cssi/SciSciGPT-SciSciNet huggingface dataset:
Selection of DNA Binding Sites by Regulatory Proteins Statistical-mechanical Theory and Application to Operators and Promoters

We present a statistical-mechanical selection theory for the sequence analysis of a set of specific DNA regulatory sites that makes it possible to predict the relationship between individual base-pair choices in the site and specific activity (affinity). The theory is based on the assumption that specific DNA sequences have been selected to conform to some requirement for protein binding (or activity), and that all sequences that can fulfil this requirement are equally likely to occur. In most cases, the number of specific DNA sequences that are known for a certain DNA-binding protein is very small, and we discuss in detail the small-sample uncertainties that this leads to. When applied to the binding sites for cro repressor in phage lambda, the theory can predict, from the sequence statistics alone, their rank order binding affinities in reasonable agreement with measured values. However, the statistical uncertainty generated by such a small sample (only 6 sites known) limits the result to order-of-magnitude comparisons. When applied to the much larger sample of Escherichia coli promoter sequences, the theory predicts the correlation between in vitro activity (k2KB values) and homology score (closeness to the consensus sequence) observed by Mulligan et al. (1984). The analysis of base-pair frequencies in the promoter sample is consistent with the assumption that base-pairs at different positions in the sites contribute independently to the specific activity, except in a few marginal cases that are discussed. When the promoter sites are ordered according to predicted activities, they seem to conform to the Gaussian distribution that results from a requirement for maximal sequence variability within the constraint of providing a certain average activity. The theory allows us to compare the number of specific sites with a certain activity to the number that would be expected from random occurrence in the genome. While strong promoters are "overspecified", in the sense that their probability of random occurrence is very low, random sequences with weak promoter-like properties are expected to occur in very large numbers. This leads to the conclusion that functional specificity is based on other properties in addition to primary sequence recognition; some possibilities are discussed. Finally, we show that the sequence information, as defined by Schneider et al. (1986), can be used directly (at least in the case of equilibrium binding sites) to estimate the number of protein molecules that are specifically bound at random "pseudosites" in the genome.(ABSTRACT TRUNCATED AT 400 WORDS)
Lorentz Transmission Electron Microscopy Investigation of Magnetically Patterned Co/Pt Multilayers

The switching behavior of magnetic patterns prepared by ion irradiation was investigated. Co/Pt multilayers with perpendicular anisotropy and large out-of-plane coercivities 5-6 kOe were grown on electron transparent SiN windows. Regularly spaced 1 micron sized regions, were magnetically pattered via ion beam irradiation through a stencil mask. Lorentz TEM was used to observe in-situ magnetization reversal processes of irradiated regions under well-defined applied magnetic fields. When the in-plane field was increased, domain wall motion was observed, resulting in the alignment of the patterns with the direction of the applied field. The switching mechanism of the in-plane patterns was by domain wall motion.
MORTAR MODELS OF PRESTRESSED CONCRETE REACTOR VESSELS.

The construction and testing of a small-scale mortar model of a prestressed concrete reactor vessel is described at Oak Ridge National Laboratory to determine to what extent small-mortar models and models of elastic materials, such as epoxy, can be used to investigate the stress distributions and the cracking and ultimate failure modes of prestressed concrete reactor vessels. Mortar model design and fabrication techniques are discussed. Test results for the various steps of the prestressing sequence, for a short creep test period, and for a pneumatic pressure test to failure are presented. Vessel failure was gradual; after extensive concrete cracking, the vessel liner failed with an immediate loss of pressure. The elastic and short-term creep behavior are compared to finite-element analysis predictions. Preliminary comparisons are also made with the test results for a second identical mortar model, tested hydraulically, and with the results for a small concrete prototype vessel.
The ionospheric wind dynamo - II. Solar tides

Abstract The methods described in Part 1 are used to investigate the electric currents generated in the ionosphere by the important solar diurnal and semidiurnal tidal modes. The currents produced by the solar diurnal (1,3), (1,-1), and (1,-3) modes and the solar semidiurnal (2,2) and (2,4) modes are calculated. The solar diurnal (1,3) mode, which is prominent in the E region, produces very little current. The fundamental solar diurnal mode, the (1,-1) mode, generates currents that resemble the Sq current pattern.
Anthropologists Need Redemption Too: Book Review

Redeeming the Sin: Social Science and Literature by Audrey Borenstein. Columbia University Press,New York, 1978
Patients With Cancer Referred to Hospice Versus a Bridge Program: Patient Characteristics, Needs for Care, and Survival

PURPOSE: The purpose of this study was to compare the characteristics and needs of patients with advanced cancer who were referred to hospice with those referred to a prehospice “bridge” program that is staffed by hospice nurses. PATIENTS AND METHODS: Data were gathered through retrospective review of computerized clinical records using precoded data fields of 284 patients with cancer enrolled in a bridge program and 1,000 who enrolled in a hospice program. Patient characteristics, needs for supportive care at the time of enrollment, and survival were assessed. RESULTS: Bridge patients were less likely to have Medicare or Medicaid (43% v 72%; odds ratio, 0.30; P < .001) and were younger (69 v 73 years, rank sum test; P < .001), more likely to be married (59% v 43%; odds ratio, 1.90; P < .001), and more likely to be in the highest income category (14% v 10%; odds ratio, 1.77; P = .009). Bridge patients had at least as many needs for care as did patients in hospice. Bridge patients lived significantly longe...
Criminal Actors: Natural Persons and Collectivities

