cssi/SciSciGPT-SciSciNet huggingface dataset:
Individualized risk for statin-induced myopathy: current knowledge, emerging challenges and potential solutions.

Skeletal muscle toxicity is the primary adverse effect of statins. In this review, we summarize current knowledge regarding the genetic and nongenetic determinants of risk for statin induced myopathy. Many genetic factors were initially identified through candidate gene association studies limited to pharmacokinetic (PK) targets. Through genome-wide association studies, it has become clear that SLCO1B1 is among the strongest PK predictors of myopathy risk. Genome-wide association studies have also expanded our understanding of pharmacodynamic candidate genes, including RYR2. It is anticipated that deep resequencing efforts will define new loci with rare variants that also contribute, and sophisticated computational approaches will be needed to characterize gene–gene and gene–environment interactions. Beyond environment, race is a critical covariate, and its influence is only partly explained by geographic differences in the frequency of known pharmacodynamic and PK variants. As such, admixture analyses wi...
The Treatment of Hyperhomocysteinemia

The unique biochemical profile of homocysteine is characterized by chemical reactivity supporting a wide range of molecular effects and by a tendency to promote oxidant stress-induced cellular toxicity. Numerous epidemiological reports have established hyperhomocysteinemia as an independent risk factor for cardiovascular disease, cerebrovascular disease, dementia-type disorders, and osteoporosis-associated fractures. Although combined folic acid and B-vitamin therapy substantially reduces homocysteine levels, results from randomized placebo-controlled clinical trials testing the effect of vitamin therapy on outcome in these diseases have generally fallen short of expectations. These results have led some to abandon homocysteine monitoring in the management of patients with cardiovascular or cognitive disorders. These trials, however, have generally included patients with only mildly elevated homocysteine levels and have not addressed several clinical scenarios in which homocysteine reduction may be effective, including the primary prevention of atherothrombotic disease in individuals at low or intermediate risk, or those with severe hyperhomocysteinemia.
Designing leakage aware multipliers

Power consumption has become a major design limiter. With the continued reduction of threshold voltages, optimizing leakage energy consumption is becoming increasingly important. Hence, the design of leakage-conscious memory and data path components is vital. This paper focuses on designing a 32-bit double precision multiplier, and shows how the appropriate choice of implementation primitives used in the design can provide significant leakage energy savings without much impact on performance.
Bone marrow cells for cardiac regeneration: the quest for the protagonist continues

See also article by Hattan et al. [11] (pages 334-344) in this issue . The past few years have witnessed an explosion of research on methods to achieve myocardial repair via cellular transplantation or mobilization of endogenous cells [1]. Several different cell types, including skeletal myoblasts [2], c-kit+/Sca-1+/lin− bone marrow (BM) cells [3], BM mesenchymal stem cells (MSCs) [4], BM ‘side-population’ (SP) cells [5], endothelial progenitor cells (EPCs) [6], and cardiac stem cells (CSCs) [7], have been utilized in an effort to achieve cardiac reconstitution and restoration of function following myocardial infarction (MI). The evidence accumulated over the past few years indicates that left ventricular (LV) function and adverse LV remodeling can be ameliorated via cell-based therapies, and the preliminary results from several small-scale, mostly non-randomized, clinical trials have been encouraging [8–10]. However, the mechanism(s) underlying the observed functional improvement remains unclear and the debate regarding the advantages of one candidate cell versus another continues unabated. So, what characteristics should a cell have in order to be selected for therapeutic use in humans? The answer is simple: it has to differentiate into cardiomyocytes that are connected both mechanically and electrically with native myocytes (contracting in synchrony with adjacent cells) and be able to form vascular structures in order to get blood supply in the scar. Thus far, very few cell types have been shown to do all of these things. In this issue of the Journal, Hattan, Kawaguchi, and colleagues … *Corresponding author. Tel.: +1 502 852 7959; fax: +1 502 852 7147. Email address: buddha{at}louisville.edu
The environment and mental retardation

A wide range of environmental factors affect intelligence and mental retardation. Biological risk factors for mental retardation include malnutrition; exposure to toxins such as lead, alcohol, and PCBs, and being born at LBW. Social influences from homes, schools, and cultures are related to intelligence and mental retardation although the direction of effect is difficult to determine. Randomized early intervention studies with children in poverty provide the best data showing that increased intelligence and adaptive behavior is possible, although significant and sustained effects only result from intensive services of long-term duration.
Strong sintered miserite glass-ceramics

Strong and tough glass-ceramic materials based on the complex chain silicate miserite (KCa5open square(Si2O7)(Si6O15)F) have been prepared using standard frit sintering and internal nucleation processes. The miserite may be accompanied by crystals of fluorite, cristobalite, xonotlite, a canasite-like phase, and fluorapatite. The highly crystalline glass-ceramics have a microstructure composed primarily of interlocked, lath- or log-shaped miserite crystals with pronounced cleavage planes. This microstructure provides abraded flexural strength values as high as 235 MPa (34 000 psi) and fracture toughness values >3.0 MPa·m1/2. These strength and toughness values are quite high for a glass-derived material. Miserite glass-ceramics may be useful for many applications in which such strength and toughness are desired.
Photoradiation Therapy of Malignant Tumors; Role of the Laser

