bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer Trends in Mexico: Essential Data for the Creation and Follow-Up of Public Policies
Authors: Mohar-Betancourt Alejandro , Reynoso-Noverón Nancy , Armas-Texta Daniel , Gutiérrez-Delgado Cristina , Torres-Domínguez Juan A.
Published: March 2017

Purpose

Cancer in a country like Mexico is a challenge for the current health system and for public health. However, the statistics about cancer in Mexico are scarce, so epidemiologic surveillance needs to be improved. The objectives of this article were to describe the extent of cancer and to estimate the national burden of cancer through 2020.

Materials and Methods

To meet this objective, an analysis of secondary official sources was performed. The cancer cases through 2020 were estimated on the basis of trends in mortality and the projection of incident cases reported by GLOBOCAN.

Results

In 2013, cancer was the cause of 12.84% of all deaths in Mexico. It is projected that the prevalence of cancer will be 904,581 by 2017 and will reach 1,262,861 by early in the next decade (ie, 2020).

Conclusion

Available data for cancer are incomplete. The development and implementation of population-based cancer registries in Mexico are essential. Assessment of the future outlook of cancer in Mexico will provide awareness of future challenges and can help health systems prepare to face them.
Secrecy, Sacrifice, and God on the Island: Christianity and Colonialism in Coetzee’sFoeand Defoe’sRobinson Crusoe
Authors: Rajiva Jay
Published: March 2017

This essay argues that at the center of Coetzee’s reading of Robinson Crusoe lies the exposure of the Christian secret in both the colonial enterprises of the characters and the authorial presences of Defoe and Coetzee. My argument draws on Jacques Derrida’s The Gift of Death, which outlines how Christianity tacitly incorporates (but does not destroy) older, non-Christian elements into its epistemic framework. Though Crusoe explicitly sets out to convert Friday to Christianity, and succeeds in that goal, their conversation on the worship of God offers a startling subversion of the Christian subject position. Foe highlights this subversion through the nonpresence of Friday, showing the work of colonial Christianity still in transition, convulsed by the repetition of what it is attempting to subordinate in secret: the non-Christian other whose sacrifice cannot be openly acknowledged.
Baldwin’s Hemingway:The Sun Also RisesinGiovanni’s Room, with a Twist
Authors: Kent Jessica
Published: March 2017

James Baldwin’s Giovanni’s Room participates in a cross-racial call and response with Ernest Hemingway’s The Sun Also Rises, illuminating both shared cultural influences and differences of race and sexuality. David’s struggle between the social force of compulsory heterosexuality and the personal force of individual desire plays out on a broader structural level as Baldwin’s gay plot is drawn toward the magnetically forceful heterosexual love triangle in Hemingway’s tale. Hemingway and Baldwin address gender normativity and sexual inadequacy from a particular American perspective that must grapple with an unattainable vision of the normal and with the crippling American myth of self-determination.
Probabilistic modeling of bifurcations in single-cell gene expression data using a Bayesian mixture of factor analyzers
Authors: Campbell Kieran R , Yau Christopher
Published: March 2017

Modeling bifurcations in single-cell transcriptomics data has become an increasingly popular field of research. Several methods have been proposed to infer bifurcation structure from such data, but all rely on heuristic non-probabilistic inference. Here we propose the first generative, fully probabilistic model for such inference based on a Bayesian hierarchical mixture of factor analyzers. Our model exhibits competitive performance on large datasets despite implementing full Markov-Chain Monte Carlo sampling, and its unique hierarchical prior structure enables automatic determination of genes driving the bifurcation process. We additionally propose an Empirical-Bayes like extension that deals with the high levels of zero-inflation in single-cell RNA-seq data and quantify when such models are useful. We apply or model to both real and simulated single-cell gene expression data and compare the results to existing pseudotime methods. Finally, we discuss both the merits and weaknesses of such a unified, probabilistic approach in the context practical bioinformatics analyses.
On the Asymptotic Optimality of Finite Approximations to Markov Decision Processes with Borel Spaces
Authors: Saldi Naci , Yüksel Serdar , Linder Tamás
Published: March 2017

Calculating optimal policies is known to be computationally difficult for Markov decision processes (MDPs) with Borel state and action spaces. This paper studies finite-state approximations of discrete time Markov decision processes with Borel state and action spaces, for both discounted and average costs criteria. The stationary policies thus obtained are shown to approximate the optimal stationary policy with arbitrary precision under quite general conditions for discounted cost and more restrictive conditions for average cost. For compact-state MDPs, we obtain explicit rate of convergence bounds quantifying how the approximation improves as the size of the approximating finite state space increases. Using information theoretic arguments, the order optimality of the obtained convergence rates is established for a large class of problems. We also show that as a pre-processing step, the action space can also be finitely approximated with sufficiently large number points; thereby, well known algorithms, such as value or policy iteration, Q-learning, etc., can be used to calculate near optimal policies.
‘Refusing to Be a Man’: Gender, feminism and queer identity in the punk culture
Authors: Ambrosch Gerfried
Published: March 2017

