cssi/SciSciGPT-SciSciNet huggingface dataset:
Translational medicine: Primed for resistance

A drug for treating melanoma is ineffective in colorectal cancers that have the same causative mutation. Studies of how cells adapt to the drug reveal why this is so, and suggest combination therapies that may be more effective. See Letter p.100 One of the most important developments in cancer therapy in recent years is the use of vemurafenib to treat melanomas. It works by inhibiting the activated BRAF oncogene. However, colon cancers with the same activating BRAF mutation are generally unresponsive to vemurafenib. Prahallad et al. now show that this is a result of feedback activation of the epidermal growth factor receptor (EGFR) in response to BRAF inhibition. Unlike in colon cancers, the EGFR is not expressed in melanomas and is therefore not activated following vemurafenib treatment. The authors demonstrate that this mechanism of resistance can be overcome by combining BRAF and EGFR inhibitors, suggesting that such combinations should be assessed in clinical trials for colon cancers that carry activating BRAF mutations.
Structural Analysis by Networks, Matrices, and Computers

The analysis of systems of structural elements, as opposed to the analysis of the behavior of individual structural members, is examined. Parts of network theory having a bearing on structural analysis, and the network formulation of structural analysis, are briefly presented. The matrix formulation is summarized, and the transformations involved are examined. The two formulations are compared, and it is shown that they yield identical equations describing the systems, but that the network formulation has conceptual and computational advantages. This formulation also makes easier the transference of techniques from other disciplines, such as Kron’s method of piecewise solutions. Finally, it is shown that the network formulation can serve as a basis for efficient and general computer programs.
The Effect of Patient Volume and Experience on Management of Menière's Disease.

Hypothesis Treatment modalities administered by Otolaryngologists vary based on patient volume and years of experience. Objective It was our goal to evaluate the current trends in treatment modalities administered by Otolaryngologists based on patient volume and years of experience. Methods An electronic questionnaire was distributed to all General Otolaryngologists and fellowship-trained Neurotologist members of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS). Respondents were separated into groups by patients per year ( 100 patients) and years in practice (0-5, 6-10, 11-15, 16-20, or >20 yrs). Results Eight hundred and sixty members replied for a response rate of 14.5% for generalists and 35% for neurotologists. Patient volume was found to have a positive association with perceived benefit of lifestyle and diet modification, and use of intratympanic steroids, intratympanic gentamycin, oral steroids, benzodiazepines, acetazolamide, endolymphatic sac procedures, vestibular nerve section, and surgical labyrinthectomy. Only endolymphatic sac procedures were found to have a significant positive association with a physician's length in practice. The only negative association was between intratympanic steroids and a physician's length in practice. Conclusion Physicians who see more MD patients annually are more likely to use these treatment modalities: diet and lifestyle modification, intratympanic steroids, intratympanic gentamycin, surgical labyrinthectomy, vestibular nerve section, acetazolamide, alprazolam, lorazepam, dexamethasone, and prednisone. Physicians with a longer length of time in practice are more likely to use only endolymphatic sac procedures, and they are less likely to use intratympanic steroids.
On the model formulations for the interaction of nonlinear waves and current

Abstract We study the model formulations of wave–current interactions in the framework of Euler equations. This work is intrigued by a recent paper from Wang et al. (2018) (hereafter WMY), which proposes such a model for the evolution of nonlinear broadband surface waves under the influence of a prescribed steady and irrotational current without vertical shear. We show that WMY’s model can be derived from a more general model accounting for an arbitrary steady and irrotational current. Under further assumption of scale separation between waves and current (i.e. horizontally slowly-varying current), WMY’s model is equivalent to an earlier model, in contrast to WMY’s claim that their model includes additional higher-order effects in wave steepness. We demonstrate the usefulness of such models in a numerical study on wave blocking by opposing current, where the nonlinear effect on the caustic location and wave amplitude amplification is elucidated. We further show that the model formulation in the framework of Euler equations form a Hamiltonian system conserving the total energy of waves and current, justifying the theoretical significance of the model equations. Finally, we generalize the formulation to nonlinear wave evolution in the presence of a rotational current with constant vorticity, which overcomes a limitation of such models that has been overlooked in previous work.
Quantifying vitreous inflammation in uveitis: an optical coherence tomography prospective study.

Abstract Objective To quantify vitreous inflammation in a uveitis cohort using optical coherence tomography and correlate findings to gold-standard Nussenblatt scores. Design Prospective cohort study. Participants 36 eyes from 19 patients primarily with pan uveitis. Methods Study participants were scanned with optical coherence tomography and evaluated by 2 independent graders using open-source ImageJ software. Graders characterized the mean intensity of the vitreous in a 67 500-pixel box immediately above the internal limiting membrane and over the fovea and divided it by the mean intensity of the retinal pigment epithelial layer (RPE). The vitreous to retinal pigment epithelial layer ratio (VIT/RPE) ratios were correlated to Nussenblatt vitreous haze scores recorded by an independent uveitis specialist blinded to the graders’ reads. Grader 1 measured intensity a second time after a 48-hour washout period, and the intraclass correlation coefficients (2,1) were calculated for intra- and intergrader reliability. Results 21 (58.3%) eyes had a Nussenblatt score of 0, 9 (25.0%) had a score of 0.5, and the remaining 6 (16.7%) had a score ranging from 1 to 4. The r values for VIT/RPE intensity ratio regressed against Nussenblatt scores were 0.670, 0.672, and 0.660 for grader 1 read 1, grader 1 read 2, and grader 2 read 1, respectively (p Conclusion The VIT/RPE intensity ratio is a clinically relevant measure that reliably captures inflammation in uveitis and correlates well with gold-standard Nussenblatt scores.
The Impact of Land Subsidence on Preservation of Cultural Heritage Sites: The Case Study of Aquileia (Venetian-Friulian Coastland, North-Eastern Italy)

