cssi/SciSciGPT-SciSciNet huggingface dataset:
REDUCTION IN IgE BINDING TO ALLERGEN VARIANTS GENERATED BY SITE-DIRECTED MUTAGENESIS: CONTRIBUTION OF DISULFIDE BONDS TO THE ANTIGENIC STRUCTURE OF THE MAJOR HOUSE DUST MITE ALLERGEN Der p 2

Site-directed mutagenesis was used to investigate the contribution of disulfide bonds to the antigenic structure of Der p 2. Single amino acid variants were generated at cysteine residues, preventing the formation of disulfide bonds at positions 21-27, 73-78, and 8-119. The variants were tested for binding to murine monoclonal antibodies (mAb) and human IgE antibodies (Ab) in an inhibition enzyme immunoassay. Removal of the disulfide linking the amino-carboxy termini (C8-C119) had no effect on mAb binding, however, IgE Ab binding was reduced by up to 10-fold. The other two disulfides form small loops and disruption of these bonds gave different binding patterns. The variant lacking the C21-C27 bond showed up to a 40-fold reduction in antibody binding, while the variant lacking the C73-C78 bond showed more than a 100-fold reduction in IgE Ab binding and failed to bind 3 of 4 mAb. Intradermal skin testing with the C73-C78 variant supported the in vitro findings; the variant was 10 to 100-fold less reactive than rDer p 2. These two bonds thus make markedly different contributions to stabilizing the antigenic determinants of Der p 2. The results suggest that the C73-C78 bond plays a critical role in stabilizing the antigenic structure of this major mite allergen.
Ethical integrative pediatric care: A new perspective

Abstract The practice of integrative medicine has raised new questions for medical ethicists and providers of care. These questions are complicated by the particular ethical considerations in the care of children and adolescents. Several authors have provided guidelines for the use of complimentary and alternative therapies in pediatric care. In this manuscript, typical case scenarios from the author's clinical experience provide a springboard for the expansion and modification of these guidelines. The implications for provision of optimal compassionate pediatric care are discussed.
Ion transport by heart mitochondria. XVIII. Swelling and contraction of heart mitochondria suspended in ammonium chloride

Bovine heart mitochondria which have been allowed to swell in isotonic NH 4 + phosphate contract in response to initiation of oxidative phosphorylation. The contraction occurs optimally at pH 6.0 and appears from inhibition studies to result from Pi uptake being slower than removal of internal Pi via phosphorylation of external ADP. Similar results are obtained when K+ + nigericin is substituted for NH 4 + . Mersalyl inhibition of Pi transport in respiring, nonphosphorylating mitochondria which have been allowed to swell in NH 4 + phosphate reveals a contractile process having an alkaline pH optimum. This contraction resembles closely the contraction observed in salts of strong acids and presumably occurs by electrophoretic ejection of Pi anions driven by electrogenic H+ ejection.
Reconciling heterogeneity in crystal zoning data: An application of shared characteristic diagrams at Chaos Crags, Lassen Volcanic Center, California

Isotope, trace element, and textural crystal zoning patterns record heterogeneity in magmatic systems not resolved by whole rock analyses. These zoning data are used to infer crystal residence times, magma mixing, and other magmatic processes in many magmatic systems. We present the shared characteristic diagram (SCD) as an organizational framework for crystal zoning data that compares information from different phases and chemical tracers in a common framework. An example from Chaos Crags in the Cascade arc, produces three main results. (1) Anorthite zoning profiles in plagioclase have fewer shared characteristics in mafic inclusions than in the host rhyodacite. (2) Single-crystal 87Sr/86Sr data from previous studies (Tepley et al. 1999) are consistent with more shared history between crystals than in anorthite profiles. This difference reflects a more homogeneous distribution of 87Sr/86Sr than the intensive parameters controlling plagioclase composition. (3) The Chaos Crags system exhibits a layer of heterogeneity in crystal populations that is not represented in whole-rock analyses that indicate only simple binary mixing. The inconsistency between 87Sr/86Sr and anorthite zoning data highlights decoupling between compositionally controlled and temperature/water-controlled zoning in plagioclase from Chaos Crags.
Phylogenetic relationships and generic boundaries in the Episcieae (Gesneriaceae) inferred from nuclear, chloroplast, and morphological data

