bluuebunny/crossref_metadata_2025 huggingface dataset:
Papers of note in
Science
Authors: VanHook Annalisa M.
Published: September 2016

This week’s articles highlight how tissue of origin affects the response of cancer cells to targeted therapies, the transmission of contractile forces in collectively migrating cells, the proteins of the inhibitory postsynaptic membrane, and a bioengineered system for following the timing and magnitude of signaling events in vivo.
Long noncoding RNA tells myeloid cells how long to live
Authors: Gough Nancy R.
Published: September 2016

A long noncoding RNA poises a proapoptotic gene for expression in myeloid cells.
DNA Targeting as a Likely Mechanism Underlying the Antibacterial Activity of Synthetic Bis-Indole Antibiotics
Authors: Opperman Timothy J. , Kwasny Steven M. , Li Jessica Bo , Lewis Mark A. , Aiello Daniel , Williams John D. , Peet Norton P. , Moir Donald T. , Bowlin Terry L. , Long Eric C.
Published: September 2016

We previously reported the synthesis and biological activity of a series of cationic bis-indoles with potent, broad-spectrum antibacterial properties. Here, we describe mechanism of action studies to test the hypothesis that these compounds bind to DNA and that this target plays an important role in their antibacterial outcome. The results reported here indicate that the bis-indoles bind selectively to DNA at A/T-rich sites, which is correlated with the inhibition of DNA and RNA synthesis in representative Gram-positive (
Staphylococcus aureus
) and Gram-negative (
Escherichia coli
) organisms. Further, exposure of
E. coli
and
S. aureus
to representative bis-indoles resulted in induction of the DNA damage-inducible SOS response. In addition, the bis-indoles were found to be potent inhibitors of cell wall biosynthesis; however, they do not induce the cell wall stress stimulon in
S. aureus
, suggesting that this pathway is inhibited by an indirect mechanism. In light of these findings, the most likely basis for the observed activities of these compounds is their ability to bind to the minor groove of DNA, resulting in the inhibition of DNA and RNA synthesis and other secondary effects.
Preclinical Evaluation of the Stability, Safety, and Efficacy of CD101, a Novel Echinocandin
Authors: Ong Voon , Hough Grayson , Schlosser Michael , Bartizal Ken , Balkovec James M. , James Kenneth D. , Krishnan B. Radha
Published: September 2016

Fungal infections pose a significant public health burden with high morbidity and mortality. CD101 is a novel echinocandin under development for the treatment and prevention of systemic
Candida
infections. Preclinical studies were conducted to evaluate the metabolic stability, plasma protein binding, pharmacokinetics, toxicity, and efficacy of CD101 at various dose levels. CD101 was stable to biotransformation in rat, monkey, and human liver microsomes and rat, monkey, dog, and human hepatocytes.
In vitro
studies suggest minimal interaction with recombinant cytochrome P450 enzymes (50% inhibitory concentrations [IC
50
s] of >10 μM). Similar to anidulafungin, CD101 bound avidly (>98%) to human, mouse, rat, and primate plasma proteins. In a 2-week repeat-dose comparison study, CD101 was well tolerated in rats (no effects on body weight, hematology, coagulation, or urinalysis). In contrast, administration of anidulafungin (at comparable exposure levels) resulted in reduced body weight, decreases in red blood cell, hemoglobin, hematocrit, mean cell volume, mean corpuscular hemoglobin, platelet, and reticulocyte counts, increases in neutrophil and eosinophil counts, polychromasia, and decreased activated partial thromboplastin time. Elevated plasma transaminases, total bilirubin, cholesterol, and globulin, dark and enlarged spleens, and single-cell hepatocyte necrosis were also observed for anidulafungin but not CD101. Hepatotoxicity may be due to the inherent chemical lability of anidulafungin generating potentially reactive intermediates. A glutathione trapping experiment confirmed the formation of a reactive species from anidulafungin, whereas CD101 did not exhibit instability or reactive intermediates. CD101 showed antifungal activity against
Candida
and
Aspergillus
infections in neutropenic mice. These preclinical studies demonstrated that CD101 is chemically and metabolically stable, well tolerated with no hepatotoxicity, and efficacious as an antifungal agent.
A Modified P1 Moiety Enhances
In Vitro
Antiviral Activity against Various Multidrug-Resistant HIV-1 Variants and
In Vitro
Central Nervous System Penetration Properties of a Novel Nonpeptidic Protease Inhibitor, GRL-10413
Authors: Amano Masayuki , Salcedo-Gómez Pedro Miguel , Zhao Rui , Yedidi Ravikiran S. , Das Debananda , Bulut Haydar , Delino Nicole S. , Sheri Venkata Reddy , Ghosh Arun K. , Mitsuya Hiroaki
Published: September 2016

