cssi/SciSciGPT-SciSciNet huggingface dataset:
Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers

Mutations of DNA mismatch repair genes, including the hMLH1 gene, have been linked to human colon and other cancers in which defective DNA repair is evidenced by the associated instability of DNA microsatellite sequences (MSI). Germ-line hMLH1 mutations are causally associated with inherited MSI colon cancer, and somatic mutations are causally associated with sporadic MSI colon cancer. Previ- ously however, we demonstrated that in many sporadic MSI colon cancers hMLH1 and all other DNA mismatch repair genes are wild type. To investigate this class of tumors further, we examined a group of MSI cancer cell lines, most of which were documented as established from antecedent MSI- positive malignant tumors. In five of six such cases we found that hMLH1 protein was absent, even though hMLH1-coding sequences were wild type. In each such case, absence of hMLH1 protein was associated with the methylation of the hMLH1 gene promoter. Furthermore, in each case, treatment with the demethylating agent 5-azacytidine induced expres- sion of the absent hMLH1 protein. Moreover, in single cell clones, hMLH1 expression could be turned on, off, and on again by 5-azacytidine exposure, washout, and reexposure. This epigenetic inactivation of hMLH1 additionally accounted for the silencing of both maternal and paternal tumor hMLH1 alleles, both of which could be reactivated by 5-azacytidine. In summary, substantial numbers of human MSI cancers appear to arise by hMLH1 silencing via an epigenetic mechanism that can inactivate both of the hMLH1 alleles. Promoter methyl- ation is intimately associated with this epigenetic silencing mechanism.
Multi-scale dynamic neural net architectures

The design of specialized trainable neural network architectures for temporal problems is described. Multilayer extensions of previous dynamic neural net architectures are considered. Two of the key attributes of these architectures are smoothing and decimation between layers. An analysis of parameters (weights) to estimate suggests a massive reduction in training data needed for multiscale topologies for networks with large temporal input windows. The standard back-propagation training rules are modified to allow for smoothing between layers, and preliminary simulation results for these new rules are encouraging. For example, a binary problem with an input of size 32 converged in three iterations with smoothing and never converged when there was no smoothing. >
High-Order Spectral Volume Method for the Navier-Stokes Equations on Unstructured Grids

In this paper, the spectral volume (SV) method is extended to solve the Navier-Stokes equations by treating the viscous terms with a mixed formulation named local Discontinuous Galerkin approach. The SV method combines two key ideas, which are the basis of the finite volume and the finite element methods, i.e., the physics of wave propagation accounted for by the use of a Riemann solver and high-order accuracy achieved through high-order polynomial reconstructions within spectral volumes. The formulation of the SV method for the two-dimensional compressible Navier-Stokes equations is described. Accuracy studies are performed on the scalar advection diffusion and the Navier-Stokes equations using problems with analytical solutions. It is shown that the designed order of accuracy is achieved for all orders of polynomial reconstructions. The solver is then used to solve other viscous laminar flow problems to shown its potential.
Role of human-modified habitat in protecting specialist species: A case study in the threatened Florida Scrub-Jay

Abstract Habitat specialists are especially vulnerable to habitat alterations in vegetation structure and composition, making them difficult to protect and restore amidst agricultural landscapes. Protection strategies in such cases require information on species’ ability to survive and reproduce on marginal and modified habitat. We examined reproductive success, survival, and foraging efficiency of the Florida Scrub-Jay ( Aphelocoma coerulescens ), an extreme habitat specialist, in a human-modified habitat – regenerating pasture – along a pasture–native scrub interface. From 1985 to 2003, Florida Scrub-Jays were equally successful at producing young in regenerating pasture and native scrub. Production of eggs, nestlings, fledglings, independent young, and yearlings were not statistically different between territories containing pasture and those containing only scrub. Similar trends were observed for nest success and survival. When in pasture, individual jays were significantly more efficient at capturing small prey items, but significantly less efficient at capturing medium and large prey items. Availability of small prey items was significantly higher in pasture than in scrub; availability of medium and large prey items was not significantly different between habitat types. We conclude that regenerating pasture provides suitable supplemental habitat for Florida Scrub-Jays when in close proximity to native scrub, suggesting a novel conservation strategy for maintaining and potentially increasing local populations in fragmented agricultural settings. This case study illustrates how a broadened definition of ‘suitable habitat’ may augment existing conservation strategies for specialist species facing substantial and rapid modification of their native habitat.
Inducible CD4+LAP+Foxp3− Regulatory T Cells Suppress Allergic Inflammation

