cssi/SciSciGPT-SciSciNet huggingface dataset:
Genome-wide histone acetylation data improve prediction of mammalian transcription factor binding sites

Motivation: Histone acetylation (HAc) is associated with open chromatin, and HAc has been shown to facilitate transcription factor (TF) binding in mammalian cells. In the innate immune system context, epigenetic studies strongly implicate HAc in the transcriptional response of activated macrophages. We hypothesized that using data from large-scale sequencing of a HAc chromatin immunoprecipitation assay (ChIP-Seq) would improve the performance of computational prediction of binding locations of TFs mediating the response to a signaling event, namely, macrophage activation. Results: We tested this hypothesis using a multi-evidence approach for predicting binding sites. As a training/test dataset, we used ChIP-Seq-derived TF binding site locations for five TFs in activated murine macrophages. Our model combined TF binding site motif scanning with evidence from sequence-based sources and from HAc ChIP-Seq data, using a weighted sum of thresholded scores. We find that using HAc data significantly improves the performance of motif-based TF binding site prediction. Furthermore, we find that within regions of high HAc, local minima of the HAc ChIP-Seq signal are particularly strongly correlated with TF binding locations. Our model, using motif scanning and HAc local minima, improves the sensitivity for TF binding site prediction by ~50% over a model based on motif scanning alone, at a false positive rate cutoff of 0.01. Availability: The data and software source code for model training and validation are freely available online at http://magnet.systemsbiology.net/hac. Contact:aderem@systemsbiology.org; ishmulevich@systemsbiology.org Supplementary information:Supplementary data are available at Bioinformatics online.
Metallothionein as a clonable tag for protein localization by electron microscopy of cells

A benign, clonable tag for the localization of proteins by electron microscopy of cells would be valuable, especially if it provided labelling with high signal-to-noise ratio and good spatial resolution. Here we explore the use of metallothionein as such a localization marker. We have achieved good success with desmin labelled in vitro and with a component of the yeast spindle pole body labelled in cells. Heavy metals added after fixation and embedding or during the process of freeze-substitution fixation provide readily visible signals with no concern that the heavy atoms are affecting the behaviour of the protein in its physiological environment. However, our methods did not work with protein components of the nuclear pore complex, suggesting that this approach is not yet universally applicable. We provide a full description of our optimal labelling conditions and other conditions tried, hoping that our work will allow others to label their own proteins of interest and/or improve on the methods we have defined.
SoxC transcription factors are essential for the development of the inner ear

Hair cells, the mechanosensory receptors of the inner ear, underlie the senses of hearing and balance. Adult mammals cannot adequately replenish lost hair cells, whose loss often results in deafness or balance disorders. To determine the molecular basis of this deficiency, we investigated the development of a murine vestibular organ, the utricle. Here we show that two members of the SoxC family of transcription factors, Sox4 and Sox11, are down-regulated after the epoch of hair cell development. Conditional ablation of SoxC genes in vivo results in stunted sensory organs of the inner ear and loss of hair cells. Enhanced expression of SoxC genes in vitro conversely restores supporting cell proliferation and the production of new hair cells in adult sensory epithelia. These results imply that SoxC genes govern hair cell production and thus advance these genes as targets for the restoration of hearing and balance.
Determinants of psychological well-being in Irish immigrants.

Immigration accounts for nearly half of the U.S. population growth in the past 20 years, and this trend is expected to continue. The purpose of this study is to examine the relationship between demographics, resilience, life satisfaction, and psychological well-being among Irish immigrants. Employing a cross-sectional design, a sample of 100 Irish immigrants completed the Demographic and Migration Questionnaire, the Resilience Scale, the Migration Quality of Life Scale, and the General Well-Being Schedule. Hierarchical regression analyses were used to test the association of psychological well-being with demographics, resilience, and life satisfaction. Findings revealed that number of annual health care appointments, higher resilience, and greater life satisfaction were the strongest predictors of psychological well-being.
Caregivers’ relationship closeness with the person with dementia predicts both positive and negative outcomes for caregivers’ physical health and psychological well-being

Closer relationships between caregivers and care recipients with dementia are associated with positive outcomes for care recipients, but it is unclear if closeness is a risk or protective factor for the health and psychological wellbeing of caregivers. We examined 234 care dyads from the population-based Cache County Dementia Progression Study. Caregivers included spouses (49%) and adult offspring (51%). Care recipients mostly had dementia of the Alzheimer’s type (62%). Linear mixed models tested associations between relationship closeness at baseline or changes in closeness prior to versus after dementia onset, with baseline levels and changes over time in caregiver affect (Affect Balance Scale, ABS), depression (Beck Depression Inventory, BDI), and mental and physical health (components of the Short-Form Health Survey, SF-12). After controlling for demographic characteristics of the caregiver, number of caregiver health conditions, and characteristics of the care recipient (type of dementia, functional ability, and behavioral disturbances), we found that higher baseline closeness predicted higher baseline SF-12 mental health scores (better mental health) and lower depression. Higher baseline closeness also predicted greater worsening over time in ABS and SF-12 mental health. In addition, caregivers who reported a loss of closeness in their relationship with the care recipient from pre- to post-dementia displayed improved scores on ABS and SF-12 mental health, but worse SF-12 physical health over the course of the study. These results suggest that closeness and loss of closeness in the care dyad may be associated with both positive and adverse outcomes for caregivers, both cross-sectionally and over time.
Xenobiotic-metabolizing cytochromes P450 in ontogeny: evolving perspective.

