cssi/SciSciGPT-SciSciNet huggingface dataset:
The Structure of HCV Membrane Protein P7 in Bilayers by NMR Spectroscopy

p7 is a 63-residue membrane protein encoded by Hepatitis C virus (HCV). It is essential for HCV proliferation. It consists of two transmembrane spanning regions connected by a short, structured cytoplasmic loop. p7 serves as a novel target for anti-viral drugs, since it is involved in assembly and release of mature virus particles. Thus, the three-dimensional structure of this protein is of considerable interest since it could contribute to the discovery drugs specific for this unique viral protein. Recently, structures of p7 from two different genotypes were determined; these structures were calculated from solution NMR measurements made on samples of two different types of p7-containing micelles. Due to the difference in sequence and/or the detergents, the two bare little resemblance to one another. Therefore, they cannot be relied upon to represent the native bilayer structure. In order to determine the structure of the protein in its native environment we incorporated expressed and purified p7 into liposomes. Rotationally aligned (RA) magic angle spinning (MAS) solid-state NMR, a recently developed method for studying membrane proteins in proteoliposomes, was utilized to determine the structure of p7 in liquid crystalline phospholipid bilayers under physiological conditions. This structure will be discussed in terms of the biological roles of p7.
K+/Na+ selectivity in K channels and valinomycin: over-coordination versus cavity-size constraints.

Abstract Potassium channels and valinomycin molecules share the exquisite ability to select K+ over Na+. Highly selective K channels maintain a special local environment around their binding sites devoid of competing hydrogen bond donor groups, which enables spontaneous transfer of K+ from states of low coordinations in water into states of over-coordination by eight carbonyl ligands. In such a phase-activated state, electrostatic interactions from these 8-fold binding sites, constrained to maintain high coordinations, result in K+/Na+ selectivity with no need for a specific cavity size. Under such conditions, however, direct coordination from five or six carbonyl ligands does not result in selectivity. Yet, valinomycin molecules achieve selectivity by providing only six carbonyl ligands. Does valinomycin use additional coordinating ligands from the solvent or does it have special structural features not present in K channels? Quantum chemical investigations undertaken here demonstrate that valinomycin selectivity is due to cavity size constraints that physically prevent it from collapsing onto the smaller sodium ion. Valinomycin enforces these constraints by using a combination of intramolecular hydrogen bonds and other structural features, including its specific ring size and the spacing between its connected ligands. Results of these investigations provide a consistent explanation for the experimental data available for the ion-complexation properties of valinomycin in solvents of varying polarity. Together, investigations of these two systems reveal how nature, despite being popular for its parsimony in recycling functional motifs, can use different combinations of phase, coordination number, cavity size, and rigidity (constraints) to achieve K+/Na+ selectivity.
Abstract 3871: Analysis of gene expression patterns downstream of multiple metastatic suppressor genes.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC In recent decades, a distinction has been made between the tumorigenesis and metastasis processes. Metastasis Suppressor Genes (MSGs) are down-regulated in the metastasis compared with the primary tumor. When re-expressed in experimental models, MSGs are able to block spread to distant sites without effecting primary tumor formation. After the discovery of the first MSG, NME1, many others have been identified. To date more than 20 genes have been described to have MSG functions. They include factors involved in cellular proliferation, motility, adhesion, invasion, resistance to apoptosis, and angiogenesis. We hypothesized that common signaling pathways mediate the effects of many MSGs. Using microarray databases of breast cancer cell lines, and siRNA down regulation of 18 MSGs in human MCF-7 breast carcinoma cells (NME1, BRMS1, CD82, CDH1, CDH2, CASP8, MKK4, MKK6, MKK7, MAPK14, GSN, ARHGDIB, AKAP12, DRG1, CD44, PEPB1, RRM1, KISS), we conducted a bioinformatic search for common pathways. Several candidate genes were identified whose expression was inversely related to at least five MSGs. These candidates include UGT1A, PDE5A, SRMS, IL11Ralpha, DNM3, OAS1, BCAR4, and CA9, many of which are previously unknown in the metastasis literature. After stable down-regulation of each candidate gene in the highly aggressive breast cancer cell line MDA-MB-231, in vitro experiments evaluating cell proliferation and motility were performed to validate their link to the metastatic property of tumor cells. Promising data have been obtained with PDE5A. PDE5 (phosphodiesterase type 5A) is a key enzyme involved in the regulation of cGMP-specific signaling pathways in processes such as smooth muscle contraction and relaxation. PDE5A mRNA expression was upregulated by siRNA to 13 MSGs: ARHGDIB, CASP8, CD44, CDH1, CDH2, CDH11, GSN, MKK4, MKK6, MKK7, NME1, PEBP1, RRM1. Stable clones down-regulating PDE5A (MDA-MB-231 shPDE5A) were tested as described above and no difference in cell proliferation was observed, while a 58% reduction in cell motility compared to the empty vector-expressing cells was measured (p=0.0001). An experimental metastasis assay was conducted to determine if altered PDE5A expression functionally contributed to breast cancer metastasis. Tail vein injection of MDA-MB-231 shPDE5A in athymic/nude mice resulted in a 62% reduction in lung metastasis formation compared to the injection of empty-vector expressing cells (p= 0.0004). This result suggests that PDE5A is a new potential therapeutic target in breast cancer metastasis. Citation Format: Natascia Marino, Joshua W. Collins, Changyu Shen, George W. Sledge, Patricia S. Steeg. Analysis of gene expression patterns downstream of multiple metastatic suppressor genes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3871. doi:10.1158/1538-7445.AM2013-3871
Heat flow studies: Constraints on the distribution of uranium, thorium and potassium in the continental crust