Episcieae is the most diverse tribe of Gesneriaceae, with 22 genera and over 700 species, or roughly 21% of all Gesneriaceae. The tribe is restricted to the Neotropics and is characterized by axillary flowers derived from a pair-flowered cyme inflorescence by reduction, a three-trace trilacunar node with split lateral bundles, superior ovaries, and with most members having a haploid chromosome number of n = 9 [n = 8 in Codonanthe and Nematanthus]. Most traditionally recognized genera in Episcieae are either known to be non-monophyletic or have not been represented adequately in phylogenetic analyses to test their monophyly. This paper presents phylogenetic analyses utilizing two molecular [the internal transcribed spacer region of 18S-26S nuclear ribosomal DNA (ITS) and the trnH-psbA intergenic spacer for 155 species] and one morphological (99 characters for 120 species) datasets, combined in a total evidence analysis. All traditionally recognized genera of Episcieae except for the monotypic genus Lampadaria are represented. Of the 21 sampled genera in Episcieae, 16 are represented by the generic type species. The genera Glossoloma and Crantzia are segregated from the genus Alloplectus as traditionally recognized. Other genera that are strongly supported as monophyletic include Alsobia, Columnea (with the inclusion of C. dielsii), Corytoplectus, and Episcia. Drymonia is weakly supported and is shown here to be morphologically diverse and in need of further evaluation. Evolution of fruit structure is examined in the context of the phylogenetic results presented here with two previously unreported features that are here referred to as capsules with tardily dehiscent and non-dehiscent endocarps. Three independent origins of resupinate flowers are inferred for Glossoloma, Nematanthus, and Crantzia. Strongly supported clades have centers of diversity in southeastern Brazil (Nematanthus, Codonanthe, Codonanthopsis, and Paradrymonia anisophylla), northern South America (Alloplectus, Drymonia, Columnea, Neomortonia), Central America (Alsobia, Oerstedina, Rufodorsia, Cobananthus), and two clades with diversity in the Guiana Shield [(Paradrymonia, Nautilocalyx, Chrysothemis) and (Lembocarpus, Cremersia, Rhoogeton)]. Neomortonia, a genus of three species, is poorly supported due to conflict among datasets.
Immune effector mechanisms in heart transplant rejection

It is well established that immunological mechanisms are responsible for the pathophysiology of several heart diseases, some contributing significantly to morbidity and mortality worldwide. Of the multiple cellular and humoral components participating in the overall immune response in heart diseases, this article mainly deals with cellular immunity mediated by cytotoxic T lymphocytes (CTL). Three important heart diseases have been associated with CTL induced myocardial damage: (1) heart transplant rejection; (2) myocarditis and dilated cardiomyopathy; (3) Chagas heart disease.
Development of a simultaneous extraction and cleanup method for pyrethroid pesticides from indoor house dust samples.

Abstract An efficient and reliable analytical method was developed for the sensitive and selective quantification of pyrethroid pesticides (PYRs) in house dust samples. The method is based on selective pressurized liquid extraction (SPLE) of the dust-bound PYRs into dichloromethane (DCM) with analysis by gas chromatography/mass spectrometry. Various adsorbents and combinations of extraction solvents and temperatures were evaluated to achieve a high-throughput sample preparation that eliminates the post-extraction cleanup step. The final method used sulfuric acid-impregnated silica (acid silica) and neutral silica together in the extraction cell with the dust sample to provide both extraction and cleanup simultaneously. The optimal ratio of dust/acid silica/silica was 1:0.8:8. The extraction was performed at 2000 psi, at 100 °C with DCM for 5 min in three cycles. Method precision and accuracy were evaluated by the analysis of triplicate aliquots of the dust samples and the samples fortified with the target PYRs. The accuracy measured as the recoveries of the PYRs in the fortified samples ranged from 85% to 120%. The precision measured as the relative standard deviation of replicate samples was within ±25%. The SPLE method was applied to 20 house dust samples collected from households that participated in two field studies regarding exposures to pesticides and other pollutants. Similar concentrations of target PYRs were obtained for the SPLE and a stepwise extraction/cleanup procedure. The SPLE procedure reduces organic solvent consumption and increases the sample throughput when compared with a traditional stepwise extraction and cleanup procedure. This study demonstrates that the SPLE procedure can be applied to complex dust matrices for analysis of PYRs for large scale exposure or environmental monitoring studies.
The policy implications of non-convex environmental damages: A smog control case study

Abstract Nitrogen oxides and hydrocarbons react to form atmospheric ozone, but, for given concentrations of either one, increasing amounts of the other give rise to declining increments of ozone. Thus, the damage functions from hydrocarbon and nitrogen oxide emissions are non-convex. A case study of control strategies in the New York metropolitan regions show that, because control costs rise so steeply for both pollutants, a cost-effective approach is to control emissions of both, despite the non-convexities. However, the loss function, for deviations from the least-cost strategy, lies well within the range of scientific uncertainty regarding precursor-ozone relationships, and the least-cost strategy choice is highly sensitive to small changes in the relative control costs. Therefore, decisions regarding controls on these emissions, especially nitrogen oxide emissions, should be based also on other considerations, such as the reduction in acid deposition.
Role of differential neuroaxial blockade in the evaluation and management of pain in chronic pancreatitis

Role of differential neuroaxial blockade in the evaluation and management of pain in chronic pancreatitis
Photonic applications with photoanisotropic nanomaterials

Linearly polarized light beam can rotate the trans-azobenzene molecules into cis-form resulting in inducing photoanisotropy. This property is used to control the transmission of nanosecond and picosecond laser pulses and also for holographic data storage applications. Studies were performed using four commercially available azobenzene dyes in different solvents and also in custom prepared nanoporous azobenzene Dendron films. Nanopores are created in a silica matrix and azobenzene molecules are attached to the inner walls of these pores to mimic solution like environment for the azobenzene molecules such that they can undergo photoinduced trans-cis-trans isomerization process at a faster rate.
Alternative Certification Pathways Filling a Gap

