bluuebunny/crossref_metadata_2025 huggingface dataset:
A heuristic approach to the multicriteria design of IaaS cloud infrastructures for Big Data applications
Authors: Arostegi María , Torre‐Bastida Ana , Bilbao Miren Nekane , Del Ser Javier
Published: January 2018

The rapid growth of new computing paradigms such as Cloud Computing and Big Data has unleashed great opportunities for companies to shift their business model towards a fully digital strategy. A major obstacle in this matter is the requirement of highly specialized ICT infrastructures that are expensive and difficult to manage. It is at this point that the IaaS (infrastructure as a service) model offers an efficient and cost‐affordable solution to supply companies with their required computing resources. In the Big Data context, it is often a hard task to design an optimal IaaS solution that meets user requirements. In this context, we propose a methodology to optimize the definition of IaaS cloud models for hosting Big Data platforms, following a threefold criterion: cost, reliability, and computing capacity. Specifically, the proposed methodology hinges on evolutionary heuristics in order to find IaaS configurations in the cloud that optimally balance such objectives. We also define measures to quantify the aforementioned metrics over a Big Data platform hosted within an IaaS cloud model. The proposed method is validated by using real information from three IaaS providers and three Big Data platforms. The obtained results provide an insightful input for system managers when initially designing cloud infrastructures for Big Data applications.
Quantifying the influences of grazing, climate and their interactions on grasslands using Landsat TM images
Authors: Xu Dandan , Koper Nicola , Guo Xulin
Published: January 2018

Appropriate grazing management ensures sustainable productivities of grassland ecosystems while maintaining grassland services. Thus, it is important to understand the influences of grazing management on grassland ecosystems, which can be monitored by measuring grassland response (e.g. leaf area index [LAI]) to grazing management. However, the measured grassland response includes the impact not only of grazing management, but also of other factors and their interactions, such as climate variability and fire. Therefore, to better study the effects of grazing management, grassland response to grazing needs to be quantified separately from that of other factors which influence grasslands and their interactions. The aim of our research was to quantify these interactions using Landsat thematic mapper (TM) images with long‐term datasets at a regional scale. We studied vegetation using a manipulative grazing experiment that applied a range of low to high cattle stocking rates from 2008 to 2011 in a northern native mixed‐prairie in Saskatchewan. Results show that precipitation, temperature, interaction between temperature and precipitation, cattle density, interaction between temperature and cattle density, and the interaction among cattle density and climate parameters explained 65.5, 14.5, 9.8, 1.7, 1.4 and 0.5% of the variation in grassland LAI, respectively; thus, precipitation has the dominant effect in mixed‐grass prairies, while temperature and the interaction between temperature and precipitation have only moderate effects, and grazing intensity and the interaction between grazing intensity and climate variations have relatively low effects. The results also suggest that grassland response to grazing can be quantitatively separated from that of climate variability with the prior knowledge of grazing intensity, even though the influences of precipitation on LAI overrode the effects of short term grazing.
Clinical, microbiological and cytomorphometric evaluation of low‐level laser therapy as an adjunct to periodontal therapy in patients with chronic periodontitis
Authors: Petrović MS , Kannosh IY , Milašin JM , Mihailović DS , Obradović RR , Bubanj SR , Kesić LG
Published: January 2018

Objective

A clinical prospective study was designed to evaluate microbiological, cytomorphometric and clinical efficacy of low‐level laser therapy (LLLT) as an adjunct to periodontal therapy in the treatment of chronic periodontitis.

Methods

Sixty subjects were included and randomly assigned into 2 groups: SRP (scaling root planning) group (n = 30) and LLLT + SRP group (n = 30). Clinical parameters were measured before intervention, after the fifth treatment, and after a month. All subjects received oral hygiene instructions and full‐mouth conservative periodontal treatment (removal of dental plaque followed by SRP). Afterwards, in group II, Kavo LLLT (980 nm, 0.2 W, 6 J/cm2) was applied. Subgingival samples were collected at baseline and after the fifth treatment to quantify Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythensis and Treponema denticola by polymerase chain reaction (PCR). Gingival swabs were taken, and direct smears were prepared on slides for cytomorphometric analysis.

Results

Evaluation using clinical parameters showed better results in LLLT group. A statistically significant decrease in the prevalence of bacteria after treatment in LLLT group was observed for the following: T. forsythensis and T. denticola (P < .001), P. gingivalis (P < .01), A. actinomycetemcomitans and P. intermedia (P < .05). The values of nuclear area, perimeter and Ferret's diameter were significantly lower in both studied groups after treatment, but statistical significance was higher in LLLT group (P < .001) than in the SRP therapy group (P < .05).