We report here that GRL-10413, a novel nonpeptidic HIV-1 protease inhibitor (PI) containing a modified P1 moiety and a hydroxyethylamine sulfonamide isostere, is highly active against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC
50
] of 0.00035 to 0.0018 μM), with minimal cytotoxicity (50% cytotoxic concentration [CC
50
] = 35.7 μM). GRL-10413 blocked the infectivity and replication of HIV-1
NL4-3
variants selected by use of atazanavir, lopinavir, or amprenavir (APV) at concentrations of up to 5 μM (EC
50
= 0.0021 to 0.0023 μM). GRL-10413 also maintained its strong antiviral activity against multidrug-resistant clinical HIV-1 variants isolated from patients who no longer responded to various antiviral regimens after long-term antiretroviral therapy. The development of resistance against GRL-10413 was significantly delayed compared to that against APV. In addition, GRL-10413 showed favorable central nervous system (CNS) penetration properties as assessed with an
in vitro
blood-brain barrier (BBB) reconstruction system. Analysis of the crystal structure of HIV-1 protease in complex with GRL-10413 demonstrated that the modified P1 moiety of GRL-10413 has a greater hydrophobic surface area and makes greater van der Waals contacts with active site amino acids of protease than in the case of darunavir. Moreover, the chlorine substituent in the P1 moiety interacts with protease in two distinct configurations. The present data demonstrate that GRL-10413 has desirable features for treating patients infected with wild-type and/or multidrug-resistant HIV-1 variants, with favorable CNS penetration capability, and that the newly modified P1 moiety may confer desirable features in designing novel anti-HIV-1 PIs.
Dietary Composition Influences Incidence of Helicobacter pylori-Induced Iron Deficiency Anemia and Gastric Ulceration
Authors: Beckett Amber C. , Piazuelo M. Blanca , Noto Jennifer M. , Peek Richard M. , Washington M. Kay , Algood Holly M. Scott , Cover Timothy L.
Published: September 2016

Epidemiologic studies have provided conflicting data regarding an association between
Helicobacter pylori
infection and iron deficiency anemia (IDA) in humans. Here, a Mongolian gerbil model was used to investigate a potential role of
H. pylori
infection, as well as a possible role of diet, in
H. pylori-
associated IDA. Mongolian gerbils (either
H. pylori
infected or uninfected) received a normal diet or one of three diets associated with increased
H. pylori
virulence: high-salt, low-iron, or a combination of a high-salt and low-iron diet. In an analysis of all infected animals compared to uninfected animals (independent of diet),
H. pylori-
infected gerbils had significantly lower hemoglobin values than their uninfected counterparts at 16 weeks postinfection (
P
< 0.0001). The mean corpuscular volume (MCV) and serum ferritin values were significantly lower in
H. pylori-
infected gerbils than in uninfected gerbils, consistent with IDA. Leukocytosis and thrombocytosis were also detected in infected gerbils, indicating the presence of a systemic inflammatory response. In comparison to uninfected gerbils,
H. pylori
-infected gerbils had a higher gastric pH, a higher incidence of gastric ulcers, and a higher incidence of fecal occult blood loss. Anemia was associated with the presence of gastric ulceration but not gastric cancer. Infected gerbils consuming diets with a high salt content developed gastric ulcers significantly more frequently than gerbils consuming a normal-salt diet, and the lowest hemoglobin levels were in infected gerbils consuming a high-salt/low-iron diet. These data indicate that
H. pylori
infection can cause IDA and that the composition of the diet influences the incidence and severity of
H. pylori-
induced IDA.
Yersinia pseudotuberculosis Blocks Neutrophil Degranulation
Authors: Taheri Nayyer , Fahlgren Anna , Fällman Maria
Published: September 2016