In the north-western coastland of the Adriatic Sea flooding hazard due to land subsidence and eustasy seriously jeopardizes the many cultural heritage sites present in the area, among which the UNESCO site of Aquileia. Located about 10 km inward from the coastline, Aquileia has recently come to the fore for the severe structural damages caused to its Patriarchal Basilica by differential ground subsidence. This study aims at highlighting the main control factors for subsidence in Aquileia framing it in a regional context. Our investigation is based on the integrated analysis of vertical displacements from Persistent Scatterers Interferometry and levelling surveys from the literature along a N-S transect from Terzo D’Aquileia to Grado. Interpretation of results is based on a geotechnical reference model of the subsoil obtained mainly from borehole data. Beside confirming the regional subsidence scenario affecting the Venetian-Friulian coastland, our study indicates that in Aquileia, differences in subsidence rates between the archeological area and the new city likely relate to diverse consolidation paths induced in the subsoil of the two sites by differential and diachronous man-mad loading over historical time. The smaller scale yet stark variability of sinking rates observed at the Patriarchal Basilica are interpreted to relate to heterogeneities in the shallow subsoil.
PTWAS: investigating tissue-relevant causal molecular mechanisms of complex traits using probabilistic TWAS analysis

We propose a new computational framework, probabilistic transcriptome-wide association study (PTWAS), to investigate causal relationships between gene expressions and complex traits. PTWAS applies the established principles from instrumental variables analysis and takes advantage of probabilistic eQTL annotations to delineate and tackle the unique challenges arising in TWAS. PTWAS not only confers higher power than the existing methods but also provides novel functionalities to evaluate the causal assumptions and estimate tissue- or cell-type-specific gene-to-trait effects. We illustrate the power of PTWAS by analyzing the eQTL data across 49 tissues from GTEx (v8) and GWAS summary statistics from 114 complex traits.
Projected climate change threatens significant range contraction of Cochemiea halei (Cactaceae), an island endemic, serpentine-adapted plant species at risk of extinction.

Aim Threats faced by narrowly distributed endemic plant species in the face of the Earth's sixth mass extinction and climate change exposure are especially severe for taxa on islands. We investigated the current and projected distribution and range changes of Cochemiea halei, an endemic island cactus. This taxon is of conservation concern, currently listed as vulnerable on the International Union for the Conservation of Nature Red List and as a species of special concern under Mexican federal law. The goals of this study are to (a) identify the correlations between climate variables and current suitable habitat for C. halei; (b) determine whether the species is a serpentine endemic or has a facultative relationship with ultramafic soils; and (c) predict range changes of the species based on climate change scenarios. Location The island archipelago in Bahia Magdalena on the Pacific coast, Baja California Sur, Mexico. Methods We used temperature and precipitation variables at 30-arc second resolution and soil type, employing multiple species distribution modeling methods, to identify important climate and soil conditions driving current habitat suitability. The best model of current suitability is used to predict possible effects of four climate change scenarios based on best-case to worst-case representative concentration pathways, with projected climate data from two general circulation models, over two time periods. Main conclusions The occurrence of the species is found to be strongly correlated with ultramafic soils. The most important climate predictor for habitat suitability is annual temperature range. The species is predicted to undergo range contractions from 21% to 53%, depending on the severity and duration of exposure to climate change. The broader implications for a wide range of narrowly adapted, threatened, and endemic plant species indicate an urgent need for threat assessment based on habitat suitability and climate change modeling.
Abstract 17241: The Impact of Overweight and Obesity on End-Organ Function in Fontan Patients

Introduction: Patients with Fontan circulation often develop multiorgan dysfunction. Obesity is a risk factor for systemic complications in the general population, but the impact of obesity in Font...
Phase Reduction and Synchronization of Coupled Noisy Oscillators.

We study the synchronization behavior of a noisy network in which each system is driven by two sources of state-dependent noise: (1) an intrinsic noise which is common among all systems and can be generated by the environment or any internal fluctuations, and (2) a coupling noise which is generated by interactions with other systems. After providing sufficient conditions that foster synchronization in networks of general noisy systems, we focus on weakly coupled networks of noisy oscillators and, using the first- and second-order phase response curves (PRCs), we derive a reduced order stochastic differential equation to describe the corresponding phase evolutions. Finally, we derive synchronization conditions based on the PRCs and illustrate the theoretical results on a couple of models.
Correlation between great saphenous length of treatment zone and diameter with improvement in symptoms after ablation.

