cssi/SciSciGPT-SciSciNet huggingface dataset:
Investigation of Arrhythmogenic Calcium Events by Initiating Local Calcium Release in Cardiomyocytes

In cardiac muscle the sarcoplasmic reticulum (SR) contains the Ca2+ that is released during excitation-contraction coupling to initiate cross-bridge cycling, sarcomere shortening and force generation. Under physiological conditions SR Ca2+ uptake by the SR/ER Ca2+ ATPase is balanced by Ca2+ “leak” out of the SR through the SR Ca2+ release channels (ryanodine receptors, RyR2). Under diverse conditions SR Ca2+ overload can develop (i.e. elevation of [Ca2+]SR) and this is associated with an increase in the open probability of the RyR2s which leads to SR Ca2+ instability. SR Ca2+ overload is thus associated with an increased Ca2+ spark rate, increased “invisible” SR Ca2+ leak and the development of a propagating chain-reaction of Ca2+-induced Ca2+ release (Ca2+ wave) within the ventricular myocyte. This abnormal Ca2+ signaling activates the sarcolemmal Na+/Ca2+ exchanger to produce an arrhythmic inward current. In order to investigate SR Ca2+ release under these conditions, local Ca2+ release was produced by photolysis of a caged paraxanthine (BiNiX, 3-(4,5-bis(carboxymethyl)-2-nitrobenzyl)-paraxanthine), a caffeine-like “activator” of RyR2. Using a newly developed photolysis system, laser flashes (354 nm) of different sizes and shapes were rapidly (millisecond) positioned on the focused image plane of a confocal microscope. A spectrum of responses in murine cardiac myocytes was observed ranging from instigating Ca2+ sparks to triggering Ca2+ waves. Eliciting a fully propagating Ca2+ wave required SR Ca2+ overload and/or an increased sensitivity of RyR2s to cytosolic Ca2+. This study was uniquely successful in triggering multiple Ca2+ waves simultaneously. Creating multiple Ca2+ wave fronts in a myocyte enabled the generation of an extrasystole triggered by a delayed after-depolarization. This new experimental technology allows systematic investigation of rare extrasystoles triggered by Ca2+ waves.
Hierarchical faunal filters: an approach to assessing effects of habitat and nonnative species on native fishes

Understanding factors related to the occurrence of species across multiple spatial and temporal scales is critical to the conservation and management of native fishes, especially for those species at the edge of their natural distribution. We used the concept of hierarchical faunal filters to provide a framework for investigating the influence of habitat characteristics and nonnative piscivores on the occurrence of 10 native fishes in streams of the North Platte River watershed in Wyoming. Three faunal filters were developed for each species: (i) large-scale biogeographic, (ii) local abiotic, and (iii) biotic. The large-scale biogeographic filter, composed of elevation and stream-size thresholds, was used to determine the boundaries within which each species might be expected to occur. Then, a local abiotic filter (i.e., habitat associations), developed using binary logistic-regression analysis, estimated the probability of occurrence of each species from features such as maximum depth, substrate composition, submergent aquatic vegetation, woody debris, and channel morphology (e.g., amount of pool habitat). Lastly, a biotic faunal filter was developed using binary logistic regression to estimate the probability of occurrence of each species relative to the abundance of nonnative piscivores in a reach. Conceptualising fish assemblages within a framework of hierarchical faunal filters is simple and logical, helps direct conservation and management activities, and provides important information on the ecology of fishes in the western Great Plains of North America.
Empirical Bayes Methods for Combining Likelihoods

Abstract Suppose that several independent experiments are observed, each one yielding a likelihood L k (θ k ) for a real-valued parameter of interest θ k . For example, θ k might be the log-odds ratio for a 2 × 2 table relating to the kth population in a series of medical experiments. This article concerns the following empirical Bayes question: How can we combine all of the likelihoods L k to get an interval estimate for any one of the θ k 's, say θ1? The results are presented in the form of a realistic computational scheme that allows model building and model checking in the spirit of a regression analysis. No special mathematical forms are required for the priors or the likelihoods. This scheme is designed to take advantage of recent methods that produce approximate numerical likelihoods L k (θ k ) even in very complicated situations, with all nuisance parameters eliminated. The empirical Bayes likelihood theory is extended to situations where the θ k 's have a regression structure as well as an empiri...
Generalized Mersenne Prime Number and Its Application to Random Number Generation

A Mersenne prime number is a prime number of the form 2k — 1. In this paper, we consider a Generalized Mersenne Prime (GMP) which is of the form R(k,p) = (p k -l)/(p - 1), where k,p and R(k,p) are prime numbers. For such a GMP, we then propose a much more efficient search algorithm for a special form of Multiple Recursive Generator (MRG) with the property of an extremely large period length and a high dimension of equidistribution. In particular, we find that (p k - l)/(p - 1) is a GMP, for k = 1511 and p = 2147427929. We then find a special form of MRG with order k = 1511 and modulus p = 2147427929 with the period length 1014100.5.Many other efficient and portable generators with various k ≤ 1511 are found and listed. Finally, for such a GMP and generator, we propose a simple and quick method of generating maximum period MRGs with the same order k. The readers are advised not to confuse GMP defined in this paper with other generalizations of the Mersenne Prime. For example, the term “Generalized Mersenne Number” (GMN) is used in Appendix 6.1 of FIPS-186-2, a publication by National Institute of Standards and Technology (NIST). In that document, GMN is a prime number that can be written as 2k ± 1 plus or minus a few terms of the form 2r.
Ablation of Neurons Expressing Melanin-Concentrating Hormone (MCH) in Adult Mice Improves Glucose Tolerance Independent of MCH Signaling

