bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-life micro vacuum chamber for a micromachined cryogenic cooler
Authors: Cao Haishan , Vermeer Cristian H. , Vanapalli Srinivas , Holland Harry J. , ter Brake H. J. Marcel
Published: July 2015

Micromachined cryogenic coolers can be used for cooling small electronic devices to improve their performance. However, for reaching cryogenic temperatures, they require a very good thermal insulation from the warm environment. This is established by a vacuum space that for adequate insulation has to be maintained at a pressure of 0.01 Pa or lower. In this paper, the challenge of maintaining a vacuum chamber with a volume of 3.6 × 10−5 m3 and an inner wall area of 8.1 × 10−3 m2 at a pressure no higher than 0.01 Pa for five years is theoretically analyzed. The possible sources of gas, the mechanisms by which these gases enter the vacuum space and their effects on the pressure in the vacuum chamber are discussed. In a long-duration experiment with four stainless steel chambers of the above dimensions and equipped with a chemical getter, the vacuum pressures were monitored for a period of two years. In that period, the measured pressure increase stayed within 0.01 Pa. This study can be used to guide the design of long-lifetime micro vacuum chambers that operate without continuous mechanical pumping.
Hemispheric Asymmetry of Supplementary Motor Area Proper: A Functional Connectivity Study of the Motor Network
Authors: Dinomais Mickael , Chinier Eva , Richard Isabelle , Ricalens Emmanuel , Aubé Christophe , Tich Sylvie N’Guyen The , Minassian Aram Ter
Published: July 2015

Cerebral asymmetry is a common feature of human functions. However, there are discrepancies in the literature about functional hemispheric asymmetries in the supplementary motor area (SMA), specifically in the posterior part (SMA-proper). We used resting state functional connectivity MRI to investigate the left-right asymmetries of the functional networks associated with primary motor cortex (M1) and SMA-proper using a “seed”-based correlation analysis in 30 healthy right-handed subjects. We showed that left M1 was more connected with areas involved in the motor system than right M1, and that right SMA-proper had more functional connections than its left counterpart. Our results are in agreement with a leftward asymmetry for M1 connectivity, whereas there is a rightward asymmetry of the SMA-proper connectivity.
The Detection Continuum for Motor Control Comprises Preparation and Adjustments
Authors: Reichenbach Alexandra
Published: July 2015

Most studies investigating movement preparation report substantial longer reaction times than studies probing response times to adjust an ongoing movement. However, both behaviors constitute control processes that transform sensory information about the environment into motor commands. Smeets, Oostwoud Wijdenes, and Brenner (2016) base their review on the hypothesis of a qualitative difference between the two sensorimotor control processes. By ruling out that the three latter movement stages proposed by Donders (1969)—identification, selection, and execution—are responsible for the difference, they argue for a specific role of the detection stage. Specifically, they reason that the detection in (target) change is only necessary for movement initiation and thus constitutes the qualitative difference between the two behaviors. In contrast to this view, I will advocate that change detection is not a qualitatively discriminating feature between the two processes. Instead, the difference in response time might rather stem from different decision criteria (Wolpert & Landy, 2012) set on the detection threshold. This threshold is rather conservative for movement initiation and more relaxed for online adjustments. However, both are states on the same continuum. Thus, movement initiation and online adjustments might even not be qualitatively different at all.
Cross-Validation of Single-Stage Treadmill Tests for Predicting Aerobic Fitness in Adolescents With Type I Diabetes
Authors: Francis Shelby L. , Singhvi Ajay , Tsalikian Eva , Tansey Michael J. , Janz Kathleen F.
Published: July 2015

Purpose:

Determining fitness is important when assessing adolescents with type 1 diabetes mellitus (T1DM). Submaximal tests estimate fitness, but none have been validated in this population. This study cross-validates the Ebbeling and Nemeth equations to predict fitness (VO2max (ml/kg/min)) in adolescents with T1DM.

Methods:

Adolescents with T1DM (n = 20) completed a maximal treadmill test using indirect calorimetry. Participants completed one 4-min stage between 2.0 and 4.5 mph and 5% grade (Ebbeling/Nemeth protocol). Speed and grade were then increased until exhaustion. Predicted VO2max was calculated using the Ebbeling and Nemeth equations and compared with observed VO2max using paired t tests. Pearson correlation coefficients, 95% confidence intervals, coefficients of determination (R2), and total error (TE) were calculated.

Results:

The mean observed VO2max was 47.0 ml/kg/min (SD = 6.9); the Ebbeling and Nemeth mean predictions were 42.4 (SD = 9.4) and 43.5 ml/kg/min (SD = 6.9), respectively. Paired t tests resulted in statistically significant (p < .01) mean differences between observed and predicted VO2max for both predictions. The association between the Ebbeling prediction and observed VO2max was r = .90 (95% CI = 0.76, 0.96), R2 = .81, and TE = 6.5 ml/kg/min. The association between the Nemeth prediction and observed VO2max was r = .81 (95% CI = 0.57, 0.92), R2 = .66, and TE = 5.6 ml/kg/min.

