cssi/SciSciGPT-SciSciNet huggingface dataset:
Unimolecular beacons for the detection of DNA-binding proteins.

A new methodology for detecting sequence-specific DNA-binding proteins has been recently developed (Heyduk, T.; Heyduk, E. Nat. Biotechnol. 2002, 20, 171). The core feature of this methodology is protein-dependent association of two fluorochrome-labeled DNA fragments, which allows generation of a fluorescence signal reporting the presence of the target protein. Previous kinetic experiments identified the association of the two DNA fragments as the rate-limiting step of the assay. Here we report on a variant of the assay, in which components of the assayfluorescent DNA fragmentswere covalently tethered by a non-DNA linker with the goal of increasing the rate of association of the two fragments. We investigated the effect of the tether on the performance of the assay under a variety of conditions using a model DNA-binding protein. Quantitative titrations and rapid kinetic stopped-flow experiments were conducted to validate the molecular model that describes the two linked equilibria: oscillation of the tet...
The ionization potentials of Agn and Aun and binding energies of Agn, Aun, Agn+ and Aun+ (n = 1–4)

Abstract The ionization potentials and binding energies of gold and silver clusters and their positive ions containing up to four atoms are investigated using a complete active space MCSCF followed by multi-reference singles + doubles CI which included up to 1.9 million configurations. The ionization potentials for both Au n and Ag n as a function of cluster size n exhibit an interesting “saw-tooth” behavior. The total binding energies of both the clusters and ions as a function of size reveal that the tetramers of gold and silver exhibit unusual stabilities. The gold clusters in general have larger AEs and IPs in comparison to silver clusters due to relativistic effects.
Can the ream and run procedure improve glenohumeral relationships and function for shoulders with the arthritic triad

Background The arthritic triad of glenoid biconcavity, glenoid retroversion, and posterior displacement of the humeral head on the glenoid is associated with an increased risk of failure of total shoulder joint replacement. Although a number of glenohumeral arthroplasty techniques are being used to manage this complex pathology, problems with glenoid component failure remain. In that the ream and run procedure manages arthritic pathoanatomy without a glenoid component, we sought evidence that this procedure can be effective in improving the centering of the humeral head contact on the glenoid and in improving the comfort and function of shoulders with the arthritic triad without the risk of glenoid component failure.
Thermodynamically self-consistent approximations to the liquidus and solidus of Hg 1-x Cd x Te

Based on liquidus and solidus temperatures and associated confidence limits reported by Brice, Capper, and Jones [J. Cryst. Growth, 75, 395 (1986)], we develop polynomial approximations to the liquidus and solidus curves for the pseudobinary material Hg1−xCdxTe. These approximations are “thermodynamically consistent” in that they satisfy the requirement that the liquidus and solidus temperatures must agree at x=0 and 1. A linear programming approach is used to find the lowest-degree polynomial approximations to the liquidus and solidus temperatures falling within the confidence limits of Brice et al. at each of their 21 compositions, and also satisfying the convexity requirement imposed by Brice et al. on their own manually-drawn curves. Finally, we present a twoparameter rational approximation that fits the tabulated segregation coefficients for Hg1−xCdxTe better than an earlier five-parameter polynomial approximation.
Challenging a surgical dictum: results from a 10-year experience on the safety of open inguinal herniorrhaphy in patients on chronic warfarin therapy

Previous reports document the safety of open inguinal herniorrhaphy in patients on chronic warfarin therapy; however, the practice remains controversial. This study is a 10-year update of our experience. A retrospective review of 1,839 consecutive patients undergoing open inguinal hernia repair was conducted from 2000 to 2010. All patients on chronic warfarin therapy were included. Three groups: continuation (CW), discontinuation (DW) and case-matched control (C) not on warfarin therapy were compared for operative details and postoperative complications. One hundred and fifty-eight patients were on chronic warfarin therapy. Of these, 40 patients (25 %) continued on warfarin during the perioperative period (CW). Average preoperative international normalized ratio (INR) was 2.15 ± 0.76 for CW and 1.38 ± 0.42 for DW, p 3, p = 0.65). Maintenance of warfarin therapy during the perioperative period for open inguinal herniorrhaphy results in equivalent operative times and postoperative complications as discontinuation.
In-line holography using a point source

Conventional scanning electron microscopes are now close to the limit of their performance for tasks such as the metrology of sub-micron design rule devices. In order to overcome these limits we are investigating the use of in-line electron holography for device metrology. This device will use ultralow energy electrons (50-250eV) emitted from a nano-tip electron source. Out of focus holograms of a mesh were simulated and reconstructed in the transmission mode of the microscope whereas in the reflection mode a sample consisting of only two points was used. In both operation modes of the microscope it is possible to change the distance from the point source (crossover of a lens) to the sample and the distance from the sample to the detector plane such that the magnification is kept constant. Series of simulated holograms consisting of only a few points reveal the distances resulting in the easiest interpretable images. When in-line holography is performed using electrons, the beams are deflected by the electric field between point source and sample. Ray tracing of the electrons performed by solving the appropriate Laplace equation can help to determine an optimum geometry for the microscope.
Migración Africana y formación social en las Américas, 1500-2000