Abstract Objective The aim of the present study was to examine the relationship between the great saphenous vein (GSV) length of segment ablated and diameter with symptom improvement. Methods Data from a multicenter, randomized, controlled prospective study of 242 patients undergoing radiofrequency ablation (RFA) or cyanoacrylate closure (CAC) of the GSV were analyzed. The venous clinical severity score (VCSS) was measured at baseline and at 1, 3, 6, 12, 24, and 36 months after ablation. The GSV diameter was evaluated for a correlation with VCSS at each time point. Using the median treatment length of 34 cm, the patients were divided into group I (treatment length ≥34 cm) vs group II ( Results The mean GSV length ablated by RFA was 35.3 ± 14 cm vs 32.6 ± 11 cm with CAC (P = NS). No significant difference was found in the VCSS (at baseline or follow-up) between RFA and CAC. The pooled data for all participants (n = 242) demonstrated a correlation between the treated GSV length and pretreatment VCSS and the ΔVCSS at 36 months (R = 0.23; P Conclusions Longer segments of GSV reflux appeared to correlate with symptom severity. We found a small to moderate correlation between the length of GSV segment ablated and symptom improvement. This might reflect the greater severity of symptoms at baseline in patients with longer segments with reflux. We found a poor correlation between the proximal GSV diameter and symptom improvement after ablation.
Nitrogen-induced hardening of refractory high entropy alloys containing laminar ordered phases

Abstract Most attempts to improve the properties of high entropy alloys (HEAs) involve the exploration of non-equimolar compositions, addition of alloying elements, and/or manipulation of the microstructure. Alternatively, this work reports on intentionally doping HEAs with non-metallic species to precipitate coherent, ordered phases in order to maximize hardness. A refractory MoNbTaW HEA was synthesized via cryogenic mechanical alloying and doped with nitrogen by using liquid nitrogen as the cryogen. Overall, the doping strategy was successful as multiple nitrogen-rich secondary phases were observed. In particular, a unique ordered laminar phase was developed and identified as tetragonal (Mo,W)(Nb,Ta)N nitride via aberration-corrected scanning transmission electron microscopy (STEM). Another complex (Nb,Ta)2CN carbonitride was also identified. The growth behaviors of the ceramic phases were studied using long term aging treatments of up to 100 hours at 1200°C. A second MoNbTaW alloy was also prepared via high-energy ball milling, without nitrogen, by using liquid Ar as the cryogen. A comparison of the two alloys’ microstructures and properties confirm that intentional formation of complex nitride phases greatly enhanced the hardness of mechanically alloyed MoNbTaW by up to 3-4 GPa.
Relationships Among Personality, Daily Speaking Voice Use, and Phonotrauma in Adult Female Singers.

Purpose This study sought to determine whether personality traits related to extraversion and impulsivity are more strongly associated with singers with nodules compared to vocally healthy singers ...
Do you know how much it costs

Economics, as a scientific discipline, deals with the production, distribution, and consumption of goods and services and is chiefly concerned with the allocation of scarce resources. From an economics standpoint, if something is scarce, it will have market value. There are two laws that every student of economics learns in the first week of the first class during the first year of their education. The first law, known very simply as the law of supply, states that, all other factors being equal, as the price of a good or service increases, the quantity of that good or service offered or sold by the suppliers of that good or service will increase. The second law (known as the law of demand) is just as elegant and states that, all other factors being equal, as the price of a good or service increases, consumer demand for that good or service will decrease. Importantly, in a perfectly competitive market, the equilibrium price of a good or service occurs at the point at which the quantity demanded and quantity supplied are equal (i.e., at the point at which the downwardsloping demand curve and the upward-sloping supply curve intersect each other, see Fig. 1). In other words, if the supply of a good or service is low, the market price will rise, as long as there is sufficient demand from consumers. If there is excess supply of a good or service, the market price will fall. In a similar way, as long as there is sufficient supply of a good or service, if consumer demand for that good or service is low, the market price will fall. Conversely, if the demand of the good or service increases, the market price will rise. Many economists would argue that the best way to allocate a scarce resource is to rely upon free market principles. A perfectly competitive market is defined as a market where prices are determined entirely by the laws of supply and demand, with little or no government control. There are three fundamental criteria that are necessary for perfect competition:
High-capacity discrete exponential BAM

A bidirectional associative memory (BAM) with high capacity for storage of pattern pairs is proposed. The associative memory takes advantage of the exponential nonlinearity in the evolution equations such that the signal-noise-ratio (SNR) is significantly increased. The increase of SNR consequently enhances the capacity of the BAM. An energy function is defined. The energy of the exponential BAM decreases as the recall process proceeds, ensuring the stability of the system. The monotonic decrease of the energy of the exponential BAM during the recall process ensures it will reach a local minimum. >
Reputation and Dispute in eBay Transactions