Abstract To study the amount of heat generated by radioactive decay in the continental crust, the usual practice in the literature is to fit to the heat flow and radioactivity data a relationship of the form: Q = Qr + D · A where Q and A are the observed heat flow and radiogenic heat production. Qr is the “reduced” heat flow and D is a depth scale. This procedure implicitly assumes that uranium, thorium and potassium have identical distributions in the crust. We suggest that significant information may be lost as the three radioelements may in fact be affected by processes operating over different depths. Data published for four heat flow provinces throughout the world are used to estimate the distributions of uranium, thorium and potassium in the continental crust. These distributions are characterized by a depth scales defined as follows: Di =∫0h Ci(z)Ci(0)dz where h is the thickness of the layer containing the bulk of radioactivity and Ci(z) the concentration of element i at depth z. Three depth scales are computed from a least-squares fit to the following relationship: Q = Qr + DU · AU + DT · AT + DK · AT where Q is the observed heat flow and Qr some constant (a reduced heat flow). Ai is the heat generation rate due to the radioactive decay of element i, and Di is the corresponding depth scale. The analysis suggests that the three distributions are different and that they have the same basic features in the four provinces considered. The depth scale for potassium is large in granitic areas, that for thorium is small and that for uranium lies between the other two. We propose a simple model according to which each radioelement essentially provides a record for one process. Potassium gives a depth scale for the primary differentiation of the crust. Thorium gives the depth scale of magmatic or metamorphic fluid circulation. Finally, the uranium distribution reflects the late effects of alteration due to meteoric water. We show that the heat flow and radioactivity data are compatible with this model. Our analysis and numerical results are supported by data from deep boreholes and by geochemical evidence, such as detailed investigations of plutonic series and studies of U-Th-Pb systematics.
Impact of HESI Specialty Exams: the ninth HESI Exit Exam validity study.

Using an ex post facto, nonexperimental design, this, the ninth validity study of Elsevier's HESI Exit Exam (E 2 ), reexamined the predictive accuracy of the E 2 . The value of administering HESI Specialty Exams within the nursing curriculum in terms of E 2 scores was also investigated. The sample was composed of nursing students ( N = 3,790) from 63 randomly selected schools—26 baccalaureate, 31 associate degree, and 6 diploma programs—throughout the United States who took the E 2 between September 2008 and August 2009. As in the previous 8 studies, the E 2 was found to be highly accurate (96.61%) in predicting success on the National Council Licensure Examination for Registered Nurses (NCLEX-RN). Findings also indicated that students who took one or more HESI Specialty Exams during their nursing curriculum had a significantly higher mean E 2 score ( P ≤ .0001) than students who did not take HESI Specialty Exams during their nursing curriculum. Of the 8 HESI Specialty Exams investigated, scores on the Critical Care, Pediatrics, and Medical–Surgical specialty exams were most predictive of NCLEX-RN success. Schools of nursing that used HESI Specialty Exams as course final exams had a significantly higher mean E 2 score ( P
Lack of timely follow-up of abnormal imaging results and radiologists' recommendations.

Abstract Purpose Abnormal imaging results may not always lead to timely follow-up. We tested whether certain aspects of communication in radiology reports influence the response of the referring providers, and hence follow-up on abnormal findings. Methods We focused on 2 communication-related items that we hypothesized could affect follow-up: expressions of doubt in the radiology report, and recommendations for further imaging. After institutional review board approval, we conducted a retrospective review of 250 outpatient radiology reports from a multispecialty ambulatory clinic of a tertiary-care Veterans Affairs facility. The selected studies included 92 cases confirmed to lack timely follow-up (ie, further tests or consultations, treatment, and/or communication to the patient within 4 weeks), as determined in a previous study. An additional 158 cases with documented timely follow-up served as controls. Doubt in the narrative was measured by the presence of key phrases (eg, "unable to exclude," "cannot exclude," "cannot rule out," "possibly," and "unlikely"), in the absence of which we used reviewer interpretation. A physician blinded to follow-up outcomes collected the data. Results Patients whose reports contained recommendations for further imaging were more likely to have been lost to follow-up at 4 weeks compared with patients without such recommendations ( P = .01). Language in the report suggestive of doubt did not affect the timeliness of follow-up ( P = .59). Conclusions Abnormal imaging results with recommendations for additional imaging may be more vulnerable to lack of timely follow-up. Additional safeguards, such as tracking systems, should be developed to prevent failure to follow up on such results.
Observations on the yolk sac and Reichert's membrane of ectopic mouse embryos.

