cssi/SciSciGPT-SciSciNet huggingface dataset:
In vivo imaging of molecular-genetic targets for cancer therapy

The major factor limiting translation of reporter gene imaging studies to patients is the transduction requirement; target tissue must be transduced with the reporter constructs for reporter gene imaging studies. At least two different reporter constructs will be required in most cases; one will be a “constitutive” reporter that will be used to identify the site, extent and duration of vector delivery, and tissue transduction (the normalizing or denominator term), and one will be an “inducible” reporter that is sensitive to endogenous transcription factors, signaling pathways, or protein-protein interactions, as described above. The initial application of such double-reporter systems in patients will most likely be performed as part of a gene therapy protocol (Jacobs et al., 2001xPositron-emission tomography of vector-mediated gene expression in gene therapy for gliomas. Jacobs, A, Voges, J, Reszka, R, Lercher, M, Gossmann, A, Kracht, L, Kaestle, C, Wagner, R, Wienhard, K, and Heiss, W.D. Lancet. 2001; 358: 727–729Abstract | Full Text | Full Text PDF | PubMed | Scopus (283)See all ReferencesJacobs et al., 2001) or an adoptive therapy protocol where the patients own cells are harvested (e.g., lymphocytes, T cells, or blood-derived progenitor cells) and can be transduced and expanded ex vivo, and then adoptively readministered to the patient. This scenario couples reporter gene imaging with existing adoptive therapies and allows for ex vivo transduction and expansion of harvested cells. For example, adoptive T cell therapy could provide a venue for imaging T cell trafficking, targeting, activation, proliferation, and persistence (Ponomarev et al., 2001xImaging TCR-Dependent NFAT-Mediated T-Cell Activation with Positron Emission Tomography In Vivo. Ponomarev, V, Doubrovin, M, Lyddane, C, Beresten, T, Balatoni, J, Bornman, W, Finn, R, Akhurst, T, Larson, S, Blasberg, R et al. Neoplasia. 2001; 3: 480–488CrossRef | PubMed | Scopus (115)See all References, Koehne et al., 2003xShort and long-term in vivo imaging of targeted migration of HSV-TK transduced human antigen-specific lymphocyets. Koehne, G, Doubrovin, M, Doubrovina, E, Zanzonico, P, Gallardo, H, Ivanova, A, Balatoni, J, Teruya-Feldstein, J, Heller, G, May, C et al. Nat. Biotechnol. 2003; 21: 405–413CrossRef | PubMed | Scopus (158)See all References). This imaging paradigm could address several important questions related to adoptive T cell therapies. For example, is there substantial proliferation of adoptively transferred T cells at the target site or does activation and proliferation occur at other sites (e.g., specific lymphoid organ sites), followed by migration and localization to the target site? This question could potentially be addressed in a quantitative manner by repetitive PET imaging of the double-reporter system described above in the same animal or subject over time.
Teaching the Evolution of the Mind Current Findings, Trends, and Controversies in Evolutionary Psychology

As the burgeoning field of evolutionary psychology continues to gain exposure and acceptance throughout the psychological community, it is important to explain this field clearly and accurately to ...
Fluorimetric determination of pyrene:protein association ratios

Abstract Two fluorimetric methods for determining pyrene:protein association ratios are described. The methods are useful for measuring the uptake by proteins of small, fluorescent molecules with limited aqueous solubility (10 -6 M or less). The association ratios (moles pyrene per mole protein) determined by the two methods were found to be:bovine β-lactoglobulin (0.32, 0.33), human serum albumin (0.44, 0.42), bovine γ-globulin (0.23, 0.20), and human γ-globulin (0.04, 0.00).
Synthesis, structure, and reactivity of β-diketiminate boron(III) complexes

Abstract The chemistry of boron supported by the β-diketiminate ligand, tolylnacnac (tolylnacnacH=2-N-p-tolylamino-4-N-p-tolylimino-2-pentene), has been investigated. (tolylnacnac)Li reacted with one equivalent of BF3·OEt2 to afford (tolylnacnac)BF2 (1) in 46% yield. The structure of compound 1 was solved indicating that the diketiminate ligand is η2-bound to B to form a six-membered heterocycle. While alkylation of compound 1 can be effected with alkyl lithium or Grignard reagents, nucleophilic addition to the diketiminate ligand occurred in the reaction between compound 1 and MeLi to afford [η2-(Me)2C(Ntolyl)CHC(Ntolyl)Me]BMe (2). For Me3SiCH2Li, deprotonation of the diketiminate ligand afforded [η2-CH2C(Ntolyl)CHC(Ntolyl)Me]BCH2SiMe3 (3). Conversely, alkyl Grignard reagents selectively delivered two alkyl groups to the boron center, and several pseudo-tetrahedral (tolylnacnac)BR2 (4a–d; a, R=Me, b, R=nPr, c, R=vinyl, d, R=allyl) complexes have been prepared. The structures of compounds 2, 3, and 4a were solved, and variations in B–N and B–C metrical data for compounds 2 and 4a were correlated to bond order, inductive effects of the co-ligands, and hybridization of the boron center. The reaction between compound 4a and tris(pentafluorophenyl)boron gave [(tolylnacnac)BMe]+[MeB(C6F5)3]− (5). Compound 5 reacted with pyridine to give an adduct, [(tolylnacnac)B(py)Me]+[MeB(C6F5)3]− (6).
Measurement of limiting activity coefficients for aqueous systems by differential ebulliometry

Abstract New data have been determined by differential ebulliometry for limiting activity coefficients of binary systems of water. Results are reported with acetone, N,N-dimethylformamide, ethyl acetate, isopropanol, methanol, nitromethane and tetrahydrofuran over a modest range of temperatures. The results are used to demonstrate the limitations of several current excess GibbS energy expressions in representing both vapour—liquid equilibrium and liqui—liquid equilibrium data from limiting activity coefficient measurements.
The diagnosis and differential diagnosis of cutaneous sarcoidosis.