Around 11 million Africans reached the New World between 1500 and 1866 in what constitutes the first massive transoceanic migration in the history of humanity. This article approaches that movement from the perspective of the history of migrations and socio-racial formations in the Americas. The first part establishes the origins, timing, and geographic distribution of the arrivals using a database with information on some 35,000 slave ship voyages. We go on to analyze how this determined the demographic impact, socio-economic development, African cultural presence, adaptation and acculturation strategies, and the construction of racial taxonomies and identities in the receiving regions.
Computer interface and algorithm determines bioelectrode impedance

Abstract A computer system for measurement of electrode impedance was developed which permits periodic and automatic determination of proper electrode contact during long-term recording sessions. In addition, the voltage gain of the entire recording system was obtained for subsequent calibration of records. The computer could then record the impedance for documentation or signal the operator for necessary electrode adjustment.
Mice Deficient in the Serine/Threonine Protein Kinase VRK1 Are Infertile Due to a Progressive Loss of Spermatogonia

The VRK1 protein kinase has been implicated as a pro-proliferative factor. Genetic analyses of mutant alleles of the Drosophila and Caenorhabditis elegans VRK1 homologs have revealed phenotypes ranging from embryonic lethality to mitotic and meiotic defects with resultant sterility. Herein, we describe the first genetic analysis of murine VRK1. Two lines of mice containing distinct gene-trap integrations into the Vrk1 locus were established. Insertion into intron 12 (GT12) spared VRK1 function, enabling the examination of VRK1 expression in situ. Insertion into intron 3 (GT3) disrupted VRK1 function, but incomplete splicing to the gene trap rendered this allele hypomorphic (approximately 15% of wild-type levels of VRK1 remain). GT3/GT3 mice are viable, but both males and females are infertile. In testes, VRK1 is expressed in Sertoli cells and spermatogonia. The infertility of GT3/GT3 male mice results from a progressive defect in spermatogonial proliferation or differentiation, culminating in the absence of mitotic and meiotic cells in adult testis. These data demonstrate an important role for VRK1 in cell proliferation and confirm that the need for VRK1 during gametogenesis is evolutionarily conserved.
Diffraction of a weak shock by a wedge

We match formal asymptotic expansions with differently scaled variables to obtain a uniform approximation to the similarity solution of the shock-wedge diffraction problem.
Thermoelectric Transport in Superlattices

A quantitative description of the power factor for thermoelectric transport in quantum well and quantum wire superlattices has been developed. The size dependence of the carrier scattering rates as well as carrier tunneling between layers are included, and results are obtained for full three-dimensional superlattice systems. In addition, model calculations of the lattice thermal conductivity of free standing wells and wires have been obtained, and their implications for the thermoelectric figure of merit are discussed. Illustrative results are given for GaAs and PbTe systems.
Undertreatment of Thick Head and Neck Melanomas: An Age-based Analysis

To determine U.S. treatment patterns for pathologic staging practices in patients with thick head and neck melanomas (HNM). Patients with thick HNM without clinical evidence of in-transit, regional, or distant metastatic spread at presentation were identified from the Surveillance Epidemiology and End Results database. Treatment trends for patients were summarized, and univariate and multivariate analyses were performed to identify associations between varying practice patterns. A total of 1,230 patients with HNM meeting the inclusion criteria were identified. Surgical staging procedures were utilized in 53.5 %, including both sentinel lymph node biopsy (37 %) and elective neck dissection (16 %). Patients undergoing a surgical staging procedure were younger (64 vs. 77 years, p < 0.001) with smaller tumors (6.3 vs. 6.6 mm, p = 0.008). The rate of occult nodal disease was 22 % in patients undergoing a surgical staging procedure. The presence of a positive regional node in this subgroup of patients was associated with a significant reduction in disease-specific (44 vs. 59 months, p < 0.001) and overall survival (40 vs. 53 months, p < 0.001) on univariate analysis. On multivariate analysis, the presence of a positive node was the most significant factor for reduced overall survival (hazard ratio 2.36, 95 % confidence interval 1.71–3.23) and disease-specific survival (hazard ratio 2.84, 95 % confidence interval 1.99–4.06). Pathologic staging procedures provide independent prognostic information for patients with thick HNM. Despite this, current practice patterns demonstrate underutilization, particularly in elderly patients. Further work is needed to address the barriers to pathologic staging implementation in patients with thick HNM.
A characterization of finite groups containing a strongly closed 2-subgroup

Throughout this paper G is a finite group and S is a subgroup of G. When S is contained in the subgroup H of G, we say S is strongly closed in H with respect to G if whenever s ∈ S and g ∈ G are such that s ∈ H, then s ∈ S. In other words, every G-conjugacy class of elements of S intersected with H is contained in S. In the case where S is a p-group for some prime p we say that S is strongly closed if it is strongly closed in some Sylow p-subgroup containing it. One easily sees that S is strongly closed if and only if it is strongly closed in NG(S) with respect to G, so strong closure is independent of the choice of Sylow p-subgroup containing S.
The Theme of Spiritual Pollution in Chinese Films of the 1930s