Photoradiation therapy, in which hematoporphyrin derivative (Hpd) is activated by visible light in situ is being investigated for the control of solid malignant tumors in man |1,2|. This method is based upon the ability of Hpd to first accumulate and be retained in malignant tissue to a greater degree than in some normal tissues |3,4,5|, and then to produce singlet oxygen (1O2) when activated by visible light, thus producing a cytotoxic effect |6|. While this latter property, known as a photodynamic effect |7|, is common to a wide range of materials, its combination with tumor localizing ability is guite unigue. Tetraphenylporphine sulfonate appears to possess similar properties to Hpd but suffers the disadvantage of prolonged retention in serum and tissues |8, 9|, thus rendering animals photosensitive for extended periods. This is also a problem with Hpd |1, 2| but is of relatively short duration (approximately 30 days, depending on dose) and can be avoided by preventing sunlight exposure. We have examined many other porphyrins as potential tumor photosensitizers in animals, but none has been found to be as effective as Hpd |10|.
Evolution And Ethics

Evolution and Ethics by Franklin Roy Bennett Advisor: Professor S.M. Cahn Does evolution inform the ancient debate about the roles that instinct (emotion/passion/sentiment/feeling) and reason do and/or should play in how we decide what to do? Evolutionary ethicists typically adopt Darwinism as a suitable explanation for evolution, and on that basis draw conclusions about moral epistemology. However, if Darwinism is to be offered as a premise from which conclusions about moral epistemology are drawn, in order to assess such arguments we must assess that premise. This reveals the highly speculative and metaphysical quality of our theoretical explanations for how evolution happens. Clarifying that helps to facilitate an assessment of the epistemological claims of evolutionary ethicists. There are four general ways that instinct and reason can function in moral deliberation: descriptive instinctivism asserts that moral deliberation is necessarily a matter of instincts because control of the instincts by our faculty of reason is regarded (descriptively) as impossible; descriptive rationalism asserts that moral deliberation is necessarily a matter of reasoning, which (descriptively) must control instinct; prescriptive instinctivism asserts that moral deliberation can involve both rationality and instinct but prescribes following our instincts; prescriptive rationalism also asserts that deliberation can be either instinctive or rational but
Urinary Excretion of Erythropoietin in Normal Men and Women

The bioassay of erythropoietin in polycythemic mice was modified to include a protein-depletion diet and a divided erythropoietin injection schedule. Although less than 0.05 unit of standard erythropoietin was not detected, a more linear dose/response relationship resulted from increasing doses of erythropoietin in the 0.1 to 1.0 unit range. The amount of erythropoietin in concentrated specimens prepared from the 24-hour urinary excretion of 25 normal subjects was measured in comparison with known quantities of standard erythropoietin. A mean daily erythropoietin excretion in men of 2.8 ± 1.3 units, in women of 0.9 ± 0.4 unit and in prepubertal boys of 1.0 unit was calculated. The higher erythropoietin excretion in adult males may be secondary to a greater production of erythropoietin in this sex.
Hyperglycemia and obesity in patients (pts) with acute lymphoblastic leukemia (ALL): Association with prevalence, response, and survival

7074 Increasing evidence suggests associations between obesity, diabetes and/or hyperglycemia (DM/HG) and solid tumors. Less is known about the relationship of these metabolic factors to the hematologic malignancies. To determine the prevalence of DM/HG and obesity in pts with ALL and whether these are predictors of response and survival, we conducted a retrospective chart review of 299 pts with newly diagnosed ALL, who were evaluated at our institution between November 1999 and May 2005 and received hyper-CVAD therapy: fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and high-dose cytarabine. Median age was 43 yrs (range 15–83). Sixty-one percent of pts were male, and 39% female. Seventy-four percent had a diagnosis (dx) of precursor B cell ALL (22% Ph+), 18% Burkitt's ALL, 6% lymphoblastic lymphoma, 2% other. Prior to therapy, the overall prevalence of DM/HG (diabetes based on reported dx prior to ALL-dx, and hyperglycemia based on baseline serum gluco...
Validation of Bicycle Counts from Pneumatic Tube Counters in Mixed Traffic Flows

FHWA and other public agencies encourage monitoring of nonmotorized traffic volumes and are collaborating with researchers in projects to test monitoring technologies and develop nonmotorized monitoring programs. This paper reports findings from research in Minnesota to validate the use of commercially available pneumatic tube counters to count bicycles in mixed traffic flows on urban roadways. Pneumatic tube counters and video cameras were installed in different configurations at two locations on arterial roadways with different traffic volumes. Bicycle counts from the tube counters were compared with manual counts from video to determine both percentage error and absolute error rates. Researchers matched time stamps from the counters and video and inspected discrepancies to determine causes of error. Calibration equations to adjust for systematic counter error were estimated by regressing hourly manual counts on hourly automated counts. The tube counters generally undercounted bicycles: error rates for ...
The NH3 Mass Accommodation Coefficient for Uptake onto Sulfuric Acid Solutions

