cssi/SciSciGPT-SciSciNet huggingface dataset:
Structural analysis of the active sites of dihydrofolate reductase from two species of Candida uncovers ligand-induced conformational changes shared among species

A novel strategy for targeting the pathogenic organisms Candida albicans and Candida glabrata focuses on the development of potent and selective antifolates effective against dihydrofolate reductase. Crystal structure analysis suggested that an essential loop at the active site (Thr 58-Phe 66) differs from the analogous residues in the human enzyme, potentially providing a mechanism for achieving selectivity. In order to probe the role of this loop, we employed chemical synthesis, crystal structure determination and molecular dynamics simulations. The results of these analyses show that the loop residues undergo ligand-induced conformational changes that are similar among the fungal and human species.
On the singularities of the scattering amplitude in a simple field theoretic model

Charged scalar fixed-point-source theory is considered in the regime of strong coupling from the standpoint of the Chew-Low equation as a model field theory within which one cannot distinguish which of two particles (e.g. nucleon and isobar) is elementary and which is a bound state of the other and a pion. In the case of the one-meson approximation, it is shown that this reciprocal relationship extends even to those values of the renormalized coupling constant for which the isobar pole becomes unphysical. The same extension of reciprocity to the second Riemann sheet also obtains in the one-meson approximation in a bound-state model recently considered by Low.
Breaking all the rules: Radically reinventing moral education through compassionate discipline

As schools struggle to address student behavioral challenges, the moral nature of discipline in schools emerges as a factor that can strengthen approaches and responses to student disciplinary issues. Given, discipline is an essentially moral act, this paper seeks to explore the ways in which schools can overcome resistance to moral and spiritual aspects of discipline. Ultimately, we contend, schools must revision a new approach to discipline that would not only result in more appropriate behavior from students but also support staff approaches to discipline in a radically different way, through compassion.
Potential Limitations of the 16S-23S rRNA Intergenic Region for Molecular Detection of Bartonella Species

PCR targeting the 16S-23S rRNA gene intergenic transcribed spacer (ITS) region has been proposed as a rapid and reliable method for the detection of Bartonella species DNA in clinical samples. Because of variation in ITS sequences among Bartonella species, a single PCR amplification can be used to detect different species within this genus. Therefore, by targeting the ITS region, multiple PCRs or additional sample-processing steps beyond the primary amplification can be avoided when attempting to achieve molecular diagnostic detection of Bartonella species. Although PCR amplification targeting this region is considered highly sensitive, amplification specificity obviously depends on primer design. We report evidence of nonspecific PCR amplification of Mesorhizobium species with previously published primers that were designed to amplify the Bartonella consensus ITS region. Use of these or other, less species-specific, primers could lead to a false-positive diagnostic test result when evaluating clinical samples. We also report the presence of Mesorhizobium species DNA as a contaminant in molecular-grade water, a series of homologous sequences in the ITS region that are common to Bartonella and Mesorhizobium species, the amplification of Mesorhizobium DNA with unpublished primers designed in our laboratory targeting the ITS region, and the subsequent design of unambiguous ITS primers that avoid nonspecific amplification of Mesorhizobium species. Our results define some potential limitations associated with the molecular detection of Bartonella species in patient samples and indicate that primer specificity is of critical importance if the ITS region is used as a diagnostic target for detection of Bartonella species.
The degree of skin involvement identifies distinct lung disease outcomes and survival in systemic sclerosis

Objective To determine whether the pattern of skin involvement can predict clinical features, risk of restrictive lung disease (RLD) and survival in a large scleroderma (SSc) cohort. Methods Demographic and clinical data collected over 30 years from 2205 patients with SSc were retrospectively analysed after subdividing subjects into four subtypes based on pattern of skin fibrosis: type 0 (no skin involvement), type 1 (limited to metacarpophalangeal joints), type 2 (distal to elbows/knees) and type 3 (proximal to elbows/knees). Clinical features associated with skin subsets were identified by regression analyses. Kaplan–Meier and Cox proportional hazards models were used to compare time to RLD and survival across subtypes. Results The presence and severity of RLD were positively associated with skin subtype (p Conclusions These data suggest that the current classification subdividing SSc into limited and diffuse cutaneous subtypes misclassifies an intermediate group of patients exhibiting unique autoantibody profile, disease course and clinical outcomes.
A vision system for real-time positioning, navigation, and video mosaicing of sea floor imagery in the application of ROVs/AUVs

A vision system has been developed based on the application of a 3D direct motion estimation algorithm to facilitate autonomous or operated-assisted missions of AUVS and ROVs near the ocean floor. The main capabilities of interest are vision-based vehicle positioning, navigation and trajectory following, as well as mosaicking of sea bed images. The system performance in enabling these functions has been demonstrated on a three-thruster surface vehicle that operates in a 6'/spl times/12'/spl times/6' water tank, with the bottom surface set up to simulate a sea floor environment. Images from a down-look camera installed on the vehicle are digitized and processed on a Windows NT Dual Pentium-200 to estimate the vehicle's motion, which is transmitted via the serial link to the vehicle control system running on a 386 processor. This information is employed to maintain or move to a desired position, follow a specified trajectory, and to construct in (near) real-time a composite image of the scene surface.
Transfer function characteristics of bluff-body stabilized, conical V-shaped premixed turbulent propane-air flames