While much is known about inducibility of the xenobiotic‐metabolizing forms of cytochrome P450, the Family 1–3 enzymes, less well understood is the purpose for the presence of some of these forms in the developing conceptus. Many cytochrome P450 forms are present in the embryo and fetus, like the anabolic forms in Families 5 and higher, and are known to produce molecules with specific functions, e.g., cholesterol, steroids, and their metabolites necessary for normal physiological functions. As we gain greater understanding of the cell cycle and its regulation, and the roles of nuclear receptors in modulating transcriptional activities, a picture begins to emerge in which cytochrome P450 forms appear as molecule‐altering enzymes producing and eliminating ligands associated with nuclear receptor activities. For these CYP enzymes to exert a developmental action, a controlled spatial and temporal expression pattern would be essential. Studies now indicate the existence of such temporal control on the appearan...
Porcine sperm surface β1,4Galactosyltransferase binds to the zona pellucida but is not necessary or sufficient to mediate sperm–zona pellucida binding

The binding of sperm to the zona pellucida is an integral part of the mammalian fertilization process, investigated most extensively in the mouse. Several sperm receptors for the murine zona pellucida have been studied (Snell WJ, White JM. 1996. Cell 85:629-637; Wassarman PM. 1999. Cell 96:175-183), but the most compelling evidence exists for beta-1,4-galactosyltransferase (GalTase). Considering that GalTase is present on the surface of porcine sperm (Larson JL, Miller DJ. 1997. Biol Reprod 57:442-453), we investigated the role of GalTase in porcine sperm-zona binding. Sperm surface GalTase catalyzed the addition of uridine diphosphate-[(3)H]galactose to the 55 kDa group of the porcine zona pellucida proteins implicated in sperm binding, demonstrating that GalTase binds the porcine zona. The functional importance of GalTase-zona pellucida binding was tested. Addition of uridine diphosphate galactose, a substrate that completes the GalTase enzymatic reaction and disrupts GalTase mediated adhesion, had no effect on binding of sperm to porcine oocytes. Furthermore, removal of the GalTase zona ligand by incubation of oocytes with N-acetylglucosaminidase had no effect on binding of sperm to oocytes. These results suggest that GalTase is not necessary for sperm to bind to the zona pellucida. Digestion of isolated porcine zona proteins with N-acetylglucosaminidase did not affect the biological activity of soluble porcine zona proteins in competitive sperm-zona binding assays, suggesting that GalTase alone is not sufficient to mediate sperm-zona attachment. From these results, it appears that, although GalTase is able to bind porcine zona proteins, its function in porcine sperm-zona binding is not necessary or sufficient for sperm-zona binding. This supports the contention that porcine sperm-zona binding requires redundant gamete receptors.
Multiple target angle tracking using sensor array outputs

The use of the output of an array of sensors to track multiple independently moving targets is reported. The output of each sensor in the array is the sum of signals received from each of the targets. The results of direction-of-arrival estimation by eigenvalue analysis are extended to derive a recursive procedure based on a matrix quadratic equation. The solution of this matrix quadratic equation is used to provide updated target positions. A linear approximation method for estimating the solution of the matrix equation is presented. The algorithm is demonstrated by the simulated tracking of two targets. The main advantage of the algorithm is that a closed-form solution for updating the target angle estimates has been obtained. Also, its application is straightforward, and the data association problem due to uncertainty in the origin of the measurements is avoided. However, it requires the inversion of an N*N as well as other linear operations, so that the computational burden becomes substantial as N becomes very large. >
Novel Copolymers of Styrene. 11. Some Ring-Substituted Methyl 2-Cyano-3-Phenyl-2-Propenoates

Electrophilic trisubstituted ethylenes, ring-substituted methyl 2-cyano-3-phenyl-2-propenoates, RPhCH˭C(CN)CO2CH3 (where R is 2-CH3CO, 3-CH3CO, 2-CN, 4-N(CH3)2, 4-N(C2H3)2, 2-I, 4-I, 3-I-4-OCH3, 5-I-2-OCH3, 2,5-Br2, 3,5-Br2) were prepared and copolymerized with styrene. The monomers were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and methyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C-NMR. All the ethylenes were copolymerized with styrene (M1) in solution with radical initiation (ABCN) at 70°C. The compositions of the copolymers were calculated from nitrogen analysis and the structures were analyzed by IR, 1H and 13C-NMR. The order of relative reactivity (1/r 1) for the monomers is 4-I (10.6) > 2-I (6.8) > 2-CN (4.8) > 3-I-4-OCH3 (2.5) > 3-CH3CO (2.3) > 5-I-2-OCH3 (1.5) > 2-CH3CO (0.8) > 3,5-Br2 (0.6) > 2,5-Br2 (0.5) > 4-N(C2H3)2 (0.4) > 4-N(CH3)2 (0.3). Relatively high T g of the copolymers in comparison with that of polystyrene i...
Racial disparities in alcohol use: comparison of 2 American Indian reservation populations with national data.

