cssi/SciSciGPT-SciSciNet huggingface dataset:
Genetics of Multiple Sclerosis: Determinants of Autoimmunity and Neurodegeneration

Since the first description of multiple sclerosis (MS) as an inheritable disease by Eichhorst [1] accumulating epidemiological observations support a genetic hypothesis. Population, family and twin studies have revealed that Mendelian transmission of a single susceptibility gene would not be compatible with the observed patterns of inheritance. Like most other common diseases, MS is a complex trait, defined by several genes, each probably exerting a relatively small effect. Complex interactions among susceptibility genes and the environment are believed to contribute to a predisposition to dysregulation of inflammatory pathways, demyelination and tissue degeneration in the central nervous system (CNS). Natural history and pathological studies, however, define that MS represents a spectrum rather than a single entity of inflammatory demyelination. Despite a growing need for identifying molecular markers of biological subtypes of MS, only limited information is available for genotype-phenotype correlations. Four full genome scans using polymorphic microsatellite markers in nuclear and multiplex MS families indicated several chromosomal regions of susceptibility. With the recently discovered, highly abundant single nucleotide polymorphisms (SNPs) and family-based association methods, the means are now available to confine these relatively large regions of interest to candidate genes and susceptibility alleles. The currently available SNP maps favor indirect association studies based on linkage disequilibrium between marker and disease alleles. Here, we review available genetic data in MS, and introduce an additional strategy which correlate genetic markers with major biological components of the disease such as autoimmunity and neurodegeneration. This approach may yield important insights with utility in clinical practice.
Loops with Transitive Automorphisms

Abstract It is shown that isotopic loops with transitive automorphism groups are in fact isomorphic. A classification of loops with transitive automorphism groups is given. This classification is compared to one given by Barlotti and Strambach (1983) for loops with sharply transitive automorphism groups, and examples of several of the classes are presented. The approach is entirely algebraic.
Asymptomatic primary hyperparathyroidism

Of 118 consecutive white patients referred for asymptomatic primary hyperparathyroidism, the diagnosis was clinically confirmed in 100, of whom 85 adults had a serum calcium less than 3.0 mM (12 mg/dl) and no skeletal, rheumatic, or significant neuropsychiatric symptoms, azotemia, or other significant illnesses. Among these 85, 68 had both asymptomatic and medically uncomplicated hyperparathyroidism, whereas 17 had historical, radiographic, or ultrasonic evidence of renal stone disease. The 20% with past or present renal calculi concentrated their urine significantly better than the 68 others (p = 0.05), but these two groups were otherwise not distinguished by the tests we performed, so all 85 patients were analyzed together. Systolic and diastolic blood pressures were normal, but premature osteopenia and/or impaired renal function were present in 29–36% of the patients. Micrometer measurements of metacarpal radiographs and 125I photon absorptiometry at the shaft of the radius revealed cortical osteopenia. Osteopenia was equally significant in the distal radius (cortical plus trabecular bone). These quantitative measurements were superior to routine bone radiography, and ROC analysis showed that 125I absorptiometry at either site was superior (p < 0.01) to metacarpal cortex measurements for detecting premature osteopenia, which was present in more than a third of these patients. Creatinine clearances (24 h) and maximum urine concentrating capacity (overnight dehydration plus the synthetic vasopressin analog DDAVP) were each significantly reduced, despite all patients' normal BUN and serum creatinine levels. Sequential performance of a 24 h creatinine clearance and a urine concentration test revealed abnormalities in the renal function of 27 of 74 patients (36%), with a specificity of 95% and a higher sensitivity than either test alone (27–29%). Testing the kidneys' ability to acidify the urine to pH 5.3 or less identified only 1 additional abnormal patient. Silent complications of primary hyperparathyroidism are thus common in “asymptomatic” patients with mild hypercalcemia. Their presence was only weakly correlated with urinary calcium excretion (measured on a low-calcium diet) and serum alkaline phosphatase. From these data, it is not possible to predict whether these complications progress in the absence of treatment or diminish with successful treatment of the primary hyperparathyroidism.
Reduction of NOx over zeolite MFI supported iron catalysts: Nature of active sites

FTIR spectroscopy, catalytic reduction of NOx with iso-C4H10, and oxidation of C16O with 18O2 have been combined to characterize the Fe entities in Fe/MFI catalysts prepared by a variety of methods, including sublimation of FeCl3 vapor onto the H-form of MFI. Iron hydroxo and oxo ions in exchange positions, iron oxide clusters inside zeolite channels, and Fe2O3 particles at the external surface have been identified. Of special interest are IR bands in the 830–1000 cm−1 region. They are assigned to the perturbations by Fe ions of zeolite lattice vibrations and discriminate between hydroxo(oxo) ions and oxide clusters. Two bands in this region are assigned to Fe3+ and Fe2+; their respective intensities follow the changes in valency of the Fe ions. When MFI containing Fe ions are treated with aqueous NaOH, small iron oxide clusters are generated. This process is largely reversible: Fe ions are regenerated upon replacing the Na+ by H+ ions and initiating protonolysis at high temperature. The high CO/CO2 ratio in the product of NOx reduction with alkanes is consistent with a dominant role of hydroxo(oxo) ions, not oxide particles, as active sites. Oxidation of C16O with 18O2 over Fe/MFI results in a remarkably high concentration of C18O2 molecules. The superiority of the sublimation method in preparing Fe/MFI catalysts for NOx reduction is mainly due to the high dispersion of the Fe. Immediately after subliming FeCl3 onto H-MFI, the 3610 cm−1 band is completely wiped out, indicating that all protons have been replaced by [FeCl2]+ ions. Terminal OH groups and internal SiOH groups in MFI with high density of lattice effects are also destroyed, but these are completely regenerated in a subsequent hydrolysis step.
Axially-Symmetric Multi-Instanton Solutions Generated by Conformal-Mappings