The political campaigns launched by the Chinese Communist Party in 1981, 1983, 1987, and 1989 to eradicate foreign "spiritual pollution,"1 a noxious byproduct of "bourgeois liberalization," can be interpreted in a variety of ways. It is apparent, for example, that in each case the leadership was looking for a way to account for corruption, lawlessness, disorder, alienation, cynicism, and other nagging social problems without having to point to the failings of the Party itself. In the political realm, these campaigns provided opportunities for cultural conservatives to gain temporary strategic advantages over reformers inside the Party who, like their Eastern European counterparts in the 1980s, were eager to dismantle the traditional Stalinist cultural system. These initiatives, some of which were comical and some of which were deadly, can also be viewed as manifestations of Chinese nationalism, as products of the modernization process in a nonWestern environment, and as attempts by the Party/state to achieve greater social control. In spite of the novelty of the terms jingshen wuran and zichanjieji ziyouhua and the uniqueness of social, economic, and political conditions that spawned these ideological and cultural crusades in the 1980s, the image of China as the innocent victim of foreign spiritual pollution is neither new, nor the brain child of post-Mao Chinese Communist theoreticians and propagandists. On several occasions during the late Qing, Republican, and socialist periods, political and intellectual elites sought to mobilize (and manipulate) ordinary people by issuing grave and sometimes hysterical warnings about the dangers of alien cultural contamination. For well over a century it has been politically expedient
Serum albumin and mortality in acutely decompensated heart failure.

Background Although hypoalbuminemia has been associated with decreased survival in chronic systolic heart failure (HF), its role for prognosticating outcomes in those with acutely decompensated heart failure (ADHF) has not been established. Methods and Results 438 consecutive patients with ADHF (mean age 75 ± 13 years, mean left ventricular ejection fraction 41% ± 20%) admitted to a large community hospital were studied. The mean serum albumin level for the group was 3.4 g/dL; quintile analysis demonstrated an inflection of risk for death below this value. Patients with hypoalbuminemia (defined as a serum albumin adjusted = 2.05, 95% CI 1.10-3.81, P = .001). Reduced serum albumin concentrations were prognostic across a wide range of body mass index but had highest HR in obese patients (HR adjusted = 4.39 [95% CI=1.66 to 11.60], P = .003). As well, hypoalbuminemia was mainly predictive of outcomes among those with systolic HF (HR adjusted = 5.00, 95% CI=2.17-11.5, P Conclusion Hypoalbuminemia is common among patients with ADHF and is independently associated with increased one year mortality in patients admitted with ADHF.
EFFECT OF GROWTH HORMONE (GH) ON GONADOTROPIN CONCENTRATIONS IN ADOLESCENT KALES WITH GROWTH HORMONE DEFICIENCY: A PRELIMINARY REPORT

EFFECT OF GROWTH HORMONE (GH) ON GONADOTROPIN CONCENTRATIONS IN ADOLESCENT KALES WITH GROWTH HORMONE DEFICIENCY: A PRELIMINARY REPORT
Enzymatic Spectrophotometric Determination of Ascorbic Acid in Commercial Vitamin C Tablets

Abstract A spectrophotometric method for the determination of ascorbic acid contents in a variety of samples involving an enzymatic reaction and a specific blank solution is proposed. The enzyme used is ascorbate oxidase, which catalyses the oxidation of ascorbic acid to dehydroascorbic acid. Then the dehydroascorbic acid is reacted with o -phenylenediamine to produce a 2,2-anhydro quinoxaline whose absorption with respect to a specially prepared blank is observed at 358 nm. The amount of ascorbic acid present and reacted with oxygen in the presence of ascorbate oxidase was measured as the increase in the absorbance of the quinoxaline. Several commercial vitamin C tablets were analyzed using this procedure. The procedure gives satisfactory results with good selectivity and sensitivity for the determination of ascorbic acid present in these samples.
On the development of the interactive web based courses on classical and modern control

The paper discusses the enhancement of the existing courses within the intelligent control track at NPS with the interactive media elements. Because of the need of shortening the stay of NPS students, on-duty officers, on campus there is a requirement to convert these courses into the distance learning format to form the certified programs to be taken prior or after their time on campus. The paper discusses six courses converted into on-line format so far, shows their standardized web layout, provides examples of different interactive media elements and ends with students' feedback.
The adjacency principle and induced movement

The apparent movement of a stationary point of light was investigated as a function of the apparent distance of the point of light with respect to the inducing frame of frames. When two frames were presented simultaneously, they were at different distances and physically moved at opposite phase in frontoparallel planes. When one frame was presented alone, it was positioned at different times at each of the two distances. The point of light was presented stereoscopically at the distance of either the near or far frame or midway in depth between these distances. With the single frame, it was found that the magnitude of the induced movement decreassed as the point of light was increasingly far in front of a frame but decreased less or remained approximately constant for distances be hind a frame. With the two frames presented simultaneously, it was found that as the depth between a particular frame and the point of light decreased, the contribution of that frame to the induced movement increased. The results illustrate the interaction of perceptions, in this case perceived depth and perceived motion, and are consistent with the adjacency principle.
Asteroid differentiation - Pyroclastic volcanism to magma oceans