This study presents a conceptual framework for determining what factors affect the likelihood of disputes in e-commerce. It hypothesizes that disputes decrease as seller and buyer reputation and experience increase, and further that the likelihood of disputes is contingent on product price, payment method, and amount of information about the product. The empirical model is tested using five goods and services. The results indicate that reputation mechanisms deter the undesirable behavior that can lead to disputes, that experienced users are less likely to be involved in disputes than inexperienced ones, that consumer-to-consumer transactions are more likely to result in disputes than transactions between businesses, and that transactions in services are more likely to result in disputes than those in goods. The implications for auction sites include the possibility for tracking disputes and improving reputation mechanisms by incorporating information about product types, payment methods, and prices.
Crime Scene Investigation--Permian

Extinction . How Life on Earth Nearly Ended 250 Million Years Ago. By Douglas H. Erwin . Princeton University Press, Princeton, NJ, 2006. 306 pp. $24.95, £15.95. ISBN 0-691-00524-9. The author discusses the end-Permian extinction--"the mother of mass extinctions"--and the numerous explanations that have been offered for it.
Ocular inflammatory effects of intravitreally-injected tumor necrosis factor

Many of the pathophysiologic effects of bacterial endotoxin have recently been attributed to a monokine, tumor necrosis factor (TNF). The rabbit eye is extremely sensitive to locally injected endotoxin. The authors have investigated the possible contribution of TNF to ocular inflammation in a rabbit model. The intravitreal injection of 10(5) to 5 X 10(5) units of recombinant human TNF produced a sustained disruption of the blood-aqueous barrier as manifested by elevated aqueous humor protein levels. In addition, 83% of rabbits receiving this dose of TNF developed hyperemia of limbal vessels and early neovascularization of the cornea. Many developed posterior synechiae (fibrous adhesions between the iris and the lens). TNF induced only a slight cellular response in the anterior chamber. Histologic studies confirmed the presence of new vessels and demonstrated a marked mononuclear infiltrate within and beneath the epithelium of the iris and ciliary body. Lower doses of TNF produced inconsistent results. Heating TNF completely destroyed its inflammatory effects. The time course of the ocular response to TNF and the quantity of recombinant protein needed to produce consistent effects were vastly different from effects observed with interleukin-1. For example, 24 hours after an intravitreal injection, 2.2 X 10(4) ng of TNF (5 X 10(5) units) produced significantly less protein extravasation and polymorphonuclear leukocyte infiltration than 4 ng of recombinant interleukin-1. Similarly, 24 hours after intravitreal injection, 1 ng of Escherichia coli endotoxin tended to be a more potent inflammatory stimulus than this quantity of TNF. These observations indicate that the ocular pathophysiologic effects of TNF can be readily distinguished from changes induced by either endotoxin or another endotoxin induced monokine, interleukin-1.
Carbon monoxide poisoning (acute).

Introduction Carbon monoxide is an odourless, colourless gas, and poisoning causes hypoxia, cell damage, and death. Exposure to carbon monoxide is measured either directly from blood samples and expressed as a percentage of carboxyhaemoglobin, or indirectly using the carbon monoxide in expired breath. Carboxyhaemoglobin percentage is the most frequently used biomarker of carbon monoxide exposure. Although the diagnosis of carbon monoxide poisoning can be confirmed by detecting elevated levels of carboxyhaemoglobin in the blood, the presence of clinical signs and symptoms after known exposure to carbon monoxide should not be ignored.
Nanoscale stratification of optical excitation in self-interacting one-dimensional arrays

The major assumption of the Lorentz-Lorenz theory about uniformity of local fields and atomic polarization in dense material does not hold in finite groups of atoms, as we reported earlier [A. E. Kaplan and S. N. Volkov, Phys. Rev. Lett. 101, 133902 (2008)]. The uniformity is broken at subwavelength scale, where the system may exhibit strong stratification of local field and dipole polarization, with the strata period being much shorter than the incident wavelength. In this paper, we further develop and advance that theory for the most fundamental case of one-dimensional arrays, and study nanoscale excitation of so-called ``locsitons'' (local field excitations) and their standing waves (strata) that result in size-related resonances and related large field enhancement in finite arrays of atoms. The locsitons may have a whole spectrum of spatial frequencies, ranging from long waves, to an extent reminiscent of ferromagnetic domains, to supershort waves, with neighboring atoms alternating their polarizations, which are reminiscent of antiferromagnetic spin patterns. Of great interest is the different kind of ``hybrid'' mode of excitation, greatly departing from any magnetic analogies. We also study differences between Ising-type near-neighbor approximation and the case where each atom interacts with all other atoms in the array. We find an infinite number of ``exponential eigenmodes'' in the lossless system in the latter case. At certain ``magic'' numbers of atoms in the array, the system may exhibit self-induced (but linear in the field) cancellation of resonant local-field suppression. We also studied nonlinear modes of locsitons and found optical bistability and hysteresis in an infinite array for the simplest modes.
Effect of providing a web-based collaboration medium for remote customer troubleshooting tasks

This study investigates the effect of providing a Web-based diagnostic tool as a collaboration medium on remote customer troubleshooting tasks with and without the assistance of a customer call center agent. The study tested three troubleshooting modes (Web tool alone, call center agent alone, and Web tool + call center agent). The hypothesis that the Web tool + call center agent mode would be faster than the other two modes was not supported. However, the results of the experiment showed that the Web-based self-help diagnostic tool can be a potentially cost-effective way of providing customer support. The performance using the Web tool alone was comparable to the call center agent.
Macrocyclic Polyamines: 1,4,7,10,13,16‐Hexaäzacycloöctadecane