It is shown that exact axially symmetric, regular self-dual multi-instanton solutions of the SU(2) Yang-Mills equations can be generated from the vacuum solution by means of singular conformal mappings of a complex plane followed by a singular gauge transformation. The regularizing gauge for the 't Hooft singular solution is found and the corresponding Yang-Mills gauge potential ${\mathit{A}}_{\ensuremath{\mu}}$ without any singularity and with the correct asymptotic behavior is given. The relations between the parameters in different forms of the solution are explored and the possible implications on the calculations of quantum effects are noted.
Supercritical burning of liquid droplets in stagnant environment.

Supercritical burning of liquid fuel droplets in stagnant environment, using flame sheet model to obtain heat and mass fields
Species of Espaces and other spurious concepts addressed to reading the invisible features of signs within systems of relations

ABSTRACTThis article proposes that signs and signage systems be understood as part of enunciative systems. These in turn perform according to different models of cultural space that are layered into the built environment. Signs might be conceived in terms of circulation, movement, spatial ordering, point of view and sight lines, as well as ideas about how social relations are spatially organized, how privacy is understood, where legal and personal boundaries exist and why, and also notions of style, scale and all the many cultural notions of power and control that these embody. Reading signs back into patterns of cultural life reveals more than their value as icons or material artifacts; it reveals the ways models of cultural order were constituted through their material, spatial, expression. The piece lays out a multi-part framework for thinking about the various scopic regimes within which space has been understood and signage established: monumental space, navigational approaches, civic notions of publ...
Necessary and sufficient condition for a scattering amplitude to correspond to a spherically symmetric scatterer

Abstract It is proved that A(θ′,θ,k) = A(θ′·θ,k) is a necessary and sufficient condition for a scattering amplitude A(θ′,θ,k) to correspond to a spherically symmetric potential q(x) = q(|x|).
Multiple action of 2'-diethylaminoethyl 2,2-diphenylpentanoate HCl (SKF 525-A) on rat liver tryptophan pyrrolase in vivo.

Abstract SKF 525-A was observed to have an early stimulatory action in vivo on liver tryptophan pyrrolase activity in intact or adrenalectomized, but not hypophysectomized, male adult rats. The stimulatory effect was abolished by co-administration of actinomycin D, puromycin, or cycloheximide in intact animals, suggesting that SKF 525-A was inducing de novo formation of apo-tryptophan pyrrolase. Concurrent with stimulation of tryptophan pyrrolase in intact animals by SKF 525-A, there was a significant decrease in adrenal ascorbate. These effects of SKF 525-A on tryptophan pyrrolase or adrenal ascorbate were not seen in hypophysectomized rats. The stimulation of tryptophan pyrrolase activity by SKF 525-A would therefore seem to involve some form of pituitary activation. When SKF 525-A was co-administered with hydrocortisone, the stimulatory effects of the two agents were merely additive. However, administration of SKF 525-A to adrenalectomized rats receiving repeated injections of hydrocortisone markedly potentiated the inducing action of hydrocortisone. This enhancement of hydrocortisone induction occurred only if SKF 525-A was administered during the early tryptophan pyrrolase induction phase, i.e. prior to development of attenuation of hydrocortisone induction. Such an effect of SKF 525-A was not obtained in hypophysectomized rats undergoing similar treatments. SKF 525-A-like enhancement of hydrocortisone-induced tryptophan pyrrolase increases could also be produced by injection of saline homogenates of rat pituitary glands during the early tryptophan pyrrolase induction phase. Animals pretreated 12 hr before with SKF 525-A showed a reduced capacity to form new tryptophan pyrrolase after hydrocortisone administration. This late “anti-induc-tive” action of SKF 525-A was also seen for a second “stimulatory” dose of SKF 525-A but was not present for substrate stimulation of tryptophan pyrrolase (caused by injected tryptophan). These latter data indicate that SKF 525-A may reduce the ability of the liver to produce tryptophan pyrrolase from other than pre-existing mRNA template. It is concluded that SKF 525-A effects on hepatic tryptophan pyrrolase are multiple, ranging from hydrocortisone-like to actinomycin-like. No simple explanation for such diverse activities can be offered but this should serve as a caution to investigators who regard SKF 525-A as pharmacologically inert (Mannering, Ann. N.Y. Acad. Sci., 123, 108 (1965); Brodie et al., Science148, 1547 (1965) or as a specific inhibitor of microsomal enzyme systems in liver.
Biochemical activity and water: the activity of heme enzymes in non-aqueous media.