A summary is presented of theoretical and speculative research on the physics of igneous processes involved in asteroid differentiation. Partial melting processes, melt migration, and their products are discussed and explosive volcanism is described. Evidence for the existence of asteroidal magma oceans is considered and processes which may have occurred in these oceans are examined. Synthesis and inferences of asteroid heat sources are discussed under the assumption that asteroids are heated mainly by internal processes and that the role of impact heating is small. Inferences of these results for earth-forming planetesimals are suggested.
Progression to Daily Smoking: Is There a Gender Difference among Cessation Treatment Seekers?

The goal of this study was to develop an understanding the developmental trajectory of smoking behaviors in adolescents who seek smoking cessation treatment to inform tailored prevention and treatment efforts; this includes identifying gender differences in smoking behaviors. Smoking trajectory was examined retrospectively in 639 treatment-seeking adolescents (59% female; 44% African American, 50% European American, mean +/- SD daily cigarettes per day [CPD] 19.16 +/- 7.2 for both girls and boys). Smoking trajectory variables examined included age at first cigarette, age at daily smoking (a proxy measure for onset of dependence), and age at treatment request. The time interval from first cigarette to daily smoking was shorter for girls than for boys (mean +/- SD 0.9 +/- 1.1 years for girls, 1.3 +/- 1.5 years for boys, p < 0.01). From this clinical sample of adolescent smokers, findings suggest only a brief window of opportunity for secondary preventive interventions before the development of tobacco dependence. Additional research is needed to explore the specific factors that differentially affect smoking trajectory in girls compared to boys.
The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease

Leucine-rich repeat kinase 2 (LRRK2) has been identified by genome-wide association studies as being encoded by a major susceptibility gene for Crohn's disease. Here we found that LRRK2 deficiency conferred enhanced susceptibility to experimental colitis in mice. Mechanistic studies showed that LRRK2 was a potent negative regulator of the transcription factor NFAT and was a component of a complex that included the large noncoding RNA NRON (an NFAT repressor). Furthermore, the risk-associated allele encoding LRRK2 Met2397 identified by a genome-wide association study for Crohn's disease resulted in less LRRK2 protein post-translationally. Severe colitis in LRRK2-deficient mice was associated with enhanced nuclear localization of NFAT1. Thus, our study defines a new step in the control of NFAT activation that involves an immunoregulatory function of LRRK2 and has important implications for inflammatory bowel disease.
All finite configurations are Almost Ramsey

Abstract We call C an Almost Ramsey configuration if for all k , ϵ > 0 there exists N so that under any k -coloration of the points of R N there exists a monochromatic configuration C ′ which may be transformed into a congruent copy of C by moving each point a distance at most ϵ.
Time course of changes in gluconeogenesis from various precursors in chronically endotoxemic rats

Abstract Rates of gluconeogenesis (GNG) from lactate and triosephosphate precursors were measured in hepatocytes isolated from rats that have received endotoxin or physiological saline by continuous infusion from an implanted pump. Six hours after the onset of infusion (day 2 postsurgery) GNG from lactate was significantly elevated in hepatocytes of endotoxemic (ET) animals. By 24 hours later, the gluconeogenic rate was depressed, compared to cells of NaCl-infused controls. However, providing ET cells with lactate at concentrations found in the in vivo milieu resulted in glucose production at rates not different from those of control cells incubated at their respective in vivo (lower) substrate levels. On day 2 postsurgery, ET rats were hyperglycemic and hyperlactacidemic; on day 3 the elevated blood lactate concentration was maintained, but the plasma glucose values were not different from those of NaCl controls. The glucagon-induced increment in glucose synthesis was depressed in cells of ET rats both on day 2 and day 3 postsurgery, although the total amount of glucose released was significantly less only on day 3. The pattern of norepinephrine stimulation was similar to that of glucagon, except for the increase above the basal rate of GNG on day 3 being the same for control and ET cells. GNG was also assessed from oxidized substrates (fructose (F) and dihydroxyacetone (DHA)) and reduced substrates (sorbitol and glycerol) entering the pathway at the triosephosphate level. On day 2 both cell populations produced glucose from each of the four precursors at comparable basal rates. At this time control cells responded to glucagon stimulation by significantly enhanced rates of glucose synthesis from F and DHA, while ET cells produced significantly more glucose only when F was the precursor. On day 3 glucose output by ET cells was significantly depressed as compared to their day 2 values, while the rates of NaCl cells were unchanged. Using the chronic mode of endotoxin infusion in nonlethal doses, we demonstrated time course and precursor-dependent changes in gluconeogenic patterns involving both mitochondrial and cytoplasmic pathways under circumstances mimicking some cardinal features in clinical sepsis. Depression of gluconeogenesis in isolated ET hepatocytes could be overcome by maintaining some of the conditions prevailing in the cells' in vivo environment.
Pharmacotherapy of Drug Abusers: Adjunctive Psychopharmacologic Management of Nonopiate Mixed Substance Abusers in an Outpatient Setting

