cssi/SciSciGPT-SciSciNet huggingface dataset:
Distinctive Inactivation Profiles of CaV1.2 Channels Encoding Different Timothy Syndrome Mutations in Various Alternative Splicing Backgrounds

Timothy Syndrome is a CaV1.2 channelopathy, wherein mutations in the S6 segment of domain II affect channel inactivation. Interestingly, different mutations (G402S or G406R) within alternatively spliced exons (8a or 8) entail characteristic disease phenotypes, including autism, syndactyly, and long QT syndrome. Investigating Timothy Syndrome thereby promises mechanistic traction into these complex outcomes. The prevalence and distribution of channels bearing exon 8 versus 8a may explain some phenotypic variation. Here, we examine such variation at a more fundamental level, resolving intrinsic differences of inactivation among distinct mutant channels. Specifically, CaV1.2 inactivation comprises two separate mechanisms, voltage-dependent inactivation (VDI), and Ca2+/calmodulin-mediated inactivation (CDI) (Barrett & Tsien PNAS 2008). Systematic mutagenesis of S6 domains in CaV1.3 suggest that VDI and CDI alterations can be dissociated, and changes in channel activation are likely (Tadross et al, this meeting). Our data here furnish remarkable examples of differing CDI/VDI effects (a, wild-type, with Ba2+ current decay showing VDI, and Ca2+ decay showing CDI; b, c, distinct CDI/VDI alterations). It would be interesting if distinctive disease phenotypes and therapeutics ultimately correspond to specified deficits of VDI, CDI, or both.View Large Image | View Hi-Res Image | Download PowerPoint Slide
THE AGE VARIABLE IN PSYCHOLOGICAL RESEARCH1

This paper examines the manner in which age is treated in the design and conception of developmental research, and the dissatisfaction with its status as a concept and its use in research. This is attributed to the widespread tendency to consider age as an independent variable, comparable to others employed in differential research, and to study age differences rather than age changes. An alternative view is presented, which treats developmental questions as analogous to other phenomena involving changes in behavior over time. Age is looked at as a dimension along which behavior changes are to be traced, forming part of the definition of the dependent variable in developmental studies. This dependent variable is to be defined in terms of specified aspects or parameters of the function describing the changes which occur with age for a given behavioral variable. Implications of this view for developmental research are brought out, with particular reference to problems of description and quantitative analysis of developmental change, to the application of the experimental method in developmental research, and to the study of individual differences in the context of developmental change.
The adsorption and reactions of enzymes and proteins on kaolinite. III. The isolation of enzyme-substrate complexes

Abstract It is known that the adsorption of a protein by a clay may reduce the rate of decomposition of the protein by soil microorganisms. In this connection it is of interest to determine how adsorption of an enzyme and/or substrate on the surfaces of clay minerals influences the kinetics of enzyme action and microbial nutrition. With kaolinite as the adsorbent, it has been found that proteolysis of adsorbed substrate is brought about predominately by the preliminary formation of a reactive enzyme-substrate-kaolinite complex and not by enzyme in the solution state. The substrate was heat-denatured lysozyme and the enzymes were chymotrypsin and trypsin. The enzyme-substrate-kaolinite complex may be prepared at low or high pH. At lowpH (4.9) it is fairly stable; at high pH (8.2–9.3) itreacts. Proteolysis of the adsorbed complex occurs at a rate comparable to the action of chymotrypsin on substrate in the absence of kaolinite; consequently, adsorbed chymotrypsin molecules must be able to move about the surface of the adsorbat at a rate comparable to that in solution. The order of addition of enzyme and substrate to the clay greatly influences the rate of reaction, however, showing a specific influence of surface on reaction rate.
Migration: a new technique to improve synthesized designs through incremental customization

A novel technique to explore the performance vs. design effort trade-off is proposed. Starting from an optimally synthesized design, performance-critical cells are incrementally and optimally selected and custom-sized to generate this trade-off. Efficient algorithms for the optimal selection, and for improving the reuse of custom-sized cells in the design are given. Significant performance gains are shown in several real circuits through the addition of very few customized cells.
Genetic determinants of lung virus titers and resistance to lethal Sendai virus pneumonia.

C 57 BL/6J mice are resistant to lethal Sendai virus pneumonia and have lower lung virus titers than susceptible DBA/2J mice. Linkage between these phenotypes was tested indirectly in segregant hybrids.Sas-1,B2m, andb on chromosomes 1, 2, and 4 were linked to significant (P P>.05). Mean lung virus titers were higher in F1 × DBA/2 J mice that were homozygous for DBA alleles atB2m, b, andd than in heterozygotes. The difference in lung virus titers was larger between mice that were dihomozygous/diheterozygous for paired combinations;B2m-d (P<.02),B2m-b (P<.06), andb–d (P<.05) and largest between mice that were trihomozygous/triheterozygous forB2m-b–d (P<.001). The distribution of virus titers among 22 recombinant inbred strains derived from C 57 BL/6 J and DBA/2 J progenitors indicated 1) that the loci linked toB2m, b, andd are among at least 4 loci that regulate lung virus titers, 2) thatSas-1 may be linked to a fourth locus, 3) that the C 57 BL/6 J genome contains at least one susceptibility locus, possibly within H-2, and 4) that some of these loci may be expressed through natural killer cell activity.
Temporal metrics for software vulnerabilities

