bluuebunny/crossref_metadata_2025 huggingface dataset:
A espiritualidade estético-erótica de Rubem Alves
Authors: Caldas Carlos
Published: July 2018

Espiritualidade, entendida como busca do transcendente e vivência pessoal do que se constitui no objeto da fé, é fundamental em qualquer manifestação religiosa. No caso do cristianismo, em todos os seus principais ramos (Catolicismo Romano, Ortodoxia Oriental e Protestantismo), a espiritualidade tem importância que dificilmente poderá ser exagerada. Rubem Alves (1933-2014), um dos mais complexos e criativos pensadores que o protestantismo brasileiro produziu, inovou por completo a compreensão da espiritualidade, entendendo-a a partir de uma perspectiva erótica, isto é, do prazer, e pela experiência da estesia – estética. O presente artigo pretende apresentar alguns elementos desta compreensão alvesiana de espiritualidade.
Essere, storia e misericordia: l’oikonomia nella discussione tra Gregorio di Nissa e Eunomio
Authors: Maspero Giulio , Solano Pinzón Orlando
Published: July 2018

Lo studio percorre gli usi del termine oikonomia e dei suoi derivati nelle opere di Gregorio di Nissa dedicate alla discussione con Eunomio. La prospettiva analitica permette di ricostruire teologicamente la valenza ontologica della misericordia dalla prospettiva del rapporto tra essere e storia. L’attualità costante del pensiero cristiano può, infatti, essere rinvenuta nella dimensione trinitaria del Dio cristiano, che in quanto caratterizzato da una relazionalità immanente si rivela come relazione nel Filiazione del Verbo che si fa carne, in modo tale da riversare nella storia stessa la propria vita. L’uso di oikonomia è, dunque, legato all’ontologia trinitaria del Nisseno.
Jean-Luc Marion y la teología.
Authors: Vinolo Stéphane
Published: July 2018

La fenomenología de Jean-Luc Marion ha tenido un impacto mayor sobre la teología contemporánea. Más allá de la simple reconfiguración de los objetos tradicionales de la teología y de la manera según la cual podemos pensarlos, la obra de Marion nos impone repensar el mismo discurso de la teología, redefiniéndola en su relación con la filosofía y la metafísica constituida en onto-teo-logía. Al oponer la teología como discurso “sobre Dios” a la teología como discurso “a Dios”, se muestra que Marion supera esta oposición pensando la teología –con Pascal– como un discurso racional que se declara desde el punto de vista del amor.
Effects of slow highly charged ion irradiation on metal oxide semiconductor capacitors
Authors: Cutshall Daniel B. , Kulkarni Dhruva D. , Harriss James E. , Field Daniel A. , Sosolik Chad E. , Harrell William R.
Published: July 2018

Measurements were performed to characterize and better understand the effects of slow highly charged ion (HCI) irradiation, a relatively unexplored form of radiation, on metal oxide semiconductor (MOS) devices. Si samples with 50 nm SiO2 layers were irradiated with ion beams of ArQ+ (Q = 4, 8, and 11) at normal incidence. The effects of the irradiation were encapsulated with an array of Al contacts forming the MOS structure. High frequency capacitance–voltage (CV) measurements reveal that the HCI irradiation results in stretchout and shifting of the CV curve. These changes in the CV curve are attributed to dangling Si bond defects at the Si/SiO2 interface and trapped positive charge in the oxide, respectively. Charge state dependencies have been observed for these effects with the CV curve stretchout having a dependence of Q∼1.7 and the CV curve shifting with a dependence of Q∼1.8. These dependencies are similar to the results of previous studies focused on the Q-dependence of the stopping power of HCIs.
One-way sound propagation via spatio-temporal modulation of magnetorheological fluid
Authors: Nanda Aditya , Karami M. Amin
Published: July 2018

This manuscript details the possibility of achieving one-way sound propagation using a smart fluid such as magnetorheological fluid (MRF) by subjecting it to a spatio-temporally varying magnetic field. The local speed of sound in MRF is dependent on applied magnetic field as demonstrated in several experimental works and this property of MRF has been leveraged, in this work, to induce one-way bandgaps. Initially, a general wave equation pertaining to fluid with space-and-time-varying material properties was derived. Assuming plane wave propagation in one dimension, an approximate Floquet solution was imposed and the dispersion relationship was obtained. A comprehensive finite element analysis was conducted and good agreement was noted between the numerical and theoretical dispersion relations. It was concluded that space-time periodic modulation of fluid density and local sound speed is necessary to induce asymmetry in the band diagram around the ω axis. The feasibility of real-world implementation using MRF has been discussed. A parametric study detailing the effect of viscosity on the one-way bandgaps has been undertaken. It was found that one-way bandgaps formed at relatively lower frequencies are more robust to viscous corruption. A real-world implementation may be feasible if the viscosity of MRF is less than 3000 Pa-s.
iac
Gene Expression in the Indole-3-Acetic Acid-Degrading Soil Bacterium Enterobacter soli LF7
Authors: Greenhut Isaac V. , Slezak Beryl L. , Leveau Johan H. J.
Published: July 2018