The uptake of NH3 onto particles with diameters of ∼100 nm composed of sulfuric acid and water was studied in a laminar flow reactor. The gas-phase loss of NH3 was monitored with a chemical ionization mass spectrometer. Temperature ranged from 287 to 296.5 K. The mass accommodation coefficient, α, was found to be close to unity for NH3 uptake onto the surface of 15−65 wt % H2SO4 solutions. The finding that α does not depend on composition over this range of acid content is at odds with recently published work on the same subject where the measured NH3 mass accommodation coefficient was observed to decrease from unity on 70 wt % H2SO4 to 0.3(±0.05) on 20 wt % H2SO4. Possible reasons for this discrepancy and consequent implications for results from that experimental technique will be discussed. A value of unity for α indicates that the neutralization of sulfuric acid particles by atmospheric ammonia will be efficient.
Parathyroid gland function and the set point for PTH release: understanding the available data

7. Bucala R, Makita Z, Vega G et al. Modification of low density lipoprotein by advanced glycation end products contributes to the dyslipidemia of diabetes and renal insufficiency. Proc Nat! AcadSci USA 1994; 91: 9441-9445 8. Horkko S, Savolainen MJ, Kervinen K, Kesflniemi YA. Carbamylation-induced ateration in low-density lipoprotein metabolism. Kidney Int 1992; 41: 1175-1181 9. Chan MK, Persaud J, Varghese Z, Kingstone D, Baillod RA, Moorhead J. Apolipoprotein B turnover in dialysis patients: its relationship to the pathogenesis of hyperlipidemia. Clin Nephrol 1989; 31: 88-95 10. Dumler F, Stalla K, Mohini R, Zasuwa G, Levin NW. Clinical experience with short-term hemodialysis. Am J Kidney Dis 1992; 19: 49-56 11. Josephson MA, Fellner SK, Dasgupta A. Improved lipid profiles Nephrol Dial Transplant 1996: Editorial Comments
Tracking the Progress of Congress Mashing with Osmolyte Concentration and Malt Extract Value in North American Barley Cultivars and Relationships Between Wort Osmolyte Concentration, Malt Extract Value, and ASBC Measures of Malt Quality

This study was conducted to test three hypotheses: 1) barley malt osmolyte concentration (OC) would increase more rapidly during mashing than malt extract (ME); 2) OC would better discriminate between differing barley malts during mashing than ME; and 3) OC after mashing would better correlate with ASBC measures of malt quality than ME. Malts of six two-row and six six-row barley cultivars were mashed in a micromasher, and aliquots were removed for wort OC and ME measurements at six time points during a 115-min mashing regime. For all cultivars combined, over the first 55 min of mashing wort OC values increased 120% compared with 91% for ME. At the end of the mashing regime (115 min) wort OC values further increased to 132%, whereas wort ME values remained approximately the same (91–92%). This indicates that the mass of material in wort remained approximately the same after 55 min but was further degraded to lower molecular weight compounds, increasing wort molarity and, thus, OC but not ME. Steptoe, a feed barley, was separated to a much greater degree from elite malting cultivars by wort OC than by ME values throughout the mashing regime. Except for very early in mashing (5 min), there was better separation of all cultivars by OC than by ME values throughout mashing, as determined with least significant difference analysis, indicating that OC may be better than ME for judging differences in cultivar malt quality. Linear correlations of time-course mash OC versus ME values were excellent for all cultivars combined (r = 0.977, P < 0.0001) and for two- and six-row cultivars separately. Correlations of the 115-min mashing OC and ME values with ASBC malt quality measurements were considerably better for OC than for ME (e.g., wort protein [r = 0.819, P = 0.001 for OC; r = 0.407, P = 0.189 for ME]; diastatic power [r = 0.765, P = 0.004 for OC; r = 0.287, P = 0.365 for ME]; alpha-amylase [r = 0.737, P = 0.006 for OC; r = 0.584, P = 0.046 for ME]; and beta-glucan [r = –0.0.754, P = 0.005 for OC; r = –0.0.595, P = 0.041 for ME]). This study supports all three hypotheses.
Binding of Atropine and Muscarone to Rat Brain Fractions and its Relation to the Acetylcholine Receptor

The binding of atropine and muscarone to subcellular fractions from whole rat brain was measured by equilibrium dialysis. At 10 nM, muscarone and atropine, but not decamethonium, dimethyltubocurarine, or nicotine, bound to a crude mitochondrial fraction from brain, and the binding was reversible. Atropine and muscarone at 10 nM did not bind to homogenates of kidney or lung. Atropine, but not muscarone, bound to liver homogenates and liver mitochondria, probably to atropinesterase. Atropine at 10 nM bound to a greater extent, on a protein basis, to fractions enriched in synaptosomes, pre- and postsynaptic membranes, and membrane of uncertain origin, than to other fractions. Muscarone showed a similar binding profile but also bound to purified mitochondrial fractions. Atropine bound to the synaptic membrane fraction at two sites present at 0.089 ± 0.018 and 0.91 ± 0.20 nmole/g of tissue (fresh weight), with binding constants of 0.6 ± 0.01 nM an d 0.9 ± 0.18 µM, respectively. Only scopolamine, of the sixteen drugs tested (at 50 nM), interfered with atropine binding at 5 nM to the same fraction. These findings are interpreted as showing that the higher-affinity site for atropine binding is the site more likely to be related to the physiological acetylcholine receptor. ACKNOWLEDGMENTS We wish especially to thank Drs. M. E. and A. T. Eldefrawi for their generous advice. We also wish to thank Dr. H. Howland for computer analysis. We are grateful to the Geigy Company of Switzerland for donating normuscarone, and to Mr. B. D. Hilton for synthesizing [3H]muscarone.
Hepatic purine enzyme profiles and uric acid overproduction in muscular dystrophy and in inherited tophaceous gout.

