cssi/SciSciGPT-SciSciNet huggingface dataset:
Assessment of Food Safety Risk: A Case Study in Marion County, Indiana

Food service operations vary in their exposure to food safety risks. The Marion County, Indiana Health Department employs a system of risk assessment in determining the frequency of annual restaurant inspections to obtain an optimal balance between public safety and a maximization of departmental resources. Risk assessment classification criteria currently stem from the Food and Drug Administration Food Code without consideration of restaurant type. The utility of the current system of risk assessment was examined to see if restaurant type should be considered in the process. The analysis revealed significant differences in the number of health inspection violations among restaurant types, supporting the study's proposal. Of note, full-service chain restaurants had more violations than full-service independent operations and cafeterias had a greater number of violations than all other restaurant types combined.
Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes

Biliary atresia is a severe cholangiopathy of early infancy that destroys extrahepatic bile ducts and disrupts bile flow. With a poorly defined disease pathogenesis, treatment consists of the surgical removal of duct remnants followed by hepatoportoenterostomy. Although this approach can improve the short-term outcome, the liver disease progresses to end-stage cirrhosis in most children. Further improvement in outcome will require a greater understanding of the mechanisms of biliary injury and fibrosis. Here, we review progress in the field, which has been fuelled by collaborative studies in larger patient cohorts and the development of cell culture and animal model systems to directly test hypotheses. Advances include the identification of phenotypic subgroups and stages of disease based on clinical, pathological and molecular features. Stronger evidence exists for viruses, toxins and gene sequence variations in the aetiology of biliary atresia, triggering a proinflammatory response that injures the duct epithelium and produces a rapidly progressive cholangiopathy. The immune response also activates the expression of type 2 cytokines that promote epithelial cell proliferation and extracellular matrix production by nonparenchymal cells. These advances provide insight into phenotype variability and might be relevant to the design of personalized trials to block progression of liver disease.
Plane xanthoma developing in photosensitive eczema. A report of three cases with a discussion of a possible mechanism for lipid accumulation in plane xanthomas.

Summary Three cases of plane xanthoma arising in chronic eczema are described. Two patients had long standing photosensitive eczema and the other actinic reticuloid. It is suggested that foam cells develop from dermal macrophages in chronically inflamed skin. Lipid accumulation may be due to a failure of a specific receptor-mediated control of cholesterol uptake into macrophages and be independent of circulating plasma lipid or lipoprotein levels.
Is it safe to treat hyperthyroid patients with I-131 without fear of thyroid storm?

Objectives Thyroid storm is extremely rare. However, hyperthyroid patients with severe thyrotoxi-cosis are frequently not treated immediately with I-131 for fear of thyroid storm but are placed on thiouracil drugs for varying periods of time. We demonstrate herein that it is safe to treat these patients with I-131, without pretreatment with thiouracil drugs, provided they do not have complicating intercurrent disease. Our definition of severe hyperthyroidism includes marked signs and symptoms of thyrotoxicosis, suppressed TSH, markedly elevated free T4 and/or free T3 and elevated radioactive iodine uptake (RAIU) (>30%) at 4 or 24 hours. Our diagnostic criteria for thyroid storm include two or more findings of fever (>38°C, 100°F), severe tachycardia, high pulse pressure, agitation with tremors, flushing, sweating, heart failure, nausea, vomiting, diarrhea, jaundice associated with high free T4 and/or free T3.
An object oriented user interface for analysis of biological data

Abstract In a previous paper we described a self-documented file and a collection of general purpose programs or tools that facilitates the management and analysis of biological data. The tools can be specified in a pipeline to accomplish a specific analysis task. However, we found that it was difficult for investigators to learn the UNIX command language for specifying pipelines, specify selection tasks through a command language, and visualize the data as they were transformed and rearranged. To alleviate these problems we developed an object-oriented user interface for the pipeline programs. The system consists of four major programs for visualization: Vedit, Vgraf, Vscan, and Vspread. Vedit is a simple text editor, Vgraf is a flexible graphics program, Vscan facilitates scanning graphically through large files, and Vspread provides spreadsheet-like capabilities. To demonstrate how the visualization programs are used together to accomplish the needed analysis we describe two case studies and then discuss how well the system accomplished the goals of visualization, short learning curve, and user adaptability.
Post-renal transplant plasma cell dyscrasia presenting as retroperitoneal plasmacytoma: A case report and literature review

Post-transplant lymphoproliferative disease (PTLD) is a rare but potentially fatal complication of organ transplanta-tion. Most cases of PTLD represent Epstein Barr virus (EBV)-related B-cell disease in a setting of pharmacological immunosuppression. Post-transplant plasma cell dyscrasia is very rare, and post-transplant plasma cell dyscrasia with extramedullary plasmacytoma is extremely rare. We report here a case of the latter, which to our knowledge is the fourth such reported case in the English literature. A 22-year-old man developed post-transplant plasma cell dyscrasia 20 years after a renal transplant while on immunosuppression. His presentation included retroperitoneal plasmacytoma, which is very rare and is probably the ﬁrst case in a renal transplant patient. The patient is in complete remission 1 year after receiving ﬁve cycles of bortezomib and dexamethasone.
Effects of mammalian gonadotropins on the ovaries and oviducts of the lizard, Lygosoma laterale.