Since its inception, transgressing heteronormative preconceptions of gender and sexuality a reaction to the prevalent ‘rock machismo’ of the 1970s, has been an important part of punk’s subversive repertoire. A number of first-wave punk artists deliberately blurred gender boundaries and toyed with signifiers pertaining to nonmainstream gender identities and sexual ‘perversion’ (consider, in this context, the common use of BDSM paraphernalia in early punk’s iconography). These transgressions had profound implications. As music journalist Lucy O’Brien puts it, ‘To find fresh meanings as a woman it was necessary to overturn the pastel shades of post-60s femininity and make an overt statement on a newly emerging, more aggressive understanding of female sexuality. Punk provided the perfect opportunity’. In the early 1990s, the feminist US punk rock group Bikini Kill, who spearheaded the riot grrrl movement, presented an assertive, unapologetic view of femininity, feminism and female sexuality, aggressively challenging male dominance in the punk milieu, where they were met sometimes with acceptance, sometimes with suspicion, and sometimes with open hostility. These developments notwithstanding, the anarchist periodical Rolling Thunder observes that ‘The average punk show is more dominated by patriarchy than a college class room’, and the transgender punk activist Alyssa Kai states, ‘[…] in reality, men run the scene, men are the scene, and men always have been and probably always will be at the center of the scene’. In other words, there is a gaping discrepancy within punk culture between egalitarian expectations, some of which verge on utopianism, and reality. ‘I think to anyone who is already slightly involved in punk and hardcore, it goes without saying that there is sexism in it’, says punk fan Lucy Hodges. Quite the same is true for homophobia.
Software como serviço: um estudo de caso
Authors: Caversan Nubia , Silva Andrea Lago da , Mello Luciana Torres Correia de
Published: March 2017

Este artigo analisa o processo de servitização em uma empresa de tecnologia de informação. Inicialmente foi realizada uma revisão de literatura, seguida de um estudo de caso na empresa de software. Observações diretas e entrevistas com os colaboradores envolvidos diretamente no processo foram realizadas, caracterizando motivações, mudanças e desafios. A partir da análise dos resultados, foi desenvolvido um checklist que auxilia as empresas na adoção de tal prática. Algumas ações são importantes na implantação da servitização: a revisão do portfólio de produtos e clientes; a preparação das equipes de linha de frente, envolvimento da gestão e liderança, a gestão de contratos e a gestão de melhorias.
Modelos matemáticos para programação de job shop com tempos de setup independentes da sequência
Authors: Fuchigami Helio Yochihiro , Moura Mirella Augusta Sousa , Branco Fábio José Ceron
Published: March 2017

Este trabalho aborda o problema de programação da produção em job shop com tempos de setup explícitos e independentes da sequência de processamento das tarefas visando minimizar a duração total da programação (makespan). Na conhecida notação de três campos, este problema é representado por Jm|sjk|Cmax. O ambiente job shop é aquele em que há um conjunto de máquinas ou recursos diferentes que devem processar um conjunto de tarefas, sendo que cada tarefa possui uma rota específica e pré-determinada para processamento nas máquinas. Para problemas com duas máquinas, nesta pesquisa propõe-se uma adaptação no clássico Algoritmo de Jackson, que fornece a solução ótima para o caso com setup incluído nos tempos de processamento das tarefas. E para problemas genéricos com m máquinas, foram elaborados e implementados dois modelos matemáticos de programação linear inteira mista para os casos de setup antecipado (aquele que pode ser iniciado antes da liberação da tarefa) e não antecipado, que fornecem soluções em tempo computacional viável para problemas-testes com até 20 tarefas e 7 máquinas.
Análise integrada para a tomada de decisão: os efeitos da modelagem no gerenciamento de estoques e o impacto sobre o indicador de rentabilidade ROI
Authors: Vargas Elisandro João de , Baccin Bruno , Sellitto Miguel Afonso
Published: March 2017

O adequado gerenciamento de estoques pode auxiliar a minimizar os efeitos de variabilidade e custos operacionais, assim como melhorar os níveis de serviço e a rentabilidade das empresas. Neste sentido, o objetivo deste artigo é integrar a modelagem sobre gerenciamento de estoques e seu impacto sobre o indicador de rentabilidade ROI. Foram modelados quatro cenários e aplicados em um caso no gerenciamento de estoques de matéria-prima, aplicado em uma empresa metal mecânica no estado do Rio Grande do Sul. Os resultados modelados foram usados para comparar e analisar os impactos gerados sobre o indicador de rentabilidade da empresa. O método de pesquisa foi a modelagem quantitativa. Os resultados indicam possibilidade de redução do custo total de operação, redução dos volumes e valores em inventário e aumento do giro de estoques. Além disso, os impactos das modelagens demonstram a possibilidade de aumento no ROI em até 58,5% no curto prazo. A análise integrada pode auxiliar na compreensão da importância do gerenciamento adequado dos estoques.
SMCQL
Authors: Bater Johes , Elliott Gregory , Eggen Craig , Goel Satyender , Kho Abel , Rogers Jennie
Published: March 2017

People and machines are collecting data at an unprecedented rate. Despite this newfound abundance of data, progress has been slow in
sharing
it for open science, business, and other data-intensive endeavors. Many such efforts are stymied by privacy concerns and regulatory compliance issues. For example, many hospitals are interested in pooling their medical records for research, but none may disclose arbitrary patient records to researchers or other healthcare providers. In this context we propose the Private Data Network (PDN), a federated database for querying over the collective data of
mutually distrustful
parties. In a PDN, each member database does not reveal its tuples to its peers nor to the query writer. Instead, the user submits a query to an honest broker that plans and coordinates its execution over multiple private databases using secure multiparty computation (SMC). Here, each database's query execution is
oblivious
, and its program counters and memory traces are agnostic to the inputs of others.

We introduce a framework for executing PDN queries named
smcql
. This system translates SQL statements into SMC primitives to compute query results over the union of its source databases without revealing sensitive information about individual tuples to peer data providers or the honest broker. Only the honest broker and the querier receive the results of a PDN query. For fast, secure query evaluation, we explore a heuristics-driven optimizer that minimizes the PDN's use of secure computation and partitions its query evaluation into scalable slices.
Plausible deniability for privacy-preserving data synthesis
Authors: Bindschaedler Vincent , Shokri Reza , Gunter Carl A.
Published: March 2017

Releasing full data records is one of the most challenging problems in data privacy. On the one hand, many of the popular techniques such as data de-identification are problematic because of their dependence on the background knowledge of adversaries. On the other hand, rigorous methods such as the exponential mechanism for differential privacy are often computationally impractical to use for releasing high dimensional data or cannot preserve high utility of original data due to their extensive data perturbation.