Abstract Sarcoidosis and the other granulomatous diseases, such as syphilis, are recognized as capable of many clinical and pathologic presentations. The capacity of the clinician to make a diagnosis depends upon the basic knowledge of the protean forms of the granulomatous diseases. Good examples of such diseases have been the recent cases of reported syphilis that presented as clinical and histopathologic sarcoidosis. 2–4 Recognition that systemic sarcoidosis may involve the skin secondarily and that no specific laboratory or other tests exist to make a specific confirmation of the diagnosis limits the capacity of the physician: all of the major granulomatous diseases (eg. syphilis, tuberculosis, leprosy, and the deep fungus infections) involve multiple organs with a granulomatous reaction. The diagnosis of sarcoidosis must be approached by eliminating specific infectious causes. Sarcoid-like changes in the skin with microscopic epithelioid granulomas are not sufficient for the diagnosis of systemic sarcoidosis. We will discuss both the clinical and histologic appearances of sarcoidosis. We also will outline the biochemical and immunologic abnormalities as they apply to the diagnosis of cutaneous sarcoidosis. A basic clinical skepticism concerning the diagnosis of sarcoidosis is always appropriate.
Case report 562

A propos d'un homme de 56 ans atteint d'un processus expansif de la fosse temporale droite. L'histoire clinique evolue depuis 2 ans. Il s'agit de douleurs episodiques progressivement croissantes, d'une surdite progressive et de vertiges. Une paresie de l'hemi-face droite et une perte de poids sont notees depuis 6 mois. Description des signes biologiques et radiologiques (tomodensitometrie, arteriographie carotidienne) et histologiques d'un granulome a cellules geantes de l'os temporal
Methodology in the radiolysis of biochemical compounds with cyclotron beams at low flux densities.

Abstract A modification of the standard beam-optics of the LBL 88-Inch Cyclotron now makes it practicable to use cyclotron radiations in the detailed study of the effects of linear energy transfer (LET) in the radiation chemistry of organic compounds in the solid state. Dosages and dose-rates are comparable to those employed in conventional γ-ray studies. The modification involves passing the focused beam through a pair of “beam-sweeping” electromagnets so that a circular target area up to 10 cm in diameter can be uniformly irradiated with beams in the nanoamp range. Yield data are given for the radiolysis of the Fricke dosimeter with beams of H+, H+2, Be+4, C+6 and Ne+10 at ∼10 MeV per nucleon. Preliminary data on the effects of LET in the radiolysis of solid glycine are reported.
Varieties of Analytic Pragmatism

In his Locke Lectures Brandom proposes to extend what he calls the project of analysis to encompass various relationships between meaning and use. As the traditional project of analysis sought to clarify various logical relations between vocabularies so Brandom’s extended project seeks to clarify various pragmatically mediated semantic relations between vocabularies. The point of the exercise in both cases is to achieve what Brandom thinks of as algebraic understanding. Because the pragmatist critique of the traditional project of analysis was precisely to deny that such understanding is appropriate to the case of natural language, the very idea of an analytic pragmatism is called into question by that critique. My aim is to clarify the prospects for Brandom’s project, or at least something in the vicinity of that project, through a comparison of it with what I will suggest we can think of as Kant’s analytic pragmatism as developed by Peirce.
Progeny analysis of glyphosate selected transgenic soybeans derived from Agrobacterium-mediated transformation.

Glyphosate selection has been implemented into an Agrobacterium-mediated transformation system for soybean [Glycine max (L.) Merr.]. Cotyledonary explants were excised from 5-d-old seedlings and inoculated with an Agrobacterium strain carrying the CP4 gene, which confers tolerance to the herbicide Roundup, and the β-glucuronidase (GUS) gene. Explants were selected on sublethal levels of glyphosate during shoot initiation and elongation. Glyphosate tolerant shoots were identifiable after 8 to 12 wk of selection. Coexpression of GUS occurred in approximately 80% of the primary transformants (R θ ). The R θ plants were fully fertile, with no apparent phenotypic abnormalities. Progeny analysis from 81 independent transgenic soybean events derived from glyphosate selection demonstrated that the majority of the transformants transmitted the transgenes as a single functional locus.
Lidocaine toxicity following subcutaneous administration

A case of a 2-year-old girl who survived grand mal seizures secondary to toxicity from massive subcutaneous administration of lidocaine is presented. She was treated with intravenous diazepam and was intubated. After 24 hours of observation she was discharged, and there have been no sequelae or recurrence of seizure activity during ten months follow up. Central nervous system, cardiac, and hematologic effects of lidocaine toxicity are discussed. Drug interactions that may potentiate lidocaine toxicity are listed.
Evaluation of the effect of CAD on observers' performance in detection of polyps in CT colonography