Female Lygosoma laterale with quiescent ovaries and oviducts were treated with 1.0 I.U. of either FSH, LH, FSH plus LH, PMS or HCG daily for 15 days to elucidate their effects on the reproductive tract. FSH increased ovary and oviduct weight and follicle diameter, but its effects were antagonized by LH. Neither HCG nor LH had an effect on ovary weight or follicle diameter, and both only slightly increased oviduct weight. The effects of PMS were similar to those of the FSH-LH combination, both causing a moderate increase in ovary and oviduct weight and follicle diameter. These results are discussed in relation to the effects of exogenous mammalian gonadotropins in other reptiles and in mammals.
Motor Cortex Broadly Engages Excitatory and Inhibitory Neurons in Somatosensory Barrel Cortex

Anatomical studies have shown that primary somatosensory (S1) and primary motor (M1) cortices are reciprocally connected. The M1 to S1 projection is thought to represent a modulatory signal that conveys motor-related information to S1. Here, we investigated M1 synaptic inputs to S1 by injecting an AAV virus containing channelrhodopsin-2 and a fluorescent tag into M1. Consistent with previous results, we found labeling of M1 axons within S1 that was most robust in the deep layers and in L1. Labeling was sparse in L4 and was concentrated in the interbarrel septa, largely avoiding barrel centers. In S1, we recorded in vitro from regular-spiking excitatory neurons and fast-spiking and somatostatin-expressing inhibitory interneurons. All 3 cell types had a high probability of receiving direct excitatory M1 input. Both excitatory and inhibitory cells within L4 were the least likely to receive such input from M1. Disynaptic inhibition was observed frequently, indicating that M1 recruits substantial inhibition within S1. Additionally, a subpopulation of L6 regular-spiking excitatory neurons received exceptionally strong M1 input. Overall, our results suggest that activation of M1 evokes within S1 a bombardment of excitatory and inhibitory synaptic activity that could contribute in a layer-specific manner to state-dependent changes in S1.
Electron transfer in cytochrome c depends upon the structure of the intervening medium

Abstract Background Long-distance electron-transfer (ET) reactions through proteins are involved in a great many biochemical processes; however, the way in which the protein structure influences the rates of these reactions is not well understood. We have therefore measured the rates of intramolecular ET from the ferroheme to a bis(2,2′ -bipyridine)imidazoleruthenium(III) acceptor at histidine 39 or 54 in derivatives of yeast iso-1-cyto- chrome c , and studied the effect of an asparagine to isoleucine mutation at position 52, a residue situated between the heme and the electron acceptor. Results The Fe 2+ → Ru 3+ rate constants demonstrate that residue 52 affects ET from the heme to His54 (Ile52 > Asn52), but not to His39 (Ile52 = Asn52). The enhanced Fe 2+ –Ru 3+ (His54) electronic coupling for the N52I/K54H protein is in good agreement with σ -tunneling calculations, which predict the length of the ET pathways between the heme and His54. Conclusions The structure of the intervening medium between the heme and electron acceptors at the protein surface influences the donor–acceptor couplings in cytochrome c .
Stress proteins and tolerance to focal cerebral ischemia

Stress proteins are induced after a variety of neuronal injuries. The inducible 72-kDa heat shock protein (hsp70) is a stress protein that protects neurons from glutamate toxicity in vitro. Hsp70 h...
Quantum entanglement of formation between qudits

We develop a fast algorithm to calculate the entanglement of formation of a mixed state, which is deflned as the minimum average entanglement of the pure states that form the mixed state. The algorithm combines conjugate gradient and steepest descent algorithms and outperforms both. Using this new algorithm, we obtain the statistics of the entanglement of formation on ensembles of random density matrices of higher dimensions than possible before. The correlation between the entanglement of formation and other quantities that are easier to compute, such as participation ratio and negativity are presented. Our results suggest a higher percentage of zero-entanglement states among zero-negativity states than previously reported.
Separable states and separability criteria

A quantum state which can be written as a convex sum of product states is a separable state; such a convex sum allows for a local description. There are many different local descriptions for a given separable state, and some new results about the minimal number of product states in the convex sum will be given in this paper. Any quantum state is either entangled or separable. However it is very difficult to tell whether a given state is separable or entangled. This difficulty has not been solved yet although a lot of separability criteria have already been proposed. The various separability criteria will also be discussed.
The role of glutamic acid-69 in the activation of Citrobacter freundii tyrosine phenol-lyase by monovalent cations.

