cssi/SciSciGPT-SciSciNet huggingface dataset:
NRF2 activation inhibits valproic acid-induced neural tube defects in mice.

Abstract Valproic acid (VPA) is a widely prescribed medication that has traditionally been used to treat epilepsy, yet embryonic exposure to VPA increases the risk of the fetus developing neural tube defects (NTDs). While the mechanism by which VPA causes NTDs is unknown, we hypothesize that VPA causes dysmorphogenesis through the disruption of redox-sensitive signaling pathways that are critical for proper embryonic development, and that protection from the redox disruption may decrease the prevalence of NTDs. Time-bred CD-1 mice were treated with 3H-1,2-dithiole-3-thione (D3T), an inducer of nuclear factor erythroid 2-related factor 2 (NRF2)—a transcription factor that activates the intracellular antioxidant response to prevent redox disruptions. Embryos were then collected for whole embryo culture and subsequently treated with VPA in vitro. The glutathione (GSH)/glutathione disulfide (GSSG) redox potential (Eh), a measure of the intracellular redox environment, was measured in the developing mouse embryos. Embryos treated with VPA exhibited a transiently oxidizing GSH/GSSG Eh, while those that received D3T pretreatment prior to VPA exposure showed no differences compared to controls. Moving to an in utero mouse model, time-bred C57BL/6 J dams were pretreated with or without D3T and then exposed to VPA, after which all embryos were collected for morphological analyses. The prevalence of open neural tubes in embryos treated with VPA significantly decreased with D3T pretreatment, as did the severity of the observed defects evaluated by a morphological assessment. These data show that NRF2 induction via D3T pretreatment protects against VPA-induced redox dysregulation and decreases the prevalence of NTDs in developing mouse embryos.
The Straight State: Sexuality and Citizenship in Twentieth-Century America

List of Illustrations ix Acknowledgments xi Introduction 1 PART I: Nascent Policing Chapter 1: IMMIGRATION "A New Species of Undesirable Immigrant": Perverse Aliens and the Limits of the Law, 1900-1924 19 Chapter 2: MILITARY "We Are Merely Concerned with the Fact of Sodomy": Managing Sexual Stigma in the World War I-Era Military, 1917-1933 55 Chapter 3: WELFARE "Most Fags Are Floaters": The Problem of "Unattached Persons" during the Early New Deal, 1933-1935 91 PART II: Explicit Regulation Chapter 4: WELFARE "With the Ugly Word Written across It": Homo-Hetero Binarism, Federal Welfare Policy, and the 1944 GI Bill 137 Chapter 5: MILITARY "Finding a Home in the Army": Women's Integration, Homosexual Tendencies, and the Cold War Military, 1947-1959 174 Chapter 6: IMMIGRATION "Who Is a Homosexual?": The Consolidation of Sexual Identities in Mid-twentieth-century Immigration Law, 1952-1983 214 Conclusion 255 Index 265
Hypoparathyroidism During Magnesium Deficiency or Excess

In humans, body magnesium content amounts to 25 g, with 66 % located in the bone, 33 % within cells, and only 1 % in the extracellular fluid (ECF), including blood [1–5] (see also Chap. 7). In the bone, magnesium as the divalent cation is adsorbed on the hydroxyapatite crystal and is in equilibrium with magnesium in the ECF. It is the most abundant intracellular cation together with potassium, reaching a concentration of approximately 0.5 mmol/l, which is thus close to that of magnesium in the ECF. Free cytosolic magnesium accounts for 5–10 % of total cellular magnesium. It binds to various organelles, 60 % of which is within mitochondria, where it is involved in phosphate transport, ATP synthesis, and utilization. ATP is synthesized by a magnesium-dependent oxidative phosphorylation process. Magnesium is a cofactor and regulator of a large series of enzymatic reactions, particularly those utilizing magnesium-ATP (glycolysis, oxidative phosphorylation), but also of DNA transcription and protein synthesis [1, 6]. In serum, 30 % of magnesium is protein bound. Circulating magnesium, which is between 0.7 and 1.0 mmol/l, is determined by bidirectional fluxes taking place at the levels of the intestine, kidney, and bone. Ionic magnesium interacts with the calcium-sensing receptor (CaSR) on parathyroid cells, and also on renal tubular cells, with a potency lower than calcium [7].
Remote Sensing of Vegetation Recovery in Grasslands after the 1988 Yellowstone Fires

In 1988, we developed an algorithm to predict green herbaceous biomass in sagebrush grassland communities of elk summer range using Landsat multi-spectral scanner (MSS) data (Merrill et al. 1988). Our objectives during this contract period were (1) to improve this predictive model and (2) to use the model for predicting vegetation recovery on grasslands burned in 1988.
Developing a Soil Quality Index

The possibility exists that a kind of “soil quality index” might be developed which would relate to the environmental impact of continuing or sustained use of chemical amendments in crop production or certain other land uses. Present concerns are mostly related to use of soluble fertilizers, including nitrogen and phosphorus; applications of weedicides and pesticides; and distribution of industrial and domestic wastes that may also include heavy metals in significant concentrations.
Lord Kames as Lord of Session and Lord of Justiciary