The purpose of this article is to examine the proliferation of alternative certification pathways through an analysis of the role and history of teacher certification and supply followed by a synth...
A sheep model for continuous intrathecal infusion of test substances

Pharmaceutical research and new drug development rely extensively on animal research. The development of novel agents for intrathecal administration requires preclinical studies of toxic effects in an animal model. We have developed a nonrodent animal model for this purpose. Our sheep model: 1 Is an animal whose neural axis is similar to the human 2 Allows for the percutaneous placement of intrathecal catheters 3 Has minimal possibilities of infection because the infusion system is totally implanted 4 Provides continuous infusion of the test agent 5 Generates behavioral, motor, neurological and histopathological information so that safety guidelines can be established prior to preclinical studies.
Parenting and research productivity: New evidence and methods

To date, studies on how having children affects the research productivity of academics, and whether the effects differ by gender, have had inconsistent findings. Using nuanced measures of parental obligations and linear growth modeling, we analyzed the effects of children on the entire careers of academics in two disciplines — linguistics and sociology — and tested for differential effects by gender. In addition, we modeled not only productivity, but also visibility, another component of scholarly success. Our findings suggest that after the birth a child, productivity growth declines, but more so for women. Thus, children account for part of the gender gap in rates of productivity over time. Children also have an impact on the research visibility of academics, but cannot account for gender differences in visibility.
Studying Normal, Everyday Social Media

Social media research has tended to focus on stand-out cases and has made use of big data methods to make claims about human experience and sociality. This commentary urges researchers to consider the everyday, normal experiences of most social media users, to consider the place of social media in a broader social context, and to consider marrying big data approaches with interviews and surveys of users.
Large-scale parallel null space calculation for nuclear configuration interaction

One of the emerging computational approaches in nuclear physics is the configuration interaction (CI) method for solving the many-body nuclear Hamiltonian in a sufficiently large single-particle basis space to obtain exact answers — either directly or by extrapolation. One particular goal is to compute a number of lowest eigenvalues and eigenvectors of the Hamiltonian Ĥ that are associated with a fixed total angular momentum J. To achieve this goal, we perform a simultaneous diagonalization of Ĥ and Ĵ2, where Ĵ2 is the total angular momentum square operator. In this approach, we first compute the invariant subspace of Ĵ2 corresponding to a fixed and known eigenvalue λ = J (J +1), and then project Ĥ into this subspace in order to extract desired spectral information from the resulting lower dimensional Hamiltonian. In this paper, we discuss how to compute the desired invariant subspace of Ĵ2 (or equivalently, the null space of Ĵ2-λI) efficiently on a large-scale distributed-memory high performance computer. We describe both the algorithms we use to solve the problem and implementation details that allow us to achieve optimal performance. We demonstrate the performance of our implementation by numerical experiments conducted for a few light nuclei.
Validation of a Scale for Measuring Attitudes toward Psychiatry in Medicine

An 80-item scale for measuring attitudes toward psychiatry in medicine was developed and tested. Item selection from the initial 160 items was based on factor analysis and internal consistency of the eight resulting subscales, six subscales exhibiting Cronbach Alpha coefficients ranging from .79 to .95, with two showing coefficients of .57 and .59.The subscales were sensitive to differences in medical specialty, with consultation-liaison psychiatrists exhibiting the most favorable attitudes and highly specialized physicians showing the least. The subscales correlated significantly with subscales of the Zimny Medical Specialties Preference Inventory related to preference for psychosocial and non-specialized medical activities.
The Development of NASA's Fault Management Handbook

NASA is developing a FM Handbook to establish guidelines and to provide recommendations for defining, developing, analyzing, evaluating, testing, and operating FM systems. It establishes a process for developing FM throughout the lifecycle of a mission and provides a basis for moving the field toward a formal and consistent FM methodology to be applied on future programs. This paper describes the motivation for, the development of, and the future plans for the NASA FM Handbook.
Developmental Trajectories in Adolescents and Adults With Autism: The Case of Daily Living Skills.

Objective This study aimed to investigate the longitudinal course of daily living skills in a large, community-based sample of adolescents and adults with autism spectrum disorders (ASD) over a 10-year period. Method Adolescents and adults with ASD (n = 397) were drawn from an ongoing, longitudinal study of individuals with ASD and their families. A comparison group of 167 individuals with Down syndrome (DS) were drawn from a linked longitudinal study. The Waisman Activities of Daily Living Scale was administered four times over a 10-year period. Results We used latent growth curve modeling to examine change in daily living skills. Daily living skills improved for the individuals with ASD during adolescence and their early 20s, but plateaued during their late 20s. Having an intellectual disability was associated with lower initial levels of daily living skills and a slower change over time. Individuals with DS likewise gained daily living skills over time, but there was no significant curvature in the change. Conclusions Future research should explore what environmental factors and interventions may be associated with continued gains in daily living skills for adults with ASD.
Flattening the Bhutan Himalaya