Tyrosine phenol-lyase (TPL) from Citrobacter freundii is activated about 30-fold by monovalent cations, the most effective being K(+), NH(4)(+), and Rb(+). Previous X-ray crystal structure analysis has demonstrated that the monovalent cation binding site is located at the interface between subunits, with ligands contributed by the carbonyl oxygens of Gly52 and Asn262 from one chain and monodentate ligation by one of the epsilon-oxygens of Glu69 from another chain [Antson, A. A., Demidkina, T. V., Gollnick, P., Dauter, Z., Von Tersch, R. L., Long, J., Berezhnoy, S. N., Phillips, R. S., Harutyunyan, E. H., and Wilson, K. S. (1993) Biochemistry 32, 4195]. We have studied the effect of mutation of Glu69 to glutamine (E69Q) and aspartate (E69D) to determine the role of Glu69 in the activation of TPL. E69Q TPL is activated by K(+), NH(4)(+), and Rb(+), with K(D) values similar to wild-type TPL, indicating that the negative charge on Glu69 is not necessary for cation binding and activation. In contrast, E69D TPL exhibits very low basal activity and only weak activation by monovalent cations, even though monovalent cations are capable of binding, indicating that the geometry of the monovalent cation binding site is critical for activation. Rapid-scanning stopped-flow kinetic studies of wild-type TPL show that the activating effect of the cation is seen in an acceleration of rates of quinonoid intermediate formation (30-50-fold) and of phenol elimination. Similar rapid-scanning stopped-flow results were obtained with E69Q TPL; however, E69D TPL shows only a 4-fold increase in the rate of quinonoid intermediate formation with K(+). Preincubation of TPL with monovalent cations is necessary to observe the rate acceleration in stopped flow kinetic experiments, suggesting that the activation of TPL by monovalent cations is a slow process. In agreement with this conclusion, a slow increase (k 100 mM) of all monovalent cations result in inhibition of wild-type TPL. This inhibition is probably due to cation binding to the ES complex to form a complex that releases pyruvate slowly.
Asymmetric Mutualism in Two- and Three-Dimensional Range Expansions

Genetic drift at the frontiers of two-dimensional range expansions of microorganisms can frustrate local cooperation between different genetic variants, demixing the population into distinct sectors. In a biological context, mutualistic or antagonistic interactions will typically be asymmetric between variants. By taking into account both the asymmetry and the interaction strength, we show that the much weaker demixing in three dimensions allows for a mutualistic phase over a much wider range of asymmetric cooperative benefits, with mutualism prevailing for any positive, symmetric benefit. We also demonstrate that expansions with undulating fronts roughen dramatically at the boundaries of the mutualistic phase, with severe consequences for the population genetics along the transition lines.
Development of a robust algorithm for detection of mine targets in image data from electro-optic and acoustic sensors

Current minefield detection research indicates that operationally no single sensor technology will likely be capable of detecting mines/minefields in a real-time manner and at a performance level suitable for a forward maneuver unit. Minefield detection involves a particularly wide range of operating scenarios and environmental conditions, which requires deployment of complementary sensor suites. We have focused, therefore, on the development of a computationally efficient and robust detection algorithm that exploits robust image processing techniques centered on meaningful target feature sets applicable to a variety of imaging sensors. This paper presents the detection technique, emphasizing its robust architecture, and provides performance results for image data generated by complementary sensors. The paper also briefly discusses the application of this detector as a component of fusion architectures for processing returns form diverse imaging sensors, including multi-channel image data from disparate sensors.
Simulation of photophysical processes of indoles in solution

Computational studies of photophysical processes in solution require accurate representations of the potential energy function. The interactions in a polar solute-solvent system are primarily electrostatic in nature, and they are, in molecular simulations, typically mediated by partial atomic charges on the solute and the solvent atoms. We have developed procedures to create partial atomic charges for any electronic state in a solute molecule from a least squares fit to the molecular electrostatic potential. The quantum mechanical electrostatic potential for the electronically excited 1La state of 3-methylindole derived from a semiempirical INDO/S configuration interaction wavefunction is presented. Partial atomic charges for the 1La state are derived from the quantum mechanical potential, and the classical and quantum mechanical electrostatic potentials are compared. Molecular dynamics simulations have been carried out on the ground (So) and two lowest excited singlet states (1Lb, 1La) of 3-methylindole in water using potential derived partial atomic charges. Solvent-induced inversion of the gas phase excited state ordering (1Lb below 1La) is computed for the excited states. A method for introducing polarization by the solvent into the solute electronic wavefunctions, and hence into the solute partial atomic charges, is introduced. A significant increase in solute dipole moment is computed for the 1La state, leading to dramatic increases in solute-solvent interaction energies and additional preferential stabilization of the 1La state over the 1Lb state.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Relationships among forage chemistry, rumination and retention time with intake and digestibility of hay by goats