Regulatory T cells (Tregs) play a critical role in the maintenance of airway tolerance. We report that inhaled soluble Ag induces adaptive Foxp3+ Tregs, as well as a regulatory population of CD4+ T cells in the lungs and lung-draining lymph nodes that express latency-associated peptide (LAP) on their cell surface but do not express Foxp3. Blocking the cytokine IL-10 or TGF-β prevented the generation of LAP+ Tregs and Foxp3+ Tregs in vivo, and the LAP+ Tregs could also be generated concomitantly with Foxp3+ Tregs in vitro by culturing naive CD4+ T cells with Ag and exogenous TGF-β. The LAP+ Tregs strongly suppressed naive CD4+ T cell proliferation, and transfer of sorted OVA-specific LAP+ Tregs in vivo inhibited allergic eosinophilia and Th2 cytokine expression in the lung, either when present at the time of Th2 sensitization or when injected after Th2 cells were formed. Furthermore, inflammatory innate stimuli from house dust mite extract, nucleotide-binding oligomerization domain containing 2 ligand, and LPS, which are sufficient for blocking airway tolerance, strongly decreased the induction of LAP+ Tregs. Taken together, we concluded that inducible Ag-specific LAP+ Tregs can suppress asthmatic lung inflammation and constitute a mediator of airway tolerance together with Foxp3+ Tregs.
Harmonic enhancement of modulated semiconductor laser with optical feedback

A harmonic conversion approach for the efficient transfer of power to the desired harmonic of a directly modulated semiconductor laser diode is presented. This approach will help to overcome the limitations of modulation bandwidth that are associated with semiconductor laser diodes. The transfer of power from the second harmonic to the fourth harmonic of the modulation signal by establishing external cavity matching to the fourth harmonic frequency is shown. The fourth harmonic at 5 GHz is at least 14 dB higher than the fundamental signal level. >
A CSTR‐hollow fiber system for continuous hydrolysis of proteins. Performance and kinetics

The effect of 4 operating variables (enzyme concentration, substrate concentration, flow rate, and reaction volume) on the performance of a continuous stirred tank reactor (CSTR)-hollow fiber membrane reactor was studied for the continuous hydrolysis of a soy protein isolate using pronase. Based on a residence time distribution study, the reactor system was modeled as an ideal CSTR in combination with the Michaelis-Menten equation of enzyme kinetics. This kinetic model correlated conversion with a space-time parameter modified to include all 4 independent variables. An empirical model based on curvilinear regression analysis was also developed. Both models predicted conversion well, although the kinetic model underpredicts at high conversion.
X-ray structural and simulation analysis of a protein mutant: The value of a combined approach

The effect of the mutation Arg 96 to His on the stability of bacteriophage T4 lysozyme has been previously studied by calorimetric experiments, X-ray crystallography, and free energy simulation techniques. The experimental and calculated values for the difference between the free energy of denaturation of the mutant and the wild type are in reasonable agreement. However, the two approaches led to different explanations for the loss in stability. To analyze the differences, a series of refinements based on the crystallographic data were performed, a number of aspects of the simulations were reexamined, and continuum electrostatic calculations were done to complement the latter. The results of those comparisons provide a better understanding of the origin of the free energy difference in this mutant. Furthermore, they show the importance of the combined use of simulations and crystallography for interpreting the effects of mutations on the energetics of the system.
"Pedagogical Creativity" as a Framework for Music Teacher Education.

Creativity research has a long history in music education, including the development of theories and strategies to foster the music creativity of students of all ages and levels. Underexplored is h...
Probabilistic techniques for constraint satisfaction problems

Constraint satisfaction problems (CSPs) are at the core of many tasks with direct practical relevance, such as hardware and software verification, planning, and scheduling to name a few. The two main solution paradigms for solving such problems are based on backtrack-style search and local search. However, recently, a new powerful technique, called survey propagation (SP), was introduced. SP can solve certain classes of problem instances with millions of variables and constraints. This discovery raised a question of whether the traditional techniques are the best one can do when tackling large and important constraint satisfaction problems. This dissertation discusses non-traditional approaches to solving CSPs. The techniques we use include probabilistic inference, statistical tools and a combination of systematic and local search. We provide a new derivation of SP based on purely combinatorial insights. Our method also enables us to derive SP-style procedures for a diverse range of constraint satisfaction problems, and provides insights into structure of solution spaces. The second part of the dissertation describes approaches to counting number of solutions of a CSP with the help of Belief Propagation and statistics. We also provide a novel hybrid algorithm for minimizing the number of violated constraints, which employs both systematic and local search, harnessing their complementary strengths. These methods are the most scalable algorithms for certain hard to solve classes of Boolean satisfiability (SAT), model counting (#SAT), and maximum satisfiability (MaxSAT) problems.
The Use of Faces to Represent Points in k- Dimensional Space Graphically

Abstract A novel method of representing multivariate data is presented. Each point in k-dimensional space, k≤18, is represented by a cartoon of a face whose features, such as length of nose and curvature of mouth, correspond to components of the point. Thus every multivariate observation is visualized as a computer-drawn face. This presentation makes it easy for the human mind to grasp many of the essential regularities and irregularities present in the data. Other graphical representations are described briefly.
Weeding book collections in the age of the Internet

The weeding project at Southeast Missouri State University presented an opportunity to identify different variables, i.e. shelf level, book jackets, added entries, and untraced series, that impacted a book’s circulation behavior and to consider the relationship between circulation and the Internet/online database activity. Using the political science collection, the investigator found that shelf level has the strongest impact on circulation among the variables studied, but the Internet and electronic reference databases have an even greater influence on circulation. Surprisingly, one of the conclusions was that 61 percent of the political science collection either circulated only once or never circulated. It is argued that because of the pressures the Internet and electronic reference databases are placing on book collections and their use it is more important than ever to identify new collection development strategies to pinpoint which titles will be used.
Magnetic design of the Advanced Light Source elliptical wiggler