Melanin-concentrating hormone (MCH)-expressing neurons have been ascribed many roles based on studies of MCH-deficient mice. However, MCH neurons express other neurotransmitters, including GABA, nesfatin, and cocaine–amphetamine-regulated transcript. The importance of these other signaling molecules made by MCH neurons remains incompletely characterized. To determine the roles of MCH neurons in vivo , we targeted expression of the human diphtheria toxin receptor (DTR) to the gene for MCH ( Pmch ). Within 2 weeks of diphtheria toxin injection, heterozygous Pmch DTR /+ mice lost 98% of their MCH neurons. These mice became lean but ate normally and were hyperactive, especially during a fast. They also responded abnormally to psychostimulants. For these phenotypes, ablation of MCH neurons recapitulated knock-out of MCH, so MCH appears to be the critical neuromodulator released by these neurons. In contrast, MCH-neuron-ablated mice showed improved glucose tolerance when compared with MCH-deficient mutant mice and wild-type mice. We conclude that MCH neurons regulate glucose tolerance through signaling molecules other than MCH.
Query-Aware Test Generation Using a Relational Constraint Solver

We present a novel approach for black-box testing of database management systems (DBMS) using the Alloy tool-set. Given a database schema and an SQL query as inputs, our approach first formulates Alloy models for both inputs, and then using the Alloy Analyzer, it generates (1) input data to populate test databases, and (2) the expected result of executing the given query on the generated data. The Alloy Analyzer results form a complete test suite (input/oracle) for verifying the execution result of a DBMS query processor. By incorporating both the schema and the query during the analysis, our approach performs query-aware data generation where executing the query on the generated data produces meaningful non-empty results. We developed a prototype tool, ADUSA, and used it to evaluate our approach. Experimental results show the ability of our approach to detect bugs in both open-source as well as commercial database management systems.
Acute Hydrocephalus associated with Brainstem Micro-Arteriovenous Malformation (P6.219)

OBJECTIVE: To describe a case of brainstem micro-arteriovenous malformation presenting with headaches and acute hydrocephalus. BACKGROUND: Obstruction of the cerebrospinal fluid (CSF) outflow is one of the most common causes of hydrocephalus. Acute hydrocephalus will typically present with signs of elevated intracranial pressure (ICP) and may be fatal if left untreated. Acquired causes include meningitis, tumors, trauma and intracranial hemorrhage. DESIGN/METHODS: We report the case of a 35 year old woman with history of migraine headaches and gastritis who presented to the hospital with severe bifrontal headaches and emesis. The headaches were more painful than usual and were associated with photophobia. She reported having mild headaches a few days prior. Neurologic examination was initially non-focal. However, over several hours she became more lethargic and reported diplopia. She then had rapid worsening of her mentation and became unresponsive with a GCS of 3 and dilated non-reactive pupils. RESULTS: Head CT revealed dilatation of third and lateral ventricles with a normal appearing fourth ventricle consistent with obstructive hydrocephalus. An emergent extra-ventricular drain was placed for prevention of impending herniation. MRI revealed a small amount of magnetic susceptibility artifact in the cerebral aqueduct consistent with hemorrhage. CTA was negative for a vascular abnormality, however, conventional angiography revealed a small tuft of vessels within the tectum and trace arteriovenous shunting suggestive of an underlying AVM. Her clinical condition gradually improved with CSF diversion and she underwent an endoscopic third ventriculostomy with good results. She will undergo a repeat MRI and subsequent cerebral angiography for interval follow up. CONCLUSIONS: Brainstem micro-AVM is a rare entity. Dynamic vascular changes or hemorrhage may be associated with acute hydrocephalus. While initial imaging may be unrevealing, this diagnosis should be considered in the workup of unexplained, acute obstructive hydrocephalus. Disclosure: Dr. Modak has nothing to disclose. Dr. Brown has nothing to disclose. Dr. Schwartz has nothing to disclose. Dr. Ollenschleger has nothing to disclose.
Fluorescent Nanoparticle Imaging Allows Noninvasive Evaluation of Immune Cell Modulation in Esophageal Dysplasia