Conclusion

Low‐level laser therapy as an adjunct to periodontal therapy demonstrates short‐term additional bacteriological, cytological and clinical benefits.
The rocky road to personalized medicine in acute myeloid leukaemia
Authors: Brinda Bryan , Khan Irum , Parkin Brian , Konig Heiko
Published: January 2018

Acute myeloid leukaemia (AML) is a malignant disorder of the myeloid blood lineage characterized by impaired differentiation and increased proliferation of hematopoietic precursor cells. Recent technological advances have led to an improved understanding of AML biology but also uncovered the enormous cytogenetic and molecular heterogeneity of the disease. Despite this heterogeneity, AML is mostly managed by a ‘one‐size‐fits‐all’ approach consisting of intensive, highly toxic induction and consolidation chemotherapy. These treatment protocols have remained largely unchanged for the past several decades and only lead to a cure in approximately 30–35% of cases. The advent of targeted therapies in chronic myeloid leukaemia and other malignancies has sparked hope to improve patient outcome in AML. However, the implementation of targeted agents in AML therapy has been unexpectedly cumbersome and remains a difficult task due to a variety of disease‐ and patient‐specific factors. In this review, we describe current standard and investigational therapeutic strategies with a focus on targeted agents and highlight potential tools that might facilitate the development of targeted therapies for this fatal disease. The classes of agents described in this review include constitutively activated signalling pathway inhibitors, surface receptor targets, epigenetic modifiers, drugs targeting the interaction of the hematopoietic progenitor cell with the stroma and drugs that target the apoptotic machinery. The clinical context and outcome with these agents will be examined to gain insight about their optimal utilization.
Ten‐year‐old traveller with fever and an exceptional exanthem
Authors: Osowicki Joshua , Badawi Mazen , Al‐Rawahi Ghada N , Rehmus Wingfield E , Sauvé Laura
Published: January 2018

See Answer
Comparison of Gonadal Development in Diploid and Triploid Hybrid Groupers, Epinephelus coioides♀ × Epinephelus lanceolatus♂
Authors: Li Shuisheng , Liu Qiongyu , Xiao Ling , Tao Min , Shu Hu , Zhang Haifa , Lin Haoran , Zhang Yong
Published: January 2018

In this study, the gonadal development of 10‐ to 43‐mo‐old diploid and triploid orange‐giant grouper hybrids, Epinephelus coioides♀ × Epinephelus lanceolatus♂, was investigated. The diploid hybrid groupers exhibited normal gonadal development and experienced vitellogenesis at 43 mo of age. In contrast, the triploid gonad was masculinized and gradually filled with spermatogenic cysts. Radioimmunoassays revealed that the diploid hybrids showed high serum E2 levels at 10 and 43 mo and high T levels at 43 mo, while the triploid hybrids showed high E2 levels at 18 and 30 mo and high T levels at 18 mo. Furthermore, the messenger RNA (mRNA) expression of genes related to reproductive regulation was examined in these hybrids. The mRNA levels of fshb, fshr, lhb, lhr, dmrt1, and sox9 varied significantly during gonadal development. Interestingly, the expression levels of fshr, lhr, dmrt1, and sox9 were higher in triploid hybrids than in diploid hybrids. The hyperactive expression of these genes may be associated with the gonadal masculinization of triploid hybrids.
Profile, risk factors and outcome of acute kidney injury in paediatric acute‐on‐chronic liver failure
Authors: Lal Bikrant B. , Alam Seema , Sood Vikrant , Rawat Dinesh , Khanna Rajeev
Published: January 2018

Background & Aims

There are no studies on acute kidney injury in paediatric acute‐on‐chronic liver failure. This study was planned with aim to describe the clinical presentation and outcome of acute kidney injury among paediatric acute‐on‐chronic liver failure patients.

Methods

Data of all children 1‐18 years of age presenting with acute chronic liver failure (Asia pacific association for the study of the liver definition) was reviewed. Acute kidney injury was defined as per Kidney Diseases—Improving Global Outcomes guidelines. Poor outcome was defined as death or need for liver transplant within 3 months of development of acute kidney injury.

Results

A total of 84 children with acute‐on‐chronic liver failure were presented to us in the study period. Acute kidney injury developed in 22.6% of patients with acute‐on‐chronic liver failure. The median duration from acute‐on‐chronic liver failure to development of acute kidney injury was 4 weeks (Range: 2‐10 weeks). The causes of acute kidney injury were hepatorenal syndrome (31.6%), sepsis (31.6%), nephrotoxic drugs (21%), dehydration (10.5%) and bile pigment related acute tubular necrosis in one patient. On univariate analysis, higher baseline bilirubin, higher international normalized ratio, higher paediatric end stage liver disease, presence of systemic inflammatory response syndrome and presence of spontaneous bacterial peritonitis had significant association with presence of acute kidney injury. On logistic regression analysis, presence of systemic inflammatory response syndrome (adjusted OR: 8.659, 95% CI: 2.18‐34.37, P = .002) and higher baseline bilirubin (adjusted OR: 1.07, 95% CI: 1.008‐1.135, P = .025) were independently associated with presence of acute kidney injury. Of the patients with acute kidney injury, 5(26.3%) survived with native liver, 10(52.6%) died and 4 (21.1%) underwent liver transplantation.

Conclusion

Acute kidney injury developed in 22.6% of children with acute‐on‐chronic liver failure. Bilirubin more than 17.7 mg/dL and presence of systemic inflammatory response syndrome were high risk factors for acute kidney injury. Development of acute kidney injury in a child with acute‐on‐chronic liver failure suggests poor outcome and need for early intervention.
Impact of dietary induced precocious gut maturation on cecal microbiota and its relation to the blood‐brain barrier during the postnatal period in rats
Authors: Marungruang N. , Arévalo Sureda E. , Lefrançoise A. , Weström B. , Nyman M. , Prykhodko O. , Fåk Hållenius F.
Published: January 2018

Background

Precocious maturation of the gastrointestinal barrier (GIB) in newborn mammals can be induced by dietary provocation, but how this affects the gut microbiota and the gut‐brain axis remains unknown. The objective of this study was to investigate effects of induced GIB maturation on gut microbiota composition and blood‐brain barrier (BBB) permeability.