The response of bluff-body stabilized conical V-shaped premixed flames to periodic upstream velocity oscillations was characterized as a function of oscillation frequency, mean flow velocity, and equivalence ratio. The flame heat release response to the imposed velocity oscillations was determined from the CH∗ chemiluminescence captured by two photomultiplier (PMT) detectors at a wavelength of 430 nm. One of the PMTs viewed flame radiation in a 10-mm horizontal slice, 50 mm above the bluff-body. The second PMT observed the overall flame radiation. The flame transfer function characteristics were determined from the spectral analysis of the velocity and PMT signals. It was found that the flame heat release amplitude response is confined to low-frequency excitation below a Strouhal number of 4. The phase relationship of the transfer function for these turbulent flames was evaluated using the signal from the spatially masked PMT. The transfer function estimate based on these data exhibits second-order characteristics with a phase lag between the velocity and heat release signals. The localized heat-release response contains frequencies that are multiples of the excitation frequency, suggesting splitting and tilting of flame structures as well as some nonlinear effects. Increase of flame equivalence ratio from lean toward stoichiometric resulted in slight amplification of the high-frequency response.
Family and community involvement in schools: results from the School Health Policies and Programs Study 2006.

Background: Family and community involvement in schools is linked strongly to improvements in the academic achievement of students, better school attendance, and improved school programs and quality. Methods: The Centers for Disease Control and Prevention conducts the School Health Policies and Programs Study every 6 years. In 2006, computer-assisted telephone interviews or self-administered mail questionnaires were completed by state education agency personnel in all 50 states plus the District of Columbia and among a nationally representative sample of school districts (n = 461). Computer-assisted personal interviews were conducted with personnel in a nationally representative sample of elementary, middle, and high schools (n = 1029) and with a nationally representative sample of teachers of required health education classes and courses (n = 912) and required physical education classes and courses (n = 1194). Results: Although family and community involvement in states, districts, and schools was limited, many states, districts, and schools collaborated with community groups and agencies to promote and support school health programs. More than half of districts and schools communicated information to families on school health program components. Teachers in 55.5% of required health education classes and courses and 30.8% of required physical education classes and courses gave students homework or projects that involved family members. Conclusions: Although family and community involvement occurred at all levels, many schools are not doing some of the fundamental things schools could do to increase family involvement. Improvements in family and community involvement can support school health programs in states, districts, schools, and classrooms nationwide.
Analysis of Phenobarbital in Relation to its Degradation Products

The effect of the degradation products of phenobarbital upon six of its quantitative literature assays has been studied. Two new colorimetric procedures and an infrared method for the determination of phenobarbital are described and the effects of degradation products upon these assays is also discussed. Differential ultraviolet spectrophotometric analysis was found to be the assay procedure most useful for the determination of phenobarbital in the presence of its degradation products. This analysis has also been successfully applied to phenobarbital in various dosage forms.
Concreteness Fading in Mathematics and Science Instruction: A Systematic Review.

A longstanding debate concerns the use of concrete versus abstract instructional materials, particularly in domains such as mathematics and science. Although decades of research have focused on the advantages and disadvantages of concrete and abstract materials considered independently, we argue for an approach that moves beyond this dichotomy and combines their advantages. Specifically, we recommend beginning with concrete materials and then explicitly and gradually fading to the more abstract. Theoretical benefits of this "con- creteness fading" technique for mathematics and science instruction include (1) helping learners interpret ambiguous or opaque abstract symbols in terms of well-understood concrete objects, (2) providing embodied perceptual and physical experiences that can ground abstract thinking, (3) enabling learners to build up a store of memorable images that can be used when abstract symbols lose meaning, and (4) guiding learners to strip away extraneous concrete properties and distill the generic, generalizable properties. In these ways, concreteness fading provides advantages that go beyond the sum of the benefits of concrete and abstract materials.
Role of auditory non-verbal working memory in sentence repetition for bilingual children with primary language impairment