This paper presents a criterion called
plausible deniability
that provides a formal privacy guarantee, notably for releasing sensitive datasets: an output record can be released only if a certain amount of input records are indistinguishable, up to a privacy parameter. This notion does not depend on the background knowledge of an adversary. Also, it can efficiently be checked by privacy tests. We present mechanisms to generate
synthetic datasets
with similar statistical properties to the input data and the same format. We study this technique both theoretically and experimentally. A key theoretical result shows that, with proper randomization, the plausible deniability mechanism generates differentially private synthetic data. We demonstrate the efficiency of this generative technique on a large dataset; it is shown to preserve the utility of original data with respect to various statistical analysis and machine learning measures.
Distributed join algorithms on thousands of cores
Authors: Barthels Claude , Müller Ingo , Schneider Timo , Alonso Gustavo , Hoefler Torsten
Published: March 2017

Traditional database operators such as joins are relevant not only in the context of database engines but also as a building block in many computational and machine learning algorithms. With the advent of big data, there is an increasing demand for efficient join algorithms that can scale with the input data size and the available hardware resources.

In this paper, we explore the implementation of distributed join algorithms in systems with several thousand cores connected by a low-latency network as used in high performance computing systems or data centers. We compare radix hash join to sort-merge join algorithms and discuss their implementation at this scale. In the paper, we explain how to use MPI to implement joins, show the impact and advantages of RDMA, discuss the importance of network scheduling, and study the relative performance of sorting vs. hashing. The experimental results show that the algorithms we present scale well with the number of cores, reaching a throughput of 48.7 billion input tuples per second on 4,096 cores.
AdaptDB
Authors: Lu Yi , Shanbhag Anil , Jindal Alekh , Madden Samuel
Published: March 2017

Big data analytics often involves complex join queries over two or more tables. Such join processing is expensive in a distributed setting both because large amounts of data must be read from disk, and because of data shuffling across the network. Many techniques based on data partitioning have been proposed to reduce the amount of data that must be accessed, often focusing on finding the best partitioning scheme for a particular workload, rather than adapting to changes in the workload over time.

In this paper, we present AdaptDB, an adaptive storage manager for analytical database workloads in a distributed setting. It works by partitioning datasets across a cluster and incrementally refining data partitioning as queries are run. AdaptDB introduces a novel
hyper-join
that avoids expensive data shuffling by identifying storage blocks of the joining tables that overlap on the join attribute, and only joining those blocks. Hyper-join performs well when each block in one table overlaps with few blocks in the other table, since that will minimize the number of blocks that have to be accessed. To minimize the number of overlapping blocks for common join queries, AdaptDB users
smooth repartitioning
to repartition small portions of the tables on join attributes as queries run. A prototype of AdaptDB running on top of Spark improves query performance by 2--3x on TPC-H as well as real-world dataset, versus a system that employs scans and shuffle-joins.
Cthrc1 lowers pulmonary collagen associated with bleomycin‐induced fibrosis and protects lung function
Authors: Binks Andrew P. , Beyer Megyn , Miller Ryan , LeClair Renee J.
Published: March 2017

Idiopathic pulmonary fibrosis (IPF) involves collagen deposition that results in a progressive decline in lung function. This process involves activation of Smad2/3 by transforming growth factor (TGF)‐β and Wnt signaling pathways. Collagen Triple Helix Repeat‐Containing‐1 (Cthrc1) protein inhibits Smad2/3 activation. To test the hypothesis that Cthrc1 limits collagen deposition and the decline of lung function, Cthrc1 knockout (Cthrc1−/−) and wild‐type mice (WT) received intratracheal injections of 2.5 U/kg bleomycin or saline. Lungs were harvested after 14 days and Bronchoalveolar lavage (BAL) TGF‐β, IL1‐β, hydroxyproline and lung compliance were assessed. TGF‐β was significantly higher in Cthrc1−/− compared to WT (53.45 ± 6.15 ng/mL vs. 34.48 ± 11.05) after saline injection. Bleomycin injection increased TGF‐β in both Cthrc1−/− (66.37 ± 8.54 ng/mL) and WT (63.64 ± 8.09 ng/mL). Hydroxyproline was significantly higher in Cthrc1−/− compared to WT after bleomycin‐injection (2.676 ± 0.527 μg/mg vs. 1.889 ± 0.520, P = 0.028). Immunohistochemistry of Cthrc1‐/‐ lung sections showed intracellular localization and activation of β‐catenin Y654 in areas of tissue remodeling that was not evident in WT. Lung compliance was significantly reduced by bleomycin in Cthrc1−/− but there was no effect in WT animals. These data suggest Cthrc1 reduces fibrotic tissue formation in bleomycin‐induced lung fibrosis and the effect is potent enough to limit the decline in lung function. We conclude that Cthrc1 plays a protective role, limiting collagen deposition and could form the basis of a novel therapy for pulmonary fibrosis.
Vascular conductance and muscle blood flow during exercise are altered by inspired oxygen fraction and arterial perfusion pressure
Authors: Villar Rodrigo , Hughson Richard L.
Published: March 2017