American Indian alcohol use has received scrutiny in recent decades,1 but data derived from samples that permit direct comparisons to other US epidemiological studies have been less commonly reported.2–4 This brief places rates of the quantity and frequency of alcohol use in 2 tribally defined reservation samples in such a comparative epidemiological context.
A concurrent algorithm for avoiding deadlocks in multiprocess multiple resource systems

In computer systems in which resources are allocated dynamically, algorithms must be executed whenever resources are assigned to determine if the allocation of these resources could possibly result in a deadlock, a situation in which two or more processes remain in an idle or blocked state indefinitely.In previous research, execution of the process requesting resources is suspended while an algorithm is executed to determine that the assignment could not cause a deadlock. In this paper, an algorithm is used to calculate all possible safe requests before they are made. This algorithm is executed concurrently with other processes between requests for resource allocations. If the determination of all safe requests has been completed and a process makes a request, the calculations required by the resource allocation are trivial.
Impact of Gin Saw-tooth Design on Fiber and Textile Processing Quality

Toothed gin saws have been used to separate cotton fiber from the seed for more than 200 years. A scientific analysis of saw-tooth design has never been published and the optimum saw-tooth design has not been found. Initial laboratory ginning evaluations of some modern gin saw teeth have shown differences among designs in ginning rate, fiber length measurements, and textile processing quality. The saw gin stand used for testing was a Continental Double Eagle that had been cut down to 46 saws. Four different sets of 16-in diameter, commercially available replacement saws were obtained from independent suppliers. These four sets, along with the standard Continental saw set, were used for five test saw treatments. The test saws varied in the number of teeth per saw from 328 to 352. Testing of the five saw treatments was replicated four times for a total of 20 ginning lots. Each ginning lot was analyzed for raw fiber quality and textile spinning performance. Most of the raw fiber properties were not significantly affected by the saw treatments. However, HVI length and length uniformity after one stage of lint cleaning and seed cotton processing rate were significantly different among saw treatments. The ginning rates varied by 34% from the lowest to the highest at 75% gin stand motor load. The ginned fiber was processed into both open-end and ring-spun yarns. There were few significant differences among saw treatments for the open-end yarn, but there were significant differences for the ring-spun yarn in ends down (a measure of spinning efficiency), yarn evenness, and yarn strength. This indicates that gin saw-tooth design might significantly affect spinning efficiency and yarn quality. Research is currently being done to further understand how gin saw-tooth design affects ginned fiber quality and textile processing quality factors.
The Friedländer Synthesis of Quinolines

Friedlander prepared quinoline in 1882 by the condensation of o-aminobenzaldehyde with acetaldehyde in the presence of sodium hydroxide. This type of reaction has since been extensively explored and, in its most general form, can be defined as an acid- or base-catalyzed condensation followed by a cyclodehydration between an o-amino-substituted aromatic aldehyde, ketone, or derivative thereof with an appropriately substituted aldehyde, ketone, or other carbonyl compound containing a reactive α-methylene group. Some quinolines can also be prepared simply by heating a mixture of the reactants with or without a solvent. Because both reactants contain a carbonyl group, certain quinolines can be prepared from a single starting compound. Of historic interest is the formation of the dye flavaniline from acetanilide. When acetanilide is heated with zinc chloride, the acetyl group of some molecules migrates to the ortho position, and that of others migrates to the para position. The resulting mixture of o-acetylaniline and p-acetylaniline then undergoes Friedlander condensation to form flavaniline. Two related quinoline syntheses, the Pfitzinger reaction and the Niementowski reaction, can be considered as extensions of the Friedlander synthesis. The Pfitzinger reaction uses an isatic acid or isatin and the Niementowski reaction uses an anthranilic acid for condensation to form a 4-quinolinecarboxylic acid and a 4-hydroxyquinoline, respectively. Several other related reactions, such as the Combes quinoline synthesis, the Doebner–Miller quinoline synthesis, and the Skraup quinoline synthesis, use different types of starting compounds. It is of interest that all of the six aforementioned syntheses of quinolines were discovered within a period of 14 years in the latter part of the nineteenth century, undoubtedly reflecting many scientific interests and commercial activities at that time, including the isolation of quinolines from coal tar, the manufacture of dyes, and studies of natural products such as alkaloids. Keywords: Friedlander synthesis; quinolines; scope; limitations; aminocarbonyl component; active methylene component; experimental procedures; aminobenzaldehdyes; condensations; aminoacetophenone hydrochloride; dimethylacetals; aminobenzophenone; aminoacroleins; amino heterocyclic carbonyls
Plasma free fatty acid and blood glucose responses to analogues of norepinephrine in man