This chapter deals with the theoretical issues that are raised by the fact that collectivities are actors and produce criminal and deviant acts. They are those actors to which individual human beings or “natural persons” are related as ‘‘members”; the members are seen to “belong to” the collectivities. Like other actors, collectivities have names and reputations. We love them, hate them, admire them, and resent them. They range from families and ball teams to nation-states. Some of the things they do are deviant. Some of the things some of them do are crimes. (Some of them cannot commit crimes for the same reason that some natural persons—e.g., idiots, infants, and the insane—cannot commit crimes: The law says they can’t, and crime is what the law says it is. The law can, of course, change its mind in these matters, and may be of a different mind in different jurisdictions.)
Robust STAP algorithms using prior knowledge for airborne radar applications

Abstract Space–time adaptive processing (STAP) schemes have shown promise for airborne radar applications. However, the majority of schemes develop an estimate of the covariance matrix for the test cell by averaging over surrounding range cells, called reference data. This method is only guaranteed to ensure good performance when a large set of homogeneous reference data is available with the same statistics as the test cell. In this paper, a new methodology is proposed for obtaining a covariance matrix that uses a priori knowledge. The approach is useful for detecting weak signals in cases with discretes in some range cells which do not appear in other range cells. The focus is on the use of a simple model for ground clutter that incorporates our prior knowledge on the structure of the ground clutter. The new methodology can be applied to most existing STAP schemes. This is illustrated by applying the methodology to three specific existing schemes. The modified schemes are generally shown to outperform the existing schemes in non-stationary measured data cases.
A boundary element—Random walk model of mass transport in groundwater

Abstract A boundary element solution to the convective mass transport in groundwater is presented. This solution produces a continuous velocity field and reduces the amount of data preparation time and bookkeeping. By combining this solution and the random walk procedure, a convective—dispersive mass transport model is obtained. This model may be easily used to simulate groundwater contamination problems. The accuracy of the boundary element model has been verified by reproducing the analytical solution to a two-dimensional convective mass transport problem. The method was also used to simulate a convective—dispersive problem.
Absorption measurements of OH using a CW tunable laser

Absorption of OH was measured using a CW tunable laser. Results indicate that this technique, when combined with frequency modulation, promises a sensitivity of 100,000 molecules/cu cm for OH monitoring in the atmosphere.
Adult populations of the sugi bark borer, Semanotus japonicus Lacordaire (Coleoptera: Cerambycidae), in japanese cedar stands: population parameters, dispersal, and spatial distribution

Adult populations of the sugi bark borer,Semanotus japonicusLacordaire, which attacks the trunks of Japanese cedar and cypress, were studied in two cedar stands in 1981 and 1984, using a band-trapping method developed by the author.
Conditional sampling revisited

Abstract There is a continued need for simple, robust, yet accurate methods for measuring the surface/atmosphere exchange of a wide variety of trace gases and particulates. Conditional sampling is a relatively new method that has received increasing attention in recent years because it is related to theoretically attractive eddy covariance, but does not require a rapid response sensor for the covariate. It does require rapid measurement of the vertical wind speed, w, and sorting of sampled air into two separate lines based on the direction of w. As originally proposed, the flux was then calculated as F=βΔCσw, where ΔC is the mean difference in concentration between the upward and downward moving eddies, σw the standard deviation of the vertical wind speed, and β an empirical coefficient. Subsequent exposition showed that β was derivable from the statistics of joint Gaussian distribution, although field experiments have consistently found values in the range of 0.56 to 0.58, somewhat lower than the theoretical expectation of ≈0.62–0.63. Here, we reexamine the method, and show that if the flux is instead expressed as F=b1σw2, where b1 is the regression-estimated slope of the concentration vs. wind speed relation, then it is exactly equivalent to eddy covariance. The aim of conditional sampling then becomes an estimation of b1 as ΔC/ΔW. We show that this quantity has a consistent positive bias when samples are sorted simply into positive and negative excursions from mean w. Inclusion of a sampling deadband, symmetric about the mean w, improves the accuracy of the slope estimate and decreases its variance as well. A potential problem with conditional sampling, regardless of which formulation may be used, is the effect of random measurement error (noise) in the wind speed measurement. We show that this introduces systematic errors into conditional sampling, while eddy covariance measurements are unaffected. Direct and indirect assessments indicate that these errors are too small to be significant for the sonic anemometer that we used, but it is probably wise for practitioners of the method to make certain that such is the case for the instruments used in their particular systems. We conclude that conditional sampling is a maturing method, with an increasing body of evidence indicating that the underlying relationships between scalar concentration and wind speed are sufficiently robust to support widespread use.
Early deficits in motor coordination and cognitive dysfunction in a mouse model of the neurodegenerative lysosomal storage disorder, Sandhoff disease

Mouse models of lysosomal storage diseases, including Sandhoff disease, are frequently employed to test therapies directed at the central nervous system. We backbred such mice and conducted a behavioral test battery which included sensorimotor and cognitive assessments. This is the first report of short-term memory deficits in a murine model of Sandhoff disease. We also document early onset of motor deficits using the balance beam test.
Child Maltreatment and Emergent Personality Organization: Perspectives from the Five-Factor Model.