A detailed thermobarometric transect of 35 samples across the Greater and Tethyan Himalayan sequences in central Bhutan demonstrates a tectonostratigraphically-intact section with uniform apparent thermal and baric field gradients of 2072 1C/km and 0.5770.08 kbar/km. Pressure–temperature paths determined from chemically-zoned garnets in 6 samples demonstrate that these P–T conditions correspond with maximum pressures. The super-lithostatic baric gradient cannot be explained by pre- to syn-metamorphic tectonic processes, or by extension within an inclined slab. Instead the data imply 50% post-peakmetamorphic flattening of the Himalayan metamorphic core, accommodated by distributed, top-to-thenorth shear, consistent with microstructural analysis. Orogenic flattening best explains the development of the South Tibetan Detachment System as a strain incompatibility feature rather than a structure bounding the top of a tectonically-inserted wedge, and helps reconcile debate attributing first-order Himalayan structural features to either wedge failure (‘‘critical taper’’) or pipe-flow (‘‘channel flow’’).
Visual spaces, norm governed places: the influence of spatial context online:

Current theories of social interaction and normative influence in Computer-Mediated Communication were developed in the era of the internet predominated by text-based interaction. With the growth of visual-spatial worlds like Second Life, these theories need to be re-examined. The evolution of thinking about social norms online has moved from a mechanistic view to a systems view of humans and communication technology intertwined in a complex relationship that includes groups, identity, communication, and norms. Missing from that system is explicit attention to context and the important role of the environment that encases interaction. This article discusses theories of how architecture and embodiment shape offline life and how such theories increasingly apply in online interaction in visual social spaces. We argue that such spaces communicate normative information that influences behavior within a given context in both conscious and unconscious ways. This article then discusses implications of visual-spat...
Functional Interactions Between A' Helices in the C-linker of Open CNG Channels

Cyclic nucleotide-gated (CNG) channels are nonselective cation channels that are activated by the direct binding of the cyclic nucleotides cAMP and cGMP. The region linking the last membrane-spanning region (S6) to the cyclic nucleotide binding domain in the COOH terminus, termed the C-linker, has been shown to play an important role in coupling cyclic nucleotide binding to opening of the pore. In this study, we explored the intersubunit proximity between the A' helices of the C-linker regions of CNGA1 in functional channels using site-specific cysteine substitution. We found that intersubunit disulfide bonds can be formed between the A' helices in open channels, and that inducing disulfide bonds in most of the studied constructs resulted in potentiation of channel activation. This suggests that the A' helices of the C-linker regions are in close proximity when the channel is in the open state. Our finding is not compatible with a homology model of the CNGA1 C-linker made from the recently published X-ray crystallographic structure of the hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channel COOH terminus, and leads us to suggest that the C-linker region depicted in the crystal structure may represent the structure of the closed state. The opening conformational change would then involve a movement of the A' helices from a position parallel to the axis of the membrane to one perpendicular to the axis of the membrane.
Effect of synthetic cationic protein on mechanoexcitability of vagal afferent nerve subtypes in guinea pig esophagus

Eosinophilic esophagitis is characterized by increased infiltration and degranulation of eosinophils in the esophagus. Whether eosinophil-derived cationic proteins regulate esophageal sensory nerve function is still unknown. Using synthetic cationic protein to investigate such effect, we performed extracellular recordings from vagal nodose or jugular neurons in ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Nerve excitabilities were determined by comparing action potentials evoked by esophageal distensions before and after perfusion of synthetic cationic protein poly-l-lysine (PLL) with or without pretreatment with poly-l-glutamic acid (PLGA), which neutralized cationic charges of PLL. Perfusion with PLL did not evoke action potentials in esophageal nodose C fibers but increased their responses to esophageal distension. This potentiation effect lasted for 30 min after washing out of PLL. Pretreatment with PLGA significantly inhibited PLL-induced mechanohyperexcitability of esophageal nodose C fibers. In esophageal nodose Aδ fibers, perfusion with PLL did not evoke action potentials. In contrast to nodose C fibers, both the spontaneous discharges and the responses to esophageal distension in nodose Aδ fibers were decreased by perfusion with PLL, which can be restored after washing out PLL for 30–60 min. Pretreatment with PLGA attenuated PLL-induced decrease in spontaneous discharge and mechanoexcitability of esophageal nodose Aδ fibers. In esophageal jugular C fibers, PLL neither evoked action potentials nor changed their responses to esophageal distension. Collectively, these data demonstrated that synthetic cationic protein did not evoke action potential discharges of esophageal vagal afferents but had distinctive sensitization effects on their responses to esophageal distension.
Effects of the herbicide dicamba on nontarget plants and pollinator visitation