Embryos developing from mouse blastocysts transplanted to the kidneys and testes of recipient mice were studied by light and electron microscopy. The yolk sac and Reichert's membrane of ectopic embryos were morphologically normal and had normal staining and histochemical properties. In electron micrographs Reichert's membrane was of low electron density and had a fine fibrillar structure. The cells of the parietal material within their ergastoplasm that closely resembled the membrane both in texture and electron density. The probability that the parietal yolk sac cells are responsible for the elaboration of Reichert's membrane in the mouse is discussed in relation to other work on the subject. The occurrence of discrete eosinophilic bodies in transplants in which the development of the inner cell mass was abortive is reported. The light microscopic appearance and fine structure of these bodies revealed close similarities to the parietal yolk sac and to Reichert's membrane. It is concluded that they represent yolk sac cells embedded in an abnormal Reichert's membrane.
The sodium/galactose symporter crystal structure is a dynamic, not so occluded state.

The recent elucidation of the sodium/galactose symporter structure from the Vibrio parahaemolyticus bacterium, vSGLT, has revealed a similarity in the core architecture with transporters from different gene families, including the leucine transporter (LeuT). Even though several transporters sharing this core have been structurally determined over the past few years, vSGLT is the only one crystallized in the substrate-bound inward-facing conformation so far. In this study, we report the first insight into the dynamics and coordination of the galactose (Gal) and proposed Na+ ion in vSGLT using a series of molecular dynamics simulations with a total time of about 0.1 μs. Our study reveals new residues, not observed in the crystal structure, which closely interact with the Na+ ion or the substrate for extended times, and shows that in the crystallized conformation, a Na+ ion placed at the site equivalent to Na2 in LeuT can escape into the intracellular (IC) space in the absence of external forces. We have identified the highly conserved Asp189 as a likely binding residue on the pathway of Na+ into the IC cavity. The release of Gal, on the other hand, requires the rotation of the side chain of the inner hydrophobic gate, Tyr263, without a significant change in vSGLT backbone conformation. Our simulations further show that the crystal structure represents but one accessible binding pose of Gal and Na+ among an ensemble of microstates, and that the Gal undergoes versatile alternate interactions at the binding pocket.
Maximum Likelihood Estimation of Models with Beta-Distributed Dependent Variables

Research in political science is often concerned with modeling dependent variables that are proportions. Proportions are relevant in a wide variety of substantive areas, including elections, the bureaucracy, and interest groups. Yet because most researchers rely upon an approach, OLS, that does not recognize key aspects of proportions, the conclusions we reach from normal models may not provide the best understanding of phenomena of interest in these areas. In this paper, I use Monte Carlo simulations to show that maximum likelihood estimation of these data using the beta distribution may provide more accurate and more precise results. I then present empirical analyses illustrating some of these differences.
Predicting field performance of Douglas-fir seedlings: comparison of root growth potential, vigor and plant moisture stress

Douglas-fir [Pseudotsuga menziesii (Mirb.) Franco] seedlings were evaluated- by three measurements of seedling quality — root growth potential or RGP, vigor, and plant moisture stress or PMS — and the results were correlated with subsequent field performance. Measurements made by each method were significantly (p≤ 0.05) correlated with first- and second-year survival and terminal height growth. Seedlings from lots that grew many new roots during a 28-day interval in a growth room (RGP evaluation) or that survived for 6 weeks in the growth room and initiated rapid budburst (vigor evaluation) or whose plant moisture stress values remained fairly constant during 1 week after potting (PMS evaluation) had the greatest field survival and height growth.
Introduction to Special Series on College Students With ADHD

Increasing empirical attention has been focused on college students with ADHD in recent years. In this special series, five studies are included that address psychosocial issues, comorbidity, and treatment of college students with ADHD. The nature and results of each study are briefly described. This special series of articles significantly advances our knowledge of critical issues with respect to psychosocial functioning, alcohol/substance use, comorbidity, and treatment of ADHD in college students.
Echelle-Type Spectrograph for the Near Infrared*

The 5-m evacuable double-passed grating spectrograph previously described has been modified so that all but 10 in. of the total optical path is now evacuable.The foreprism system has been redesigned so that overlapping high-order infrared spectra can be separated allowing the use of coarse gratings. Provision is made to keep the band pass of the foreprism monochromator in synchronization with the rotation of the grating.An addition to the scanning system provides wavelength markers on the recorder chart. The wavelength marker system is arranged so that accelerated scanning can be performed in traversing regions where lines are not being measured. The marker system is also useful in expediting the measurement of small frequency shifts.The procedure used for accurate determination of the dispersion by means of interferometric calibration is described.
Quantitative fluorescence measurements of AO-stained normal and malignant bladder cells.