Esophageal tumors provide unique challenges and opportunities for developing and testing surveillance imaging technology for different tumor microenvironment components, including assessment of immune cell modulation, with the ultimate goal of promoting early detection and response evaluation. In this context, accessibility through the lumen using a minimally invasive approach provides a means for repetitive evaluation longitudinally by combining fluorescent endoscopic imaging technology with novel fluorescent nanoparticles that are phagocytized by immune cells in the microenvironment. The agent we developed for imaging is synthesized from Feraheme (ferumoxytol), a Food and Drug Administration-approved monocrystaline dextran-coated iron oxide nanoparticle, which we conjugated to a near-infrared fluorochrome, CyAL5.5. We demonstrate a high level of uptake of the fluorescent nanoparticles by myeloid-derived suppressor cells (MDSCs) in the esophagus and spleen of L2Cre;p120ctnflox/flox mice. These mice develop esophageal dysplasia leading to squamous cell carcinoma; we have previously demonstrated that dysplastic and neoplastic esophageal lesions in these mice have an immune cell infiltration that is dominated by MDSCs. In the L2Cre;p120ctnflox/flox mice, evaluation of the spleen reveals that nearly 80% of CD45+ leukocytes that phagocytized the nanoparticle were CD11b+Gr1+ MDSCs. After dexamethasone treatment, we observed concordant decreased fluorescent signal from esophageal lesions during fluorescent endoscopy and decreased CyAL5.5-fluorescent-positive immune cell infiltration in esophageal dysplastic lesions by fluorescence-activated cell sorting analysis. Our observations suggest that this translatable technology may be used for the early detection of dysplastic changes and the serial assessment of immunomodulatory therapy and to visualize changes in MDSCs in the esophageal tumor microenvironment.
Talking Back: Sending Soil Vibration Signals to Lekking Prairie Mole Cricket Males

SYNOPSIS. The male prairie mole cricket, Gryllotalpa major, native of the tallgrass prairie of the south central U.S., constructs a specialized acoustical burrow in the spring in the prairie soil from which he generates an airborne calling song that attracts flying females for mating. Males do not phonorespond to manipulations involving playbacks of airborne sounds. At the same time, vibrations with the same temporal scale and pattern as the airborne signal are produced in the substrate through an unknown mechanism. These ground vibrations can be distinguished from background vibrations in the soil at distances up to 3 m depending on soil conditions and conditions that control the background vibration environment (e.g., wind, highway traffic). We hypothesize that males use the vibration component of the call as information for spacing as they form display arenas, or leks. We used modified field recordings of soil vibrations from singing males with an electromechanical vibration exciter to simulate the vibration component of a calling song in playback experiments. Airborne sounds of males were monitored for two minutes before and two minutes after the introduction of the ground vibration stimulus with a tape recorder microphone placed 20 cm from the burrow opening. Males did respond to the manipulation experiment; although, we observed individual variation in the level of response.
Mechanistic species distribution modelling as a link between physiology and conservation

Climate change conservation planning relies heavily on correlative species distribution models that estimate future areas of occupancy based on environmental conditions encountered in present-day ranges. The approach benefits from rapid assessment of vulnerability over a large number of organisms, but can have poor predictive power when transposed to novel environments and reveals little in the way of causal mechanisms that define changes in species distribution or abundance. Having conservation planning rely largely on this single approach also increases the risk of policy failure. Mechanistic models that are parameterized with physiological information are expected to be more robust when extrapolating distributions to future environmental conditions and can identify physiological processes that set range boundaries. Implementation of mechanistic species distribution models requires knowledge of how environmental change influences physiological performance, and because this information is currently restricted to a comparatively small number of well-studied organisms, use of mechanistic modelling in the context of climate change conservation is limited. In this review, we propose that the need to develop mechanistic models that incorporate physiological data presents an opportunity for physiologists to contribute more directly to climate change conservation and advance the field of conservation physiology. We begin by describing the prevalence of species distribution modelling in climate change conservation, highlighting the benefits and drawbacks of both mechanistic and correlative approaches. Next, we emphasize the need to expand mechanistic models and discuss potential metrics of physiological performance suitable for integration into mechanistic models. We conclude by summarizing other factors, such as the need to consider demography, limiting broader application of mechanistic models in climate change conservation. Ideally, modellers, physiologists and conservation practitioners would work collaboratively to build models, interpret results and consider conservation management options, and articulating this need here may help to stimulate collaboration.
Transitions in Riding With an Alcohol/Drug-Impaired Driver From Adolescence to Emerging Adulthood in the United States.

Objective:The purpose of this study was to examine changes and predictors of changes in riding with an alcohol/drug-impaired driver (RWI) from 10th grade through the first post–high school year.Method:Transition models were used to estimate the association of four waves (W1–W4) of RWI with W4 environmental-status variables and time-varying covariates in the NEXT Generation Health Study, a nationally representative cohort of U.S. 10th graders (N = 2,785).Results:Overall, 33% (weighted) of adolescents reported RWI in the past 12 months in W1, and slightly declined in W2 (24%), W3 (27%), and W4 (26%). Across time, transition models with generalized estimating equations showed that RWI was more likely among those who previously reported RWI (ORs from 3.62 to 3.66, p < .001), substance use (ORs from 1.81 to 1.82, p < .001), and heavy episodic drinking (ORs from 1.85 to 1.86, p < .001). Those living on college campuses were somewhat more likely to engage in RWI (OR = 1.38, .05 < p <.10) than those living at hom...
Strategies to Deliver Safe, Technology-Enhanced Care in Pediatric Settings