In 1752, then, at his age fifty-six, Henry Home of Karnes, Advocate, was elevated to the bench of the Court of Session, the highest civil court in Scotland, as Lord Kames. Immediately after his appointment, his friend Lord Deskford, Earl of Finlater, congratulated him thus, in a letter dated 11 February, 1752.
The Properties of Thyroglobulin XI. THE REDUCTION OF THE DISULFIDE BONDS

Abstract The extent of reduction of the disulfide groups in thyroglobulin by β-mercaptoethanol has been investigated as a function of pH in aqueous media and in 8 m urea. The products of reduction of thyroglobulin in dilute urea and in concentrated urea and guanidine solutions have been characterized by sedimentation and viscosity. Cleavage of a few disulfide bonds produces a smaller molecule of the same molecular weight as that obtained by quantitative reduction of all the bonds. On reduction in 5m guanidine, the 12 S subunit of thyroglobulin of ⅓ million molecular weight is cleaved into two equal or similar sized molecules.
Correlation of optic nerve head tomography with visual field sensitivity in papilledema

PURPOSE. To quantify the relationship between optic nerve head tomography and perimetric sensitivity in patients with papilledema. METHODS. Eight patients with variable degrees of recently diagnosed papilledema associated with idiopathic intracranial hypertension (IIH) were evaluated with confocal scanning laser ophthalmoscopy (CSLO) and automated perimetry. Patients were followed up with serial measurements over a period of 5 to 30 months (mean 6 SD, 17.1 6 9), while under medical treatment (acetazolamide). The tomographic parameters, volume above reference (VAR), volume above surface (VAS), effective mean height (EMH), and maximum height in contour (MxHC), were obtained by tomography, either globally or from predefined disc sectors. The perimetric indices, mean deviation (MD) and pattern SD (PSD), were evaluated. The results from patients’ right eyes and the individual intereye differences in both tomographic and perimetric parameters, were statistically evaluated by nonparametric correlational (Spearman) and repeated measures (Wilcoxon) analyses. RESULTS. At baseline, all tomographic parameters were negatively correlated with MD in global (r 52 0.8) and sectorial (r 52 0.6) evaluations. The interocular differences in overall tomographic parameters were correlated with corresponding differences in perimetric MD (r 52 0.8) and PSD (r 5 0.6). During the follow-up period, volumetric disc parameters decreased (P , 0.02), whereas perimetric MD increased (P 5 0.02) at comparable times. CONCLUSIONS. In patients with recently diagnosed papilledema, optic nerve head tomographic abnormalities are quantitatively correlated with visual field sensitivity losses. Therapeutic improvement of volumetric parameters may be paralleled by recovery in perimetric sensitivity. The data support the possible use of both techniques in combination to monitor the amount of papilledema and the effectiveness of treatments designed to reduce intracranial hypertension. (Invest Ophthalmol Vis Sci. 2001;42:1487‐1494)
Uso da água e sustentabilidade da agricultura

O modelo de agricultura convencional e considerado potencialmente impactante, pela possibilidade de degradar o ambiente onde esta inserido, por apresentar altos custos em funcao dos tratos culturais empregados e pela baixa produtividade. O principal insumo utilizado na producao agricola e a agua e com o grande aumento da populacao mundial, que alem de exigir maior quantidade de agua potavel para consumo humano, exige tambem um maior uso dos recursos hidricos para a producao de alimentos. Em funcao destes problemas cada vez mais sao empregadas restricoes quanto ao uso desse bem, ficando evidente a necessidade de se empregar tecnicas de cultivo menos agressivas, ou que aproveitem aguas residuarias de outros sistemas, abrandando as acoes antropicas. Esta revisao objetivou realizar um levantamento das principais formas de uso sustentavel da agua em agroecossistemas discutindo os beneficios correlatos ao seu uso adequado.
A comparison study between two visco-plastic sea-ice models

A comparative study between two visco-plastic sea-ice models is presented. The two models are (i) the standard visco-plastic (SVP) approach with an elliptical yield curve and a normal flow rule and (ii) a granular material (GRAM) approach with a Mohr-Coulomb yield curve and a double-sliding deformation law with dilatancy included. Various numerical experiments in simple domains and forced with uniform winds are presented to illustrate the behaviour of each model and clearly see the influence of the ice interaction term on the flow field. The results highlight some irregularities with the SVP model, and with the GRAM approach when dilatation effects are not considered. In particular, simulated velocity fields from the SVP model in the presence of large thickness or concentration gradient, are sometimes not realistic; in the standard GRAM approach (without dilatation), the shear resistance of the material tend to be too low and the mobility of the pack ice too large. When dilatation effects are included, the internal ice pressure and shear viscosity increase and the simulated velocity fields are more realistic than the one obtained from the SVP model. The main difference between the two approaches (more important than the choice of yield curve or flow rule) lies in the way the internal ice pressure is calculated. In the SVP model, the internal ice pressure is specified independently of the sea ice deformation field (as a function of ice thickness and concentration), as opposed to the the GRAM approach where the specification of the ice pressure follows naturally from the double-sliding deformation law and does not depend on parameterization. In general, irregularities associated with the SVP model are subtle and do not prevent realistic simulations of the large scale sea-ice characteristics. However, the physical basis of the GRAM approach is considered more sound and therefore provides a better starting point for further model development. Whether drift pattern and ice thickness/concentration characteristics are sensitive to such details of the rheology remains to be determined.
Finding the assumptions in the law: Social analytic jurisprudence, disability, and aging workers