Nearly 80% of all pesticides applied to row crops are herbicides, and these applications pose potentially significant ecotoxicological risks to nontarget plants and associated pollinators. In response to the widespread occurrence of weed species resistant to glyphosate, biotechnology companies have developed crops resistant to the synthetic-auxin herbicides dicamba and 2,4-dichlorophenoxyacetic acid (2,4-D); and once commercialized, adoption of these crops is likely to change herbicide-use patterns. Despite current limited use, dicamba and 2,4-D are often responsible for injury to nontarget plants; but effects of these herbicides on insect communities are poorly understood. To understand the influence of dicamba on pollinators, the authors applied several sublethal, drift-level rates of dicamba to alfalfa (Medicago sativa L.) and Eupatorium perfoliatum L. and evaluated plant flowering and floral visitation by pollinators. The authors found that dicamba doses simulating particle drift (≈1% of the field application rate) delayed onset of flowering and reduced the number of flowers of each plant species; however, plants that did flower produced similar-quality pollen in terms of protein concentrations. Further, plants affected by particle drift rates were visited less often by pollinators. Because plants exposed to sublethal levels of dicamba may produce fewer floral resources and be less frequently visited by pollinators, use of dicamba or other synthetic-auxin herbicides with widespread planting of herbicide-resistant crops will need to be carefully stewarded to prevent potential disturbances of plant and beneficial insect communities in agricultural landscapes.
Soluble tumor necrosis factor receptor type I enhances tumor development and persistence in vivo.

Secretion of human soluble tumor necrosis factor receptor type I (sTNFRI) by the mouse fibrosarcoma cell line, L929, previously has been demonstrated to confer resistance to in vitro lysis by TNF and to LAK- and CTL-mediated cytolysis. These findings suggest that, in vivo, sTNFRI contributes to tumor survival by inhibiting these immunologic mechanisms. To evaluate this hypothesis, we compared the growth of sTNFRI-secreting L929 cells with that of the unmodified parental fibrosarcoma in an in vivo mouse transplantation model. Secretion of sTNFRI by L929 cells markedly enhanced their tumorigenicity and persistence in syngeneic recipients. This benefit was abrogated by sTNFRI-neutralizing antibodies induced by immunization prior to tumor challenge. These data demonstrate that sTNFRI directly influences tumor formation and persistence in vivo and suggest the selective removal and/or inactivation of sTNFRI as a promising new avenue for cancer immunotherapy.
High Frequency Intergeneric and Intrageneric Conjugal Transfer of Drug Resistance Plasmids in Leuconostoc mesenteroides ssp. cremoris

Abstract Transfer of the broad host range conjugative plasmids pAMβ1, pVA797:: Tn 917 , and pIP501 between Lactococcus lactis and Leuconostoc mesenteroides ssp. cremoris occurred at high frequency via a conjugation-like process on solid surface agar. Frequencies of 10 –1 to 10 –3 transconjugants per input donor cell were observed from L. lactis to three strains of Leuc. mesenteroides ssp. cremoris . Reverse intergeneric transfer from Leuc. mesenteroides ssp. cremoris to L. lactis occurred at frequencies up to 10 –4 transconjugants per donor cell. Intrageneric transfer between Leuc. mesenteroides ssp. cremoris strains was also observed at frequencies as high as 10 –3 transconjugants per donor cell. The ability to transfer these plasmids to and among Leuc. mesenteroides ssp. cremoris at high frequencies provides a method of genetic transfer, making them available to cloning strategies developed in other Gram-positive bacteria.
Effects of a 2,3-Diphenylindene Derivative (U-11,555A) on the Reproductive System of Female Domestic Fowl

Abstract THE water soluble, non-steroidal, synthetic compound U-11,555A 1 (triethylamine, 2-[p-(6-methoxy-2 phenylinden-3-yl)—phenoxy] hydrochloride), was tested by Duncan et al. (1962) on rats, mice, guinea pigs and rabbits. It was found to be a potent antifertility agent for these species. After extensive tests on rats, these workers concluded that U-11,555A inhibits the uterine and vaginal response to endogenous and exogenous estrogen and that the compound manifests neither antigonadotropic, progestational, androgenic, nor estrogenic activity. Duncan and Lyster (1962) have shown that blastocyst implantation occurs in treated rats, but not golden hamsters, if an estrogen is administered concurrently with U-11,555A. It is well known that endogenous sex hormones inhibit the growth of the rudimentary right gonad of domestic fowl. It was the purpose of this study to investigate the action of U-11,555A in birds and to determine if it would cause a proliferation of the rudimentary gonad through an antiestrogenic action. MATERIALS AND METHODS…
The Effect of Oxygen Plasma on Some Experimental Polymers Containing Silicon and Phosphorus

As part of a NASA program on high performance polymers for space applications, polymers containing silicon and phosphorus were prepared, characterized and exposed to an oxygen plasma under vacuum. Thin films of polyimides containing pendent siloxane groups, thermosetting resins contain ing silicon and poly(arylene ether)s containing phenylphosphine oxide were ex posed to a radio frequency generated oxygen plasma to assess their stability. The weight loss of the films was monitored as a function of exposure time and compared with that of Ultem® and Kapton® polyimide films of the same thick ness exposed under identical conditions. All of the experimental materials ex hibited better weight retention than either of the commercial polyimides. The thermosetting resins containing silicon and poly(arylene ether)s containing phosphine oxide exhibited only minor weight loss (0-5%) compared to that ex hibited by Ultem® (75-100%) and Kapton® (35-82%). Organic polymers con taining silicon are known to form silicates a...
The Vibrio cholerae VprA-VprB Two-Component System Controls Virulence through Endotoxin Modification