The Five-Factor Model was used to examine personality organization in 211 six-year-old children (135 maltreated and 76 nonmaltreated). Longitudinal assessments were conducted at ages 7, 8, and 9. Six-year-old maltreated children exhibited lower agreeableness, conscientiousness, and openness to experience and higher neuroticism than did nonmaltreated children. Maltreated children also were more frequently represented in less adaptive personality clusters than were their nonmaltreated counterparts. A particularly vulnerable profile occurred predominantly among maltreated children and was related to experiencing both abuse and neglect. Child maltreatment and personality clusters were related to individual differences perceived by peers. Longitudinal stability of the personality dimensions also was assessed. At age nine, evidence was found for maintenance of the organization of the personality clusters obtained at age six and for continuity of maltreated children's personality liabilities.
Steroid-dependent postvaricella encephalomyelitis.

Postinfectious encephalomyelitis is an acute demyelinating illness that usually has its onset 3 to 7 days after the onset of a viral exanthem and has a monophasic course over 2 to 4 weeks. Recurren...
Induction of acidic fibroblast growth factor and full-length platelet-derived growth factor expression in human cardiac allografts. Analysis by PCR, in situ hybridization, and immunohistochemistry.

BACKGROUNDFurther understanding of cardiac allograft vasculopathy (CAV) is needed to improve long-term survival after cardiac transplantation. The diffuse hyperplasia of coronary intima characteristic of CAV suggests that growth factors may play a role in the development of CAV. Fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) are potent mitogens for smooth muscle cells (SMCs), and PDGF is an important cofactor in the pathogenesis of native coronary atherosclerosis.METHODS AND RESULTSReverse transcriptase/polymerase chain reaction (RT/PCR), in situ hybridization, and immunohistochemistry were used to determine whether transplantation results in increased cardiac expression of acidic (a) FGF, basic (b) FGF, and PDGF-A and -B chains. Sixty-eight myocardial biopsies from 36 heart transplant recipients and 7 normal hearts were analyzed by PCR. aFGF mRNA was present in 54 of 61 allograft biopsies and was not found in any normal heart. In situ hybridization and immunohistochemistry demon...
Proactive Compared With Passive Adverse Event Recognition: Calcium Channel Blocker–Associated Edema

This article examines the concept of passive compared with proactive surveillance for monitoring adverse events occurring with antihypertensive medications, using the example of calcium channel blocker (CCB)-induced peripheral edema. Monitoring adverse events and clinical trial safety are important functions and dependent on investigator protocols and data and safety monitoring teams. Compared with proactive surveillance, voluntary reporting systems tend to yield a lower frequency of adverse events occurrence. Limitation of data has the potential to directly influence clinical and prescribing practices. This discussion addresses advantages of proactive surveillance accomplished by patient solicitation of adverse events and investigators' direct clinical examination. A literature search between the years 2000 and 2007 was conducted on MEDLINE for randomized clinical trials and meta-analyses reporting the incidence of dihydropyridine-associated peripheral edema. The incidence of edema was high in clinical trials in which patients were actively questioned about edema development and tended to be higher than reported in the prescribing information. The incidence of dihydropyridine CCB-induced edema appears to be dependent on the method of edema assessment.
Intensive immunosuppression with high dose cyclophosphamide but without stem cell rescue for severe autoimmunity: Advantages and disadvantages

Hematopoietic stem cell transplantation (HSCT) for the treatment of severe autoimmune disorders continues to show great promise. The morbidity and mortality of the approach is relatively low and clinical benefit has been demonstrated in many, but not all patients. Furthermore, relapse following HSCT is not uncommon. Most centers now prefer onmyeloablative conditioning regimens using high dose cyclophosphamide prior to SCT; however, emerging data show that high dose cylophosphamide can be adminstered safely without the need for HSCT. Eliminating the use of HSCT after high dose cyclophosphamide shortens the duration of the procedure by several weeks, markedly reduces the cost of the procedure and eliminates the potential of reinfusing autoreactive lymphoctes with the autograft.
Association of hydrophilic versus lipophilic angiotensin-converting enzyme inhibitor use on pneumonia-related mortality.