It is widely recognized that metrics are important to information security. Metrics can be an effective tool for companies and information security professionals to measure, control, and improve their security control and mechanisms. However, common security metrics are often qualitative, subjective, and informal in the sense that they are lacking formal models and automated support. This paper discussed our work on temporal metrics for software vulnerabilities based on the Common Vulnerability Scoring System 2.0. A mathematical model is provided to calculate the severity and risk of a vulnerability, which is time dependent including exploitability, remediation level, and report confidence attributes of an information asset in a computing environment. A prototype of an automated tool, CVSSWizzard, is illustrated with examples.
Using galvanostatic electroforming of Bi 1–x Sb x nanowires to control composition, crystallinity, and orientation

Using galvanostatic pulse deposition, we studied the factors influencing the quality of electroformed Bi1–xSbx nanowires with respect to composition, crystallinity, and preferred orientation for high thermoelectric performance. Two nonaqueous baths with different Sb salts were investigated. The Sb salts used played a major role in both crystalline quality and preferred orientations. Nanowire arrays electroformed using an SbI3-based chemistry were polycrystalline with no preferred orientation, whereas arrays electroformed from an SbCl3-based chemistry were strongly crystallographically textured with the desired trigonal orientation for optimal thermoelectric performance. From the SbCl3 bath, the electroformed nanowire arrays were optimized to have nanocompositional uniformity, with a nearly constant composition along the nanowire length. Nanowires harvested from the center of the array had an average composition of Bi0.75Sb0.25. However, the nanowire compositions were slightly enriched in Sb in a small region near the edges of the array, with the composition approaching Bi0.70Sb0.30.
What Infants and Breasts Can Teach Us about Natural Protection from HIV Infection

Most individuals exposed to human immunodeficiency virus (HIV), adults and children alike, do not become infected. Understanding the basis of this protection depends on systematically and comprehensively defining factors that determine the infectiousness of the host and the susceptibility of the recipient. Successful transmission depends on the relative balance between infectiousness and susceptibility, both of which are influenced by biologic, behavioral, and environmental factors. In this review, we discuss the advantages and disadvantages of mother‐to‐child HIV transmission as a model in which to elucidate correlates of immune protection.
Synthesis, in vitro affinity, and efficacy of a bis 8-ethynyl-4H-imidazo[1,5a]- [1,4]benzodiazepine analogue, the first bivalent alpha5 subtype selective BzR/GABA(A) antagonist.

The synthesis and in vitro affinity of the α5β3γ2 (α5) subtype selective BzR/GABAA antagonist 7 is described. This ligand is selective for α5 subtypes in vitro and is a potent antagonist of the effects of diazepam only at α5β3γ2 subtypes (oocytes). Ligands such as 7 will be important in the determination of which physiological function(s) are subserved by this GABAA α5 subtype.
Food availability affects Osmia pumila (Hymenoptera: Megachilidae) foraging, reproduction, and brood parasitism

Food limitation can reduce reproductive success directly, as well as indirectly, if foraging imposes a risk of predation or parasitism. The solitary bee Osmia pumila suffers brood parasitism by the cleptoparasitic wasp Sapyga centrata, which enters the host nest to oviposit while the female bee is away. I studied foraging and reproduction of O. pumila nesting within cages stocked with rich or sparse floral resources, and the presence or absence of S. centrata to test (1) the response of nesting female O. pumila to food shortages, (2) the response of nesting female O. pumila to the presence of parasites, and (3) whether brood produced under scarce resources are more likely to be parasitized by S. centrata. The rate of brood cell production was significantly lower in cages with sparse floral resources, although females in sparse cages did not produce significantly fewer brood cells overall. Sapyga centrata did not influence the rate of brood cell production, but females exposed to the cleptoparasites had marginally significantly lower reproductive output. Nests in parasite cages had significantly fewer brood cells than those in parasite free cages. The mean duration of foraging bouts made by female O. pumila in sparse cages was not significantly longer than that in rich cages. O. pumila spent less time in the nest between pollen and nectar foraging bouts in sparse cages with S. centrata than those in other cages suggesting that these individuals made more frequent food foraging trips. Despite the weak effects of parasites and bloom density on foraging behavior, O. pumila brood cells experienced a 15-fold higher probability of parasitism by S. centrata in cages with sparse bloom than in those with rich bloom. These results support the hypothesis that indirect effects of food scarcity increase O. pumila susceptibility to brood parasitism, although the exact mechanism is not entirely clear yet.
Multi-component reactive transport modeling of natural attenuation of an acid groundwater plume at a uranium mill tailings site