Bacterial
iac
genes code for the enzymatic conversion of the plant hormone indole-3-acetic acid (IAA) to catechol. Here, we demonstrate that the
iac
genes of soil bacterium
Enterobacter soli
LF7 enable growth on IAA by coarrangement and coexpression with a set of
pca
and
cat
genes that code for complete conversion of catechol to central metabolites. This work contributes in a number of novel and significant ways to our understanding of
iac
gene biology in bacteria from (non-)plant environments. More specifically, we show that LF7's response to IAA involves derepression of the MarR-type transcriptional regulator IacR, which is quite fast (less than 25 min upon IAA exposure), highly specific (only in response to IAA and chlorinated IAA, and with few genes other than
iac
,
cat
, and
pca
induced), relatively sensitive (low micromolar range), and seemingly tailored to exploit IAA as a source of carbon and energy.
Alcohol Acetyltransferase Eat1 Is Located in Yeast Mitochondria
Authors: Kruis Aleksander J. , Mars Astrid E. , Kengen Servé W. M. , Borst Jan Willem , van der Oost John , Weusthuis Ruud A.
Published: July 2018

Ethyl acetate is a common bulk chemical that is currently produced from petrochemical sources. Several Eat1-containing yeast strains naturally produce large amounts of ethyl acetate and are potential cell factories for the production of bio-based ethyl acetate. Rational design of the underlying metabolic pathways may result in improved production strains, but it requires fundamental knowledge on the function of Eat1. A key feature is the location of Eat1 in the yeast cell. The precursors for ethyl acetate synthesis can be produced in multiple cellular compartments through different metabolic pathways. The location of Eat1 determines the relevance of each pathway, which will provide future targets for the metabolic engineering of bulk ethyl acetate production in yeast.
Epstein-Barr Virus-Induced Nodules on Viral Replication Compartments Contain RNA Processing Proteins and a Viral Long Noncoding RNA
Authors: Park Richard , Miller George
Published: July 2018

In order to make protein, mRNA transcribed from DNA in the nucleus must enter the cytoplasm. Nuclear export of mRNA requires correct processing of mRNAs by enzymes that function in splicing and nuclear export. During the Epstein-Barr virus (EBV) lytic cycle, nuclear export of cellular mRNAs is blocked, yet export of viral mRNAs is facilitated. Here we report the dispersal and dramatic reorganization of cellular (SC35, SON, SRp20, Y14, ALY, and NXF1) and viral (BMLF1 and BGLF5) proteins that play key roles in pre-mRNA processing and export of mRNA. These virus-induced nuclear changes culminate in formation of VINORCs, novel nodular structures composed of viral and cellular RNA splicing and export factors. VINORCs localize to the periphery of viral replication compartments, where viral mRNAs reside. These EBV-induced changes in nuclear organization may contribute to blockade of nuclear export of host mRNA, while enabling selective processing and export of viral mRNA.
Quaternary faulting along the Dandridge-Vonore fault zone in the Eastern Tennessee seismic zone
Authors: Cox R.T. , Hatcher R.D. , Counts R. , Gamble E. , Glasbrenner J. , Warrell K.
Published: July 2018

This field guide describes three accessible sites along the Dandridge-Vonore fault zone in the Eastern Tennessee seismic zone. These sites reveal bedrock faulted against Quaternary river sediments, including (1) a thrust fault on the Little River near Alcoa, Tennessee; (2) a series of thrust faults exposed in a drainage ditch that thrust Conasauga Shale against Quaternary colluvium in the footwall; and (3) a normal fault at Tellico Lake near Vonore, Tennessee, with Quaternary sediments faulted against Conasauga Shale.
Sibling influence on children’s objectively measured physical activity: a meta-analysis and systematic review
Authors: Kracht Chelsea L , Sisson Susan B
Published: July 2018

Children without siblings (only children) have higher rates of obesity than children with siblings. Childhood obesity may be prevented by minimising sedentary behaviour and accumulating sufficient physical activity in young children. A growing number of articles have examined the influence of siblings on physical activity and sedentary behaviour, yet these articles have not been synthesised. 

Objective

To synthesise literature and describe the influence of siblings on objectively measured physical activity and sedentary behaviour of children (ages 2–18 years). 

Design

Outcomes were analysed in a systematic review and meta-analysis. 

Data sources

PubMed, EMBASE, Web of Science and Medline OVID were searched for articles related to siblings, physical activity, sedentary behaviour and obesity outcomes from 1947 to March 2018. 

Eligibility criteria

Articles that evaluated sibling status on physical activity objectively measured by accelerometer or pedometer were included. 

Results

Nineteen articles, representing 17 independent datasets, were included in the review. Nine were included in the quantitative analysis. Pooled data from nine articles indicated children with siblings had higher moderate-to-vigorous physical activity (MVPA) relative to only children, with a potential dose response for higher number of children in household and higher MVPA (Mean Difference=3.13, 95% CI 1.90 to 4.35, p=0.001). Findings were mixed for the influence of siblings on sedentary behaviour and light physical activity.

Summary/Conclusion

Children with siblings had healthier physical activity patterns, as measured by accelerometer or pedometer, than did only children. Suggested mechanisms include peer modelling, encouraging active transport and sports participation, opportunity for playmate and serving as additional caregivers.

Trial registration number

CRD42017055463.
Methods to improve medication adherence in patients with chronic inflammatory rheumatic diseases: a systematic literature review
Authors: Lavielle Matthieu , Puyraimond-Zemmour Déborah , Romand Xavier , Gossec Laure , Senbel Eric , Pouplin Sophie , Beauvais Catherine , Gutermann Loriane , Mezieres Maryse , Dougados Maxime , Molto Anna
Published: July 2018

Objective

Lack of adherence to treatment is frequent in chronic inflammatory rheumatic diseases and is associated with poorer outcomes. The objective of this study was to describe and evaluate interventions that have been proposed to enhance medication adherence in these conditions.