Abstract We conducted an observer study to evaluate the effect of computer-aided detection (CAD) on human readers' performance in the detection of polyps in CT colonography (CTC). Twenty data sets including 11 polyps were retrospectively selected from our CTC database. A sequential test was used, in which four observers interpreted CTC examinations by use of our colon CAD workstation in two sequential sessions: one without CAD and the other with CAD. At each session, the observers rated the confidence level regarding whether the case was abnormal, i.e., at least one polyp>5 mm was present in the colon. Receiver operating characteristic (ROC) analysis was performed based on the confidence levels for the abnormality of the CTC data sets, and the area under the ROC curve (Az) was calculated as a measure of the observers' detection performance. The results showed that, for all of the observers, the detection performance increased with use of CAD. The average Az values without and with CAD were 0.70 and 0.85, respectively. A two-tailed t -test showed that the difference between these Az values was statistically significant ( p =0.025). The result indicates that CAD can be a useful tool for improving human readers' performance in the detection of polyps in CTC.
Analysis and design of output feedback control systems with actuator saturation

A dynamic output feedback controller design approach based on cone complementary linearisation procedure is proposed for linear time-invariant (LTI) systems with actuator saturation. First, the estimation of the domain of attraction is given. Then, a design method to find a larger estimation of the domain of attraction is presented. In the process of design, nonconvex conditions are obtained, so a cone complementary linearisation procedure is exploited to solve the nonconvex feasibility problem. Two examples are given to illustrate the efficiency of the design method.
Nondestructive volumetric imaging of tissue microstructure with benchtop x-ray phase-contrast tomography and critical point drying

The in vitro investigation of many optically opaque biological microstructures requires 3D analysis at high resolution over a large field of view. We demonstrate a new nondestructive volumetric imaging technique that eliminates the structural and computational limitations of conventional 2D optical microscopy by combining x-ray phase-contrast tomography with critical point drying sample preparation. We experimentally demonstrate the enhancement of small features afforded by phase-contrast imaging and show the contrast improvement afforded by the drying of a hydrated specimen. We further demonstrate the biological application of this technique by imaging the microstructure of the accommodative apparatus in a primate eye using a benchtop phase-contrast tomography system.
Comparing optical & OTN switching architectures in next-gen 100Gb/s networks

Bandwidth efficiency for 100Gb/s WDM and switch architectures are compared in a North American long-haul network. Results show that OTN grooming utilizes fewest WDM wavelengths, and integrated WDM/switch architecture utilizes fewest client service interfaces.
A study on the localization of contractile proteins in the muscle of the horseshoe crab (Limulus polyphemus).

Abstract When the glycerinated, blended and washed fibrils of the cross-striated skeletal muscle of Limulus polyphemus are extracted with solutions of high KCl concentrations containing pyrophosphate or ATP the A bands are removed. The protein removed from the fibrils (approximately 38% from the washed or 12% from the glycerinated unwashed fibril) consists predominately of actomyosin. This is in contrast to the results of similar treatment of rabbit fibrils in which myosin with traces of actin is extracted when the A bands are removed.
Econometric Estimation of Foresight: Tax Policy and Investment in the United States

We develop a method for measuring the foresight agents have. We first dichotomize an agent's information at current date t into knowledge up to date t 1 f and expectations after t 1 f. We then form a residual-based test statistic that allows us to compare prediction errors for econometric models based on different values of f. We illustrate the method, examining investment around tax reforms to measure the foresight firms have about tax policy. In this illustration, current investment appears to reflect currently available information but little foresight other than foresight of enacted policy changes.
What the Nigerien coup d'état means to the world

Mohammedou Tandia is considered Niger's first two-term democratically elected leader (1999–2009), though some Nigeriens are ready to place him on trial for treason (Clottey 2010). The reasons for t...
Effects of Corticosterone, Dexamethasone and Surgical Isolation of the Medial Basal Hypothalamus on Rapid Feedback Control of Stress-Induced Corticotropin Secretion in Female Rats1

These studies were designed to determine whether physiological transients in plasma corticosterone levels exert a rapid or rate-sensitive feedback inhibition of the pituitary-adrenal response to ether stress, to compare effects of corticosterone and dexamethasone (Dex) on such control and to determine whether brain structures located outside of the medial basal hypothalamus (MBH) are essential for rapid feedback. Ten-minute infusions of corticosterone ip into pentobarbital-anesthetized rats at rates of 4 or 8 μg/min produced elevations in plasma corticosterone levels which were physiological in time course and amplitude. To study the effect of such infusions on adrenocortical responses to stress, rats were exposed to ether for 2 min during or at various times after infusion; blood samples were obtained 15 min after stress. Whereas infusion of vehicle was compatible with corticosterone responses to stress at all times tested, corticosterone infused at 4 μg/min blocked the response to ether if this stress w...
Effect of vitamin E on the induction and evolution of enzyme-altered foci in the liver of rats treated with diethylnitrosamine