S ta f f educa tors need to continually assess nurses’ informatics competencies, an imperative part of patient care delivery. THE HEALTH CARE environment is becoming increasingly complex. In free standing children's hospitals, advances in technology occur frequently not only to improve care but to enhance patient safety. Specific types of health information technology (IT) can improve patient safety under the right conditions. Pediatric nurses come to work with the best of intentions to care for a vulnerable patient population and nurses are acutely aware of their responsibility to provide safe care to children. Even with the best of intentions, what happens when the nurse is lacking in informatics competencies, or when the electronic health record (EHR) is not design to meet the needs of the nurse's work flow? In some cases, nurses may choose to work around the health IT systems that were built with the intent of protecting patients (Scalise, 2015). It is troublesome to think that some nurses might knowingly take a risk and choose to workaround the EHR (Scalise, 2015). To understand why nurses might take this risk, it is important to understand why nurses create workarounds. “Workarounds are claimed to increase when the complexity of the task is incompatible with the degree of structure imposed by the system and when users feel ‘controlled’ by the system, with end user resistance contributing to their implementation” (Debono et al., 2012, p.2). When end users (nurses) avoid using technology, it created challenges to units' “culture, processes, data collection/analysis, budget, and ultimately patient safety” (Scalise, 2015, para.11). Numerous health care agencies wrote reports calling for technology to be utilized in creating a safer, more efficient
Field Biology and Host Range of a Mesquite Looper, Semiothisa cyda (Lepidoptera: Geometridae), in Central Texas

Larvae of the geometrid moth, Semiothisa cyda (Druce), fed only on the foliage of mesquite trees. Larvae developed completely and pupated only on four species of mesquite in our tests (all in section Algarobia, series Chilensis, of the genus Prosopis ); listed in order of suitability, they were: honey mesquite, Prosopis glandulosa Torrey var. glandulosa , western honey mesquite, P. glandulosa var. torreyana (L. Benson) M. C. Johnston, velvet mesquite, P. velutina Wooten, and the Argentine white mesquite, P. alba Grisebach. Two species of screwbean mesquites ( Prosopis , section Strombacarpa) from Texas were not hosts, nor were 17 other species of legumes tested. Mortality of overwintering pupae in field cages was 72 to 80%. In the field, females emerged about 1 April and were followed by four generations of larvae, but populations were always low (maximum of ca. 20 per tree) and caused no apparent damage to the trees. Parasitism of larvae was 9 to 15%; major parasites were the tachinid Hesperomyia erythocera Brauer and Bergenstamm and the braconids Rogas spp.
Three-cylinder engines from Volkswagen

The trend towards vehicle powertrains that are ever more frugal is increasingly leading to the use of three-cylinder engines. This is because the concept makes it possible to save fuel with a turbocharged three-cylinder engine compared to a four-cylinder engine of the same power. Volkswagen is a pioneer in this powertrain concept and, at the request of MTZ, presents this overview of current developments.
Chemically bonded ceramic matrix composites: Densification and conversion to diffusion bonding

Chemically bonded ceramics appear to be a promising alternative route for near-net shape fabrication of multi-phase ceramic matrix composites (CMC’s). The hydraulic (and refractory) properties of fine mono-calcium aluminate (CaAl2O4) powders were used as the chemically bonding matrix phase, while calcia stabilized zirconia powders were the second phase material. Samples containing up to 70 wt% (55 vol%) zirconia have been successfully compacted and sintered. Various processing techniques were evaluated. Processing was optimized based on material properties, dilatometry and simultaneous thermal analysis (DTA’TGA ). The physical characteristics of this novel CMC were characterized by hardness, density, and fracture toughness testing. Microstructures were evaluated by SEM and phase identification was verified using XRD.
New insights into the transport and field-enhancement effects in sol-gel derived colossal magnetoresistive thin films

The transport mechanism underlying the colossal magnetoresistance (CMR) of doped manganites is not yet understood and their technological applications are limited by the high fields (~IT) required to obtain any significant MR. Following the development of a polymeric chemical synthesis route, we have investigated the O2p unoccupied density of states in sol-gel derived La1-xSrxMnO3 (0 ≤ x ≤ 0.7) thin films grown epitaxially on LaAlO3, by electron energy-loss spectroscopy at sub-eV resolution. The spectra show a distinct prepeak in the OK edge at the Fermi level, the intensity of which correlates directly with the conductivity of the film. Similar correlation was also obtained for La0.7Sr0.3MnO3-z annealed in vacuum to obtain well defined oxygen content (z) in the film. This confirms that the charge carriers in these manganese perovskites have significant oxygen 2p hole character and suggests that the “double exchange” mechanism has to be modified. In another set of experiments we have studied room-temperature field amplification effects to enhance the low-field sensitivity of La0.7Sr0.3MnO3-z films sandwiched between two thin rectangular slices of either α-Fe or Mn-Zn ferrite. This field amplification leads to an enhanced low-field MR value as high as 6% at an external field of 500 Oe which is 6 times the value observed without the amplification.
The Existing Problems and Countermeasures of Agricultural Sci-technical Innovation and Extension System