ABSTRACT The bacterial cell surface is the first structure the host immune system targets to prevent infection. Cationic antimicrobial peptides of the innate immune system bind to the membrane of Gram-negative pathogens via conserved, surface-exposed lipopolysaccharide (LPS) molecules. We recently reported that modern strains of the global intestinal pathogen Vibrio cholerae modify the anionic lipid A domain of LPS with a novel moiety, amino acids. Remarkably, glycine or diglycine addition to lipid A alters the surface charge of the bacteria to help evade the cationic antimicrobial peptide polymyxin. However, the regulatory mechanisms of lipid A modification in V. cholerae are unknown. Here, we identify a novel two-component system that regulates lipid A glycine modification by responding to important biological cues associated with pathogenesis, including bile, mildly acidic pH, and cationic antimicrobial peptides. The histidine kinase Vc1319 (VprB) and the response regulator Vc1320 (VprA) respond to these signals and are required for the expression of the almEFG operon that encodes the genes essential for glycine modification of lipid A. Importantly, both the newly identified two-component system and the lipid A modification machinery are required for colonization of the mammalian host. This study demonstrates how V. cholerae uses a previously unknown regulatory network, independent of well-studied V. cholerae virulence factors and regulators, to respond to the host environment and cause infection. IMPORTANCE Vibrio cholerae, the etiological agent of cholera disease, infects millions of people every year. V. cholerae El Tor and classical biotypes have been responsible for all cholera pandemics. The El Tor biotype responsible for the current seventh pandemic has displaced the classical biotype worldwide and is highly resistant to cationic antimicrobial peptides, like polymyxin B. This resistance arises from the attachment of one or two glycine residues to the lipid A domain of lipopolysaccharide, a major surface component of Gram-negative bacteria. Here, we identify the VprAB two-component system that regulates the charge of the bacterial surface by directly controlling the expression of genes required for glycine addition to lipid A. The VprAB-dependent lipid A modification confers polymyxin B resistance and contributes significantly to pathogenesis. This finding is relevant for understanding how Vibrio cholerae has evolved mechanisms to facilitate the evasion of the host immune system and increase bacterial fitness.
Thermal Properties of Thermochromic Asphalt Binders by Modulated Differential Scanning Calorimetry

Thermochromic materials are substances that can reversibly change their colors in response to temperature. These materials can be designed to have high solar reflectance at high temperature and low solar reflectance at low temperature. They are therefore potential new smart materials that can improve pavement thermal conditions. The innovation of this study was to develop thermochromic asphalt binders possessing dynamic solar reflectance in response to environmental temperature. The preliminary study indicated that the thermochromic binder coating achieved a temperature reduction as high as 6.4°C under the conditions of a typical summer day in Cleveland, Ohio. A comparison of measurements under cold conditions in Cleveland demonstrated that thermochromic asphalt binder could remain warmer than conventional asphalt binder. This attribute helps to improve the resistance of asphalt pavement to low-temperature cracking, delays ice formation on the road surface, and potentially improves the durability and safe...
The asymmetric synthesis of β-lactam antibiotics - I. application of chiral oxazolidones in the staudinger reaction.

Abstract The reactions of oxazolidone 1 with N-benzylimines proceed with exceptional levels of asymmetric induction to form the cycloadducts 2. Subsequent dissolving metal reduction affords the homochiral β-lactam derivatives 3 in good overall yield (eq 1).
Symbolic integration of a class of algebraic functions

In this presentation we describe the outline of an algorithmic approach to handle a class of algebraic integrands. (It is important to stress that for an extended abstract of the present form, we can at best convey the flavor of the approach, with numerous details missing.) We shall label this approach Carlson's algorithm because it is based on a series of analyses rendered by Carlson and his associates in the last ten years (Refs. 2, 3, 4, 8, and 12). The class of integrands is of the form r(x, y), where y2 is a polynomial in x, and r a rational function in x and y. This is the type of integrand that classically led to the study of elliptic integrals. At first glance this is a rather restricted class of algebraic functions. But in fact many trigonometric and hyperbolic integrands reduce to this form. The richness of this class of integrands is exemplified by a recently published handbook of 3000 integral formulas (Ref. 1). Our proposed approach will cover fifty to seventy percent of the items in the handbook. Furthermore the non-classical approach we shall describe holds great promise of developing to the case where definite integrals can be evaluated in terms of a host of other well-known functions (e.g., Bessel and Legendre).
A nuclear strike against Listeria--the evolving life of LXR

Abstract LXRs are members of the nuclear receptor superfamily and function as master regulators of cholesterol metabolism. In the macrophage, they control cholesterol efflux and inhibit the transcription factor NF-κB-mediated proinflammatory responses. In this issue of Cell , Joseph et al. (2004) discover surprising, protective functions for LXRα in innate immunity.
Tax Havens and Tax Equity

The phrase "tax haven" is often used in political debate about tax equity, generally in a negative tone. The purpose of this paper is to examine the ways tax havens are used by U.S. taxpayers, and to comment on the effect of tax havens on tax equity.
Sideroflexin 4 Deficiency Results In An Erythroid Differentiation Defect