Background Sentence repetition performance is attracting increasing interest as a valuable clinical marker for primary (or specific) language impairment (LI) in both monolingual and bilingual populations. Multiple aspects of memory appear to contribute to sentence repetition performance, but non-verbal memory has not yet been considered. Aims To explore the relationship between a measure of non-verbal auditory working memory (NVWM) and sentence repetition performance in a sample of bilingual children with LI. Methods & Procedures Forty-seven school-aged Spanish–English bilingual children with LI completed sentence repetition and non-word repetition tasks in both Spanish and English as well as an NVWM task. Hierarchical multiple linear regression was used to predict sentence repetition in each language using age, non-word repetition and NVWM. Outcomes & Results NVWM predicted unique variance in sentence repetition performance in both languages after accounting for chronological age and language-specific phonological memory, as measured by non-word repetition. Conclusions & Implications Domain-general memory resources play a unique role in sentence repetition performance in children with LI. Non-verbal working memory weaknesses may contribute to the poor performance of children with LI on sentence repetition tasks.
Oral N-Carbamylglutamate Supplementation Increases Protein Synthesis in Skeletal Muscle of Piglets

This study investigated the potential mechanisms by which oral supplementation of N-carbamylglutamate (NCG), an analogue of endogenous N-acetylglutamate (an activator of arginine synthesis) increases growth rate in sow-reared piglets. Two piglets of equal body weight (BW) and of the same gender from each lactating sow were allotted to receive oral administration of 0 (control) or 50 mg of NCG/kg BW every 12 h for 7 d. Piglets (n=32; BW=3 kg) were studied in the food-deprived or fed state following the 7 d of treatment. Overnight food-deprived piglets were given NCG or water (control) at time 0 and 60 min. Piglets studied in the fed state were gavage-fed sow's milk with their respective NCG treatment at 0 and 60 min. At 60 min, the piglets were administered a flooding dose of [3H]phenylalanine and killed at 90 min to measure tissue protein synthesis. Piglets treated with NCG gained 28% more weight than control pigs (P<0.001) over the 7-d period. Fed pigs had greater rates of protein synthesis in longissimus dorsi and gastrocnemius muscles and duodenum compared with food-deprived pigs (P<0.001). Absolute protein synthesis rates in longissimus dorsi (P=0.050) and gastrocnemius (P=0.068) muscles were 30 and 21% greater, respectively, in NCG-treated compared with control pigs. Piglets supplemented with NCG also had greater plasma concentrations of arginine and somatotropin than control pigs (P<0.001). The results suggest that oral NCG supplementation increases plasma arginine and somatotropin levels, leading to an increase in growth rate and muscle protein synthesis in nursing piglets.
Beyond the Supermarket Solution: Linking Food Deserts, Neighborhood Context, and Everyday Mobility

Most research on urban food deserts has employed spatial measures of accessibility, recording distances to various food stores from place of residence. Despite the popularity of this approach, empirical support for its prediction of dietary and health outcomes has been inconsistent. One reason might be the ways in which food deserts frame food access as fundamentally an issue of food supply. This article suggests a complementary approach that examines how store characteristics, neighborhood context, and individual mobility interact to shape food provisioning practices. I recruited thirty-eight participants living in two low-income neighborhoods of Minneapolis, Minnesota, tracking their daily mobility and the food sources they used over a five-day study period. Follow-up interviews gathered more information on the food stores used by participants. Project results show that participants were highly mobile in their food shopping, visiting 153 different locations on 217 different shopping trips at an average ...
Behavioral Approaches to Primary and Secondary Prevention of Coronary Heart Disease

Coronary heart disease (CHD) is a chronic, progressive disease widely prevalent in industrial societies, including the United States. More than 3,400 Americans suffer myocardial infarctions each day, incurring an annual estimated economic cost of $60 billion. A first step in the prevention of this disease has been the identification of characteristics, or risk factors, that are present in individuals prone to develop CHD. Epidemiological studies have found these factors to include a family history of heart disease, elevations in blood pressure and serum cholesterol, cigarette smoking, obesity, a sedentary lifestyle, and the Type A behavior pattern.
Approach to the Treatment of Chronic Metabolic Acidosis in CKD

Chronic metabolic acidosis is not uncommon in patients with chronic kidney disease (CKD). Clinical practice guidelines suggest that clinicians administer alkali to maintain serum bicarbonate level at a minimum of 22 mEq/L to prevent the effects of acidosis on bone demineralization and protein catabolism. Small interventional studies support the notion that correcting acidosis slows CKD progression as well. Furthermore, alkaline therapy in persons with CKD and normal bicarbonate levels may also preserve kidney function. Observational studies suggest that targeting a serum bicarbonate level near 28 mEq/L may improve clinical outcomes above and beyond targeting a value ≥ 22 mEq/L, yet values > 26 mEq/L have been reported to be associated with incident heart failure and mortality in the CRIC (Chronic Renal Insufficiency Cohort) Study. Furthermore, correcting acidosis may provoke vascular calcification. This teaching case discusses several uncertainties regarding the management of acidosis in CKD, such as when to initiate alkali treatment, potential side effects of alkali, and the optimum serum bicarbonate level based on current evidence in CKD. Suggestions regarding the maximum sodium bicarbonate dose to administer to patients with CKD to achieve the target serum bicarbonate concentration are offered.
Effects of Clinical Pathways: Do They Work?