The effects of dietary vitamin E (VE) on the steps of hepatocarcinogenesis, the induction and growth of gamma-glutamyltranspeptidase (GGT)-positive foci and their evolution into persistent nodules, were analyzed in the liver of rats treated with diethylnitrosamine (DEN). The induction of GGT-positive foci was inhibited by a diet containing 0.36-1.5% VE given after initiation with 200 mg/kg body weight (b.w.) DEN for 6 weeks with partial hepatectomy (PH) on week 3. The numbers and areas of GGT-positive foci were enhanced by diets containing 0.36 and 0.72% VE, given for 1 week after initiation with 10 mg/kg b.w. DEN and PH, followed by selection by 0.02% 2-acetylaminofluorene (AAF) and carbon tetrachloride (CCl4), but these were not enhanced by a diet containing 1.5% VE. Remodeling of hyperplastic nodules was not affected by the diet containing 0.72% VE given after initiation with DEN and selection for 12 weeks. The staining characteristics of GGT were different between remodeling and persistent nodules, except for those of the glutathione-S-transferase placental form (GST-P). The results obtained suggest that VE could prevent the very early events during hepatocarcinogenesis, the induction of phenotypically altered foci, but could no longer affect the later stages, the evolution of foci into persistent nodules.
The fate of organic matter during planetary accretion: Preliminary studies of the organic chemistry of experimentally shocked murchison meteorite

It is possible that Earth's biologic precursors were delivered by late-impacting asteroids or comets, and it is possible that these objects were a source of Earth's volatile inventory. To understand the behavior of organic matter in carbonaceous meteorites during hypervelocity impact (1–2 km s−1), three samples of the Murchison (CM2) carbonaceous chondrite were shocked to 19, 20 and 36 GPa and analyzed by very sensitive thermal-desorption photoionization mass spectrometry (SALI). Thermal-desorption (25–800 °C) SALI mass spectra of unshocked Murchison reveal indigenous aliphatic, aromatic, sulfur and organosulfur compounds. Samples shocked to ≈20 GPa exhibit little or no loss of organic matter relative to the unshocked material. This is consistent with the earlier work of Tyburczyet al. (1986) which showed that incipient devolatilization of Murchison occurs at peak shock pressures near 20 GPa. The small amount of organic matter lost appears to have occurred by volatilization of elemental sulfur, amines and aliphatic compounds. In the sample shocked to 36 GPa, approximately 70% of the organic matter was volatilized as a result of impact. The residual organic matter desorbed at somewhat higher temperatures and displayed a different chemical signature. In particular, the shocked material has a lower alkene/alkane ratio than that of the starting material. The preliminary data suggest that it is unlikely that the indigenous organic matter in carbonaceous chondrite-like planetesimals could have survived impact on the Earth in the later stages of Earth's accretion. However, chemical reactions that produce organic compounds with greater thermal stabilities may occur during impact or subsequent to impact by condensation of the impact-produced vapor plume.
Using Lorenz Curves to Characterise Urban Elderly Populations

This study measures urban elderly distributions using Lorenz curves and Gini coefficients estimated from 1980 Census data. The results suggest ways that such summary measures can be used to examine...
110. A Novel Teen Community Health Advisor Program to Reduce Sexual Risk Behaviors

Purpose: Alabama high school students are more sexually active, initiate sex at an earlier age, and are less likely to use condoms when compared to U.S. adolescents. Additionally only 25% of Alabama’s adolescent females have completed the Human Papillomavirus (HPV) Vaccine series; Healthy People 2020 strives for 80% vaccine coverage. In an effort to address these behaviors, a program was developed and implemented in an urban high school in Birmingham, Alabama. The goal of the program was to reduce high-risk health behaviors including those associated with HPV acquisition and increaseHPV vaccination rates among adolescents by using peer health educators, known as Teen Community Health Advisors (CHAs). Methods: Fifteen CHAs participated in the program to increase knowledge of sexually transmitted diseases and reduce risky behaviors. The training curriculum utilized the Reducing the Risk (RTR) curriculum for basic sexual health education and an investigatordeveloped HPV curriculum. Topics from the curriculum included abstinence, refusal skills, delay tactics, practicing safer sex, and information onHPV transmission, disease, and prevention. The CHA training program consisted of 2.5 days of training and 3 booster sessions over an 8week period. At the end of each session, CHAs completed an evaluation form which assessed knowledge and suggestions for session changes/additions. During the process evaluation, three coders independently identified knowledge themes, and discussed each theme until agreement was reached. Results: Predominant knowledge themes identified by participants were refusal techniques (45%), delay tactics (25%), sexually transmitted disease information (22.5%), relationship advice (5%); birth control methods (32%), sexually transmitted disease (19%), warning signs of sex (15%), pregnancy information (11%), condoms (11%), health care access (4%), HPV/cervical cancer (35%), social norms (22%), condoms (17%). Suggestions for improvement included the addition of more role plays (50%) during the training sessions. Sixtysix percent of students expressed that the sessions were beneficial/ enjoyable. Conclusions: The teen community health advisor model was well received in this pilot program and may be a promising tool for reducing risky behaviors among peer adolescents. Sources of Support:University of North Carolina Gillings School of Public Health, Cervical Cancer Free Initiative.
Feasibility and acceptability of interventions to delay gun access in VA mental health settings.