Neutrophils are essential components of immunity and are rapidly recruited to infected or injured tissue. Upon their activation, neutrophils release granules to the cell's exterior, through a process called degranulation. These granules contain proteins with antimicrobial properties that help combat infection. The enteropathogenic bacteriumYersinia pseudotuberculosissuccessfully persists as an extracellular bacterium during infection by virtue of its translocation of virulence effectors (Yersiniaouter proteins [Yops]) that act in the cytosol of host immune cells to subvert phagocytosis and proinflammatory responses. Here, we investigated the effect ofY. pseudotuberculosison neutrophil degranulation upon cell contact. We found that virulentY. pseudotuberculosiswas able to prevent secondary granule release. The blocking effect was general, as the release of primary and tertiary granules was also reduced. Degranulation of secondary granules was also blocked in primed neutrophils, suggesting that this mechanism could be an important element of immune evasion. Further, wild-type bacteria conferred a transient block on neutrophils that prevented their degranulation upon contact with plasmid-cured, avirulentY. pseudotuberculosisandEscherichia coli. Detailed analyses showed that the block was strictly dependent on the cooperative actions of the two antiphagocytic effectors, YopE and YopH, suggesting that the neutrophil target structures constituting signaling molecules needed to initiate both phagocytosis and general degranulation. Thus, via these virulence effectors,Yersiniacan impair several mechanisms of the neutrophil's antimicrobial arsenal, which underscores the power of its virulence effector machinery.
Evidence for Eocene–Oligocene glaciation in the landscape of the East Greenland margin
Authors: Bernard Thomas , Steer Philippe , Gallagher Kerry , Szulc Adam , Whitham Andrew , Johnson Christopher
Published: September 2016

Assessing the onset and extent of Northern Hemisphere glaciation is required to understand Cenozoic climate change and its impact on topography. While the onset of accelerated Cenozoic erosion is generally associated with the Quaternary at mid-latitudes, some high-latitude passive margins may have undergone earlier glaciation starting at 38–30 Ma or even 45 Ma. Here we document a rapid phase of exhumation in the East Greenland margin between 68°N and 76°N starting at 30 ± 5 Ma. The timing is coincident with the dramatic worldwide fall of surface temperature at the Eocene-Oligocene transition. Our inference is based on apatite fission track and apatite helium data. We suggest that a transition from an Eocene fluvial to an Oligocene glacial-dominated landscape triggered a period of enhanced erosion. This study provides the first onshore potential evidence of the onset of continental ice in East Greenland margin at the Eocene-Oligocene transition (ca. 34 Ma), contemporaneously with the onset of Antarctica glaciation and erosion. Our interpretation is consistent with that based on the oldest ice-rafted debris found in the sedimentary records offshore East Greenland and implies that East Greenland exhibits the oldest onshore record of Cenozoic glacial erosion on Earth.
The Neogene de-greening of Central Asia
Authors: Caves Jeremy K. , Moragne Danielle Y. , Ibarra Daniel E. , Bayshashov Bolat U. , Gao Yuan , Jones Matthew M. , Zhamangara Aizhan , Arzhannikova Anastasia V. , Arzhannikov Sergey G. , Chamberlain C. Page
Published: September 2016