Quantitative, corrected fluorescence emission spectra from the nuclei of acridine orange-stained bladder epithelial cells were obtained with a corrected spectrum microspectrofluorophotometer (MSF)5 which is calibrated with a phosphor particle fluorescence standard. The spectra demonstrated that the green fluorescence band (λmax≅530 nm) is stoichiometrically related to the amount of nucleic acids (NA) present in a given nucleus, provided this spectroscopic species has reached saturation. The shape of this spectral band is constant. On the basis of this information, we used a simple microfluorometer, (SFM), calibrated with the phosphor particle standard, to routinely measure the amount of green fluorescence emission from the nuclei of AO-stained bladder epithelial cells. The amount of green fluorescence per normal nucleus never exceeded 0.5 phosphor particle units (ppu). In contrast, in every sample containing malignant or cancerrelated cells, one or more cells contained nuclei that exhibited more than 0.5 ppu total green nuclear fluorescence. Results obtained with the SFM on 794 AO-stained cells from 80 samples taken from 40 patients are reported here. Samples consisted of urine specimens, bladder washings, and biopsies. One or more malignant cells from every grade 3 or 4 tumor and 17 of 17 grade 1 or 2 tumors showed markedly elevated levels of total (integrated) green nuclear fluorescence indicating the presence of DNA aneuploidy, strongly, suggestive of the presence of malignant or potentially malignant cells. Comparison with diagnoses based on H and E-stained biopsy material and Papanicolaou-stained cytological preparations show excellent correlation. The quantitative fluorescence measurements demonstrate a clear difference between negatives and positives with linear ordering up through Grade 4 and CIS. Grades 1 and 2 were clearly different from 3 and 4 (p<0.001). The results indicate that the quantitative fluorescence methodology reveals the presence and extent of DNA aneuploidy which may prove to be a more sensitive cytologic method for detection of low grade tumors and may also provide an objective biochemical basis for tumor grade classification. Detecting the presence of DNA aneuploidy may even serve to provide earlier detection than is possible with conventional means, but this remains to be confirmed by longitudinal studies.
Gestational glucose tolerance and cord blood leptin levels predict slower weight gain in early infancy.

Objective To determine the extent to which known prenatal and perinatal predictors of childhood obesity also predict weight gain in early infancy. Study design We studied 690 infants participating in the prospective cohort Project Viva. We measured length and weight at birth and at 6 months. Using multivariable linear regression, we examined relationships of selected maternal and infant factors with change in weight-for-length z -score (WFL- z ) from 0 to 6 months. Results Mean (standard deviation) change in WFL- z from 0 to 6 months was 0.23 (1.11), which translates to 4500 grams gained from birth to 6 months of life in an infant with average birth weight and length. After adjustment for confounding variables and birth weight-for-gestational age z -score (-0.28 [95% confidence interval, -0.37, -0.19] per unit), cord blood leptin (-0.40 [95% confidence interval, -0.61, -0.19] per 10 ng/mL), and gestational diabetes -0.50 [95% confidence interval, -0.88, -0.11] versus normal glucose tolerance) were each associated with slower gain in WFL- z from 0 to 6 months. Conclusions Higher neonatal leptin and gestational diabetes predicted slower weight gain in the first 6 months of life. The hormonal milieu of the intrauterine environment may determine growth patterns in early infancy and thus later obesity.
Pain interference, gambling problem severity, and psychiatric disorders among a nationally representative sample of adults

Abstract Background and aims A paucity of studies has examined the association between gambling and pain interference. We examined differences in the associations of gambling problem severity and psychiatric disorders among a nationally representative sample of adults with varying levels of pain interference. Methods Chi-square tests and logistic regression analyses were performed on National Epidemiologic Survey on Alcohol and Related Conditions data from 41,987 adult respondents (48% men; 52% women), who were categorized according to two levels of pain interference (i.e., no or low pain interference [NLPI] or moderate or severe pain interference [MSPI]) and three levels of gambling problem severity (i.e., non-gamblers or low-frequency gamblers [NG], low-risk or at-risk gamblers [LRG], and problem or pathological gamblers [PPG]). Results MSPI respondents exhibited higher rates of PPG than NLPI respondents. Categories of Axis I disorders and clusters of mood, anxiety and substance-use disorders showed sim...
The effect of nitrogen fertilization on the phenology of roots in a barrier island sand dune community

Little work has been done on the phenology of root growth and senescence largely due to methodological difficulties. The application of minirhizotron technology has enabled the tracking of individual roots through an entire growing season. As a result, direct measures of mortality, root growth, and an analysis of cohorts can be obtained. This study examined the belowground response of vegetation in a nutrient limited system to nitrogen addition. Small plots on a 36 year old dune on Hog Island, a barrier island in the Virginia Coast Reserve Long Term Ecological Research Site, were fertilized with nitrogen. Minirhizotron tubes were installed in each fertilized and control plot. Each tube was sampled monthly for nine months, March through October of 1992. Root length density increased throughout the growing season with the greatest root length density in the top 20 cm of the soil profile. The fertilized plots had greater root length densities (14.1 mm cm-2) than the unfertilized plots (2.9 mm cm-2). There was no significant depth × treatment interaction. Root mortality did not significantly change with fertilization. The largest loss of roots for a cohort occurred within the first month. The dune grassland community did not respond to fertilization with large changes in root distribution or increases in mortality in this study.
Kinetic analysis of ammonia synthesis catalyzed by barium-promoted ruthenium supported on zeolite X