Perioxidase and catalase activity in nonaqueous media, noting survival independent of water properties and relevance to nonaqueous biosystems
Copy number variation prevalence in known asthma genes and their impact on asthma susceptibility

SummaryBackground Genetic studies have identified numerous genes reproducibly associated with asthma, yet these studies have focussed almost entirely on single nucleotide polymorphisms (SNPs), and virtually ignored another highly prevalent form of genetic variation: Copy Number Variants (CNVs). Objective To survey the prevalence of CNVs in genes previously associated with asthma, and to assess whether CNVs represent the functional asthma-susceptibility variants at these loci. Methods We genotyped 383 asthmatic trios participating in the Childhood Asthma Management Program (CAMP) using a competitive genomic hybridization (CGH) array designed to interrogate 20 092 CNVs. To ensure comprehensive assessment of all potential asthma candidate genes, we purposely used liberal asthma gene inclusion criteria, resulting in consideration of 270 candidate genes previously implicated in asthma. We performed statistical testing using FBAT-CNV. Results Copy number variation in asthma candidate genes was prevalent, with 21% of tested genes residing near or within one of 69 CNVs. In six instances, the complete candidate gene sequence resides within the CNV boundaries. On average, asthmatic probands carried six asthma-candidate CNVs (range 1–29). However, the vast majority of identified CNVs were of rare frequency (< 5%) and were not statistically associated with asthma. Modest evidence for association with asthma was observed for 2 CNVs near NOS1 and SERPINA3. Linkage disequilibrium analysis suggests that CNV effects are unlikely to explain previously detected SNP associations with asthma. Conclusions and Clinical Relevance Although a substantial proportion of asthma-susceptibility genes harbour polymorphic CNVs, the majority of these variants do not confer increased asthma risk. The lack of linkage disequilibrium (LD) between CNVs and asthma-associated SNPs suggests that these CNVs are unlikely to represent the functional variant responsible for most known asthma associations.
Induction by 5-fluorouracil of a major phase difference in the circadian profiles of DNA synthesis between the Ehrlich ascites carcinoma and five normal organs

Abstract DNA synthetic activity (DNA-SA) was measured by the incorporation of tritiated thymidine (TDR) into chemically isolated DNA. DNA-SA was monitored every 3 h over a 60-h period in the Ehrlich ascites carcinoma (EAC), tongue, bone marrow, ileum, stomach and rectum in mice which had received 50 mg/kg 5-fluorouracil (FU) at 17:00 h. FU was given in an attempt to induce major phase differences in the circadian profiles of DNA-SA between the EAC and the normal organs. Subsequent to the FU treatment, a time period 15 h in duration, was identified when DNA-SA in the EAC was at or near a maximal level (125–190 cpm/μg DNA) whereas DNA-SA in all 5 normal organs was at or near a minimal level (
Isolating GaSb Membranes Grown Metamorphically on GaAs Substrates Using Highly Selective Substrate Removal Etch Processes

The etch rates of NH4OH:H2O2 and C6H8O7:H2O2 for GaAs and GaSb have been investigated to develop a selective etch for GaAs substrates and to isolate GaSb epilayers grown on GaAs. The NH4OH:H2O2 solution has a greater etch rate differential for the GaSb/GaAs material system than C6H8O7:H2O2 solution. The selectivity of NH4OH:H2O2 for GaAs/GaSb under optimized etch conditions has been observed to be as high as 11,000 ± 2000, whereas that of C6H8O7:H2O2 has been measured up to 143 ± 2. The etch contrast has been verified by isolating 2-μm-thick GaSb epilayers that were grown on GaAs substrates. GaSb membranes were tested and characterized with high- resolution x-ray diffraction and atomic force microscopy.
Loss of calcineurin Aα results in altered trafficking of AQP2 and in nephrogenic diabetes insipidus

The serine/threonine phosphatase calcineurin is an important signaling molecule involved in kidney development and function. One potential target of calcineurin action is the water channel aquaporin 2 (AQP2). In this study, we examined the effect of loss of calcineurin Aα (CnAα) on AQP2 function in vivo. CnAα null mice were found to have defective post-natal urine-concentrating ability and an impaired urine-concentrating response to vasopressin. Expression of AQP2 is normal but, paradoxically, vasopressin-mediated phosphorylation of the channel is decreased compared with wild-type littermates and there is no accumulation of AQP2 in the apical membrane. Calcineurin protein and activity was found in innermedullary collecting duct vesicles, and loss of calcineurin expression and activity was associated with a loss of AQP2 in the vesicle fraction. As such, the lack of vasopressin-mediated phosphorylation of AQP2 might be the result of a defect in normal trafficking of AQP2 to apical-targeted vesicles. Likewise, treatment of wild-type mice with cyclosporin A to inhibit calcineurin produces a similarly impaired urine-concentrating response to vasopressin and alterations in AQP2 phosphorylation and trafficking. These experiments demonstrate that, CnAα is required for normal intracellular trafficking of AQP2 and loss of calcineurin protein or activity disrupts AQP2 function.
The Origins of FBI Counterintelligence – By Raymond J. Batvinis

After receiving his BA and MA in history, Raymond J. Batvinis joined the FBI, serving twenty‐two of a twenty‐five‐year Bureau career in counterintelligence, including a stint in the training unit o...
Alternative immunoassay for tartrate-resistant acid phosphatase isoform 5b using the fluorogenic substrate naphthol ASBI-phosphate and heparin.