Abstract Natural attenuation of an acidic plume in the aquifer underneath a uranium mill tailings pond in Wyoming, USA was simulated using the multi-component reactive transport code phreeqc . A one-dimensional model was constructed for the site and the model included advective–dispersive transport, aqueous speciation of 11 components, and precipitation–dissolution of six minerals. Transport simulation was performed for a reclamation scenario in which the source of acidic seepage will be terminated after 5 years and the plume will then be flushed by uncontaminated upgradient groundwater. Simulations show that successive pH buffer reactions with calcite, Al(OH) 3 (a), and Fe(OH) 3 (a) create distinct geochemical zones and most reactions occur at the boundaries of geochemical zones. The complex interplay of physical transport processes and chemical reactions produce multiple concentration waves. For SO 4 2− transport, the concentration waves are related to advection–dispersion, and gypsum precipitation and dissolution. Wave speeds from numerical simulations compare well to an analytical solution for wave propagation.
Key aspects of organizational buying: conceptualization and measurement

Much research has been devoted to organizational buying. Unfortunately, few studies focus on the development of specific measures of organizational buying behavior. And although many concepts in the literature are useful for describing and discussing buying behavior, they often cut across other buying activities and therefore may not be empirically distinct. This research applies a combination of literature- and field-based approaches to develop four distinct constructs that underlie the numerous activities in which buyers engage: procedural control, proactive focusing, use of analysis techniques, and search for information. Measurement scales for these constructs are created and then evaluated through a survey of purchasing professionals. The procedure resulted in a set of constructs and measures that may be applied to several complex areas of organizational buying research.
Determinants of retinopathy progression in type 1 diabetes mellitus.

Abstract PURPOSE: To determine the risk factors for retinopathy progression in type 1 (insulin-dependent) diabetes mellitus in a prospective cohort study. SUBJECTS AND METHODS: Subjects were 485 participants in the Sorbinil Retinopathy Trial, a randomized trial of aldose reductase inhibition among patients aged 18 to 56 years with type 1 diabetes mellitus (duration of 1 to 15 years) and no or only mild retinopathy. Retinopathy progression, assessed by seven-field stereoscopic fundus photography, was defined as worsening by two or more levels on a standardized grading scale at the end of follow-up (median, 41 months). RESULTS: The relative risks for retinopathy progression according to successively greater quintiles of total glycosylated hemoglobin level at baseline, after adjusting for age, diabetes duration, sorbinil assignment, and other variables, were 1.0, 2.0, 1.6, 3.7, and 4.4 ( P trend P for trend=0.04). Diastolic blood pressure was a significant risk factor for progression in participants with mild baseline retinopathy ( P for trend P for trend=0.03) but not when it was examined as a continuous variable or when hypercholesterolemic patients were compared with those with normal levels. Furthermore, when cholesterol levels were updated in subsequent visits, it was not a significant predictor of progression, and low density lipoprotein (LDL) cholesterol levels did not predict progression no matter how analyzed. Smoking was not associated with progression of retinopathy. CONCLUSIONS: Levels of hyperglycemia and diastolic blood pressure predicted progression of retinopathy in type 1 diabetes mellitus. We found only a suggestion of an association between total cholesterol level (but not of LDL cholesterol level) and progression of retinopathy; resolution of this issue will require additional studies with larger sample sizes and longer follow-up.
Nuanced roles of cytokines in three major human brain disorders

The three most prevalent human disorders of the CNS in which immunity and inflammation are likely to have vital roles (excluding infection of the CNS) are fever, multiple sclerosis (MS), and Alzheimer disease (AD). As reviewed here, cytokines are critical in the induction of fever, the pathogenesis of MS, and the pathobiology of AD. Indeed, antibodies targeting cytokines have been used as a therapy for individuals with unusual and persistent febrile reactions not responsive to common antipyretics, while a recombinant cytokine is the most popular treatment for the relapsing-remitting form of MS. Although cytokine-modulating therapies are not currently in clinical use for the treatment of AD, cytokines can ameliorate disease pathology in certain experimental models of AD, suggesting a potential for future therapeutic opportunities.
TEST‐RETEST ANALYSES OF THE TEST OF ENGLISH AS A FOREIGN LANGUAGE

The present study provides two kinds of information that have not previously been available in a single research report on the Test of English as a Foreign Language (TOEFL) with regard to its total and component scores. First, the study provides comparative global and component estimates of test-retest, alternate-form, and internal-consistency reliability. This complies with the joint standards of the American Psychological Association, the American Educational Research Association, and the National Council for Measurement in Education by controlling for sources of measurement error that may be inherent both among the examinees and within the testing administration context, and not merely within the examination itself. Secondly, the study provides information about differential change in subtest difficulty on repeated application over a small interval of time (viz., eight days). This second concern is related to the phenomenon of “item bounce” and reflects the comparative stabilities of difficulty estimates within item type over repeated test administrations. This comparative stability information may provide useful insights into the functioning of particular TOEFL® subtest item types and the suitability of those item types for anchoring in test equating. Although test-length-adjusted reliability estimates were found to be adequately high across reported component and total test scores, with raw score test-retest coefficients ranging from .87 to .98 (with a mean of .93 over 22 total coefficients), raw score internal-consistency coefficients ranging from .79 to .98 (with a mean of .94 over 88 total coefficients), and raw score alternate-form coefficients ranging from .78 to .97 (with a mean of .90 over 22 total coefficients), the study contained several inherent limitations. Chief among these limitations was the comparatively small sample involved. Only 329 total subjects participated, and, due to attrition and design features, test-retest reliability estimates were based on separate repeating subgroups of only 101 and 91 persons. Alternate-form reliability estimates were based on separate repeating subgroups of only 52 and 25 persons. Although estimates were replicated across two TOEFL forms and at least two distinct samples, it was not possible within the existing project constraints to identify repeating samples that were perfectly representative of the current TOEFL examinee population in regard to language background and mean language proficiency.
Correlation of the Average Water Diffusion Constant with Cerebral Blood Flow and Ischemic Damage After Transient Middle Cerebral Artery Occlusion in Cats