Macrocyclic polyamines: 1,4,7,10,13,16-hexaazacyclooctadecane intermediate: N,N′,N″-Tris(p-tolylsulfonyl)diethylenetriamine (1) intermediate: N,N′,N″-Tris(p-tolysulfonyl)diethylenetriamine-N,N″-disodium salt (2) intermediate: 3,6,9-Tris(p-tolylsulfonyl)-3,6,9-triazaundecane-1,11-diol (3) intermediate: 3,6,9-Tris(p-tolylsulfonyl)-3,6,9-triazaundecane-1,11-dimethanesulfonate (4) intermediate: 1,4,7,10,13,16-Hexakis(p-tolylsulfonyl)-1,4,7,10,13,16-hexaazacyclooctadecane (5) product: 1,4,7,10,13,16-hexaazacyclooctadecane (6) Keywords: alkylation, N-alkylation; annulation, heterocyclic-[>6]; cyclization, condensation; hydrolysis, miscellaneous; sulfonation, O-sulfonation; sodium ethoxide solution, preparation
Polysaccharide-gelatin complexes in acidified ethanol solutions

Abstract Numerous polysaccharides of diverse monomeric constituents and modes of linkage (such as galactan, isolichenan, laminaran, levans, lichenan, pullulan, and yeast mannan) combine with gelatin to form macromolecular complexes soluble in 0.83% trichloroacetic acid −83% ethanol. In contrast, inulin, nigeran, and yeast d -glucan do not complex with gelatin. Dextrans having various contents of α- d -(1→6), α- d -(1→4), and α- d -(1→3) linkages appear to bind gelatin more effectively than either glycogen or soluble starch. Decreased stoichiometric binding has been correlated with increased branching of the dextran polymers; conversely, the branched-chain levans bind gelatin, whereas inulin, a linear polymer, does not. With the exception of starch acetate, esterification of neutral glycans with formic, acetic, or phosphoric acid either enhances, or has no effect on, formation of complex.
Stabilization of hepatitis C virus RNA by an Ago2–miR-122 complex

MicroRNAs (miRNAs) are small noncoding RNAs that regulate eukaryotic gene expression by binding to regions of imperfect complementarity in mRNAs, typically in the 3′ UTR, recruiting an Argonaute (Ago) protein complex that usually results in translational repression or destabilization of the target RNA. The translation and decay of mRNAs are closely linked, competing processes, and whether the miRNA-induced silencing complex (RISC) acts primarily to reduce translation or stability of the mRNA remains controversial. miR-122 is an abundant, liver-specific miRNA that is an unusual host factor for hepatitis C virus (HCV), an important cause of liver disease in humans. Prior studies show that it binds the 5′ UTR of the messenger-sense HCV RNA genome, stimulating translation and promoting genome replication by an unknown mechanism. Here we show that miR-122 binds HCV RNA in association with Ago2 and that this slows decay of the viral genome in infected cells. The stabilizing action of miR-122 does not require the viral RNA to be translationally active nor engaged in replication, and can be functionally substituted by a nonmethylated 5′ cap. Our data demonstrate that a RISC-like complex mediates the stability of HCV RNA and suggest that Ago2 and miR-122 act coordinately to protect the viral genome from 5′ exonuclease activity of the host mRNA decay machinery. miR-122 thus acts in an unconventional fashion to stabilize HCV RNA and slow its decay, expanding the repertoire of mechanisms by which miRNAs modulate gene expression.
Structure of the propene⋅sulfur dioxide complex

The rotational spectra of eight isotopomers of the propene⋅SO2 complex have been observed with a Fourier transform microwave spectrometer. The rotational constants of the normal species are A=4269.564 MHz, B=1577.2661 MHz, and C=1469.6335 MHz. The structure of the complex was derived from least‐squares fitting of the 24 moments of inertia. It has a stacked, near‐parallel planes configuration. The distance between the centers of mass of the two monomers is 3.26(5) A. The sulfur atom is approximately above the propene double bond. The C2 axis of SO2 nearly eclipses the carbon–carbon single bond with the oxygen atoms towards the methyl group. The dipole moment of the complex was determined by Stark effect measurements to be μ=1.34(3) D. The binding energy is estimated to be 2.9 kcal/mol from the pseudodiatomic model. Both electrostatic and ab initio calculations have been carried out to rationalize the structure and properties of the complex. The effect of methyl group substitution on the structures and properties of the ethylene⋅SO2, propene⋅SO2, and toluene⋅SO2 complexes is discussed.
A new mechanism of leukemia drug resistance

The resistance of leukemic blast cells to asparaginase may depend on their biochemical niche in the bone marrow.
Duality invariant string algebra and D = 4 effective actions