Conventional practice in treating nonopiate mixed substance abusers has avoided the use of pharmaceuticals because of the strong drug orientation of this patient population. The authors' impressions are that this is a maladaptive treatment polarization, and that psychopharmacotherapy of this group of patients is not only sometimes useful but necessary for some individuals. Diagnostic syndromata and problems specific to this patient population are delineated along with our experience in pharmacotherapy.
Assessing teratogenicity of antiretroviral drugs: monitoring and analysis plan of the Antiretroviral Pregnancy Registry

This paper describes the Antiretroviral Pregnancy Registry's (APR) monitoring and analysis plan. APR is overseen by a committee of experts in obstetrics, pediatrics, teratology, infectious diseases, epidemiology and biostatistics from academia, government and the pharmaceutical industry. APR uses a prospective exposure-registration cohort design. Clinicians voluntarily register pregnant women with prenatal exposures to any antiretroviral therapy and provide fetal/neonatal outcomes. A birth defect is any birth outcome > or = 20 weeks gestation with a structural or chromosomal abnormality as determined by a geneticist. The prevalence is calculated by dividing the number of defects by the total number of live births and is compared to the prevalence in the CDC's population-based surveillance system. Additionally, first trimester exposures, in which organogenesis occurs, are compared with second/third trimester exposures. Statistical inference is based on exact methods for binomial proportions. Overall, a cohort of 200 exposed newborns is required to detect a doubling of risk, with 80% power and a Type I error rate of 5%. APR uses the Rule of Three: immediate review occurs once three specific defects are reported for a specific exposure. The likelihood of finding three specific defects in a cohort of < or = 600 by chance alone is less than 5% for all but the most common defects. To enhance the assurance of prompt, responsible, and appropriate action in the event of a potential signal, APR employs the strategy of 'threshold'. The threshold for action is determined by the extent of certainty about the cases, driven by statistical considerations and tempered by the specifics of the cases.
PDRG1, a novel tumor marker for multiple malignancies that is selectively regulated by genotoxic stress

We have previously cloned and characterized a novel p53 and DNA damage-regulated gene named PDRG1. PDRG1 was found to be differentially regulated by ultraviolet (UV) radiation and p53. In this study, we further investigated stress regulation of PDRG1 and found it to be selectively regulated by agents that induce genotoxic stress (DNA damage). Using cancer profiling arrays, we also investigated PDRG1 expression in matching normal and tumor samples representing various malignancies and found its expression to be upregulated in multiple malignancies including cancers of the colon, rectum, ovary, lung, stomach, breast and uterus when compared to their respective matched normal tissues. Western blot and immunohistochemical analyses were also performed on select specimen sets of colon cancers and matching normal tissues and the results also indicated PDRG1 overexpression in tumors relative to normal tissues. To gain insight into the function of PDRG1, we performed PDRG1 knockdown in human colon cancer cells and found its depletion to result in marked slowdown of tumor cell growth. These results suggest that PDRG1 may be linked to cell growth regulation. Yeast two-hybrid screening also led to the identification of PDCD7, CIZ1 and MAP1S as PDRG1-interacting proteins that are involved in apoptosis and cell cycle regulation which further implicate PDRG1 in controlling cell growth regulation. Taken together, our results indicate that PDRG1 expression is increased in multiple human malignancies suggesting it to be a high-value novel tumor marker that could play a role in cancer development and/or progression.
Effects of liver damage and nephrectomy on anticonvulsant activity of mysoline and phenobarbital.

Mysoline and phenobarbital were tested after their oral administration in normal, liver-damaged, and nephrectomized rats for their ability to prevent the tonic extensor component of maximal electroshock seizures. The results were analyzed for the effect of these procedures on the intensity and the duration of anticonvulsant action of these compounds. Liver damage significantly increased the anticonvulsant activity and the duration of action of both drugs. Nephrectomy increased the anticonvulsant activity and the duration of action of Mysoline but not of phenobarbital. The results suggest that, in the rat, both the liver and the kidney are important for the degradation and elimination of Mysoline, whereas the liver is the principal organ for the degradation of phenobarbital into products devoid of anticonvulsant activity.
Optical antenna design for fluorescence enhancement in the ultraviolet