We tested the hypothesis during the combined challenges of altered inspired O2 fraction (FIO2) and posture changes at lower power output regardless of body position that the vascular conductance (VC) recruitment to the exercising muscle would not limit muscle perfusion and estimated O2 delivery (DO2est). However, in head‐down tilt at the higher power output exercise in hypoxia, the recruitment of VC would have a functional limitation which would restrict muscle blood flow (MBF) leading to a limitation in DO2est with consequent increases in metabolic stress. Ten healthy volunteers repeated plantar flexion contractions at 20% (low power output = LPO) and 30% (higher power output = HPO) of their maximal voluntary contraction in horizontal (HOR), 35° head‐down‐tilt (HDT) and 45° head‐up‐tilt (HUT). Popliteal diameter and muscle blood flow velocity were measured by ultrasound determining MBF. VC was estimated by dividing MBF flow by MPP, and DO2est was estimated by MBF times saturation. LPOHUT in hypoxia was associated with no changes in VC and MBF leading to reduced DO2est. In LPOHDT under hypoxia, despite no apparent functional limitation in the VC recruitment, rise in MBF to maintain DO2est was associated with marked increase in muscle electromyographic activity, indicating greater metabolic stress. In HPOHDT under hypoxia, a functional limitation for the recruitment of VC constrained MBF and DO2est. Elevated muscle electromyographic signal in HPOHDT under hypoxia was consistent with challenged aerobic metabolisms which contributed to a greater increase in the relative stress of the exercise challenge and advance the onset of muscle fatigue.
Antibody‐mediated inhibition of EGFR reduces phosphate excretion and induces hyperphosphatemia and mild hypomagnesemia in mice
Authors: Ortega Bernardo , Dey Jason M. , Gardella Allison R. , Proano Jacob , Vaneerde Deanna
Published: March 2017

Monoclonal antibody therapies targeting the EGF receptor (EGFR) frequently result in hypomagnesemia in human patients. In contrast, EGFR tyrosine kinase inhibitors do not affect Mg2+ balance in patients and only have a mild effect on Mg2+ homeostasis in rodents at elevated doses. EGF has also been shown to affect phosphate (Pi) transport in rat and rabbit proximal convoluted tubules (PCT), but evidence from studies targeting EGFR and looking at Pi excretion in whole animals is still missing. Thus, the role of EGF in regulating reabsorption of Mg2+ and/or Pi in the kidney remains controversial. Here, we inject mice with the anti‐EGFR monoclonal antibody ME‐1 for 2 weeks and observe a significant increase in serum Pi and mild hypomagnesemia, but no changes in Pi or Mg2+ excretion. In contrast, a single injection of ME‐1 resulted in hyperphosphatemia and a significant reduction in Pi excretion 2 days after treatment, while no changes in serum Mg2+ or Mg2+ excretion were observed. Dietary Mg2+ deprivation is known to trigger a rapid Mg2+ conservation response in addition to hyperphosphatemia and hyperphosphaturia. Interestingly, one dose of ME‐1 did not significantly modify the response of mice to 2 days of Mg2+ deprivation. These data show that EGFR plays a significant role in regulating Pi reabsorption in the kidney PCT, but suggest only a minor role in long‐term regulation of Mg2+ transport in the distal convoluted tubule.
The effects of dual PPARα/γ agonism compared with ACE inhibition in the BTBRob/ob mouse model of diabetes and diabetic nephropathy
Authors: Ericsson Anette , Tonelius Pernilla , Lal Mark , Sabirsh Alan , Böttcher Gerhard , William‐Olsson Lena , Strömstedt Maria , Johansson Camilla , Hyberg Gina , Tapani Sofia , Jönsson‐Rylander Ann‐Cathrine , Unwin Robert
Published: March 2017

The leptin‐deficient BTBRob/ob mouse develops progressive albuminuria and morphological lesions similar to human diabetic nephropathy (DN), although whether glomerular hyperfiltration, a recognized feature of early DN that may contribute to renal injury, also occurs in this model is not known. Leptin replacement has been shown to reverse the signs of renal injury in this model, but in contrast, the expected renoprotection by angiotensin‐converting enzyme (ACE) inhibition in BTBRob/ob mice seems to be limited. Therefore, to investigate the potential renal benefits of improved metabolic control in this model, we studied the effect of treatment with the dual peroxisome proliferator‐activated receptor (PPAR) α/γ agonist AZD6610 and compared it with the ACE inhibitor enalapril. AZD6610 lowered plasma glucose and triglyceride concentrations and increased liver size, but had no significant effect in reducing albuminuria, whereas enalapril did have an effect. Nephrin and WT1 mRNA expression decreased in the kidneys of BTBRob/ob mice, consistent with podocyte injury and loss, but was unaffected by either drug treatment: at the protein level, both nephrin and WT1‐positive cells per glomerulus were decreased. Mesangial matrix expansion was reduced in AZD6610‐treated mice. GFR, measured by creatinine clearance, was increased in BTBRob/ob mice, but unaffected by either treatment. Unexpectedly, enalapril‐treated mice showed intrarenal arteriolar vascular remodeling with concentric thickening of vessel walls. In summary, we found that the BTBRob/ob mouse model shows some similarities to the early changes seen in human DN, but that ACE inhibition or PPARα/γ agonism afforded limited or no kidney protection.
β‐GPA treatment leads to elevated basal metabolic rate and enhanced hypoxic exercise tolerance in mice
Authors: Ross Trenton T. , Overton Jeffrey D. , Houmard Katelyn F. , Kinsey Stephen T.
Published: March 2017