ABSTRACT Background Recent studies suggest that angiotensin-converting enzyme (ACE) inhibitors may have beneficial effects for patients with or at risk for pneumonia. However, other studies have not found a survival benefit. Other research suggests that ACE inhibitors that are lipophilic may be superior to hydrophilic ACE inhibitors in terms of tissue penetration and inhibition of ACE. Our aim was to examine the associations of prior outpatient use of lipophilic and hydrophilic ACE inhibitors on mortality for patients hospitalized with community-acquired pneumonia. Methods A retrospective cohort study of subjects hospitalized with pneumonia at 2 tertiary teaching hospitals. We examined whether the prior outpatient use of hydrophilic or lipophilic ACE inhibitors was associated with 30-day mortality in a logistic regression analysis that adjusted for potential confounders using a propensity score. Results Data were abstracted on 787 subjects at the 2 hospitals. In our cohort, 24% (n = 186) were on ACE inhibitors at presentation: 111 lipophilic and 74 hydrophilic. Mortality was 9.2% at 30 days. In the multivariable model, lipophilic ACE inhibitor use (odds ratio 0.3, 95% confidence interval 0.1–0.8), but not hydrophilic ACE inhibitor use (0.7, 0.3–1.7), was significantly associated with 30-day mortality. Conclusions Our study suggests that future research of ACE inhibitors in pneumonia must describe the specific medications received. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect.
Intravenous immunoglobulin induction treatment in flow cytometry cross-match-positive kidney transplant recipients.

Abstract Many recent studies have demonstrated increased acute humoral, cellular, subclinical, or chronic rejection, and decreased allograft survival in flow cytometry cross-match—positive kidney transplant recipients. The use of newer techniques and more sensitive of enzyme-linked immunosorbent assay (ELISA) or Flow Beads (microparticle based methods), donor-specific anti—human leukocyte antigen (HLA) antibodies have been detected in these immunologically high-risk patients. Intravenous immunoglobulin (IVIG) has immunomodulatory effects and has been demonstrated to downregulate anti-HLA antibodies in highly sensitized dialysis patients awaiting transplantation. Our initial studies demonstrate that IVIG induction treatment is promising in flow cytometry cross-match—positive kidney transplant recipients, and thus, those patients should not be excluded from receiving transplantation despite a positive flow cytometry cross match. Further studies with long-term follow-up are required to determine the effective dose and duration of IVIG treatment, and additional studies are needed to determine the most accurate tests for risk stratification.
Weighted ℓ1-penalized corrected quantile regression for high dimensional measurement error models

Abstract Standard formulations of prediction problems in high dimension regression models assume the availability of fully observed covariates and sub-Gaussian and homogeneous model errors. This makes these methods inapplicable to measurement errors models where covariates are unobservable and observations are possibly non sub-Gaussian and heterogeneous. We propose a weighted penalized corrected quantile estimator for regression parameters in linear regression models with additive measurement errors, where unobservable covariate is nonrandom. The proposed estimators forgo the need for the above mentioned model assumptions. We study these estimators in a high dimensional sparse setup where the dimensionality can grow exponentially with the sample size. We provide bounds for the statistical error associated with the estimation, that hold with asymptotic probability 1, thereby providing the l 1 -consistency of the proposed estimator. We also establish the model selection consistency in terms of the correctly estimated zero components of the parameter vector. A simulation study that investigates the finite sample accuracy of the proposed estimator is also included in the paper.
Changes in Sodium Levels in Processed and Restaurant Foods, 2005 to 2011

Importance Excess consumption of sodium is an important cause of hypertension, a major risk factor for heart disease and stroke. The higher the level of consumption, the greater is a person’s likelihood of developing hypertension. Numerous organizations have recommended reductions in sodium intake in the United States. Roughly 80% of the sodium consumed by Americans has been added by food manufacturers and restaurants. Objective To compare the mean (SD) levels of sodium for identical products ascertained in 2005, 2008, and 2011. Design and Setting Comparison study in an academic research setting. Participants and Exposures Center for Science in the Public Interest staff have monitored sodium levels in selected processed foods and fast-food restaurant foods for many years. Main Outcomes and Measures The sodium content in identical foods, as measured in 2005, 2008, and 2011. Results Between 2005 and 2011, the sodium content in 402 processed foods declined by approximately 3.5%, while the sodium content in 78 fast-food restaurant products increased by 2.6%. Although some products showed decreases of at least 30%, a greater number of products showed increases of at least 30%. The predominant finding is the absence of any appreciable or statistically significant changes in sodium content during 6 years. Conclusions and Relevance Based on our sample, reductions in sodium levels in processed and restaurant foods are inconsistent and slow. These findings are in accord with other data indicating the slow pace of voluntary reductions in sodium levels in processed and restaurant foods. Stronger action (eg, phased-in limits on sodium levels set by the federal government) is needed to lower sodium levels and reduce the prevalence of hypertension and cardiovascular diseases.
Effect of dipyridamole therapy on myocardial ischemia in patients with stable angina pectoris receiving concurrent anti-ischemic therapy