There remains substantial debate concerning the relative roles of tectonics and global climate in driving the evolution of climate in Central Asia. Today, interior Asia—including the Taklamakan, Gobi, and Ordos Deserts—is exceptionally arid and is surrounded by distinct rainfall boundaries, such as those generated by the Asian monsoon systems to the east and south and those generated by high topography to the north and west. Determining how and why these boundaries have varied over the Neogene is hindered by the lack of a single proxy that can be broadly applied through space and time. We construct isoscapes of pedogenic carbonate δ13C (δ13Cc) over the Neogene in Asia by combining a compilation of 2236 published measurements with new data from three localities in northern Central Asia. Pedogenic carbonate δ13C records local aridity—excepting localities impacted by C4 grasslands and during large changes in atmospheric pCO2—through variations in soil respiration, depth of carbonate formation, and the effect of water stress on plant δ13C. Together, these effects reflect changes in both primary productivity and mean annual precipitation. Throughout the Neogene, we find consistent and exceptionally high δ13Cc in interior Asia with a ring of lower δ13Cc that demarcates higher precipitation. This persistent ring of lower δ13Cc corresponds in the south and east with the influence of the Asian monsoon systems; in the west and north, it reflects both orographic rainfall due to uplift of the Tian Shan and to moisture delivery by the mid-latitude westerlies. Finally, δ13Cc and, hence, aridity increases regionally in the latest Neogene, reflecting the effects of Northern Hemisphere glaciation and cooling. This widespread “de-greening” would have increased regional albedo and modified basin-scale water balances, resulting in greater dust fluxes due to reduced vegetative cover and precipitation.
Aspergillosis complicating a microwave ablation cavity
Authors: Singh Saurabh , Bandula Steven , Brown Jeremy , Whelan Jeremy , Illing Rowland
Published: September 2016

We present a case of a patient who following chemotherapy developed semi-invasive pulmonary aspergillosis and an aspergilloma in a lung cavity previously formed by microwave ablation (MWA). A 55-year-old woman presented with cough and shortness of breath after finishing three cycles of chemotherapy for a metastatic nerve sheath tumour. She had been treated by MWA for pulmonary metastases 2 years previously which resulted in a residual right apical lung cavity. Postchemotherapy imaging showed that this cavity had enlarged, developed a thicker wall and contained lobulated soft tissue with a crescent sign on coronal reformats. In addition, the patient'sAspergillus-specific IgG was markedly raised. Treatment with itraconazole improved the symptoms and reduced the cavity size and wall thickness. This case shows that persisting lung cavities after MWA are a potential site for semi-invasive aspergillosis and has implications for the timing of chemotherapy in patient with metastatic lung disease.
Giant oesophageal leiomyoma causing severe hypertension
Authors: Lovece Andrea , Milito Pamela , Asti Emanuele , Bonavina Luigi
Published: September 2016

Leiomyoma is the most common oesophageal tumour and is symptomatic in about half of the patients. Dysphagia is the most common symptom. A 41-year-old woman presented with recent onset of severe orthostatic hypertension. During the cardiological work-up, a mediastinal mass was found at transthoracic echocardiogram. Further investigation (upper gastrointestinal endoscopy, endoscopic ultrasonography, CT scan and cardiac MRI) confirmed the diagnosis of a large oesophageal submucosal mass compressing the supradiaphragmatic inferior vena cava. The mass was resected through a minimally invasive right thoracoscopic approach with complete relief of symptoms and compression on the vena cava.
Gut microbiota, metabolome and immune signatures in patients with uncomplicated diverticular disease
Authors: Barbara Giovanni , Scaioli Eleonora , Barbaro Maria Raffaella , Biagi Elena , Laghi Luca , Cremon Cesare , Marasco Giovanni , Colecchia Antonio , Picone Gianfranco , Salfi Nunzio , Capozzi Francesco , Brigidi Patrizia , Festi Davide
Published: September 2016

Objective

The engagement of the gut microbiota in the development of symptoms and complications of diverticular disease has been frequently hypothesised. Our aim was to explore colonic immunocytes, gut microbiota and the metabolome in patients with diverticular disease in a descriptive, cross-sectional, pilot study.

Design

Following colonoscopy with biopsy and questionnaire phenotyping, patients were classified into diverticulosis or symptomatic uncomplicated diverticular disease; asymptomatic subjects served as controls. Mucosal immunocytes, in the diverticular region and in unaffected sites, were quantified with immunohistochemistry. Mucosa and faecal microbiota were analysed by the phylogenetic platform high taxonomic fingerprint (HTF)-Microbi.Array, while the metabolome was assessed by1H nuclear magnetic resonance.