An elliptical wiggler has been designed for installation in the Advanced Light Source at the Lawrence Berkeley Laboratory. The design has been optimized for the production of circularly polarized light in the 50 eV to 10 KeV energy range. The device will be 3.4 m long consisting of vertical and horizontal periodic structures. The period length for both is 20 cm. The vertical structure is a hybrid permanent magnet design which produces a peak field of 2.0 T. The horizontal magnetic structure is an iron core electromagnetic design shifted longitudinally by one-quarter period relative to the vertical structure; it has a peak field of 0.096 T. The polarity of the horizontal field can be switched at a rate of up to 1 Hz, which results in a modulation of the chirality of the circularly polarized radiation on-axis. This paper discusses the magnetic design and presents the results of radiation spectrum calculations used for determining optimal field parameter settings.
On the schrödinger spin-exchange ferromagnet

The thermodynamic behavior of a ferromagnet whose interactions are described by the Schrodinger spin-exchange operator is investigated. The transition temperatures, magnetization, susceptibility, exchange energy, heat capacity, and entropy are calculated for general spin and lattice coordination number using the constant-coupling approximation. Both first- and second-order phase transitions are found. Comparison with some results of the high-temperature expansion method shows some qualitative agreement. Es wird das thermodynamische Verhalten eines Ferromagneten untersucht, dessen Wechselwirkungen durch den Schrodinger Spin-Austausch-Operator beschrieben werden. Die Ubergangstemperaturen, die Magnetisierung, die Suszeptibilitat, die Austauschenergie, die Warmekapazitat und die Entropie werden unter Verwendung der „constant-coupling”-Naherung fur allgemeine Spins und Gitterkoordinations-Zahlen berechnet. Sowohl Ubergange erster als auch zweiter Ordnung werden gefunden. Ein Vergleich mit Ergebnissen aus der Hochtemperatur-Entwicklungsmethode zeigt gewisse qualitative Ubereinstimmung.
Increased Functionality of Continuation-Based Nonlinear System Analysis

The high complexity of modern autonomous aerospace systems has created a need for new, powerful analysis techniques for control design and validation. This paper exploits the capabilities of continuation algorithms to derive a numerical analysis method that provides a systematic way to investigate how system properties local to the equilibrium condition around which the system is operated change throughout the operational envelope. The method is based on computing subsets of the system’s equilibrium manifold with particular properties that are specified by equality constraints. The contribution of this work lies in the derivation of extended systems of equations that enable the definition of constraints on the eigenvalues and eigenvectors of the linearized dynamics, so that sets of equilibrium points with particular characteristics of the local dynamical behavior can be computed. The capabilities of the method are demonstrated through application to a fully nonlinear aircraft model with six degrees of fre...
Late-Onset Hypoglycemia in Term Newborns With Poor Breastfeeding

Brain injury as a result of significant neonatal hypoglycemia has been recognized for many years. Recently, several case reports from around the world have documented that neonatal hypoglycemia in term infants can result from inadequate intake related to breastfeeding.1 Clinical manifestations can vary from no symptoms, to hypotonia and lethargy, to seizures.2 The blood glucose level and duration of hypoglycemia that lead to neurodevelopmental sequelae have not been established.3 For many years, it was thought that hypoglycemic brain injury was localized to the occipital lobes; however, more recent research has shown that the damage can occur anywhere in the brain.4,5 There have been minimal follow-up data in this patient population to determine long-term prognosis.6 We report a cohort of 11 term neonates who were admitted to the Cincinnati Children’s Hospital Medical Center (CCHMC) NICU for treatment of hypoglycemia that was not due to endocrinopathies, sepsis, hypoxic-ischemic encephalopathy, or maternal medical problems such as diabetes. All of the infants were discharged from their birth hospitals and within a few days were admitted to the NICU with hypoglycemia. A retrospective search was conducted to identify all neonates admitted to the CCHMC NICU from January 2010 to December 2013 with the following diagnosis codes: “neonatal convulsions” and/or “neonatal hypoglycemia.” The research was conducted with approval of the CCHMC Institutional Review Board (Protocol 2014-0607). A chart review was performed for all 47 patients identified. Patients were excluded if they had any other diagnosis that could cause hypoglycemia such as: hypoxic-ischemic encephalopathy, meconium aspiration syndrome, sepsis, prematurity, micropenis, ambiguous genitalia, intrauterine growth restriction, small for gestational age, or those who were hypoglycemic immediately …
Aldehyde and Ketone Synthesis by P450-Catalyzed Oxidative Deamination of Alkyl Azides