Methods

Suckling rats were studied at 72 h after gavage with phytohemagglutinin (PHA) or microbial protease (PT) to induce maturation of GIB. For comparison, untreated suckling and weaned rats were included (n = 10). Human serum albumin (HSA) was administered orally and analyzed in blood to assess permeability of the GIB, while intraperitoneally injected bovine serum albumin (BSA) was measured in the brain tissue for BBB permeability. The cecal microbial composition, plasma lipopolysaccharide‐binding protein (LBP) levels and short‐chain fatty acids in serum and brain were analyzed.

Key Results

Cessation of HSA passage to blood after PHA or PT treatment was similar to that seen in weaned rats. Interestingly, concomitant increases in cecal Bacteroidetes and plasma LBP levels were observed after both PHA and PT treatments. The BBB passage of BSA was surprisingly elevated after weaning, coinciding with lower plasma LBP levels and specific microbial taxa and increased acetate uptake into the brain.

Conclusions & Inferences

This study provides evidence that the gut microbiota alteration following induced precocious GIB maturation may induce low‐grade systemic inflammation and alter SCFAs utilization in the brain which may also play a potential role in GIB‐BBB dysfunction disorders in neonates.
The “hidden” concealed left‐sided accessory pathway: An uncommon cause of SVT in young people
Authors: Pass Robert H. , Liberman Leonardo , Silver Eric S. , Janson Christopher M. , Blaufox Andrew D. , Nappo Lynn , Ceresnak Scott R.
Published: January 2018

Background

Concealed left‐sided accessory pathways (CLAP) are a cause of supraventricular tachycardia (SVT) in the young. Most are mapped with right ventricular (RV) apical/outflow pacing. Rarely, alternative means of mapping are required. We review our experience from three pediatric electrophysiology (EP) centers with a rare form of “hidden” CLAP.

Methods

All patients <21 years undergoing EP study from 2008 to 2014 with a “hidden” CLAP (defined as an accessory pathway [AP] for which RV pacing at cycle lengths [CL] stable for mapping did not demonstrate eccentric retrograde conduction) were included. Exclusion criteria: preexcitation. Demographic, procedural, and follow‐up data were collected.

Results

A total of 23 patients met the criteria (median age, 14.3 years [range 7–21], weight, 51 kg [31–99]). 21 (96%) had SVT and one AFIB (4%). APs were adenosine sensitive in 7/20 patients (35%) and VA conduction was decremental in six (26%). CLAP conduction was demonstrable with orthodromic reentrant tachycardia in all patients, with RV extrastimulus testing in seven (30%) and with rapid RV pacing (<CL 300) in three (13%). Left ventricular (LV) pacing demonstrated CLAP conduction in 17/17 (100%) patients in whom it was used. All 23 CLAPs were successfully ablated (100%) via transseptal approach with radiofrequency energy. Specific ablation techniques included: 16 (70%) during LV paced rhythm, four (17%) during orthodromic reciprocating tachycardia (ORT; 3/4 ventricular entrained), and three (13%) with brief rapid RV pacing. There were no complications. At 18 months (range 3–96), there was one recurrence (4%).

Conclusions

Some CLAPs are only demonstrable with LV pacing, entrained ORT, or rapid RV pacing. LV pacing facilitated preferential AP conduction, allowing for mapping while maintaining stable hemodynamics.
Establishing RNA virus resistance in plants by harnessing CRISPR immune system
Authors: Zhang Tong , Zheng Qiufeng , Yi Xin , An Hong , Zhao Yaling , Ma Siqi , Zhou Guohui
Published: January 2018

Recently, CRISPR‐Cas (clustered, regularly interspaced short palindromic repeats–CRISPR‐associated proteins) system has been used to produce plants resistant to DNA virus infections. However, there is no RNA virus control method in plants that uses CRISPR‐Cas system to target the viral genome directly. Here, we reprogrammed the CRISPR‐Cas9 system from Francisella novicida to confer molecular immunity against RNA viruses in Nicotiana benthamiana and Arabidopsis plants. Plants expressing FnCas9 and sgRNA specific for the cucumber mosaic virus (CMV) or tobacco mosaic virus (TMV) exhibited significantly attenuated virus infection symptoms and reduced viral RNA accumulation. Furthermore, in the transgenic virus‐targeting plants, the resistance was inheritable and the progenies showed significantly less virus accumulation. These data reveal that the CRISPR/Cas9 system can be used to produce plant that stable resistant to RNA viruses, thereby broadening the use of such technology for virus control in agricultural field.
Big Data and the Innovation Cycle
Authors: Lee Hau L.
Published: January 2018

Big data and the related methodologies could have great impacts on operations and supply chain management. Such impacts could be realized through innovations leveraging big data. The innovations can be described as first improving existing processes in operations through better tools and methods; second expanding the value propositions through expansive usage or incorporating data not available in the past; and third allowing companies to create new processes or business models to serve customers in new ways. This study describes this framework of the innovation cycle.
Dynamic Modeling of Solar Radiation Disturbances Based on a Biomimetic Cloud Shading Model
Authors: García Jesús , Portnoy Iván , Vasquez Padilla Ricardo , Sanjuan Marco E.
Published: January 2018