Abstract An infinite-dimensional gauge algebra (DISG) is defined in terms of string vertex operators. The DISG reproduce the gauge algebra of 4D, N = 4 compactifications of the heterotic string, and is invariant under the full internal duality group O(6, 22, Z ). The DISG is an indefinite signature lattice algebra which contains affine Lie algebras of any level. It uniquely specifies the N = 4 low-energy effective lagrangian for gravitational and matter N = 4 multiplets. The gauge symmetries are broken on any background to a finite-dimensional gauge group. Orbifold truncations to N = 1, 2 are defined and studied for the case of Z N orbifolds. Inclusion of higher spin fields and the appearance of “duality forms” due to integration of massive fields are discussed.
Local Galois theory in dimension two

This paper proves a generalization of Shafarevich's Conjecture, for fields of Laurent series in two variables over an arbitrary field. This result says that the absolute Galois group GK of such a field K is quasi-free of rank equal to the cardinality of K, i.e. every non-trivial finite split embedding problem for GK has exactly cardK proper solutions. We also strengthen a result of Pop and Haran–Jarden on the existence of proper regular solutions to split embedding problems for curves over large fields; our strengthening concerns integral models of curves, which are two-dimensional.
Fluorescence in situ hybridization: A brief review

Fluorescence in situ hybridization (FISH) is used for many purposes, including analysis of chromosomal damage, gene mapping, clinical diagnostics, molecular toxicology and cross-species chromosome homology. FISH allows an investigator to identify the presence and location of a region of cellular DNA or RNA within morphologically preserved chromosome preparations, fixed cells or tissue sections. This report describes in situ hybridization, and discusses the past, present and future applications of this method for genetic analysis and molecular toxicology.
The local field correction to the optical potential at high energy

Abstract A key assumption in the derivation of the optical potential for high energy hadron-nucleus scattering is that no target nucleon is struck more than once. The local field (rescattering) amplitude gives the probability for the projectile to strike a target nucleon twice with an intermediate interaction with another nucleon. This rescattering amplitude generates a correction to the basic high energy optical potential, and it must be small for the above assumption to be valid. We evaluate the local field correction to the optical potential using the formalism of Foldy and Walecka. The projectile-nucleon potential is assumed to have a finite range, and the target nucleons are kept sufficiently far apart by a hard core correlation function that there is no overlap between target particles, and all off-energy-shell effects vanish. With a specific form for the high energy behavior of the on-shell projectile-nucleon scattering amplitude, we find that the local field correction vanishes rapidly at high energy.
Diabetes and cardiovascular disease: changing the focus from glycemic control to improving long-term survival.

Diabetes mellitus (DM) is the fifth-leading cause of death worldwide and contributes to leading causes of death, cancer and cardiovascular disease, including CAD, stroke, peripheral vascular disease, and other vascular disease. While glycemic management remains a cornerstone of DM care, the co-management of hypertension, atherosclerosis, cardiovascular risk reduction, and prevention of long-term consequences associated with DM are now well recognized as essential to improve long-term survival. Clinical trial evidence substantiates the importance of glycemic control, low-density cholesterol–lowering therapy, blood pressure lowering, control of albuminuria, and comprehensive approaches targeting multiple risk factors to reduce cardiovascular risk. This article presents a review of the role of DM in the pathogenesis of atherosclerosis and cardiac dysfunction, recent evidence on the degree of glycemic control and mortality, and available evidence for a multifaceted approach to improve long-term outcomes for patients.
Steroid Hormones Block Amyloid Fibril-Induced 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) Formazan Exocytosis: Relationship to Neurotoxicity

Perhaps the most reproducible early event induced by the interaction of amyloid beta peptide (A beta) with the cell is the inhibition of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. We recently demonstrated that cytotoxic amyloid peptides such as A beta and human amylin inhibit cellular MTT reduction by dramatically enhancing MTT formazan exocytosis. We now show the following: (a) Insulin and glucagon, when converted to fibrils with beta-pleated sheet structure, induce MTT formazan exocytosis that is indistinguishable from that induced by A beta. NAC35, an amyloidogenic fragment of alpha-synuclein (or NACP), also induces MTT formazan exocytosis. (b) All protein fibrils with the beta-pleated sheet structure examined are toxic to rat hippocampal neurons. (c) Many sterol sex hormones (e.g., estradiol and progesterone) block amyloid fibril-enhanced MTT formazan exocytosis as well as MTT formazan exocytosis in control cells by acting at a common late step in the exocytic pathway. Steroids fail, however, to protect hippocampal neurons from acute amyloid fibril toxicity. These findings suggest that the ability to enhance MTT formazan exocytosis and to induce neurotoxicity are common biological activities of protein fibrils with beta-pleated sheet structure but that enhanced MTT formazan exocytosis is not sufficient for acute A beta neurotoxicity.
Operating principle verification and scaling benefits of SGLC eNVM

The authors demonstrated and verified the operation of a SGLC eNVM cell using 3D and 2D TCAD simulations. In addition, we have explained the benefits of the SGLC NVM cell as CMOS process design rules shrink. The novel SGLC cell shows a smaller size than 6T SRAM for beyond the 65 nm technology node. The SGLC cell shows ideal characteristics for eNVM, such as a fast program speed, multi-time programmable support, over-erase free features as well as an SRAM comparable cell size without any additional process steps.
Tensile modulus of carbon nanotube/polypropylene composites - A computational study based on experimental characterization