Abstract The kinetics of ammonia synthesis from dinitrogen and dihydrogen were studied at 20.7 atm total pressure over a series of zeolite X supported Ru (∼2 wt.%) catalysts that were promoted by occluded barium. For comparison, two different Cs-promoted Ru/MgO catalysts were also included. In general, the reaction was first order in dinitrogen, about negative one order in dihydrogen, and weakly inhibited by ammonia. The average turnover frequencies of the Ba-promoted Ru/zeolite catalysts were within a factor of two of the highly active Cs-promoted Ru/MgO catalysts. The effect of Ba loading on an average turnover frequency and overall Ru metal utilization indicated an optimal content of 20 excess Ba cations per unit cell. A uniform surface model, assuming dinitrogen adsorption is the rate-determining step and both nitrogen and hydrogen atoms are present on the surface, reproduced well the measured kinetics over a wide range of temperatures and feed ratios. Results from fitting the kinetic parameters suggest that addition of basic promoters to supported Ru lowers the activation barrier for dinitrogen adsorption.
Can false memories be corrected by feedback in the DRM paradigm

Normal processes of comprehension frequently yield false memories as an unwanted by-product. The simple paradigm now known as the Deese/Roediger-McDermott (DRM) paradigm takes advantage of this fact and has been used to reliably produce false memory for laboratory study. Among the findings from past research is the difficulty of preventing false memories in this paradigm. The purpose of the present experiments was to examine the effectiveness of feedback in correcting false memories. Two experiments were conducted, in which participants recalled DRM lists and either received feedback on their performance or did not. A subsequent recall test was administered to assess the effect of feedback. The results showed promising effects of feedback: Feedback enhanced both error correction and the propagation of correct recall. The data replicated other data of studies that have shown substantial error perseveration following feedback. These data also provide new information on the occurrence of errors following feedback. The results are discussed in terms of the activation-monitoring theory of false memory.
Phonetically Governed Voicing Onset and Offset in Preschool Children Who Stutter

Abstract Phonetically governed changes in the fundamental frequency (F0) of vowels that immediately precede and follow voiceless stop plosives have been found to follow consistent patterns in adults and children as young as four years of age. In the present study, F0 onset and offset patterns in 14 children who stutter (CWS) and 14 children who do not stutter (CWNS) were investigated to evaluate differences in speech production. Participants produced utterances containing two VCV sequences. F0 patterns in the last ten vocal cycles in the preceding vowel (voicing offset) and the first ten vocal cycles in the subsequent vowel (voicing onset) were analyzed. A repeated measures ANOVA revealed no group differences between the CWS and CWNS in either voicing onset or offset gestures. Both groups showed patterns of F0 onset and offset that were consistent with the mature patterns seen in children and adults in previous studies. These findings suggest that in both CWS and CWNS, a mature pattern of voicing onset and offset is present by age 3;6. This study suggests that there is no difference between CWS and CWNS in the coordination of respiratory and laryngeal systems during voicing onset or offset. Educational objectives: The reader will be able to: (a) discuss the importance of investigating children who stutter close to the onset of stuttering; (b) describe the typical change in F0 during voicing onset; (c) discuss the potential implications of these results with regard to future research.
Electrochemical synthesis of cobalt hydroxide films with tunable interlayer spacings

An electrochemical synthetic condition is developed to produce cobalt hydroxide films with significantly increased basal spacings (d001 ≥ 25.0 A) by incorporating anionic surfactants (i.e. sodium dodecyl sulfate and 1-hexadecanesulfonate) into the interlayer regions via electrodeposition.
The efficacy and comfort of full-body vacuum splints for cervical-spine immobilization

Abstract We performed a prospective crossover study to determine the cervical spine immobilization and comfort level of healthy subjects on a full-body vacuum splint in comparison with a standard backboard, with and without cervical spine collars. Twenty-six healthy volunteers were immobilized on a backboard (BB) and a full-body vacuum splint (VS), both with and without a cervical collar (CC). Pre- and post-immobilization cervical spine range-of-motion measurements were made using an electronic digital inclinometer and a standard hand-held goniometer. Subjects were also asked to subjectively grade their immobilization and discomfort both overall and in seven specific body regions. No statistically significant difference was found between the VS+CC and the BB+CC for flexion and rotation, although the VS+CC combination provided significantly superior immobilization to the BB+CC for extension and lateral bending. The VS alone, in all cases except extension, provided superior immobilization to the BB alone. A statistically significant difference in subjective perception of immobilization was noted, with the BB being less effective than the other three alternatives and the VS+CC providing the best immobilization. A significant difference in overall comfort and occipital region comfort, favoring the vacuum splint, was found. In conclusion, the vacuum splint is an effective and more comfortable alternative to the backboard for cervical spine immobilization.
Problems associated with the application of short‐term tests for mutagenicity in mass‐screening programs

The application of short-term tests for toxicological evaluation of environmental chemicals is certainly a reality in the near future as a result of the Toxic Substances Control Act, as well as other regulations under development [de Serres, 1977]. Many of the problems associated with this testing in the area of genetic toxicology are under study at the National Institute of Environmental Health Sciences in our National Toxicology Program and at the Environmental Protection Agency in their Gene-Tox Program. The other problems that I have discussed in connection with standardization of protocols, protocol review and modification, and training of personnel are not being pursued aggressively. Perhaps with their definition and acceptance as meaningful problems, mechanisms will be established for their resolution. It is in these latter areas that I hope that this society can provide the forceful leadership that will result in their resolution in the near future.
Channel-opening mechanism of a kainate-activated glutamate receptor: Kinetic investigations using a laser-pulse photolysis technique