Methods

A systematic literature review was performed in Pubmed, Cochrane, Embase and clinicaltrials.gov databases completed by the rheumatology meeting (ACR, EULAR and SFR) abstracts from last 2 years. All studies in English or French evaluating an intervention to improve medication adherence in chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondyloarthritis (SpA), crystal related diseases, connective tissue diseases, vasculitis and Still’s disease) were included. Interventions on adherence were collected and classified in five modalities (educational, behavioural, cognitive behavioural, multicomponent interventions or others).

Results

1325 abstracts were identified and 22 studies were finally included (18 studies in RA (72%), 4 studies in systemic lupus erythematosus (16%), 2 studies in SpA (8%) and 1 study in gout (4%)). On 13 randomised controlled trials (RCT) (1535 patients), only 5 were positive (774 patients). Educational interventions were the most represented and had the highest level of evidence: 8/13 RCT (62%, 1017 patients) and 4/8 were positive (50%). In these studies, each patient was individually informed or educated by different actors (physicians, pharmacists, nurses and so on). Supports and contents of these educational interventions were heterogenous.

Conclusion

Despite the importance of medication adherence in chronic inflammatory rheumatic disorders, evidence on interventions to improve medication adherence is scarce.
Raymond Hopes
Authors: Rossdale Peter , Hunt Michael , Peace Colin , Ricketts Sidney , Digby Nicholas Wingfield , Greet Timothy , Steven Neil , Pilsworth Robert , McGladdery Andrew , Carson Deidre , Barrelet Frederic , Shepherd Michael , Payne Richard , Ramzan Peter , Bathe Andrew
Published: July 2018

One of Rossdales early partners, he developed the racehorses‐in‐training services of the Newmarket practice, stimulating the development of new diagnostic and therapeutic techniques that are taken for granted today.
A family of polynomial invariants for knotoids
Authors: Kim Sera , Im Young Ho , Lee Sunho
Published: July 2018

We introduce a family of polynomial invariants for knotoids. Via the corresponding Gauss diagrams for knotoids, we investigate the method to calculate these polynomial invariants. Also, we give some properties and examples.
Faithful equivalence of equivalent ribbon surface-links
Authors: Kawauchi Akio
Published: July 2018

A chord graph in [Formula: see text]-space is constructed from a ribbon surface-link in [Formula: see text]-space. In earlier papers, the three moves on the diagrams of chord graphs (namely, the chord diagrams) were introduced to describe the faithful equivalence of a ribbon surface-link. In this paper, it is shown that any two equivalent ribbon surface-links are faithfully equivalent, so that any chord diagrams of any two equivalent ribbon surface-links are connected by a finite number of these three moves. By combining it with an earlier result, it is shown that any two TOP-equivalent ribbon surface-links are equivalent. In other words, there is no exotic ribbon surface-link, generalizing an earlier result on the trivial ribbon surface-knot. In another earlier result, the three moves on the chord diagrams were modified into the 16 moves on the chord diagrams without base crossing. In this paper, further modified moves of the 16 moves on the chord diagrams without base crossing are also introduced to describe how the set of ribbon torus-links is produced from the set of welded virtual links.
Quasi-trivial quandles and biquandles, cocycle enhancements and link-homotopy of pretzel links
Authors: Elhamdadi Mohamed , Liu Minghui , Nelson Sam
Published: July 2018

We investigate some algebraic structures called quasi-trivial quandles and we use them to study link-homotopy of pretzel links. Precisely, a necessary and sufficient condition for a pretzel link with at least two components being trivial under link-homotopy is given. We also generalize the quasi-trivial quandle idea to the case of biquandles and consider enhancement of the quasi-trivial biquandle cocycle counting invariant by quasi-trivial biquandle cocycles, obtaining invariants of link-homotopy type of links analogous to the quasi-trivial quandle cocycle invariants in Inoue’s paper [A. Inoue, Quasi-triviality of quandles for link-homotopy, J. Knot Theory Ramifications 22(6) (2013) 1350026, doi:10.1142/S0218216513500260, MR3070837].
Biquandle (co)homology and handlebody-links
Authors: Ishii Atsushi , Iwakiri Masahide , Kamada Seiichi , Kim Jieon , Matsuzaki Shosaku , Oshiro Kanako
Published: July 2018

In this paper, we introduce the (co)homology group of a multiple conjugation biquandle. It is the (co)homology group of the prismatic chain complex, which is related to the homology of foams introduced by J. S. Carter, modulo a certain subchain complex. We construct invariants for [Formula: see text]-oriented handlebody-links using [Formula: see text]-cocycles. When a multiple conjugation biquandle [Formula: see text] is obtained from a biquandle [Formula: see text] using [Formula: see text]-parallel operations, we provide a [Formula: see text]-cocycle (or [Formula: see text]-cocycle) of the multiple conjugation biquandle [Formula: see text] from a [Formula: see text]-cocycle (or [Formula: see text]-cocycle) of the biquandle [Formula: see text] equipped with an [Formula: see text]-set [Formula: see text].
Biquandle cohomology and state-sum invariants of links and surface-links
Authors: Kamada Seiichi , Kawauchi Akio , Kim Jieon , Lee Sang Youl
Published: July 2018

In this paper, we discuss the (co)homology theory of biquandles, derived biquandle cocycle invariants for oriented surface-links using broken surface diagrams and how to compute the biquandle cocycle invariants from marked graph diagrams. We also develop the shadow (co)homology theory of biquandles and construct the shadow biquandle cocycle invariants for oriented surface-links.
Annihilator-stability and unique generation in C(X)
Authors: Azarpanah F. , Farokhpay F. , Ghashghaei E.
Published: July 2018