Abstract Objectives The majority of VA patient suicides are completed with firearms. Interventions that delay patients' gun access during high-risk periods may reduce suicide, but may not be acceptable to VA stakeholders or may be challenging to implement. Using qualitative methods, stakeholders' perceptions about gun safety and interventions to delay gun access during high-risk periods were explored. Methods Ten focus groups and four individual interviews were conducted with key stakeholders, including VA mental health patients, mental health clinicians, family members and VA facility leaders ( N =60). Transcripts were consensus-coded by two independent coders, and structured summaries were developed and reviewed using a consensus process. Results All stakeholder groups indicated that VA health system providers had a role in increasing patient safety and emphasized the need for providers to address gun access with their at-risk patients. However, VA mental health patients and clinicians reported limited discussion regarding gun access in VA mental health settings during routine care. Most, although not all, patients and clinicians indicated that routine screening for gun access was acceptable, with several noting that it was more acceptable for mental health patients. Most participants suggested that family and friends be involved in reducing gun access, but expressed concerns about potential family member safety. Participants generally found distribution of trigger locks acceptable, but were skeptical about its effectiveness. Involving Veteran Service Organizations or other individuals in temporarily holding guns during high-risk periods was acceptable to many participants but only with numerous caveats. Conclusions Patients, clinicians and family members consider the VA health system to have a legitimate role in addressing gun safety. Several measures to delay gun access during high-risk periods for suicide were seen as acceptable and feasible if implemented thoughtfully.
Returns to Education: Evidence from UK Twins: Comment

Twin studies are increasingly being used in economics to identify the causal effect of education on earnings. In an article published in the December 2003 American Economic Review, Dorothe Bonjour et al. used a dataset based on a sample of 428 female monozygotic twins from the Twins Research Unit, St. Thomas' Hospital to provide further evidence on the returns to education for the United Kingdom. Among other conclusions, the within-twin estimated return to one year of education was 7.7 percent and statistically significant at the 5 percent level. This comment illustrates that the point estimate conclusion is driven by one twin pair, which is an outlier in the dataset. More specifically, this twin pair has an extremely large differ ence of £94.18 in their hourly wage with only a difference of two years of education. In comparison, the average wage differential for twins with a difference of two years of education is £7.74.' If one eliminates this twin pair, then the estimated return to education is 5.1 percent and statistically significant at the 10 percent level only. Further estimation using quantile regressions does however suggest that Bonjour et al.'s main conclusion of an estimated rate of return of 7.7 percent is robust to outly ing twin pairs identified in this comment. The dataset used by Bonjour et al. was obtained from the AER website.2 Figure la plots the within-twin differences in education against within-twin differences in log hourly wages. This is a replication of Figure 1 in Bonjour et al.. Based on Figure la Bonjour et al. point out that there is a cluster around zero since 55 percent of twin pairs have the same years of education. The presence of outliers is, at first, not fully obvious. As an alternative perspective, Figure lb plots the absolute differences in twins' education and hourly wages. Given the difference in education, most of the twin pairs have relatively small differences in wages. However, it is evident from Figure lb that there are four outliers, which are labeled on both figures. Twin pairs 2 and 3 have no difference in education, thus they do not contribute to the identifica
New validations of PERT times

This paper defends the classical PERT formulas for computing the mean and variance of the random activity time. We show three new validations for them by examining the kurtosis of the beta distribution employed in PERT.
Natural strain variation and antibody neutralization of dengue serotype 3 viruses.

Dengue viruses (DENVs) are emerging, mosquito-borne flaviviruses which cause dengue fever and dengue hemorrhagic fever. The DENV complex consists of 4 serotypes designated DENV1-DENV4. Following natural infection with DENV, individuals develop serotype specific, neutralizing antibody responses. Monoclonal antibodies (MAbs) have been used to map neutralizing epitopes on dengue and other flaviviruses. Most serotype-specific, neutralizing MAbs bind to the lateral ridge of domain III of E protein (EDIII). It has been widely assumed that the EDIII lateral ridge epitope is conserved within each DENV serotype and a good target for vaccines. Using phylogenetic methods, we compared the amino acid sequence of 175 E proteins representing the different genotypes of DENV3 and identified a panel of surface exposed amino acids, including residues in EDIII, that are highly variant across the four DENV3 genotypes. The variable amino acids include six residues at the lateral ridge of EDIII. We used a panel of DENV3 mouse MAbs to assess the functional significance of naturally occurring amino acid variation. From the panel of antibodies, we identified three neutralizing MAbs that bound to EDIII of DENV3. Recombinant proteins and naturally occurring variant viruses were used to map the binding sites of the three MAbs. The three MAbs bound to overlapping but distinct epitopes on EDIII. Our empirical studies clearly demonstrate that the antibody binding and neutralization capacity of two MAbs was strongly influenced by naturally occurring mutations in DENV3. Our data demonstrate that the lateral ridge “type specific” epitope is not conserved between strains of DENV3. This variability should be considered when designing and evaluating DENV vaccines, especially those targeting EDIII.
Scaled measurement of geographic and social speech data