Analysis of the current state of research in disability and age discrimination in the workplace shows a field that is lacking in theoretical organization. The literature remains scattered and therefore lacking in solid conclusions about the presence or effect of discrimination in the workplace because of these factors. This discussion encourages the use of social analytic jurisprudence to guide future research in these areas and to serve better those who can use the research findings to effect change in the workplace. After reviewing recent changes in the law in areas of age and disability discrimination, the authors identify gaps in legal assumptions and recommend empirical research that would help replace these holes with knowledge about how people react to older and disabled workers.
Conclusions from the Commentary

Since this whole book is not to be given over to the Tractatus, we have devoted a disproportionate amount of space to it already, and our conclusions from it will perforce have to be brief. We shall begin, then, with a glance at the background.
Colloquia familiaria aetate litterarum renatarum scripta ne spernamus

We hope to bring to the attention of modern readers a genre of works composed in great numbers during the Renaissance, which were designed to complement the practice of conversational Latin. We single out these particular texts, because, in our opinion, teachers of Latin in our own time can still find them useful. They take the form of simple dialogues which are usually brief. They are typically called colloquia, and are filled with pure and idiomatic Latin phrases pertaining to daily life. The most famous humanists of the sixteenth and seventeenth centuries, including Erasmus, Vives, Corderius, Sturmius, Pontanus among others, are numbered among the authors of colloquia . We hope to outline the main features of these texts, to explain why they were published in such large numbers in the humanistic age, and what benefits students and teachers of Latin today can gain from such colloquia .
Advances in Statistical Methods to Map Quantitative Trait Loci in Outbred Populations

Statistical methods to map quantitative trait loci (QTL) in outbred populations are reviewed, extensions and applications to human and plant genetic data are indicated, and areas for further research are identified. Simple and computationally inexpensive methods include (multiple) linear regression of phenotype on marker genotypes and regression of squared phenotypic differences among relative pairs on estimated proportions of identity-by-descent at a locus. These methods are less suited for genetic parameter estimation in outbred populations but allow the determination of test statistic distributions via simulation or data permutation; however, further inferences including confidence intervals of QTL location require the use of Monte Carlo or bootstrap sampling techniques. A method which is intermediate in computational requirements is residual maximum likelihood (REML) with a covariance matrix of random QTL effects conditional on information from multiple linked markers. Testing for the number of QTLs on a chromosome is difficult in a classical framework. The computationally most demanding methods are maximum likelihood and Bayesian analysis, which take account of the distribution of multilocus marker-QTL genotypes on a pedigree and permit investigators to fit different models of variation at the QTL. The Bayesian analysis includes the number of QTLs on a chromosome as an unknown.
Electron exchange coupling in a naturally occurring tetramangano cluster in the mineral helvite, (Mn4S)(SiBeO4)3

Abstract The mineral helvite, (Mn 4 S)(BeSiO 4 ) 3 , contains discrete tetrahedral Mn 4 S +6 clusters in which the S −2 is tetrahedrally coordinated and each Mn(II) is in a distorted tetrahedron of one S −2 and three oxygens; the cluster is situated within an encompassing lattice of SiO 4 −4 and BeO 4 −6 tetrahedra. Mn 4 S +6 centers provide an interesting model for comparison to the polynuclear manganese center that is associated with photosynthetic water oxidation. Magnetic susceptibility data between 77 and 298 K have been measured for a natural helvite sample containing principally Mn 4 S +6 centers but with significant contamination from Mn 3 FeS +6 and Mn 3 CaS +6 . The data exhibited Curie-Weiss behavior with μ eff = 5.969 B.M. and θ = 178.3 K. An analysis of the magnetic susceptibility, based on Van Vleck's formalism, demonstrated the presence of antiferromagnetic coupling, with a coupling constant J = −5.83 cm −1 . Mossbauer spectra of Mn 3 FeS centers in helvite and of Fe 4 S centers in the related mineral danalite have also been recorded. Isomer shifts show little temperature dependence and lie in the range 1.23–1.43 mm sec. . This range is typical of tetrahedrally coordinated Fe(II) in several ionic crystals but is significantly above that of Fe(II) in ferredoxins and below that in the [quinone-Fe(II)-quinone] complex of the photosynthetic bacterium, Rhodopseudomonas sphaeroides . Quadrupole splittings are highly temperature dependent, ranging from 2.4 mm sec at 4.2 K to less than 0.5 mm sec at 248 K.
Action of intracerebroventricular epinephrine on gross behavior, locomotor activity and hexobarbital sleeping times in rats