Eight species of forage, a cool-season perennial (tall fescue ( Festuca arundinacea)) and annual grass (winter wheat (Triticum aestivum)), four warm-season perennial grasses (caucasian (Bothriochloa caucasica), plains (B. ischaemum), old world bluestem, bermudagrass (Cynodon dactylon), and eastern gamagrass (Tripsacum dactyloides)), a warm season annual (crabgrass (Digitaria sanguinalis)) and a perennial legume (alfalfa (Medicago sativa)), were each cut at two or three maturities to provide a wide array of quality difference (n = 20). Twenty wether goats (Capra hicus) were fed the hays in four different trials using an incomplete block design so that four different goats received each hay. Alfalfa produced the highest (25 g kg −1 body weight (BW)) and wheat the lowest (13.6 g kg −1 BW) organic matter (OM) intake. A number of the grasses provided less than 20 g kg −1 BW OM intake. Digestion of OM was also highest for alfalfa (>715 g kg −1 ) and lowest for bermudagrass (508 g kg −1 ). All measures and expressions of intake and digestibility were better related to ruminating and retention time than to forage chemistry, with the exception of crude protein digestibility. The best equations for predicting intake included a combination of mean retention time and forage acid detergent fiber (ADF) content (reciprocal and quadratic); that for digestibility included permanganate lignin (reciprocal), and the quadratic for ruminating and retention time. Equations for predicting the constraint on intake and digestible organic matter intake produced higher r 2 than those for either intake or digestibility. Digestibility of ADF and neutral detergent fiber (NDF) were poorly predicted with either chemistry ( r 2 ≤ 0.20), or ruminating time (r 2 = 0.43), but combinations of permanganate lignin content of NDF, retention and ruminating time produced reasonable equations. Published by Elsevier Science B.V.
Review of the ARPA speech understanding project

In September of 1976, four speech understanding systems were demonstrated, signifying the end of a five‐year program of research and development sponsored by the Advanced Research Projects Agency (ARPA). The best performance was displayed by the Harpy system developed at Carnegie–Mellon University. Harpy satisfied a set of design goals that were specified at the beginning of the program, including the gal of understanding over 90% of a set of naturally spoken sentences composed from a 1000‐word lexicon. After defining the nature of the speech understanding problem, the four systems are described and critically evaluated. Based on this review, a structure for a next‐generation speech understanding system is proposed and parts of it are considered as a possible model of the early stages of speech perception. The perceptual model addresses the issue of lexical access and includes a decoding network composed of expected spectral sequences for all word strings of English.
Stereospecific effects of ascorbic acid and analogues on D1 and D2 agonist binding.

Ascorbic acid inhibited the specific binding of both the D1 agonist, [3H] SKF 38393, and the D2 agonist, [3H] N-0437 at physiologically relevant concentrations. This inhibition was both stereospecific and receptor selective. Using ligand concentrations approximating their KD's, the IC50's for ascorbate and two structural analogues, isoascorbate and D-glucoascorbate, were determined. The rank order of IC50's at both D1 and D2 were D-glucoascorbate > isoascorbate > ascorbate. However, the IC50 for each compound was greater at D1 than D2. Evaluation of the relationship between the IC50 for ascorbate and the ligand concentration using both the D1 and the D2 ligand yielded data inconsistent with competitive inhibition models. Preliminary experiments were conducted to evaluate the site and type of inhibition with results consistent with an allostearic effect at the level of the receptor.
Adaptive Value of Thermally Inefficient Male Incubation in Barn Swallows (Hirundo Rustica)

Abstract Most male passerines do not develop brood patches. Despite this, some, including Barn Swallows (Hirundo rustica), apparently incubate. Male incubation should stabilize and enhance average egg temperature over the course of embryonic development and allow females more time to forage before eggs cool to suboptimal temperatures. We recorded egg temperatures and monitored incubation behavior in three Barn Swallow colonies. Female incubation and male nest attendance produced higher average egg temperatures than periods of unattended egg cooling. Females reheated eggs at significantly higher rates than males. Eggs normally cooled during male on-bouts and when unattended, though male nest attendance slowed cooling significantly. Incubation cycles with male nest attendance had less thermal variation than those that lacked male assistance. Embryonic development time was not correlated with male nest attendance. Although male nest attendance is unlikely to enhance embryonic development, it appears to play ...
Mutual Interests: The Case for Increasing Dialogue between Political Science and Neuroscience

Can neuroscientific techniques shed light on important questions in political science? The author argues for increased dialogue across disciplines as wide ranging as evolutionary psychology and bio...
Synthesis of p-nitrophenyl 2-O-α-D-mannopyranosyl-α-D-mannopyranoside and p-nitrophenyl 6-O-α-D-mannopyranosyl-α-D-mannopyranoside

Abstract Crystalline 2- O -α- D -mannopyranosyl-β- D -mannopyranose octaacetate was synthesized by condensation of tetra- O -acetyl-α- D -mannopyranosyl bromide ( 3 ) with 1,3,4,6-tetra- O -acetyl-β- D -mannopyranose. 6- O -α- D -mannopyranosyl-α- D -mannopyranose octaacetate was prepared by condensation of 3 with 1,2,3,4-tetra- O -acetyl-6- O -trityl-α- D -mannopyranose. Fusion of each mannobiosyl octaacetate with p -nitrophenol was followed by deacetylation, to give the corresponding p -nitrophenyl (1→2)- and (1→6)-α- D -mannobioside.
In vivo biosynthesis and turnover of 35S-labeled glomerular basement membrane

Abstract Renal glomerular basement membrane was labeled in vivo by the injection of tracer amounts of radioactive sulfate into normal adult rats. The biosynthesis and turnover of [35S]glycosaminoglycans in purified basement membrane was determined from the specific activity of 35S in pronase digests of basement membranes isolated 1–7 days after injection. Peak radioactive labeling occurred 24 h after injection following which the specific activity of basement membrane sulfate, expressed as cpm/μg uronic acid, progressively declined over the ensuing period of study. The biologic half-life of radioactive sulfate in basement membrane was estimated at about 7 days, which is within the range previously reported for [35S]glycosaminoglycans in whole renal cortex. The findings indicate that 35S-labeled components of glomerular basement membrane have a relatively rapid turnover.
JNK1 Deficiency Does Not Enhance Muscle Glucose Metabolism in Lean Mice