One of the principle signs that speech is a complex system is the nonlinear arrangement of frequencies of variants in linguistic survey data. When the counts are charted by frequency, they form an asymptotic hyperbolic curve (A-curve) at every scale of analysis. The shape of the curve is sensitive to sample size: a small sample is unlikely to show an A-curve. So, too, categorization: too large a number of categories makes the data appear linear because of the small number of tokens in each category, while allowing too few categories, such as the two data points from binary categories, also gives us a line, not a curve. The A-curve can only be observed when the number of categories into which the data are sorted lies between these two extremes. Common practice in dialectology and sociolinguistics has been to establish a small number of possible categories such as phonemes for pronunciation, or to notice only the few most frequently occurring variants and to ignore the rest. Such methods cannot address the underlying complexity of the data. In this essay, we discuss the Gini coefficient, used in economics, as a means to measure optimal nonlinearity. In an experiment where pronunciation data from survey research on the American English vowel system are analyzed in various subsamples, we demonstrate that A-curves do exist in the data in all cases, and we establish parameters for the interaction of sample size and number of categories in the design of valid and reliable experiments.
Protein-carbohydrate interaction I. The interaction of polysaccharides with concanavalin A

Abstract The precipitin reaction between concanavalin A, a globulin isolated from jackbean meal, and certain polysaccharides has been examined. Using a turbidimetric assay and a partially purified concanavalin A preparation, it has been shown that only branched polysaccharides possessing α- d -glucopyranosyl or α- d -mannopyranosyl units will interact with the protein to form a precipitate. The extent of precipitate formation is dependent on the concentration of both concanavalin A and polysaccharide and the reaction appears to be analogous to an antibody-antigen system. The frequency of branching of the polysaccharide molecule plays an important role in the extent of interaction with concanavalin A. Dextrans may be classified according to their extent of reaction with the protein.
Electronic structure of γ-FeSi2: angle resolved valence band photoemission and Si 2p photoemission

Abstract We have investigated the electronic properties of γ-FeSi 2 thin films using angle resolved valence band photoemission and Si2p core level photoemission. We find two features in the valence band data which are not present in the calculated density of states (DOS). One of these has a constant final state energy and we identify it as being due to a final state effect. Another feature, found near —1.8 eV binding energy, is located in an energy gap of the bulk DOS and is identified as a surface state. We have measured the energy dispersion of this surface state and of two bulk-like states. The surface state has a total energy shift of 0.4 eV and exhibits band extrema near positions of the (2×2) reconstructed surface Brillouin zone boundaries. High resolution Si 2p photoemission spectra on samples of varying thickness show that the Si 2p binding energy is higher in the suicide than in bulk silicon by 0.49 eV. We find no evidence of silicon adatoms in our Si 2p photoemission results.
Free Energy of the Hydrophobic Interaction from Molecular Dynamics Simulations: The Effects of Solute and Solvent Polarizability

Molecular dynamics simulations are used to calculate the free energy of methane association in water, using the polarizable fluctuating charge model that treats the charges on atomic sites as dynamical variables. Compared with previous studies using nonpolarizable potentials, the inclusion of polarizability leads only to small differences in the methane pair potential of mean force. This is in contradistinction to two previous studies using other polarizable models, which do not agree with the nonpolarizable results or with each other. The potential of mean force is calculated at three different temperatures (283, 298, and 313 K) from which the temperature dependence and also the entropic part of the free energy is examined. It is found that the tendency for methane molecules to aggregate increases with increasing temperature and that aggregation is stablized by entropy.
Heart Rate Variability Predicts Trauma Patient Outcome as Early as 12 h: Implications for Military and Civilian Triage

Background Our previous work demonstrated dense physiological data capture in the intensive care unit (ICU), defined a new vital sign Cardiac Volatility Related Dysfunction (CVRD) reflecting reduced heart rate variability, and demonstrated CVRD predicts death during the hospital stay adjusting for age and injury severity score (ISS). We hypothesized a more precise definition of variability in integer heart rate improves predictive power earlier in ICU stay, without adjusting for covariates. Methods Approximately 120 million integer heart rate (HR) data points were prospectively collected and archived from 1316 trauma ICU patients, linked to outcome data, and de-identified. HR standard deviation was computed in each 5-min interval (HR SD5 ). HR SD5 logistic regression identified ranges predictive of death. The study group was randomly divided. Integer heart rate variability (% time HR SD5 in predictive distribution ranges) models were developed on the first set (N = 658) at 1, 2, 4, 6, 8, 12, and 24 h after ICU admission, and validated on the second set (N = 658). Results HR SD5 is bimodal, predicts death at low (0.1–0.9 bpm) and survival at high (1.8–2.6 bpm) ranges. HRV predicts death as early as 12 h (ROC = 0.67). HRV in a moving 1-h window is a simple graphic display technique. Conclusions Dense physiological data capture allows calculation of HRV, which: 1) Independently predicts hospital death in trauma patients at 12 h; 2) Shows early differences by mortality in groups of patients when viewed in a moving window; and 3) May have implications for military and civilian triage.
Perioperative treatment with aspirin or clonidine and risk of acute kidney injury.