Summary l -Epinephrine administered via the lateral cerebral ventricle was found to decrease exploratory locomotor activity and potentiate hexobarbital sleeping time in rats. Both effects were dose-dependent and occurred with microgram quantities (3·3–125 μg) of epinephrine. Additional signs of a central depressant effect were noted in gross behavior. Although subcutaneous injections of l -epinephrine (0·025 and 1·0 mg/kg) also depressed locomotor activity, intraventricular injections proved much more effective. Lethality of l -epinephrine was enhanced by the intraventricular route, but the observed depressant effects occurred at doses well below the ld 50 and were observed to be completely reversible. The importance of the catechol moiety for the central depressant effects of epinephrine was emphasized by the results obtained from studying the effect on locomotor activity of a series of sympathomimetic amines. The parent compound, phenylethylamine, which is devoid of hydroxyl groups on the benzene ring and aliphatic side chain, was found to be excitant rather than depressant. Rank order of potency studies indicated that the depressant effect of catecholamines on locomotor activity might be mediated through central adrenergic receptors of the β-type. Studies with adrenergic blocking agents did not support this idea, however, and suggested that the central receptors involved are not identical to either the classical α or β adrenergic receptor.
The Dercum-Muybridge collaboration for sequential photography of neurologic disorders

Objective: To analyze the contributions of American photographer Eadweard Muybridge (1830–1904) and Philadelphia neurologist Francis Dercum (1856–1931) toward creating the first motion-picture sequences of patients with neurologic disorders. Background: In the late 1870s and 1880s, prior to the development of movie cameras or projectors, Muybridge photographed sequential images of people and animals in motion, using arrays of sequentially triggered single-image cameras and multilens cameras. Methods: Examination of published writings and photographic sequences by Muybridge and Dercum, and primary source documents, including letters from Dercum. Results: In 1885, Philadelphia neurologist Francis Dercum (1856–1931) collaborated with Muybridge at the University of Pennsylvania to photograph sequential images of patients with various neurologic disorders involving abnormal movements. Subjects were recruited from the neurology services of the University Hospital and the Philadelphia Hospital. Muybridge and Dercum photographed patients with tabes dorsalis, hemiparesis, paraparesis, athetotic cerebral palsy, lead encephalopathy, congenital hydrocephalus with diparesis, poliomyelitis, pseudoseizures, psychogenic movement disorder, and other conditions. Conclusions: These are the first motion-picture sequences of neurologic disorders ever filmed, and provide an important visual archive and teaching resource for neurologic disorders that were prevalent in the late 19th century.
On the role of eyes and brain photoreceptors in the sparrow: Entrainment to light cycles

The eyes and extraretinal brain photoreceptor(s) of the House Sparrow (Passer domesticus) both contribute to entrainment of the locomotor rhythm. During exposure to a light cycle of low intensity 25 sparrows were entrained and eight free-ran (Table 1). Birds free-running under these conditions became entrained after the intensity of light reaching the brain was increased by plucking their head feathers (Fig. 1). Following carbon black injection beneath the skin over the skull of 23 of these entrained birds, 13 remained entrained and 10 free-ran (Figs. 1 and 2). The injected-entrained birds resynchronized to a 6 hour phase delay in the light cycle. Six of these birds were blinded (bilateral orbital enucleation) and subsequently free-ran. When the carbon black was then removed they re-entrained (Fig. 3).
Comment on the validity of first-order paraxial theory for electron and ion sources with needle-type or pointed geometry

An essential feature of first-order paraxial theory is the assumption that if the potential along the axis of an axially symmetric system is known, then the potential (fields) near the axis can be obtained by a power-series expansion about points lying on axis. However, in traditional first-order theory, which commonly assumes systems with cylindrical symmetry, only terms up to second-order in the coordinate transverse to the beam axis are retained. In this letter we argue that a consequence of this restriction is that traditional first-order paraxial theory should not be applicable to electron and ion sources with pointed or needle-type geometries. In order to treat non-parallel trajectories which occur in the pointed geometries present, say, in field emission liquid metal ion sources, a modified paraxial theory is suggested which describes two-dimensional particle dynamics.
EGG HATCHABILITY INCREASES WITH COLONY SIZE IN CLIFF SWALLOWS

Abstract The percentage of otherwise successful nests containing ≥ 1 unhatched egg in Cliff Swallows (Petrochelidon pyrrhonota) varied inversely with colony size in southwestern Nebraska. Colony-site characteristics other than colony size had no significant effect on egg hatchability. The incidence of unhatched eggs at a colony site did not vary significantly with year, mean date of first egg laying, mean incubation period, extent of ectoparasitism, or mean body mass of nestlings or adults. This suggests that increased hatching failure in smaller colonies was unrelated to ectoparasitism by fleas and cimicid bugs, foraging success, or egg inattendance. Furthermore, because reproductive interference and incidence of brood parasitism do not increase in smaller colonies, these variables seem unlikely to account for the relationship between egg hatchability and colony size. More frequent matings between genetically similar individuals and reduced opportunities for females to seek extrapair fertilizations with ...
SU-F-BRD-11: Prediction of Dosimetric Endpoints From Patient Geometry Using Neural Nets