l -Norepinephrine, l -epinephrine, dl -isoproterenol, and l -α-methyl norepinephrine produced pronounced elevations of plasma free fatty acid (FFA) concentrations in five normal subjects during 30-minute constant infusions at dose rates adjusted to give a pressor response of 45 ± 20 mm Hg. dl -Synephrine produced moderate increases, and tyramine produced minimal increases in FFA levels. Equipressor infusions of dopamine, l -phenylephrine, dl -normetanephrine and l -N-methyl epinephrine produced no significant FFA elevations. The observations suggest that, in derivatives of phenylethylamine, hydroxyl substitution at the para position and on the β-carbon and the presence of a primary or secondary amine structure are associated with the potent ability to elicit elevations of FFA in man. The phenolic hydroxyl group in the meta position appears to be of lesser, though significant, importance. Changes in blood glucose concentration did not always correlate with plasma FFA changes. During infusions of dl -isoproterenol, FFA rose significantly while glucose did not. During infusions of dopamine and l -N-methyl epinephrine, glucose rose significantly while FFA did not.
Tests of the adaptive modulation hypothesis for dietary control of intestinal nutrient transport

According to the adaptive modulation hypothesis, an intestinal transporter should be repressed when its biosynthetic and other costs (of maintenance) exceed the benefits it provides. This leads to two contrasting predictions: transport of a sugar or amino acid worth calories should tend to be increased by its substrate, and transport of a vitamin should be modulated downwards by its substrate and upmodulated in deficiency. In a test of the first prediction, omnivorous desert iguanas eating alfalfa pellets (a high-carbohydrate diet) were compared with desert iguanas eating mealworms (a low-carbohydrate, higher-protein diet). In accord with the prediction, intact intestinal sleeves from the former group had higher rates of carrier-mediated D-glucose uptake/centimeter across the brush border than sleeves from the latter group. But in contrast to the first prediction, mealworm eaters had lower (not higher) proline uptake rates, and the ratio of glucose/proline uptake in the two groups did not differ. I review similar tests in 12 other species and show that overall the hypothesis has been quite robust with regard to the first prediction. Cases in which the hypothesis is rejected may reflect complications associated with changes in other dietary factors or phylogenetic constraints. In a test of the second prediction, uptake of the water-soluble vitamin choline was not increased in choline-deficient chicks, nor was it decreased in adults that have no dietary requirement for choline. I review similar tests for four other vitamins and five essential minerals. Dietary control of transport of the minerals and two of the vitamins seems to be in accord with the hypothesis. But transport rate for three vitamins (choline, pantothenic acid, ascorbic acid) seems not to be increased in deficiency. The best explanation seems to be that vitamin transport is modulated only if it is primarily by a carrier-mediated pathway.
Hematocrit and Protein Concentration of Black Vulture and Turkey Vulture Blood

Blood protein concentration and hematocrit (packed cell volume) values are easily obtained and can be useful in determining the health of trapped or captive birds (Hunter and Powers 1980, Duke and Redig 1984). However, if these parameters are to be useful, there must be baseline data for comparison. Bond and Gilbert (1958), Hunter and Powers (1980), and Gessaman et al. (1986) have provided data for a variety of raptors, yet information on vultures is lacking. Our purpose is to provide baseline data on the blood characteristics of the Black Vulture (Coragyps atratus) and the Turkey Vulture (Cathartes aura).
Validation of a Low Reynolds Number Aerodynamic Characterization Facility

The characterization of a new wind tunnel at the University of Florida’s Research and Engineering Education Facility is presented. The tunnel is specifically designed to operate in the low Reynolds number regime in which Micro Air Vehicles operate. The wind tunnel is driven by a 60 inch, 50 hp axial blower controlled by a variable frequency drive. The tunnel entrance consists of a flow conditioning section and a 8:1 area contraction ratio that results in a 42” square entrance to the open jet test section. The enclosure surrounding the test section has a volume of nearly 2000 ft with an axial length of 10 ft. The free stream velocities in the tunnel range from nominally 0 to 22 m/s by altering the frequency on the variable frequency drive. Flow uniformity studies for free stream velocities of 2 and 15 m/s were conducted demonstrating a potential core throughout the test section of at least 60% of the 1.14 m contraction exit. Experiments using hot wire anemometry were also performed and the turbulence intensities were found to be less 0.22% for free stream velocities greater than 1m/s.
Microexplosions in the Upgrading of Biomass-Derived Pyrolysis Oils and the Effects of Simple Fuel Processing

The development of biofuels produced from biomass-derived pyrolysis oils (bio-oil) requires a deeper understanding of the bio-oil vaporization required for catalytic hydrodeoxygenation, reforming and combustion processes. Through the use of high-speed photography, bio-oil droplets on a 500 °C alumina disk in nitrogen gas were observed to undergo violent microexplosions capable of rapidly dispersing the fuel. High speed photography of the entire droplet lifetime was used to determine explosion times, frequency and evaporation rates of the bio-oil samples that have been preprocessed by filtering or addition of methanol. Filtration of the oil prior to evaporation significantly reduced the fraction of droplets that explode from 50% to below 5%. Addition of methanol to bio-oil led to uniform vaporization while also increasing the fraction of droplets that exploded. Experiments support the necessity of dissolvable solids for the formation of a volatile core and heavy shell which ruptures and rapidly expands to ...
The limits of soft balancing: the frozen conflict in Transnistria and the challenge to EU and NATO strategy