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Gill reported receiving an investigator-initiated research grant from Astellas Canada and serving as a consultant for Astellas Canada. Dr Knoll reported receiving an investigator-initiated research grant from Astellas Canada and Pfizer Canada. Dr Humar reported receiving research grant support from Astellas Canada, Novartis Canada, and Roche Canada.
A numerical study of a marine subtropical stratus cloud layer and its stability

A model for numerical simulation of stratus cloud layers is constructed by combining a second-order closure, turbulent transfer model with a thermal radiative transfer model. The turbulent transfer model allows water vapor saturation. The combined turbulence-radiation model is applied to both a horizontally uniform one-dimensional case and a horizontally nonuniform two-dimensional case. In the latter, the dynamics of mesoscale circulations are also incorporated. Results of the two-dimensional simulation show that the layer cloud instability occurs where the sea surface temperature is high and the large-scale subsidence is weak. The simulated instability is analyzed in view of an instability criterion, the eddy kinetic energy budget, and evaporative cooling near the cloud top.
Short-term voluntary overfeeding disrupts brain insulin control of adipose tissue lipolysis

Insulin controls fatty acid (FA) release from white adipose tissue (WAT) through direct effects on adipocytes and indirectly through hypothalamic signaling by reducing sympathetic nervous system outflow to WAT. Uncontrolled FA release from WAT promotes lipotoxicity, which is characterized by inflammation and insulin resistance that leads to and worsens type 2 diabetes. Here we tested whether early diet-induced insulin resistance impairs the ability of hypothalamic insulin to regulate WAT lipolysis and thus contributes to adipose tissue dysfunction. To this end we fed male Sprague-Dawley rats a 10% lard diet (high fat diet (HFD)) for 3 consecutive days, which is known to induce systemic insulin resistance. Rats were studied by euglycemic pancreatic clamps and concomitant infusion of either insulin or vehicle into the mediobasal hypothalamus. Short term HFD feeding led to a 37% increase in caloric intake and elevated base-line free FAs and insulin levels compared with rats fed regular chow. Overfeeding did not impair insulin signaling in WAT, but it abolished the ability of mediobasal hypothalamus insulin to suppress WAT lipolysis and hepatic glucose production as assessed by glycerol and glucose flux. HFD feeding also increased hypothalamic levels of the endocannabinoid 2-arachidonoylglycerol after only 3 days. In summary, overfeeding impairs hypothalamic insulin action, which may contribute to unrestrained lipolysis seen in human obesity and type 2 diabetes.
Economic model predictive control using Lyapunov techniques: Handling asynchronous, delayed measurements and distributed implementation

This work focuses on economic model predictive control of nonlinear systems. First, an economic model predictive control algorithm that efficiently handles asynchronous and delayed measurements is presented and its application to a chemical process example is demonstrated. This algorithm uses suitable Lyapunov-based constraints to ensure closed-loop stability for a well-defined set of initial conditions. Second, a distributed economic model predictive control architecture for nonlinear systems is presented. In this architecture, the distributed controllers communicate in a sequential fashion, optimize their inputs through maximizing a plant-wide (global) economic objective function and guarantee practical stability of the closed-loop system.
Wilms' tumor suppressor (WT1) is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer's disease.

Wilms’ tumor suppressor (WT1), a 52- to 54-kda transcription factor, is the gene product of Wilms’ tumor 1 (wt1), one of at least three genes involved in the development of a pediatric kidney cancer. Expression patterns of WT1 indicate that it is not restricted to the kidney but may play a role in the development and homeostasis of other tissues as well. WT1 has been implicated in various cellular processes including proliferation, differentiation, and apoptosis. High levels of WT1 induce apoptosis independent of p53, whereas low levels of WT1 inhibit apoptosis. Because apoptosis has been suggested to play a role in neurodegeneration in Alzheimer’s disease (AD), immunohistochemistry of WT1 and paired helical filament (PHF) in serial sections was carried out. Immunohistochemical localization of WT1 and PHF showed the presence of WT1 in approximately 42% of PHF-positive neurofibrillary tangle containing-neurons. Laser confocal microscopy of hippocampal neuron cultures undergoing apoptosis induced by amyloid beta peptide (Aβ) or staurosporine demonstrated significant time-dependent elevations of WT1 correlating with increased levels of apoptosis. Blockade of WT1 transcription by antisense oligonucleotide reduced WT1 expression and prevented neuronal apoptosis in both Aβ- and staurosporine-treated cultures. Together, these data suggest a role for WT1 in the neurodegeneration observed in AD brain.
Suicide risk factors in children and adolescents with bipolar disorder

Suicidal behavior in children and adolescents with bipolar disorder is a major public health problem that remains understudied. Most research on suicidal behavior in bipolar disorder has been conducted in older adolescents and adults and is limited by retrospective design. Although preliminary research suggests that the early onset of bipolar disorder is associated with increased suicide risk, few studies have prospectively examined the effects of prior suicidal behavior, clinical course, comorbid psychiatric disorders, familial suicidality, and psychosocial factors on suicidal behavior in bipolar youths. More systematic research is needed to better understand suicidal behavior in bipolar children and adolescents. Increased knowledge of the risk factors that contribute to suicidal behavior should lead to better prevention and treatment.
Quantum Chemistry Comes of Age

