an ophiolitic thrust sheet east of the Smartville Complex, is 200-210 Ma, which precludes previous correlations with ca. 160 Ma rocks of the Smartville Complex. The Slate Creek Complex tectonically overlies chert-rich Paleozoic-early Mesozoic units along a low-angle fault that is cut by 163-168 Ma and 158-161 Ma plutons. Seven new ages of 160-163 Ma for plutonic rocks in the Smartville Complex agree with previous ages from Smartville volcanic rocks, sheeted dikes, and other plutons. In addition, one tonalite is 198 Ma and is cut by a 163 Ma dike, thus providing the first evidence of the basement of the ca. 160 Ma rocks. The 198 Ma tonalitic basement is probably correlative with the Slate Creek Complex, which contains the only other ca. 200 Ma tonalite in the northern Sierra Nevada. Thrust emplacement of the Slate Creek Complex between 200 and 163 Ma was followed by locally extensional arc magmatismmore » in the Smartville Complex at about 160 Ma, then by Nevadan contractional deformation, a sequence of Jurassic deformation similar to that in the Klamath Mountains. Nevadan deformation could be part of a noncollisional deformation or a long-lived arc (Slate Creek Complex) collision.« less
Anterior decompression and fusion for thoracolumbar fractures with neurological deficits.

Anterior spinal decompression and fusion was used as the primary treatment for thoracolumbar fractures in eleven patients with neurological deficits. Each patient achieved stability by interbody fusion. Significant progressive kyphosis did not occur. No patient with a complete neurological deficit was improved by operation, but all eight patients with partial neurological deficits showed improved lower extremity motor function postoperatively. Bladder function improved in five of the eight patients with incomplete lesions. The authors recommend this operative approach for spinal stabilization and removal of anteriorly located bone or disc fragments causing progressing and stable partial neurological deficits, and find second-stage posterior fixation with Harrington rods unnecessary in the great majority of cases.
A Stress-Dependent Hysteresis Model for PZT-Based Transducers

A ferroelastic switching model for single crystal piezoceramic compounds is developed. The model is based on a phenomenological Landau-Devonshire type thermodynamic theory for the materials. The model incorporates externally applied electric fields and compressive stress inputs to the crystals and models the 90° and 180° ferroelastic and ferroelectric switching induced by the inputs. Properties of the ferroelastic model are qualitatively similar to experimental PLZT data.
Experimental test of an infrared phase conjugation adaptive array

Results of an experimental program to investigate the properties of an infrared phase conjugation adapative array are described. Both linear and planar adaptive arrays of up to 7 elements using a new integrated frequency phase control technique at 10.6 μm are discussed. The results presented include correction for atmospheric turbulence at ranges of 1, 6, and 9.5 km. Beam broadening induced by turbulence is reduced to the array diffraction limit and target irradiance fluctuations are decreased by a factor of ≈ 20 in strong turbulence. Received irradiance fluctuations are reduced by ≈ 50 db out to 2 kHz. Beam pointing, scanning, and automatic target acquistion and tracking are demonstrated over the 1 mrad array field of view.
Motion sickness: more than nausea and vomiting

Motion sickness is a complex syndrome that includes many features besides nausea and vomiting. This review describes some of these factors and points out that under normal circumstances, many cases of motion sickness go unrecognized. Motion sickness can occur during exposure to physical motion, visual motion, and virtual motion, and only those without a functioning vestibular system are fully immune. The range of vulnerability in the normal population varies about 10,000 to 1. Sleep deprivation can also enhance susceptibility. Systematic studies conducted in parabolic flight have identified velocity storage of semicircular canal signals—velocity integration—as being a key factor in both space motion sickness and terrestrial motion sickness. Adaptation procedures that have been developed to increase resistance to motion sickness reduce this time constant. A fully adequate theory of motion sickness is not presently available. Limitations of two popular theories, the evolutionary and the ecological, are described. A sensory conflict theory can explain many but not all aspects of motion sickness elicitation. However, extending the theory to include conflicts related to visceral afferent feedback elicited by voluntary and passive body motion greatly expands its explanatory range. Future goals should include determining why some conflicts are provocative and others are not but instead lead to perceptual reinterpretations of ongoing body motion. The contribution of visceral afferents in relation to vestibular and cerebellar signals in evoking sickness also deserves further exploration. Substantial progress is being made in identifying the physiological mechanisms underlying the evocation of nausea, vomiting, and anxiety, and a comprehensive understanding of motion sickness may soon be attainable. Adequate anti-motion sickness drugs without adverse side effects are not yet available.
Mass spectrometry-based protein footprinting characterizes the structures of oligomeric apolipoprotein E2, E3, and E4.