Magnetic resonance water diffusion imaging can detect early ischemic changes in stroke. Using a middle cerebral artery occlusion model, we examined which range of values of the orientation-independent diffusion quantity is an early noninvasive indicator of reduced cerebral perfusion and focal brain injury. Cats underwent either a 30-min occlusion followed by 3.5 h reperfusion (n = 7) or a 60-min occlusion followed by 4-h reperfusion (n = 6). Repeated measurements of CBF were made with radiolabeled microspheres, and acute focal injury was measured with triphenyltetrazolium chloride (TTC) staining. During occlusion, the decrease in Dav correlated with CBF for caudate [30-min occlusion (n = 13): p < 0.0001; 60-min occlusion (n = 6): p < 0.02] and for cortex [30-min occlusion (n = 12): p < 0.0001; 60-min occlusion (n = 5): p < 0.04]. Variable caudate and hemispheric injury levels were found among cats in both groups. The area of tissue injury demarcated by TTC began to correlate with the area of reduced Dav b...
RNA synthesis and stability in UV-irradiated and nonirradiated mouse L cells.

In mouse L cells, relatively low doses of UV light (e.g., about 35 J/m2) induced the rapid breakdown of the molecules of many RNA species transcribed shortly before irradiation. This included 28S, 18S, 5.8S, and 5S rRNA, U1, U2, U3, U4, and U5 small nuclear RNA, but not the main band of transfer RNAs or 7SL RNA. At higher UV doses, an RNA band that contains tRNAleu was also degraded rapidly after UV irradiation. RNA molecules synthesized long before irradiation (e.g., 22 h for small RNAs, 4 h for large rRNAs) were not affected. Our results suggest that the maturation and/or assembly into fully mature ribonucleoprotein particles of several small RNA species is not completed 4 h after transcription. The effect of UV radiation occurred in mouse L cells, but not in human HeLa or KB cells. In a previous report, L cells were transformed by DNA transfection with two mouse U1b RNA genes, named U1.1 and U1.2. We observed now that, in L cells transformed with the U1.2 gene, the ratio of radioactivity in the apparent U1b and U1a RNA precursors after 5 min of labeling was about 20 times higher than (a) this ratio in briefly labeled L cells that had been transformed with the U1.1 gene, and (b) the ratio of radioactive mature U1b and U1a RNA after 20 h of chase in L cells transformed with the U1.2 gene. These results suggest that very high levels of U1b RNA are transcribed from the exogenous U1.2 gene copies, followed by the rapid degradation of most of these transcripts.
Ecology and evolution of pine life histories

& Introduction Pinus is a diverse genus of trees widely distributed throughout the Northern Hemisphere. Understanding pine life history is critical to both conservation and fire management. & Objectives Here I lay out the different pathways of pine life history adaptation and a brief overview of pine evolution and the very significant role that fire has played. & Results Pinus originated ~150 Ma in the mid-Mesozoic Era and radiated across the northern continent of Laurasia during the Cretaceous Period. Pines have followed two evolutionary strategies interpreted as responses to competition by the newly emergingangiosperms.TheStrobuslineage mostly hasradiated into stressful sites of low nutrie nt soils and extremes in cold or heat. The Pinus (subgenus) lineage has radiated into fire-prone landscapes with diverse fire regimes. Examination of life history traits illustrates syndromes associated with fire-avoider, fire-tolerater, fire-embracer ,a ndfire-refuge strategies. & Conclusion Understanding the current pattern of pine distribution requires interpreting their evolution in terms of climate, geology, and fire. All three of these factors have played a role since the Mesozoic origin of the genus. All are important to the appropriate management of these resources.
An investigation of a super-Earth exoplanet with a greenhouse-gas atmosphere using a general circulation model