Treatments that increase basal metabolic rate (BMR) and enhance exercise capacity may be useful therapeutic approaches for treating conditions such as type 2 diabetes, obesity, and associated circulatory problems. β‐guanidinopropionic acid (β‐GPA) supplementation decreases high‐energy phosphate concentrations, such as ATP and phosphocreatine (PCr) resulting in an energetic challenge that is similar to both exercise programs and hypoxic conditions. In this study, we administered β‐GPA to mice for 2 or 6 weeks, and investigated the effect on muscle energetic status, body and muscle mass, muscle capillarity, BMR, and normoxic and hypoxic exercise tolerance (NET and HET, respectively). Relative [PCr] and PCr/ATP ratios significantly decreased during both treatment times in the β‐GPA fed mice compared to control mice. Body mass, muscle mass, and muscle fiber size significantly decreased after β‐GPA treatment, whereas muscle capillarity and BMR were significantly increased in β‐GPA fed mice. NET significantly decreased in the 2‐week treatment, but was not significantly different in the 6‐week treatment. HET significantly decreased in 2‐week treatment, but in contrast to NET, significantly increased in the 6‐week‐treated mice compared to control mice. We conclude that β‐GPA induces a cellular energetic response in skeletal muscle similar to that of chronic environmental hypoxia, and this energetic perturbation leads to elevated BMR and increased hypoxic exercise capacity in the absence of hypoxic acclimation.
The Glycoside Oleandrin Reduces Glioma Growth with Direct and Indirect Effects on Tumor Cells
Authors: Garofalo Stefano , Grimaldi Alfonso , Chece Giuseppina , Porzia Alessandra , Morrone Stefania , Mainiero Fabrizio , D'Alessandro Giuseppina , Esposito Vincenzo , Cortese Barbara , Di Angelantonio Silvia , Trettel Flavia , Limatola Cristina
Published: March 2017

Oleandrin is a glycoside that inhibits the ubiquitous enzyme Na+/K+-ATPase. In addition to its known effects on cardiac muscle, recentin vitroandin vivoevidence highlighted its potential for anticancer properties. Here, we evaluated for the first time the effect of oleandrin on brain tumors. To this aim, mice were transplanted with human or murine glioma and analyzed for tumor progression upon oleandrin treatment. In both systems, oleandrin impaired glioma development, reduced tumor size, and inhibited cell proliferation. We demonstrated that oleandrin does the following: (1) enhances the brain-derived neurotrophic factor (BDNF) level in the brain; (2) reduces both microglia/macrophage infiltration and CD68 immunoreactivity in the tumor mass; (3) decreases astrogliosis in peritumoral area; and (4) reduces glioma cell infiltration in healthy parenchyma. In BDNF-deficient mice (bdnftm1Jae/J) and in glioma cells silenced for TrkB receptor expression, oleandrin was not effective, indicating a crucial role for BDNF in oleandrin's protective and antitumor functions. In addition, we found that oleandrin increases survival of temozolomide-treated mice. These results encourage the development of oleandrin as possible coadjuvant agent in clinical trials of glioma treatment.

SIGNIFICANCE STATEMENTIn this work, we paved the road for a new therapeutic approach for the treatment of brain tumors, demonstrating the potential of using the cardioactive glycoside oleandrin as a coadjuvant drug to standard chemotherapeutics such as temozolomide. In murine models of glioma, we demonstrated that oleandrin significantly increased mouse survival and reduced tumor growth both directly on tumor cells and indirectly by promoting an antitumor brain microenvironment with a key protective role played by the neurotrophin brain-derived neurotrophic factor.
Mesoscale Architecture Shapes Initiation and Richness of Spontaneous Network Activity
Authors: Okujeni Samora , Kandler Steffen , Egert Ulrich
Published: March 2017

Spontaneous activity in the absence of external input, including propagating waves of activity, is a robust feature of neuronal networksin vivoandin vitro. The neurophysiological and anatomical requirements for initiation and persistence of such activity, however, are poorly understood, as is their role in the function of neuronal networks. Computational network studies indicate that clustered connectivity may foster the generation, maintenance, and richness of spontaneous activity. Since this mesoscale architecture cannot be systematically modified in intact tissue, testing these predictions is impracticablein vivo. Here, we investigate how the mesoscale structure shapes spontaneous activity in generic networks of rat cortical neuronsin vitro. In these networks, neurons spontaneously arrange into local clusters with high neurite density and form fasciculating long-range axons. We modified this structure by modulation of protein kinase C, an enzyme regulating neurite growth and cell migration. Inhibition of protein kinase C reduced neuronal aggregation and fasciculation of axons, i.e., promoted uniform architecture. Conversely, activation of protein kinase C promoted aggregation of neurons into clusters, local connectivity, and bundling of long-range axons. Supporting predictions from theory, clustered networks were more spontaneously active and generated diverse activity patterns. Neurons within clusters received stronger synaptic inputs and displayed increased membrane potential fluctuations. Intensified clustering promoted the initiation of synchronous bursting events but entailed incomplete network recruitment. Moderately clustered networks appear optimal for initiation and propagation of diverse patterns of activity. Our findings support a crucial role of the mesoscale architectures in the regulation of spontaneous activity dynamics.