Heme-containing proteins have recently attracted increasing attention for their ability to promote synthetically valuable transformations not found in nature. Following the recent discovery that engineered variants of myoglobin can catalyze the direct conversion of organic azides to aldehydes, we investigated the azide oxidative deamination reactivity of a variety of hemoproteins featuring different heme coordination environments. Our studies show that although several heme-containing enzymes possess basal activity in this reaction, an engineered variant of the bacterial cytochrome P450 CYP102A1 constitutes a particularly efficient biocatalyst for promoting this transformation, exhibiting a broad substrate scope along with high catalytic activity (up to 11,300 TON), excellent chemoselectivity, and enhanced reactivity toward secondary alkyl azides to yield ketones. Mechanistic studies and Michaelis-Menten analyses provided insights into the mechanism of the reaction and the impact of active site mutations on the catalytic properties of the P450. Altogether, these studies demonstrate that engineered P450 variants represent promising biocatalysts for the synthesis of aryl aldehydes and ketones via the oxidative deamination of alkyl azides under mild reaction conditions.
Wave Intensity Fluctuations in a One Dimensional Discrete Random Medium

The propagation of electromagnetic waves in a one dimensional discrete random medium is considered. It is assumed that the medium is bounded within a slab of thickness L and the random inhomogeneities are distributed according to a Poisson impulse process of density A. In the absence of absorption, an exact equation is obtained for the m-moments of the wave intensity using the Kolmogorov-Feller approach. In the limit of low concentration of inhomogeneities, we use a two-variable perturbation technique, valid for A small and L large, to obtain approximate solutions for the moments of the intensity. It is shown that the wave intensity increases with the slab thickness and the peak of the higher moments occur inside the medium.
Midterm Results of Porous Tantalum Femoral Cones in Revision Total Knee Arthroplasty

Background: Severe bone loss during a revision total knee arthroplasty (TKA) remains a challenging problem. The purpose of this study was to determine the midterm clinical outcomes, fixation as evaluated radiographically, and survivorship of tantalum femoral cones used during revision TKAs in patients with severe femoral bone loss. Methods: From 2003 to 2011, 159 tantalum metaphyseal femoral cones were implanted in 157 patients at a single institution. Knee Society scores, radiographic results, and implant survivorship were analyzed. Two patients were lost to follow-up. Nineteen died of causes unrelated to the surgery but had been followed for >2 years and thus were included in the study. The mean age at the time of the index surgery was 64 years, and 82 patients were male. The mean duration of follow-up was 5 years (range, 2 to 10 years). Results: The mean Knee Society score increased from 47 preoperatively to 65 at the most recent follow-up evaluation (p = 0.1). Radiographically, all 134 unrevised femoral cones were seen to be well fixed without any evidence of loosening. At 5 years, 23 cones had been revised: 14 because of infection, 6 because of aseptic loosening of the cone (all in hinged TKAs in patients with a Type-3 defect), and 3 because of ligamentous instability. The 5-year survivorship was 96% when the end point was revision of the cone due to aseptic loosening, 84% when it was revision of the cone for any reason, and 70% when it was any reoperation. Conclusions: In what we believe to be the largest series of such implants, femoral cones provided a durable and reliable option for metaphyseal fixation during revision TKA with severe femoral bone loss. Aseptic failure of the femoral cone was associated with use of a hinged TKA in a patient with a Type-3 bone defect. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Verita$: Harvard's Hidden History

About 25 years ago I was listening to one of the premier conservative radio pundits claim that the only institution “we” do not yet control is the university. That statement was prophetic in that a...
Beyond Medication Reconciliation: The Correct Medication List

Medication reconciliation is a major focus of quality measurement activities, and according to The Joint Commission, primary care clinicians are expected to reconcile a patient’s medications at every visit.1 In principle, medication reconciliation is quite important; in practice, however, it has failed to have a demonstrable effect on patient outcomes. This may partly be because the lack of agreement about what constitutes medication reconciliation makes it difficult to decide when it has occurred and therefore difficult to study its effect.
Doubling of coastal flooding frequency within decades due to sea-level rise

Global climate change drives sea-level rise, increasing the frequency of coastal flooding. In most coastal regions, the amount of sea-level rise occurring over years to decades is significantly smaller than normal ocean-level fluctuations caused by tides, waves, and storm surge. However, even gradual sea-level rise can rapidly increase the frequency and severity of coastal flooding. So far, global-scale estimates of increased coastal flooding due to sea-level rise have not considered elevated water levels due to waves, and thus underestimate the potential impact. Here we use extreme value theory to combine sea-level projections with wave, tide, and storm surge models to estimate increases in coastal flooding on a continuous global scale. We find that regions with limited water-level variability, i.e., short-tailed flood-level distributions, located mainly in the Tropics, will experience the largest increases in flooding frequency. The 10 to 20 cm of sea-level rise expected no later than 2050 will more than double the frequency of extreme water-level events in the Tropics, impairing the developing economies of equatorial coastal cities and the habitability of low-lying Pacific island nations.
Relationships Between Scores on the General Purpose Abbreviated Battery of Stanford-Binet IV, Peabody Picture Vocabulary Test-Revised, Columbia Mental Maturity Scale, and Goodenough-Harris Drawing Test