The effects of oral dipyridamole on exercise performance and anginal symptoms were evaluated in 15 men with stable angina pectoris. In a double-blind, randomized, crossover design, patients received 75 mg of dipyridamole or placebo every 8 hours for 2 weeks in addition to their previously prescribed cardiac medications. Graded exercise tolerance testing was performed twice before randomization, at the end of each treatment period, and after single-blind placebo washout. When compared with baseline tests, the time to onset of 0.1 mV ST-segment depression was similar between dipyridamole and placebo treatments (316 +/- 89 vs 345 +/- 102 seconds, respectively, p = not significant). No significant differences existed between treatments in the peak systolic blood pressure-heart rate product or in the duration of exercise. Angina pectoris occurred during all 3 baseline exercise tests in 7 of the 15 subjects; the time to onset of angina was unchanged by either treatment. Analysis of symptom diaries conducted in 13 patients revealed no significant alteration in reported anginal symptoms during dipyridamole treatment compared with placebo treatment (0.6 +/- 0.9 vs 0.3 +/- 0.4 episodes per week). Ambulatory electrocardiographic monitoring in 12 patients revealed few episodes of ischemia during daily activities with no alteration in frequency of episodes during treatment periods. Plasma concentrations of dipyridamole did not correspond with the outcomes of exercise testing. It is concluded that chronic oral dipyridamole therapy given in its usual clinical dose does not adversely affect exercise performance, daily anginal episodes or ambulatory ischemia in patients receiving concurrent anti-ischemic medication.
Cure behavior of DGEBA vinyl ester–styrene resins near silane‐treated interfaces

An experimental technique using FTIR-ATR was developed for monitoring the copolymerization behavior of a DGEBA-based vinyl ester (VE) and styrene (ST) near the surface of a germanium internal reflection element. The data were compared to previously obtained bulk measurements of the cure behavior. It was found that the extent of conversion may be slightly greater for ST and slightly lower for VE near an untreated interface compared to the bulk. The cure behavior of VE–ST in the vicinity of a germanium IRE surface treated with a styryl amine silane (Dow Corning Z-6032) was also investigated. In this case the effect on the cure was more dramatic, as exhibited by a more rapid consumption of ST compared to VE, thus resulting in a greatly reduced final conversion of VE double bonds compared to the bulk. These results suggest that, in glass fiber–reinforced composites, such sizings could significantly alter the composition of the crosslinked network in the vicinity of a fiber surface with the potential for a lower Tg interphase being formed that is rich in homopolymerized styrene. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2784–2792, 2006
Effects of naloxone, metenkephalin, and morphine on phencyclidine-induced behavior in the rat

The effects of naloxone, metenkephalin, and morphine were tested on phencyclidine(PCP)-induced stereotyped behaviors, ataxia, and hyperactivity in the rat. Naloxone (8 mg/kg) significantly decreased stereotypy, ataxia, and hyperactivity across all PCP doses tested (2.0, 4.0, and 6.0 mg/kg). Metenkephalin (40 μg/kg) and morphine (5 and 10 mg/kg) increased ataxia at the 4.0 and 6.0 mg/kg PCP doses. Stereotypy was altered by the opiates in a dose-dependent manner; enhanced by metenkephalin (40 μg/kg) at 2.0 mg/kg and inhibited by metenkephalin (40 μg/kg) and morphine (10 mg/kg) at 4.0 and 6.0 mg/kg PCP. Locomotor activity was increased by morphine (5 mg/kg) at 2 mg/kg PCP. These results suggest an involvement of central opiate receptor mechanisms in the mediation of PCP-induced behaviors in the rat.
Heating of electrons in turbulence around the space shuttle

A model is proposed in which the strong hydrodynamic shock forming around the Space Shuttle, and occasionally detaching, generates strong hydrodynamic turbulence downstream. The level of this turbulence is found to be sufficiently great to account for the heating of electrons that has been observed. A shock formed in front of the Orbiter is shown to satisfy the Rankine-Hugoniot momentum and pressure balance equations. The hydrodynamic turbulence is coupled through ion-neutral collisions to the O2(+) and N2(+) ions of outgas.
Geometry Dependence of the Field-Induced-Guide/Antiguide Modulator

Using the field-induced-guide (FIG) concept [1], guide/antiguide modulator with on/off ratio larger than 22dB, and optical bandwidth larger than 0.55µm has been reported [2]. The device is formed with a central guide sandwich between two antiguides. For the on-state, a guide situation is created, and the input light will be confined and propagated in the central guide region. For the off-state, a antiguide situation is created, and the input light will be diffracted out of the central guide region [2]. It is obvious that the performance of the guide/antiguide modulator depends upon the geometrical dimensions of the gap G between the guide and antiguide electrodes, the active region length L, and the central guide width W. In order to understand the geometric dependence of the modulator, devices of different dimensions have been investigated, and both calculated and experimental results are reported here.
A site to remember: H3K36 methylation a mark for histone deacetylation

Chromatin structure exerts vital control over gene expression, DNA replication, recombination, and repair. In addition to altering RNA polymerase II's (Pol II) accessibility to DNA, histones are involved in the recruitment of activator and repressor complex(es) to regulate gene expression. Histone deacetylase Rpd3 exists in two distinct forms, Rpd3S and Rpd3L. Several recent studies demonstrated that the Eaf3 chromodomain, an Rpd3S subunit, recognizes Set2-methylated histone H3K36, initiating Rpd3 deacetylase activity in the wake of transcribing Pol II. Eaf3 and Set2 inhibit internal initiation within mRNA coding regions, similar to the transcription elongation factor and histone chaperone, FACT. Recent studies reviewed here demonstrate that histone deacetylation on the body of a transcribed gene is regulated via Set2-mediated methylation of histone H3-K36. These modifications provide restoration of normal chromatin structure in the wake of elongating Pol II and prevent inappropriate initiation within protein-coding regions masked by chromatin.
Mapping Quantitative Trait Loci With Censored Observations