Abstract Objective: Our purpose was to develop a specific immunoassay for tartrate-resistant acid phosphatase (TRACP) 5b using naphthol ASBI phosphate (N-ASBI-P) as a selective substrate for isoform 5b and heparin as a selective inhibitor of isoform 5a. Methods: Serum TRACP 5a and 5b and recombinant TRACP 5a were used to optimize and standardize the immunoassay for specificity, linearity, analytical recovery, sensitivity and reproducibility. Serum N-telopeptide cross-links (NTX) and bone alkaline phosphatase (bone ALP) were also measured. The clinical sensitivity and specificity were assessed in healthy control subjects and patients with osteoarthritis (OA), rheumatoid arthritis (RA) and endstage renal disease (ESRD). Results: TRACP 5b specificity was achieved at pH 6.3 with 2.5 mmol/l substrate and 25 U/ml heparin. Isoform 5b specificity was increased over our original immunoassay using 4-nitrophenyl phosphate (4-NPP) without heparin. The alternative immunoassay was linear with 110% analytical recovery and no serum matrix effects. The average intra-assay error was 10.65%; the average inter-assay error was 10.11% for values of 1–3 U/l and 6.5% for values of 7–11 U/l. Mean serum TRACP 5b in OA and RA were not significantly different from control using either immunoassay. Mean serum TRACP 5b was significantly increased in ESRD with both immunoassays. Serum TRACP 5b levels correlated significantly with NTX and bone ALP in the disease groups, but not always in the control group. Conclusion: This alternative immunoassay for TRACP 5b activity is highly specific. It should have applications in evaluating patients with bone disease and will improve our understanding of the biological significance of TRACP 5b expression in health and disease.
Management of Atrial Fibrillation: Review of the Evidence for the Role of Pharmacologic Therapy, Electrical Cardioversion, and Echocardiography

This review, which supports the recommendations of the American Academy of Family Physicians and the American College of Physicians, summarizes the available evidence about the efficacy of medicati...
Binary rare earth-vanadium systems

Abstract Available data concerning the phase equilibria in the rare earth vanadium binary systems were accumulated and evaluated. The atypical Sc-V, Y-V, Ce-V, Eu-V and Y-V systems were deleted. The experimental data for each of the remaining systems was then used to evaluate an initial set of interaction parameters. Refined parameters were developed by plotting the initial parameters against the atomic numbers of the rare earths and smoothing the trends. These refined parameters were then used to calculate phase equilibria for the various systems. The refined parameters show quite good agreement with estimated values generated by the Mi edema approximations.
Exploring landscape structure effect on termite territory size using a model approach.

Abstract The foraging territory of the Formosan subterranean termite, Coptotermes formosanus Shiraki, was simulated by using a lattice model in order to study how landscape structure affects the foraging territory. Three kinds of landscape were generated on lattice space: ideal, random and fractal landscape. Each lattice cell had a value ranging from 0.0 to 1.0, interpreted as transition probability, P trans , which represents spatially distributed property of the landscapes. The heterogeneity of the fractal landscape was characterized by a parameter, H , controlling aggregation of lattice cells with higher value of P trans . Higher H values corresponded to higher aggregation levels. The model made use of minimized local rules based on empirical data that determines the development of the foraging territory. Additionally, seasonal cycle (summer and winter season), and obstacles which hinder the growth of the territory were incorporated in the model as environmental variables. Territory size was largest in the ideal landscape while it was larger in the random landscape than in the fractal landscape. As obstacle density increased, the territory size decreased. In the fractal landscape, the territory size increased, decreased, and increased again as H increased.
Inhibition of growth ofPhytophthora parasitica var.nicotianae by aromatic acids and coumarins in a laboratory bioassay.

Hydroxy-, dihydroxy-, trihydroxy-, methoxy-, dimethoxy-, hydroxy-+methoxy-, amino-, chloro-, and nitro-substituted benzoic, phenylacetic, phenylpropanoic, and phenylpropenoic (cinnamic) acids were evaluated for activity against the growth ofPhytophthora parasitica var.Nicotianae, Races 0 and 1, in a laboratory bioassay. Several substituted coumarins were also tested. In general, for Race 0, the phenylpropenoic acids were more active (on a millimolar basis), than the corresponding benzoic, phenylacetic, or phenylpropionic acids (9 of 14 series). Among the most active acids wereo-hydroxycinnamic and the chloro- and methoxycinnamic acids. The activities of unsubstituted benzoic and phenylpropionic acids were comparable to the most active compounds tested. Monohydroxyaromatic acids were more active than most dihydroxy acids of the same chain length. Dihydro-3,4-dihydroxycinnamic acid was slightly more active than the corresponding cinnamic acid, while the reverse was true for the mono-p-hydroxycinnamic acid versusp-hydroxyphenylpropionic acid. Coumarin was more active than its hydroxy, methyl, hydroxymethyl, or methoxy derivatives. In general, Race 1 was even more significantly affected by the aromatic acids. Glycosylated coumarins were inactive in the bioassay, compared to their aglycones.
Application of optical diffraction to helical structures in the bacteriophage tail