Abstract Mice deficient in c-jun-NH2-terminal kinase 1 (JNK1) exhibit decreased fasting blood glucose and insulin levels, and protection against obesity-induced insulin resistance, suggesting increased glucose disposal into skeletal muscle. Thus, we assessed whether JNK1 deficiency enhances muscle glucose metabolism. Ex vivo insulin or contraction-induced muscle [3H]2-deoxyglucose uptake was not altered in JNK1 knockout mice, demonstrating that JNK1 does not regulate blood glucose levels via direct alterations in muscle. In vivo muscle [3H]2-deoxyglucose uptake in response to a glucose injection was also not enhanced by JNK1 deficiency, demonstrating that a circulating factor was not required to observe altered muscle glucose uptake in the knockout mice. JNK1 deficiency did not affect muscle glycogen levels or the protein expression of key molecules involved in glucose metabolism. This study is the first to directly demonstrate that enhanced skeletal muscle glucose metabolism does not underlie the beneficial effects of JNK1 deficiency in lean mice.
Surface processes in low pressure plasmas

Abstract In many high technology industries low pressure plasmas have become indispensable for advanced materials processing: the microelectronics industry employs plasma-based etching to produce sub-micron device features in thin films with precisely controlled dimensions and uses plasma-enhanced chemical vapor deposition methods to synthesize insulators, conductors, diamond thin films and high-temperature superconductors. Plasmas are also used to harden the surfaces of cutting tools and modify the surfaces of polymers and other materials. Even the simplest plasma processing reactor is scientifically extremely complex, and the characterization and understanding of plasma-surface interactions is one of the least understood parts of the overall problem. We review scientific issues, the experimental tools to study these, and survey results of surface process characterization of plasma etching processes of microelectronic materials. We will show that the process etch quality in a low pressure plasma is often directly related to the thickness and composition of the reaction layers that form on the various surface that are exposed to the plasma. The characteristics of the surface reaction layers are controlled by the chemical composition of the discharge, the ion bombardment energy and ion fluxes at the substrate.
The ability of the skin to absorb heat; The effect of repeated exposure and age

Background When heat is applied to the skin, it is dissipated due to conductive heat flow in the tissue and the blood. While heat flow has been studied after applying a single heat exposure, the physiology of repeated exposures to local heat has not been well investigated.
Protein adsorption drastically reduces surface-enhanced Raman signal of dye molecules

There is an increasing interest in developing surface enhancement Raman spectroscopy methods for intracellular biomolecule and for in vitro protein detection that involve dye or protein–dye conjugates. In this work, we have demonstrated that protein adsorption on silver nanoparticle (AgNP) can significantly attenuate the surface-enhanced Raman spectroscopy (SERS) signal of dye molecules in both protein/dye mixtures and protein/dye conjugates. SERS spectra of 12 protein/dye mixtures were acquired using 4 proteins [bovine serum albumin (BSA), lysozyme, trypsin, and concanavalin A] and three dyes [Rhodamine 6G, adenine, and fluorescein isothiocyanate (FITC)]. Besides the protein/dye mixtures, spectra were also obtained for the free dyes and four FITC-conjugated proteins. While no SERS signal was observed in protein/FITC mixtures or conjugates, a significantly reduced SERS intensity (up to 3 orders of magnitude) was observed for both R6G and adenine in their respective protein mixtures. Quantitative estimation of the number of dye molecules absorbed onto AgNP implied that the degree of R6G SERS signal reduction in the R6G/BSA sample is 2 to 3 orders of magnitude higher than what could be accounted for by the difference in the amount of the absorbed dyes. This finding has significant implications for both intracellular SERS analyses and in vitro protein detection using SERS tagging strategies that rely on Raman dyes as reporter molecules. Copyright © 2009 John Wiley & Sons, Ltd.
Preschoolers' Social Information Processing and Early School Success: The Challenging Situations Task.

As part of a larger longitudinal project on the assessment of preschoolers' social-emotional development, children's social information processing (SIP) responses to unambiguous hypothetical situations of peer provocation were assessed for 298 four-year-olds from Head Start and private childcare settings. Measurement focused on emotions children would feel during these situations, and their behaviour response decisions. Participants most often chose sad and angry emotions, and socially competent and passive behaviours. Relations were found between sad emotion and socially competent behaviour choices, as well as between angry emotion and aggressive behaviour choices. Sad emotion and socially competent behaviour responses contributed to variance in contemporaneous and later school adjustment and kindergarten academic readiness. There was evidence that the contributions of sad emotion responses were mediated by those of socially competent behaviour choices. Results bolstered calls to include emotion in SIP measures, supported predictive validity for this SIP measure in a large representative sample of preschoolers, and pointed to fruitful pathways for future research.
Distinct neuroblastoma-associated alterations of PHOX2B impair sympathetic neuronal differentiation in zebrafish models.