Variation in direct solar radiation is one of the main disturbances that any solar system must handle to maintain efficiency at acceptable levels. As known, solar radiation profiles change due to earth's movements. Even though this change is not manipulable, its behavior is predictable. However, at ground level, direct solar radiation mainly varies due to the effect of clouds, which is a complex phenomenon not easily predictable. In this paper, dynamic solar radiation time series in a two-dimensional (2D) spatial domain are obtained using a biomimetic cloud-shading model. The model is tuned and compared against available measurement time series. The procedure uses an objective function based on statistical indexes that allow extracting the most important characteristics of an actual set of curves. Then, a multi-objective optimization algorithm finds the tuning parameters of the model that better fit data. The results showed that it is possible to obtain responses similar to real direct solar radiation transients using the biomimetic model, which is useful for other studies such as testing control strategies in solar thermal plants.
Optimal Paths for Polygonal Robots in SE(2)
Authors: Kennedy Monroe , Thakur Dinesh , Ani Hsieh M. , Bhattacharya Subhrajit , Kumar Vijay
Published: January 2018

We consider planar navigation for a polygonal, holonomic robot in an obstacle-filled environment in SE(2). To determine the free space, we first represent obstacles as point clouds in the robot configuration space (C). A point-wise Minkowski sum of the robot and obstacle points is then calculated in C using obstacle points and robot convex hull points for varying robot configurations. Using graph search, we obtain a seed path, which is used in our novel method to compute overlapping convex regions for consecutive seed path chords. The resulting regions provide collision-free space useful for finding feasible trajectories that optimize a specified cost functional. The key contribution is the proposed method's ability to easily generate a set of convex, overlapping polytopes that effectively represent the traversable free space. This, in turn, lends itself to (a) efficient computation of optimal paths in ℝ3 and (b) extending these basic ideas to the special Euclidean space SE(2). We provide simulated examples and implement this algorithm on a KUKA youBot omnidirectional base.
Thermally Induced Mechanical Response of Metal Foam During Laser Forming
Authors: Bucher Tizian , Young Adelaide , Zhang Min , Chen Chang Jun , Lawrence Yao Y.
Published: January 2018

To date, metal foam products have rarely made it past the prototype stage. The reason is that few methods exist to manufacture metal foam into the shapes required in engineering applications. Laser forming is currently the only method with a high geometrical flexibility that is able to shape arbitrarily sized parts. However, the process is still poorly understood when used on metal foam, and many issues regarding the foam's mechanical response have not yet been addressed. In this study, the mechanical behavior of metal foam during laser forming was characterized by measuring its strain response via digital image correlation (DIC). The resulting data were used to verify whether the temperature gradient mechanism (TGM), well established in solid sheet metal forming, is valid for metal foam, as has always been assumed without experimental proof. Additionally, the behavior of metal foam at large bending angles was studied, and the impact of laser-induced imperfections on its mechanical performance was investigated. The mechanical response was numerically simulated using models with different levels of geometrical approximation. It was shown that bending is primarily caused by compression-induced shortening, achieved via cell crushing near the laser irradiated surface. Since this mechanism differs from the traditional TGM, where bending is caused by plastic compressive strains near the laser irradiated surface, a modified temperature gradient mechanism (MTGM) was proposed. The densification occurring in MTGM locally alters the material properties of the metal foam, limiting the maximum achievable bending angle, without significantly impacting its mechanical performance.
Stability-controlled hybrid adaptive feedback cancellation scheme for hearing aids
Authors: Nordholm Sven , Schepker Henning , Tran Linh T. T. , Doclo Simon
Published: January 2018

Adaptive feedback cancellation (AFC) techniques are common in modern hearing aid devices (HADs) since these techniques have been successful in increasing the stable gain. Accordingly, there has been a significant effort to improve AFC technology, especially for open-fitting and in-ear HADs, for which howling is more prevalent due to the large acoustic coupling between the loudspeaker and the microphone. In this paper, the authors propose a hybrid AFC (H-AFC) scheme that is able to shorten the time it takes to recover from howling. The proposed H-AFC scheme consists of a switched combination adaptive filter, which is controlled by a soft-clipping-based stability detector to select either the standard normalized least mean squares (NLMS) algorithm or the prediction-error-method (PEM) NLMS algorithm to update the adaptive filter. The standard NLMS algorithm is used to obtain fast convergence, while the PEM-NLMS algorithm is used to provide a low bias solution. This stability-controlled adaptation is hence the means to improve performance in terms of both convergence rate as well as misalignment, while only slightly increasing computational complexity. The proposed H-AFC scheme has been evaluated for both speech and music signals, resulting in a significantly improved convergence and re-convergence rate, i.e., a shorter howling period, as well as a lower average misalignment and a larger added stable gain compared to using either the NLMS or the PEM-NLMS algorithm alone. An objective evaluation using the perceptual evaluation of speech quality and the perceptual evaluation of audio quality measures shows that the proposed H-AFC scheme provides very high-quality speech and music signals. This has also been verified through a subjective listening experiment with N = 15 normal-hearing subjects using a multi-stimulus test with hidden reference and anchor, showing that the proposed H-AFC scheme results in a better perceptual quality than the state-of-the-art PEM-NLMS algorithm.
Pterostilbene, a Potential MCR-1 Inhibitor That Enhances the Efficacy of Polymyxin B
Authors: Zhou Yonglin , Liu Shui , Wang Tingting , Li Hui , Tang Shusheng , Wang Jianfeng , Wang Yang , Deng Xuming
Published: January 2018