Objective:Evaluation of the effect of implementing clinical pathways is a relatively new field in health care research. Little is known about the way in which practice is influenced by the implementation of clinical pathways, and to what degree. This review takes significant steps in answering these questions by describing the parameters that are used in literature as indicators to evaluate clinical pathways.Methods:A Medline-based review of literature published between 2000 and 2002 was carried out using the keywords ‘clinical pathway’, ‘critical pathway’, ‘care map’, ‘care pathway’ and ‘integrated care pathway’. Articles were selected if they contained any form of evaluation, outcome or indicator concerning the use of clinical pathways. This included all types of research design and sample size. A total of 200 articles were selected. Relevant data were summarized using the following characteristics: country of origin, clinical field of expertise, research design, sample size, clinical outcome indicators...
Robust efficiency measures for linear knapsack problem variants

Abstract Numerous combinatorial optimization applications, such as the mobile retailer product mix problem, utilize the multidemand, multidimensional knapsack problem variant in which there are multiple knapsack constraints requiring a weighted summation of the variables to be less than or equal to a nonnegative value and multiple demand constraints requiring a weighted summation of the variables to be greater than or equal to a nonnegative value. The purpose of this paper is to demonstrate that core variables and efficiency measures, concepts used in the most efficient solvers to-date for binary knapsack problems and some of its variants, can be extended to the multidemand, multidimensional knapsack problem variant. Specifically, new efficiency measure calculations are provided and their properties are mathematically proven and experimentally demonstrated. The contribution of such measures to knapsack problem research is that these measures are applicable to all knapsack problem variants with a single linear objective function and linear constraints of any quantity. The applicability of these new measures is demonstrated through the development of three heuristic procedures: a Fixed-Core heuristic, a Genetic Algorithm, and a Kernel Search heuristic. The results from these tests are compared with the results from a commercial solver and an existing heuristic. The findings from these tests demonstrate that the Fixed-Core and Kernel Search heuristics developed for this paper are the most efficient solvers to-date for hard multidemand, multidimensional knapsack problems.
Nuclear ‘Defence’ — or Conflict Resolution

This was not an episode from ‘Star Trek’ or an update of H. G. Wells’s War of the Worlds. It was a real alert. Bombers were about to take off; men in silos were ready to turn the keys that would fire off nuclear-loaded rockets. All because of a malfunctioning ‘electronic chip, about the size of a dime, which costs forty-six cents’. On such potential failures hangs the fate of the Earth.
Seeing small: Enabling new discoveries in energy materials through advanced transmission electron microscopy

A transmission electron microscopy (TEM)/ scanning transmission electron microscopy (STEM) and in-situ TEM have emerged as powerful tools for the characterization of energy materials. Aberration-corrected TEM/STEM enables atomic and structural imaging resolution below 0.1 nanometers while performing chemical analysis at the atomic level. In-situ TEM allows dynamic real-time imaging of energy materials behavior. In this talk, a brief overview of aberration-corrected TEM/STEM and in-situ TEM will be presented and related to the quest for investigating energy materials. Subsequently, the power of these techniques in providing scientific insight into developing Li-ion batteries, proton exchange membrane fuel cells and catalyst nanoparticles will be discussed. Paulo J. Ferreira, J Material Sci Eng 2013, 2:4 http://dx.doi.org/10.4172/2169-0022.S1.010
A new vector 2D photolithography simulation tool

A new vector optical lithography simulator, METROPOLE, is presented. Rigorous simulations run quickly on a workstation for complex 2D regular and phase shifting masks, substrate bleaching, optical metrology and alignment problems. An analysis of a novel phase shifting techniques is undertaken to highlight the usefulness of the program. >
God and apple pie: religious myths and visions of America, by Christopher Buck, Kingston, NY, Educator’s International Press, 2015, xiv + 421 pp., US$26.95 (hardcover), ISBN 978 1981928 154

I grew up in a town that held annual weeklong revival meetings each autumn, co-sponsored by all of the churches (or at least the Protestant ones) in the town. Together they provided a budget suffic...
Examining students' concerns related to online delivery of an introductory computer programming course

Many institutions are offering online courses, as part of their regular schedule, to provide more flexible course offerings to students with the hope of some cost savings in the end. In this paper, we will focus on examining some of the students' ratings and comments that have been reported in student rating of teaching effectiveness (SRTE) surveys, for an online introductory programming course, during the past few years. We will look at the issues that we have identified to play a role in the SRTE surveys of our online course and examine the teaching from several different perspectives that include effectiveness/appropriateness of online courses for students. The paper includes a set of specific and general recommendations to address the legitimate students' concerns that, we believe, would make the course delivery more effective and enjoyable for students.
Fatigue testing of biomaterials and their interfaces