Heterozygous germline mutations and deletions in PHOX2B, a key regulator of autonomic neuron development, predispose to neuroblastoma, a tumor of the peripheral sympathetic nervous system. To gain insight into the oncogenic mechanisms engaged by these changes, we used zebrafish models to study the functional consequences of aberrant PHOX2B expression in the cells of the developing sympathetic nervous system. Allelic deficiency, modeled by phox2b morpholino knockdown, led to a decrease in the terminal differentiation markers th and dbh in sympathetic ganglion cells. The same effect was seen on overexpression of two distinct neuroblastoma-associated frameshift mutations, 676delG and K155X - but not the R100L missense mutation - in the presence of endogenous Phox2b, pointing to their dominant-negative effects. We demonstrate that Phox2b is capable of regulating itself as well as ascl1, and that phox2b deficiency uncouples this autoregulatory mechanism, leading to inhibition of sympathetic neuron differentiation. This effect on terminal differentiation is associated with an increased number of phox2b+, ascl1+, elavl3− cells that respond poorly to retinoic acid. These findings suggest that a reduced dosage of PHOX2B during development, through either a heterozygous deletion or dominant-negative mutation, imposes a block in the differentiation of sympathetic neuronal precursors, resulting in a cell population that is likely to be susceptible to secondary transforming events.
An evaluation of staining techniques for marking daily growth in scleractinian corals

article i nfo Article history: Keywords: Alizarin Calcein Calcification Coral Isotope Stain In situ skeletal markers have been widely used to quantify skeletal growth rates of scleractinian corals on sub-annual time-scales. Nevertheless, an evaluation of different techniques, both in terms of their efficacy and potential impacts on the growth process itself, has not been undertaken. Here the effects of exposure to four different dyes (alizarin, alizarin complexone, calcein, and oxytetracycline) and isotope spikes (Ba and Sr) on the growth rates of scleractinian corals are compared. Oxytetracycline increased coral growth. Alizarin, alizarin complexone, calcein, and Sr and Ba isotope spikes had no significant effect on coral growth, but polyp extension appeared reduced during exposure to alizarin and alizarin complexone. Calcein provided a more intense fluorescent mark than either alizarin or alizarin complexone. Isotope spikes were challenging to locate using isotope ratio analysis techniques. Thus, calcein appears best suited for marking short-term cal- cification increments in corals, while a combination of alizarin or alizarin complexone and calcein may be useful for dual labeling experiments as there is little overlap in their fluorescence spectra.
Isolation of Covalently Closed Circular DNA of High Molecular Weight From Bacteria

Abstract A simple method is described in detail for the efficient isolation of high molecular weight covalently closed circular DNA (ccc-DNA) from Agrobacterium . Although this method was developed for isolating ccc-DNA of molecular weights greater than 10 8 daltons in Agrobacterium , the technique also proves to be useful in isolating ccc-DNA of varying sizes from a variety of other bacteria. The technique involves the shearing and alkali denaturation of the chromosomal DNA, followed by the preferential removal of the single-stranded DNA by phenol extraction. The DNA which remains is largely ccc-DNA. The DNA is then concentrated, and the ccc-DNA is separated from the chromosomal DNA by centrifugation in a cesium chloride-ethidium bromide density gradient. By this technique, ccc-DNA of varying sizes has also been isolated from species of Escherichia, Rhizobium, Citrobacter , and Lactobacillus .
"Asplenic syndrome" in association with rudimentary spleen.

Abstract A case is reported which demonstrated the cardiac anomalies most frequently associated with congenital asplenia, in which an ectopic form of rudimentary splenic tissue was present, but the spleen as such was absent. This case, and the experience of others, strongly suggest that common factors control organogenesis of the spleen and of the cardiovascular system. Developmental anomalies of the spleen, taking the form of absence, a rudimentary state or polysplenia, have a strong tendency to be associated with cardiovascular malformations.
Some model calculations of Coulomb mixing

Abstract The nucleus 56Co offers a good case for testing various mechanisms of isospin mixing. The analog state is bound making the mixing calculation easier than for isobaric analog resonances. There is, however, a direct correspondence between the mechanisms in the bound case and in the continuum case. The analog states of this nucleus are at low excitation so there is hope of making detailed model calculations of all the states involved in the mixing. For these calculations we consider the J = 0+ T = 2 state of 56Co as a simple 2p-2h shell-model state. Four possibilities are offered for a nearby T = 1 0+ state. The external mixing mechanism of continuum calculations is a second-order perturbation in this case which gives matrix elements several keV in magnitude. The internal mixing caused by the off-diagonal matrix elements of the Coulomb force has been neglected in continuum calculations, but we find that in this case it can be comparatively large, of the same order of magnitude as the other mechanisms. There is sufficient disparity between the matrix elements calculated for the different models to distinguish among the models experimentally. For 56Co, experimental data can be interpreted to give a mixing of 33 keV with a nearby state. This is large enough to exclude two of the models.
Kallikrein Gene Delivery Attenuates Myocardial Infarction and Apoptosis After Myocardial Ischemia and Reperfusion