Using the equivalence of unique generation and cleanness of [Formula: see text], we give affirmative answers to questions raised in [I. Kaplansky, Elementary divisors and modules, Trans. Amer. Math. Soc.  66 (1949) 464–491] and [D.D. Anderson et al., When are associates unit multiples? Rocky Mountain J. Math.  34 (2004) 811–828] for rings of real-valued continuous functions. In fact, we show that if [Formula: see text] is [Formula: see text] (uniquely generated) then [Formula: see text] is too, and [Formula: see text] is strongly associate if and only if [Formula: see text] is, where [Formula: see text]. We give topological characterizations of [Formula: see text] and [Formula: see text] (annihilator-stable) elements of [Formula: see text] for continuum spaces [Formula: see text] and using this, we observe that the product of two UG elements need not be [Formula: see text]. It is shown that the set of elements in [Formula: see text] which have stable range 1 and the set of [Formula: see text] elements of [Formula: see text] coincide and several examples are given which show that the set of [Formula: see text] elements, the set of [Formula: see text] elements and the set of clean elements of [Formula: see text] can differ. Finally, we characterize spaces [Formula: see text] for which every clean element of [Formula: see text] or every element of [Formula: see text] which has stable range 1 is [Formula: see text].
Asymptotic stability of viscous contact wave and rarefaction waves for the system of heat-conductive ideal gas without viscosity
Authors: Fan Lili , Gong Guiqiong , Tang Shaojun
Published: July 2018

This paper is concerned with the Cauchy problem of heat-conductive ideal gas without viscosity, where the far field states are prescribed. When the corresponding Riemann problem for the compressible Euler system has the solution consisting of a contact discontinuity and rarefaction waves, we show that if the strengths of the wave patterns and the initial perturbation are suitably small, the unique global-in-time solution exists and asymptotically tends to the corresponding composition of a viscous contact wave with rarefaction waves, which extended the results by Huang–Li–Matsumura [Asymptotic stability of combination of viscous contact wave with rarefaction waves for one-dimensional compressible Navier–Stokes system, Arch. Ration. Mech. Anal. 197 (2010) 89–116.], where they treated the viscous and heat-conductive ideal gas.
Screen Connections between Malaysia, Taiwan, Hong Kong, and China
Authors: BARKER THOMAS ALEXANDER CHARLES
Published: July 2018

To date Malaysia has occupied a peripheral position in studies of Chinese cinemas and East Asian pop culture, often overlooked in favor of the more productive centers in Hong Kong, Taiwan, and increasingly China. By engaging with the field of Chinese transnationalism as developed by Aihwa Ong and others, this paper reconsiders Malaysia’s place in the broader Chinese media landscape and the role of Chinese Malaysians as agents driving Malaysia’s engagement with Taiwan, Hong Kong, and China. Focusing on Malaysia, this paper explores Malaysia’s screen connections to China through the two vectors of Malaysian migration and Chinese co-productions entering Malaysia. Increasingly, Malaysian creative workers who are already quite mobile are moving in increasing numbers to Mainland China and working on Chinese entertainment projects. Primarily, they take on intermediary roles within China’s growing entertainment industries which need cosmopolitan, multi-lingual creative labor as it increasingly globalizes and seeks foreign partners. Conversely, as China’s industry expands outwards, it seeks co-production partners and locations and has found Malaysia to be conducive. In outlining this new screen industry relationship, this paper suggests cultural and economic implications and futures for Chinese cinemas in Southeast Asia and the role of Malaysia’s ethnic Chinese population.
Relative Cayley graphs of finite groups
Authors: Farrokhi D. G. M. , Rajabian M. , Erfanian A.
Published: July 2018

The relative Cayley graph of a group [Formula: see text] with respect to its proper subgroup [Formula: see text] is a graph whose vertices are elements of [Formula: see text] and two vertices [Formula: see text] and [Formula: see text] are adjacent if [Formula: see text] for some [Formula: see text], where [Formula: see text] is an inverse-closed subset of [Formula: see text]. We study the relative Cayley graphs and, among other results, we discuss on their connectivity and forbidden structures, and compute some of their important numerical invariants.
Rainbow edge domination numbers in graphs
Authors: Ahangar H. Abdollahzadeh , Jahani H. , Rad N. Jafari
Published: July 2018

A 2-rainbow edge dominating function (2REDF) of a graph [Formula: see text] is a function [Formula: see text] from the edge set [Formula: see text] to the set of all subsets of the set [Formula: see text] such that for any edge [Formula: see text] with [Formula: see text] the condition [Formula: see text] is fulfilled, where [Formula: see text] is the open neighborhood of [Formula: see text]. The weight of a 2REDF [Formula: see text] is the value [Formula: see text]. The minimum weight of a 2REDF is the 2-rainbow edge domination number of [Formula: see text], denoted by [Formula: see text]. In this paper, we initiate the study of 2-rainbow edge domination in graphs. We present various sharp bounds, exact values and characterizations for the 2-rainbow edge domination number of a graph.
Big Data: Business, Technology, Education, and Science
Authors: Johnson Jeffrey , Tesei Luca , Piangerelli Marco , Merelli Emanuela , Paci Riccardo , Stojanovic Nenad , Leitão Paulo , Barbosa José , Amador Marco
Published: July 2018