Purpose: The previously-published overlap volume histogram (OVH) technique lends itself naturally to prediction of the dose received by a given volume of tissue (e.g. D90) in intensity-modulated radiotherapy (IMRT) treatment plans. Here we extend the OVH technique using artificial neural networks in order to predict the volume of tissue receiving a given dose (e.g. V90) in both prostate IMRT and conventional breast radiotherapy. Methods: Twenty-nine prostate treatment plans and forty-three breast treatment plans were analyzed. The spatial relationships between the prostate and rectum and between the breast and ipsilateral lung were characterized using OVHs. The OVH is a cumulative histogram representing the fractional volume of the risk organ overlapped by a series of isotropic expansions of the planning target volume (PTV). Seven cases were identified as outliers and replanned. OVH points were used as inputs to a one hidden layer feed forward artificial neural network with quality parameters of the corresponding plan, such as the rectum V50, as targets. A 3-fold cross-validation was used to estimate the prediction error. Results: The root mean square (RMS) error between the predicted rectum V50s and the planned values was 2.3, which was 35% of the standard deviation of V50 for the twenty-nine plans. The RMS error of prediction of V20 of the ipsilateral lung in breast cases was 3.9, which was 90% of the standard deviation of the V20 values in the breast plan database. Conclusion: This study demonstrates that artificial neural nets can be used to extend the OVH technique to predict dosimetric endpoints taking the form of a volume receiving a given dose, rather than the minimum dose received by a given volume. Prediction of ipsilateral lung dose in breast radiotherapy using the OVH technique remains a work in progress.
A Model‐based Dependence of the Human Tissue/Blood Partition Coefficients of Chemicals on Lipophilicity and Tissue Composition

Partitioning of up to thirty-six nonionizable chemicals between seven tissues (fat, liver, brain, kidney, muscle, lung, heart) and blood in humans was modeled using membrane accumulation, protein binding, and distribution in the aqueous phases as relevant processes. The extent of membrane accumulation and protein binding of individual compounds was described as the Collander-type function of their lipophilicity expressed by the 1-octanol/water partition coefficients. The resulting model-based expression described satisfactorily the tissue/blood partition coefficients as a nonlinear function of lipophilicity and tissue composition (a standard content of lipids, proteins, and water). The calibrated model is suitable for prediction of the tissue/blood partition coefficients for non-amphiphilic nonionizable chemicals with the 1-octanol/water partition coefficients varying between 0.01 and 100,000, i.e. practically in the whole range for which equilibrium tissue/blood distribution can be used in physiologically based pharmacokinetic models.
Mission Performance Considered as Point Performance in Aircraft Design

DOI: 10.2514/1.C031290 The cruise or loiter performance of an aircraft is intimately tied to its wing loading and its thrust-to-weight ratio. Paradoxically, mission performance is often not considered when these fundamental aircraft parameters are determined in conceptual design. In this paper, the traditional constraint diagram is extended to include contours of range or endurance parameter. These performance metrics represent the mission-performance capability of the aircraft without sizing the aircraft to a particular mission. This gives the designer an immediate and intuitive understanding of the tradeoff between the point and mission performance of the aircraft. The potential freedom for the designer to choose the operating condition of the aircraft is also considered. This improved constraint diagram presents the designer with a more complete basis for understanding and weighing the consequences of decisions.
Brewster phenomena in lossy structures

Abstract We show that the energy of a plane wave incident on a layered structure can be totally absorbed if one of the layers has either dielectric or metallic losses. By interpreting this phenomenon in terms of a leaky-wave interaction, we explain similar total absorption effects that have been reported in the context of metallic gratings.
Enzyme and metabolite levels in mammary and abdominal adipose tissue of lactating dairy cows.

Abstract Compared to hay, when concentrates were fed three- to fourfold, increases occurred in the activities of enzymes associated with fatty acid synthesis and esterification in adipose tissue, whereas mammary enzyme levels were relatively unaffected. The proportion of stearic acid in milk fat, presumably arising from adipose tissue, was significantly depressed in the high response group (severe milk fat depression) but not in the low response group (moderate milk fat depression). Differences in dietary effects upon mammary intermediary metabolite levels between the high and low response groups suggested a relatively lower availability of energy to mammary glands of cows in the high response group when fed concentrate. A number of changes in adipose tissue metabolite levels were noted in concentrate-fed animals, the most interesting being a twofold increase in the level of α -glycerol-P in the high response group. These observations were consistent, with a previous suggestion that severe milk fat depression can be attributed, in part, to a decrease in the availability of long-chain fatty acids for milk synthesis. Alterations in mammary gland metabolism may occur, even though no significant enzymatic changes occur in mammary tissue when milk fat percentage is depressed.
Thermal stress concentrations in a tooth