Abstract Micromechanical and computational models significantly over-predict the tensile modulus of composites, as they ignore many experimentally observed factors. Computational models that capture the effect of polymer-filler contact, the presence of carbon nanotube (CNT) agglomerates and the alignment of CNTs with respect to the applied load on the tensile modulus of CNT-reinforced polypropylene (PP) are proposed and discussed in detail in this study. The CNT/PP composites are made by melt mixing and injection molding. The CNT/PP contact area is characterized in terms of width and modulus using Atomic Force Microscope (AFM). The presence, including the size and distribution of CNT agglomerates, is characterized using Scanning Electron Microscope (SEM). The tensile modulus of CNT/PP composites, measured as a function of CNT content according to ASTM D638, is compared to predictions made using numerical methods based on Finite Element Analysis (FEA) within the composite’s elastic regime. The model over-predicts the modulus of the CNT/PP composites by 85% for 5 wt.% CNT/PP composites assuming perfect filler–polymer interfacial contact. When imperfect CNT/PP contact, CNT agglomerates and alignment are accounted for in the model the effective composite modulus predicted is in good agreement with the experimental data. The computational design tools proposed in this study by systematically incorporating experimentally observed characteristics, in combination with the manufacturing method used to make the CNT/PP composites, can lead to composites with engineered properties made by a scalable and cost effective method.
Accounting for Follow-up Bias in Estimation of Human Immunodeficiency Virus Incidence Rates

The objective of this paper is to describe methods for estimating current incidence rates for human immunodeficiency virus (HIV) that account for follow-up bias. Follow-up bias arises when the incidence rate among individuals in a cohort who return for follow-up is different from the incidence rate among those who do not return. The methods are based on the use of early markers of HIV infection such as p24 antigen. The first method, called the cross-sectional method, uses only data collected at an initial base-line visit. The method does not require follow-up data but does require a priori knowledge of the mean duration of the marker (μ). A confidence interval procedure is developed that accounts for uncertainty in μ. The second method combines the base-line data from all individuals together with follow-up data from those individuals who return for follow-up. This method has the distinct advantage of not requiring prior information about μ. Several confidence interval procedures for the incidence rate are compared by simulation. The methods are applied to a study in India to estimate current HIV incidence. These data suggest that the epidemic is growing rapidly in some subpopulations in India.
Postural prioritization defines the interaction between a reaction time task and postural perturbations.

Concurrent demands for postural and cognitive control processes are now known to induce interference, e.g., information processing speed may decrease during postural adjustment. It is less clear whether postural control may, at least in many situations, take precedence over cognitive control (“postural prioritization”). The purpose of this study was to determine if postural dual-task effects are the result of a postural prioritization effect. Twelve young subjects (6 female; 24.1 ± 4.1) performed a discrete choice reaction time (RT) task in combination with a platform perturbation. To assess the effect of postural prioritization on RT and center of pressure (COP) parameters, destabilizing perturbations were randomly interspersed with non-destabilizing perturbations. Furthermore, stimulus order and the time interval of the RT stimulus relative to the platform perturbation were manipulated. COP and RT data obtained in these manipulations were compared to single-task baseline data. The results suggested that, irrespective of the degree of threat to postural stability, postural task processes are prioritized. Furthermore, anticipation of a postural stimulus negatively affects RT. However, once a perturbation commences subsequent RTs are speeded. Postural reactions were unaffected by a concurrent RT task, however. The RT stimulus acted as a cue to initiate biomechanical adaptations for an upcoming perturbation.
Tax evasion as ade facto vote of disapproval of PAC contributions

In this study, it is hypothesized that higher (rising) real PAC election campaign contributions may lead the public to increasingly distrust and resent politicians because of the perceived political influence that these contributions exercise. It is further hypothesized that to express that distrust and resentment, the public may make greater efforts to evade income taxation so as to deny tax revenues to the Treasury and “influence-peddling” politicians. Instrumenatal Variable (IV) estimates in first differences that allow for income tax rates, IRS audit rates, IRS penalty assessments on detected unreported income, and the public's dissatisfaction with government per se, find strong, albeit only preliminary, empirical evidence that tax evasion is an increasing function of real PAC election campaign contributions.
Correlates for mortality in patients presented with acute myocardial infarct complicated by cardiogenic shock