Conclusion:

The Nemeth submaximal treadmill protocol provides a better estimate of fitness than the Ebbeling in adolescents with T1DM.
Cross-Validation of Aerobic Capacity Prediction Models in Adolescents
Authors: Burns Ryan D. , Hannon James C. , Brusseau Timothy A. , Eisenman Patricia A. , Saint-Maurice Pedro F. , Welk Greg J. , Mahar Matthew T.
Published: July 2015

Cardiorespiratory endurance is a component of health-related fitness. FITNESSGRAM recommends the Progressive Aerobic Cardiovascular Endurance Run (PACER) or One mile Run/Walk (1MRW) to assess cardiorespiratory endurance by estimating VO2 Peak. No research has cross-validated prediction models from both PACER and 1MRW, including the New PACER Model and PACER-Mile Equivalent (PACER-MEQ) using current standards. The purpose of this study was to cross-validate prediction models from PACER and 1MRW against measured VO2 Peak in adolescents. Cardiorespiratory endurance data were collected on 90 adolescents aged 13–16 years (Mean = 14.7 ± 1.3 years; 32 girls, 52 boys) who completed the PACER and 1MRW in addition to a laboratory maximal treadmill test to measure VO2 Peak. Multiple correlations among various models with measured VO2 Peak were considered moderately strong (R = .74–0.78), and prediction error (RMSE) ranged from 5.95 ml·kg-1, min-1 to 8.27 ml·kg-1.min-1. Criterion-referenced agreement into FITNESSGRAM’s Healthy Fitness Zones was considered fair-to-good among models (Kappa = 0.31–0.62; Agreement = 75.5–89.9%; F = 0.08–0.65). In conclusion, prediction models demonstrated moderately strong linear relationships with measured VO2 Peak, fair prediction error, and fair-to-good criterion referenced agreement with measured VO2 Peak into FITNESSGRAM’s Healthy Fitness Zones.
Perceived Teammate Acceptance and Sport Commitment in Adolescent Female Volleyball Players
Authors: Garn Alex
Published: July 2015

Grounded in Scanlan’s sport commitment model (SCM), the purpose of this study was to explore the relationship between feelings of teammate acceptance and sport commitment in a sample of adolescent female volleyball players (N = 209). Despite theoretical justification for including social forms of influence such as social support and social acceptance as direct sources of sport commitment, empirical evidence has not been supportive of this association. Therefore, direct and indirect relationships between teammate acceptance and sport commitment within the SCM were tested. Findings supported the indirect relationship between teammate acceptance and sport commitment through sport enjoyment, personal investments, social constraints, and investment opportunities, accounting for 48% of the variance in sport commitment. It appears that teammate acceptance may be better situated as a distal source of sport commitment, but further research with more diverse samples is necessary. Sports psychologists who can collectively help athletes, coaches, and parents develop responsive interpersonal skills while reducing corporal punishment and aggression tactics can facilitate greater levels of social acceptance.
Needs and Strengths of Australian Para-Athletes: Identifying Their Subjective Psychological, Social, and Physical Health and Well-Being
Authors: Macdougall Hannah , O’Halloran Paul , Sherry Emma , Shields Nora
Published: July 2015

The well-being needs and strengths of para-athletes in a global and sport-specific context were investigated across subjective psychological, social, and physical health and well-being dimensions. Data were drawn from (a) semistructured interviews with Australian para-athletes (n = 23), (b) a focus group with the Australian Paralympic Committee (n = 9), and (c) a confirmatory para-athlete focus group (n = 8). The well-being needs and strengths of para-athletes differed across gender, sport, level of competition, and nature of impairment. Well-being needs were an interaction between physical pain, emotional regulation, lacking purpose outside of sport, and a lack of self-acceptance, especially for athletes with acquired impairments. Well-being strengths were perceived to increase as athletes increased their level of competition, and included personal growth, optimism, strong social support networks, and contributing to multiple communities. The importance of well-being as a multidimensional concept within the global and sport-specific context for para-athletes is discussed.
Salicylic acid modulates colonization of the root microbiome by specific bacterial taxa
Authors: Lebeis Sarah L. , Paredes Sur Herrera , Lundberg Derek S. , Breakfield Natalie , Gehring Jase , McDonald Meredith , Malfatti Stephanie , Glavina del Rio Tijana , Jones Corbin D. , Tringe Susannah G. , Dangl Jeffery L.
Published: July 2015

Immune signals shape root communities

To thwart microbial pathogens aboveground, the plantArabidopsisturns on defensive signaling using salicylic acid. InArabidopsisplants with modified immune systems, Lebeiset al.show that bacterial communities change in response to salicylic acid signaling in the root zone as well (see the Perspective by Haney and Ausubel). Abundance of some root-colonizing bacterial families increased at the expense of others, partly as a function of whether salicylic acid was used as an immune signal or as a carbon source for microbial growth.

Science, this issue p.860; see also p.788
Draft Genome Sequence of a Fluconazole-Resistant
Candida auris
Strain from a Candidemia Patient in India
Authors: Sharma Cheshta , Kumar Nitin , Meis Jacques F. , Pandey Rajesh , Chowdhary Anuradha
Published: July 2015

Candida auris
is a multidrug-resistant yeast incriminated in a wide spectrum of invasive infections, especially in intensive care settings. The first draft genome sequence of
C. auris
, VPCI 479/P/13, from a case with fungemia was sequenced using the Illumina MiSeq platform. The estimated genome size is 12.3 Mb, with 6,675 coding sequences.
Complete Genome Sequences of Four Novel Escherichia coli Bacteriophages Belonging to New Phage Groups
Authors: Carstens Alexander B. , Kot Witold , Hansen Lars H.
Published: July 2015