Abstract We use the Massachusetts Institute of Technology general circulation model (GCM) dynamical core, in conjunction with a Newtonian relaxation scheme that relaxes to a gray, analytical solution of the radiative transfer equation, to simulate a tidally locked, synchronously orbiting super-Earth exoplanet. This hypothetical exoplanet is simulated under the following main assumptions: (1) the size, mass, and orbital characteristics of GJ 1214b (Charbonneau, D. [2009]. Nature 462, 891–894), (2) a greenhouse-gas dominated atmosphere, (3), the gas properties of water vapor, and (4) a surface. We have performed a parameter sweep over global mean surface pressure (0.1, 1, 10, and 100 bar) and global mean surface albedo (0.1, 0.4, and 0.7). Given assumption (1) above, the period of rotation of this exoplanet is 1.58 Earth-days, which we classify as the rapidly rotating regime. Our parameter sweep differs from Heng and Vogt (Heng, K., Vogt, S.S. [2011]. Mon. Not. R. Astron. Soc. 415, 2145–2157), who performed their study in the slowly rotating regime and using Held and Suarez (Held, I.M., Suarez, M.J. [1994]. Bull. Am. Meteorol. Soc. 75 (10), 1825–1830) thermal forcing. This type of thermal forcing is a prescribed function, not related to any radiative transfer, used to benchmark Earth’s atmosphere. An equatorial, westerly, superrotating jet is a robust feature in our GCM results. This equatorial jet is westerly at all longitudes. At high latitudes, the flow is easterly. The zonal winds do show a change with global mean surface pressure. As global mean surface pressure increases, the speed of the equatorial jet decreases between 9 and 15 h local time (substellar point is located at 12 h local time). The latitudinal extent of the equatorial jet increases on the nightside. For the two greatest initial surface pressure cases, an increasingly westerly component of flow develops at middle to high latitudes between 11 and 18 h local time. On the nightside, the easterly flow in the midlatitudes also increases in speed as global mean surface pressure increases. Furthermore, the zonal wind speed in the equatorial and midlatitude jets decreases with increasing surface albedo. Also, the latitudinal width of the equatorial jet decreases as surface albedo increases.
Gender, Place, and Social Contacts: Understanding Awareness of Vulnerability to Terrorism

Abstract Creating resiliency, accomplished in part by individuals preparing for disaster, is the primary strategy outside of law enforcement for responding to the threat of urban terrorism. Individuals prepare when they perceive a need to do so, yet little is known about what shapes a person's awareness of vulnerability to terrorism. Because evidence indicates that social contacts act as conduits of information and affect perception of risk to natural hazards, it is possible that such contacts also affect terrorism vulnerability awareness. Because social contacts are also known to be systematically segmented by gender and location, we hypothesized that conversations about terrorism vary by gender and place, specifically the home and work place. Drawing on data from 93 interviews with householders in Boston, the study demonstrates that: (1) family networks generated discussions of home preparedness, whereas workplace networks engaged a wider variety of topics; (2) women discussed terrorism more frequently ...
Fezf1 and Fezf2 are required for olfactory development and sensory neuron identity

The murine olfactory system consists of main and accessory systems that perform distinct and overlapping functions. The main olfactory epithelium (MOE) is primarily involved in the detection of volatile odorants, while neurons in the vomeronasal organ (VNO), part of the accessory olfactory system, are important for pheromone detection. During development, the MOE and VNO both originate from the olfactory pit; however, the mechanisms regulating development of these anatomically distinct organs from a common olfactory primordium are unknown. Here we report that two closely related zinc-finger transcription factors, FEZF1 and FEZF2, regulate the identity of MOE sensory neurons and are essential for the survival of VNO neurons respectively. Fezf1 is predominantly expressed in the MOE while Fezf2 expression is restricted to the VNO. In Fezf1-deficient mice, olfactory neurons fail to mature and also express markers of functional VNO neurons. In Fezf2-deficient mice, VNO neurons degenerate prior to birth. These results identify Fezf1 and Fezf2 as important regulators of olfactory system development and sensory neuron identity.
Do infants learn grammar with algebra or statistics

The report “Rule learning by seven-month-old infants” by G. F. Marcus et al . (1 Jan. p. [77][1]) adds to a growing body of evidence concerning the remarkable learning abilities of infants. This evidence indicates that children acquire much more knowledge of language from experience than one
Preliminary efficacy of a Web-based family problem-solving treatment program for adolescents with traumatic brain injury

Objective Preliminary report of the efficacy of a Web-based treatment program to improve adolescent and family psychosocial functioning following traumatic brain injury (TBI). Participants Families of 9 adolescents with TBI (2 severe and 7 moderate) injured less than 24 months ago participated in this study. Intervention A Web-based family treatment program designed to enhance family problem solving and adjustment, as well as reduce adolescent behavioral and social problems that are common sequelae of moderate-to-severe TBI was used as intervention. The program consisted of 10 core sessions and up to 4 supplemental sessions, each consisting of self-guided Web exercises followed by a videoconference therapy session. Results Significant improvements were found in parent-reported adolescent internalizing behaviors, self-reported adolescent depressive symptoms, parental depression, and parent-adolescent conflict. Effect sizes were in the medium-to-high range for these same contrasts. Exploratory analyses suggested that providing audio with the Web site may enhance some outcomes. Conclusions This study provides preliminary evidence of the feasibility and efficacy of family-centered online intervention for improving adolescent and family adaptation following pediatric TBI.
Visualization of longitudinal convection roll instabilities in an inclined enclosure heated from below