With the rise of the worldwide agricultural science and technology revolution,agricultural sci-technical innovation and extension system in China faced a big challenge.This paper analyzed the existing problems and the causes in the progress of the development of agricultural sci-technical innovation and extension system,and put forward the countermeasures by taking the technological innovation and extension of Fujian Academy of Agricultural Sciences as example.
Performance deviation calculation and reliability eval- uation of solid rocket motors

The calculation equations of the standard deviations for thrust,specific impulse,total impulse,flow rate and pressure of solid rocket motors are derived. According to the application requirements of solid rocket motors and based on the analysis of some important factors which affect these deviations, the equations are further simplified. The methods for predicting thrust performance deviation and evaluating reliability for solid rocket motors are given by using the error analysis theory and single factor test results.
A Novel Variant of Autosomal Recessive Lower Motor Neuron Disease

A genome-wide linkage analysis to map the underlying genetic defect was performed in a consanguineous African family with five patients affected with a novel variant of autosomal recessive lower motor neuron disease (LMND), in a study at Hopital Necker Enfants Malades and other centers, Paris, France.
Safe Motion Planning for Imprecise Robotic Manipulators by Minimizing Probability of Collision

Robotic manipulators designed for home assistance and new surgical procedures often have significant uncertainty in their actuation due to compliance requirements, cost constraints, and size limits. We introduce a new integrated motion planning and control algorithm for robotic manipulators that makes safety a priority by explicitly considering the probability of unwanted collisions. We first present a fast method for estimating the probability of collision of a motion plan for a robotic manipulator under the assumptions of Gaussian motion and sensing uncertainty. Our approach quickly computes distances to obstacles in the workspace and appropriately transforms this information into the configuration space using a Newton method to estimate the most relevant collision points in configuration space. We then present a sampling-based motion planner based on executing multiple independent rapidly exploring random trees that returns a plan that, under reasonable assumptions, asymptotically converges to a plan that minimizes the estimated collision probability. We demonstrate the speed and safety of our plans in simulation for (1) a 3-D manipulator with 6 DOF, and (2) a concentric tube robot, a tentacle-like robot designed for surgical applications.
Small-area Variation in Hypertension Prevalence among Black and White Medicaid Enrollees.

Objectives: To examine within-state geographic heterogeneity in hypertension prevalence and evaluate associations between hypertension prevalence and small area contextual characteristics for Black and White South Carolina Medicaid enrollees in urban vs rural areas. Design: Ecological Setting: South Carolina, United States. Main Outcome Measure: Hypertension prevalence Methods: Data representing adult South Carolina Medicaid recipients enrolled in fiscal year 2013 (N=409,907) and ZIP Code Tabulation Area (ZCTA)-level contextual measures (racial segregation, rurality, poverty, educational attainment, unemployment and primary care physician adequacy) were linked in a spatially referenced database. Optimized Getis-Ord hotspot mapping was used to visualize geographic clustering of hypertension prevalence. Spatial regression was performed to examine the association between hypertension prevalence and small-area contextual indicators. Results: Significant (alpha=.05) hotspot spatial clustering patterns were similar for Blacks and Whites. Black isolation was significantly associated with hypertension among Blacks and Whites in both urban (Black, b=1.34, P<.01; White, b=.66, P<.01) and rural settings (Black, b=.71, P=.02; White, b=.70, P<.01). Primary care physician adequacy was associated with hypertension among urban Blacks (b=-2.14, P<.01) and Whites (b=-1.74, P<.01). Conclusions: The significant geographic overlap of hypertension prevalence hotspots for Black and White Medicaid enrollees provides an opportunity for targeted health intervention. Provider adequacy findings suggest the value of ACA network adequacy standards for Medicaid managed care plans in ensuring health care accessibility for persons with hypertension and related chronic conditions. Ethn Dis. 2016;26(3):331-338; doi:10.18865/ed.26.3.331
Glutamine therapy of cystinuria.

Cystinuria is an inherited disorder characterized by abnormalities in the transport of cystine, lysine, ornithine, arginine, and possibly cysteine in both the intestinal tract and renal tubule. Clinically this is important only because of the insolubility of cystine in the urine with resultant cystine calculus formation.
Linkages Between Patient-centered Medical Homes and Addiction Treatment Organizations: Results From a National Survey.

Background:To meet their aims of providing comprehensive and coordinated care, patient-centered medical homes (PCMHs) need to coordinate services for individuals with substance use disorders. Yet, the 14,000 addiction treatment (AT) organizations across the United States that provide services for mo
DNMT1 Regulates Epithelial-Mesenchymal Transition and Cancer Stem Cells, Which Promotes Prostate Cancer Metastasis