This study investigated the correlations among the “General Purpose Abbreviated Battery” of the Stanford-Binet IV: Fourth Edition, the Peabody Picture Vocabulary Test-Revised, the Columbia Mental Maturity Scale, and the Goodenough-Harris Drawing Test. A third-grade class of 23 children (11 boys, 12 girls) took all four of the tests, and the intercorrelations of the total scores of the four tests were calculated. The Binet IV and Peabody correlation was statistically significant (p .05).
Whole Blood Assay detects endotoxin and non-endotoxin pyrogens (P3098)

Pyrogenic contaminations may precipitate adverse effects that range from fever to death. There is limited surveillance on non-endotoxin pyrogens and a sensitive technique to detect them is essential. Cells of the immune system come in contact with pyrogens; this causes the release of mediators that induce fever. The Whole Blood Assay (WBA) exploits this human physiological response; human whole blood is incubated with test samples, and interleukin-1 beta (IL-1β) induced in the presence of pyrogenic contamination is measured by ELISA. In this study, we demonstrate the ability of WBA to detect non-endotoxin pyrogens. Human whole blood was incubated with different doses of the following non-endotoxin pyrogenic stimuli: lipoteichoic acid (gram positive bacteria cell wall), Pam2CSK4, FSL-1 (bacterial diacylated lipoproteins), zymosan (fungal [1, 3] - beta glucan) and fungal spores. Levels of induced IL-1β were compared with endotoxin stimulated blood and unstimulated blood as positive and negative controls respectively. All tested stimuli showed pro-inflammatory response compared to the negative control (p
Phosphoinositide 3-Kinase p110δ Is Dispensable for HoxA9/Meis1 and MLL-AF9 Mediated Leukemogenesis.

The Phosphoinositide 3-kinase(PI3K)/PTEN pathway has been implicated in the pathogenesis of a number of hematopoietic malignancies and solid tumors. The only PI3K subunit invariably expressed in AML blasts is the catalytic p110δ. Recent reports have demonstrated that impairment of p110δ activity prevents growth of AML blasts in culture and increases their sensitivity to apoptosis inducing agents. However, a definitive requirement for p110δ in AML pathogenesis remains undefined. To identify the requirement of p110δ in AML initiation, the transforming potential of two retroviral models of AML (HoxA9/Meis1 and MLL-AF9) was compared in hematopoietic progenitors from wildtype (WT) and p110δ D910A/D910A mice (homozygous knock-in for a catalytically inactive form of p110δ). Mice transplanted with p110δ D910A/D910A progenitors expressing either HoxA9/Meis1 or MLL-AF9 oncogenes developed a phenotypically similar AML at rates comparable to those transplanted with transformed WT progenitors. Moreover, tumors derived from p110δ D910A/D910A progenitors were transplantable to secondary recipients. These results indicate that the catalytic activity of p110δ is not required for HoxA9/Meis1 or MLL-AF9 driven leukemogenesis, suggesting that there are compensatory mechanisms that require further investigation.
Insights on the Intersection of Health Equity and School Nutrition Policy Implementation: An Exploratory Qualitative Secondary Analysis:

Background. Recent federal policies aimed to ensure that all children have equitable access to healthy school nutrition environments. However, historically, disparities have persisted in the quality of school nutrition environments across geographic and socioeconomic groups. There is limited literature addressing if and how recent efforts to reform the school nutrition environment have influenced such disparities. The main objective of this study was to explore stakeholders’ insights on how school nutrition reform intersected with issues of inequity. Method. Qualitative secondary analysis (QSA) offers a unique method to examine existing data with a related but distinct inquiry. This QSA analyzed three primary studies, including stakeholder interviews and focus group data with school professionals and students (total 60 transcripts). Two trained analysts iteratively coded all transcripts in Atlas.ti Version 7 and followed principles of constant comparative analysis. Measures to enhance “trustworthiness” we...
Dissociation of Functional Markers in Bacterial Membranes

While much is known of the gross structural, chemical and biochemical properties of biological membranes, (1–4) little is yet known of their existing structure — function relationships, (5) intermolecular architecture, (6) inherent informational content or possible dynamic changes occurring in response to extra — and intracellular stimuli. There exists no universally accepted model of membrane architecture and, indeed, several patterns may exist, not only in different membranes, but in portions of the same membrane.
Quality of life and psychosocial care in pediatric heart failure

Abstract Advances in both medical and surgical management of children living with cardiovascular disease have resulted in improved survival in this population. However, children living with cardiovascular disease are often required to abide by physical activity restrictions, medications, and chronic long-term follow-up, which can impair health-related quality of life (HRQOL). Additionally, advanced therapies including implantable cardioverter–defibrillators (ICDs), cardiac resynchronization therapy (CRT), and increasingly utilized mechanical circulatory support (MCS) in this population can further affect HRQOL. Additionally, heart failure (HF) is increasingly appreciated as a syndrome affecting many organ systems including the brain, mental health, and HRQOL. HRQOL is appreciated as an important long-term outcome measure in the management of adults living with HF and is increasingly appreciated as such in the pediatric HF population.
Searching for God: Illness-Related Mortality Threats and Religious Search Volume in Google in 16 Nations.