Megaloblastic anemia characterizes molecularly heterogeneous disorders, most commonly marked by macrocytosis, red blood cell enlargement, and abnormal nuclear maturation. Aside from vitamin B12 and folate deficiencies, genetic defects may be responsible for hereditary forms of megaloblastic anemia, though some remain unknown (Ghersim C, et al. 2013 J. Biol. Chem .). Loss of function of the gene Sideroflexin-4 ( SFXN4 ) has been implicated as a cause for combined macrocytic anemia and mitochondriopathy. We have previously shown a defect in SFXN4 in humans and successfully modeled the erythroid and mitochondrial defects in the zebrafish (Hildick-Smith GJ, et al. 2013 AJHG ). Here, we expand on prior studies involving SFXN4 in zebrafish and human fibroblasts by generating a murine cultured cell model deficient in SFXN4 . Clustered regularly interspaced short palindromic repeats (CRISPR)-cas targeting technology (Cong L, et al. 2013 Science ) was utilized to generate SFXN4 knockout Friend mouse erythroid leukemia (MEL) clones. We conducted a screen of clones using qRT-PCR to select MEL clones with the lowest expression of Sfxn4 mRNA. The CRISPR knockout clone shows significantly reduced Sfxn4 mRNA relative to wild type (Panel A). Furthermore, the CRISPR knockout's reduced Sfxn4 mRNA is comparable to Sfxn4 mRNA levels in clones silenced by shRNA hairpin constructs (data now shown) . We also investigated the differentiation and maturation potential of the CRISPR-derived SFXN4 knockout clone. Initially, the MEL clone was differentiated for 3-5 days with DMSO treatment. o -dianisidine stains revealed that the CRISPR knockout clone had a reduction in hemoglobinization. Furthermore, Wright-Giemsa staining demonstrated that the same clone possessed megaloblastic features with immature maturation and a high nuclear to cytoplasmic ratio (Panel B). Both sets of results from experiments support the hypothesis for an essential role of SFXN4 in vertebrate red cell development. In summary, our data: (1) supports the hypothesis of SFXN4's involvement in erythropoiesis and candidacy as a gene for combined macrocytic anemia and mitochondriopathy, and (2) demonstrates the promise of shRNA knockdown and now CRISPR SFXN4 knockout clones as tools for further studying the biochemical relationship between SFXN4 and megaloblastic anemia. ![Figure][1] Disclosures: No relevant conflicts of interest to declare. [1]: pending:yes
Percutaneous Decompression of the Left Ventricle in Cardiogenic Shock Patients on Venoarterial Extracorporeal Membrane Oxygenation

Objective Extracorporeal membrane oxygenation is an important therapeutic option for patients with refractory cardiogenic shock. Adequate decompression of the left ventricular in these patients is a key predictor of successful recovery. The currently available percutaneous decompression techniques are limited by their partial unloading capability. Method We describe a series of four consecutive patients with refractory cardiogenic shock in whom adequate left ventricular decompression was achieved by integrating a transseptally placed left ventricular cannula into the existing extracorporeal membrane oxygenation circuit. Results From May to June 2015, four consecutive patients underwent transvenous transseptal left ventricular decompression with a 22 French cannula that was integrated into the extracorporeal membrane oxygenation circuit in a Y fashion. The mean age was 47.5 ± 20 years. All patients had refractory shock, and three patients failed prior decompression with an intra-aortic balloon pump. Fluoroscopy time was 12.15 ± 2.6 minutes. No procedural complications were noted. All patients had significant reduction in their pulmonary capillary wedge pressure and resolution of their pulmonary edema. Two patients died during the hospitalization due to sepsis and/or multiorgan failure. Conclusion Antegrade transseptal left ventricular decompression is feasible in patients on extracorporeal membrane oxygenation and persistent pulmonary edema. doi: 10.1111/jocs.12696 (J Card Surg 2016;31:177–182)
Enhancing EDP of multicore processors through DVFS

Dynamic voltage and frequency scaling (DVFS) is a well-known technique to optimize the power dissipation of electronic systems without significantly compromising overall system performance. DVFS exploits the periods of inter-core data exchange (memory-bound operations) to reduce the voltage and frequency (V/F) of the cores in order to reduce the power dissipation during the execution flow of an application running on the CMP. As the lengths of the idle and busy periods of the cores vary depending on the benchmarks, it is crucial for any DVFS technique to maximize the power saving without losing a significant performance. In this work we present two power optimization methodologies that are integrated into a full-system simulator to make online predictions about the voltage and frequency of the cores during the execution time of the benchmarks. We evaluate these methodologies in terms of the V/F predictions vs. the actual utilization of each core periodically. We also compare the overall execution time, energy dissipation, and energy-delay product (EDP) of the power optimization methodologies for various benchmarks.
Brain Activation and Psychomotor Speed in Middle-Aged Patients with Type 1 Diabetes: Relationships with Hyperglycemia and Brain Small Vessel Disease