Here, we describe the sequencing and genome annotations of a set of four
Escherichia coli
bacteriophages (phages) belonging to newly discovered groups previously consisting of only a single phage and thus expand our knowledge of these phage groups.
Complete Genome Sequence of Corynebacterium pseudotuberculosis Strain 12C
Authors: Sousa Thiago Jesus , Mariano Diego , Parise Doglas , Parise Mariana , Viana Marcus Vinicius Canário , Guimarães Luis Carlos , Benevides Leandro Jesus , Rocha Flávia , Bagano Priscilla , Ramos Rommel , Silva Artur , Figueiredo Henrique , Almeida Sintia , Azevedo Vasco
Published: July 2015

We present here the complete genome sequence of
Corynebacterium pseudotuberculosis
strain 12C, isolated from a sheep abscess in the Brazil. The sequencing was performed with the Ion Torrent Personal Genome Machine (PGM) system, a fragment library, and a coverage of ~48-fold. The genome presented is a circular chromosome with 2,337,451 bp in length, 2,119 coding sequences, 12 rRNAs, 49 tRNAs, and a G+C content of 52.83%.
Genome Sequence of the Urethral Isolate Pseudomonas aeruginosa RN21
Authors: Wibberg Daniel , Tielen Petra , Narten Maike , Schobert Max , Blom Jochen , Schatschneider Sarah , Meyer Ann-Kathrin , Neubauer Rüdiger , Albersmeier Andreas , Albaum Stefan , Jahn Martina , Goesmann Alexander , Vorhölter Frank-Jörg , Pühler Alfred , Jahn Dieter
Published: July 2015

Pseudomonas aeruginosa
is known to cause complicated urinary tract infections (UTI). The improved 7.0-Mb draft genome sequence of
P. aeruginosa
RN21, isolated from a patient with an acute UTI, was determined. It carries three (pro)phage genomes, genes for two restriction/modification systems, and a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system.
Complete Genome Sequence of Chikungunya Virus Isolated from an Aedes aegypti Mosquito during an Outbreak in Yemen, 2011
Authors: Fahmy Nermeen T. , Klena John D. , Mohamed Amr S. , Zayed Alia , Villinski Jeffrey T.
Published: July 2015

Chikungunya virus is recognized as a serious public health problem. The complete genome was sequenced for a chikungunya virus isolated from the mosquito
Aedes aegypti
during a 2011 outbreak in Al Hodayda, Yemen, which resulted in significant human fatalities. Phylogenetic analysis demonstrated that this Yemeni isolate is most closely related to Indian Ocean strains of the east/central/south African genotype.
Genome Sequence of
Halomonas
sp. Strain MCTG39a, a Hydrocarbon-Degrading and Exopolymeric Substance-Producing Bacterium
Authors: Gutierrez Tony , Whitman William B. , Huntemann Marcel , Copeland Alex , Chen Amy , Kyrpides Nikos , Markowitz Victor , Pillay Manoj , Ivanova Natalia , Mikhailova Natalia , Ovchinnikova Galina , Andersen Evan , Pati Amrita , Stamatis Dimitrios , Reddy T. B. K. , Ngan Chew Yee , Chovatia Mansi , Daum Chris , Shapiro Nicole , Cantor Michael N. , Woyke Tanja
Published: July 2015

Halomonas
sp. strain MCTG39a was isolated from coastal sea surface water based on its ability to utilize
n
-hexadecane. During growth in marine medium the strain produces an amphiphilic exopolymeric substance (EPS) amended with glucose, which emulsifies a variety of oil hydrocarbon substrates. Here, we present the genome sequence of this strain, which is 4,979,193 bp with 4,614 genes and an average G+C content of 55.0%.
First Complete Genome Sequences of Staphylococcus aureus subsp.
aureus
Rosenbach 1884 (DSM 20231
T
), Determined by PacBio Single-Molecule Real-Time Technology
Authors: Shiroma Akino , Terabayashi Yasunobu , Nakano Kazuma , Shimoji Makiko , Tamotsu Hinako , Ashimine Noriko , Ohki Shun , Shinzato Misuzu , Teruya Kuniko , Satou Kazuhito , Hirano Takashi
Published: July 2015

The first complete genome sequences of
Staphylococcus aureus
subsp.
aureus
Rosenbach 1884 strain DSM 20231
T
, the type strain of the bacterium causing staphylococcal disease, were determined using PacBio RS II. The sequences represent the chromosome (2,755,072 bp long; G+C content, 32.86%) and a plasmid (27,490 bp long; G+C content, 30.69%).
An unusual case of KBG syndrome with unique oral findings
Authors: Hafiz Abdul , Mufeed Abdulla , Ismael Mohamad , Alam Mheboob
Published: July 2015

KBG syndrome is a condition characterised by macrodontia, neurological disturbance, short stature, a distinct cranio-facial appearance, and skeletal anomalies. The authors describe what appears to be the first case of KBG syndrome reported from the Indian subcontinent. Meticulous evaluation of the dental findings helps to identify such cases which may otherwise remain undiagnosed. Further research is warranted to determine the classic and variant presentations of this condition, with follow-up data providing valuable insights into its natural history and long-term prognosis.
Sociodemographic and health behavioural factors associated with access to and utilisation of eye care in Korea: Korea Health and Nutrition Examination Survey 2008–2012
Authors: Rim Tyler Hyungtaek , Choi Moonjung , Yoon Jin Sook , Kim Sung Soo
Published: July 2015

Objective

To determine the sociodemographic and health behavioural factors associated with access to and utilisation of eye care in Korea.

Design

Nationwide cross-sectional study

Methods

25 752 Koreans over the age of 30 were assessed from a national representative survey. We analysed independent variables of self-reporting eye clinic visits through multivariable analyses of sociodemographic factors. The time since the last visit to an eye clinic was used to assess access to and utilisation of eye care.