Transforming the latent value of big data into real value requires the great human intelligence and application of human-data scientists. Data scientists are expected to have a wide range of technical skills alongside being passionate self-directed people who are able to work easily with others and deliver high quality outputs under pressure. There are hundreds of university, commercial, and online courses in data science and related topics. Apart from people with breadth and depth of knowledge and experience in data science, we identify a new educational path to train "bridge persons" who combine knowledge of an organization's business with sufficient knowledge and understanding of data science to "bridge" between non-technical people in the business with highly skilled data scientists who add value to the business. The increasing proliferation of big data and the great advances made in data science do not herald in an era where all problems can be solved by deep learning and artificial intelligence. Although data science opens up many commercial and social opportunities, data science must complement other science in the search for new theory and methods to understand and manage our complex world.
Revisiting the discharge time of a cylindrical leaking bucket
Authors: Corless Robert M. , Jankowski Julia E.
Published: July 2018

In [2] we find an exploration of a new mathematical model of the flow in a leaking bucket suitable for beginning students. The model is derived using the non-steady Bernoulli's Principle, and results in a more sophisticated model than the simple ordinary differential equation [EQUATION] derived using the steady Bernoulli's Principle. The simpler model goes sometimes by the name of Torricelli's Law and is very well studied; indeed it is a favourite example in many textbooks. This present paper provides an alternative derivation of the new model that uses an energy balance, and carefully lays out some numerical issues omitted from the treatment in [2]. We also provide an analytic solution in terms of
2
F
1
hypergeometric functions, which, while possibly unfamiliar to the student, are available to them via computer algebra systems. Even before that solution, an intermediate equation [EQUATION] is derived, which already explains the similarity of the solutions to the more sophisticated model to the ones from the simple Torricelli's Law. This paper gives a useful example for use of a CAS in a classroom setting.
A few conjectures about the multiple zeta values
Authors: Combariza Germán A. G.
Published: July 2018

The multiple zeta values (MZVs) form a set of real numbers with, what we believe and module Zagier's Conjecture, a beautiful structure as an algebra over the rational numbers. In this paper we show partial solutions to five well known conjectures about the MZV obtained by using linear systems and shuffle products. We use computer algebra systems to study these conjectures and make our code available online.

We describe how to compute the shuffle minus stuffle product to obtain relations of the MZVs, together with the xtaylor algorithm, to verify the conjectures mentioned above. We note that it is only necessary to solve a linear system, not in MZV but in its powers and products, to find all the relations. We also made all the code available online.
An attack scenario and mitigation mechanism for enterprise BYOD environments
Authors: Siboni Shachar , Shabtai Asaf , Elovici Yuval
Published: July 2018

The recent proliferation of the Internet of Things (IoT) technology poses major security and privacy concerns. Specifically, the use of personal IoT devices, such as tablets, smartphones, and even smartwatches, as part of the Bring Your Own Device (BYOD) trend, may result in severe network security breaches in enterprise environments. Such devices increase the attack surface by weakening the digital perimeter of the enterprise network and opening new points of entry for malicious activities. In this paper we demonstrate a novel attack scenario in an enterprise environment by exploiting the smartwatch device of an innocent employee. Using a malicious application running on a suitable smartwatch, the device imitates a real Wi-Fi direct printer service in the network. Using this attack scenario, we illustrate how an advanced attacker located outside of the organization can leak/steal sensitive information from the organization by utilizing the compromised smartwatch as a means of attack. An attack mitigation process and countermeasures are suggested in order to limit the capability of the remote attacker to execute the attack on the network, thus minimizing the data leakage by the smartwatch.
Help us celebrate 50 SIGCSE technical symposiums
Authors: Decker Adrienne , Eiselt Kurt , Alphonce Carl
Published: July 2018

Following quickly on the heels of the 50th anniversary of the formation of SIGCSE (the organization), we find ourselves preparing to celebrate the 50th SIGCSE Technical Symposium, SIGCSE 2019. SIGCSE 2019 will be held February 27 -- March 2, 2019 in Minneapolis, Minnesota.
Member Highlight
Authors: Porter Leo
Published: July 2018

In this feature of the Bulletin, we highlight members of the SIGCSE community. In this issue, Bulletin co-editor Leo Porter interviewed Bob Aiken. In 1995 Bob received the SIGCSE Outstanding Contribution Computer Science Education Award and in 1999 received the ACM SIGCSE Lifetime Service to Computer Science Education for his advocacy for computer science education both in the US and abroad. Bob was elected an ACM Fellow in 2002. His background is in artificial intelligence, educational uses of computers, and online collaboration tools. He is working on an article about the history of SIGCSE which will appear in the December issue of Inroads for the 50th year celebration of SIGCSE.
Advancing broadening participation research at RESPECT
Authors: Payton Jamie , Thiruvathukal George K.
Published: July 2018

Understanding how to apply fundamental computer science problem solving skills is quickly becoming a required competency. It is critical to address issues of equity and inclusion so that we can engage all people in learning key concepts in computing. The Conference for Research on Equity and Sustained Participation in Engineering, Computing, and Technology (RESPECT) is intended to address these needs, serving to build a strong community, theory, and foundation for research on broadening participation.
Motion Perception: From Detection to Interpretation
Authors: Nishida Shin'ya , Kawabe Takahiro , Sawayama Masataka , Fukiage Taiki
Published: July 2018