Slower psychomotor speed is very common in patients with type 1 diabetes mellitus (T1D), but the underlying mechanisms are not clear. We propose that hyperglycemia is associated with slower psychomotor speed via disruption of brain activation. Eighty-five adults (48% women, mean age: 49.0 years, mean duration: 40.8) with childhood onset T1D were recruited for this cross-sectional study. Median response time in seconds (longer = worse performance) and brain activation were measured while performing a psychomotor speed task. Exposure to hyperglycemia, measured as glycosylated hemoglobin A1c, was associated with longer response time and with higher activation in the inferior frontal gyrus and primary sensorimotor and dorsal cingulate cortex. Higher activation in inferior frontal gyrus, primary sensorimotor cortex, thalamus, and cuneus was related to longer response times; in contrast, higher activation in the superior parietal lobe was associated with shorter response times. Associations were independent of small vessel disease in the brain or other organs. In this group of middle-aged adults with T1D, the pathway linking chronic hyperglycemia with slower processing speed appears to include increased brain activation, but not small vessel disease. Activation in the superior parietal lobe may compensate for dysregulation in brain activation in the presence of hyperglycemia.
Alvaro Obregón and Anticlericalism in the 1910 Revolution

A social revolution must concern itself immediately with the past, since it is a basic conviction of the revolutionist that the moribund and corrupt order which causes society's distress makes impossible the kind of future that he sees as desirable and necessary. Old institutions, structures, and habits of thought must be abolished or severely modified, and persons who direct or personify those vestiges must change, step aside, or be removed from positions of power and influence. Religious institutions and beliefs present a peculiarly complicated problem to a social revolution. Invariably associated with traditional ways, they are often too deeply rooted in the national mentality and sentiment to admit of any easy or rapid modification. Obliteration, even if though to be the desirable solution, is usually recognized as impossible; and to change mass attitudes by persuasion alone, is at best a long and uncertain process.
Convention the Structure Charging a Cigarette for Supporting an Environment Builds and Discusses Under the Frame

The whole world already has the negotiation that more than 190 country has participated in, signs sum promise, but honours an agreement in every country dynamics and progresses at present, condition is very unlike but, ... Investigate whose cause , be sustained "environment existence mainly because of society has a smoke" and "charge cigarette aspect for being caused by formation not yet effectively" . But, make a general observation of our country "environment complicated degree and population trend having a smoke" , Chinese having been confronted with maximal tobacco of the whole world producing the country and consuming the national austere form, and there exists the tobacco job is long the monopoly not declining greatly manages the pattern , " economic growth pattern, cigarette product being dependent on tobacco" excessively become the social contact catalyst , the behavior a series such as being hardly restricted , being given up smoking being short of the support environment fostering the behavior false reason heretical ideas having a smoke being in flood , having a smoke problem. Therefore, must pass legislation synthetical means such as charging a cigarette, building government leading factor mechanism , banning "the tobacco economic growth pattern " , locking the target crowd who "bans opium , strengthening the second-hand cigarette sufferer's unceasingly to charge cigarette consciousness and the ability " , structure society step by step charging a cigarette for supporting an environment.
Drawing Prospects to E-Commerce Websites

ABSTRACT As marketing moves into the internet era, new research projects are needed to learn what works best in E-commerce. This study investigates an unexplored area: executing Jutkins9 (1999) suggestion to use traditional advertising media to promote a website. Five different traditional direct mail advertisements were developed and sent out to prospects to determine which type of advertisement, if any, could draw more customers to a commercial website. Each of the five advertisements promoted a distinct website address (URL) so to provide an accurate calculation of website ‘hits’ produced by each of the test advertisements. A postal questionnaire survey was also reported.
A New Technique of using the in Situ Appendix as a Catheterizable Stoma in Continent Urinary Reservoirs

AbstractA new technique of using the in situ appendix to construct a continent catheterizable stoma is described in a patient who underwent continent urinary diversion, and the technical aspects of this procedure are illustrated in detail. The appendix is remodeled by invaginating its base into the cecum for 1cm., cecoplicating the middle portion for 2cm. and bringing the distal end to the skin as a cutaneous stoma. This new technique demonstrates that the in situ appendix can be constructed successfully to provide continence without the need for isolating it from the cecum and implanting the distal end into the urinary reservoir as described in the Mitrofanoff technique.
Evaluation of Low-Dose Ultraviolet Light C for Reduction of Select ESKAPE Pathogens in a Canine Skin and Muscle Model.

Abstract Objective: This study aimed at comparing the ability of low-dose UVC, 0.05% chlorhexidine, and combined UVC with 0.05% chlorhexidine to reduce colony-forming units (CFUs) on select ESKAPE pathogens (Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecium) in a canine skin and muscle model. Background data: Surgical site infections (SSIs) result in increased morbidity and cost. UVC damages DNA, rendering bacteria nonviable and does not discriminate between drug-sensitive and multi-drug-resistant organisms. Materials and methods: Specimens were inoculated with one of three pathogens. Samples were treated with a 254 nm UVC mercury lamp or a 270 nm UVC LED light at 0.015, 0.03, or 0.04 J/cm2 doses; 0.05% and 2% chlorhexidine were used as positive controls. To evaluate synergism, 0.05% chlorhexidine was used with 0.015 J/cm2 of UVC. CFUs were counted and compared against the negative control. Results: There were no significant differences in CFU counts between samples of the same tissue...