SummaryAlthough uric acid overproduction frequently, but not always, leads to gout in humans, it is not known if different biochemical aberrations in purine metabolism might be responsible for that uric acid overproduction which culminates in gout and that which does not. To investigate this possibility hepatic purine enzymes were measured in a line of chickens which overproduced uric acid but did not develop clinical gout (dystrophic) and in another line of the same strain which overproduced uric acid and developed severe tophaceous gout (dystrophic gouty). Adenosine and adenylate deaminases and nucleoside phosphorylase were elevated in both the dystrophic and dystrophic gouty chickens compared with controls. The activities of these three enzymes were not different between the dystrophic and dystrophic gouty groups. 5′-nucleotidase and adenosine kinase were elevated only in dystrophic gouty chickens. Hypoxanthine phosphoribosyltransferase was elevated in dystrophic chickens and was further elevated in dy...
Co-existing aluminum silicates in quartz veins: A quantitative approach for determining andalusite-sillimanite equilibrium in natural samples using oxygen isotopes

ABS T RAC T Massive quartz veins with large andalusite and sillimanite crystals in textural equilibrium were found in a Proterozoic province in the northern Colorado Front Range. The δ 1 8 O values of the andalusite and sillimanite are identical, supporting the idea that these aluminum-silicate (AS) polymorphs crystallized at the same time. These data are consistent with the findings of Sharp (1995), who reported no fractionation associated with polymorphism of the aluminum silicates. Quartz-aluminum-silicate fractionations from veins in textural equilibrium and disequilibrium are 2.63-2.93 and 2.20-2.25‰, respectively. Temperature estimates from quartz-aluminum-silicate oxygen isotope fractionations range from 603-652 °C for equilibrium veins, and geologically unreasonable temperatures of 728-788 °C from veins in textural disequilibrium. Formation temperatures determined from isotope thermometry constrain the location of the veins on the andalusite = sillimanite univariant curve, thus defining a pressure range of 1.2-2.6 kbar for vein formation. The vein P-T estimates from this study agree well with previous host rock P-T estimates from nearby localities and, in conjunction with available Ar thermochronology, indicate that the veins likely formed during a Mesoproterozoic magmatic event in the Colorado Front Range.
Correction for Inhibition Leads to an Allosteric Co-Agonist Model for Pentobarbital Modulation and Activation of α1β3γ2L GABAA Receptors.

Background Pentobarbital, like propofol and etomidate, produces important general anesthetic effects through GABAA receptors. Photolabeling also indicates that pentobarbital binds to some of the same sites where propofol and etomidate act. Quantitative allosteric co-agonist models for propofol and etomidate account for modulatory and agonist effects in GABAA receptors and have proven valuable in establishing drug site characteristics and for functional analysis of mutants. We therefore sought to establish an allosteric co-agonist model for pentobarbital activation and modulation of α1β3γ2L receptors, using a novel approach to first correct pentobarbital activation data for inhibitory effects in the same concentration range. Methods Using oocyte-expressed α1β3γ2L GABAA receptors and two-microelectrode voltage-clamp, we quantified modulation of GABA responses by a low pentobarbital concentration and direct effects of high pentobarbital concentrations, the latter displaying mixed agonist and inhibitory effects. We then isolated and quantified pentobarbital inhibition in activated receptors using a novel single-sweep “notch” approach, and used these results to correct steady-state direct activation for inhibition. Results Combining results for GABA modulation and corrected direct activation, we estimated receptor open probability and optimized parameters for a Monod-Wyman-Changeux allosteric co-agonist model. Inhibition by pentobarbital was consistent with two sites with IC50s near 1 mM, while co-agonist model parameters suggest two allosteric pentobarbital agonist sites characterized by KPB ≈ 5 mM and high efficacy. The results also indicate that pentobarbital may be a more efficacious agonist than GABA. Conclusions Our novel approach to quantifying both inhibitory and co-agonist effects of pentobarbital provides a basis for future structure-function analyses of GABAA receptor mutations in putative pentobarbital binding sites.
The niobium oxoazides [NbO(N3)3], [NbO(N3)3·2CH3CN], [(bipy)NbO(N3)3], Cs2[NbO(N3)5] and [PPh4]2[NbO(N3)5]

Niobium oxotriazide, [NbO(N3)3], was prepared in a fluoride–azide exchange reaction between [NbOF3] and an excess of Me3SiN3 in SO2 solution. In acetonitrile solution, the fluoride–azide exchange resulted in the isolation of the adduct [NbO(N3)3·2CH3CN]. The subsequent reaction of [NbO(N3)3] with 2,2′-bipyridine (bipy) resulted in the isolation of the bipyridine adduct [(bipy)NbO(N3)3]. The pentaazido anion [NbO(N3)5]2− was obtained by the reaction of [NbO(N3)3] with two equivalents of ionic azide. The novel niobium oxoazides were fully characterized by their vibrational spectra, impact, friction and thermal sensitivity data and, in the case of [(bipy)NbO(N3)3], Cs2[NbO(N3)5], and [PPh4]2[NbO2(N3)5] by their X-ray crystal structures.
Obstructive renal cysts.