Through rational design, we compare the performance of three plasmonic antenna structures for UV fluorescence enhancement. Among the antenna performance metrics considered are the local increase in excitation intensity and the increase in quantum efficiency, the product of which represents the net fluorescence enhancement. With realistic structures in aluminum, we predict that greater than 100× net enhancement can be obtained.
Induction Chemotherapy Meta-Analysis in Head and Neck Cancer: Right Answer, Wrong Question

to 0.86; P .001) was demonstrated for concomitant treatment. 3 Nooverallsurvivalbenefitwasidentifiedfromtheinductionchemotherapyschedules,althoughamarginalimprovementwasseenin those trials using the fluorouracil and cisplatin combination. Patterns of failure differed between the two treatment schedules. Induction chemotherapy significantly improved the rate of distant metastases (HR, 0.73; 95% CI, 0.61 to 0.88; P .001) but did not influence locoregional failure. The concomitant schedules markedly improved the locoregional control (HR, 0.74; 95% CI, 0.70 to 0.79; P .001) with a significant but less impressive improvement in distant control (HR, 0.88; 95% CI, 0.77 to 1.00; P .04). These reports solidified concomitant chemoradiotherapy as a treatment standard in the definitive management of locoregionally advanced HNSCC. Induction chemotherapy remained investigational except in the larynx preservation setting. Thisclearimpactondistantmetastasesfueledcontinuedinterest
Modeling and design of controlled flying proximity sliders for head-media spacing variation suppression in ultra-low flying air bearings

In this paper, a novel controlled flying proximity (CFP) slider is presented. A new 3-DOF analytic model is proposed to describe the dynamics of the piezoelectric actuated slider. The air bearing parameters, such as stiffness and damping, are identified by a modal analysis method. Then, an observer-based nonlinear sliding mode controller is designed to compensate the short-range attractive forces and to suppress the FHM of ultra-low flying height air-bearing sliders in proximity, in which the magnetic signal is used for real-time FHM measurement. The attractive forces are included in the model as a highly nonlinear term and the effect of disk morphology is modeled as unknown but bounded disturbances. Numerical simulations investigate the performance of the controller.
Enhancing Native Forb Establishment and Persistence Using a Rich Seed Mixture

Establishing native forbs is crucial for invasive plant management and restoring a desirable plant community. Our objectives were to determine (1) if increasing forb seed density results in increased forb establishment; (2) if a species-rich mixture of forbs has greater establishment and survivorship than a single species; and (3) if mixtures of forbs are more competitive with Spotted knapweed (Centaurea maculosa) than a forb monoculture. To test our first two objectives, we seeded monocultures of Purple coneflower (Echinacea angustifolia), Arrowleaf balsamroot (Balsamorhiza sagittata), Annual sunflower (Helianthus annuus), Dotted gayfeather (Liatris punctata), Western white yarrow (Achillea millefolium), Sticky geranium (Geranium viscosissimum), as well as a mixture of all forbs. Pots were seeded at 800 or 2,000 seeds/m 2 and watered twice or thrice weekly. The highest seed density produced the highest plant density, which averaged 4.35 plants/pot. The density of the mixture was similar to the mean density seen for individual species, and it doubled in response to the highest seed density. To test our third objective, Spotted knapweed and Purple coneflower were arranged in an addition series matrix with a maximum total density of 4,000 seeds/pot. We found that the forb mixture was seven times more competitive with Spotted knapweed than Purple coneflower alone. Using a mixture of forbs rather than a single species enhances forb establishment in various and unpredictable environments because the mixture possesses a variety of traits that may match year‐year and site‐site conditions. Once established, the mixture may have a greater chance of persisting than a monoculture.
Hydrologic and geochemical controls on soluble benzene migration in sedimentary basins

The effects of groundwater flow and biodegradation on the long-distance migration of petroleum-derived benzene in oil-bearing sedimentary basins are evaluated. Using an idealized basin representation, a coupled groundwater flow and heat transfer model computes the hydraulic head, stream function, and temperature in the basin. A coupled mass transport model simulates water washing of benzene from an oil reservoir and its miscible, advective/dispersive transport by groundwater. Benzene mass transfer at the oil–water contact is computed assuming equilibrium partitioning. A first-order rate constant is used to represent aqueous benzene biodegradation. A sensitivity study is used to evaluate the effect of the variation in aquifer/geochemical parameters and oil reservoir location on benzene transport. Our results indicate that in a basin with active hydrodynamics, miscible benzene transport is dominated by advection. Diffusion may dominate within the cap rock when its permeability is less than 10 m. Miscible benzene transport can form surface anomalies, sometimes adjacent to oil fields. Biodegradation controls the distance of transport down-gradient from a reservoir. We conclude that benzene detected in exploration wells may indicate an oil reservoir that lies hydraulically up-gradient. Geochemical sampling of hydrocarbons from springs and exploration wells can be useful only when the oil reservoir is located within about 20 km. Benzene soil gas anomalies may form due to regional hydrodynamics rather than separate phase migration. Diffusion alone cannot explain the elevated benzene concentration observed in carrier beds several km away from oil fields.
Subunit specific monoclonal antibodies show different steady-state levels of various cytochrome-c oxidase subunits in chronic progressive external ophthalmoplegia