SIGNIFICANCE STATEMENTComputational studies predict richer and persisting spatiotemporal patterns of spontaneous activity in neuronal networks with neuron clustering. To test this, we created networks of varying architecturein vitro. Supporting these predictions, the generation and spatiotemporal patterns of propagation were most variable in networks with intermediate clustering and lowest in uniform networks. Grid-like clustering, on the other hand, facilitated spontaneous activity but led to degenerating patterns of propagation. Neurons outside clusters had weaker synaptic input than neurons within clusters, in which increased membrane potential fluctuations facilitated the initiation of synchronized spike activity. Our results thus show that the intermediate level organization of neuronal networks strongly influences the dynamics of their activity.
Reduction of Ether-Type Glycerophospholipids, Plasmalogens, by NF-κB Signal Leading to Microglial Activation
Authors: Hossain Md. Shamim , Abe Yuichi , Ali Fatma , Youssef Mohammed , Honsho Masanori , Fujiki Yukio , Katafuchi Toshihiko
Published: March 2017

Neuroinflammation characterized by activation of glial cells is observed in various neurodegenerative diseases including Alzheimer's disease (AD). Although the reduction of ether-type glycerophospholipids, plasmalogens (Pls), in the brain is reported in AD patients, the mechanism of the reduction and its impact on neuroinflammation remained elusive. In the present study, we found for the first time that various inflammatory stimuli reduced Pls levels in murine glial cells via NF-κB activation, which then downregulated a Pls-synthesizing enzyme, glycerone phosphate O-acyltransferase (Gnpat) through increased c-Myc recruitment onto theGnpatpromoter. We also found that systemic injection of lipopolysaccharide, aging, and chronic restraint stress reduced brain Pls contents that were associated with glial NF-κB activation, an increase in c-Myc expression, and downregulation ofGnpatin the mouse cortex and hippocampus. More interestingly, the reduction of Pls contents in the murine cortex itself could increase the activated phenotype of microglial cells and the expression of proinflammatory cytokines, suggesting further acceleration of neuroinflammation by reduction of brain Pls. A similar mechanism ofGnpatreduction was also found in human cell lines, triple-transgenic AD mouse brain, and postmortem human AD brain tissues. These findings suggest a novel mechanism of neuroinflammation that may explain prolonged progression of AD and help us to explore preventive and therapeutic strategies to treat neurodegenerative diseases.

SIGNIFICANCE STATEMENTEther-type glycerophospholipids, plasmalogens (Pls), are reduced in the brain of Alzheimer disease (AD) patients. We found that inflammatory stimuli reduced Pls contents by downregulation of the Pls-synthesizing enzyme glycerone phosphate O-acyltransferase (Gnpat) through NF-κB-mediated recruitment of c-Myc onto theGnpatpromoter in both murine and human cell lines. Murine brains after systemic lipopolysaccharide, chronic stress, and aging, as well as triple-transgenic AD mice and postmortem human AD brain tissues all showed increased c-Myc and reducedGnpatexpression. Interestingly, knockdown ofGnpatitself activated NF-κB in glial cell lines and microglia in mouse cortex. Our findings provide a new insight into the mechanism of neuroinflammation and may help to develop a novel therapeutic approach for neurodegenerative diseases such as AD.
Molecular Determinants of the Regulation of Development and Metabolism by Neuronal eIF2α Phosphorylation in Caenorhabditis elegans
Authors: Kulalert Warakorn , Sadeeshkumar Harini , Zhang Ying K , Schroeder Frank C , Kim Dennis H
Published: March 2017

Cell-nonautonomous effects of signaling in the nervous system of animals can influence diverse aspects of organismal physiology. We previously showed that phosphorylation of Ser49 of the α-subunit of eukaryotic translation initiation factor 2 (eIF2α) in two chemosensory neurons by PEK-1/PERK promotes entry of Caenorhabditis elegans into dauer diapause. Here, we identified and characterized the molecular determinants that confer sensitivity to effects of neuronal eIF2α phosphorylation on development and physiology of C. elegans. Isolation and characterization of mutations in eif-2Ba encoding the α-subunit of eIF2B support a conserved role, previously established by studies in yeast, for eIF2Bα in providing a binding site for phosphorylated eIF2α to inhibit the exchange factor eIF2B catalytic activity that is required for translation initiation. We also identified a mutation in eif-2c, encoding the γ-subunit of eIF2, which confers insensitivity to the effects of phosphorylated eIF2α while also altering the requirement for eIF2Bγ. In addition, we show that constitutive expression of eIF2α carrying a phosphomimetic S49D mutation in the ASI pair of sensory neurons confers dramatic effects on growth, metabolism, and reproduction in adult transgenic animals, phenocopying systemic responses to starvation. Furthermore, we show that constitutive expression of eIF2α carrying a phosphomimetic S49D mutation in the ASI neurons enhances dauer entry through bypassing the requirement for nutritionally deficient conditions. Our data suggest that the state of eIF2α phosphorylation in the ASI sensory neuron pair may modulate internal nutrient sensing and signaling pathways, with corresponding organismal effects on development and metabolism.
Categorization of National Pediatric Quality Measures
Authors: House Samantha A. , Coon Eric R. , Schroeder Alan R. , Ralston Shawn L.
Published: March 2017

BACKGROUND AND OBJECTIVE:

The number of quality measures has grown dramatically in recent years. This growth has outpaced research characterizing content and impact of these metrics. Our study aimed to identify and classify nationally promoted quality metrics applicable to children, both by type and by content, and to analyze the representation of common pediatric issues among available measures.

METHODS:

We identified nationally applicable quality measure collections from organizational databases or clearinghouses, federal Web sites, and key informant interviews and then screened each measure for pediatric applicability. We classified measures as structure, process, or outcome using a Donabedian framework. Additionally, we classified process measures as targeting underuse, overuse, or misuse of health services. We then classified measures by content area and compared disease-specific metrics to frequency of diagnoses observed among children.

RESULTS:

A total of 386 identified measures were relevant to pediatric patients; exclusion of duplicates left 257 unique measures. The majority of pediatric measures were process measures (59%), most of which target underuse of health services (77%). Among disease-specific measures, those related to depression and asthma were the most common, reflecting the prevalence and importance of these conditions in pediatrics. Conditions such as respiratory infection and otitis media had fewer associated measures despite their prevalence. Other notable pediatric issues lacking associated measures included care of medically complex children and injuries.