First, a brief account is given of the principles underlying the use of the optical diffraction pattern of a perfectly helical particle to determine its helical lattice. The practical value and difficulties of this method are then revealed by a survey of its application to three different helical components of the T-even bacteriophage tail. The analysis of the structure of contracted sheath is much facilitated by the existence of two kinds of particle (contracted sheath and polysheath) with apparently the same helical lattice. Polysheath yields excellent optical diffraction patterns, and contracted sheath (which does not) reveals directly the number of helices in one set (information unobtainable from polysheath). The clear annuli of the extended sheath simplify the determination of all its structural parameters except for the number of helices in any set. For estimating this number, visual inspection is in one respect superior to optical diffraction, but an unambiguous solution has not hitherto been possible. The helical structure of the core is so faint that optical diffraction is indispensable for obtaining reliable structural data. Even with this method, only one structural parameter has been determined so far: the core is composed of annuli whose spacing is apparently identical with that of the annuli of the extended sheath.
Potassium and veratrine-stimulated l-[3H]cysteine sulfinate and l-[3H]glutamate release from rat brain slices☆

Abstract The release of l -[3H]cysteine sulfinic acid, l -[3H]glutamatic acid and [3H]GABA from preloaded slices of various rat brain regions in response to either 30 mM K+ or veratrin was investigated. All these aminoacids were released by both depolarizing agents, which did not produce any changes in the spontaneous efflux of [3H]lysine. The K+ stimulated cysteine sulfinate release from superfused slices was found partly Ca2+-dependent in the subiculum, and mainly Ca2+-independent in the hippocampus whereas the K+-elicited glutamate release was partly Ca2+-dependent in both regions. The veratrine-induced release of both cysteine sulfinate and glutamate was blocked by verapamil in a dose-dependent way, although a small verapamil concentration independent release remained. The release pattern of both amino acids was heterogeneous, but roughly correlated among brain regions, except in the subiculum and hypothalamus. These findings demonstrate the releasability of both substances from various brain regions and suggest that those releases occur from different pools, being probably mainly of neuronal origin. They give further evidence that cysteine sulfinate as well as glutamate may serve a neurotransmitter role in the CNS.
Metal-dependent amyloid β-degrading catalytic antibody construct.

Catalytic antibodies (catabodies) that degrade target antigens rapidly are rare. We describe the metal-dependence of catabody construct 2E6, an engineered heterodimer of immunoglobulin light chain variable domains that hydrolyzes amyloid β peptides (Aβ) specifically. In addition to the electrophilic phosphonate inhibitor of serine proteases, the metal chelators ethylenediaminetetraacetic acid (EDTA) and 1,10-phenanthroline completely inhibited the hydrolysis of Aβ by catabody 2E6. Formation of catabody-electrophilic phosphonate inhibitor adducts was unaffected by EDTA, suggesting that the metal exerts a favorable effect on a catalytic step after the initial catabody nucleophilic attack on Aβ. The EDTA inactivated catabody failed to disaggregate fibrillar Aβ, indicating the functional importance of the Aβ hydrolytic activity. Treating the EDTA-inactivated catabody with Zn2+ or Co2+ restored the Aβ hydrolytic activity, and Zn2+-induced catabody conformational transitions were evident by fluorescence emission spectroscopy. The studies reveal the absolute catabody dependence on a metal cofactor.
Characteristics of hypervelocity impact debris clouds

Abstract This paper describes an experimental investigation of hypervelocity impact debris clouds produced by impacting metal rods with Kapton flyers in an electric gun facility. Soft copper witness plates placed in the path of the debris were cratered and coated with rod material. From the sizes of the craters on the witness plates we could obtain values for a cratering parameter containing the ,asses and velocities of the debris fragments that formed the craters. By combining the cratering parameter with rough estimates of the fragment masses, we then estimated the fragment velocities. By measuring the thickness and extent of the coating on the witness plates, we obtained a bound on the amount of material vaporized by the impact.
Introversion and working memory: central executive differences

Abstract The relationship between introversion and working memory was tested. Prior studies have either not focused directly on working memory or have focused only on the storage component of working memory. Neuroanatomical and neurochemical relationships between dorsolateral prefrontal cortex and the reticular formation suggest that the executive component of working memory is the most likely to differ across introverts and extraverts. Using Sternberg’s [Sternberg, S. (1975). Memory scanning: new findings and current controversies. Quarterly Journal of Experimental Psychology, 27, 1–32.] memory scanning paradigm, which taps the central executive component of working memory, results indicate that introverts are slower than extraverts in comparing the contents of working memory to an external target. Social psychological consequences of this central executive difference in working memory are discussed.
Selenium and maternal blood pressure during childbirth.

Evidence suggests selenium concentrations outside the nutritional range may worsen cardiovascular health. This paper examines the relationship between selenium and maternal blood pressure (BP) among 270 deliveries using umbilical cord serum as a proxy for maternal exposure levels. Multivariable models used linear splines for selenium and controlled for gestational age, maternal age, race, median household income, parity, smoking, and prepregnancy body mass index. Non-parametric analysis of this dataset was used to select spline knots for selenium at 70 and 90 μg/l. When selenium was 90 μg/l. Other studies indicate that the maternal/cord selenium ratio is 1.46 (95% CI: 1.28, 1.65). This u-shaped relationship between selenium and BP is consistent with a dual role of selenium as an essential micronutrient that is nonetheless a toxicant at higher concentrations; however, this needs to be studied further.
The second riboflavin-binding myeloma IgGλDOT I. Biochemical and functional characterization