Results

Of the 25 752 respondents, 8237 (32.0%) visited an eye clinic in the past year, 11 028 (42.8%) were seen more than 1 year ago, while 6487 (25.2%) had never seen an ophthalmologist. Eye clinic utilisation was statistically associated with older age, female sex, higher household income, higher education levels, living in an urban area, and having comorbidities including diabetes and hypertension. Middle-aged men between 30 and 49 years were found to be less likely to receive eye care compared to the rest of the population, and the proportion that did plummeted after the financial crisis of 2007.

Conclusions

There is a substantial sociodemographic disparity in eye care utilisation in Korea, and men with low financial income and education level are especially at risk. Use of eye care among middle-aged men has decreased since the global financial crisis that began in 2007, and therefore healthcare policies and public interventions should be targeted at vulnerable groups to promote access to medical care.
Reducing the incidence of oxyhaemoglobin desaturation during rapid sequence intubation in a paediatric emergency department
Authors: Kerrey Benjamin T , Mittiga Matthew R , Rinderknecht Andrea S , Varadarajan Kartik R , Dyas Jenna R , Geis Gary Lee , Luria Joseph W , Frey Mary E , Jablonski Tamara E , Iyer Srikant B
Published: July 2015

Objectives

Rapid sequence intubation (RSI) is the standard for definitive airway management in emergency medicine. In a video-based study of RSI in a paediatric emergency department (ED), we reported a high degree of process variation and frequent adverse effects, including oxyhaemoglobin desaturation (SpO2<90%). This report describes a multidisciplinary initiative to improve the performance and safety of RSI in a paediatric ED.

Methods

We conducted a local improvement initiative in a high-volume academic paediatric ED. We simultaneously tested: (1) an RSI checklist, (2) a pilot/copilot model for checklist execution, (3) the use of a video laryngoscope and (4) the restriction of laryngoscopy to specific providers. Data were collected primarily by video review during the testing period and the historical period (2009–2010, baseline). We generated statistical process control charts (G-charts) to measure change in the performance of six key processes, attempt failure and the occurrence of oxyhaemoglobin desaturation during RSI. We iteratively revised the four interventions through multiple plan-do-study-act cycles within the Model for Improvement.

Results

There were 75 cases of RSI during the testing period (July 2012–September 2013). Special cause variation occurred on the G-charts for three of six key processes, attempt failure and desaturation, indicating significant improvement. The frequency of desaturation was 50% lower in the testing period than the historical (16% vs 33%). When all six key processes were performed, only 6% of patients experienced desaturation.

Conclusions

Following the simultaneous introduction of four interventions in a paediatric ED, RSI was performed more reliably, successfully and safely.
Living actively in the face of impending death: constantly adjusting to bodily decline at the end-of-life
Authors: Morgan Deidre D , Currow David C , Denehy Linda , Aranda Sanchia A
Published: July 2015

Context

People with advanced cancer experience bodily change resulting in debilitating functional decline. Although inability to participate in everyday activities (occupation) contributes to profound suffering, limited research has examined the relationship between altered bodily experience (embodiment) and functional ability.

Objectives

The purpose of this study was to better understand the lived experience of functional decline for people with advanced cancer living at home.

Methods

Indepth interviews were conducted with 10 community dwelling people with advanced cancer about their bodily experiences of functional decline. This study employed a pragmatic qualitative approach, informed by hermeneutic phenomenology.

Results

People described living with rapidly disintegrating bodies and how this affected their ability to participate in everyday activities. Analysis identified themes which were evaluated against conceptual frameworks of ‘occupation’ and ‘embodiment’. People experienced a shifting sense of self. They had to continuously reinterpret changing bodies. Previously automatic movements became disjointed and effortful. Simple actions like standing or getting out of bed required increasing concentration. Relentless bodily breakdown disrupted peoples’ relationship with time, hindering their ability, but not their desire, to participate in everyday activities. Contending with this deterioration is the work of adaptation to functional decline at the end-of-life.

Conclusions

This study highlights the role active participation in everyday activities plays in mediating adjustment to functional decline. These findings challenge us to look beyond palliation of physical symptoms and psychospiritual care as ends in themselves. Symptom control and palliation should be viewed as mechanisms to optimise active participation in essential and valued activities.
Evaluation of promoter hypomethylation and expression ofp73as a diagnostic and prognostic biomarker in Wilms’ tumour
Authors: Song Dongjian , Yue Lifang , Wu Gang , Ma Shanshan , Yang Heying , Liu Qiuliang , Zhang Da , Xia Ziqiang , Jia Jia , Wang Jiaxiang
Published: July 2015

Aims

A member of the p53 family, thep73gene is essential for the maintenance of genomic stability, DNA repair and apoptosis regulation. This study was designed to evaluate the utility of expression and DNA methylation patterns of thep73gene in the early diagnosis and prognosis of Wilms’ tumour (WT).

Methods

Methylation-specific PCR, semi-quantitative (sq-PCR), real-time quantitative PCR (qRT–PCR), receiver operating characteristic (ROC), and survival and hazard function curve analyses were utilised to measure the expression and DNA methylation patterns ofp73in WT tissue samples with a view to assessing diagnostic and prognostic value.