Abstract Monoclonal antibodies recognizing the mitochondrially encoded subunits I and II, and the nuclear-encoded subunits IV, Va, Vb and VIc of human cytochrome- c oxidase were generated. These antibodies are highly specific and allow the assessment of subunit steady-state levels in crude cell extracts and tissue sections. In the experimental human cell line 143B206, which is devoid of mitochondrial DNA, immunovisualization with the antibodies revealed that the nuclear-encoded subunits IV and Va were present in amounts close to that of the parental cell line despite the absence of the mitochondrially encoded subunits. In contrast, the nuclear-encoded subunits Vb and VIc were severely reduced in cell line 143B206, suggesting the unassembled nuclear-encoded subunits are degraded at different rates. In skeletal muscle sections of a patient with chronic progressive external ophthalmoplegia known to harbor the ‘common deletion’ in a subpopulation of her mitochondrial DNA, most cytochrome- c oxidase activity negative fibers had greatly reduced levels of subunits I, II, Va, Vb and VIc of cytochrome- c oxidase. The steady-state level of subunit IV, however, was less affected. This was particularly evident in cytochrome- c oxidase activity negative fibers with accumulated mitochondria (‘ragged-red’ fibers) where immunodetection with anti-subunit IV resulted in intense staining. The data presented in this paper demonstrate that the battery of monoclonal antibodies can be employed for diagnostic purposes to analyze steady-state levels of mitochondrially and nuclear-encoded subunits of cytochrome- c oxidase.
Do herbivores associate flavours with specific consequences in flavour aversion learning

Goats were first offered a novel, maple-flavoured diet paired with either lithium chloride (LiCl) or oxalic acid (OA) delivered intraruminally. Aversion to maple diet persisted for 6 days, regardless of toxin. Following a 10-day intermission, aversion to maple diet was reacquired (spontaneous recovery) among subjects previously dosed with LiCl but not for subjects receiving OA. All subjects were then offered two diets: the maple diet previously paired with LiCl or OA and a novel grape-flavoured diet. Immediately following consumption of both diets, all subjects were dosed with LiCl. Preference for maple and grape diets was assessed by two-choice test. Goats avoided maple diet for only 1 day, regardless of their previous experience with maple diet (paired with LiCl or OA). These results indicate that goats generalized the postingestive consequences of the two toxins. Furthermore, presence of a novel flavour (grape) during toxin exposure contributed to rapid extinction of the aversion to maple flavour.
Methods of Analysis

The majority of investigators interested in carrying out quantitation of bone biopsies count the cells within a certain area using a grid. The grid is placed in the eyepiece of the microscope and is projected onto the field at a magnification of about 100 times. The grid may be a series of points on a number of lines or it may consist of a cross-hatched area or merely an array of lines. If the grid is cross-hatched or if lines with points are used, it is most common to evaluate the event that is occurring at the grid intersections or at the point where the line crosses the bone surface to be analyzed. In a bone biopsy the presence of an osteoblast, of an osteoclast, or of an inactive surface are the three major events recorded. If enough events or hits are recorded to provide statistically valid results, the average number of events as a percentage of the total number of points is representative of the area of active cells as a fraction of the total area of the sample, which in turn reflects the section. Courpron, Merz, Bordier, Schultz, Sedlin, Teitelbaum, and Sherrard all utilize grids and point-count methods for evaluation of bone turnover (Courpron et al., 1974; Merz and Schenk, 1970; Bordier et al., 1964; Schultz and Delling, 1976a; Sedlin et al., 1963; Sherrard et al., 1974 and Teitelbaum et al., 1976a). The exception is Jowsey who evaluates what is occurring on all of the surface rather than a finite number of randomly selected samples of the surface (see below).
Parent and Adolescent Views on Barriers to Adolescent Preventive Health Care Utilization

Objectives To determine adolescent and parent views of barriers to annual adolescent preventive care. Study design A nationally recruited cross-sectional study of adolescents between ages 13 and 18 years, and parents of adolescents from different families, were recruited. The primary outcome was self-report of preventive care in the last 12 months. Demographic, family health discussions, physical/emotional health importance, and preventive care barriers were gathered from adolescents and parents. Results The majority of the sample (500 adolescents and 504 parents in different families) reported a primary care visit within 12 months (parents = 78.7%; adolescents = 66.9%). Adolescent participants identified more barriers than parents (parents = 0.69; adolescents = 1.42). Adolescent who reported having discussions with parents about health (aOR 1.57, 95% CI 1.26-1.98) and seeing a subspecialist provider (aOR 3.72, CI 1.21-11.47) were more likely to report preventive visits. Barriers for parents and adolescents include the belief that an appointment is only needed when a child is sick (parent aOR 0.21, CI 0.08-0.61; adolescent aOR 0.29, CI 0.17-0.51) and family cannot afford cost (parent aOR 0.34, CI 0.15-0.81; adolescent aOR 0.50, CI 0.26-0.97). Barriers for parents include the child sees a specialist (aOR 0.26, CI 0.08-0.88) and their child does not need a checkup (aOR 0.12, CI 0.05-0.34). Lastly, a barrier for adolescents was parents never schedule preventive visits (aOR 0.31, CI 0.17-0.58). Conclusions The Affordable Care Act has the potential to limit preventive care barriers. The results of the current study find there are parental and adolescent issues regarding preventive services that should be addressed.
Cross-Bridges Affect Both TnC Structure and Calcium Affinity in Muscle Fibers