Visual motion processing can be conceptually divided into two levels. In the lower level, local motion signals are detected by spatiotemporal-frequency-selective sensors and then integrated into a motion vector flow. Although the model based on V1-MT physiology provides a good computational framework for this level of processing, it needs to be updated to fully explain psychophysical findings about motion perception, including complex motion signal interactions in the spatiotemporal-frequency and space domains. In the higher level, the velocity map is interpreted. Although there are many motion interpretation processes, we highlight the recent progress in research on the perception of material (e.g., specular reflection, liquid viscosity) and on animacy perception. We then consider possible linking mechanisms of the two levels and propose intrinsic flow decomposition as the key problem. To provide insights into computational mechanisms of motion perception, in addition to psychophysics and neurosciences, we review machine vision studies seeking to solve similar problems.
Spliceosome Mutations Induce R Loop-Associated Sensitivity to ATR Inhibition in Myelodysplastic Syndromes
Authors: Nguyen Hai Dang , Leong Wan Yee , Li Weiling , Reddy Pavankumar N.G. , Sullivan Jack D. , Walter Matthew J. , Zou Lee , Graubert Timothy A.
Published: July 2018

Heterozygous somatic mutations in spliceosome genes (U2AF1, SF3B1, ZRSR2, or SRSF2) occur in >50% of patients with myelodysplastic syndrome (MDS). These mutations occur early in disease development, suggesting that they contribute to MDS pathogenesis and may represent a unique genetic vulnerability for targeted therapy. Here, we show that RNA splicing perturbation by expression of the U2AF1(S34F) mutant causes accumulation of R loops, a transcription intermediate containing RNA:DNA hybrids and displaced single-stranded DNA, and elicits an ATR response. ATR inhibitors (ATRi) induced DNA damage and cell death in U2AF1(S34F)-expressing cells, and these effects of ATRi were enhanced by splicing modulating compounds. Moreover, ATRi-induced DNA damage was suppressed by overexpression of RNaseH1, an enzyme that specifically removes the RNA in RNA:DNA hybrids, suggesting that the ATRi sensitivity of U2AF1(S34F)-expressing cells arises from R loops. Taken together, our results demonstrate that ATR may represent a novel therapeutic target in patients with MDS carrying the U2AF1(S34F) mutation and potentially other malignancies harboring spliceosome mutations.

Significance: This study provides preclinical evidence that patients with MDS or other myeloid malignancies driven by spliceosome mutations may benefit from ATR inhibition to exploit the R loop–associated vulnerability induced by perturbations in splicing. Cancer Res; 78(18); 5363–74. ©2018 AACR.
mTOR Inhibition via Displacement of Phosphatidic Acid Induces Enhanced Cytotoxicity Specifically in Cancer Cells
Authors: Nguyen Tra-Ly , Nokin Marie-Julie , Egorov Maxim , Tomé Mercedes , Bodineau Clément , Di Primo Carmelo , Minder Lætitia , Wdzieczak-Bakala Joanna , Garcia-Alvarez Maria Concepcion , Bignon Jérôme , Thoison Odile , Delpech Bernard , Surpateanu Georgiana , Frapart Yves-Michel , Peyrot Fabienne , Abbas Kahina , Terés Silvia , Evrard Serge , Khatib Abdel-Majid , Soubeyran Pierre , Iorga Bogdan I. , Durán Raúl V. , Collin Pascal
Published: July 2018

The mTOR is a central regulator of cell growth and is highly activated in cancer cells to allow rapid tumor growth. The use of mTOR inhibitors as anticancer therapy has been approved for some types of tumors, albeit with modest results. We recently reported the synthesis of ICSN3250, a halitulin analogue with enhanced cytotoxicity. We report here that ICSN3250 is a specific mTOR inhibitor that operates through a mechanism distinct from those described for previous mTOR inhibitors. ICSN3250 competed with and displaced phosphatidic acid from the FRB domain in mTOR, thus preventing mTOR activation and leading to cytotoxicity. Docking and molecular dynamics simulations evidenced not only the high conformational plasticity of the FRB domain, but also the specific interactions of both ICSN3250 and phosphatidic acid with the FRB domain in mTOR. Furthermore, ICSN3250 toxicity was shown to act specifically in cancer cells, as noncancer cells showed up to 100-fold less sensitivity to ICSN3250, in contrast to other mTOR inhibitors that did not show selectivity. Thus, our results define ICSN3250 as a new class of mTOR inhibitors that specifically targets cancer cells.

Significance: ICSN3250 defines a new class of mTORC1 inhibitors that displaces phosphatidic acid at the FRB domain of mTOR, inducing cell death specifically in cancer cells but not in noncancer cells. Cancer Res; 78(18); 5384–97. ©2018 AACR.
Network Propagation Predicts Drug Synergy in Cancers
Authors: Li Hongyang , Li Tingyang , Quang Daniel , Guan Yuanfang
Published: July 2018

Combination therapies are commonly used to treat patients with complex diseases that respond poorly to single-agent therapies. In vitro high-throughput drug screening is a standard method for preclinical prioritization of synergistic drug combinations, but it can be impractical for large drug sets. Computational methods are thus being actively explored; however, most published methods were built on a limited size of cancer cell lines or drugs, and it remains a challenge to predict synergism at a large scale where the diversity within the data escalates the difficulty of prediction. Here, we present a state-of-the-field synergy prediction algorithm, which ranked first in all subchallenges in the AstraZeneca-Sanger Drug Combination Prediction DREAM Challenge. The model was built and evaluated using the largest drug combination screening dataset at the time of the competition, consisting of approximately 11,500 experimentally tested synergy scores of 118 drugs in 85 cancer cell lines. We developed a novel feature extraction strategy by integrating the cross-cell and cross-drug information with a novel network propagation method and then assembled the information in monotherapy and simulated molecular data to predict drug synergy. This represents a significant conceptual advancement of synergy prediction, using extracted features in the form of simulated posttreatment molecular profiles when only the pretreatment molecular profile is available. Our cross-tissue synergism prediction algorithm achieves promising accuracy comparable with the correlation between experimental replicates and can be applied to other cancer cell lines and drugs to guide therapeutic choices.