Abstract Objective The objective of this article is to describe the importance of fatigue to the success of restorative dentistry, with emphasis on the methods for evaluating the fatigue properties of materials in this field, and the durability of their bonded interfaces. Methods The stress-life fatigue and fatigue crack growth approaches for evaluating the fatigue resistance of dental biomaterials are introduced. Emphasis is placed on in vitro studies of the hard tissue foundation, restorative materials and their bonded interfaces. The concept of durability is then discussed, including the effects of conventional “mechanical” fatigue combined with pervasive threats of the oral environment, including variations in pH and the activation of endogenous dentin proteases. Results There is growing evidence that fatigue is a principal contributor to the failure of restorations and that measures of static strength, used in qualifying new materials and practices, are not reflective of the fatigue performance. Results of selected studies show that the fundamental steps involved in the placement of restorations, including the cutting of preparations and etching, cause a significant reduction to the fatigue strength of the hard tissue foundation. In regards to the bonded interface, results of studies focused on fatigue resistance highlight the importance of the hybridization of resin tags, and that a reduction in integrity of the dentin collagen is detrimental to the durability of dentin bonds. Significance Fatigue should be a central concern in the development of new dental materials and in assessing the success of restorative practices. A greater recognition of contributions from fatigue to restoration failures, and the development of approaches with closer connection to in vivo conditions, will be essential for extending the definition of lifelong oral health.
The Privacy Paradox: A Facebook Case Study

The utility of social networks is contingent on information sharing, which constrains privacy. Engaging in online social networks is seen to indicate that the participants either do not care about privacy, do not understand the risks of information sharing, or find privacy controls to be unusable. Given the contextual nature of privacy all three models may exist in the population and in fact in a single person. We introduce the three distinct academic threads leading to each model, i.e. rational economics, risk behavior, and human computer interaction. Further, we conduct a survey based study to elicit the relative strengths of these explanations for information sharing on Facebook (n=384). Our findings indicate that while all three explanations are relevant, their relative strengths are different. The perceived risk of sharing information is the most important determinant of privacy behaviors; to a lesser extent usability of privacy controls is important. Finally, privacy preferences is the least important factor; thus, the explanation that people don’t care is weakest explanation of the privacy paradox (on Facebook).We argue that Facebook should invest in both more usable privacy controls and awareness of those controls. In general better controls and more information increased information sharing and lowered the perceptions of risk, thereby aligning expressed attitudes with observed behaviors and addressing the paradox. We note that privacy risks behaviors are determined by dread risk and familiarity on Facebook, as for risks offline. Thus, Facebook privacy efforts should leverage prior research in risk communication offline. Specifically, risk averse behaviors can be encouraged if risk communication focuses on severe, catastrophic, and rare consequences of information sharing.
Trauma and the role of the school-based occupational therapist

Recent research has shown that experiencing trauma in childhood may have a significant effect on school performance, particularly in the occupational performance areas of education, social particip...
Role of Striatal A2A Receptor Subpopulations in Neurological Disorders

A very significant density of adenosine A2A receptors (A2AR) is present in the striatum, where they are preferentially localized postsynaptically in enkephalinergic-GABAergic-medium spiny neurons (enkephalinergic MSN). In this localization, different subpopulations of A2AR with different functions exist. Their differential function seems to depend mostly on their ability to form heteromers with other G-protein-coupled receptors, such as dopamine D2, cannabinoid CB1 and glutamate mGlu5 receptors. Furthermore, striatal A2AR are also localized presynaptically, in corticostriatal glutamatergic terminals that contact dynorphinergic-GABAergic-medium spiny neurons (dynorphinergic MSN). These presynaptic A2AR heteromerize with A1 receptors and their activation facilitates glutamate release. Pharmacological tools are becoming available that allow the functional evaluation of some of these different subpopulations of A2AR, which can therefore provide selective targets for drug development in different basal ganglia disorders. In fact, alterations in the function of different A2AR subpopulations have recently been observed in Parkinson’s disease and in animal models of Huntington disease and Restless Legs Syndrome.
School spirits: alcohol and collegiate sports fans.

While studies have addressed alcohol use and related problems among college athletes, little is known about the drinking patterns of non-athletes who are sports fans. This study examines the relationship between alcohol use and interest in collegiate sports on two levels. First, do sports fans in college binge drink more and exhibit more negative alcohol-related outcomes than other students? Second, do colleges with large numbers of sports fans have higher rates of heavy drinking and accompanying secondhand effects affecting other students? The study analyzed the responses of a nationally representative sample of students who completed questionnaires in the spring of 1999 regarding their extracurricular activities and substance use. The responses of 3445 student sports fans were compared to those of 8405 students who were not sports fans. More sports fans drank alcohol, engaged in binge drinking, had a heavy drinking style and reported alcohol-related problems than nonfans. The percentage of sports fans at a school was associated with binge drinking rates and the secondhand effects. The implications for those working with college athletics and for alcohol prevention personnel are discussed.
Comparison of microwave oven and convection oven for acid hydrolysis of dietary fiber polysaccharides