We tested predictions about religiosity and terror management processes in 16 nations. Specifically, we examined weekly variation in Google search volume in each nation for 12 years (all weeks for which data were available). In all 16 nations, higher than usual weekly Google search volume for life-threatening illnesses (cancer, diabetes, and hypertension) predicted increases in search volume for religious content (e.g., God, Jesus, prayer) in the following week. This effect held up after controlling for (a) recent past and annual variation in religious search volume, (b) increases in search volume associated with religious holidays, and (c) variation in searches for a non-life-threatening illness (“sore throat”). Terror management threat reduction processes appear to occur across the globe. Furthermore, they may occur over much longer periods than those studied in the laboratory. Managing fears of death via religious belief regulation appears to be culturally pervasive.
Giving Voice to Ancient Texts: Manuscript Scholarship in the Digital Era

The study of manuscripts was traditionally the preserve of scholar-curators in research libraries who devoted their lives to the exhaustive study and description of collections that were often gathered from several sources. The expected result of their solitary labor was a printed catalog that might describe at most a few hundred manuscripts from a particular linguistic or religious culture. That model has been challenged by the advent of large-scale digital projects that aggregate thousands or even tens of thousands of manuscripts from multiple libraries in a single database or portal.
A Tablet-Based Educational Tool: Toward More Comprehensive Pediatric Patient Education.

There is a paucity of data on the impact of mobile technology on physician-led education in the pediatric population. We performed a prospective pilot study in a pediatric diabetes clinic to evalua...
Diamond Compounds for Polishing Metallographic Specimens

Diamond compounds are perhaps the most common abrasive material in use today for intermediate and final polishing of metallographic specimens. And, even though a significant quantity of the micron-size diamonds that are produced each year are consumed in the preparation of metallographic samples, only very limited technical information has been made available to the metallographer to enable him to determine what characteristics a diamond compound should have for his particular application. Very few scientific studies of diamond polishing in metallography have been reported. Studies of the influence of polishing speed and polishing time (1) and a study comparing the polishing behavior of “normal” diamond to a compound containing diamonds made from a powder produced by an explosive compacting method (2) have been reported. Some work regarding the use of diamond compounds for lapping (3,4) has been reported also, but little else can be found in the literature. Unfortunately, it has not been possible, or economical, for even the largest metallographic laboratories, who use only a few-thousand-dollars worth of diamond abrasives each year, to perform any significant scientific evaluations of the available diamond compounds to find out which compound is best suited for his purpose. Therefore, a metallographer must choose the diamond material he is going to use on the basis of some intuitive belief, perhaps based on many years of experience, that one material is best for him.
Edge-Controlled Mechanical Failure of Si and SiC Semiconductor Chips

Silicon (Si) and silicon carbide (SiC) semiconductor chips are subjected to thermal gradients during service, have coefficient of thermal expansion mismatches with the constituents they are attached to, and are therefore subjected to thermomechanical tensile stresses that can initiate their fracture. Because of inherent brittleness, their probabilistic (Weibull) tensile failure strength was examined to understand sustainable tensile stresses and any exhibition of strength-size-scaling. Failure stress testing of entire (10-mm-square) chips was conducted using uniaxial flexure (3-point-bending) and biaxial flexure (anticlastic bending). The advantage of the anticlastic bend test is all eight primary edges are subjected to identical sinusoidal stress distribution so tensile failure stress is concurrently sensitive to edge-state quality, surface-state quality, crystallographic orientation, and any strength anisotropies of any of those. Tensile stress tolerance of both Si and SiC chips was limited by extrinsic strength-limiting flaws located at their edges and on lapped surfaces too in the case of the Si. Both materials exhibited strength-size scaling; namely, a larger chip is likely to fail at a lower tensile stress. The anticlastic bend test method was effective for evaluating edge failure stress provided surface-type strength-limiting flaws were not dominant. Edge-strength anisotropy (i.e., crystallographic orientation dependence) was observed with both themore » Si and SiC chips. Surface-strength anisotropy also occurred with Si chips because one side was lapped and the other polished. Lastly, the SiC chips failed at much higher tensile stresses than Si chips; however, that strength difference could be a ramification of differences in edge-slicing quality and not necessarily from intrinsic material differences.« less
Umbilical Cord Blood Transplantation for Inherited Metabolic Diseases

Inherited metabolic diseases (IMD) belonging to lysosomal storage disorders (Hurler syndrome, Krabbe disease, metachromatic leukodystrophy, and others) and peroxisomal disorders (adrenoleukodystrophy) cause progressive degeneration of the nervous system, neurocognitive deterioration, disabilities, and premature death. Umbilical cord blood transplantation (UCBT) leads to development of donor-derived cells in the brain and other organs resulting in stabilization of disease and prevention of further damage. This chapter describes preclinical studies, treatment options, comparative analysis of outcomes for cord blood and bone marrow transplant, current controversies, and future directions. Umbilical cord blood (UCB) provides rapid and increased access to transplantation with favorable outcomes. Data from our center as well as other centers will be reviewed to show that the morbidity, quality of life, and survival outcomes are significantly better if transplant is performed early in the course of the disease.
In Vivo Photolabeling of Cells in the Colon to Assess Migratory Potential of Hematopoietic Cells in Neonatal Mice