Results

The relative expression ofp73mRNA was higher, while the promoter methylation level was lower in the WT than the control group (p<0.05) and closely associated with poor survival prognosis in children with WT (p<0.05). Increased expression and decreased methylation ofp73were correlated with increasing tumour size, clinical stage and unfavourable histological differentiation (p<0.05). ROC curve analysis showed areas under the curve of 0.544 for methylation and 0.939 for expression in WT venous blood, indicating the higher diagnostic yield of preoperativep73expression.

Conclusions

Preoperative venous bloodp73level serves as an underlying biomarker for the early diagnosis of WT.p73overexpression and concomitantly decreased promoter methylation are significantly associated with poor survival in children with WT.
Auscultating heart and breath sounds through patients’ gowns: who does this and does it matter?
Authors: Rankin Alastair J , Rankin Stephen H , Rankin Andrew C
Published: July 2015

Background

Doctors are taught to auscultate with the stethoscope applied to the skin, but in practice may be seen applying the stethoscope to the gown.

Objectives

To determine how often doctors auscultate heart and breath sounds through patients’ gowns, and to assess the impact of this approach on the quality of the sounds heard.

Methods

A sample of doctors in the west of Scotland were sent an email in 2014 inviting them to answer an anonymous questionnaire about how they auscultated heart and breath sounds. Normal heart sounds from two subjects were recorded through skin, through skin and gown, and through skin, gown and dressing gown. These were played to doctors, unaware of the origin of each recording, who completed a questionnaire about the method and quality of the sounds they heard.

Results

206 of 445 (46%) doctors completed the questionnaire. 124 (60%) stated that they listened to patients’ heart sounds, and 156 (76%) to patients’ breath sounds, through patients’ gowns. Trainees were more likely to do this compared with consultants (OR 3.39, 95% CI 1.74 to 6.65). Doctors of all grades considered this practice affected the quality of the sounds heard. 32 doctors listened to the recorded heart sounds. 23 of the 64 (36%) skin and 23 of the 64 (36%) gown recordings were identified. The majority of doctors (74%) could not differentiate between skin or gown recordings, but could tell them apart from the double layer recordings (p=0.02). Trainees were more likely to hear artefactual added sounds (p=0.04).

Conclusions

Many doctors listen to patients’ heart and breath sounds through hospital gowns, at least occasionally. In a short test, most doctors could not distinguish between sounds heard through a gown or skin. Further work is needed to determine the impact of this approach to auscultation on the identification of murmurs and added sounds.
Effective Social Graph Deanonymization Based on Graph Structure and Descriptive Information
Authors: Fu Hao , Zhang Aston , Xie Xing
Published: July 2015

The study of online social networks has attracted increasing interest. However, concerns are raised for the privacy risks of user data since they have been frequently shared among researchers, advertisers, and application developers. To solve this problem, a number of anonymization algorithms have been recently developed for protecting the privacy of social graphs. In this article, we proposed a graph node similarity measurement in consideration with both graph structure and descriptive information, and a deanonymization algorithm based on the measurement. Using the proposed algorithm, we evaluated the privacy risks of several typical anonymization algorithms on social graphs with thousands of nodes from Microsoft Academic Search, LiveJournal, and the Enron email dataset, and a social graph with millions of nodes from Tencent Weibo. Our results showed that the proposed algorithm was efficient and effective to deanonymize social graphs without any initial seed mappings. Based on the experiments, we also pointed out suggestions on how to better maintain the data utility while preserving privacy.
Online Planning for Large Markov Decision Processes with Hierarchical Decomposition
Authors: Bai Aijun , Wu Feng , Chen Xiaoping
Published: July 2015

Markov decision processes (MDPs) provide a rich framework for planning under uncertainty. However, exactly solving a large MDP is usually intractable due to the “curse of dimensionality”— the state space grows exponentially with the number of state variables. Online algorithms tackle this problem by avoiding computing a policy for the entire state space. On the other hand, since online algorithm has to find a near-optimal action online in almost real time, the computation time is often very limited. In the context of reinforcement learning, MAXQ is a value function decomposition method that exploits the underlying structure of the original MDP and decomposes it into a combination of smaller subproblems arranged over a task hierarchy. In this article, we present MAXQ-OP—a novel online planning algorithm for large MDPs that utilizes MAXQ hierarchical decomposition in online settings. Compared to traditional online planning algorithms, MAXQ-OP is able to reach much more deeper states in the search tree with relatively less computation time by exploiting MAXQ hierarchical decomposition online. We empirically evaluate our algorithm in the standard Taxi domain—a common benchmark for MDPs—to show the effectiveness of our approach. We have also conducted a long-term case study in a highly complex simulated soccer domain and developed a team named WrightEagle that has won five world champions and five runners-up in the recent 10 years of RoboCup Soccer Simulation 2D annual competitions. The results in the RoboCup domain confirm the scalability of MAXQ-OP to very large domains.
From Small Space to Small Width in Resolution
Authors: Filmus Yuval , Lauria Massimo , Mikša Mladen , Nordström Jakob , Vinyals Marc
Published: July 2015

In 2003, Atserias and Dalmau resolved a major open question about the resolution proof system by establishing that the space complexity of a Conjunctive Normal Form (CNF) formula is always an upper bound on the width needed to refute the formula. Their proof is beautiful but uses a nonconstructive argument based on Ehrenfeucht-Fraïssé games. We give an alternative, more explicit, proof that works by simple syntactic manipulations of resolution refutations. As a by-product, we develop a “black-box” technique for proving space lower bounds via a “static” complexity measure that works against any resolution refutation—previous techniques have been inherently adaptive. We conclude by showing that the related question for polynomial calculus (i.e., whether space is an upper bound on degree) seems unlikely to be resolvable by similar methods.
Dynamic Maintenance of a Shortest-Path Tree on Homogeneous Batches of Updates
Authors: D'Andrea Annalisa , D'Emidio Mattia , Frigioni Daniele , Leucci Stefano , Proietti Guido
Published: July 2015