We characterized the synergistic effect produced between pterostilbene and polymyxin B (fractional inhibitory concentration [FIC] index = 0.156 or 0.188) against MCR-producing
Escherichia coli
strains of both human and animal origins. The time-killing assays showed that either pterostilbene or polymyxin B failed to eradicate the
mcr-1
- and NDM-positive
E. coli
strain ZJ487, but the combination eliminated the strain by 1 h postinoculation. The survival rate of mice after intraperitoneal infections was significantly enhanced from 0% to 60% in the group in which combination therapy was applied.
Retrospective review of Synacthen testing in infants
Authors: Tan Timothy Shao Ern , Manfredonia Claire , Kumar Rakesh , Jones Julie , O’Shea Elaine , Padidela Raja , Skae Mars , Ehtisham Sarah , Ivison Fiona , Tetlow Lesley , Clayton Peter E , Banerjee Indraneel , Patel Leena
Published: January 2018

Background

A subnormal cortisol response (30 min level (C30min)<550 nmol/L) to synthetic adrenocorticotrophic hormone/Synacthen test (SDST) in all infants does not necessarily indicate underlying or persistent hypothalamic–pituitary–adrenal axis pathology.

Methods

We retrospectively evaluated the diagnoses and outcomes in 68 infants who had a SDST at age <6 months from 2011 to 2014.

Results

29 (43%) infants had a subnormal SDST. Causative pathology was identified in 9/29 (31%). In 20/29 (69%) with no identified pathology, repeat SDST was normal in 18/20 (90%) at median age 0.6 (range 0.1–3.2) years but persistently subnormal in 2. Those with a transient abnormality were more likely to be small for gestational age (P=0.03) and had higher initial SDST C30min (390 nmol/L vs 181 nmol/L, P=0.01) than those with pathology.

Conclusion

Specific aetiology can be identified in a third of infants with a subnormal SDST. When the aetiology remains elusive, adrenal function should be reassessed as the problem can be transient.
Public health guide to field developments linking ecosystems, environments and health in the Anthropocene
Authors: Buse Chris G , Oestreicher Jordan Sky , Ellis Neville R , Patrick Rebecca , Brisbois Ben , Jenkins Aaron P , McKellar Kaileah , Kingsley Jonathan , Gislason Maya , Galway Lindsay , McFarlane Ro A , Walker Joanne , Frumkin Howard , Parkes Margot
Published: January 2018

The impacts of global environmental change have precipitated numerous approaches that connect the health of ecosystems, non-human organisms and humans. However, the proliferation of approaches can lead to confusion due to overlaps in terminology, ideas and foci. Recognising the need for clarity, this paper provides a guide to seven field developments in environmental public health research and practice: occupational and environmental health; political ecology of health; environmental justice; ecohealth; One Health; ecological public health; and planetary health. Field developments are defined in terms of their uniqueness from one another, are historically situated, and core texts or journals are highlighted. The paper ends by discussing some of the intersecting features across field developments, and considers opportunities created through such convergence. This field guide will be useful for those seeking to build a next generation of integrative research, policy, education and action that is equipped to respond to current health and sustainability challenges.
Microrna-452 Exerts Growth-Suppressive Activity against T-Cell Acute Lymphoblastic Leukemia
Authors: Wang Haihao , Guo Qiannan , Zhu Guizhi , Zhu Shuo , Yang Peiwen , Zhang Mingsheng
Published: January 2018

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer. Although microRNA (miR)-452 serves as a tumor suppressor in multiple solid tumors, its expression and function in hematological cancers including T-ALL is largely unknown. We measured the expression of miR-452 in 38 T-ALL and 22 normal lymph node samples by real-time PCR analysis. The methylation levels in the promoter of miR-452 were determined using MethyLight assay. The effects of miR-452 overexpression on proliferation, cell cycle distribution, and tumorigenesis were explored. It was found that miR-452 expression levels were significantly lower in T-ALL specimens than in normal lymph node biopsies (P=0.0079). T-ALL specimens had a significantly higher methylation level in the promoter of miR-452 than normal lymph node tissues (P=0.0014). Consistently, miR-452 was downregulated in Jurkat and Molt-4 T-ALL cells, whose expression was restored after treatment with a demethylation agent 5-aza-2′-deoxycytidine. Ectopic expression of miR-452 inhibited the proliferation of Jurkat and Molt-4 cells and induced a G0/G1 cell cycle arrest. Overexpression of miR-452 suppressed the protein expression of BMI1 in T-ALL cells. Rescue experiments revealed that overexpression of BMI1 partially reversed the growth-suppressive effect of miR-452 on T-ALL cells. Xenograft tumor studies confirmed that overexpression of miR-452 suppressed tumor growth in nude mice and reduced the expression of BMI1. Collectively, miR-452 is epigenetically silenced and targets BMI1 to exert a growth suppressive activity in T-ALL. Restoration of miR-452 expression may represent a promising therapeutic strategy for this malignancy.
Reducing sedentary behaviour to decrease chronic low back pain: the stand back randomised trial
Authors: Barone Gibbs Bethany , Hergenroeder Andrea L , Perdomo Sophy J , Kowalsky Robert J , Delitto Anthony , Jakicic John M
Published: January 2018

Objective

The Stand Back study evaluated the feasibility and effects of a multicomponent intervention targeting reduced prolonged sitting and pain self-management in desk workers with chronic low back pain (LBP).