Hydrolysis of dietary fiber polysaccharides (DFP) is an integral part of any enzymatic-chemical method for dietary fiber analysis. Residues obtained after enzyme treatments of fiber-containing foods are usually suspended in 12 M sulfuric acid and kept at or slightly above ambient temperature for at least 1 h, and then the mixtures are diluted with deionized water to a final concentration of 1 M or 2 M acid, followed by heating at 100 degrees C in a water bath or convection oven for 1 or 2 h. Under these hydrolytic conditions, some degradation of the released monosaccharides generally takes place over the duration of hydrolysis. We investigated the feasibility of using microwave energy as a heat source to reduce time and minimize degradation. Preliminary tests were done on the well-characterized soy polysaccharide Fibrim. With a microwave digestion system equipped with temperature and pressure monitors and control lines, optimum settings of power (5%, 75%), time (up to 3 min and 30 s), temperature (35 degrees-55 degrees C), and pressure (45-65 psi) were determined for different foods depending on the residue weight and volume of acid. Results were comparable for microwave oven and convection oven hydrolysis of DFP from 5 foods with good correlations for neutral sugar values; r2 = 0.997 for arabinose, 0.925 for galactose, 0.981 for glucose, 0.969 for mannose, and 0.990 for xylose.
A Maximum-Likelihood Approach to Estimating the Insertion Frequencies of Transposable Elements from Population Sequencing Data

Transposable elements (TEs) contribute to a large fraction of the expansion of many eukaryotic genomes due to the capability of TEs duplicating themselves through transposition. A first step to understanding the roles of TEs in a eukaryotic genome is to characterize the population-wide variation of TE insertions in the species. Here, we present a maximum-likelihood (ML) method for estimating allele frequencies and detecting selection on TE insertions in a diploid population, based on the genotypes at TE insertion sites detected in multiple individuals sampled from the population using paired-end (PE) sequencing reads. Tests of the method on simulated data show that it can accurately estimate the allele frequencies of TE insertions even when the PE sequencing is conducted at a relatively low coverage ( = 5X). The method can also detect TE insertions under strong selection, and the detection ability increases with sample size in a population, although a substantial fraction of actual TE insertions under selection may be undetected. Application of the ML method to genomic sequencing data collected from a natural Daphnia pulex population shows that, on the one hand, most ( > 90%) TE insertions present in the reference D. pulex genome are either fixed or nearly fixed (with allele frequencies > 0.95); on the other hand, among the nonreference TE insertions (i.e., those detected in some individuals in the population but absent from the reference genome), the majority ( > 70%) are still at low frequencies ( < 0.1). Finally, we detected a substantial fraction (∼9%) of nonreference TE insertions under selection.
Abstract B179: The regulation of silent apoptotic cell-clearance in tissue-resident macrophages

When normal, healthy cells die by apoptosis, they must be cleared to ensure tissue homeostasis. Failure to clear apoptotic cells (ACs) efficiently enables the release of inflammatory stimuli, such as nucleic acids, leading to tissue injury and, ultimately, autoimmunity. Clearance of ACs is largely performed by tissue-resident macrophages. Despite expressing many innate immune receptors, these cells do not respond to the potentially stimulatory ligands within ACs. Recently, the Barton Lab has identified several populations of AC-engulfing macrophages with many common features. These features include the expression of AC-recognition receptors and reduced TLR responsiveness to nucleic acids. The transcription factors KLF2 and KLF4 appear to contribute to this expression program both in vitro and in vivo in distinct AC-clearing macrophage populations. Macrophages that are removed from their environments lose this program and the program can be adopted by transferring TLR responsive macrophages into environments where endogenous silent residents are maintained. This coordinated silent immune program allows tissue-resident macrophages to maintain homeostasis while efficiently clearing ACs. Citation Format: Kathleen Pestal, Gregory M. Barton. The regulation of silent apoptotic cell-clearance in tissue-resident macrophages [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B179.
Bone Tissue Physiology

Structural support for body and protection of internal organs. Provision of levers for muscles, allowing for movement. Storage of minerals/lipids and regulation of mineral homeostasis and pH balance. Production of blood cells.
Collateral Arterial Growth and Reactivity: Lessons from the Limb and Renal Blood Supply

The extraordinary prevalence of coronary atherosclerosis and its contribution to morbidity and to mortality in Western society has focused interest on the growth and function of the coronary collateral arterial tree (1, 2). On the other hand, occlusive arterial disease is not rare in other vascular beds and many — possibly more —important lessons have been learned from the examination of collateral growth and reactivity elsewhere. To what extent lessons learned in one region are applicable to other regions is incompletely delineated, and clearly will be an important element of research in the next decade.
Capacity Scaling for Cloud Radio Access Networks with Limited Orthogonal Fronthaul

Uplink and downlink cloud radio access networks are modeled as two-hop K-user L-relay networks, whereby small base-stations act as relays and are connected to a central processor via orthogonal fronthaul links of finite capacities. Based on noisy network coding and distributed decode–forward inner bounds on the capacity regions for uplink and downlink, respectively, the total fronthaul link capacity required to approach the centralized MIMO sum-rate is characterized. The capacity scaling law when the network size increases is examined under certain uplink and downlink network models, both theoretically and via simulations.
The Efficacy of Technology-Based Interventions for Alcohol and Illicit Drug Use Among Women of Childbearing Age: A Systematic Review and Meta-Analysis.