The three common isoforms of apolipoprotein E (ApoE) differ at two sites in their 299 amino acid sequence; these differences modulate the structure of ApoE to affect profoundly the isoform associations with disease. The e4 allele in particular is strongly associated with Alzheimer’s disease. The study of the structural effects of these mutation sites in aqueous media is hampered by the aggregation proclivity of each ApoE isoform. Hence, understanding the differences between isoforms has thus far relied on lower resolution biophysical measurements, mutagenesis, homology studies, and the use of truncated ApoE variants. In this study, we report two comparative studies of the ApoE family by using the mass spectrometry-based protein footprinting methods of FPOP and glycine ethyl ester (GEE) labeling. The first experiment examines the three full-length WT isoforms in their tetrameric state and finds that the overall structures are similar, with the exception of M108 in ApoE4 which is more solvent-accessible in ...
Degradation and Recycling of the Substrate-binding Subunit of Type II Iodothyronine 5′-Deiodinase in Astrocytes

Abstract Thyroxine dynamically regulates levels of type II iodothyronine 5′-deiodinase (5′D-II) by modulating enzyme inactivation and targeting the enzyme to different pathways of internalization. 5′D-II is an ∼200-kDa multimeric protein containing a 29-kDa substrate-binding subunit (p29) and an unknown number of other subunits. In the absence of thyroxine (T4), p29 is slowly endocytosed and transported to the lysosomes. T4 treatment rapidly activates an actin-mediated endocytotic pathway and targets the enzyme to the endosomes. In this study, we have characterized the influence of T4 on the intracellular trafficking of 5′D-II. We show that T4 accelerates the rate of 5′D-II inactivation by translocating the enzyme to the interior of the cell and by sequestering p29 in the endosomal pool without accelerating the rate of degradation of p29. This dichotomy between the rapid inactivation of catalytic activity and the much slower degradation of p29 is consistent with the reuse of p29 in the production of 5′D-II activity. Immunocytochemical analysis with a specific anti-p29 IgG shows that pulse affinity-labeled p29 reappears on the plasma membrane ∼2 h after enzyme internalization in the presence of T4, indicating that p29 is recycled. Despite the ability of p29 to be recycled in the T4-treated cell, 5′D-II catalytic activity requires ongoing protein synthesis, presumably of another enzyme component(s) or an accessory enzyme-related protein. In the absence of T4, enzyme inactivation and p29 degradation are temporally linked, and pulse affinity-labeled p29 is internalized and sequestered in discrete intracellular pools. These data suggest that T4 regulates fundamental processes involved with the turnover of integral membrane proteins and participates in regulating the inter-relationships between the degradation, recycling, and synthetic pathways.
Chemisorption of NO and NH3 on cobalt: Studies by UPS, XPS, and work-function measurements

Abstract Chemisorption of NO and NH 3 on cobalt has been studied by UV and X-ray photoelectron spectroscopy (UPS and XPS) and work-function measurements. The 25°C data for NO are consistent with dissociative chemisorption below ∼5 L exposure followed by molecular chemisorption at higher exposures; complete dissociation occurs after heating to 500°C. The UPS of molecularly chemisorbed NO exhibit peaks at ∼2.7, 10.2 and 14 eV below E F , corresponding to ionization of the 2π*, (1π + 5σ), and 4σ MO's. The UPS data for NH 3 exhibit peaks at 7.9 and 11.4 eV below E F , consistent with ionization of the 3 a 1 and 7 e MO's of NH 3 and/or MO's of the fragments NH 2 and/or NH.
Thermodynamic phase of maritime Antarctic clouds from FTIR and supplementary radiometric data