Significance: This study presents a novel network propagation–based method that predicts anticancer drug synergy to the accuracy of experimental replicates, which establishes a state-of-the-field method as benchmarked by the pharmacogenomics research community involving models generated by 160 teams. Cancer Res; 78(18); 5446–57. ©2018 AACR.
A Coclinical Radiogenomic Validation Study: Conserved Magnetic Resonance Radiomic Appearance of Periostin-Expressing Glioblastoma in Patients and Xenograft Models
Authors: Zinn Pascal O. , Singh Sanjay K. , Kotrotsou Aikaterini , Hassan Islam , Thomas Ginu , Luedi Markus M. , Elakkad Ahmed , Elshafeey Nabil , Idris Tagwa , Mosley Jennifer , Gumin Joy , Fuller Gregory N. , de Groot John F. , Baladandayuthapani Veera , Sulman Erik P. , Kumar Ashok J. , Sawaya Raymond , Lang Frederick F. , Piwnica-Worms David , Colen Rivka R.
Published: July 2018

Purpose:

Radiomics is the extraction of multidimensional imaging features, which when correlated with genomics, is termed radiogenomics. However, radiogenomic biological validation is not sufficiently described in the literature. We seek to establish causality between differential gene expression status and MRI-extracted radiomic-features in glioblastoma.

Experimental Design:

Radiogenomic predictions and validation were done using the Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data glioblastoma patients (n = 93) and orthotopic xenografts (OX; n = 40). Tumor phenotypes were segmented, and radiomic-features extracted using the developed radiome-sequencing pipeline. Patients and animals were dichotomized on the basis of Periostin (POSTN) expression levels. RNA and protein levels confirmed RNAi-mediated POSTN knockdown in OX. Total RNA of tumor cells isolated from mouse brains (knockdown and control) was used for microarray-based expression profiling. Radiomic-features were utilized to predict POSTN expression status in patient, mouse, and interspecies.

Results:

Our robust pipeline consists of segmentation, radiomic-feature extraction, feature normalization/selection, and predictive modeling. The combination of skull stripping, brain-tissue focused normalization, and patient-specific normalization are unique to this study, providing comparable cross-platform, cross-institution radiomic features. POSTN expression status was not associated with qualitative or volumetric MRI parameters. Radiomic features significantly predicted POSTN expression status in patients (AUC: 76.56%; sensitivity/specificity: 73.91/78.26%) and OX (AUC: 92.26%; sensitivity/specificity: 92.86%/91.67%). Furthermore, radiomic features in OX were significantly associated with patients with similar POSTN expression levels (AUC: 93.36%; sensitivity/specificity: 82.61%/95.74%; P = 02.021E−15).

Conclusions:

We determined causality between radiomic texture features and POSTN expression levels in a preclinical model with clinical validation. Our biologically validated radiomic pipeline also showed the potential application for human–mouse matched coclinical trials.
Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers
Authors: Sharma Anu , Subudhi Sumit K. , Blando Jorge , Scutti Jorge , Vence Luis , Wargo Jennifer , Allison James P. , Ribas Antoni , Sharma Padmanee
Published: July 2018

Purpose:

CTLA-4 was the first inhibitory immune checkpoint to be identified. Two mAbs, ipilimumab (IgG1) and tremelimumab (IgG2), which block the function of CTLA-4, have demonstrated durable clinical activity in a subset of patients with advanced solid malignancies by augmenting effector T-cell–mediated immune responses. Studies in mice suggest that anti-CTLA-4 mAbs may also selectively deplete intratumoral FOXP3+ regulatory T cells via an Fc-dependent mechanism. However, it is unclear whether the depletion of FOXP3+ cells occurs in patients with cancer treated with anti-CTLA-4 therapies.

Experimental Design:

Quantitative IHC was used to evaluate the densities of intratumoral CD4+, CD8+, and FOXP3+ cells in stage-matched melanoma (n = 19), prostate cancer (n = 17), and bladder cancer (n = 9) samples treated with ipilimumab and in paired melanoma tumors (n = 18) treated with tremelimumab. These findings were corroborated with multiparametric mass cytometry analysis of tumor-infiltrating cells from paired fresh melanoma tumors (n = 5) treated with ipilimumab.

Results:

Both ipilimumab and tremelimumab increase infiltration of intratumoral CD4+ and CD8+ cells without significantly changing or depleting FOXP3+ cells within the tumor microenvironment.

Conclusions:

Anti-CTLA-4 immunotherapy does not deplete FOXP3+ cells in human tumors, which suggests that their efficacy could be enhanced by modifying the Fc portions of the mAbs to enhance Fc-mediated depletion of intratumoral regulatory T cells.