Background Alcohol and illicit drug use is prevalent among women of childbearing age and may lead to higher risk for substance-exposed pregnancy and related health consequences for both women and their offspring. Technology-based interventions (TBIs) are increasingly used to prevent or reduce substance use among women of childbearing age. The efficacy of these approaches, however, is unclear. This review critically reviewed existing research evidence from randomized controlled trials (RCTs) on the efficacy of TBIs in preventing and reducing alcohol and illicit drug use among childbearing-aged women. Methods Seven electronic databases were searched to identify eligible studies. Two reviewers independently screened studies, extracted data, and assessed risks of bias. Robust variance estimation in meta-regression was used to estimate effect sizes and conduct moderator analyses. Results Fifteen RCTs including 3,488 participants were included in the systematic review. Meta-analysis results based on 13 RCTs suggest that TBIs were efficacious relative to control conditions in preventing and reducing substance use among women of childbearing age (d = 0.19, 95% CI = 0.02, 0.35). Preliminary moderator analysis results suggest that the efficacy of TBIs might not vary by participant age, race/ethnicity, the type of technology used, or whether a virtual health assistant was used. TBIs' efficacy in terms of specific substance use types (alcohol use and illicit drug use) or control types (inactive control and active controls) was inconclusive, due to the limited number of studies in each category. Conclusions This systematic review and meta-analysis found evidence of TBIs' efficacy in reducing alcohol and illicit drug use among women of childbearing age. Implications for future research and practice are discussed.
Phenotypic Shifts in Neurons of the Dorsal Motor Nucleus of the Vagus Resulting from Chronic Cardiac Ischemia

Abstract Heart disease remains the number one cause of mortality in the world in spite of significant efforts aimed at treatment. The use of vagal stimulation in the treatment of heart failure has shown mixed successes (Dicarlo et al. 2013; Zannad et al. 2015), suggesting that the treatment has potential, but that the mechanism incompletely understood. Vagal activity confers a robust cardioprotective effect in both humans and animal models, preferentially originating specifically from the dorsal motor nucleus of the vagus (DMV) and deriving a significant benefit from intact gut projections, not just cardiac (Shinlapawittayatorn et al. 2013; Mastitskaya et al. 2012; Basalay et al. 2012). In order to examine the DMV response to heart failure, myocardial infarction was induced in male Sprague Dawley rats. DMV neurons were isolated in small pools of single cells using laser capture microdissection 1 week and 3 weeks after infarction and their gene expression assayed. The results show a transcriptional shift towards a neurosecretory phenotype starting at 1 week and increasing in recruitment of neurons to 3 weeks. The LAD ligation shift appears mediated in part by upregulation of Pax4a, a transcription factor most active during stem cell development of neurosecretory cells during embryonic development. This phenotype is characterized by upregulation of Cacna1d (Cav1.3) and Hcn2 along with increased expression of Cck and Sst. This work suggests that the neurons of the DMV adaptively respond to the dynamics present in the periphery, elucidating the means by which the nature of vagal activity responds to heart failure. Significance Statement The autonomic nervous system plays a significant role in the pathogenesis of cardiovascular disease. Through demonstration of shifting neuronal phenotypes in central neurons in response to peripheral stimuli, we suggest that neuron peptide or neurotransmitter phenotypes are not static in adult rodents. This suggests that even “reflexes” are modifiable dynamic systems. With such plasticity in the transcriptional programming existing in autonomic brain regions there can be new potential therapeutic interventions for cardiovascular disease aimed at leveraging the autonomic nervous system.
Developing scandium and yttrium coordination chemistry to advance theranostic radiopharmaceuticals

The octadentate siderophore analog 3,4,3-LI(1,2-HOPO), denoted 343-HOPO hereafter, is known to have high affinity for both trivalent and tetravalent lanthanide and actinide cations. Here we extend its coordination chemistry to the rare-earth cations Sc3+ and Y3+ and characterize fundamental metal–chelator binding interactions in solution via UV-Vis spectrophotometry, nuclear magnetic resonance spectroscopy, and spectrofluorimetric metal-competition titrations, as well as in the solid-state via single crystal X-ray diffraction. Sc3+ and Y3+ binding with 343-HOPO is found to be robust, with both high thermodynamic stability and fast room temperature radiolabeling, indicating that 343-HOPO is likely a promising chelator for in vivo applications with both metals. As a proof of concept, we prepared a 86Y-343-HOPO complex for in vivo PET imaging, and the results presented herein highlight the potential of 343-HOPO chelated trivalent metal cations for therapeutic and theranostic applications. Radionuclide pairs 44Sc/47Sc and 86Y/90Y possess great promise in the development of theranostic agents, but realizing the full potential of these isotopes necessitates improving rare-earth chelation chemistry. Here the authors show that a hydroxypyridinone-based ligand is a promising candidate for applications in this arena.
Improved health outcomes in integrative medicine visits may reflect differences in physician and patient behaviors compared to standard medical visits.