Enteric bacterial communities are established early in life and influence immune cell development and function. The neonatal microbiota is susceptible to numerous external influences including antibiotics use and diet, which impacts susceptibility to autoimmune and inflammatory diseases. Disorders such as Inflammatory Bowel Disease (IBD) are characterized by a massive influx of immune cells to the intestines. However, immune cells conditioned by the microbiota may additionally emigrate out of the intestines to influence immune responses at extra-intestinal sites. Thus, there is a need to identify and characterize cells that may carry microbial messages from the intestines to distal sites. Here, we describe a method to label cells in the colon of newborn mice in vivo that enables their identification at extra-intestinal sites after migration.
Protein engineering strategies for improving the selective methylation of target CpG sites by a dCas9-directed cytosine methyltransferase in bacteria.

Mammalian gene expression is a complex process regulated in part by CpG methylation. The ability to target methylation for de novo gene regulation could have therapeutic and research applications. We have previously developed a dCas9-MC/MN protein for targeting CpG methylation. dCas9-MC/MN is composed of an artificially split M.SssI methyltransferase (MC/MN), with the MC fragment fused to a nuclease-null CRISPR/Cas9 (dCas9). Guide RNAs directed dCas9-MC/MN to methylate target sites in E. coli and human cells but also caused some low-level off-target methylation. Here, in E. coli, we show that shortening the dCas9-MC linker increases methylation of CpG sites located at select distances from the dCas9 binding site. Although a shortened linker decreased methylation of other CpGs proximal to the target site, it did not reduce off-target methylation of more distant CpG sites. Instead, targeted mutagenesis of the methyltransferase’s DNA binding domain, designed to reduce DNA affinity, significantly and preferentially reduced methylation of such sites.
Cloud Based System for Detecting Children in Automobiles

Children and infants being left in cars on hot summer days is a major public health issue across the world. With modern sensor and connectivity technology, it should be possible to detect these scenarios by uploading raw data to the cloud. In the cloud, systems will be able to respond to this data and make judgements to notify proper response personnel. In this paper, we explore cloud technology to process updates from a sensor system and how it could be used to send notifications to prevent these tragic occurrences.
Adolescent stress reactivity: Examining physiological, psychological and peer relationship measures with a group stress protocol in a school setting.

Abstract Introduction Adolescents experience enhanced social sensitivity and biopsychosocial changes that can be challenging. Much remains unknown about the effect of psychological characteristics and peer relationships on adolescents’ physiological responses to stress, due in part to methodological limitations. Methods To test how adolescents’ peer relationships and psychological characteristics are associated with their physiological and psychological response to stress, we administered the Group Public Speaking Task for Adolescents (GPST-A) to 54 adolescents (n = 40 girls; Mage = 16.6 years) in two high schools in the United States. Salivary cortisol and alpha-amylase (sAA), and positive and negative affect were measured six times. Relationships among group members were measured, resulting in whole-network data. State and trait rumination, five factors of coping, and emotional reappraisal and suppression were measured along with symptoms of depression and anxiety. Results Greater levels of negative evaluation and victimization among group members were associated with a steeper increase and decline in the negative affect response, yet not associated with the physiological response to stress. Greater positive affect was associated with decreased cortisol reactivity, whereas negative affect was associated with steeper cortisol and sAA reactivity. Rumination, disengagement coping, and depression symptoms were related to the physiological response to stress. Conclusions The GPST-A is feasible to administer in a school context with adolescents to collect both physiological and psychological stress responses. Findings from the present study suggest peer relationships are important for understanding adolescents' psychological response to stressors while psychological characteristics are important for adolescents’ physiological response to stress.
Ovarian and Hypothalamic Aging

Female reproductive aging is a complex process that involves all organs of reproductive axis, from hypothalamus to the ovaries. Although life expectancy almost doubled during the last century, the reproductive life span remained relatively constant. Oocyte attrition leading to loss of ovarian function has been viewed as the hallmark of reproductive aging leading to menopause; however, recent evidence suggests both hypothalamus and pituitary may play an active role in reproductive senescence. Yet, the mechanisms governing reproductive senescence are largely unknown. This chapter focuses on the physiology of reproductive aging, both at the hypothalamic-pituitary and the ovarian level.
A Heart Team or a Heart Failure Interventionalist

The past several decades have witnessed an enormous increase in the number of patients with heart failure, especially advanced or “end-stage” disease. Several factors have contributed to this incre...
[Determination of 25-hydroxyl vitamin D in serum by isotope dilution ultra-fast liquid chromatography-tandem mass spectrometry].