Results

Compared with controls, patients with diverticula, regardless of symptoms, had a >70% increase in colonic macrophages. Their faecal microbiota showed depletion ofClostridiumcluster IV.Clostridiumcluster IX,Fusobacteriumand Lactobacillaceae were reduced in symptomatic versus asymptomatic patients. A negative correlation was found between macrophages and mucosalClostridiumcluster IV andAkkermansia. Urinary and faecal metabolome changes in diverticular disease involved the hippurate and kynurenine pathways. Six urinary molecules allowed to discriminate diverticular disease and control groups with >95% accuracy.

Conclusions

Patients with colonic diverticular disease show depletion of microbiota members with anti-inflammatory activity associated with mucosal macrophage infiltration. Metabolome profiles were linked to inflammatory pathways and gut neuromotor dysfunction and showed the ability to discriminate diverticular subgroups and controls. These data pave the way for further large-scale studies specifically aimed at identifying microbiota signatures with a potential diagnostic value in patients with diverticular disease.
Team Science as Interprofessional Collaborative Research Practice: A Systematic Review of the Science of Team Science Literature
Authors: Little Meg M , St Hill Catherine A , Ware Kenric B , Swanoski Michael T , Chapman Scott A , Lutfiyya M Nawal , Cerra Frank B
Published: September 2016

The National Institute of Health's concept of team science is a means of addressing complex clinical problems by applying conceptual and methodological approaches from multiple disciplines and health professions. The ultimate goal is the improved quality of care of patients with an emphasis on better population health outcomes. Collaborative research practice occurs when researchers from >1 health-related profession engage in scientific inquiry to jointly create and disseminate new knowledge to clinical and research health professionals in order to provide the highest quality of patient care to improve population health outcomes. Training of clinicians and researchers is necessary to produce clinically relevant evidence upon which to base patient care for disease management and empirically guided team-based patient care. In this study, we hypothesized that team science is an example of effective and impactful interprofessional collaborative research practice. To assess this hypothesis, we examined the contemporary literature on the science of team science (SciTS) produced in the past 10 years (2005–2015) and related the SciTS to the overall field of interprofessional collaborative practice, of which collaborative research practice is a subset. A modified preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach was employed to analyze the SciTS literature in light of the general question: Is team science an example of interprofessional collaborative research practice? After completing a systematic review of the SciTS literature, the posed hypothesis was accepted, concluding that team science is a dimension of interprofessional collaborative practice.
Costs of drugs for treatment of rheumatic diseases
Authors: Westhovens Rene , Annemans Lieven
Published: September 2016

The cost of drugs is becoming an issue worldwide, in particular for inflammatory rheumatic diseases. In the current review, an overview of the scene is given with a specific emphasis on accessibility for those patients in real need of the available expensive treatments. The authors propose 7 principles for discussion that need to be addressed and are a responsibility for all stakeholders in rheumatology.
Frizzledgene expression and negative regulation of canonical WNT–β-catenin signaling in mouse F9 teratocarcinoma cells
Authors: Golenia Gregory , Gatie Mohamed I. , Kelly Gregory M.
Published: September 2016