CONCLUSIONS:

Pediatric quality measures are predominated by process measures targeting underuse of health care services. The content represented among these measures is broad, although there remain important gaps.
Variación espacial de la composición de 222Rn en los acuíferos Barva y Colima Superior, Costa Rica
Authors: Sánchez-Murillo Ricardo
Published: March 2017

MEN: El 222Rn es un trazador natural que permite determinar la conectividad entre las aguas subterráneas y las superficiales. El estudio presenta el primer análisis espacial de 222Rn en aguas subterráneas, superficiales y agua potable de la red de abastecimiento en los acuíferos Barva y Colima Superior en el Valle Central de Costa Rica. Se analizó la composición de 222Rn, δ18O y otras variables físico-químicas in situ en un total de 40 sitios de muestreo. En general, las nacientes de la zona norte presentaron una composición homogénea de 222Rn con una concentración promedio de 21,3 Bq/L. La concentración de 222Rn en los pozos varió entre 2,0 Bq/L y 50,5 Bq/L. Las altas concentraciones de 222Rn en algunos pozos pueden atribuirse a la desgasificación profunda a través de los fallamientos locales. En la red de abastecimiento de agua potable, la concentración de 222Rn varió entre 4,7 Bq/L y 30,8 Bq/L. Los valores encontrados en la red de abastecimiento, superiores al límite sugerido por la Agencia de Protección Ambiental de los Estados Unidos (11,1 Bq/L) para agua de consumo humano, pueden atribuirse al corto tiempo de residencia del agua de extracción subterránea en la red de abastecimiento. La utilización de tanques de almacenamiento o captación permitiría aumentar el tiempo de residencia del agua antes de ingresar a la red de consumo, facilitando la pérdida de 222Rn hacia la atmósfera o por decaimiento radioactivo. Asimismo, un análisis espacial es requerido a escala nacional, especialmente, en áreas de fallas activas o actividad volcánica.
New monophyletic branches of the Teloschistaceae (lichen-forming Ascomycota) proved by three gene phylogeny
Authors: Kondratyuk S. Y. , Lőkös L. , Upreti D. K. , Nayaka S. , Mishra G. K. , Ravera S. , Jeong M.-H. , Jang S.-H. , Park J. S. , Hur J.-S.
Published: March 2017

Seventeen robust monophyletic branches newly discovered in the phylogenetic tree of the Teloschistaceae after separate nrITS, nrLSU and mtSSU, as well as combined phylogenetic analysis are proposed to consider as the following separate genera: Dijigiella S. Y. Kondr. et L. Lőkös gen. nov. for the D. kaernefeltiana group, Elixjohnia S. Y. Kondr. et J.-S. Hur gen. nov. for the Sirenophila jackelixii group, Fominiella S. Y. Kondr., D. Upreti et J.-S. Hur gen. nov. for the F. tenerifensis group; Gintarasiella S. Y. Kondr. et J.-S. Hur gen. nov. for Caloplaca aggregata, Hanstrassia S. Y. Kondr. gen. nov. for the Elenkiniana lenae group, Harusavskia S. Y. Kondr. gen. nov. for H. elenkinianoides sp. n., Huriella S. Y. Kondr. et D. Upreti gen. nov. for H. loekoesiana sp. n., Ikaeria S. Y. Kondr., D. Upreti et J.-S. Hur gen. nov. for Caloplaca aurantiellina, Klauderuiella S. Y. Kondr. et J.-S. Hur gen. nov. for the Variospora thallincola group, Laundonia S. Y. Kondr., L. Lőkös et J.-S. Hur gen. nov. for the Gyalolechia flavovirescens group, Lazarenkoiopsis S. Y. Kondr., L. Lőkös et J.-S. Hur gen. nov. for Caloplaca ussuriensis, Nevilleiella S. Y. Kondr. et J.-S. Hur gen. nov. for the Caloplaca marchantii group, Opeltia S. Y. Kondr. et L. Lőkös gen. nov. for the Caloplaca neobaltistanica group, Oxneriopsis S. Y. Kondr., D. Upreti et J.-S. Hur gen. nov. for the Caloplaca oxneri group, Teuvoahtiana S. Y. Kondr. et J.-S. Hur gen. nov. for the Caloplaca rugulosa group, Tomnashia S. Y. Kondr. et J.-S. Hur gen. nov. for the Polycauliona rosei group, and Xanthaptychia S. Y. Kondr. et S. Ravera gen. nov. for the Seirophora orientalis group.

Hitherto missing molecular data on three gene sequences of the type species of the genera Seirophora and Sirenophila are completed within this study.

Six new to science species (Dijigiella kaernefeltiana S. Y. Kondr. sp. n., D. subaggregata S. Y. Kondr. et Kärnefelt sp. n., Fominiella tenerifensis S. Y. Kondr., Kärnefelt, A. Thell et T. Feuerer sp. n., Hanstrassia jaeseounhurii S. Y. Kondr., Ch.-H. Park et L. Lőkös sp. n., Harusavskia elenkinianoides S. Y. Kondr., X. Y. Wang, S.-O. Oh et J.-S. Hur sp. n., Huriella loekoesiana S. Y. Kondr. et D. Upreti sp. n.) are described, compared with closely related taxa.