AbstractRenal cysts usually are asymptomatic, produce no harm to the kidney and require no treatment once diagnosed. However, an occasional expanding cyst causes progressive obstruction to caliceal or pelvic outflow. Herein is reported observations on 4 patients in whom cysts produced significant obstruction to the pelvic or major caliceal outflow. In 3 cases treatment was by decompression, with resolution of the obstruction.Two requirements must be met for a cyst to obstruct: 1) it must lie at or near the hilus and 2) it must have turgor sufficient to overcome the pressure of the intrapelvic urine. In contrast to most renal cysts those producing significant obstruction require operation.
Climate Change and Wine: A Review of the Economic Implications*

In this article, we provide an overview of the extensive literature on the impact of weather and climate on grapes and wine with the goal of describing how climate change is likely to affect their production. We start by discussing the physical impact of weather on vine phenology, berry composition, and yields and then survey the economic literature measuring the effects of temperature on wine quality, prices, costs, and profits and how climate change will affect these. We also describe what has been learned so far about possible adaptation strategies for grape growers that would allow them to mitigate the economic effects of climate change. We conclude that climate change is likely to produce winners and losers, with the winners being those closer to the North and South Poles. There are also likely to be some substantial short-run costs as growers adapt to climate change. Nevertheless, wine making has survived through thousands of years of recorded history, a history that includes large climate changes. (JEL Classifications: Q54, Q13)
The Medieval Spains: Christian reconquista and African Empire, 1009–1157

The century and a half which followed the collapse of the caliphate of Cordova was to see a fundamental reorganization of peninsular society. The respective positions of Christianity and Islam would achieve something like an equilibrium. After 711, all of the peninsula and its great river valleys were held by the Muslim and only the mountain country of Asturias was left to the Christian. By 1157, the latter had repossessed the basins of the Ebro, the Duero, and the Tajo as well as the Galician and north Portuguese coast. To al-Andalus was left the basins of the Guadiana and the Guadalquivir, the Levantine coast south of Tortosa and the Portuguese coast south of the Tajo. During the same period, however, Christian Iberia had gradually forged ever closer commercial, religious and cultural ties with western Europe while retaining a vigorous and autonomous political development of its own. Spanish Islam, on the other hand, after suffering political fragmentation was incorporated progressively into one or the other of the rising northern kingdoms or into that Moroccan Berber empire of the Murābit, which latter's culture was but a pale reflection of its own. This massive reorientation of human society in the peninsula has many causes but one of the basic of them was demography. At some point in the tenth century the population of the northern, mountainous rim of Iberia began to expand sufficiently to enable it to flow southward and, with the aid of the Mozarab current of emigres flowing northward from al-Andalus, to maintain itself in those new climes.
First-principles Study of Diffusion Coefficients of Alloy Elements in Dilute Mg Alloys

The equilibrium thermodynamic properties of Mg alloys are reasonably well understood, but the kinetics of these alloys is explored to a far lesser extent, especially diffusion coefficients of alloying elements in Mg. In the present work, first-principles calculations based on the Density Functional Theory (DFT) were used to calculate the dilute tracer diffusion coefficients in Mg for 61 elements, including rare earths, as a function of temperature using an 8-frequency model. An improved generalized gradient approximation of PBEsol was used in the present work, which is able to well describe both vacancy formation energies and vibrational properties. Systematic trends of diffusion activation energies of various solutes were analyzed. Remarkable agreements of the calculated results compared with available experimental data were obtained.
Self-powered Sensing for Vibration and Biomedical Monitoring

Self-powered sensors can be generally realized by using the actively generated electrical signals in response to a stimulation/triggering from the ambient environment. Owing to the low-frequency sensitivity of TENG, it is ideally suited for sensing vibration and biological signals related to human health. The magnitude, frequency, number of periods and fine details in the voltage and current signals are directly determined by input mechanical behaviors. The voltage signal is a measure of the vibration amplitude, and the current signal characterizes the dynamic processes of the vibration. This chapter systematically presents the applications of TENG for detection of sound waves, heat beating behavior and cardiac signals.
Study of the Kidney Tumor-Parenchymal Interface after Neoadjuvant Treatment with Axitinib for Locally Advanced Clear Cell Renal Cell Carcinoma: Matched Analysis from a Phase II Trial

Purpose: The aim of this study was to evaluate histological changes in the tumor-parenchymal interface in clear cell renal cell carcinoma after neoadjuvant axitinib treatment.Materials and Methods: We obtained clinical and pathology materials from 23 patients with clear cell renal cell carcinoma treated with neoadjuvant axitinib in a phase II clinical trial and from 23 matched patients with clear cell renal cell carcinoma who underwent upfront surgery. Histology of the tumor pseudocapsule and the peritumor kidney parenchymal change was evaluated and compared between the 2 cohorts.Results: A tumor pseudocapsule was noted in all 23 patients who received neoadjuvant axitinib and in all 23 control patients. Most pseudocapsules were noncontinuous and only partially covered the tumor, including in 17 of 23 axitinib cases (74%) and 19 of 23 controls (83%). In axitinib cases the median thickness of the intrarenal and extrarenal pseudocapsule was 1.4 and 2.4 mm, respectively, which was significantly thicker than i...
Preferred Healthy Food Nudges, Food Store Environments, and Customer Dietary Practices in 2 Low-Income Southern Communities.