A dynamic graph algorithm is called
batch
if it is able to update efficiently the solution of a given graph problem after
multiple
updates at a time (i.e., a batch) take place on the input graph. In this article, we study batch algorithms for maintaining a
single-source shortest-path tree
in graphs with positive real edge weights. In particular, we focus our attention on
homogeneous
batches, that is, either
incremental
(containing only edge insertion and weight decrease operations) or
decremental
(containing only edge deletion and weight increase operations) batches, which model realistic dynamic scenarios like transient vertex failures in communication networks and traffic congestion/decongestion phenomena in road networks.

We propose two new algorithms to process either incremental or decremental batches, respectively, and a combination of these two algorithms that is able to process arbitrary sequences of incremental and decremental batches. All these algorithms are
update sensitive
; namely, they are efficient with respect to the number of vertices in the shortest-path tree that change their parents and/or their distances from the source as a consequence of a batch. This makes unfeasible an effective comparison on a theoretical basis of our new algorithms with the solutions known in the literature, which in turn are analyzed with respect to others and different parameters. For this reason, in order to evaluate the quality of our approach, we provide also an extensive experimental study including our new algorithms and the most efficient previous batch algorithms. Our experimental results complement previous studies and show that the various solutions can be consistently ranked on the basis of the type of homogeneous batch and of the underlying network. As a result, our work can be helpful in selecting a proper solution depending on the specific application scenario.
Workshop on Internet economics (WIE2014) Report
Authors: claffy kc , Clark David D.
Published: July 2015

On December 10-11 2014, we hosted the 4th interdisciplinary Workshop on Internet Economics (WIE) at the UC San Diego's Supercomputer Center. This workshop series provides a forum for researchers, Internet facilities and service providers, technologists, economists, theorists, policy makers, and other stakeholders to inform current and emerging regulatory and policy debates. The objective for this year's workshop was a structured consideration of whether and how policy-makers should try to shape the future of the Internet. To structure the discussion about policy, we began the workshop with a list of potential aspirations for our future telecommunications infrastructure (a list we had previously collated), and asked participants to articulate an aspiration or fear they had about the future of the Internet, which we summarized and discussed on the second day. The focus on aspirations was motivated by the high-level observation that before discussing regulation, we must agree on the objective of the regulation, and why the intended outcome is justified. In parallel, we used a similar format as in previous years: a series of focused sessions, where 3-4 presenters each prepared 10-minute talks on issues in recent regulatory discourse, followed by in-depth discussions. This report highlights the discussions and presents relevant open research questions identified by participants. Slides presented and a copy of this report are available at http://www.caida.org/workshops/wie/1412/.
Dietary Fatty Acids and Their Potential for Controlling Metabolic Diseases Through Activation of FFA4/GPR120
Authors: Ulven Trond , Christiansen Elisabeth
Published: July 2015

It is well known that the amount and type of ingested fat impacts the development of obesity and metabolic diseases, but the potential for beneficial effects from fat has received less attention. It is becoming clear that the composition of the individual fatty acids in diet is important. Besides acting as precursors of potent signaling molecules, dietary fatty acids act directly on intracellular and cell surface receptors. The free fatty acid receptor 4 (FFA4, previously GPR120) is linked to the regulation of body weight, inflammation, and insulin resistance and represents a potential target for the treatment of metabolic disorders, including type 2 diabetes and obesity. In this review, we discuss the various types of dietary fatty acids, the link between FFA4 and metabolic diseases, the potential effects of the individual fatty acids on health, and the ability of fatty acids to activate FFA4. We also discuss the possibility of dietary schemes that implement activation of FFA4.
Adaptation of iron requirement to hypoxic conditions at high altitude
Authors: Gassmann Max , Muckenthaler Martina U.
Published: July 2015

Adequate acclimatization time to enable adjustment to hypoxic conditions is one of the most important aspects for mountaineers ascending to high altitude. Accordingly, most reviews emphasize mechanisms that cope with reduced oxygen supply. However, during sojourns to high altitude adjustment to elevated iron demand is equally critical. Thus in this review we focus on the interaction between oxygen and iron homeostasis. We review the role of iron 1) in the oxygen sensing process and erythropoietin (Epo) synthesis, 2) in gene expression control mediated by the hypoxia-inducible factor-2 (HIF-2), and 3) as an oxygen carrier in hemoglobin, myoglobin, and cytochromes. The blood hormone Epo that is abundantly expressed by the kidney under hypoxic conditions stimulates erythropoiesis in the bone marrow, a process requiring high iron levels. To ensure that sufficient iron is provided, Epo-controlled erythroferrone that is expressed in erythroid precursor cells acts in the liver to reduce expression of the iron hormone hepcidin. Consequently, suppression of hepcidin allows for elevated iron release from storage organs and enhanced absorption of dietary iron by enterocytes. As recently observed in sojourners at high altitude, however, iron uptake may be hampered by reduced appetite and gastrointestinal bleeding. Reduced iron availability, as observed in a hypoxic mountaineer, enhances hypoxia-induced pulmonary hypertension and may contribute to other hypoxia-related diseases. Overall, adequate systemic iron availability is an important prerequisite to adjust to high-altitude hypoxia and may have additional implications for disease-related hypoxic conditions.
Myocardial hypertrophy and its role in heart failure with preserved ejection fraction
Authors: Heinzel Frank R. , Hohendanner Felix , Jin Ge , Sedej Simon , Edelmann Frank
Published: July 2015

Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is driven by neurohumoral activation, increased mechanical load, and cytokines associated with arterial hypertension, chronic kidney disease, diabetes, and other comorbidities. Here we discuss the experimental and clinical evidence that links LVH to diastolic dysfunction and qualifies LVH as one diagnostic marker for HFpEF. Mechanisms leading to diastolic dysfunction in LVH are incompletely understood, but may include extracellular matrix changes, vascular dysfunction, as well as altered cardiomyocyte mechano-elastical properties. Beating cardiomyocytes from HFpEF patients have not yet been studied, but we and others have shown increased Ca2+ turnover and impaired relaxation in cardiomyocytes from hypertrophied hearts. Structural myocardial remodeling can lead to heterogeneity in regional myocardial contractile function, which contributes to diastolic dysfunction in HFpEF. In the clinical setting of patients with compound comorbidities, diastolic dysfunction may occur independently of LVH. This may be one explanation why current approaches to reduce LVH have not been effective to improve symptoms and prognosis in HFpEF. Exercise training, on the other hand, in clinical trials improved exercise tolerance and diastolic function, but did not reduce LVH. Thus current clinical evidence does not support regression of LVH as a surrogate marker for (short-term) improvement of HFpEF.
Implication of a Chromosome 15q15.2 Locus in Regulating UBR1 and Predisposing Smokers to MGMT Methylation in Lung
Authors: Leng Shuguang , Wu Guodong , Collins Leonard B. , Thomas Cynthia L. , Tellez Carmen S. , Jauregui Andrew R. , Picchi Maria A. , Zhang Xiequn , Juri Daniel E. , Desai Dhimant , Amin Shantu G. , Crowell Richard E. , Stidley Christine A. , Liu Yushi , Swenberg James A. , Lin Yong , Wathelet Marc G. , Gilliland Frank D. , Belinsky Steven A.
Published: July 2015

O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that protects cells from carcinogenic effects of alkylating agents; however, MGMT is silenced by promoter hypermethylation during carcinogenesis. A single-nucleotide polymorphism (SNP) in an enhancer in the MGMT promoter was previously identified to be highly significantly associated with risk for MGMT methylation in lung cancer and sputum from smokers. To further genetic investigations, a genome-wide association and replication study was conducted in two smoker cohorts to identify novel loci for MGMT methylation in sputum that were independent of the MGMT enhancer polymorphism. Two novel trans-acting loci (15q15.2 and 17q24.3) that were identified acted together with the enhancer SNP to empower risk prediction for MGMT methylation. We found that the predisposition to MGMT methylation arising from the 15q15.2 locus involved regulation of the ubiquitin protein ligase E3 component UBR1. UBR1 attenuation reduced turnover of MGMT protein and increased repair of O6-methylguanine in nitrosomethylurea-treated human bronchial epithelial cells, while also reducing MGMT promoter activity and abolishing MGMT induction. Overall, our results substantiate reduced gene transcription as a major mechanism for predisposition to MGMT methylation in the lungs of smokers, and support the importance of UBR1 in regulating MGMT homeostasis and DNA repair of alkylated DNA adducts in cells. Cancer Res; 75(15); 3108–17. ©2015 AACR.
Nicotine Induces Tumor Growth and Chemoresistance through Activation of the PI3K/Akt/mTOR Pathway in Bladder Cancer
Authors: Yuge Kazuyuki , Kikuchi Eiji , Hagiwara Masayuki , Yasumizu Yota , Tanaka Nobuyuki , Kosaka Takeo , Miyajima Akira , Oya Mototsugu
Published: July 2015

Continued smoking is highly associated with not only a higher incidence but also greater risk of tumor recurrence, progression, and acquired chemoresistance of urothelial carcinoma. We investigated whether nicotine affects urothelial carcinoma, and the detailed mechanism by which nicotine could induce tumor growth and any associated chemoresistance. Cell viability was evaluated in the human bladder cancer cell line T24 exposed to nicotine with or without cisplatin (CDDP) and NVP-BEZ235 as a PI3K/mTOR dual inhibitor by the WST-1 assay. Protein expression of the PI3K/Akt/mTOR pathway was investigated by Western blotting or immunohistochemical analysis. The influence of nicotine on tumor growth was also evaluated with or without CDDP and/or NVP-BEZ235 in a subcutaneous bladder tumor model. The result demonstrated that cell proliferation was increased in T24 cells after exposure to nicotine. Phospho-specific Akt (pAkt) and phospho-specific p70 S6 kinase (pS6) were significantly upregulated by nicotine exposure. Tumor growth in vivo was significantly induced by nicotine exposure in accordance with increased pS6 expression. Nicotine attenuated inhibition of T24 cell growth by CDDP and further upregulated pS6 expression in vitro and in vivo. NVP-BZE235 inhibited T24 cell proliferation and pAkt and pS6 expression induced after exposure to nicotine and/or CDDP. In conclusion, nicotine increases tumor growth and induces acquired chemoresistance through activation of the PI3K/Akt/mTOR pathway in bladder cancer. Mol Cancer Ther; 14(9); 2112–20. ©2015 AACR.
Anti-Endosialin Antibody–Drug Conjugate: Potential in Sarcoma and Other Malignancies
Authors: Rouleau Cecile , Gianolio Diego A. , Smale Robert , Roth Stephanie D. , Krumbholz Roy , Harper Jay , Munroe Kenneth J. , Green Tessa L. , Horten Bruce C. , Schmid Steven M. , Teicher Beverly A.
Published: July 2015