On December 10, 1998, the 102nd anniversary of Alfred Nobel’s death, in Stockholm’s Konserthus (Concert Hall), Sweden’s King Carl XVI Gustav awarded one half of the 1998 Nobel Prize in Chemistry (3,800,000 kronor, about $489,000) to Professor John A. Pople, 73, of Northwestern University, Evanston, Illinois “for his development of computational methods in quantum chemistry.”The remaining half of the prize, the ne plus ultra of chemistry, was awarded to Professor Walter Kohn, 75, of the University of California, Santa Barbara “for his development of the density-functional theory” [1–9]. Because of health problems in his family, Kohn was unable to attend the ceremony but presented his Nobel lecture in Stockholm on January 28, 1999. According to the Royal Swedish Academy of Sciences: “The laureates have each made pioneering contributions in developing methods that can be used for theoretical studies of the properties of molecules and the chemical processes in which they are involved” [7].
A 228 $\mu$ W 750 MHz BPSK Demodulator Based on Injection Locking

An ultra-low-power BPSK demodulator based on injection locked oscillators (ILOs) is introduced in this paper. Two second harmonic ILOs are employed to convert BPSK signals to ASK signals, which are then demodulated by an envelope detector to baseband. For sub-GHz applications, the ILOs are implemented using ring oscillators to allow compact chip area and ultra-low power dissipation. Bit error rate (BER) analysis of this demodulator indicates erroneous polarity flipping of demodulated bits due to phase noise of ILO. The prototype chip is fabricated in a 65 nm CMOS technology that consumes 228 μW of power and occupies 0.014 mm2 of die area. Measurement results reveal the demodulation of 750 MHz 5 Mb/S differential BPSK signal with sensitivity of -43 dBm. Theoretical BER analysis has been verified with erroneous flipping observed in the measurement and its probability close to the prediction.
Complex Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus Isolates From Children With Cystic Fibrosis in the Era of Epidemic Community-Associated Methicillin-Resistant S aureus

Background Limited data exist about the molecular types of methicillin-resistant Staphylococcus aureus (MRSA) strains found in children with cystic fibrosis (CF). We sought to characterize MRSA strains from these patients and compare them with MRSA strains from non-CF pediatric patients. Methods All MRSA isolates were collected prospectively at Children's Medical Center in Dallas, TX, and the University of Chicago Comer Children's Hospital in 2004 to 2005. All CF MRSA isolates underwent susceptibility testing, multilocus sequence typing, Panton-Valentine leukocidin gene detection ( pvl+ ), and staphylococcal chromosome cassette mec (SCC mec ) typing. Results A total of 22 of 34 MRSA isolates (64.7%) from patients with CF belonged to clonal complex (CC) 5 and contained SCC mec II, so-called health-care associated MRSA (HA-MRSA) strains. Nine of 34 MRSA strains (26.5%) were CC 8, and contained SCC mec IV, so-called community-associated MRSA (CA-MRSA) strains. The CA-MRSA strains tended to be isolated from newly colonized CF patients. In contrast, CC8 isolates predominated among the non-CF patients (294 of 331 patients; 88.8%). MRSA isolates from children with CF were more likely to be resistant to clindamycin (65% vs 19%, respectively) and ciprofloxacin (62% vs 17%, respectively) compared with strains from non-CF patients (p pvl+ isolate recovery from children with CF undergoing a surveillance culture (7 of 23 children) compared with those with pulmonary exacerbation (3 of 11 children; p=1.0). Conclusions Both CA-MRSA (CC8) isolates and HA-MRSA (CC5) isolates populate the respiratory tracts of children with CF. HA-MRSA isolates predominated, but CA-MRSA strains predominated among CF patients with newly acquired MRSA strains and among the non-CF patients. The presence of CA-MRSA strains in children with CF was not associated with exacerbation or necrotizing pneumonia.
Realistic worst-case SPICE file extraction using BSIM3

In this paper, a methodology for generating worst-case SPICE files is presented. This methodology is based upon the identification and evaluation of circuit building blocks within a design. Correlations between these block are determined for a specific circuit variable. The results show there is a high degree of correlation between NAND, NOR, inverter logic gates and NAND gates implemented in Complementary Pass Transistor Logic (CPL) with regards to speed and power dissipation. A method of resolving multiple SPICE files is also presented which produces a realistic prediction of circuit performance.
Incidence of exudative age-related macular degeneration among elderly americans

Abstract Purpose To estimate the 3-year incidence of exudative age-related macular degeneration (AMD) and its treatment by laser photocoagulation in elderly Americans. Design Population-based cohort study using insurance claims data. Participants A random 5% sample of Medicare beneficiaries, age 65 and older. Methods Incidence of exudative AMD and of laser photocoagulation for this condition was assessed based on four categories of ascertainment criteria that included procedure and diagnosis codes associated with exudative AMD, choroidal neovascularization, and its treatment. Main outcome measures Incidence of AMD and of associated laser photocoagulation. Results Overall, the 3-year incidence of exudative AMD is estimated to be between 9.4 per 1000 and 11.4 per 1000 Americans age 65 and older (depending on ascertainment criteria), based on those diagnosed and treated by ophthalmologists for the condition. These estimates bracket the measured incidence of exudative AMD in the Beaver Dam Eye Study and lie within its 95% confidence interval. The 3-year incidence of exudative AMD with attendant laser photocoagulation was 2.3 per 1000. Women were found to have a slightly higher incidence of AMD than men using all ascertainment criteria ( P P Conclusions The reported incidence of exudative AMD identified in the population of Medicare beneficiaries suggests that measurements on incidence for this condition derived from the Beaver Dam Eye Study can be generalized to the U.S. population.