A human monoclonal immunoglobulin, IgGDOT, with flavin-binding capacity has been obtained from an elderly woman with multiple myeloma who developed yellow skin and yellow hair. The case presented a remarkable similarity with that previously reported by Farhangi and Osserman [N. Engl. J. Med. 294, 177–183 (1976)]. Purified IgGDOT was bright yellow and the ligand was identified as riboflavin and its oxidation products by thin layer chromatography, proton nuclear magnetic resonance and mass spectroscopy. Competitive binding studies with different haptens demonstrated highest affinity for riboflavin, followed by flavin mononucleotide and flavin adenine dinucleotide; no significant binding was detected for several other non-flavin compounds tested. The hapten was associated with the protein in vivo, as well as with the purified antibody. Removal of the already bound riboflavin from the combining site was associated with irreversible denaturation of the monoclonal protein. By the fluorescence quenching technique it was determined that there were 0.68 available combining sites for riboflavin molecule in IgGDOT with a binding constant of 8.5 × 108/M, while FabDOT presented 0.27 available combining sites with a binding constant of 5.1 × 108/M. The fact that 1.2 and 0.81 mol riboflavin/mol protein were already bound to IgGDOT and FabDOT, respectively, is consistent with the usual hapten/antibody stoichiometry. The heavy chain subclass of IgGDOT was identified as γ2. as in the previously reported case of riboflavin-binding protein IgGGAR. However, the λ chain subclass was different and no idiotype cross-reactivity was found.
Laboratory Culture of Tautog

Abstract Spawning of field-captured adult tautog Tautoga onitis was accomplished under laboratory conditions. Natural spawning of tautog produced more viable embryos and larvae than did strip-spawning. Embryos were cultured to hatching and raised successfully through the larval stage to juveniles. Newly hatched larvae were fed protozoans from day 0 to day 6 posthatch, rotifers from day 2 to day 20 posthatch, and brine shrimp Artemia salina from day 7 to several months posthatch. Rotifers and brine shrimp were enriched with highly unsaturated fatty acids. Supplementing cultured foods with natural plankton enhanced larval survival. Slow flow-through green-water culture proved superior to static culture methods. Handling resulted in high larval mortality. Laboratory-cultured brine shrimp and a commercial food provided an adequate diet for juvenile tautog.
Domoic Acid Neurotoxicity in Cultured Cerebellar Granule Neurons Is Mediated Predominantly by NMDA Receptors that Are Activated as a Consequence of Excitatory Amino Acid Release

The participation of NMDA and non-NMDA receptors in domoic acid-induced neurotoxicity was investigated in cultured rat cerebellar granule cells (CGCs). Neurons were exposed to 300 microM L-glutamate or 10 microM domoate for 2 h in physiologic buffer at 22 degrees C followed by a 22-h incubation in 37 degrees C conditioned growth media. Excitotoxic injury was monitored as a function of time by measurement of lactate dehydrogenase (LDH) activity in both the exposure buffer and the conditioned media. Glutamate and domoate evoked, respectively, 50 and 65% of the total 24-h increment in LDH efflux after 2 h. Hyperosmolar conditions prevented this early response but did not significantly alter the extent of neuronal injury observed at 24 h. The competitive NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid and the non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX) reduced glutamate-induced LDH efflux totals by 73 and 27%, respectively, whereas, together, these glutamate receptor antagonists completely prevented neuronal injury. Domoate toxicity was reduced 65-77% when CGCs were treated with competitive and noncompetitive NMDA receptor antagonists. Unlike the effect on glutamate toxicity, NBQX completely prevented domoate-mediated injury. HPLC analysis of the exposure buffer revealed that domoate stimulates the release of excitatory amino acids (EAAs) and adenosine from neurons. Domoate-stimulated EAA release occurred almost exclusively through mechanisms related to cell swelling and reversal of the glutamate transporter. Thus, whereas glutamate-induced injury is mediated primarily through NMDA receptors, the full extent of neurodegeneration is produced by the coactivation of both NMDA and non-NMDA receptors. Domoate-induced neuronal injury is also mediated primarily through NMDA receptors, which are activated secondarily as a consequence of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor-mediated stimulation of EAA efflux.
System Interaction of Dummy-Elicited Behavior in the Jewel Cichlid, Hemichromis Bimaculatus Gill

The responses of male Hemichromis bimaculatus toward stationary dummies presented for time intervals of 15-60 minutes were studied. The following results were obtained: I) The fish responded to the dummies with many of the same activities shown during encounters with live conspecifics. 2) At low frequency or duration activities directed toward the dummy were often diverse but at relatively high levels certain activities dominated behavior during dummy presentation. The latter led to categorization of behavior into response types, biting-, quivering-, fluttering-, and finrest-dominated, which are negatively correlated with each other at high levels. 3) A male which previously responded to a dummy with a quivering-dominated response while unpaired switched to a biting-dominated response to the dummy when paired with a live female. 4) Certain activities, namely lateral display and tailbeating, occurred during both biting-dominated and quivering-dominated responses but gradually decreased during the course of an observation period. It was concluded that each response type reflects a dominance of corresponding tendencies or systems in the fish's behavior and that certain activities associated with these systems are mutually inhibitory. Furthermore, there is evidence suggesting that two of these systems (fluttering and finrest) comprise behavior that is usually regarded as a single system. Lateral display, tailbeating and quivering are considered in terms of interaction between systems.
Transfer Learning across Cancers on DNA Copy Number Variation Analysis