A complex variable theory of plane thermoelasticity is used to determine closed form expressions for the steady-state stress and displacement fields in an elastic half-plane containing a symmetrical, tooth-shaped projection. A singular line heat source pierces the half-plane at an arbitrary point. The tooth surface is assumed to be traction free and to satisfy either isothermal or adiabatic thermal boundary conditions. Graphical results are presented for a particular tooth geometry with the singular heat source located at a point on the axis of symmetry (i) near the tooth surface, and (ii) remote from the tooth. Of particular interest is the fact that the maximum stresses do not occur at the minimum radius of curvature of the tooth.
Sequence of Events in the Extracellular Half of the Transport Cycle in Glutamate Transporter

The crystal structure of GltPh, a bacterial homologue of glutamate transporter (GlT), revealed the structure of the outward-facing occluded state including the substrate and two Na+ (Na1 and Na2). It has been well established, however, that substrate transport in GltPh is catalyzed by the co-transport of three Na+ ions. However, the location of the third Na+ (Na3) binding site remains unknown. Furthermore, only little is known regarding the sequence of binding events of the substrate and the co-transported ions to GltPh. In the present study, we investigate the binding sequence of substrate and Na+ ions to their extracellular binding sites using molecular dynamics simulations of various bound states of the transporter characterizing the solvent accessibility of key residues involved in ion binding and identifying the resulting conformational changes in the transporter. The results show that extracellular water cannot access Asp312 (the putative Na3 binding site) in the apo and substrate-bound states, and that this residue becomes only accessible from the extracellular side upon Na+ binding to the Na1 binding site. Based on the simulations, we propose that Na3 binds first to the Na1 binding site in the apo state, resulting in hydration of Asp312, and then moves into the Na3 binding site, the latter step likely being driven by membrane potential. The subsequent binding of a second Na+ ion (Na1) and the substrate results in a partial closure of the extracellular gate and the formation of the Na2 binding site. Finally, Na2 enters its binding site and locks the extracellular gate resulting in formation of the occluded state. We also propose a putative Na3 binding site composed of three highly conserved residues, namely, Asp312, Thr92 and Asn310.
Grain size-acoustic emission relationships in hydrogen induced delayed cracking

A detailed characterization of acoustic emission signals generated during hydrogen induced cracking in 300M steel has been conducted. Decreasing the prior austenite grain size resulted in less acoustic emission activity at a given applied stress intensity. For a given microstructure, acoustic emission activity increased with increasing applied stress intensity. The extrapolation of the count rate (or event rate) curves to zero activity coincided with the threshold value. Variations in the acoustic emission response are explained by considering the grain size dependency of the emission event peak amplitude.
Long Terminal Repeat and nef Gene Variants of Human Immunodeficiency Virus Type 1 in Perinatally Infected Long-Term Survivors and Rapid Progressors

HIV-1 sequences from perinatally infected children were analyzed in the long terminal repeat (LTR) region and nef in order to investigate associations of viral variation and disease progression. Four long-term survivors who reached 10 years of age or older, and four rapid progressors who survived less than 2 years, participated in this study. LTR sequences of multiple independent viral variants from each individual were compared. No sequence pattern within the LTR consistently distinguished long-term survivors from rapid progressors or vice versa. Deletions and insertions within transcription factor binding sites of the LTR and nef ranging from 8 to 341 bp were found in viral variants from the eldest long-term survivor (LTS047). These deletions and duplications may be associated with the survival of LTS047 via an unknown mechanism. Among all children in this study, the sites in the untranslated region (NF-κB, SP1, and TATA box) were more conserved than the sites in the nef/LTR overlap region (NFAT, purine...
Lovastatin triggers an apoptosis-like cell death process in the fungus Mucor racemosus

The filamentous dimorphic fungus Mucor racemosus possesses three ras genes, Mras1, 2, and 3, whose expression is correlated to morphogenesis of the fungus. Lovastatin, an indirect inhibitor of protein prenylation, altered the processing of MRas1 protein, blocked the accumulation of MRas3 protein, and caused the MRas1/p20 protein complex to disappear in M. racemosus. Concurrently it arrested sporangiospore germination, decreased growth rate, caused a loss of cell viability accompanied by cell shrinkage, increased cell density and cytoplasm condensation, and triggered DNA fragmentation, resulting in nucleosomes and nucleosome multimers. The specific morphological and biochemical events seen in Mucor cell death, particularly DNA fragmentation, resemble the best known characteristics of classical apoptosis in mammalian cells and prompted us to classify lovastatin-induced cell death as an apoptosis-like process. Lovastatin did not cause cell death in a leucine auxotroph of Mucor grown in YNB minimal medium, conditions which support only spherical growth during spore germination. Exogenous dibutyryl-cAMP initiated morphogenesis from hyphal (polar) growth to yeast-like (spherical) growth during spore germination and strongly prevented cell death which resulted from lovastatin treatment. Wortmannin added together with dibutyryl-cAMP showed a synergistic effect in the prevention of fungal cell death. These data suggest that the regulation of lovastatin-induced cell death in Mucor requires a signal transduction pathway(s) involving cAMP whose function is specific to a particular developmental stage.
Annular Protofibrils Are a Structurally and Functionally Distinct Type of Amyloid Oligomer