Abstract Cancer metastasis is a multistep process associated with the induction of an epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). Although significant progress has been made in understanding the molecular mechanisms regulating EMT and the CSC phenotype, little is known of how these processes are regulated by epigenetics. Here we demonstrate that reduced expression of DNA methyltransferase 1 (DNMT1) plays an important role in the induction of EMT and the CSC phenotype by prostate cancer (PCa) cells, with enhanced tumorigenesis and metastasis. First, we observed that reduction of DNMT1 by 5-azacitidine (5-Aza) promotes EMT induction as well as CSCs and sphere formation in vitro . Reduced expression of DNMT1 significantly increased PCa migratory potential. We showed that the increase of EMT and CSC activities by reduction of DNMT1 is associated with the increase of protein kinase C. Furthermore, we confirmed that silencing DNMT1 is correlated with enhancement of the induction of EMT and the CSC phenotype in PCa cells. Additionally, chromatin immunoprecipitation assay reveals that reduction of DNMT1 promotes the suppression of H3K9me3 and H3K27me3 on the Zeb2 and KLF4 promoter region in PCa cells. Critically, we found in an animal model that significant tumor growth and more disseminated tumor cells in most osseous tissues were observed following injection of 5-Aza pretreated–PCa cells compared with vehicle-pretreated PCa cells. Our results suggest that epigenetic alteration of histone demethylation regulated by reduction of DNMT1 may control induction of EMT and the CSC phenotype, which facilitates tumorigenesis in PCa cells and has important therapeutic implications in targeting epigenetic regulation.
Enzymatic decomposition and electrochemical study of alkali lignin by laccase (Trametes versicolor) in the presence of a natural mediator (methyl syringate)

The aerobic-enzymatic decomposition of alkali lignin in the presence of laccase from Trametes versicolor (LTV) and the natural mediator methyl syringate in acetic acid–sodium acetate buffer solution (pH = 4.5) at 40 °C in an oxygen-rich (aerobic) environment is studied. SEM and BET analyses are used to characterize the changes in the surface area and morphology of lignin that occurred during the exposure to the laccase–mediator system (LMS) for 72 h. The LMS interaction causes a 2-fold improvement in the surface area from 4.9 to 9.8 m2 g−1, due to significant changes in the mesoporous structure of lignin within a pore size of 2–120 nm. This could be due to an efficient interaction of the surface phenolic groups and internal mesoporous β-O-4 network of lignin with the LMS in an aerobic environment. To further understand the enzymatic degradation of lignin, electrochemical oxidation of a thin film of lignin on the surface of a glassy carbon electrode (GCE) is performed under aerobic vs. anaerobic conditions in the presence of the LMS. A synergistic lignin electrooxidation in the aerobic environment is observed due to the promotion of LMS activity by a parallel oxygen reduction reaction (ORR). Based on the electrochemical studies, a mechanism for understanding the role of oxygen in the enzymatic oxidation of lignin in an aerobic environment and the stability of the mediator radical (MS˙) is proposed.
Abstract 3202: Single cell analysis of ascites macrophages in ovarian cancer

Macrophages compose a major part of the tumor microenvironment (TME) in several types of cancer, including ovarian cancer [1]. Studies have shown that a high percentage of tumor associated macrophages (TAMs) correlates with a poor prognosis in ovarian cancer [2], due to the crucial role of TAMs in promoting tumor growth and angiogenesis [3,4]. Yet not much investigation has been executed to reveal the function of macrophages in ovarian cancer ascites, a hallmark of ovarian cancer. Previous gene expression analysis in TAMs often used bulk samples [5,6]. However, due to the complexity of the peritoneal environment, this approach had the effect of “dampening” rare and potentially informative signals from a heterogeneous population such as ascites macrophages. Therefore, we resorted to single-cell expression analysis to dissect the heterogeneity of ascites macrophages. Recent breakthroughs in single cell RNA-seq techniques have made it more cost effective to process a large number of samples at single cell resolutions. Here we used Fluidigm9s Single-Cell Auto Prep System, a state-of-art technology for automate single cell cDNA synthesis [7]. We sequenced single ascites macrophages from ID8 murine ovarian cancer model and single alternatively activated bone marrow derived macrophages (BMDM-M2). When comparing the single cell expression profiles of ascites macrophages to BMDM using principle component analysis (PCA), we observed that the ascites macrophages scattered broadly and could be further divided into two groups, whereas BMDM were tightly clustered into one group. Furthermore, gene oncology (GO) analysis of highly expressed genes in each group revealed that ascites macrophages had a distinct gene expression profile from BMDM, highlighting the metabolic pathways, especially catabolic process. We are currently working on validating these findings in human patients with ovarian carcinoma. In summary, this work sheds light on the understanding of the role of ascites macrophages in ovarian cancer. 1. Qian BZ, Pollard JW. Cell. 2010;141:39-51. 2. He YF, Zhang MY, Wu X, et al. PLoS One. 2013;8:e79769. 3. Mantovani A, Germano G, Marchesi F, et al. Eur J Immunol 2011;41:2522-25. 4. Murray PJ, Wynn TA. Nat Rev Immunol, 2011;11:723-37. 5. The Cancer Genome Atlas Research Network. Nature. 2014;511:543-50. 6. The Cancer Genome Atlas Research Network. Nature. 2014;513:202-9. 7. Wu AR, Neff NF, Kalisky T, et al. Nat Methods. 2014;11:41-6. Citation Format: Huanhuan Mahsa He, Feiqiao Brian Yu, Stephen R. Quake, Oliver Dorigo. Single cell analysis of ascites macrophages in ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3202. doi:10.1158/1538-7445.AM2015-3202
Principles of Nonunions