Methods

This randomised controlled trial recruited 27 individuals with chronic LBP, Oswestry Disability Index (ODI) >10% and desk jobs (sitting ≥20 hours/week). Participants were randomised within strata of ODI (>10%–<20%, ≥20%) to receive bimonthly behavioural counselling (in-person and telephone), a sit-stand desk attachment, a wrist-worn activity-prompting device and cognitive behavioural therapy for LBP self-management or control. Self-reported work sitting time, visual analogue scales (VAS) for LBP and the ODI were assessed by monthly, online questionnaires and compared across intervention groups using linear mixed models.

Results

Baseline mean (SD) age was 52 (11) years, 78% were women, and ODI was 24.1 (10.5)%. Across the 6-month follow-up in models adjusted for baseline value, work sitting time was 1.5 hour/day (P<0.001) lower comparing intervention to controls. Also across follow-up, ODI was on average 8 points lower in intervention versus control (P=0.001). At 6 months, the relative decrease in ODI from baseline was 50% in intervention and 14% in control (P=0.042). LBP from VAS was not significantly reduced in intervention versus control, though small-to-moderate effect sizes favouring the intervention were observed (Cohen’s d ranged from 0.22 to 0.42).

Conclusion

An intervention coupling behavioural counselling targeting reduced sedentary behaviour and pain self-management is a translatable treatment strategy that shows promise for treating chronic LBP in desk-bound employees.

Trial registration number

NCT0224687; Pre-results.
Development of a methodology to backcalculate pavement layer moduli using the traffic speed deflectometer
Authors: Elbagalati Omar , Mousa Momen , Elseifi Mostafa A. , Gaspard Kevin , Zhang Zhongjie
Published: January 2018

Backcalculation analysis of pavement layer moduli is typically conducted based on falling weight deflectometer (FWD) measurements; however, the stationary nature of FWD requires lane closure and traffic control. To overcome these limitations, a number of continuous deflection devices were introduced in recent years. The objective of this study was to develop a methodology to incorporate traffic speed deflectometer (TSD) measurements in the backcalculation analysis. To achieve this objective, TSD and FWD measurements were used to train and to validate an artificial neural network (ANN) model that would convert TSD deflection measurements to FWD deflection measurements. The ANN model showed acceptable accuracy with a coefficient of determination of 0.81 and a good agreement between the backcalculated moduli from FWD and TSD measurements. Evaluation of the model showed that the backcalculated layer moduli from TSD could be used in pavement analysis and in structural health monitoring with a reasonable level of accuracy.
Landau problem and electron vortex in pure gauge fields
Authors: Tiwari S. C.
Published: January 2018

Recently, electron vortices have attracted attention both experimentally and theoretically. A study on the Landau–Dirac problem is made to understand the nature of electron vortices. This line of investigation is motivated by the recent literature on the Landau problem that throws new insights on the nature of orbital angular momentum, i.e. canonical versus kinetic in the context of QCD. The significance of pure gauge vector potential, nontrivial topology and exchange of modular orbital angular momentum to understand the physical origin of electron vortices in the Landau–Dirac problem are new contributions of this paper.
First-principles study on the stability and magnetoelectric properties of multiferroic materials XTiO3 (X = Mn, Fe, Co, Ni)
Authors: Chen Xing-Yuan , Lai Guo-Xia , Gu Di , Zhu Wei-Ling , Lai Tian-Shu , Zhao Yu-Jun
Published: January 2018

The XTiO3 (X = Mn, Fe, Co and Ni) materials with R3c structure could be grown under critical conditions based on first-principles calculations and thermodynamic stability analysis. FeTiO3 and MnTiO3 could be synthesized relatively easily under metal-rich and O-poor conditions, while NiTiO3 could be stable under Ni-rich, O-rich and Ti-poor conditions. The predicted R3c CoTiO3 under thermodynamic equilibrium conditions is suggested to be synthesized under Co-rich, O-rich and Ti-poor conditions, but the calculated phonon dispersion indicates R3c CoTiO3 becomes unstable under the dynamical conditions. The ferroelectric behavior in the XTiO3 (X = Mn, Fe, Co and Ni) system could be dominated by the Ti ion with d0 state and the strong hybridization between Ti and O, while the magnetic property is mainly caused by the contribution of 3d transition metal.
EXPLORING THE IMPACTS OF SERVICE INNOVATION ON CUSTOMER SATISFACTION IN THE TELECOM INDUSTRY: A PERSPECTIVE FROM INTERACTIVE AND SUPPORTIVE SERVICE INNOVATIONS
Authors: TA DAO THI , YANG CHIA-HAN
Published: January 2018

The impact of service innovation on customer perception has been investigated in many studies. This paper provides a unique view of service innovation by categorizing service innovation into two forms, interactive and supportive service innovations, and exploring their effects on customer satisfaction and retention in the context of telecommunication services. A dataset of 402 telecom service users from Vietnam is collected for empirical hypotheses testing of the relationships among supportive/interactive service innovation, customer satisfaction, and customer retention. The findings show that the two components of service innovation, interaction and support, are the key determinants of customer satisfaction and customer retention, which provides important information for telecom managers in service strategy planning. The study suggests that service firms should differentiate themselves by investing in supportive service innovations since interactive services are characterized by ease of copying, especially in the telecom sector, which is a highly technology-mediated environment.
Information and Inventories in High-Frequency Trading
Authors: Muhle-Karbe Johannes , Webster Kevin
Published: January 2018