Amyloid oligomers are believed to play causal roles in several types of amyloid-related neurodegenerative diseases. Several different types of amyloid oligomers have been reported that differ in morphology, size, or toxicity, raising the question of the pathological significance and structural relationships between different amyloid oligomers. Annular protofibrils (APFs) have been described in oligomer preparations of many different amyloidogenic proteins and peptides as ring-shaped or pore-like structures. They are interesting because their pore-like morphology is consistent with numerous reports of membrane-permeabilizing activity of amyloid oligomers. Here we report the preparation of relatively homogeneous preparations of APFs and an antiserum selective for APFs (αAPF) compared with prefibrillar oligomers (PFOs) and fibrils. PFOs appear to be precursors for APF formation, which form in high yield after exposure to a hydrophobic-hydrophilic interface. Surprisingly, preformed APFs do not permeabilize lipid bilayers, unlike the precursor PFOs. APFs display a conformation-dependent, generic epitope that is distinct from that of PFOs and amyloid fibrils. Incubation of PFOs with phospholipids vesicles results in a loss of PFO immunoreactivity with a corresponding increase in αAPF immunoreactivity, suggesting that lipid vesicles catalyze the conversion of PFOs into APFs. The annular anti-protofibril antibody also recognizes heptameric α-hemolysin pores, but not monomers, suggesting that the antibody recognizes an epitope that is specific for a β barrel structural motif.
Microfossil correlation of the Coosawhatchie Clay (Hawthorn Formation, Miocene) of South Carolina, and its equivalent in Georgia

Abstract The diatom and silicoflagellate assemblages of the Coosawhatchie Clay member of the Hawthorn Formation at Dawsons Landing, South Carolina, are correlative with those of a clay bed exposed in low bluffs on the Georgia side of the Savannah River, near Berrys Landing. The Berrys Landing exposure contains calcareous nannoplankton and planktonic foraminifera, in addition to diatoms and silicoflagellates. Multiple floral and faunal correlations of these strata with standard zonations from deep-sea cores and the Serravallian stratotype are presented. This is the first integrated use of siliceous microfossil groups to correlate southeastern coastal plain outcrops and core samples from the U.S.A. to European and deep-sea stratigraphies. The silicoflagellate assemblage can be placed in theDistephanus stauracanthus Subzone of theC. triacantha Zone. The diatom assemblage can be placed in the upper part of theCraspedodiscus coscinodiscus Zone and tentatively within North Pacific Diatom (N.P.D.) Zone XX. Planktonic foraminifera from the Berrys Landing exposure and from the subsurface in Georgia suggest correlation with zones N11 to lower N12. Calcareous nannoplankton recovered from the Berrys Landing exposure suggest correlation with theCoccolithus miopelagicus Subzone. These microfossil assemblages are correlative with the lower to middle Serravallian stratotype, and can be further correlated with upper Unit 15 to lower Unit 18 from the Calvert and Choptank Formations of Maryland.
Stable Generalized Finite Element Method (SGFEM)

Abstract The Generalized Finite Element Method (GFEM) is a Partition of Unity Method (PUM), where the trial space of standard Finite Element Method (FEM) is augmented with non-polynomial shape functions with compact support. These shape functions, which are also known as the enrichments, mimic the local behavior of the unknown solution of the underlying variational problem. GFEM has been successfully used to solve a variety of problems with complicated features and microstructure. However, the stiffness matrix of GFEM is badly conditioned (much worse compared to the standard FEM) and there could be a severe loss of accuracy in the computed solution of the associated linear system. In this paper, we address this issue and propose a modification of the GFEM, referred to as the Stable GFEM (SGFEM). We show that SGFEM retains the excellent convergence properties of GFEM, does not require a ramp-function in the presence of blending elements, and the conditioning of the associated stiffness matrix is not worse than that of the standard FEM. Moreover, SGFEM is very robust with respect to the parameters of the enrichments. We show these features of SGFEM on several examples.
Opioid and Opiate Immunoregulatory Processes

The discovery of the ability of the nervous system to communicate through "public" circuits with other systems of the body is attributed to Ernst and Berta Scharrer, who described the neurosecretory process in 1928. Indeed, the immune system has been identified as another important neuroendocrine target tissue. Opioid peptides are involved in this communication (i.e., neuroimmune) and with that of autoimmunoregulation (communication between immunocytes). The significance of opioid neuropeptide involvement with the immune system is ascertained from the presence of novel δ, μ., and κ receptors on inflammatory cells that result in modulation of cellular activity after activation, as well as the presence of specific enzymatic degradation and regulation processes. In contrast to the relatively uniform antinociceptive action of opiate and opioid signal molecules in neural tissues, the presence of naturally occurring morphine in plasma and a novel μ3 opiate-specific receptor on inflammatory cells adds to the growing knowledge that opioid and opiate signal molecules may have antagonistic actions in select tissues. In examining various disorders (e.g., human immunodeficiency virus, substance abuse, parasitism, and the diffuse inflammatory response associated with surgery) evidence has also been found for the involvement of opiate/opioid signaling in prominent mechanisms. In addition, the presence of similar mechanisms in man and organisms 500 million years divergent in evolution bespeaks the importance of this family of signal molecules. The present review provides an overview of recent advances in the field of opiate and opioid immunoregulatory processes and speculates as to their significance in diverse biological systems.
Opiate antagonist facilitation of time-dependent memory processes: dependence upon intact norepinephrine function.