The management of nonunions can be very difficult. They have a significant impact on one’s function and can be debilitating. It requires a thorough understanding of the factors that can result in a nonunion. This includes patient factors as well as surgical factors. Nonunions can occur because of biological factors, mechanical factors, or both. Smoking , diabetes, and vitamin D deficiency all have been linked to potential risk factors for nonunions. It is important also to understand how nonunions are classified which can guide treatment principles. Evaluation requires a history of the original injury including the treatment rendered, medical history of the patient to include a social history with regard to habits and a careful physical examination. Appropriate radiographs, laboratory studies, and advanced imaging may be warranted. Infection must always be suspected and ruled out. An analysis of the original treatment is required. If operative intervention was performed, the implants used should be critically evaluated as to the technique and appropriateness of the fixation construct. If there was inadequate stability, a hypertrophic nonunion can develop. If the soft tissue envelope is not respected or there was significant soft tissue injury as in open fractures, an inadequate biological environment may occur leading to a nonunion. The etiology must be addressed whether it is improving the mechanical stability, providing a biological stimulus with bone grafts or other biologic adjuncts or both.
Repurposing Theoretical Linguistic Data for Tool Development and Search

For the majority of the world’s languages, the number of linguistic resources (e.g., annotated corpora and parallel data) is very limited. Consequently, supervised methods, as well as many unsupervised methods, cannot be applied directly, leaving these languages largely untouched and unnoticed. In this paper, we describe the construction of a resource that taps the large body of linguistically analyzed language data that has made its way to the Web, and propose using this resource to bootstrap NLP tool development.
Comparative biochemical analysis of UHRF proteins reveals molecular mechanisms that uncouple UHRF2 from DNA methylation maintenance

UHRF1 is a histone- and DNA-binding E3 ubiquitin ligase that functions with DNMT1 to maintain mammalian DNA methylation. UHRF1 facilitates DNMT1 recruitment to replicating chromatin through a coordinated mechanism involving histone and DNA recognition and histone ubiquitination. UHRF2 shares structural homology with UHRF1, but surprisingly lacks functional redundancy to facilitate DNA methylation maintenance. Molecular mechanisms uncoupling UHRF2 from DNA methylation maintenance are poorly defined. Through comprehensive and comparative biochemical analysis of recombinant human UHRF1 and UHRF2 reader and writer activities, we reveal conserved modes of histone PTM recognition but divergent DNA binding properties. While UHRF1 and UHRF2 diverge in their affinities toward hemi-methylated DNA, we surprisingly show that both hemi-methylated and hemi-hydroxymethylated DNA oligonucleotides stimulate UHRF2 ubiquitin ligase activity toward histone H3 peptide substrates. This is the first example of an E3 ligase allosterically regulated by DNA hydroxymethylation. However, UHRF2 is not a productive histone E3 ligase toward purified mononucleosomes, suggesting UHRF2 has an intra-domain architecture distinct from UHRF1 that is conformationally constrained when bound to chromatin. Collectively, our studies reveal that uncoupling of UHRF2 from the DNA methylation maintenance program is linked to differences in the molecular readout of chromatin signatures that connect UHRF1 to ubiquitination of histone H3.
Effect of the length of the poloidal ducts on flow balancing in a liquid metal blanket

Abstract To address concerns associated with liquid metal (LM) flow balancing among multiple poloidal channels of a LM blanket, we investigate the factors (first of all the length of the channels) that influence the flow distribution when the duct walls are electrically insulated. We simulate LM MHD flow through multiple channels fed by a prototypical manifold for a range of channel lengths using a 3D MHD solver, HIMAG. The simplified manifold geometry consists of a rectangular, electrically insulated feeding duct which suddenly expands such that the duct thickness in the magnetic field direction abruptly increases by a factor of 4. After a short length downstream of the expansion, the flow is divided into three identical parallel channels. By measuring the flow rate in each of the channels, we conclude that flow balance among the channels is improved by increasing the length of the channels. An effort is made to obtain scaling laws that characterize flow balancing as a function of the flow parameters and the manifold geometry using a Resistor Network Model (RNM). Associated Hartman and Reynolds numbers in the computations were ∼103 and 102 respectively. Compared to the full 3D analysis, the proposed RNM suggests a relatively quick and simpler way of computing the blanket length that might be needed to provide balanced flow among the parallel channels.
Docker vs. KVM: Apache spark application performance and ease of use

In this paper, we compare the performance and ease of use of an Apache Spark application deployed via Docker and alternatively via KVM. Docker containers have rapidly grown in popularity for dynamic cloud computing and for general-use application deployment and collaboration. Recent work comparing the performance of Docker versus VM deployments has found that Docker's reduced overhead results in better performance. We compare Docker versus VM deployments of an Apache Spark application in regard to ease of use in a collaborative development environment. We expect that developing the application in a containerized environment will result in fewer post-deployment tests that fail compared to application versions that are developed in non-virtual or VM environments. Future work will closely examine the performance of these two implementations and more generally investigate potential trade-offs between performance and ease of use.
Therapy for heart failure with preserved ejection fraction: current status, unique challenges, and future directions

Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF. Among elderly women, HFpEF comprises more than 80% of incident HF cases. Adverse outcomes—exercise intolerance, poor quality of life, frequent hospitalizations, and reduced survival—approach those of classic HF with reduced EF (HFrEF). However, despite its importance, our understanding of the pathophysiology of HFpEF is incomplete, and despite intensive efforts, optimal therapy remains uncertain, as most trials to date have been negative. This is in stark contrast to management of HFrEF, where dozens of positive trials have established a broad array of effective, guidelines-based therapies that definitively improve a range of clinically meaningful outcomes. In addition to providing an overview of current management status, we examine evolving data that may help explain this paradox, overcome past challenges, provide a roadmap for future success, and that underpin a wave of new trials that will test novel approaches based on these insights.
Principles of in Vivo EPR

The basic principles of in vivo EPR are presented and the possible implications of imaging free radicals to provide functional information such as in vivo pO2. The importance of performing EPR imaging at radio frequency regime and the relative importance of CW vs FT EPR methods are briefly outlined.
Muscle gene expression in heterokaryons.

One approach to the study of how gene regulation occurs during muscle differentiation and development is to put a non-muscle cell into an environment where it is reprogrammed to synthesize muscle proteins, which it would never normally express. One way to do this is to fuse two cells together. In this talk I will show you how this kind of fusion system can be used to ascertain the requirements for gene expression and to address certain questions about the determination and differentiation.
Health crusades and tropical diseases.

Worldwide attempts to eradicate yaws, malaria, and smallpox have all been effective to varying extents, and all have taught some valuable lessons that should be taken into account as a new global crusade is mounted against tropical diseases. But it should not be forgotten that infectious disease remains a major public health problem in the U.S., and new diseases are arising to replace those already vanquished.
Molecular Events Associated with Peripheral Nerve Regeneration

The early events associated with nerve regeneration probably involve strong neuron-environment interactions. Observations on axonally transported proteins can aid in exploring such interactions at a number of levels.
Orthography, Reading, and Cerebral Functions

Research on reading has regained the attention of experimental psychologists in the last two decades (Tzeng, 1981). The new field is markedly interdisciplinary, and addresses questions of practical application as readily as questions of pure theory or knowledge. These questions have been attacked from a number of different perspectives, using various experimental paradigms. Some studies record patterns of eye movements and relate them to various phases of information pickup during reading comprehension (Thibadeau, Just, & Carpenter, 1982). Others look into specific characteristics of word perception, e.g., the word-superiority effect, and attempt to build interactive models of human information processing (Rumelhart, 1985). A third type of study examines the consequences of becoming literate in more than one writing system. For example, differences as subtle as phonemic awareness and as general as problem-solving strategies have been observed in such comparative reading studies (Scribner & Cole, 1978; Liberman, Liberman, Mattingly, & Shankweiler, 1980; Tzeng & Hung, 1981).
Climate change impacts in Missouri State Parks: Perceptions from engaged park users

Abstract Frequent visitors to natural areas may be more receptive to climate change messages and more likely to act on their environmental values. To aid in developing targeted communication strategies, this exploratory study assessed how engaged state park users perceive climate change impacts and what they view as the agency role in climate change mitigation, education, and communication. Photo elicitation and semi-structured interviews were conducted with 18 members of the Missouri Parks Association (MPA), an advocacy group. While participants expressed concern about the threat of climate change to state parks, some doubted their ability to identify impacts. Despite this, participants accurately identified most of the regional threats predicted by experts, including increased flooding and drought, early blooming, invasive species, and extreme weather. Some reported that participation in the study inspired them to observe climate impacts more closely. Participants affirmed that state parks should lead climate change education and mitigation efforts, while acknowledging the challenges of addressing a politically charged subject. Regarding communication, MPA members recommend focusing on the science behind climate change and ecological mitigation. Although this study focused on Missouri state parks, results may be applicable to visitors in other Midwestern states. Management implications ● Study participants supported managerial action on climate change adaptation through education and ecological management. ● They acknowledged the political challenges managers face. This study supports presenting scientific evidence to the public and framing climate-change communication around specific, resource-related impacts, especially vegetation, wildlife, and landscape themes that visitors identify as locally salient. ● Alternatively, park management could focus natural resource-based climate change education on the broader ecological benefits of environmental behavior. ● Staff can also highlighting environmental efforts underway in parks, such as adoption of energy efficient technology and landscape management practices aimed at increasing ecological resilience. ● Staff should be educated, empowered and encouraged to deliver locally-relevant climate change interpretation.
Long-wavelength topography on Mercury is not from folding of the lithosphere

Abstract Previous work suggested that the lithosphere of Mercury could undergo folding in response to global contraction, and indeed observations from the MESSENGER mission revealed several regions where long-wavelength topography is present. Here, we test, via finite-element simulations that use a more realistic rheological model than that earlier work, lithospheric folding as a formation mechanism for long-wavelength topography on Mercury from interior secular cooling over the last 3.8 Gyr. This radial contraction has been estimated from geological observations to be less than 10 km, which translates into small amounts of horizontal shortening of