The tissue kallikrein-kinin system is present in the heart, and kinin has been shown to have cardioprotective effects. In this study, we investigated the potential role of tissue kallikrein in myocardial ischemia/reperfusion injury through adenovirus-mediated human kallikrein gene delivery. One week after gene delivery, the rats were subjected to a 30-minute coronary occlusion followed by a 2-hour reperfusion. Kallikrein gene delivery caused significant decreases in the ratio of infarct size to ischemic area at risk (from 69.6% to 44.5%, n=10 and 8, P<0.01) and in the incidence of ventricular fibrillation (from 64.3% to 16.7%, n=14 and 24, P<0.01) compared with the group injected with control adenovirus. Kallikrein gene delivery also attenuated programmed cell death in the ischemic area compared with the control area as assessed with the terminal deoxynucleotidyl transferase-mediated nick end labeling assay (n=6, P<0.01). Icatibant, a specific bradykinin B(2) receptor antagonist, abolished these kallikrein-mediated beneficial effects. The expression of human tissue kallikrein mRNA was identified in rat heart, kidney, lung, liver, and adrenal gland. After kallikrein gene delivery, cardiac kinin and cGMP levels were significantly elevated compared with the control (29.6+/-12.7 versus 6.1+/-2.1 pg/mg protein, n=7, P<0.01; 1.30+/-0.06 versus 0.86+/-0.09 pmol/mg protein, n=5, P<0.05). These results indicate that kallikrein gene delivery protects against myocardial infarction, ventricular arrhythmias, and apoptosis in ischemia/reperfusion injury via kinin-cGMP signal pathway. The successful application of this technology may have potential therapeutic value in the treatment of coronary artery diseases.
Figure Associated Text Summarization and Evaluation

Biomedical literature incorporates millions of figures, which are a rich and important knowledge resource for biomedical researchers. Scientists need access to the figures and the knowledge they represent in order to validate research findings and to generate new hypotheses. By themselves, these figures are nearly always incomprehensible to both humans and machines and their associated texts are therefore essential for full comprehension. The associated text of a figure, however, is scattered throughout its full-text article and contains redundant information content. In this paper, we report the continued development and evaluation of several figure summarization systems, the FigSum+ systems, that automatically identify associated texts, remove redundant information, and generate a text summary for every figure in an article. Using a set of 94 annotated figures selected from 19 different journals, we conducted an intrinsic evaluation of FigSum+. We evaluate the performance by precision, recall, F1, and ROUGE scores. The best FigSum+ system is based on an unsupervised method, achieving F1 score of 0.66 and ROUGE-1 score of 0.97. The annotated data is available at figshare.com (http://figshare.com/articles/Figure_Associated_Text_Summarization_and_Evaluation/858903).
Related Leucine-based Cytoplasmic Targeting Signals in Invariant Chain and Major Histocompatibility Complex Class II Molecules Control Endocytic Presentation of Distinct Determinants in a Single Protein

Leucine-based signals in the cytoplasmic tail of invariant chain (Ii) control targeting of newly synthesized major histocompatibility complex class II molecules to the endocytic pathway for acquisition of antigenic peptides. Some protein determinants, however, do not require Ii for effective class II presentation, although endocytic processing is still necessary. Here we demonstrate that a dileucine-based signal in the cytoplasmic tail of the class II β chain is critical for this Ii-independent presentation. Elimination or mutation of this signal reduces the rate of re-entry of mature surface class II molecules into the endocytic pathway. Antigen presentation controlled by this signal does not require newly synthesized class II molecules and appears to involve determinants requiring only limited proteolysis for exposure, whereas the opposite is true for Ii-dependent determinants. This demonstrates that related leucine-based trafficking signals in Ii and class II control the functional presentation of protein determinants with distinct processing requirements, suggesting that the peptide binding sites of newly synthesized versus mature class II molecules are made available for antigen binding in distinct endocytic compartments under the control of these homologous cytoplasmic signals. This permits capture of protein fragments produced optimally under distinct conditions of pH and proteolytic activity.
Gifts of Biology

I'm writing this article in January, just as I return to classes after the winter break. It was a wonderful respite, in part because I had time to do some uninterrupted reading, to lie on the couch and really get into a book, and then another, and another. Fortunately, I received several great books as Christmas gifts –– and I augmented this stack with a few gifts to myself. There was no real rhyme or reason to the selection, but as I look back over my reading spree, I notice that a couple of themes weave the books together, and I'd like to examine them here. I began the holidays with Sara Maitland's (2008) The Book of Silence, which describes her exploration over a number of years of silence and solitude. They go together. It's difficult to have true silence in the company of others, as Maitland discovered when she slowly moved toward a silent life. First, separation from her husband found her living alone, but that didn't seem to be enough for her, so she tried a number of experiments in deeper silence. These included a six-week retreat on the Isle of Skye. She had stocked up on food and other necessities so she wouldn't have to interact with anyone, though she does admit to having had a cell phone and a car radio for emergencies. She found this a deeply transforming experience, which just made her hunger for more silence. This led to three years in a small house in an isolated part of England, a silent retreat in the desert, and another in the primeval woods of Scotland. Maitland finally built her own retreat because she simply didn't want to give up the silence she had discovered. Actually, Maitland discovered more than one silence. She found that …
The Inhibition of Polo Kinase by Matrimony Maintains G2 Arrest in the Meiotic Cell Cycle