Both the EU and NATO have greatly expanded efforts to address the frozen conflict in Transnistria since 2003. These efforts by and large fall neatly into the category of ‘soft balancing’ actions ag...
Evaluation on linear growth of children with hypothyroidism

Objective To observe and analyze the change of growth velocity(GV),height age(HA)and bone age(BA)of children with hypothyroidism before and after treatment with levothyroxine sodium,which reveal the regularity of linear growth.Methods Twenty-six children's X-ray films of left hands and wrists were observed as well as GV and HA,at the same time.Serum levels of T3,T4,FT3,FT4,thyrotrophic stimulating hormone(TSH),thyroid peroxidase antibody(TPOAb)and thyroglobulin antibody(TGAb)were detected by means of chemiluminescence immunoassay.Results The HA and BA of children with hypothyroidism were younger than their chronological age(CA)before treatment.They achieved catch-up growth that the ΔBA and ΔHA were faster than ΔCA after treatment.During the treatment,the ΔBA and ΔHA presented decrement tendency and kept parallel.In addition,the growth retardations or arrests were improved.Conclusions Levothyroxine sodium has the effect of promoting linear growth for children with hypothyroidism.HA and BA inspection have important instructional significance in diagnosis,therapeutic effect and prognosis judgement of hypothyroidism in children.
Behavior of Listeria monocytogenes in the Presence of Flavobacteria in Skim Milk at 7 or 13°C

Sterile samples of skim milk were inoculated with Listeria monocytogenes (strain Scott A, California, or V7), Flavobacterium lutescens or Flavobacterium species, or a combination of L. monocytogenes plus flavobacteria and incubated at 7 or 13°C for 8 weeks. McBride Listeria agar was used to determine populations of L. monocytogenes at 0, 7, 14, 28, 42, or 56 d, and plate count agar was used to enumerate flavobacteria at the same time intervals. Growth of L. monocytogenes was significantly (P<0.05) enhanced during incubation at 7 or 13°C in mixed cultures with F. lutescens . When tested with Flavobacterium sp. ATCC 21429, numbers of L. monocytogenes decreased insignificantly (P<0.05) in mixed cultures compared to pure cultures. L. monocytogenes did not affect growth of flavobacteria; also, no marked changes in pH of the milk were caused either by L. monocytogenes alone or by mixed cultures.
The Effect of Bacillus Calmette-Guerin on the Urinary System of Pigs

Abstract An experimental study was conducted to determine the changes in structure and function of the pig kidney and renal pelvis following intrarenal infusion of bacillus Calmette-Guerin (BCG). Bilateral nephrostomy tubes were inserted in six pigs through a subcostal (flank) retroperitoneal approach. One week later, antegrade pyelograms and renal scans with hippuran I-131 were obtained. The left kidney was then infused weekly for six weeks with two ampules of BCG (Tice strain) dissolved in 75 cc of saline. The right kidney, serving as a control, was infused concomitantly with 75 cc of saline. On week 7, bilateral antegrade pyelograms and renal scans were repeated. Two pigs were sacrificed at four, eight and 12 weeks after completion of BCG therapy. In all pigs, antegrade pyelograms of the left kidney before BCG instillation were identical to those obtained after completion of treatment and to those of the saline infused kidneys. The isotope renal scan in five pigs showed no significant change in image appearance or relative renal plasma flow in the pre-treatment and post-treatment images. In one pig, there was a decrease in the relative clearance of hippuran in the saline infused kidney. In this kidney, an upper pole abscess was found. Microscopic examination of the renal cortex, medulla, pelvis and ureter of the BCG infused kidneys was normal and identical to the saline infused kidneys. The urothelium was intact and no inflammatory changes were noted in the renal cortex or medulla. These results show that direct infusion of BCG into the renal collecting system has no adverse effect on the structure and function of pig kidneys when followed one to three months after treatment.
Informed consent in oncology clinical trials: A Brown University Oncology Research Group prospective cross-sectional pilot study.