We study how short-term informational advantages can be monetized in a high-frequency setting, when large inventories are explicitly penalized. We find that if most of the additional information is revealed regardless of the high-frequency traders’ actions, then fast inventory management allows one to minimize positions with only second-order losses to expected returns. This is no longer possible if most of the additional information is only revealed through trades.
Consistency-Aware Scheduling for Weakly Consistent Programs
Authors: Dabaghchian Maryam , Rakamaric Zvonimir , Ozkan Burcu K. , Mutlu Erdal , Tasiran Serdar
Published: January 2018

Modern geo-replicated data stores provide high availability by relaxing the underlying consistency requirements. Programs layered over such data stores are called weakly consistent programs. Due to the reduced consistency requirements, they exhibit highly nondeterministic behaviors, some of which might violate program invariants. Therefore, implementing correct weakly consistent programs and reasoning about them is challenging. In this paper, we present a systematic scheduling approach that is aware of the underlying consistency model. Our approach dynamically explores all possible program behaviors allowed by the used data store consistency model, and it evaluates program invariants during the exploration. We implement the approach in a prototype model checker for Antidote, which is a causally consistent key-value data store with convergent con ict handling. We evaluate our tool on several benchmarks. The results show that our approach is e effective in detecting buggy behaviors in weakly consistent programs.
JPR
Authors: Wang Kaiyuan , Khurshid Sarfraz , Gligoric Milos
Published: January 2018

Java PathFinder (JPF) is a backtrackable Java Virtual Machine (JVM), which is implemented in Java and runs on a standard JVM (e.g., Oracle HotSpot). Thus, a JPF developer can use off-the- shelf Java debuggers (e.g., jdb) when debugging code that makes up JPF. JPF explores all non-deterministic executions of a given target program and monitors for property violations. To facilitate debugging of the target program, JPF can capture and replay the execution trace that leads to a property violation. While the deterministic replay is invaluable, the replay with JPF does not allow the developer to attach an off-the-shelf Java debugger to the target program (e.g., step through the application code, set breakpoints, etc.).

We present a technique, dubbed JPR, to improve the debugging experience of the JPF captured traces by migrating the JPF traces to a new format that can be executed using the standard JVM. JPR annotates each JPF trace, during the capture phase, with ex- tra data (e.g., instruction index, instruction count, etc.); the an- notated trace is then used to instrument Java bytecode to enforce the same execution trace on a standard JVM. JPR is compatible with various optimizations, e.g., state matching and partial-order reduction. We evaluated JPR on all multi-threaded Java pro- grams in the official JPF distribution. Our results show that JPR successfully replayed all JPF traces on the standard JVM with reasonable overhead during both recording and replaying.
How Easy it is to Write Software for Heterogeneous Systems?
Authors: Sarkar Santonu , Alavani Gargi
Published: January 2018

Every other personal computer today is provided with a coprocessor making it a heterogeneous computing environment. As the heterogeneous and high-performance computing (HPC) infrastructure becomes a commodity, the need to improve software development productivity to build efficient parallel programs for this infrastructure becomes all the more crucial. While the mainstream software development methodology focuses on modular design, reusability, ease of understanding and so on, parallel program development emphasizes on performance, optimal use of a hardware resource, scalability, execution correctness, and portability across multiple hardware platforms. In this paper, we identify a few unique software development productivity requirements for heterogeneous systems. These requirements are concerned with design abstraction, reusability, and design verification. While these requirements are applicable for a conventional software as well, their implications are far reaching in the context of parallel programs. Here we discuss significant e orts in building tools and frameworks to i) provide powerful abstraction over the hardware, ii) build software libraries for parallel hardware access and iii) implement verification mechanisms to check the correctness of a program behavior in a heterogeneous runtime environment. We also identify several important gaps in the existing work that needs to be addressed in order to make the current body of work useful in practice.
Immune Responses in the Liver
Authors: Kubes Paul , Jenne Craig
Published: January 2018

The liver is a key, frontline immune tissue. Ideally positioned to detect pathogens entering the body via the gut, the liver appears designed to detect, capture, and clear bacteria, viruses, and macromolecules. Containing the largest collection of phagocytic cells in the body, this organ is an important barrier between us and the outside world. Importantly, as portal blood also transports a large number of foreign but harmless molecules (e.g., food antigens), the liver's default immune status is anti-inflammatory or immunotolerant; however, under appropriate conditions, the liver is able to mount a rapid and robust immune response. This balance between immunity and tolerance is essential to liver function. Excessive inflammation in the absence of infection leads to sterile liver injury, tissue damage, and remodeling; insufficient immunity allows for chronic infection and cancer. Dynamic interactions between the numerous populations of immune cells in the liver are key to maintaining this balance and overall tissue health.
Breast Cancer Targeting through Inhibition of the Endoplasmic Reticulum-Based Apoptosis Regulator Nrh/BCL2L10
Authors: Nougarede Adrien , Popgeorgiev Nikolay , Kassem Loay , Omarjee Soleilmane , Borel Stephane , Mikaelian Ivan , Lopez Jonathan , Gadet Rudy , Marcillat Olivier , Treilleux Isabelle , Villoutreix Bruno O. , Rimokh Ruth , Gillet Germain
Published: January 2018