The existing statistical methods for mapping quantitative trait loci (QTL) assume that the phenotype follows a normal distribution and is fully observed. These assumptions may not be satisfied when the phenotype pertains to the survival time or failure time, which has a skewed distribution and is usually subject to censoring due to random loss of follow-up or limited duration of the experiment. In this article, we propose an interval-mapping approach for censored failure time phenotypes. We formulate the effects of QTL on the failure time through parametric proportional hazards models and develop efficient likelihood-based inference procedures. In addition, we show how to assess genome-wide statistical significance. The performance of the proposed methods is evaluated through extensive simulation studies. An application to a mouse cross is provided.
Long-term follow-up of patients undergoing myotomy/myectomy for obstructive hypertrophic cardiomyopathy.

Abstract The long-term results of patients undergoing myotomy/myectomy of the ventricular septum for obstructive hypertrophic cardiomyopathy are documented in 31 patients (15 women, 16 men, age range 21 to 80 years [mean 55]) with mean New York Heart Association functional class III to IV congestive heart failure, who underwent radical myotomy/myectomy at the Brigham and Women's Hospital from 1972 to 1991. Preoperative gradients by catheterization or echocardiography ranged from 26 to 240 mm Hg (average 96). There were no operative deaths. Two patients developed early postoperative complete heart block requiring a transvenous pacemaker. Clinical follow-up was 1 to 14 years (mean 6.5). All surviving patients were restudied by echocardiography and clinical examination. The mean postoperative functional class was II. Postoperative gradients ranged from 0 to 30 mm Hg (mean 4.5) (p
Medication Administration Practices in Pennsylvania Schools

As a result of various health concerns, children are receiving an increased number of medications while at school. In Pennsylvania, the School Code mandates a ratio of 1 certified school nurse to 1,500 students, which may mean that 1 school nurse is covering 3-5 buildings. This implies that unlicensed personnel are administering medications, a violation of licensing laws in Pennsylvania. The purpose of this study was to determine the policies and practices that Pennsylvania public schools have in place regarding medication administration. The sample consisted of 314 state-certified school nurses who returned a 71-question survey. Findings indicated that school nurses are very concerned about issues related to medication administration. Additional findings identified the lack of standing orders to administer over-the-counter medications, the increase in medication errors when the school nurse had responsibility for multiple buildings, and the lack of understanding of the ramifications of the Nurse Practice Act on school nursing practice in regard to delegation. Recommendations for practice include development of detailed policies and procedures and collaboration among all stakeholders in the development of policies that address legal issues.
Improved Convergence and Robustness of USM3D Solutions on Mixed Element Grids (Invited)

Several improvements to the mixed-element USM3D discretization and defect-correction schemes have been made. A new methodology for nonlinear iterations, called the Hierarchical Adaptive Nonlinear Iteration Method, has been developed and implemented. The Hierarchical Adaptive Nonlinear Iteration Method provides two additional hierarchies around a simple and approximate preconditioner of USM3D. The hierarchies are a matrix-free linear solver for the exact linearization of Reynolds-averaged Navier–Stokes equations and a nonlinear control of the solution update. Two variants of the Hierarchical Adaptive Nonlinear Iteration Method are assessed on four benchmark cases, namely, a zero-pressure-gradient flat plate, a bump-in-channel configuration, the NACA 0012 airfoil, and a NASA Common Research Model configuration. The new methodology provides a convergence acceleration factor of 1.4 to 13 over the preconditioner-alone method representing the baseline solver technology.
Natural convection in a shallow porous cavity—the Brinkman model

Abstract The natural convection in a shallow porous rectangular cavity with differentially heated sidewalls is examined using the Brinkman model. The heat transfer rate through the cavity is determined in terms of a Nusselt number, in the limit of vanishingly small aspect ratio. Two types of boundary conditions are considered. Case I deals with a cavity with all rigid boundaries so that the no-slip boundary conditions can be imposed. In case II, the cavity has a free upper surface. The present analysis shows that the Brinkman model and Darcy's law give virtually the same result for the heat transfer rate when the Darcy number, based on the depth of the cavity, is less than the order of 10 −4 . We also find that the presence of a free surface can significantly increase the heat transfer rate through the cavity, especially when the permeability of the medium is high.
EUS-guided ethanol versus saline solution lavage for pancreatic cysts: a randomized, double-blind study.