Kainate is an excitatory neurotransmitter that binds to the kainate and AMPA receptor subtypes of the glutamate receptor and triggers the formation of cation permeable transmembrane channels in these receptors. In the present report the channel-opening mechanism of the AMPA receptors by kainate has been determined in rat hippocampal neurons using two different kinetic methods, namely, the rapid-flow method (cell-flow) with a 10 ms time resolution and a laser-pulse photolysis technique with a approximately 65 microseconds time resolution. The whole-cell currents induced by kainate, using the cell-flow method, are nondesensitizing and inhibited significantly by CNQX and hence pertain to activation of the AMPA receptors and not the kainate receptors. The cell-flow measurements were used to evaluate the constants pertaining to the minimum mechanism that could account for the concentration of the receptor in the open-channel form over a 500-fold range of kainate concentration. These constants, namely, the intrinsic dissociation constant of kainate from the AMPA receptor and the channel-opening equilibrium constant, were determined to be 140 +/- 30 microM and 8 +/- 2, respectively. On the other hand, the kinetics of the steps leading to channel opening was evaluated using the laser-pulse photolysis techniques. In this technique whole-cell currents were obtained by releasing kainate in the submillisecond time scale near the cell by photolysis of N-(alpha-carboxy-2-nitrobenzyl) kainate. The concentration of the released kainate was calculated by comparing the whole-cell currents obtained from the laser-pulse photolysis experiments with the whole currents obtained with 100 microM kainate on the same cell using cell-flow measurements. The rate constants for channel opening and closing were then determined from the observed rate constants for the current rise obtained as a function of kainate concentration. These rates were 5000 +/- 2000 and 640 +/- 30 s-1, respectively. The rate and equilibrium constants obtained in the present report allow an evaluation of the fraction of the receptors in the open-channel form as a function of time and kainate concentration, hence providing insight into the role of kainate in neuronal signal transmission.
Interaction of Gelatin-Stabilized Radiogold Colloid and Plasma Proteins

SummaryThe relative mobilities of Aurcoloid and gelatin have been demonstrated in vivo and in vitro by paper electrophoretic methods. Addition of Aurcoloid and gelatin to plasma resulted in a radiogold-gelatin complex which migrated at the same rate as alpha globulins. Aurcoloid in plasma did not migrate. The formation of an Aurcoloid-gelatin complex was associated with a decreased rate of disappearance of radiogold from the circulation.
The Reactions Al(2P) + H2 → AlH2(12A‘, 22A‘) → AlH2(X2A1) or AlH(X1Σ+) + H: Unusual Conical Intersections and Possible Nonadiabatic Recrossing

The energies and derivative couplings are computed in the vicinity of the 12A‘−22A‘ seam of conical intersections for AlH2. It is shown that the reaction path for the decomposition of excited vibrational levels of AlH2(X2A1) to Al + H2 passes quite close to the minimum energy crossing point (MECP), the minimum energy point on the seam of conical intersections. Near the MECP the seam of conical intersections exhibits an unusual trifurcation with a C2v portion dividing into a branch that preserves C2v symmetry and two symmetry equivalent branches that have only Cs symmetry.
Global Protein Stability Profiling in Mammalian Cells

The abundance of cellular proteins is determined largely by the rate of transcription and translation coupled with the stability of individual proteins. Although we know a great deal about global transcript abundance, little is known about global protein stability. We present a highly parallel multiplexing strategy to monitor protein turnover on a global scale by coupling flow cytometry with microarray technology to track the stability of individual proteins within a complex mixture. We demonstrated the feasibility of this approach by measuring the stability of ∼8000 human proteins and identifying proteasome substrates. The technology provides a general platform for proteome-scale analysis of protein turnover under various physiological and disease conditions.
Step-edge energetics of the Ge/GaAs(001)-(1 × 2) superstructure

Abstract For the first time the step-edge energies have been measured for a superstructure resulting from nonpolar/polar heteroepitaxy. Using scanning tunneling microscopy, we have investigated the morphology of the Ge/GaAs(001)-(1 × 2) reconstructed surface using substrates miscut by 1° and 2° toward the [110] direction to expose the A-type steps. The superstructure has well-defined step edges and smooth terraces, even when the initial substrate is rough. The primary defect structures are antiphase domain boundaries remaining from the formation of the (1 × 2) reconstruction. The kink energies are similar to those for the A-type steps on both the GaAs(001)-(2 × 4) and Si(100)-(2 × 1) surfaces. In addition, there is an apparent kink-kink attraction of about 120 meV between nearest-neighbor kinks. Using the model incorporating nearest-neighbor interactions between kinks developed for the Ge/GaAs(001)-(1 × 2) superstructure, the kink-kink repulsion observed on GaAs(001)-(2 × 4) is discussed quantitatively and shown to involve energies significantly higher than those which could be reasonably attributed to dipole-dipole interactions.
Limitations of the bowel bag contouring technique in the definitive treatment of cervical cancer