Abstract Objective This study aimed to explore the correlates for mortality in patients treated with both primary percutaneous coronary intervention (PCI) and intra-aortic balloon pump counter-pulsation (IABP). Background Acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) is associated with high mortality rates. Methods From a cohort of patients with AMI, treated with both primary PCI and IABP and who met strict definitions for CS to identify correlates associated with mortality, the study compared patients who died in-hospital to those who survived to discharge. Results A cohort of 93 patients met the inclusion/exclusion criteria. Of them, 66.7% were male, and the average age was 64.96 ± 13.06 years. The overall in-hospital mortality rate for this cohort was 33%. The baseline characteristics were balanced save for older average age and left ventricular ejection fraction in those who died (p = 0.049 and p = 0.014, respectively). Insertion of IABP pre-PCI and cardiac arrest at the catheterization lab were more frequent in those who died (p = 0.027 and p = 0.008, respectively). The insertion of IABP pre-PCI, cardiac arrest at the cath lab, and lower ejection fraction were correlated with in-hospital mortality (ORs 2.68, 5.93, and 0.02, respectively). Conclusions In the era of primary PCI and IABP as standard of care in AMI complicated by CS, patients with low EF, those who necessitate IABP insertion pre-PCI, and those who necessitate cardiopulmonary resuscitation during PCI are at higher risk for in-hospital mortality and should be considered for more robust hemodynamic support devices with an attempt to improve their prognosis.
Pharmacology, in vitro activity, and in vivo efficacy of new antifungal agents

Invasive fungal infections remain significant clinical challenges and are associated with high morbidity and mortality in immunocompromised patients. Despite the availability of new antifungal agents, response rates against many of these infections remain suboptimal. In addition, many of the clinically available agents have limited oral bioavailability, are associated with adverse effects due to similarities between fungal and mammalian cells, or have significant drug-drug interactions. For these reasons, there is great interest in developing new antifungal drugs, including those with novel mechanisms of action. This article reviews the pharmacology, in vitro activity, and in vivo effectiveness of new antifungal agents, including members of new classes with novel mechanisms of action and at various stages of preclinical and clinical development. These agents include the triazole isavuconazole, the echinocandin aminocandin, the histone deacetylase inhibitor MGCD290, and the sordarin derivative FR290581.
Scope of Problem and History of Patient Safety

Creating a safe environment in our incredibly complex health care system requires a major culture change. While it may be frustratingly slow and halting, that change is occurring and beginning to show results. This article addresses the issue of patient safety, discussing its history, and organizations and practices that are helping to make it more of a reality in today's health care environment.
Children's play and the processing of information: An integrative study

Levels of novelty and complexity in two toy puzzles were manipulated to test an arousal‐seeking theory of play. Preschool children played with either a simple or complex toy puzzle; fifteen‐minute sessions of play and task‐oriented behaviors were videotaped and assigned to one of nine behavioral categories. Differences in duration to puzzle solution were found to be a function of complexity level, and of prior exposure with the same or different complexity level of puzzle. With resolution of the task demand, subjects began manipulating various aspects of the testing environment as an alternative to boredom. When little new stimulation could be elicited from the testing apparatus, playful behaviors were initiated. Individual variability was high on the playful behavioral categories but low on categories involving resolution of the puzzle task. This provides support for the view that the typology of play activities is unique to each player and that activity‐based definitions of play are of little explanator...
Intensional Double Glueing, Biextensional Collapse, and the Chu Construction

The superficial similarity between the Chu construction and the Hyland-Tan double glueing construction G has been observed widely. This paper establishes a more formal mathematical relationship between the two. We show that double glueing on relations subsumes the Chu construction on sets: we present a full monoidal embedding of the category chu(Set, K) of biextensional Chu spaces over K into G(Rel^K), and a full monoidal embedding of the category Chu(Set, K) of Chu spaces over K into IG(Rel^K ), where we define IG, the intensional double glueing construction, by substituting multisets for sets in G. We define a biextensional collapse from IG to G which extends the familiar notion on Chu spaces. This yields a new interpretation of the monic specialisation implicit in G as a form of biextensionality.
PTSD is a chronic, fluctuating disorder affecting the mental quality of life in older adults.

Objectives: Examine the longitudinal course of posttraumatic stress disorder (PTSD) in older adults and its influence on mental health quality of life (MHQoL). Design: Evaluation performed at baseline, and 3a nd 6 months postrandomization as part of al ongitudinal trial.Participants and settings: A total of 1,185 participants, with am ean ( � SD) age of 73.53 (� 5.98) years, at seven primary care sites (including five Veterans Affairs clinics), were divided into four groups, namely, no trauma (n ¼ 661), trauma only (n ¼ 319), partial PTSD (n ¼ 114), and PTSD (n ¼ 81), based on reports of trauma and associated PTSD symptoms. Measurements: The prevalence of comorbid depression, anxiety, and alcohol use disorders, assessed using the Diagnostic and Statistical Manual, Fourth Edition, criteria and changes in MHQoL, as assessed by the Short Forme36 mental component score. Results: At baseline, the PTSD group had higher frequencies of comorbid depression and anxiety disorders and worse MHQoL than the other groups. Bothchronic(participantsdiagnosedwithPTSD atallthree assessments)and fluctuating (participants moving to or from one of the other groups) trajectories of course were observed during the follow-up period, which appeared to be separate from that of the comorbid disorders. Even after accounting for those comorbid disorders, PTSD had an independent association with poorer MHQoL at multiple time points, especially in men, whereas trauma without PTSD symptoms (trauma only) had better MHQoL. Conclusions: PTSDhadchronicand fluctuatingcourses,withnegativeeffectsonMHQoL, while partial PTSD might represent a transitional state, underscoring the need to better identifyandtreatPTSDatanyphaseinlaterlife.(AmJGeriatrPsychiatry2014;22:86e97)