Background Surgery for pancreatic cysts is associated with significant morbidity. A pilot study previously demonstrated the safety of EUS-guided ethanol lavage of pancreatic cysts. Objective To determine whether EUS-guided ethanol lavage would decrease pancreatic cyst size more than saline solution lavage. Design Prospective, multicenter, randomized trial. Setting Two tertiary referral hospitals in the United States. Patients Patients referred for EUS with a 1- to 5-cm unilocular pancreatic cyst were randomized to blinded ethanol or saline solution lavage. Three months later, the cyst diameter was remeasured by EUS, and a second unblinded ethanol lavage was performed. Interventions EUS-guided pancreatic cyst lavage. Main Outcome Measurements Cyst ablation based on size changes from follow-up EUS, CT, and histology of resected specimens. Results Of 58 patients randomized, 16 were excluded and 42 underwent initial ethanol (n = 25) or saline solution (n = 17) lavage. Ethanol lavage resulted in a greater mean percentage of decrease in cyst surface area (−42.9; 95% CI, −58.4 to −27.4) compared with saline solution alone (–11.4; 95% CI, −25.0 to 2.2; P = .009). Nineteen (76.0%) of 25 and 14 (82.3%) of 17 patients randomized to ethanol and saline solution, respectively, underwent a second ethanol lavage. A follow-up CT scan demonstrated resolution in 12 (33.3%) of 36 cysts. Histology of 4 resected cysts demonstrated epithelial ablation ranging from 0% (saline solution alone) to 50% to 100% (1 or 2 ethanol lavages). Complication rates were similar in all groups. Limitation Short-term follow-up. Conclusions EUS-guided ethanol lavage results in a greater decrease in pancreatic cyst size compared with saline solution lavage with a similar safety profile. Overall CT-defined complete pancreatic cyst ablation was 33.3%. (This study is registered at ClinicalTrials.gov, identifier NCT00233038.)
Vesicular Stomatitis Virus (Indiana Serotype): Transovarial Transmission by Phlebotomine Sandflies

Transovarial transmission of vesicular stomatitis virus (Indiana serotype) by experimentally infected Lutzomyia trapidoi and Lutzomyia ylephiletrix to their progeny was demonstrated. Virus was recovered from all developmental stages; mean virus titers from egg to first generation adult showed a four-log increase, indicating that virus multiplication occurred during development of the sandflies. Virus titers in first generation adult females were comparable to those found in their parents. These infected female sandflies transmitted vesicular stomatitus virus Indiana by bite to susceptible animals and transmitted the virus transovarially to their offspring (second generation). Results demonstrate a possible mechanism for transmission and maintenance of this virus in nature without a vertebrate (heat) host reservoir.
Discovery and Initial Structure-Activity Relationships of N-Benzyl Tricyclic Indolines as Antibacterials for Methicillin-Resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent drug resistant bacteria. In 2012, over 11,000 fatalities in the United States were directly attributable to MRSA. In an effort to develop novel structural and mechanistic classes of antibacterial agents to fight against MRSA, we have optimized a hit compound, Of4, previously discovered in a screening campaign of a bio-inspired polycyclic indoline library previously developed in our lab. We took advantage of our concise and versatile synthetic strategy to conduct initial structure-activity relationship studies of Of4, and we now report the discovery of compound 4k as a more potent antibacterial agent against S. aureus. Compound 4k also displayed equivalent activity in four MRSA and a methicillin-susceptible strains while demonstrating an improved mammalian cytotoxicity profile compared to Of4. Interestingly, 4k shares the same tricyclic indoline core as Of1, a β-lactam-selective resistance-modifying agent, but harbors a distinct modification pattern conferring unique bioactivity. This phenomenon is reminiscent of many bioactive natural products.
Distinct early and late subcomponents of the photic blink reflex: Response characteristics in patients with retrogeniculate lesions

To assess cortical contributions to the photic blink reflex, signal averaged electromyograms (EMG) were compared for responses to strobe flashes presented within the blind and sighted hemifields of 13 patients with occipital lobe lesions. Reflexes evoked by flashes within the scotoma were virtually identical to those evoked by flashes within the intact visual field. This suggests that both the early and late components of this reflex (R50 and R80, respectively) are mediated by subcortical structures that do not require, or benefit from, conscious visual processing. Additional findings included larger R80s at the eyelid contralateral to the lesion, regardless of stimulated hemifield. This presumably reflects the loss of a tonic descending influence of visual cortex onto the motor limb of the reflex arc. The R80 was also larger for stimuli activating the crossed (temporal hemifield) rather than the uncrossed (nasal hemifield) afferent pathway.
A fault-tolerant switching scheme for a high-power high-frequency-link inverter

A modulation-based fault-tolerant switching scheme (FTSS) is outlined for an isolated high-frequency-link (HFL) inverter. It comprises a front-end Dc/pulsating-Dc converter followed by an Ac/Ac converter. At first, the lost phase in the Dc/Ac Converter is identified based on the type of distorted output line voltages and then modulation references are changed accordingly so as to restore the output line voltages. The proposed FTSS ensures operation under different types of fault conditions in the front-end Dc/pulsating-Dc converter without redundant circuits. Detailed results on the switching scheme as well as experimental validation using a fabricated prototype are presented.
Effects of thyroid hormone on bone