In vertebrate striated muscle, calcium binding to troponin initiates contraction, a strong interaction of actin and myosin. In isolated proteins and skinned fibers, the strong interaction of myosin with actin also affects troponin. Fluorescent labels attached to troponin C show structural changes in the TnC environment with crossbridge attachment and also with calcium binding. Evidence that this effect of crossbridges also occurs in intact striated muscle comes from studies in partially activated cardiac or skeletal muscle by others and in barnacle muscle by us. Length changes which detach myosin cross-bridges produce a brief burst of extra calcium that can be detected by aequorin in activated, voltage clamped single barnacle muscle fibers. That this calcium is coming from calcium bound to the activating site (troponin-C) is supported by several pieces of evidence. Studies on the dependence of the extra calcium on force and the time of the length change are consistent with the amplitude of the extra calcium being proportional to the bound calcium (CaTnC) and with increased cross-bridge attachment and force increasing calcium binding to troponin-C by up to a factor of 10. Importantly, stretch of active muscle (which first detaches cross-bridges and then enhances steady force) gives a biphasic response: first extra calcium (presumably due to cross-bridge detachment) and then, decreased calcium (presumably due to enhanced calcium binding to TnC). The enhanced calcium binding we see with elevated force (via strained cross-bridges) implies that calcium binding to TnC is enhanced not only be cross-bridge attachment but also by cross-bridge (or thin filament) strain.
First-in-human dose escalation study of LY2875358 (LY), a bivalent MET antibody, as monotherapy and in combination with erlotinib (E) in patients with advanced cancer.

8093 Background: Activation of the hepatocyte growth factor (HGF)/MET receptor pathway promotes tumor growth, invasion and dissemination. LY is a humanized IgG4 monoclonal bivalent antibody against MET which inhibits ligand dependent- and ligand independent activation of MET. Based on preclinical results, we examined LY alone in patients with advanced solid tumors and LY+E in advanced NSCLC patients. Methods: LY monotherapy was administered 20-2,000 mg Q2W IV to 23 patients with advanced solid tumors. Combination therapy with 700-2,000 mg Q2W IV of LY and E (150 mg QD) was completed in 14 patients with advanced NSCLC. The primary objective was to determine a recommended phase II dose (RPTD) for LY and LY+E. Secondary objectives included assessment of toxicity, PK, PD (including MET extracelluar domain and HGF), and antitumor activity. Results: LY and LY+E were well tolerated. No dose-limiting toxicities, serious adverse events, or ≥ Grade 3 adverse events (AEs) possibly related to LY have been observed. T...
Validation data for models of contaminant dispersal : scaling laws and data needs.

Contaminant dispersal models for use at scales ranging from meters to miles are widely used for planning sensor locations, first-responder actions for release scenarios, etc. and are constantly being improved. Applications range from urban contaminant dispersal to locating buried targets from an exhaust signature. However, these models need detailed data for model improvement and validation. A small Sandia National Laboratories Laboratory Directed Research and Development (LDRD) program was funded in FY04 to examine the feasibility and usefulness of a scale-model capability for quantitative characterization of flow and contaminant dispersal in complex environments. This report summarizes the work performed in that LDRD. The basics of atmospheric dispersion and dispersion modeling are reviewed. We examine the need for model scale data, and the capability of existing model test methods. Currently, both full-scale and model scale experiments are performed in order to collect validation data for numerical models. Full-scale experiments are expensive, are difficult to repeat, and usually produce relatively sparse data fields. Model scale tests often employ wind tunnels, and the data collected is, in many cases, derived from single point measurements. We review the scaling assumptions and methods that are used to relate model and full scale flows. In particular, wemore » examine how liquid flows may be used to examine the process of atmospheric dispersion. The scaling between liquid and gas flows is presented. Use of liquid as the test fluid has some advantages in terms of achieving fully turbulent Reynolds numbers and in seeding the flow with neutrally buoyant tracer particles. In general, using a liquid flow instead of a gas flow somewhat simplifies the use of full field diagnostics, such as Particle Image Velocimetry and Laser Induced Fluorescence. It is also possible to create stratified flows through mixtures of fluids (e.g., water, alcohol, and brine). Lastly, we describe our plan to create a small prototype water flume for the modeling of stratified atmospheric flows around complex objects. The incoming velocity profile could be tailored to produce a realistic atmospheric boundary layer for flow-in-urban-canyon measurements. The water tunnel would allow control of stratification to produce, for example, stable and unstable atmospheric conditions. Models ranging from a few buildings to cityscapes would be used as the test section. Existing noninvasive diagnostics would be applied, including particle image velocimetry for detailed full-field velocity measurement, and laser induced fluorescence for noninvasive concentration measurement. This scale-model facility will also be used as a test-bed for data acquisition and model testing related to the inverse problem, i.e., determination of source location from distributed, sparse measurement locations. In these experiments the velocity field would again be measured and data from single or multiple concentration monitors would be used to locate the continuous or transient source.« less