A total of 34 new combinations for genera mentioned above are proposed.
New and noteworthy lichen-forming and lichenicolous fungi 6
Authors: Kondratyuk S. Y. , Lőkös L. , Halda J. P. , Roux C. , Upreti D. K. , Schumm F. , Mishra G. K. , Nayaka S. , Farkas E. , Park J. S. , Lee B. G. , Liu D. , Woo J.-J. , Hur J.-S.
Published: March 2017

Eighteen new to science species, i.e.: 13 taxa from South Korea (Astroplaca loekoesiana S. Y. Kondr., E. Farkas, J.-J. Woo et J.-S. Hur, Buellia ulleungdoensis S. Y. Kondr., L. Lőkös et J.-S. Hur, Candelariella hakulinenii S. Y. Kondr., L. Lőkös et J.-S. Hur, Flavoplaca laszloana S. Y. Kondr. et J.-S. Hur, Lichenostigma epiporpidiae S. Y. Kondr., L. Lőkös et J.-S. Hur, Mikhtomia geumohdoensis S. Y. Kondr., Liu D. et J.-S. Hur, Orientophila dodongensis S. Y. Kondr., L. Lőkös et J.-S. Hur, Physcia orientostellaris S. Y. Kondr., L. Lőkös et J.-S. Hur, Placynthiella hurii S. Y. Kondr. et L. Lőkös, Protoparmeliopsis kopachevskae S. Y. Kondr., L. Lőkös et J.-S. Hur, Psoroglaena sunchonensis S. Y. Kondr., L. Lőkös et J.-S. Hur, Rufoplaca kaernefeltiana S. Y. Kondr., L. Lőkös et J.-S. Hur, Vezdaea poeltiana S. Y. Kondr., L. Lőkös, J. Halda et J.-S. Hur), two species from India (Rusavskia indica S. Y. Kondr. et D. K. Upreti, and R. upretii S. Y. Kondr., G. K. Mishra et S. Nayaka), and two species from Atlantic Europe, i.e.: Spain and Portugal (Xanthoria schummii S. Y. Kondr. and X. lapalmaensis F. Schumm et S. Y. Kondr.), as well as a lichenicolous fungus Leptosphaeria Oxneriae Cl. Roux et S. Y. Kondr. from Asia (Russia and India) are described, illustrated and compared with closely related taxa. Forty species of lichen forming and lichenicolous fungi (i.e.: Acarospora cf. rufescens, Agonimia allobata, A. aff. blumii, Anema decipiens, Anisomeridium aff. albisedum, Bacidia laurocerasi, Cercidospora aff. epipolytropa, C. aff. lobothallia, Dictyocatenulata alba, Fuscopannaria dissecta, Lecanora ussuriensis, Lecidella aff. carpatica, Lemmopsis arnoldiana, Leptosphaeria crozalsii, Lichenostigma cf. bolacinae, L. aff. rupicolae, Lichinella stipatula, L. cribellifera, L. iodopulchra, L. aff. myriospora, Melaspilea proximella, Micarea alabastrites, Opegrapha aff. thelotrematis, Orientophila leucerythrella, Pectenia plumbea, Placynthium tantaleum, Porpidia flavicunda, Psorula rufonigra, Pyrenocarpon aff. thelostomum, Pyrenodesmia duplicata, Pyrenopsis aff. haematina, Ramboldia haematites, Rhizoplaca subdiscrepans, Rimularia gibbosa, Rinodina oxydata, Staurothele frustulenta, Stigmidium cf. clauzadei, Strigula australiensis, Thelenella luridella, Vezdaea leprosa) are for the first time recorded for Korea. Additional locality records for South Korea (74 species) and China (3 species) are also given.

Four new combinations, i.e.: Orientophila chejuensis (for Caloplaca chejuensis S. Y. Kondr. et Hur), Orientophila diffluens (for Lecanora diffluens Hue), Orientophila leucerythrella (for Lecanora leucerythrella Nyl.), and Pyrenodesmia duplicata (for Lecanora duplicata Vain.) are also proposed.
Novel Therapeutic Strategies Targeting Molecular Pathways of Cystogenesis in Autosomal Polycystic Kidney Disease
Authors: Salvadori Maurizio , Tsalouchos Aris
Published: March 2017

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease that results from mutations in PKD1 or PKD2. The disease is characterized by the progressive development of fluid-filled cysts derived from renal tubular epithelial cells that destroy the architecture of the renal parenchyma and lead to kidney failure. Until recently, the causes and the molecular pathways that lead to cystogenesis remained obscure. In the last decade, enormous progress has been made in understanding the pathogenesis of ADPKD and the development of new therapies. The purpose of this review is to update on the promising therapies that are being developed and tested based on knowledge of recent advances in molecular and cellular targets involved in cystogenesis.
Influence of Duroc breed inclusion into Polish Landrace maternal line on pork meat quality traits
Authors: GUZEK DOMINIKA , GŁĄBSKA DOMINIKA , GŁĄBSKI KRZYSZTOF , WIERZBICKA AGNIESZKA
Published: March 2017

Crossbreeding with Duroc breed allows to improve meat quality, but no data is available regarding specific influence of Duroc breed on characteristics of meat in the case of crossbreeding with various breeds. The aim of the present research was to evaluate the effect of crossbreeding Polish Landrace dames with Duroc sires on quality features of meat in reference to Polish Landrace breed. The objects of the study were Longissimus dorsi lumborum pork muscles obtained from Polish Landrace breed and Polish Landrace x Duroc crossbreed animals. Sarcomere length measurements were conducted using microscopic method and basic chemical composition measurement was analyzed using spectrophotometric scanning. Texture analysis of meat samples, performed after thermal treatment was expressed by Warner-Bratzler shear force and color analysis was obtained using CIE L*a*b* color system. No differences in sarcomere length, shear force as well as components of color values between pork meat originated from Polish Landrace breed and Polish Landrace x Duroc crossbreed were observed. Analysis of basic chemical composition revealed higher fat and lower ash contents in the case of meat of Polish Landrace breed animals. It was concluded that the actual impact of breed on meat characteristics is possibly altered by other factors. It may be suggested that influence of basic chemical composition on color of meat is breed-related.