Abstract Objective To examine how food store environments can promote healthful eating, including (1) preferences for a variety of behavioral economics strategies to promote healthful food purchases, and (2) the cross-sectional association between the primary food store where participants reported shopping, dietary behaviors, and body mass index. Methods Intercept survey participants (n = 342) from 2 midsized eastern North Carolina communities completed questionnaires regarding preferred behavioral economics strategies, the primary food store at which they shopped, and consumption of fruits, vegetables, and sugary beverages. Results Frequently selected behavioral economic strategies included: (1) a token and reward system for fruit and vegetable purchases; and (2) price discounts on healthful foods and beverages. There was a significant association between the primary food store and consumption of fruits and vegetables ( P = .005) and sugary beverages ( P = .02). Conclusions and Implications Future studies should examine associations between elements of the in-store food environment, purchases, and consumption.
Performance modeling of simultaneous TDRSS support of Space Station and Space Shuttle

Performance modeling of simultaneous tracking and data-relay satellite system (TDRSS) support of existing Space Shuttle and planned Space Station communications is discussed. Eight Ku- and S-band forward and return links are considered. The modeling of each of the communications link includes the modulation format, data rate, convolutional coding, pseudonoise coding, high power amplification, filtering, synchronization, and detection. The interference link models include the modulation format, data rate, pseudonoise coding, filtering, high power amplification, and signal-to-interference ratio. The communication links, with the models described, are simulated by computer and the performance results are presented in an accompanying paper (see ibid., p.11-19). >
The C. elegans NF2/Merlin Molecule NFM-1 Non-Autonomously Regulates Neuroblast Migration and Interacts Genetically with the Guidance Cue SLT-1/Slit

During nervous system development, neurons and their progenitors often migrate to their final destinations. In Caenorhabditis elegans, the bilateral Q neuroblasts and their descendants migrate long distances in opposite directions, despite being born in the same posterior region. QR on the right migrates anteriorly and generates the AQR neuron positioned near the head, and QL on the left migrates posteriorly, giving rise to the PQR neuron positioned near the tail. In a screen for genes required for AQR and PQR migration, we identified an allele of nfm-1, which encodes a molecule similar to vertebrate NF2/Merlin, an important tumor suppressor in humans. Mutations in NF2 lead to Neurofibromatosis Type II, characterized by benign tumors of glial tissues. These molecules contain Four-point-one Ezrin Radixin Moesin (FERM) domains characteristic of cytoskeletal-membrane linkers, and vertebrate NF2 is required for epidermal integrity. Vertebrate NF2 can also regulate several transcriptional pathways including the Hippo pathway. Here we demonstrate that in C. elegans, nfm-1 is required for complete migration of AQR and PQR, and that it likely acts outside of the Q cells themselves in a non-autonomous fashion. We also show a genetic interaction between nfm-1 and the C. elegans Slit homolog slt-1, which encodes a conserved secreted guidance cue. In vertebrates, NF2 can control Slit2 mRNA levels through the hippo pathway in axon pathfinding, suggesting a conserved interaction of NF2 and Slit2 in regulating migration.
IoT AND INNOVATION

This chapter covers the what, why, who, where, when and how of Innovation. Most innovation research was focused on improving product performance. There is however equal opportunities to create a competitive advantage in areas other than product and technology such as process, service, management, marketing, sales, and business model. By determining problem and domain definition, one can build a 2 × 2 Innovation Management Matrix encompassing four types of innovation: Basic, Breakthrough, Sustaining, and Disruptive. Innovation creates growth and economic wealth, increases productivity, and avoids stagnation and product obsolescence. Innovation also reduces waste and environmental damage. There are seven essential traits and habits of the highly innovative people: Curiosity, Resilience, Experimenting, Attentive, Thoughtful, Environmental, and Disciplined, the acronym spells out the word CREATED. This chapter reviews some of the top “Internet of Things (IoT) innovations”, including medical and healthcare systems, environmental monitoring, smart homes, and urban infrastructure management.
Global social acceptance of prosthetic devices

Social and societal pressures play an enormous role in the acceptance and use of prosthetic devices. Over the past 15 years, the United States has seen a radical shift in the mentality around prosthetic devices as amputees now choose function over form and encourage broader social acceptance of prostheses. This transition is not a global change, however, as seen in two different international studies: a preliminary study in Haiti that interviewed eight potential recipients about their interest in eNABLE-type partial hand devices; another which fit four patients in Jordan for such devices. In the Haiti study, in all but one case the devices were rejected on the basis of appearance (and resulting social and cultural implications), regardless of functional enhancements the devices might provide. To address these issues, and potentially increase social acceptance for amputees globally, new efforts and designs are being discussed.
Comparison of Qualifications-Based Selection and Best-Value Procurement for Construction Manager–General Contractor Highway Construction