DNA copy number variations (CNVs) are prevalent in all types of tumors. It is still a challenge to study how CNVs play a role in driving tumorgenic mechanisms that are either universal or specific in different cancer types. To address the problem, we introduce a transfer learning framework to discover common CNVs shared across different tumor types as well as CNVs specific to each tumor type from genome-wide CNV data measured by array CGH and SNP genotyping array. The proposed model, namely Transfer Learning with Fused LASSO (TLFL), detects latent CNV components from multiple CNV datasets of different tumor types to distinguish the CNVs that are common across the datasets and those that are specific in each dataset. Both the common and type-specific CNVs are detected as latent components in matrix factorization coupled with fused LASSO on adjacent CNV probe features. TLFL considers the common latent components underlying the multiple datasets to transfer knowledge across different tumor types. In simulations and experiments on real cancer CNV datasets, TLFL detected better latent components that can be used as features to improve classification of patient samples in each individual dataset compared with the model without the knowledge transfer. In cross-dataset analysis on bladder cancer and cross-domain analysis on breast cancer and ovarian cancer, TLFL also learned latent CNV components that are both predictive of tumor stages and correlate with known cancer genes.
Deposition of Inhaled Particles in the Oral Airway During Oronasal Breathing

The deposition efficiency of inhaled particles in the oral airway was examined under experimental conditions that simulated natural oronasal breathing during moderate and heavy exercise in three human volunteers. Monodisperse, spherical, nonhygroscopic particles were generated by condensing di-2-ethylhexyl sebacate vapor onto nuclei of sodium fluorescein, a fluorescent tracer. The mass median aerodynamic diameter ranged between 3 and 16 μm. The aerosol was inhaled by mouth without a mouthpiece. After inhalation, the subject gargled to remove the deposited fluorescent tracer from the oral airway. On average, during simulated moderate exercise, 58% of the 10 μm diameter particles and 79% of the 15 μm particles deposited in the oral airway. During simulated heavy exercise, deposition efficiency in the oral airway was lower than during moderate work. The site of particle deposition as determined with a radioactive aerosol was influenced by how widely the mouth was opened, either naturally in heavy exercise, o...
Underwater containment for power reactors

Abstract The purpose of this study was to investigate the feasibility and potential advantages of containing large nuclear power reactors in underwater caissons. The reference design described consists of a 715 MWe boiling-water reactor housed in a concrete caisson located one-half mile offshore. The turbine-generator is located on a ten-acre artificial island, which surrounds the caisson. Seawater is employed for containment cooling and to reduce the outleakage of fission products in the event of a reactor loss-of-coolant accident. It is estimated that the activity release rates to the environment would be several orders of magnitude smaller than for the corresponding above-ground containment system. Significant contamination of the sea appears unlikely. It is suggested that this new containment approach be considered for power reactors near metropolitan areas that require augmented reactor safety and that are adjacent to a suitable lake, river, or ocean. A significant reduction of overall plant cost appears achievable at sites with high land values.
A computational study of the thermochemistry of bromine- and iodine-containing methanes and methyl radicals.

Article on a computational study of the thermochemistry of bromine- and iodine-containing methanes and methyl radicals.
Intermolecular chiral recognition probed by enantiodifferential excited-state quenching kinetics

Time-resolved chiroptical luminescence (TR-CL) measurements are used to study the kinetics of chirality-dependent excited-state quenching processes in aqueous solution. Experiments are carried out on samples that contain a racemic mixture of chiral luminophore molecules (L) in solution with a small, optically active concentration of chiral quencher molecules (Q). The luminophores are excited with a pulse of unpolarized light to create an initially racemic excited-state population of lambda L* and delta L* enantiomers, and TR-CL measurements are then used to monitor the differential decay kinetics of the lambda L* and delta L* subpopulations. Observed differences between the lambda L* and delta L* decay kinetics reflect differential rate processes and efficiencies for lambda L*-Q versus delta L*-Q quenching actions, and they are diagnostic of chiral discriminatory interactions between the luminophore and quencher molecules. In this study, the luminophores are either Eu(dpa)3(3-) or Tb(dpa)3(3-) coordination complexes (where dpa denotes a dipicolinate dianion ligand), and the quenchers are diastereomeric structures of Cr(H2O)4(ATP), Rh(H2O)4(ATP) and Rh(H2O)3(ATP) (where ATP identical to adenosine triphosphate). The Ln(dpa)3(3-) (Ln identical to En3+ or Tb3+) complexes have three-bladed propeller-like structures of D3 symmetry, and in aqueous solution they exist as a racemic mixture of left-handed (lambda) and right-handed (delta) configurational isomers (enantiomers). The results show that the chiral quencher molecules can distinguish between the lambda and delta enantiomeric structures of the luminophores in their excited-state quenching actions. The degree and sense of enantiomeric preference in these quenching actions are governed by the electronic and stereochemical properties of the quencher molecules. Twenty-one different luminophore-quencher systems are examined in this study, and they exhibit interestingly diverse enantiodifferential quenching kinetics. The results reflect the extraordinary sensitivity of chiral recognition and discrimination processes to relatively small, and sometimes subtle, changes in molecular electronic and stereochemical structure.
Airway smooth muscle cells enhance C3a-induced mast cell degranulation following cell-cell contact