Abstract Post-training administration of opiate antagonists improves retention of recent learning in laboratory animals tested on a variety of tasks. We examined the possibility that this effect of opiate antagonist treatment might be due to release of brain norepinephrine (NE) function from opioid peptide inhibition. The behavioral testing procedure in these experiments consisted of one-trial passive avoidance conditioning. Rats received post-training treatments immediately after the training trial and retention was tested 24 h later. Lesions of the dorsal noradrenergic bundle (DNB) that were induced by 6-hydroxydopamine (6-OHDA) were found to prevent the memory enhancing effect of post-training naloxone administration. The memory enhancing effect of naloxone was restored when NE neurons were protected from 6-OHDA by pretreatment with a NE uptake inhibitor. Earlier research indicated that the amygdala complex is one brain site that is sensitive to the effects of opiate manipulations on memory processes. In this study, lesions of the DNB were also found to prevent the memory enhancing effect of intracranial opiate antagonist administration into the amygdala complex.
Highly oxygenated flavonoid aglycones from gutierrezia grandis

Abstract Twelve known and nine new highly oxygenated flavonoid aglycones, some of which exhibit 2′-oxygenation, were isolated from Gutierrezia grandis .
Simple Veneziano Model for np Charge-Exchange Scattering

The $\mathrm{np}\ensuremath{\rightarrow}\mathrm{pn}$ amplitudes are written in simple Veneziano form. Only an $M=0$ pion pole and an $M=1$ pion parity doublet with corresponding exchange-degenerate $B$ are considered in our case to give rise to a sharp peak in $\frac{d\ensuremath{\sigma}}{\mathrm{dt}}$ at $t=0$, giving qualitative agreement with experimental data.
Functional Diversification and Specialization of Cytosolic 70-kDa Heat Shock Proteins

A fundamental question in molecular evolution is how protein functional differentiation alters the ability of cells and organisms to cope with stress and survive. To answer this question we used two paralogous Hsp70s from mouse and explored whether these highly similar cytosolic molecular chaperones, which apart their temporal expression have been considered functionally interchangeable, are differentiated with respect to their lipid-binding function. We demonstrate that the two proteins bind to diverse lipids with different affinities and therefore are functionally specialized. The observed lipid-binding patterns may be related with the ability of both Hsp70s to induce cell death by binding to a particular plasma-membrane lipid, and the potential of only one of them to promote cell survival by binding to a specific lysosomal-membrane lipid. These observations reveal that two seemingly identical proteins differentially modulate cellular adaptation and survival by having acquired specialized functions via sequence divergence. Therefore, this study provides an evolutionary paradigm, where promiscuity, specificity, sub- and neo-functionalization orchestrate one of the most conserved systems in nature, the cellular stress-response.
Photodecomposition kinetics of formic acid in aqueous solution

The photodecomposition of aqueous solutions of formic acid was studied as a model reaction for removing organic pollutants from water. The process was carried out in a tubular-flow reactor, operated continuously. The cylindrical reactor was irradiated from the outside by placing the cylindrical lamp and the reactor at the foci of an elliptical reflector. Measurements made at differential operating conditions permitted calculation of rates of reaction as a function of formic acid concentration and light intensity for the temperature range 25° to 60°C. Carbon dioxide and carbon monoxide were the only observed products of the decomposition. The rate was first order in absorbed light intensity and between zero and first order in formic acid. These results correspond to a combination of chain and non-chain kinetics occurring simultaneously. Rate constant ratios and quantum yields were calculated from the data and the kinetics model. A few measurements were made by adding ferric chloride and ferrous chloride to the feed to the reactor. An order of magnitude increase in rate was observed with these sensitizers.
Synthesis and evaluation of substrate analogue inhibitors of trypanothione reductase

Trypanothione reductase (TR) is found in the trypanosomatid parasites, where it catalyses the NADPH-dependent reduction of the glutathione analogue, trypanothione, and is a key player in the parasite's defenses against oxidative stress. TR is a promising target for the development of antitrypanosomal drugs; here, we report our synthesis and evaluation of compounds 3-5 as low micromolar Trypanosoma cruzi TR inhibitors. Although 4 and 5 were designed as potential irreversible inhibitors, these compounds, as well as 3, displayed reversible competitive inhibition. Compound 3 proved to be the most potent inhibitor, with a K(i) = 2 µM.
Phencyclidine binding to striatal cocaine receptors.

Abstract PCP and related compounds inhibit 3 H-mazindol binding to the cocaine receptor on dopamine transporters. The relative potencies of these compounds are such that some of the behavioral effects of PCP could be related to its action at the cocaine receptor; however, the affinity of PCP at the cocaine site (K i = 1.59 μM) is less than its affinity at its own receptor (K i about 0.12 μM). More data will be needed to conclusively implicate the cocaine receptor in the action of PCP.