Mouse F9 cells differentiate into primitive endoderm (PrE) following the activation of the canonical WNT–β-catenin pathway. The upregulation of Wnt6 and activation of β-catenin–TCF–LEF-dependent transcription is known to accompany differentiation, but the Frizzled (FZD) receptor responsible for transducing the WNT6 signal is not known. Eight of the 10 Fzd genes were found to be expressed in F9 cells, with Fzd7 being the most highly expressed, and chosen for further analysis. To alter steady-state Fzd7 levels and test the effect this has on differentiation, siRNA and overexpression approaches were used to knock-down and ectopically express the Fzd7 message, respectively. siRNA knock-down of Fzd7 resulted in reduced DAB2 levels, and the overexpression activated a TCF–LEF reporter, but neither approach affected differentiation. Our focus turned to how canonical WNT6 signaling was attenuated to allow PrE cells to form parietal endoderm (PE). Dkk1, encoding a WNT antagonist, was examined and results showed that its expression increased in F9 cells treated with retinoic acid (RA) or overexpressing Wnt6. F9 cells overexpressing human DKK1 or treated with DKK1-conditioned medium and then treated with RA failed to differentiate, indicating that a negative feedback loop involving WNT6 and DKK1 attenuates canonical WNT–β-catenin signaling, thereby allowing PE cells to differentiate.
Setting biological reference points for sea scallops (Placopecten magellanicus) allowing for the spatial distribution of productivity and fishing effort
Authors: Smith Stephen J. , Sameoto Jessica A. , Brown Craig J.
Published: September 2016

Management for the major sea scallop (Placopecten magellanicus) fisheries in Canada is based on maximum sustainable yield (MSY) biomass and fishing mortality reference points applied to the whole stock, under the assumption that fishing mortality is uniformly distributed in space. However, scallop fishing vessels concentrate fishing in areas that consistently exhibit high densities resulting in a nonuniform spatial distribution of fishing effort. This study applies a spatial model for fishing effort derived from satellite vessel monitoring system data, scallop habitat suitability maps, and relative scallop density from a spatial stock assessment model to evaluate precautionary approach reference points in support of sustainable management. Target harvest rates were evaluated in terms of MSY for the higher habitat suitability areas. The results indicated that although MSY for the spatial model were similar to those when assuming a uniform distribution of effort, the biomass and catch rates over all areas were higher. The spatial model predicted that the MSY would be taken with less fishing effort, potentially lessening the benthic impacts from the scallop fishery.
Competition alters tree growth responses to climate at individual and stand scales
Authors: Ford Kevin R. , Breckheimer Ian K. , Franklin Jerry F. , Freund James A. , Kroiss Steve J. , Larson Andrew J. , Theobald Elinore J. , HilleRisLambers Janneke
Published: September 2016

Understanding how climate affects tree growth is essential for assessing climate change impacts on forests but can be confounded by effects of competition, which strongly influences tree responses to climate. We characterized the joint influences of tree size, competition, and climate on diameter growth using hierarchical Bayesian methods applied to permanent sample plot data from the montane forests of Mount Rainier National Park, Washington State, USA, which are mostly comprised of Abies amabilis Douglas ex Forbes, Tsuga heterophylla (Raf.) Sarg., Pseudotsuga menziesii (Mirb.) Franco, and Thuja plicata Donn ex D. Don. Individual growth was sensitive to climate under low but not high competition, likely because tree ability to increase growth under more favorable climates (generally greater energy availability) was constrained by competition, with important variation among species. Thus, climate change will likely increase individual growth most in uncrowded stands with lower competition. However, crowded stands have more and (or) larger trees, conferring greater capacity for aggregate absolute growth increases. Due to these contrasting effects, our models predicted that climate change will lead to greater stand-scale growth increases in stands with medium compared with low crowding but similar increases in stands with medium and high crowding. Thus, competition will mediate the impacts of climate change on individual- and stand-scale growth in important but complex ways.
Assessing the structure of primeval and managed beech forests in the Ukrainian Carpathians using remote sensing
Authors: Rehush Nataliia , Waser Lars T.
Published: September 2016

Forest structure reflects the forest disturbance regime and can provide important information about the rate of human impact. A better understanding of the structural variability and large-scale dynamics of natural forests is crucial for “close to nature” forest management planning. In this study, we developed a partly automated approach to assess the structure of potential primeval and managed beech forests in the Ukrainian Carpathians using WorldView-2 imagery. We analyzed the local (50 m × 50 m scale) canopy closure of these forests by extracting the canopy gaps and determined four forest structure types ranging from very closed to low density. The occurrence and frequencies of these structure types were significantly different in the primeval and managed beech forests. The four forest structure types were predicted and mapped using multinomial logistic regression based on the textural features derived from the original image bands and two vegetation indices. A 10-fold cross-validation resulted in an overall accuracy of 83% and a kappa coefficient of 75%, with the highest agreement for the very closed structure type (87%) and the lowest agreement for the medium density and low density structure types (79%). The forest structure type maps can be helpful for planning management activities in beech forests.
Low energy determination of the QCD strong coupling constant on the lattice
Authors: Maezawa Yu , Petreczky Peter
Published: September 2016