Drug resistance and metastatic relapse remain a top challenge in breast cancer treatment. In this study, we present preclinical evidence for a strategy to eradicate advanced breast cancers by targeting the BCL-2 homolog Nrh/BCL2L10, which we discovered to be overexpressed in >45% of a large cohort of breast invasive carcinomas. Nrh expression in these tumors correlated with reduced metastasis-free survival, and we determined it to be an independent marker of poor prognosis. Nrh protein localized to the endoplasmic reticulum. Mechanistic investigations showed that Nrh made BH4 domain–dependent interactions with the ligand-binding domain of the inositol-1,4,5-triphosphate receptor (IP3R), a type 1/3 Ca2+ channel, allowing Nrh to negatively regulate ER-Ca2+ release and to mediate antiapoptosis. Notably, disrupting Nrh/IP3R complexes by BH4 mimetic peptides was sufficient to inhibit the growth of breast cancer cells in vitro and in vivo. Taken together, our results highlighted Nrh as a novel prognostic marker and a candidate therapeutic target for late stage breast cancers that may be addicted to Nrh.

Significance: These findings offer a comprehensive molecular model for the activity of Nrh/BCL2L10, a little studied antiapoptotic molecule, prognostic marker, and candidate drug target in breast cancer. Cancer Res; 78(6); 1404–17. ©2018 AACR.
Demethylation-Induced Overexpression of Shc3 Drives c-Raf–Independent Activation of MEK/ERK in HCC
Authors: Liu Yun , Zhang Xinran , Yang Baicai , Zhuang Hao , Guo Hua , Wei Wen , Li Yuan , Chen Ruibing , Li Yongmei , Zhang Ning
Published: January 2018

Invasion and intrahepatic metastasis are major factors of poor prognosis in patients with hepatocellular carcinoma (HCC). In this study, we show that increased Src homolog and collagen homolog 3 (Shc3) expression in malignant HCC cell lines associate with HCC invasion and metastasis. Shc3 (N-Shc) was significantly upregulated in tumors of 33 HCC patient samples as compared with adjacent normal tissues. Further analysis of 52 HCC patient samples showed that Shc3 expression correlated with microvascular invasion, cancer staging, and poor prognosis. Shc3 interacted with major vault protein, resulting in activation of MEK1/2 and ERK1/2 independently of Shc1 and c-Raf; this interaction consequently induced epithelial–mesenchymal transition and promoted HCC cell proliferation and metastasis. The observed increase in Shc3 levels was due to demethylation of its upstream promoter, which allowed c-Jun binding. In turn, Shc3 expression promoted c-Jun phosphorylation in a positive feedback loop. Analysis of metastasis using a tumor xenograft mouse model further confirmed the role of Shc3 in vivo. Taken together, our results indicate the importance of Shc3 in HCC progression and identify Shc3 as a novel biomarker and potential therapeutic target in HCC.

Significance: Ectopic expression of Shc3 forms a complex with MVP/MEK/ERK to potentiate ERK activation and plays an important role in sorafinib resistance in HCC. Cancer Res; 78(9); 2219–32. ©2018 AACR.
Clinical Utility of a STAT3-Regulated miRNA-200 Family Signature with Prognostic Potential in Early Gastric Cancer
Authors: Yu Liang , Wu Di , Gao Hugh , Balic Jesse J. , Tsykin Anna , Han Tae-Su , Liu You Dong , Kennedy Catherine L. , Li Ji Kun , Mao Jie Qi , Tan Patrick , Oshima Masanobu , Goodall Gregory J. , Jenkins Brendan J.
Published: January 2018

Purpose: The majority of gastric cancer patients are diagnosed with late-stage disease, for which distinct molecular subtypes have been identified that are potentially amenable to targeted therapies. However, there exists no molecular classification system with prognostic power for early-stage gastric cancer (EGC) because the molecular events promoting gastric cancer initiation remain ill-defined.

Experimental Design: miRNA microarrays were performed on gastric tissue from the gp130F/F preclinical EGC mouse model, prior to tumor initiation. Computation prediction algorithms were performed on multiple data sets and independent gastric cancer patient cohorts. Quantitative real-time PCR expression profiling was undertaken in gp130F/F-based mouse strains and human gastric cancer cells genetically engineered for suppressed activation of the oncogenic latent transcription factor STAT3. Human gastric cancer cells with modulated expression of the miR-200 family member miR-429 were also assessed for their proliferative response.

Results: Increased expression of miR-200 family members is associated with both tumor initiation in a STAT3-dependent manner in gp130F/F mice and EGC (i.e., stage IA) in patient cohorts. Overexpression of miR-429 also elicited contrasting pro- and antiproliferative responses in human gastric cancer cells depending on their cellular histologic subtype. We also identified a miR-200 family–regulated 15-gene signature that integrates multiple key current indicators of EGC, namely tumor invasion depth, differentiation, histology, and stage, and provides superior predictive power for overall survival compared with each EGC indicator alone.

Conclusions: Collectively, our discovery of a STAT3-regulated, miR-200 family–associated gene signature specific for EGC, with predictive power, provides a molecular rationale to classify and stratify EGC patients for endoscopic treatment. Clin Cancer Res; 24(6); 1459–72. ©2018 AACR.