Faster project delivery and the infusion of contractor knowledge into design are the primary drivers for choosing construction manager–general contractor (CM-GC) project delivery. This study focuses on the use of qualifications-based selection (QBS) and best-value (BV) procurement approaches, how and why agencies use each approach, and their associated opportunities and obstacles. Data for this study were obtained from a majority of federally funded CM-GC projects completed between 2004 and 2015. It was found that the use of BV procurement versus QBS procurement had no statistically significant difference in project characteristics or in performance of the projects in the data set. The choice of BV or QBS procurement coincided with an agency’s CM-GC stage of organizational development and influences of nonagency stakeholders on the CM-GC process. When agencies and the local industry were new to CM-GC, they were found to use BV procurement because it is closer to the traditional procurement culture and is ...
WSe2-contact metal interface chemistry and band alignment under high vacuum and ultra high vacuum deposition conditions

Contact metals (Au, Ir, and Cr) are deposited on bulk WSe2 under ultra-high vacuum (UHV, 1 × 10−9 mbar) and high vacuum (HV, 5 × 10−6 mbar) conditions and subsequently characterized with x-ray photoelectron spectroscopy (XPS) to elucidate the effects of reactor base pressure on resulting interface chemistry, contact chemistry, and band alignment. Au forms a van der Waals interface with WSe2 regardless of deposition chamber ambient. In contrast, Ir and Cr form a covalent interface by reducing WSe2 to form interfacial metal selenides. When Cr is deposited under HV conditions, significant oxygen incorporation is observed resulting in the thermodynamically favorable formation of tungsten oxyselenide and a substantial concentration of Cr x O y . Regardless of contact metal, WO x (2.63 < x < 2.92) forms during deposition under HV conditions which may positively affect interface transport properties. Cr and Ir form unexpectedly large electron and hole Schottky barriers, respectively, when deposited under UHV conditions due to interfacial reactions that contribute to anomalous band alignment. These results reveal the true interface chemistry formed between metals and WSe2 under UHV and HV conditions and demonstrate the impact on the Fermi level position following contact formation on WSe2.
Prediction Algorithms: Complexity, Concentration and Convexity

Abstract In this paper, we review two families of algorithms used lo estimate large-scale statistical models for prediction problems. kernel methods and boosting algorithms. We focus on the computational and statistical properties of prediction algorithms of this kind. Convexity plays an important role for these algorithms. since they exploit the computational advantages of convex optimization procedures. However, in addition to its computational advantages, the use of convexity in these methods also confers some Attractive statistical properties. We present some recent results that show the advantages of convexity for estimation rates, the rates at which the prediction accuracies approach their optimal values. In addition, we present results that quantify the cost of using a convex loss function in place of the real loss function of interest.
Synthesis of Oil-Laden Poly(ethylene glycol) Diacrylate Hydrogel Nanocapsules from Double Nanoemulsions.

Multiple emulsions have received great interest due to their ability to be used as templates for the production of multicompartment particles for a variety of applications. However, scaling these complex droplets to nanoscale dimensions has been a challenge due to limitations on their fabrication methods. Here, we report the development of oil-in-water-in-oil (O1/W/O2) double nanoemulsions via a two-step high-energy method and their use as templates for complex nanogels comprised of inner oil droplets encapsulated within a hydrogel matrix. Using a combination of characterization methods, we determine how the properties of the nanogels are controlled by the size, stability, internal morphology, and chemical composition of the nanoemulsion templates from which they are formed. This allows for identification of compositional and emulsification parameters that can be used to optimize the size and oil encapsulation efficiency of the nanogels. Our templating method produces oil-laden nanogels with high oil enca...
A bit of both science and economics: a non-traditional STEM identity narrative

Black males, as one non-dominant population, remain underrepresented and less successful in science, technology, engineering, and mathematics (STEM). Researchers focused on non-dominant populations are advised against generalizations and to examine cultural intersections (i.e. race, ethnicity, gender, and more) and also to explore cases of success, in addition to cases of under-achievement and underrepresentation. This study has focused on one African American male, Randy, who expressed high-achieving STEM career goals in computer science and engineering. Furthermore, recognizing that culture and identity development underlie STEM engagement and persistence, this long-term case study focused on how Randy developed a STEM identity during the course of the study and the implications of that process for his STEM career exploration. Etienne Wenger’s (1999) communities-of-practice (CoP) was employed as a theoretical framework and, in doing so, (1) the informal STEM program in which Randy participated was characterized as a STEM-for-social-justice CoP and (2) Randy participated in ways that consistently utilized an “economics” lens from beyond the boundaries of the CoP. In doing so, Randy functioned as a broker within the CoP and developed a non-traditional STEM identity-in-practice which integrated STEM, “economics”, and community engagement. Randy’s STEM identity-in-practice is discussed in terms of the contextual factors that support scientific identity development (Hazari et al. in J Res Sci Teach 47:978–1003, 2010), the importance of recognizing and supporting the development of holistic and non-traditional STEM identities, especially for diverse populations in STEM, and the implications of this new understanding of Randy’s STEM identity for his long-term STEM career exploration.
Sex differences in the hippocampal cytokine response following systemic lipopolysaccharide