We present a determination of the strong coupling constant from lattice quantum chromodynamics (QCD) using the moments of pseudo-scalar charmonium correlators calculated using highly improved staggered quark action. We obtain a value [Formula: see text], which is the lowest energy determination of the strong coupling constant so far.
Newton law in covariant unimodular F(R) gravity
Authors: Nojiri S. , Odintsov S. D. , Oikonomou V. K.
Published: September 2016

We investigate the Newton law in the unimodular F(R) gravity. In the standard F(R) gravity, due to the extra scalar mode, there often appear the large corrections to the Newton law and such models are excluded by the experiments and/or the observations. In the unimodular F(R) gravity, however, the extra scalar mode become not to be dynamical due to the unimodular constraint and there is not any correction to the Newton law. Even in the unimodular Einstein gravity, the Newton law is reproduced but the mechanism is a little bit different from that in the unimodular F(R) gravity. We also investigate the unimodular F(R) gravity in the covariant formulation. In the covariant formulation, we include the three-form field. We show that the three-form field could not have any unwanted property, like ghost nor correction to the Newton law. In the covariant formulation, however, the above extra scalar mode becomes dynamical and could give a correction to the Newton law. We also show that there are no difference in the Friedmann–Robertson–Walker (FRW) dynamics in the non-covariant and covariant formulation.
Nonlinear model of elastic field sources
Authors: Lev B. I. , Zagorodny A. G.
Published: September 2016

A general concept of the long-range elastic interactions in continuous medium is proposed. The interaction is determined as a consequence of symmetry breaking of the elastic field distribution produced by the topological defect as isolated inclusions. It is proposed to treat topological defects as the source of elastic field that can be described in terms of this field. The source is considered as a nonlinear object which determines the effective charge of the field at large distances in the linear theory. The models of the nonlinear source are proposed.
Classifying bilinear differential equations by linear superposition principle
Authors: Zhang Lijun , Khalique Chaudry Masood , Ma Wen-Xiu
Published: September 2016

In this paper, we investigate the linear superposition principle of exponential traveling waves to construct a sub-class of [Formula: see text]-wave solutions of Hirota bilinear equations. A necessary and sufficient condition for Hirota bilinear equations possessing this specific sub-class of [Formula: see text]-wave solutions is presented. We apply this result to find [Formula: see text]-wave solutions to the (2+1)-dimensional KP equation, a (3+1)-dimensional generalized Kadomtsev–Petviashvili (KP) equation, a (3+1)-dimensional generalized BKP equation and the (2+1)-dimensional BKP equation. The inverse question, i.e., constructing Hirota Bilinear equations possessing [Formula: see text]-wave solutions, is considered and a refined 3-step algorithm is proposed. As examples, we construct two very general kinds of Hirota bilinear equations of order 4 possessing [Formula: see text]-wave solutions among which one satisfies dispersion relation and another does not satisfy dispersion relation.
Operational characteristics of single-particle heat engines and refrigerators with time-asymmetric protocol
Authors: Pal P. S. , Saha Arnab , Jayannavar A. M.
Published: September 2016

We have studied the single-particle heat engine and refrigerator driven by time-asymmetric protocol of finite duration. Our system consists of a particle in a harmonic trap with time-periodic strength that drives the particle cyclically between two baths. Each cycle consists of two isothermal steps at different temperatures and two adiabatic steps connecting them. The system works in irreversible mode of operation even in the quasistatic regime. This is indicated by finite entropy production even in the large cycle time limit. Consequently, Carnot efficiency for heat engine or Carnot coefficient of performance (COP) for refrigerators is not achievable. We further analyzed the phase diagram of heat engines and refrigerators. They are sensitive to time-asymmetry of the protocol. Phase diagram shows several interesting features, often counterintuitive. The distribution of stochastic efficiency and COP is broad and exhibits power-law tails.
Link prediction based on local community properties
Authors: Yang Xu-Hua , Zhang Hai-Feng , Ling Fei , Cheng Zhi , Weng Guo-Qing , Huang Yu-Jiao
Published: September 2016