Abstract Purpose Incidence of acute grade 3 and 4 small bowel toxicity in the definitive treatment of cervical cancer is approximately 15%. Given uncertainties in position of the bowel at time of treatment, techniques including the contouring of a bowel bag have been suggested. The purpose of this study is to describe interfraction variability in bowel location for the female pelvis with intact reproductive organs and to characterize the ability of the bowel bag technique, as described in the Radiation Therapy Oncology Group pelvic normal tissue contouring guidelines, to account for organ motion in this specific clinical setting. Methods and Materials Bowel position was assessed for 45 computed tomographic scans used in treatment planning for 9 consecutive cervical cancer patients. After a single operator contoured bowel loops, most superior, anterior, posterior, and inferior positions of bowel were recorded. Mixed effects models were used to assess significance of interfraction variability. Frequency of bowel loop migration outside of the bowel bag was then considered for each patient given all potential bowel bag volumes. Standardized scoring was used to determine additional margins that would be required to account for 95%, 90%, and 85% of significant bowel motion. Results Interfraction variability in the inferior-most bowel position was significant (P = .002). Median maximum variation in the inferior bowel position was 2.1 cm (range, 0.9 cm-4.8 cm). When applying the bowel bag technique, 100% of bowel motion was accounted for as the bowel translated laterally, anteriorly, posteriorly, and superiorly, though accounted for just 70.3% of motion in the inferior direction. A 4-cm inferior margin was required to account for 90% of motion in the inferior direction. Conclusions In the intact female pelvis, the bowel bag technique is successful in accounting for most interfraction variability in bowel position but underestimates inferior motion. Until an improved approach to predicting small bowel motion can be routinely implemented, a focus on decreasing dose to potential bowel space should be emphasized.
Role of environmental factors and mine geometry in thermal IR mine signatures

Thermal IR signatures of buried land mines are affected by various environmental conditions as well as the mine's composition, size and burial geometry. In this work we present quantitative relations for the effect of those factors on the signature's peak contrast and apparent diameter. We begin with a review of the relevant phenomena and the underlying physics. A three-dimensional simulation tool developed by the authors is used to simulate signatures for the case of a static water distribution. We discuss efforts to validate the model using experimental data collected at Fort A.P. Hill, VA. Using this simulation tool a variety of factors are considered, including soil water content, soil sand content, wind speed, mine diameter and mine burial depth.
Activated ERK2 Is a Monomer in Vitro with or without Divalent Cations and When Complexed to the Cytoplasmic Scaffold PEA-15

The extracellular signal-regulated protein kinase, ERK2, fully activated by phosphorylation and without a His6 tag, shows little tendency to dimerize with or without either calcium or magnesium ions when analyzed by light scattering or analytical ultracentrifugation. Light scattering shows that ∼90% of ERK2 is monomeric. Sedimentation equilibrium data (obtained at 4.8–11.2 μM ERK2) with or without magnesium (10 mM) are well described by an ideal one-component model with a fitted molar mass of 40180 ± 240 Da (without Mg2+ ions) or 41290 ± 330 Da (with Mg2+ ions). These values, close to the sequence-derived mass of 41711 Da, indicate that no significant dimerization of ERK2 occurs in solution. Analysis of sedimentation velocity data for a 15 μM solution of ERK2 with an enhanced van Holde–Weischet method determined the sedimentation coefficient (s) to be ∼3.22 S for activated ERK2 with or without 10 mM MgCl2. The frictional coefficient ratio (f/f0) of 1.28 calculated from the sedimentation velocity and equil...
Structural Characterization of the Boca/Mesd Maturation Factors for LDL-Receptor-Type β Propeller Domains

Folding and trafficking of low-density lipoprotein receptor (LDLR) family members, which play essential roles in development and homeostasis, are mediated by specific chaperones. The Boca/Mesd chaperone family specifically promotes folding and trafficking of the YWTD β propeller-EGF domain pair found in the ectodomain of all LDLR members. Limited proteolysis, NMR spectroscopy, analytical ultracentrifugation, and X-ray crystallography were used to define a conserved core composed of a structured domain that is preceded by a disordered N-terminal region. High-resolution structures of the ordered domain were determined for homologous proteins from three metazoans. Seven independent protomers reveal a novel ferrodoxin-like superfamily fold with two distinct β sheet topologies. A conserved hydrophobic surface forms a dimer interface in each crystal, but these differ substantially at the atomic level, indicative of nonspecific hydrophobic interactions that may play a role in the chaperone activity of the Boca/Mesd family.
Possible involvement of a hypothalamic dopaminergic receptor in development of genetic obesity in mice