Background Informed consent forms (ICFs) for oncology clinical trials have grown increasingly longer and more complex. We evaluated objective understanding of critical components of informed consent among patients enrolling in contemporary trials of conventional or novel biologic/targeted therapies. Methods We evaluated ICFs for cancer clinical trials for length and readability, and patients registered on those studies were asked to complete a validated 14-question survey assessing their understanding of key characteristics of the trial. Mean scores were compared in groups defined by trial and patient characteristics. Results Fifty patients, of whom half participated in trials of immunotherapy or biologic/targeted agents and half in trials of conventional therapy, completed the survey. On average, ICFs for industry-originated trials (N = 9 trials) were significantly longer (P < .0001) and had lower Flesch ease-of-reading scores (P = .003) than investigator-initiated trials (N = 11). At least 80% of patients incorrectly responded to three key questions which addressed the experimental nature of their trial therapy, its purported efficacy and potential risks relative to alternative treatments. The mean objective understanding score was 76.9±8.8, but it was statistically significantly lower for patients who had not completed high school (P = .011). The scores did not differ significantly by type of cancer therapy (P = .12) or trial sponsor (P = .38). Conclusions Many participants enrolled on cancer trials had poor understanding of essential elements of their trial. In order to ensure true informed consent, innovative approaches, such as expanded in-person counseling adapted to the patient’s education level or cultural characteristics should be evaluated across socio-demographic groups. Trial registration Clinicaltrials.gov NCT01772511
Expanding the Paracrine Hypothesis of Stem Cell-Mediated Repair in the Heart: When the Unconventional Becomes Conventional.

Recent interest in mechanisms of stem cell–mediated repair in the heart have spawned the paracrine hypothesis, which posits that stem cells release beneficial substances that improve regeneration and function of the injured and diseased myocardium. In support of this hypothesis are studies showing that stem cells release small membranous vesicles called exosomes that deliver beneficial cargo to other cells in the heart. However, in addition to exosomes, which are released by the unconventional secretory pathway, are many other potentially beneficial factors released by the unconventional and the conventional secretory pathways. Therefore, a broader perspective of mechanisms of secretion, as well as an appreciation for the ways in which the secretion of a wide range of different types of molecules can be regulated, will spawn new avenues of thought necessary to move us beyond the exosome-centric view that drives much of the current thinking of those who study of stem cell–mediated repair in the heart. Secretion is what cells do; excretion is what the kidney does. Secretion is an active process by which cells release materials into the surrounding environment. Among the first secretion mechanisms studied were those involved in the regulated release of peptide hormones from endocrine cells. After release, substances can signal to cells afar via the blood stream (endocrine) and to neighboring cells (paracrine), as well as the cell of origin (autocrine). Additionally, some substances signal within the cell of origin (intracrine). Endocrine, paracrine, and autocrine signaling all involve the release of communicator substances directly into the interstitial spaces surrounding the cells of origin. Secretion into a duct, such as salivary or digestive enzyme secretion, is exocrine. Cells secrete many different substances, including proteins, lipids, steroids, nucleic acids, nucleotides, metabolites, and ions. Generally, these substances are secreted to facilitate communication with other cells and to affect the structure …
Effective Interaction in α-Nucleus Scattering

Elastic $\ensuremath{\alpha}$-nucleus differential cross-section data (15\ifmmode^\circ\else\textdegree\fi{}-175\ifmmode^\circ\else\textdegree\fi{}) are analyzed using a potential model. The real potential is calculated using an effective potential obtained from a global analysis of nucleon-$\ensuremath{\alpha}$ data. The resulting four-parameter model given an excellent representation of the $\ensuremath{\alpha}$-nucleus data. This representation is significantly better than can be obtained with a six-parameter optical model and is sensitive to the nuclear-nucleon density distribution.
HIGHER AMBULATORY HEART RATES PREDICT INCREASED LONG TERM MORTALITY IN PATIENTS WITH HFREF

Background: Prior studies have shown short term (up to 1 year) increased adverse outcomes in heart failure with reduced ejection fraction (HFrEF) patients with higher heart rates (HR). We investigated long term effect of ambulatory HR on mortality in patients with HFrEF. Methods: We queried the
Elotuzumab as a novel anti-myeloma immunotherapy

Treatment of multiple myeloma has undergone significant change in the last decade with the introduction of new immunomodulatory agents, proteasome inhibitors, and immunotherapeutic approaches. Elotuzumab is a humanized monoclonal antibody targeting CS1, which is a member of the SLAM (Signaling Lymphocyte Activation Molecule) family of proteins, expressed on the surface of myeloma plasma cells. Here we review the preclinical investigations that led to the development of elotuzumab and the clinical studies that resulted in its approval for the treatment of relapsed/refractory multiple myeloma. Although preclinical data looked very promising, elotuzumab monotherapy did not result in objective clinical responses in patients with relapsed/refractory multiple myeloma. However, combination treatment with immunomodulators and proteasome inhibitors resulted in substantial clinical activity in relapsed/refractory MM. Currently, there are several clinical trials ongoing investigating the role of elotuzumab in newly diagnosed myeloma patients and in patients receiving maintenance therapy.
On the formation and migration entropies of vacancies in metals

Abstract An approach has been developed for calculating defect entropies from an entirely discrete vibrational point of view. Calculations have been performed within a discrete finite spherical array of atoms which includes all contributions to the defect entropy predicted by linear isotropic continuum elasticity. The method used, however, does not demand an explicit knowledge of the strength of the defect and thus avoids certain conceptual difficulties that arise in both the elastic and the combined discrete-elastic approaches. The vibrational spectra for the various defect configurations have been obtained using a quasiharmonic Einstein model in conjunction with a modified Morse function as force law. Values of the vacancy formation and migration entropies were computed for the cases of copper, nickel and aluminum. Where experimental values were available for comparison, fair agreement was found with the calculated entropies. In addition, Arrhenius D 0 's calculated on the assumption that diffusion is controlled by the migration of single vacancies were found to be lower than experimental D 0 's, thus lending support to previous suggestions in the literature that divacancies make a significant contribution to the diffusion flux in f.c.c. metals at high temperatures.
Development of the Aim to Decrease Anxiety and Pain Treatment for Pediatric Functional Abdominal Pain Disorders.