The neuroimmune system is crucial for carrying out normal cognitive processes, and aberrant neuroimmune signaling is associated with psychiatric and neurodegenerative diseases. Significant sex differences are observed in immune activation following insult or injury as well as in the incidence of affect and memory disorders. Despite a strong link between the sex biases in inflammation and disease prevalence, sex-specific patterns of cytokines produced in the brain following an inflammatory event remain largely unknown. Thus, we characterized the profile of hippocampal cytokines in male and female mice following systemic lipopolysaccharide (LPS). We gave intraperitoneal injections of either 250 μg/kg LPS or PBS, and collected hippocampus samples at five acute time points to examine the resulting cytokine response. Overall, males had significantly greater levels of CSF1 and 2 and classic cytokines such as TNFα, IFNγ, and regulatory IL-10, whereas females had greater levels of CSF3 and the IL-2 cytokine family including IL-15 and regulatory IL-4. Notably, females showed a more rapid onset of increased cytokine levels and faster recovery to baseline as compared with males. Striking differences in the patterns and kinetics of cytokine production suggest males and females have different mechanisms of immune regulation. These data highlight complex sex-specific effects of the hippocampal immune response following LPS, which may prove to be important in long-lasting consequences of immune activation and contribute to sex differences in disease prevalence.
Fate of Lawn Care Pesticides During the Composting of Yard Trimmings

There is a growing emphasis on the composting of yard trimmings because of governmental bans on land-filling and incineration of leaves, grass and brush in many parts of the U.S. A primary concern with the composting of yard trimmings is the lack of knowledge about the fate of commonly used lawn care pesticides during composting. The purpose of this report is to summarize our recent findings on the fate of the most widely used lawn care pesticides 2,4–D (2,4–dichlorophenoxy acetic acid), Diazinon (O,O–diethyl O–[2-isopropyl–4–methyl–6–pyrimidinyl] phosphorothioate) and Pendimethalin (N–1–[ethylpropyl] 3,4–dimethyl 2,6–dini-trobenzamine) during the composting of yard trimmings.
Noradrenergic Activity in the Human Brain: A Mechanism Supporting the Defense Against Hypoglycemia.

Context Hypoglycemia, one of the major factors limiting optimal glycemic control in insulin-treated patients with diabetes, elicits a brain response to restore normoglycemia by activating counterregulation. Animal data indicate that local release of norepinephrine (NE) in the hypothalamus is important for triggering hypoglycemia-induced counterregulatory (CR) hormonal responses. Objective To examine the potential role of brain noradrenergic (NA) activation in humans during hypoglycemia. Design A hyperinsulinemic-hypoglycemic clamp was performed in conjunction with positron emission tomographic imaging. Participants Nine lean healthy volunteers were studied during the hyperinsulinemic-hypoglycemic clamp. Design Participants received intravenous injections of (S,S)-[11C]O-methylreboxetine ([11C]MRB), a highly selective NE transporter (NET) ligand, at baseline and during hypoglycemia. Results Hypoglycemia increased plasma epinephrine, glucagon, cortisol, and growth hormone and decreased [11C]MRB binding potential (BPND) by 24% ± 12% in the raphe nucleus (P < 0.01). In contrast, changes in [11C]MRB BPND in the hypothalamus positively correlated with increments in epinephrine and glucagon levels and negatively correlated with glucose infusion rate (all P < 0.05). Furthermore, in rat hypothalamus studies, hypoglycemia induced NET translocation from the cytosol to the plasma membrane. Conclusions Insulin-induced hypoglycemia initiated a complex brain NA response in humans. Raphe nuclei, a region involved in regulating autonomic output, motor activity, and hunger, had increased NA activity, whereas the hypothalamus showed a NET-binding pattern that was associated with the individual's CR response magnitude. These findings suggest that NA output most likely is important for modulating brain responses to hypoglycemia in humans.
From Tree to Tape: Direct Synthesis of Pressure Sensitive Adhesives from Depolymerized Raw Lignocellulosic Biomass.

We report a new and robust strategy toward the development of high-performance pressure sensitive adhesives (PSAs) from chemicals directly obtained from raw biomass deconstruction. A particularly unique and translatable aspect of this work was the use of a monomer obtained from real biomass, as opposed to a model compound or lignin-mimic, to generate well-defined and nanostructure-forming polymers. Herein, poplar wood depolymerization followed by minimal purification steps (filtration and extraction) produced two aromatic compounds, 4-propylsyringol and 4-propylguaiacol, with high purity and yield. Efficient functionalization of those aromatic compounds with either acrylate or methacrylate groups generated monomers that could be easily polymerized by a scalable reversible addition–fragmentation chain-transfer (RAFT) process to yield polymeric materials with high glass transition temperatures and robust thermal stabilities, especially relative to other potentially biobased alternatives. These lignin-derive...