Many meiotic systems in female animals include a lengthy arrest in G2 that separates the end of pachytene from nuclear envelope breakdown (NEB). However, the mechanisms by which a meiotic cell can arrest for long periods of time (decades in human females) have remained a mystery. The Drosophila Matrimony (Mtrm) protein is expressed from the end of pachytene until the completion of meiosis I. Loss-of-function mtrm mutants result in precocious NEB. Coimmunoprecipitation experiments reveal that Mtrm physically interacts with Polo kinase (Polo) in vivo, and multidimensional protein identification technology mass spectrometry analysis reveals that Mtrm binds to Polo with an approximate stoichiometry of 1:1. Mutation of a Polo-Box Domain (PBD) binding site in Mtrm ablates the function of Mtrm and the physical interaction of Mtrm with Polo. The meiotic defects observed in mtrm/+ heterozygotes are fully suppressed by reducing the dose of polo+, demonstrating that Mtrm acts as an inhibitor of Polo. Mtrm acts as a negative regulator of Polo during the later stages of G2 arrest. Indeed, both the repression of Polo expression until stage 11 and the inactivation of newly synthesized Polo by Mtrm until stage 13 play critical roles in maintaining and properly terminating G2 arrest. Our data suggest a model in which the eventual activation of Cdc25 by an excess of Polo at stage 13 triggers NEB and entry into prometaphase.
CONSTRAINTS ON QUASAR LIFETIMES AND BEAMING FROM THE He II Lyα FOREST

We show that comparisons of He II Ly{alpha} forest lines of sight to nearby quasar populations can strongly constrain the lifetimes and emission geometry of quasars. By comparing the He II and H I Ly{alpha} forests along a particular line of sight, one can trace fluctuations in the hardness of the radiation field (which are driven by fluctuations in the He II ionization rate). Because this high-energy background is highly variable-thanks to the rarity of the bright quasars that dominate it and the relatively short attenuation lengths of these photons-it is straightforward to associate features in the radiation field with their source quasars. Here we quantify how finite lifetimes and beamed emission geometries affect these expectations. Finite lifetimes induce a time delay that displaces the observed radiation peak relative to the quasar. For beamed emission, geometry dictates that sources invisible to the observer can still create a peak in the radiation field. We show that both these models produce substantial populations of 'bare' peaks (without an associated quasar) for reasonable parameter values (lifetimes {approx}10{sup 6}-10{sup 8} yr and beaming angles {approx}< 90 deg.). A comparison to existing quasar surveys along two He II Ly{alpha} forest lines of sight rules outmore » isotropic emission and infinite lifetime at high confidence; they can be accommodated either by moderate beaming or lifetimes {approx}10{sup 7}-10{sup 8} yr. We also show that the distribution of radial displacements between peaks and their quasars can unambiguously distinguish these two models, although larger statistical samples are needed.« less
A gas-liquid chromatographic method for the quantitative determination of methadone in human plasma and urine.

Abstract A method employing solvent extraction and gas-liquid chromatography is described which can detect as little as 0.015 μg of methadone per ml of human plasma. The method has been used to determine the concentration of methadone in plasma samples from normal volunteers given a single dose of methadone, from cancer patients receiving multiple doses for pathological pain and from former heroin addicts in a methadone treatment program. The concentration of methadone and its two metabolites in the urine of normal volunteers has also been determined. Following the intramuscular administration of 10 mg of methadone to three normal volunteers the drug disappeared from plasma with an average biologic halflife of 7.3 h.
Human Papillomavirus Type 16 E6 Induces Self-Ubiquitination of the E6AP Ubiquitin-Protein Ligase

The E6 protein of the high-risk human papillomaviruses (HPVs) and the cellular ubiquitin-protein ligase E6AP form a complex which causes the ubiquitination and degradation of p53. We show here that HPV16 E6 promotes the ubiquitination and degradation of E6AP itself. The half-life of E6AP is shorter in HPV-positive cervical cancer cells than in HPV-negative cervical cancer cells, and E6AP is stabilized in HPV-positive cancer cells when expression of the viral oncoproteins is repressed. Expression of HPV16 E6 in cells results in a threefold decrease in the half-life of transfected E6AP. E6-mediated degradation of E6AP requires (i) the binding of E6 to E6AP, (ii) the catalytic activity of E6AP, and (iii) activity of the 26S proteasome, suggesting that E6-E6AP interaction results in E6AP self-ubiquitination and degradation. In addition, both in vitro and in vivo experiments indicate that E6AP self-ubiquitination results primarily from an intramolecular transfer of ubiquitin from the active-site cysteine to one or more lysine residues; however, intermolecular transfer can also occur in the context of an E6-mediated E6AP multimer. Finally, we demonstrate that an E6 mutant that is able to immortalize human mammary epithelial cells but is unable to degrade p53 retains its ability to bind and degrade E6AP, raising the possibility that E6-mediated degradation of E6AP contributes to its ability to transform mammalian cells.