SPECIFIC AIMSStudies with animal models and immunohistochemistry analysis of lung tissue indicate that anaphylatoxins (C3a and C5a) may regulate airway hyperresponsiveness (AHR) in asthma via activation of their cell surface G-protein-coupled receptors in airway smooth muscle (ASM) cells. The purpose of this study was to test the hypothesis that C3a and C5a receptors are expressed in cultured primary human and murine ASM cells and to determine the signal transduction pathways whereby the functions of these receptors are regulated.PRINCIPAL FINDINGS1. Mast cells and monocytes/macrophages express C3a and C5a receptors (C3aR and C5aR) but ASM cells do notC3aR and C5aR are endogenously expressed in human mast cells and circulating leukocytes. RT-PCR was performed to determine whether mRNA for these receptors is present in cultured human ASM cells. A human mast cell line, HMC-1, purified human monocytes that constitutively express C3aR and C5aR, served as a control. As shown in Fig. 1⤻ A, C3aR and C5aR mRNA wa...
N retention and transformation in urban streams

AbstractNutrient spiraling in theory and application provides a framework for comparing nutrient retention efficiency of urban streams to relatively unaltered streams. Previous research indicated that streams of the southwestern USA deserts are highly retentive of N because of N limitation, high productivity, and high channel complexity (in particular, extensive transient storage associated with the hyporheic zone). Most southwestern urban streams have extensively modified channels and experience N loading from urban runoff and inputs of NO3−-contaminated groundwater. Therefore, we predicted southwestern urban streams are neither N-limited nor retentive. For some urban streams, however, restoration efforts reestablish flow in long-dry channels, create nonstructural flood-management solutions, and design riparian areas as a public recreation amenity. These human modifications may, in part, restore N retention functions if channel complexity and heterogeneity are as important to N retention efficiency as be...
Metal Resistance and Lithoautotrophy in the Extreme Thermoacidophile Metallosphaera sedula

Archaea such as Metallosphaera sedula are thermophilic lithoautotrophs that occupy unusually acidic and metal-rich environments. These traits are thought to underlie their industrial importance for bioleaching of base and precious metals. In this study, a genetic approach was taken to investigate the specific relationship between metal resistance and lithoautotrophy during biotransformation of the primary copper ore, chalcopyrite (CuFeS2). In this study, a genetic system was developed for M. sedula to investigate parameters that limit bioleaching of chalcopyrite. The functional role of the M. sedula copRTA operon was demonstrated by cross-species complementation of a copper-sensitive Sulfolobus solfataricus copR mutant. Inactivation of the gene encoding the M. sedula copper efflux protein, copA, using targeted recombination compromised metal resistance and eliminated chalcopyrite bioleaching. In contrast, a spontaneous M. sedula mutant (CuR1) with elevated metal resistance transformed chalcopyrite at an accelerated rate without affecting chemoheterotrophic growth. Proteomic analysis of CuR1 identified pleiotropic changes, including altered abundance of transport proteins having AAA-ATPase motifs. Addition of the insoluble carbonate mineral witherite (BaCO3) further stimulated chalcopyrite lithotrophy, indicating that carbon was a limiting factor. Since both mineral types were actively colonized, enhanced metal leaching may arise from the cooperative exchange of energy and carbon between surface-adhered populations. Genetic approaches provide a new means of improving the efficiency of metal bioleaching by enhancing the mechanistic understanding of thermophilic lithoautotrophy.
The effect of various dentifrices on surface roughness and gloss of resin composites

Abstract Objectives The purpose of this study was to evaluate the effect of different levels of abrasiveness (RDA) of dentifrices on the gloss and surface roughness of resin composites after toothbrushing. Methods Sixty disk-shaped composite specimens (D = 10.0 mm, 2-mm thick, n = 15 per material) were made of: microfill (Durafill), nanofill (Filtek Supreme), minifill hybrid (Filtek 250), and nanohybrid (Premise). One side of each specimen was finished with a carbide bur and polished with Enhance and Pogo. Five specimens of each composite were randomly assigned to one of the dentifrices, Colgate Total (CT; RDA 70), Colgate baking soda & peroxide whitening (CBS; RDA 145), and Colgate tartar control & whitening (CTW; RDA 200). Surface gloss was measured with a glossmeter and surface roughness with a profilometer before and after toothbrushing with a 1:2 slurry (dentifrice/deionised water) at 5760 strokes in a brushing machine (∼1 Hz). Results were analyzed by three-way ANOVA/Tukey's (p Results There was a significant reduction in gloss and increase in surface roughness after brushing with all dentifrices. There was no significant difference in gloss when Durafill was brushed with any dentifrice; the other composites showed less gloss reduction when brushed with CT. Durafill, Supreme and Premise did not show significantly different surface roughness results and CBS and CTW did not produce significantly different results. Conclusions Dentifrices of lower abrasivity promote less reduction in gloss and surface roughness for composites of different particle sizes after brushing. Composites containing smaller average fillers showed less reduction in gloss and less increase in surface roughness than ones with larger fillers.