Endosialin/TEM1/CD248 is a cell surface protein expressed at high levels by the malignant cells of about 50% of sarcomas and neuroblastomas. The antibody–drug conjugate (ADC) anti-endosialin-MC-VC-PABC-MMAE was selectively cytotoxic to endosialin-positive cells in vitro and achieved profound and durable antitumor efficacy in preclinical human tumor xenograft models of endosialin-positive disease. MC-VC-PABC-MMAE was conjugated with anti-endosialin with 3–4 MMAE molecules per ADC. The anti-endosialin-MC-VC-PABC-MMAE conjugate was tested for activity in four human cell lines with varied endosialin levels. The HT-1080 fibrosarcoma cells do not express endosialin, A-673 Ewing sarcoma cells and SK-N-AS neuroblastoma cells are moderate expressers of endosialin, and SJSA-1 osteosarcoma cells express very high levels of endosialin. To determine whether endosialin expression was maintained in vivo, A-673 Ewing sarcoma, SK-N-AS neuroblastoma, and SJSA-1 osteosarcoma cells were grown as xenograft tumors in nude mice. The SK-N-AS neuroblastoma and the A-673 Ewing sarcoma lines were selected for in vivo efficacy testing of the anti-endosialin-MC-VC-PABC-MMAE conjugate. The treatment groups included a vehicle control, unconjugated anti-endosialin, an admix control consisting of anti-endosialin and a dose of free MMAE equivalent to the dose administered as the ADC, and the anti-endosialin-MC-VC-PABC-MMAE conjugate. The unconjugated anti-endosialin had no antitumor activity and resulted in similar tumor growth as the vehicle control. The admix control produced a modest tumor growth delay. Administration of the anti-endosialin-MC-VC-PABC-MMAE conjugate resulted in a marked prolonged tumor response of both xenograts. These proof-of-concept results break new ground and open a promising drug discovery approach to these rare and neglected tumors. Mol Cancer Ther; 14(9); 2081–9. ©2015 AACR.
CDKN2B Loss Promotes Progression from Benign Melanocytic Nevus to Melanoma
Authors: McNeal Andrew S. , Liu Kevin , Nakhate Vihang , Natale Christopher A. , Duperret Elizabeth K. , Capell Brian C. , Dentchev Tzvete , Berger Shelley L. , Herlyn Meenhard , Seykora John T. , Ridky Todd W.
Published: July 2015

Deletion of the entire CDKN2B–CDKN2A gene cluster is among the most common genetic events in cancer. The tumor-promoting effects are generally attributed to loss of CDKN2A-encoded p16 and p14ARF tumor suppressors. The degree to which the associated CDKN2B-encoded p15 loss contributes to human tumorigenesis is unclear. Here, we show that CDKN2B is highly upregulated in benign melanocytic nevi, contributes to maintaining nevus melanocytes in a growth-arrested premalignant state, and is commonly lost in melanoma. Using primary melanocytes isolated directly from freshly excised human nevi naturally expressing the common BRAFV600E-activating mutation, nevi progressing to melanoma, and normal melanocytes engineered to inducibly express BRAFV600E, we show that BRAF activation results in reversible, TGFβ-dependent, p15 induction that halts proliferation. Furthermore, we engineer human skin grafts containing nevus-derived melanocytes to establish a new, architecturally faithful, in vivo melanoma model, and demonstrate that p15 loss promotes the transition from benign nevus to melanoma.

Significance: Although BRAFV600E mutations cause melanocytes to initially proliferate into benign moles, mechanisms responsible for their eventual growth arrest are unknown. Using melanocytes from human moles, we show that BRAF activation leads to a CDKN2B induction that is critical for restraining BRAF oncogenic effects, and when lost, contributes to melanoma. Cancer Discov; 5(10); 1072–85. ©2015 AACR.

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A National Survey of Traumatic Brain Injuries Admitted to Hospitals in Sweden from 1987 to 2010
Authors: Pedersen Kyrre , Fahlstedt Madelen , Jacobsson Anders , Kleiven Svein , von Holst Hans
Published: July 2015

Background: With an increasing and aging population, there is a global demand for improving the primary prevention strategies aimed at reducing traumatic brain injuries (TBIs). The objective of the present epidemiological study was to evaluate the pattern of TBI in Sweden over a 24 years period (1987-2010). Methods: The Swedish Hospital Discharge Register was used, where in-patient care with a main diagnosis of TBI according to ICD9/10 was included. External factors, age and gender distribution was evaluated. Results: A decreasing number of annual incidence was observed, that is, from 230 to 156 per 100,000 inhabitants. A steady decrease of concussion was observed while other intracranial injuries increased especially traumatic subdural hemorrhage and subarachnoid hemorrhage. The study identified 3 groups of patients - young, adults and elderly. The highest incidence and the largest increase of incidence were seen in the oldest age group (85+ years) while the population under 65 years had a decreasing incidence of TBI. The most frequent etiology was fall accidents (57%) with a relative constant trend over the study period. Conclusions: More effort should be focused on different strategies for different age groups, especially the elderly group. A well-planned strategy for primary prevention guidelines for different age groups will have the chance to further reduce not only the health-care costs but also complications among elderly care.