See related commentary by Quezada and Peggs, p. 1130
Beyond the Beyond: A Case of an Extraordinary Response to Multiple Lines of Therapy in a de novo Metastatic HER2-Negative Gastric Cancer Patient
Authors: Baldessari Cinzia , Gelsomino Fabio , Spallanzani Andrea , Pugliese Giuseppe , Reggiani Bonetti Luca , Bettelli Stefania , Cascinu Stefano
Published: July 2018

Background: Gastric cancer is the fourth cause of cancer-related death in Europe and the prognosis of these patients remains dismal. It has been demonstrated that chemotherapy improved survival compared with best supportive care and recently, subsequent lines of therapy, also with new drugs, obtained positive results. Summary: We present the case of a patient diagnosed with a de novo metastatic gastric cancer who experienced an extraordinary long response to multiple lines of chemotherapy (FOLFOX6, paclitaxel plus ramucirumab, FOLFIRI, rechallenge with FOLFOX6). Key Message: Gastric cancer therapy should be considered as the result of a strategy based on the patient’s condition, and tolerance and response to various therapies. The emerging evidence of the role of subsequent lines of therapy, along with the recognition of the pivotal role of nutritional support and the availability of new drugs, should help clinicians in the management of patients with gastric cancer. Practical Implications: We propose a practical therapeutic algorithm in order to help clinicians who deal with patients with gastric cancer.
A Novel Intraoperative Laser Light Imaging System to Simultaneously Visualize Visible Light and Near-Infrared Fluorescence for Indocyanine Green Videoangiography
Authors: Sato Taku , Bakhit Mudathir , Suzuki Kyouichi , Sakuma Jun , Fujii Masazumi , Murakami Yuta , Ito Yuhei , Sure Ulrich , Saito Kiyoshi
Published: July 2018

Background: Intraoperative indocyanine green videoangiography (ICG-VA) has been reported to be utilized in various cerebrovascular surgeries, wherein the blood flow is noticeably shown in white with a black background. ICG flow alone, but not other structures, can be observed using ICG-VA. We developed a novel high-resolution intraoperative imaging system using laser light source for simultaneously visualizing both visible light and near-infrared (NIR) fluorescence images of ICG-VA. Methods: We used a novel system for 14 cerebrovascular cases. The operative field was illuminated via an operating microscope using a novel laser light source with four bands at 464 (blue), 532 (green), 640 (red), and 785 nm (NIR region). The observed light from the operative field was split using a beam splitter cube into visible (420– 660 nm) and NIR fluorescence emission light (832–900 nm). Images from the color video and NIR fluorescence emission windows were merged for visualization on a monitor screen simultaneously. Laser light was compared with xenon light, and both setups were tested for cerebrovascular surgeries. Results: Laser light has numerous advantages over xenon light. The present setup clearly visualized the color operative field with enhanced blood flow. Complete clipping or incomplete clipping with neck remnant or remnant flow into an aneurysm was confirmed in aneurysm surgeries. Feeding arteries and draining veins were easily distinguished in case of arteriovenous malformation. Conclusions: Using the present setup, we can observe the color operative field and enhanced blood flow using ICG in real time. This setup could facilitate various cerebrovascular surgeries.
Neurosarcoidosis following Immune Checkpoint Inhibition
Authors: Dunn-Pirio Anastasie M. , Shah Suma , Eckstein Christopher
Published: July 2018

Recently, immune checkpoint inhibitors have revolutionized cancer care by enhancing anti-tumor immunity. However, by virtue of stimulating the immune system, they can lead to immune-related adverse events (irAEs). Neurologic irAEs are uncommon but are becoming increasingly recognized and can be quite serious or even fatal. Furthermore, central nervous system (CNS) manifestations may be difficult to distinguish from CNS metastases, posing management challenges. Here, we describe a patient who developed exacerbation of sarcoidosis leading to CNS involvement following dual checkpoint blockade with nivolumab and ipilimumab for metastatic melanoma and review the relevant literature.
An Enduring Monument
Authors: Rauh Elizabeth
Published: July 2018

On the morning of 18 March 2011, Bahrain’s state television broadcast the razing of the Pearl Roundabout and its iconic sculpture. This event, unsurprisingly, failed to quell the struggle between activists and the ruling elite. Rather, the destruction of the Pearl Monument (Luʾluʾ) and Bahrain’s ‘Pearl Square’ offered demonstrators a readymade symbol embodying the traumatic and violent days of the 2011 demonstrations and the ongoing government suppression of reform movements. Rematerializations of the Luʾluʾ through photographs, graffiti, digital art, sculptural maquettes and even costumes echo the physical structure in miniature and continue to regenerate and multiply the monument like a viral meme. Through such manifestations and reanimations the now-vanished monument continues to occupy Bahrain’s public spaces and civic memory, enduringly resisting the state’s efforts to erase it and all it represents. In examining the ‘lifecycle’ of the Luʾluʾ, this article explores how an act of iconoclasm can result in an outpouring of new creative activities.
Beeshu’s Laugh
Authors: Mulder Stephennie
Published: July 2018

Although the Syrian uprising initially seemed poised to proceed along a path similar to that of revolutions in other parts of the Arab world, the situation quickly devolved into one of the bloodiest and most destructive conflicts since World War II. Against the backdrop of nearly unprecedented devastation and harsh repression, a popular ‘arts of self-satire’ has flourished, creating a form of visual critique directed simultaneously at the regime and the self. On the surface, such works appear to be deeply cynical but in fact serve as a means of visual and social empowerment. In this article I argue that self-satire—and the ‘involvement’ it reveals, exposes and displays—creates a distinctly Syrian form of popular artistic production whose goal is to create a sense of agency and provoke intra-communal and public empathy with the suffering of the Syrian people. Thus, in Syria, the arts of the uprising are often darkly cynical and self-mocking, but that very self-satire becomes the means by which Syrians insist to themselves, and the world, that their circumstances must be revealed, witnessed and radically identified with.