[1] A Fourier Transform Infrared (FTIR) spectroradiometer was deployed at Palmer Station, Antarctica, from 1 September to 17 November 1991. This instrument is similar to the Atmospheric Emitted Radiance Interferometer (AERI) deployed with the U.S. Department of Energy Atmospheric Radiation Measurement (ARM) program. The instrument measured downwelling zenith radiance in the spectral interval 400–2000 cm−1, at a resolution of 1 cm−1. The spectral radiance measurements, which can be expressed as spectral brightness temperature Tb(ν), contain information about cloud optical properties in the middle infrared window (800–1200 cm−1, 8.3–12.5 μm). In this study, this information is exploited to (1) provide additional characterization of Antarctic cloud radiative properties, and (2) demonstrate how multisensor analysis of ARM data can potentially retrieve cloud thermodynamic phase. Radiative transfer simulations demonstrate how Tb(ν) is a function of cloud optical depth τ, effective particle radius re, and thermodynamic phase. For typical values of τ and re, the effect of increasing the ice fraction of the total optical depth is to flatten the slope of Tb(ν) between 800–1000 cm−1. For optically thin clouds (τ ∼ 3) and larger ice particles (re (ice) > 50 μm) the behavior of Tb(ν) in this interval switches from a decrease with increasing wavenumber ν to an increase with ν, once the ice fraction of the total optical depth exceeds ∼0.7. The FTIR spectra alone cannot be interpreted to obtain thermodynamic phase, because a relatively small slope in Tb(ν) between 800–1000 cm−1 could represent either an optically thin cloud in the ice or mixed phase, or an optically thick cloud radiating as a blackbody. Sky observations and ancillary radiometric data are needed to sort the FTIR spectra into categories of small cloud optical depth, where the mid-IR window data can be interpreted; and larger cloud optical depth, where the FTIR data contain information only about cloud base temperature. Spectral solar ultraviolet (UV) irradiance measurements from the U.S. National Science Foundation's UV Monitor at Palmer Station are used to estimate area-averaged effective cloud optical depth τsw, and these estimates are used to sort the FTIR data. FTIR measurements with colocated τsw < 16 are interpreted to estimate cloud thermodynamic phase. Precipitating cloud decks generally show flatter slopes in Tb(ν), consistent with the ice or mixed phase. Altostratus decks show a larger range in Tb(ν) slope than low cloud decks, including increasing slopes with ν, suggesting a more likely occurrence of the ice phase. This study illustrates how cloud thermodynamic phase can be defensibly retrieved from FTIR data if high quality shortwave radiometric data are also available to sort the FTIR measurements by cloud opacity, and both data types are available at the ARM sites.
Health of Adolescents and Young Adults: Trends in Achieving the 21 Critical National Health Objectives by 2010

PURPOSE: The 21 Critical National Health Objectives (CNHOs) for Adolescents and Young Adults derived from Healthy People 2010 addressed the most significant threats to the health of individuals aged 10-24 years. This study assessed trends in the 21 CNHOs between 1991 and 2009, and from baseline years for which 2010 targets were established to 2009, and the extent to which targets were achieved. METHODS: For one CNHO (new HIV diagnoses), national data were not available. For CNHOs measured by census systems, the percentage of change in each health outcome was calculated between 1991 and 2009 and between baseline years and 2009. Any change ≥5% was considered as an improvement or deterioration. For CNHOs measured by national probability-based surveillance surveys, multivariate logistic regression was conducted using Stata Version 10.0 (StataCorp, College Station, TX) to calculate odds ratios for each outcome from 1991, and from baseline years to 2009, controlling for gender, race/ethnicity, and age or school grade-level. To calculate the percentage of targets being achieved, the difference between baseline data and 2009 data was divided by that between baseline data and target. RESULTS: Adolescents and young adults achieved two targets (rode with a driver who had drunk alcohol, physical fighting), improved for 12 CNHOs, made mixed progress by sub-objective for two, showed no progress in four, and regressed in achieving two (Chlamydia infections; overweight). Progress varied by demographic variables. CONCLUSION: Although encouraging trends were seen in young people's health, the United States achieved only two CNHOs. Attention is needed to improve the health and reduce disparities among young people. Language: en
Inactivation of Methionine Synthetase by Nitrous Oxide in Mice

To characterize the nitrous oxide-induced inhibition of the enzyme, methionine synthetase, we measured enzyme inactivation as a function of nitrous oxide concentration and exposure time. Mice exposed to 0.8 atm nitrous oxide exhibited more than a 50 per cent decrease in liver methionine synthetase activity within 30 min, and activity dropped to 5--25 per cent of the original value after a 4-hour exposure. Although 4-hour exposures to low nitrous oxide partial pressures (less than 0.05 atm) did not significantly alter methionine synthetase activity, higher concentrations of nitrous oxide caused a progressive inhibition over this time period. Continuous exposure to trace levels of nitrous oxide (approximately 1100 ppm) for eight to 22 days produced a small but significant reduction in liver and brain methionine synthetase activity. Methionine synthetase activity returned to control levels two to four days following inactivation. Other anesthetics (xenon, halothane, isoflurane, enflurane) did not produce inactivation.
“A woman's worst enemy”;: Reflections on a narrative of organizational life and female identity

Abstract Although feminist thought increasingly infuses the study of organizational communication, much of the feminist literature to date has failed to engage the practices of women in actual organizations. This case study moves to address that neglect, using data gathered in an organization founded by and largely comprised of women. Specifically, the essay emphasizes the contribution of women as active agents who construct their work community, and it illuminates the ways in which women may participate in the devaluation of women. The first section articulates the feminist perspective that informs our analysis. After describing the organization in question, we explore the existence of a narrative of collective self‐awareness as a distinctly “female”; community. Although this narrative includes positive themes, members tell the tale of a divisiveness—a “cattiness"—that they perceive as a uniquely “female”; practice. We discuss the theoretical and pragmatic implications of this narrative of identity. As a...