Abstract Objective To identify differences in patient-physician interactions associated with improvements in GERD symptoms in a randomized controlled trial comparing integrative medicine and primary care/standard visits. Methods We analyzed video recordings of 2-minute excerpts (thin slices) from the beginning, middle, and end of 21 study visits (11 standard, 10 integrative medicine). Results According to blind coders’ analysis of the excerpts, prospective improvement in GERD symptoms was most highly correlated with patients appearing pleased (r = 0.71, p Conclusion The expanded history-taking questions asked by integrative clinicians may enhance relationship building, modifying patients’ responses and improving patient-centered behaviors from clinicians,ultimately facilitating symptom improvement. Practice Implications Analysis of nonverbal behaviors may facilitate a better understanding of patient-clinician interactions in integrative medicine visits and yield insights to improve clinical interactions in conventional medicine.
Local Atomic Environments in the Manganese-Aluminum Icosahedral Phase

The atomic scale structure of icosahedral phase MnAl was derived from experimental diffraction data. The resulting structure is compared to theoretical work and to other experimental data. A large array of this self-modulated structure, which is space-filling, was used for site topology studies.
Feasibility of dual‐task gait to estimate Alzheimer's related cognitive decline in Down syndrome

Author(s): Van Pelt, Kathryn L; Koehl, Lisa; Caban-Holt, Allison; Anderson-Mooney, Amelia; Head, Elizabeth; Schmitt, Frederick A | Abstract: IntroductionThe striatum and frontal lobes have been shown to have early Alzheimer's disease (AD) neuropathology and are critical for motor and cognitive function. We hypothesized gait would be associated with early-stage dementia in Down syndrome (DS), a cohort at risk for AD.MethodsTwenty-eight participants with DS were enrolled in the study. Participants walked at their self-selected pace and while completing a dual task (counting, obstacle, or counting+obstacle).ResultsAll participants were able to complete the self-paced condition and 78.57-96.42% completed the dual-task conditions. There was a trend for greater dual-task effects on gait velocity based on dementia diagnosis. Gait velocity had stronger associations with clinical dementia assessments than age or diagnosis.DiscussionA dual-task gait paradigm is feasible to conduct with adults with DS and is associated with age and cognitive impairment. Dual-task gait may serve as an indicator of early stage dementia in DS.
Toward Using Twitter for PrEP-Related Interventions: An Automated Natural Language Processing Pipeline for Identifying Gay or Bisexual Men in the United States

Background: Pre-exposure prophylaxis (PrEP) is highly effective at preventing the acquisition of Human Immunodeficiency Virus (HIV). There is a substantial gap, however, between the number of people in the United States who have indications for PrEP and the number of them who are prescribed PrEP. While Twitter content has been analyzed as a source of PrEP-related data (e.g., barriers), methods have not been developed to enable the use of Twitter as a platform for implementing PrEP-related interventions. Objective: Men who have sex with men (MSM) are the population most affected by HIV in the United States. Therefore, the objective of this study was to develop and assess an automated natural language processing (NLP) pipeline for identifying men in the United States who have reported on Twitter that they are gay, bisexual, or MSM. Methods: Between September 2020 and January 2021, we used the Twitter Streaming Application Programming Interface (API) to collect more than 3 million tweets containing keywords that men may include in posts reporting that they are gay, bisexual, or MSM. We deployed handwritten, high-precision regular expressions on the tweets and their user profile metadata designed to filter out noise and identify actual self-reports. We identified 10,043 unique users geolocated in the United States, and drew upon a validated NLP tool to automatically identify their ages. Results: Based on manually distinguishing true and false positive self-reports in the tweets or profiles of 1000 of the 10,043 users identified by our automated pipeline, our pipeline has a precision of 0.85. Among the 8756 users for which a United States state-level geolocation was detected, 5096 (58.2%) of them are in the 10 states with the highest numbers of new HIV diagnoses. Among the 6240 users for which a county-level geolocation was detected, 4252 (68.1%) of them are in counties or states considered priority jurisdictions by the Ending the HIV Epidemic (EHE) initiative. Furthermore, the majority of the users are in the same two age groups as the majority of MSM in the United States with new HIV diagnoses. Conclusions: Our automated NLP pipeline can be used to identify MSM in the United States who may be at risk for acquiring HIV, laying the groundwork for using Twitter on a large scale to target PrEP-related interventions directly at this population.