Experiments have been performed on the stability of buoyancy-driven flows of a high-Prandtl-number fluid in an inclined rectangular enclosure. Visualization of the stable planform of convection for various Rayleigh numbers and inclination angles is provided by a temperature-sensitive liquid crystal and gold-coated film heater assembly which serves as the lower surface of the enclosure. This assembly produces a nearly constant heat flux surface with a thermal conductivity of the same order as that of the test fluid. The results indicate that for large angles of inclination from the horizontal a steady transverse roll(s) structure is stable. As the angle of inclination is decreased steady longitudinal rolls replace the transverse roll(s) and for low angles a steady square-cell convection planform is observed. A region of unsteady wavy longitudinal rolls is also observed at sufficiently high Rayleigh numbers for low to moderate angles of inclination. In general the wavenumber of the longitudinal rolls increases with angle of inclination from the horizontal. Two distinct types of instability mechanisms are observed which modify the wavenumber of the longitudinal rolls: a cross-roll instability, which is a disturbance perpendicular to the original roll axis; and a pinching mechanism which combines two neighbouring longitudinal roll pairs into a longer wavelength roll pair.
A Role for the Class A Penicillin-Binding Protein PonA2 in the Survival of Mycobacterium smegmatis under Conditions of Nonreplication

Class A penicillin-binding proteins (PBPs) are large, bifunctional proteins that are responsible for glycan chain assembly and peptide cross-linking of bacterial peptidoglycan. Bacteria in the genus Mycobacterium have been reported to have only two class A PBPs, PonA1 and PonA2, that are encoded in their genomes. We report here that the genomes of Mycobacterium smegmatis and other soil mycobacteria contain an additional gene encoding a third class A penicillin-binding protein, PonA3, which is a paralog of PonA2. Both the PonA2 and PonA3 proteins contain a penicillin-binding protein and serine/threonine protein kinase-associated (PASTA) domain that we propose may be involved in sensing the cell cycle and a C-terminal proline-rich region (PRR) that may have a role in protein-protein or protein-carbohydrate interactions. We show here that an M. smegmatis ΔponA2 mutant has an unusual antibiotic susceptibility profile, exhibits a spherical morphology and an altered cell surface in stationary phase, and is defective for stationary-phase survival and recovery from anaerobic culture. In contrast, a ΔponA3 mutant has no discernible phenotype under laboratory conditions. We demonstrate that PonA2 and PonA3 can bind penicillin and that PonA3 can partially substitute for PonA2 when ponA3 is expressed from a constitutive promoter on a multicopy plasmid. Our studies suggest that PonA2 is involved in adaptation to periods of nonreplication in response to starvation or anaerobiosis and that PonA3 may have a similar role. However, the regulation of PonA3 is likely different, suggesting that its importance could be related to stresses encountered in the environmental niches occupied by M. smegmatis and other soil-dwelling mycobacteria.
THE LOST-LETTER TECHNIQUE: PREDICTING ELECTIONS

The lost-letter technique was validated against the 1968 Presidential, Senatorial and Congressional elections. Placement on car windshields predicted the trend in all 3 races when only the major ca...
Phylogeny and genetic diversity of Bridgeoporus nobilissimus inferred using mitochondrial and nuclear rDNA sequences

The genetic diversity and phylogeny of Bridgeoporus nobilissimus have been analyzed. DNA was extracted from spores collected from individual fruiting bodies representing six geographically dis- tinct populations in Oregon and Washington. Spore samples collected contained low levels of bacteria, yeast and a filamentous fungal species. Using taxon- specific PCR primers, it was possible to discriminate among rDNA from bacteria, yeast, a filamentous as- sociate and B. nobilissimus. Nuclear rDNA internal transcribed spacer (ITS) region sequences of B. no- bilissimus were compared among individuals repre- senting six populations and were found to have less than 2% variation. These sequences also were used to design dual and nested PCR primers for B. nobi- lissimus-specific amplification. Mitochondrial small- subunit rDNA sequences were used in a phylogenetic analysis that placed B. nobilissimus in the hymeno- chaetoid clade, where it was associated with Oxyporus and Schizopora.
H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation

Enhancers play a central role in cell-type-specific gene expression and are marked by H3K4me1/2. Active enhancers are further marked by H3K27ac. However, the methyltransferases responsible for H3K4me1/2 on enhancers remain elusive. Furthermore, how these enzymes function on enhancers to regulate cell-type-specific gene expression is unclear. In this study, we identify MLL4 (KMT2D) as a major mammalian H3K4 mono- and di-methyltransferase with partial functional redundancy with MLL3 (KMT2C). Using adipogenesis and myogenesis as model systems, we show that MLL4 exhibits cell-type- and differentiation-stage-specific genomic binding and is predominantly localized on enhancers. MLL4 co-localizes with lineage-determining transcription factors (TFs) on active enhancers during differentiation. Deletion of Mll4 markedly decreases H3K4me1/2, H3K27ac, Mediator and Polymerase II levels on enhancers and leads to severe defects in cell-type-specific gene expression and cell differentiation. Together, these findings identify MLL4 as a major mammalian H3K4 mono- and di-methyltransferase essential for enhancer activation during cell differentiation. DOI: http://dx.doi.org/10.7554/eLife.01503.001.
Autonomic function, as self-reported on the SCOPA-autonomic questionnaire, is normal in essential tremor but not in Parkinson’s disease