It is relatively well established that thyroid hormone has a clinically significant effect on bone. Although some aspects, such as the bone mineral loss associated with overt thyrotoxicosis have been relatively well described, others remain much less clear. A major focus of this review is on the effects of chronic exogenous thyroid hormone administration on bone physiology. When thyroid hormone dosage is supraphysiologic, an iatrogenic clinical model is produced comparable to endogenous “subclinical hyperthyroidism”. Indeed, literature on bone mineral changes in the latter entity may be analyzed as representative of effects of excessive circulating thyroid hormone. At the molecular level, thyroid hormone receptors as well as thyroid-stimulating hormone (TSH) receptors have been identified on osteoblasts and osteoclasts, and have been shown to mediate significant effects on bone physiology. In reviewing the literature extant on this subject, an important clinical distinction has to be made between the effects on bone of thyroid hormone given in “suppressive” dosage vs “replacement” dosage. Some, albeit rare, earlier studies reported or implied a potentially harmful effect of physiologic replacement dosage of thyroid hormone on bone. Retrospective analysis indicates that these studies were plagued with a number of problems. Insensitive TSH assays hampered the ability to accurately determine if the replacement dosage was truly physiological, and other problems were related to patient population selection and the techniques used to assess bone mineral density. Data on fracture risk is particularly scant with most studies failing to identify thyroid hormone therapy as a risk factor for fracture. Rather, it would appear that when bone mineral loss is seen in men or premenopausal women on replacement dosage of thyroid hormone, there will be some other confounding element playing the dominant etiologic role. In postmenopausal women, the most important contributing factor to osteoporosis is estrogen deficiency, and bone loss in estrogen-deficient women will be clearly accelerated by concomitant suppressive dosage of thyroid homone. Availability of sensitive TSH assays allows us to carefully titrate thyroid hormone dosage and avoid excesses. The risks of even slight thyroid hormone excess on the heart have been recognized for the past decade, and those risks taken together with the risk of bone loss should cause us to re-examine the indications for suppressive dosage of thyroid hormone. When suppressive dosage is necessary (e.g., for patients with residual or recurrent thyroid cancer), the bone-resorptive effects of thyroid hormone should be tempered by eliminating all other factors contributing to bone loss and considering the addition of a boneenhancing therapeutic agent such as a bisphosphonate.
Competing for the Crown Inter-rebel Competition and Civilian Targeting in Civil War

What factors contribute to the victimization of civilians during civil war? Drawing on research from various disciplines, we argue that increasing competition within a civil conflict system brought on by the entrance of new factions contributes to an increase in civilian targeting by existing rebel groups. Specifically, we argue that existing groups are more likely to target civilians immediately upon the entrance of new rivals due to the perceived threat to control over resources and because the arrival of new groups diminishes the gains existing groups expect from either victory or successful conflict bargaining. We further argue that violence against civilians increases during periods in which rival factions engage in direct, violent conflict with one another. Our analysis diverges from existing studies by arguing and demonstrating that fluctuations in competition rather than the simple presence of competing groups produce spikes in civilian targeting by nonstate actors. We evaluate and find support for our argument using monthly data for African conflicts between 1989 and 2010.
Effect of nonuniform target motion on radar backscattered waveforms

The effect of nonuniform motion on radar waveforms is discussed. By considering the physical model of a perfectly reflecting mirror with an arbitrary law of motion r(t), it is possible to determine the functional form of the scattered wave at the receiver for any waveform in general. The particular example of an interrupted continuous wave waveform is used to analyse the effect of nonuniform motion on the return spectrum. These models provide a theoretical foundation for the observations of micro-Doppler that have been discussed by a number of authors. Finally, some of the implications, both physical and mathematical, of nonuniform motion for time–frequency methods are addressed.
SERU: An Alternative to Licensing—An Interview with Selden Durgom Lamoureux

Abstract The Shared E-Resources Understanding (SERU) initiative ( www.niso.org/committees/seru ) became an official working group of the National Information Standards Organization (NISO) at the end of 2006. This initiative seeks to create best practices for licensing as an alternative to traditional licensing and has created a draft document to support this purpose. Selden Durgom Lamoureux has been integrally involved in shaping this alternative to licensing. Within the context of this interview, she discusses the early development and timeline of this initiative, the initial purpose and objectives, partners who have assisted in furthering the initiative’s development, NISO’s involvement and the outcomes of the group. A “Best Practice Option” document discussing the issues behind this initiative and written by Judy Luther, one of the co-chairs of SERU, is included as an appendix.
Basic pharmacology relevant to drug abuse assessment: tramadol as example

Tramadol is a centrally acting analgesic in widespread use throughout the world. Although there is extensive preclinical, clinical, post-marketing and epidemiological data indicating relatively low--but not zero--abuse/dependence, questions continue to arise about its abuse potential and appropriate regulatory classification. This article considers these questions from the point of view of the basic pharmacology of tramadol. There is nothing unique about tramadol in this regard, but its multimodal mechanism of action, pharmacologically active enantiomers, and active metabolite make it a particularly instructive and relevant example.