Objectives To evaluate the feasibility and acceptability of the Aim to Decrease Anxiety and Pain Treatment (ADAPT), a brief, on-line and in-person behavioral intervention targeting pain and anxiety in youth with functional abdominal pain disorders (FAPDs). Methods Patients were recruited from several outpatient pediatric gastroenterology clinics. Nine participants (ages 9-13) completed the full protocol. Thematic analysis of detailed qualitative feedback was obtained via semistructured patient and caregiver interviews after treatment was conducted. Feasibility and preliminary outcomes were examined using nonparametric tests. Results Preliminary results indicate that the ADAPT treatment is feasible, acceptable, and potentially effective for youth with FAPD. Treatment completers reported that they enjoyed the program and used the skills to manage their pain and worry. Results also indicated that the majority of participants experienced a reduction in anxiety and several reported reductions in pain and functional disability levels. Conclusions Findings from this study suggest that targeting both pain and anxiety may positively impact outcomes in youth with FAPD. The ADAPT intervention has the potential to provide a cost effective and practical application of cognitive behavioral therapy using an innovative combination of in-person and technology-based platforms. Overall, the ADAPT intervention is a promising and innovative intervention to improve the outcomes of youth with FAPD.
Mechanics of inter-modal tunneling in nonlinear waveguides

Abstract In this article, we investigate the mechanics of nonlinearly induced inter-modal energy tunneling between flexurally-dominated and axially-dominated modes in phononic waveguides. Special attention is devoted to elucidating the role played by the coupling between axial and flexural degrees of freedom in the determination of the available mode hopping conditions and the associated mechanisms of deformation. Waveguides offer an ideal test bed to investigate the mechanics of nonlinear energy tunneling, due to the fact that they naturally feature, even at low frequencies, families of modes (flexural and axial) that are intrinsically characterized by extreme complementarity. Moreover, thanks to their geometric simplicity, their behavior can be explained by resorting to intuitive structural mechanics models that effectively capture the dichotomy and interplay between flexural and axial mechanisms. After having delineated the fundamental mechanics of flexural-to-axial hopping using the benchmark example of a homogeneous structure, we adapt the analysis to the case of periodic waveguides, in which the complex dispersive behavior due to periodicity results in additional richness of mode hopping mechanisms. We finally extend the analysis to periodic waveguides with internal resonators, in which the availability of locally-resonant bandgaps implies the possibility to activate the resonators even at relatively low frequencies, thus increasing the degree of modal complementarity that is available in the acoustic range. In this context, inter-modal tunneling provides an unprecedented mechanism to transfer conspicuous packets of energy to the resonating microstructure.
An Empirical Study of the Race, Ethnicity, Gender, and Age of Copyright Registrants

Who is the author in copyright law? Knowing who our copyright system currently incentivizes to create which works is a necessary precondition for any effective copyright reform, yet copyright scholarship has thus far treated authors only through a priori conceptual analysis. This Article explores the author empirically. Do those who self-identify as blacks (a U.S. Census category) register more music than members of other races per capita? Are Jewish authors particularly productive in registering literary works? What percentage of registrations represents works created by women? Which works tend to be registered by older authors? This Article provides answers to these questions—which happen to be yes, very likely, one third, and literary works—and to many more by statistically analyzing the records of all fifteen million works registered with the Copyright Office from 1978 through 2012. It characterizes the modern-day American author along the axes of race and ethnicity, gender, and age. The Article spells out the implications for copyright theory, policy, law, and reform. Copyright theory must explicitly account for the mechanism by which the copyright carrot induces authors of different demographics to create different types of works. This mechanism appears to contain substantial situated components—including social, cultural, and gender-related characteristics—that the major theories of copyright law that assume author uniformity do not acknowledge.
Estimation for Possibly Nonminimum Phase Schemes

At an earlier point maximum likelihood estimates of parameters were discussed for Gaussian ARMA schemes. Quasi-Gaussian likelihood estimates were considered in the case of minimum phase non-Gaussian ARMA schemes. At that point one had already remarked that maximum likelihood ought to yield more efficient estimates even for minimum phase non-Gaussian ARMA schemes. We shall now consider non-Gaussian autoregressive schemes that may be nonminimum phase and consider estimation of parameters. Our discussion is an idealization since it is assumed that the scaled density function g of the independent random variables ξ t generating the stationary autoregressive sequence of order p $$ {x_{t}} - {\phi _{1}}{x_{{t - 1}}} - \cdots - {\phi _{p}}{x_{{t - p}}} = {\xi _{t}} $$ is known. A discussion of ARMA schemes is more complicated but of a similar character and remarks on them will be made.
Simulation of the Potential Impacts of Acidic Deposition on Forest Soils in the South