Abstract Objective To compare autonomic function of subjects with Parkinson's disease (PD) and essential tremor (ET) relative to controls. Background It has been reported that patients with PD have autonomic dysfunction while no literature exists regarding autonomic function in ET. Methods Subjects with PD, ET, and controls had autonomic function measured using the SCOPA-Autonomic questionnaire, with the total and domain scores transformed to a scale of 0–100 points. Results 62 subjects with PD, 84 with ET, and 291 controls were included. Women were more prevalent in control (69%) compared to PD (44%) and ET (44%) groups, and mean age was significantly younger in PD (73 yrs) and older in ET (83) compared to controls (81). The mean SCOPA-Aut Total score in PD was significantly higher than controls, with no difference in ET. No autonomic dysfunction was found in any domain in ET but in PD there were significant abnormalities in gastrointestinal, cardiovascular, urinary, and thermoregulatory domains. Individual question data revealed a significantly higher percentage of subjects with dysfunction on 11/23 questions in the PD group but only 1 question (sialorrhea) in the ET group compared with controls. Conclusion Autonomic scores, particularly gastrointestinal, cardiovascular, urinary, and thermoregulatory were increased in patients with PD, as assessed by SCOPA-Aut. Patients with ET did not exhibit autonomic dysfunction, with the exception of sialorrhea.
Successful implementation of an alcohol-withdrawal pathway in a general hospital.

Background Although alcohol use and abuse are common among general-hospital inpatients, many patients are inadequately assessed and treated for alcohol withdrawal. Objective The purpose of this study was to determine whether the implementation of a clinical pathway for the treatment of alcohol withdrawal in medical inpatients would result in improvements in clinical practice and patient outcomes. Method Authors retrospectively reviewed 80 patient records (including 40 of those treated before the implementation of a pathway and 40 of those treated after pathway implementation). Results Assessment procedures and ordering patterns of physicians (medical house staff and staff physicians) shifted in a fashion consistent with the new treatment guidelines. Patient outcomes (e.g., length of stay and the incidence of delirium) improved for those patients who received benzodiazepines within the range of the pathway guidelines. Conclusions Timely assessment and staff education can shift prescription patterns, increase patient monitoring, and reduce costs associated with alcohol withdrawal.
Practice-based Assessment of Tobacco Usage in Southwestern Primary Care Patients: A Research Involving Outpatient Settings Network (RIOS Net) Study

Purpose: Primary care clinicians rely, perhaps erroneously, on general population-based data about risk factors to help form their strategies for allocating time in the brief primary care encounter. We conducted a case study using rates of tobacco usage among people presenting for primary care to explore comparability to general population-based rates. Methods: Clinicians in RIOS Net, a practice-based research network, gathered data on tobacco use for all patients presenting during a 2-week period. We compared those data to population-based data by gender and ethnicity. Results: Ninety-one primary care clinicians reported data on 2442 patients. Primary care smoking rates differed in important ways from general population-based rates. Hispanic women smoked at more than twice the national population-based rate (25% vs 12%). Youth smoked at higher rates as well, particularly young Native American men. Conclusions: Patients seen in primary care differ in important ways in rates and patterns of tobacco usage when compared with rates reported in population-based surveys. These differences could have important implications for preventive care within the context of multiple competing demands in the primary care encounter.
Why Should We Lower Our Defenses About Defense Mechanisms

Personality and social psychologists already use ideas that are closely related to defense mechanisms, but few of our paradigms include extensive theoretical or empirical treatment of such mechanisms. Yet defense mechanisms focus on negative affect and protection of the self, and many of the controversies, issues, and impasses contemporary researchers confront also concern negative affect and self-protection. This article discusses whether we might find systematic consideration of defense mechanisms and defensive processing to be broadly useful across several related areas of personality and social psychology in which the relationships between self and affect are implicated. Areas considered include positive illusions and adaptation, the interpretation of reports of negative affect, and related concepts from the coping, self-regulation, affect regulation, and goals literature. Thinking about defense mechanisms would seem to have both specific value for sharpening our understanding of different possible interpretations of our data, and broad heuristic value for thinking about personality integration and social behavior.
Radioactive and radiogenic isotope research

The number of laboratories and workers in the field of radioactive isotope research has grown rapidly over the past four years. With this growth has come a large increase in the volume of literature on the subject. Consequently the bibliography, given below is meant to include the more significant or more complete investigations. The references are restricted to papers published by U.S. laboratories from approximately January 1967 through October 1970.
Mild opioid deprivation increases the degree that opioid-dependent outpatients discount delayed heroin and money.