OBJECTIVE To establish a rapid and accurate method for determination of 25-hydroxyl vitamin D2, 25-hydroxyl vitamin D3 and 3-epi-25-hydroxyl vitamin D3 in serum by isotope dilution ultra-fast liquid chromatography-tandem mass spectrometry(UFLC-MS/MS). METHODS The serum sample was extracted by nhexane after methanol/acetonitrile precipitation protein, and then the extract was concentrated by nitrogen and volumed with the primary mobile phase. The chromatographic separation was carried out on a Phenomenex Kinetex F5 column(2. 1 mm × 150 mm, 1. 7 μm) by using 0. 1%(V/V) formic acid and 0. 1%(V/V) formic acid/methanol solution as the mobile phase with the gradient elution. Detection was performed in positive multi-reaction monitoring(MRM) mode with the isotope internal labeling method for quantification. RESULTS The baseline separation was obtained within 6 min for the epimer 25-hydroxyl vitamin D3 and 3-epi-25-hydroxyl vitamin D3, and the accurate qualification was obtained for the simultaneous determination of 25-hydroxyl vitamin D2, 25-hydroxyl vitamin D3 and 3-epi-25-hydroxyl vitamin D3. The three analytes showed good linear relationship within the range of 0. 5-50. 0 μg/L with a correlation coefficient r >0. 9995. The limits of detection(LODs) and the limits of quantitation(LOQs) of the method were 0. 15 μg/L and 0. 5 μg/L, respectively. The recoveries of the method were84. 3%-109. 0%(n = 11) at the three spiked levels of 1. 0, 10. 0 and 30. 0 μg/L, and the relative standard deviations(RSDs) were between 0. 8%-6. 8%. At the same time, the certified standard reference materials(SRM) of the America National Institute of Standards and Technology(NIST) Level 1, Level 2, Level 3 and Level 4(SRM 972 a)were used as the quality control samples for verification, the relative deviations of the measurement result were less than 5% compared with the reference values. CONCLUSION The developed method has the characteristics of simplicity, rapidity, sensitivity and accuracy, and is suitable for the simultaneous rapid determination of 25-hydroxyl vitamin D2, 25-hydroxyl vitamin D3 and 3-epi-25-hydroxyl vitamin D3 in serum.
FALSE ATRIAL FIBRILLATION ALERTS FROM IMPLANTABLE LOOP RECORDERS IN PATIENTS WITH EMBOLIC STROKE OF UNDETERMINED SOURCE

Implantable loop recorders (ILR) are frequently placed after embolic stroke of undetermined source (ESUS) to monitor for occult atrial fibrillation. High false alerts from ILR have been described in routine monitoring practice. We sought to determine the incidence, timing, cause, and frequency of
The evolutionarily conserved ESRE stress response network is activated by ROS and mitochondrial damage

Mitochondrial dysfunction causes or contributes to a wide variety of pathologies, including neurodegenerative diseases, cancer, metabolic diseases, and aging. Cells actively surveil a number of mitochondrial readouts to ensure that cellular homeostasis is maintained. In this article, we characterize the role of the ethanol and stress response element (ESRE) pathway in mitochondrial surveillance and show that it is robustly activated when the concentration of reactive oxygen species (ROS) in the cell increases. While experiments were mostly performed in Caenorhabditis elegans, we observed similar gene activation profile in human cell lines. The linear relationship between ROS and ESRE activation differentiates ESRE from known mitochondrial surveillance pathways, such as the mitochondrial unfolded protein response (UPRmt), which monitor mitochondrial protein import. The ability of the ESRE network to be activated by increased ROS allows the cell to respond to oxidative and reductive stresses. The ESRE network works in tandem with other mitochondrial surveillance mechanisms as well, in a fashion that suggests a partially redundant hierarchy. For example, mutation of the UPRmt pathway results in earlier and more robust activation of the ESRE pathway. Interestingly, full expression of ATFS-1, a key transcription factor for the UPRmt, requires the presence of an ESRE motif in its promoter region. The ESRE pathway responds to mitochondrial damage by monitoring ROS levels. This response is conserved in humans. The ESRE pathway is activated earlier when other mitochondrial surveillance pathways are unavailable during mitochondrial crises, potentially to mitigate stress and restore health. However, the exact mechanisms of pathway activation and crosstalk remain to be elucidated. Ultimately, a better understanding of this network, and its role in the constellation of mitochondrial and cellular stress networks, will improve healthspan.
Mobilization and Countermobilization: The Effect of Candidate Visits on Campaign Donations in the 2016 Presidential Election

Political scientists studying the impact of campaign visits by presidential candidates have come to conflicting conclusions on whether campaigns change voter behavior in even small ways. In this ar...
Abstract 14846: Artificial Intelligence and Clinical Stability After the Norwood Operation

Background: Postoperative management of the neonate following the Norwood operation is among the most complex and challenging in pediatric critical care. Artificial intelligence is poised to assist...
Assigning Credit Union Deposits to Credit Union Branches

We describe a method to allocate U.S. credit union deposits to the credit union branch level. Credit union deposit data is only available at the aggregate firm level. Our method takes advantage of FFIEC Home Mortgage Disclosure Act (HMDA) to identify loans at the credit union branch level. We show that credit union deposits at the branch level are highly correlated with credit union loans at the branch level for 2010-2012. We then allocate aggregate firm level credit union deposits to the credit union branch level based on the proportion of total loan portfolio at each branch for 2004-2012.