Various criteria have been used to evaluate the sensitivity of soils and waters to acidic desposition (Chap. 5), but these criteria remain largely unvalidated. Two approaches to test the relevance of these criteria are computer simulation modeling and long-term field studies. Simulation models have the advantage of rapid evaluation, but the key processes depicted in models need to be tested against field data to develop confidence in model predictions. Long-term field studies can provide definitive evaluations of sensitivity criteria; unfortunately, long-term historical data are currently limited and cannot be used for regional assessments. In the absence of regionally representative data from long-term projects, we used the MAGIC model (Modeling Acidification of Groundwater in Catchments, Cosby et al. 1985a) to evaluate the sensitivity of a representative set of southern forest soils. We chose this model over others currently available because it depicts critical chemical processes that are thought to control soil water acidification and because its limited data requirements allowed us to use information available in the South (unlike more complicated, data-intensive models such as the Integrated Lake-Watershed Acidification Study [ILWAS]) (Goldstein et al. 1985). Sensitivity of soils was gauged by (1) depletion of exchangeable basic cations, (2) increases in soil-solution concentrations of aluminum, and (3) the alkalinity of drainage waters.
The Academic and Vocational Classrooms

The pedagogy of the Rainbow School is characterized by two instruction traditions known as intent community participation and didactic (or rote) instruction or assembly-line instruction. Barbara Rogoff and her colleagues have described these pedagogical models in their work. The school uses the model of intent community participation to teach social and vocational skills. In this model, adults and students work together on daily activities in their community, and learning occurs through feedback, modeling, and participation. In contrast, math and literacy are taught using rote methods based on didactic or assembly-line instruction, the common form of teaching employed in most Tanzanian public schools. This model views the teacher as the expert, pencil–and-paper activities are common, and students demonstrate their knowledge through questions and answers. The academic and vocational classrooms look very different, and children are learning differently.
Evolution of an empathetic digital entity: phase one

This demonstration highlights the first of seven segments designed to develop a digital entity that will possess the potential for human empathy. The experiences in the first phase of the digital entity Zoe (Zero-One Entity) parallel a subset of learning and development activities encountered by human beings during their first nine months of existence. A website has been created to provide a window to observe Zoe's experiences and action selection process in order to make her basic learning observable, cumulative, and evolutionary. The human observer is invited to influence her action selection by setting the intensity of Zoe's digital personality traits such as assertiveness, reasoning ability, and disposition. Actions generate body-based and emotive-based feelings which are stored in memory structures. Significantly, these structures serve as a foundation for later stages of learning, understanding and reasoning.
Comment on "Predicting reaction performance in C-N cross-coupling using machine learning".

Ahneman et al . (Reports, 13 April 2018) applied machine learning models to predict C–N cross-coupling reaction yields. The models use atomic, electronic, and vibrational descriptors as input features. However, the experimental design is insufficient to distinguish models trained on chemical features from those trained solely on random-valued features in retrospective and prospective test scenarios, thus failing classical controls in machine learning.
Demographic determinants of public service motivation: a meta-analysis of PSM-age and -gender relationships

Although age and gender are among the most analysed determinants of public service motivation (PSM), their effects on PSM development remain unclear due to contradictory findings among studies. To ...
Research Pioneers in Emergency Medicine-Reflections on Their Paths to Success and Advice to Aspiring Researchers: A Qualitative Study.

Study objective Research in basic, translational, and clinical emergency medicine has made great strides since the formalization of emergency medicine as a specialty. Our objective is to identify and analyze strategies used by emergency medicine research pioneers to inform further advancement of research in emergency medicine, particularly for aspiring researchers and those in emerging areas, using emergency medicine medical education as one example. Methods This was a prospective, grounded-theory, qualitative study, using a constructivist/interpretivist paradigm. Leading basic science, translational, and clinical emergency medicine researchers who completed residency before 1995 were eligible for structured interviews. Thematic coding followed an iterative process until saturation was reached. A theoretic model was developed and analyzed. Results Research pioneers valued advanced methodological training and mentorship. Barriers to funding were lack of recognition of emergency medicine as a specialty, absence of a research history, and lack of training and funding resources. Deliberate interventions to improve emergency medicine research included educational sessions at national meetings, external (to emergency medicine) mentor pairings, targeted funding by emergency medicine organizations, and involvement with funding agencies. Pioneers facilitate research excellence by serving as mentors and allocating funds or protected time to develop researchers. To advance emerging subfields of research in emergency medicine, pioneers recommend advanced methodological training that is specific to the area, deliberate mentorship, and the formation of research consortia to conduct generalizable outcomes-based studies. Conclusion Research pioneers in emergency medicine cite mentorship, advanced skills obtained through fellowship or graduate degrees, deliberate collaboration with experienced researchers, support from emergency medicine organizations, and forming networks as the cornerstones of success.