Abstract Rationale. A growing literature suggests that excessive temporal discounting of delayed rewards may be a contributing factor in the etiology of substance abuse problems. Little is known, however, about how drug deprivation may affect temporal discounting of delayed rewards by drug-dependent individuals. Objective. To examine the extent to which opioid deprivation affects how opioid-dependent individuals discount small, medium and large quantities of delayed heroin and money. Methods. Thirteen opioid-dependent individuals maintained on buprenorphine completed a hypothetical choice task in which they choose between a constant delayed reward amount and an immediate reward amount that was adjusted until they expressed indifference between both outcomes. The task was completed for three values of heroin and money rewards during eight sessions under conditions of opioid deprivation (four sessions) and satiation (four sessions). Results. Across conditions, hyperbolic functions provided a good fit for the discounting data. Degree of discounting was significantly higher when subjects were opioid deprived. Consistent with previous findings, degree of discounting was higher for heroin than money and inversely related to the magnitude of the reward. Conclusion. Opioid deprivation increased the degree to which dependent individuals discounted delayed heroin and money. Understanding the conditions that affect how drug-dependent individuals discount delayed rewards might help us understand the myopic choices made by such individuals and help improve treatment outcomes.
Stochastic modelling of transverse wave instability in a liquid-propellant rocket engine

The combustion stability of a liquid-propellant rocket engine experiencing a random, finite perturbation from steady-state conditions is examined. The probability is estimated for a nonlinear resonant limit-cycle oscillation to be triggered by a random disturbance. Transverse pressure waves are considered by using a previously published two-dimensional nonlinear pressure wave equation coupled with Euler equations governing the velocity components. The cylindrical combustion chamber is a complex system containing multiple co-axial methane‐oxygen injectors; each co-axial jet is analysed for mixing and burning on its own local grid scheme, with the energy release rate coupled to the wave oscillation on the more global grid. Two types of stochastic forcing for the random disturbance are explored: a travelling Gaussian pressure pulse and an oscillating pressure dipole source. The random variables describing the pulse are magnitude, location, duration and orientation of the disturbances. The polynomial chaos expansion (PCE) method is used to determine the long-time behaviour and infer the asymptote of the solution to the governing partial differential equations. Depending on the random disturbance, the asymptote could be the steady-state solution or a limit-cycle oscillation, e.g. a first tangential travelling wave mode. The asymptotic outcome is cast as a stochastic variable which is determined as a function of input random variables. The accuracy of the PCE application is compared with a Monte Carlo calculation and is shown to be significantly less costly for similar accuracy.
Recurrent exercises for introductory human computer interaction courses

Introductory human computer interaction (HCI) courses are fundamental in the computer science curriculum as there is not only a need for teaching students to solve problems, but also to map their solutions to end-users. Currently, there are several high level approaches to teaching such courses. Many of these courses can gain benefit through reformatting or augmenting current course structures with recurrent exercises. This paper suggests two types of recurrent exercises and contains data on one semester of a course using this methodology of teaching.
Random matrices: Universal properties of eigenvectors

The four moment theorem asserts, roughly speaking, that the joint distribution of a small number of eigenvalues of a Wigner random matrix (when measured at the scale of the mean eigenvalue spacing) depends only on the first four moments of the entries of the matrix. In this paper, we extend the four moment theorem to also cover the coefficients of the eigenvectors of a Wigner random matrix. A similar result (with different hypotheses) has been proved recently by Knowles and Yin, using a different method. As an application, we prove some central limit theorems for these eigenvectors. In another application, we prove a universality result for the resolvent, up to the real axis. This implies universality of the inverse matrix.
A VLSI system architecture for real-time intelligent decision making

In this paper, we describe a VLSI system architecture for real-time intelligent decision making. The architecture integrates the adaptability of a backpropagation based neural network and the decision making ability of a rule based fuzzy expert system on a chip. The intelligent decision making system consists of a back-propagation based neural network for adaptive learning and a rule-based fuzzy expert system for decision making. Both the neural network and the expert system are realized as linear systolic arrays. Thus, the entire system can be implemented in VLSI with a few basic cells. The architecture exploits the principles of pipelining and parallelism to the maximum possible extent in order to achieve high speed and throughput. The proposed hardware can yield a real-time decision every 5ns based on a 200 MHz clock. Currently, a prototype CMOS VLSI chip implementing the proposed architecture is being built and verified.
Differential and single ended elliptical antennas for 3.1-10.6 GHz ultra wideband communication

The paper introduces differential and single ended antenna designs for ultra wideband 3.1-10.6 GHz communication. The primary design is an ultra thin, low profile differential antenna with an incorporated ground plane for use with a UWB IC receiver. The differential capability eases the design complexity of the RF front-end, and the incorporation of a ground plane enables conformability with small electronic UWB devices. Two single ended designs are also presented for use with a UWB IC transmitter. Both designs result in excellent bandwidth, efficiency, and nearly omnidirectional radiation patterns. Viability of these antennas is tested with a UWB pulse transmitter. Time domain responses are compared to that of a commercial 1-18 GHz double ridged waveguide horn.
Effect of Particle Size Distribution on the Melting of Soda‐Lime‐Silica Glass

Research has been conducted on the effects of the particle size distribution of a glass batch on the reaction path leading up to the first glassy phase. The research has involved DTA/TGA, X-ray diffraction, and SEM/EDS studies of particle size effects on the reaction path. The results of the studies were compiled to give a description of the reaction path for three soda-lime-silica batches, each with a different silica particle size distribution. The purpose of this work was to determine the effect of the silica particle size distribution on the reaction path and to determine the feasibility of building a predictive computer model consistent with these results.