Abstract We have studied the binding of the dopaminergic agonist 2-[5,8- 3 H]amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene ([ 3 H]ADTN) to hypothalamic membranes from the genetically diabetic-obese (db/db) mice and their lean littermates. The specific binding of [ 3 H]ADTN was defined as the difference between the radioligand binding to the membranes in the absence or presence of 1 μM (+)-butaclamol. In order to control nonspecific binding, all binding assays were performed in the presence of 0.1 mM catechol and 0.3 mM ascorbic acid. Binding of [ 3 H]ADTN was rapid, dissociable, saturable and stereoselective. (+)-Butaclamol was very potent whereas (−)-butaclamol was ineffective in inhibiting the binding of this radioligand. Concentration-dependent binding experiments and Scatchard analysis of the data yielded dissociation constatne ( K d ) of 3.5–4.2 nM and number of binding sites ( n ) equivalent to 170–200 fmol/mg protein for lean mice. For db/db mice, the data yielded a K d of 4.0–4.7 nM and an n equivalent to 170–200 fmol/mg protein. It was also shown that the anorexic drugs, amphetamine and fenfluramine, inhibited [ 3 H]ADTN binding in a dose-dependent manner. Binding parameters, obtained using membranes from mice made obese by parenteral administration of gold thioglucose, were not significantly different from those obtained for the lean mice. It is concluded that the regulation of the hypothalamic dopaminergic receptors may be related to the lesion in the genetically obese mice.
Women's Bodies Aging: Culture, Context, and Social Work Practice

Women's bodies at every age are expressions of self and culture. In a culture that values slender, taut-skinned youth, the embodied selves of postmenopausal women are dismissed and devalued, jeopar...
Outcomes of Children After Esophagogastroduodenoscopy for Chronic Abdominal Pain

Background & Aims Chronic abdominal pain is the most common indication for esophagogastroduodenoscopy (EGD) in children. However, little is known about the accuracy of EGD-based diagnosis or the outcomes of the patients who undergo this procedure. We examined the diagnostic yield of EGD and short-term outcomes of children who underwent this procedure for chronic abdominal pain. Methods We conducted a prospective study of 290 children (4–18 years old; mean age, 11.9 ± 3.5 years; 93 girls) who underwent EGD for the primary indication of chronic abdominal pain (216 with at least 1 alarm feature) at a US pediatric gastroenterology referral center. We collected data on demographic features (age, sex), clinical characteristics (alarm features, Rome III criteria), and EGD results for each patient. All subjects with diagnostic lesions were followed for at least 1 year after EGD to determine short-term outcomes. Results Overall, EGD provided an accurate diagnosis for 109 children (38%). Diagnoses included esophagitis (21.0%), eosinophilic gastroenteritis (4.1%), eosinophilic esophagitis (3.8%), Helicobacter pylori infection (2.0%), celiac disease (0.6%), and Crohn's disease (0.4%). Short-term outcomes were available for 81% of patients with diagnostic findings, and medical therapy was effective in approximately 67% of these children. Conclusions EGD is valuable for the diagnosis of children with abdominal pain, with a 38% diagnostic yield. EGD identified disorders for which medical therapy was effective in 67% of children during the year after diagnosis.
Regional Patterns in Carbon Cycling Across the Great Plains of North America

The large organic carbon (C) pools found in noncultivated grassland soils suggest that historically these ecosystems have had high rates of C sequestration. Changes in the soil C pool over time are a function of alterations in C input and output rates. Across the Great Plains and at individual sites through time, inputs of C (via aboveground production) are correlated with precipitation; however, regional trends in C outputs and the sensitivity of these C fluxes to annual variability in precipitation are less well known. To address the role of precipitation in controlling grassland C fluxes, and thereby soil C sequestration rates, we measured aboveground and belowground net primary production (ANPP-C and BNPP-C), soil respiration (SR-C), and litter decomposition rates for 2 years, a relatively dry year followed by a year of average precipitation, at five sites spanning a precipitation gradient in the Great Plains. ANPP-C, SR-C, and litter decomposition increased from shortgrass steppe (36, 454, and 24 g C m−2 y−1) to tallgrass prairie (180, 1221, and 208 g C m−2 y−1 for ANPP-C, SR-C, and litter decomposition, respectively). No significant regional trend in BNPP-C was found. Increasing precipitation between years increased rates of ANPP-C, BNPP-C, SR-C, and litter decomposition at most sites. However, regional patterns of the sensitivity of ANPP-C, BNPP-C, SR-C, and litter decomposition to between-year differences in precipitation varied. BNPP-C was more sensitive to between-year differences in precipitation than were the other C fluxes, and shortgrass steppe was more responsive than were mixed grass and tallgrass prairie.
Tensor and vector spin observables in p-d elastic scattering at 600, 800, and 1000 MeV

Measurements of the tensor and vector spin observables C(0,NN,0,0), C(0,SS,0,0), and C(0,N,0,0), in p-d elastic scattering at 600, 800, and 1000 MeV equivalent proton bombarding energy, are reported. The data were taken in the range 0.1<-t<1.2 (GeV/c)/sup 2/. The experiment employed a polarized deuteron beam with tensor and vector components of +- 0.75 and +- 0.25, respectively, a liquid hydrogen target, and a single arm magnetic spectrometer. The tensor and vector spin parameters C(0,N,0,0) and C(0,NN,0,0) were extracted from the data with beam polarization normal to the scattering plane. The observable C(0,SS,0,0) was obtained by precessing the deuteron polarization into the scattering plane. Comparison of the data with the predictions of a relativistic multiple scattering theory is made.
Times Square, Disneyphobia, Hegemickey, the Ricky Principle, and the Downside of the Entertainment Economy: It’s Fun-Dumb-Mental

This paper reviews some recent contributions to the study of commercialism in popular culture in general and to our understanding of the role played by the Disney Corporation in particular. From th...