The link prediction algorithm is one of the key technologies to reveal the inherent rule of network evolution. This paper proposes a novel link prediction algorithm based on the properties of the local community, which is composed of the common neighbor nodes of any two nodes in the network and the links between these nodes. By referring to the node degree and the condition of assortativity or disassortativity in a network, we comprehensively consider the effect of the shortest path and edge clustering coefficient within the local community on node similarity. We numerically show the proposed method provide good link prediction results.
Structural characteristics of a three-dimensional Ising-like system in the critical region
Authors: Pylyuk I. V. , Kozlovskii M. P.
Published: September 2016

An analytic technique for calculating the correlation function and correlation radius of systems belonging to the universality class of the three-dimensional Ising model is elaborated within the collective variables (CV) method. The calculations of these nonuniversal characteristics are performed for the temperatures [Formula: see text], [Formula: see text] and [Formula: see text] ([Formula: see text] is the phase transition temperature) on the microscopic level in the approximation of the quartic distribution for modes of spin moment density oscillations (the [Formula: see text] model). Proceeding from the expression for the Fourier transform of the correlation function, we have also obtained the susceptibility of the system. The correction to scaling and the potential averaging correction are taken into account in our calculations.
Impact of Single Event Upset on Voltage and Current Behaviors of CNTFET SRAM and a Comparison with CMOS SRAM
Authors: Rajalakshmi T. R. , Sudhakar R.
Published: September 2016

Carbon nanotubes (CNTs) provide a better alternative of silicon when it comes to nanoscales. Thanks to the high stability and high performance of carbon nanotube, CNT-based FET (CNTFET) devices are gaining popularity of late. They provide high packaging densities. Not much study had been done to analyze the characteristics of CNTFET SRAM in the presence of single event upset (SEU). The aim of this paper is to analyze the way in which SEU brings alterations in CNTFET SRAM characteristics and perform its comparison with respect to CMOS 6T SRAM. This paper analyzes the impact of SEU on voltage and current characteristics in CNTFET-based SRAM cell during three different conditions —read, write and hold modes. In the analysis, CNTFET SRAM showed that even small amount of radiations can cause flipping in cells and special circuitries are required to detect and correct the errors for SEU affected SRAM.
Optimization of quantum Hamiltonian evolution: From two projection operators to local Hamiltonians
Authors: Patel Apoorva , Priyadarsini Anjani
Published: September 2016

Given a quantum Hamiltonian and its evolution time, the corresponding unitary evolution operator can be constructed in many different ways, corresponding to different trajectories between the desired end-points and different series expansions. A choice among these possibilities can then be made to obtain the best computational complexity and control over errors. It is shown how a construction based on Grover's algorithm scales linearly in time and logarithmically in the error bound, and is exponentially superior in error complexity to the scheme based on the straightforward application of the Lie–Trotter formula. The strategy is then extended first to simulation of any Hamiltonian that is a linear combination of two projection operators, and then to any local efficiently computable Hamiltonian. The key feature is to construct an evolution in terms of the largest possible steps instead of taking small time steps. Reflection operations and Chebyshev expansions are used to efficiently control the total error on the overall evolution, without worrying about discretization errors for individual steps. We also use a digital implementation of quantum states that makes linear algebra operations rather simple to perform.
An intrinsic and exterior form of the Bianchi identities
Authors: Do Thoan , Prince Geoff
Published: September 2016

We give an elegant formulation of the structure equations (of Cartan) and the Bianchi identities in terms of exterior calculus without reference to a particular basis and without the exterior covariant derivative. This approach allows both structure equations and the Bianchi identities to be expressed in terms of forms of arbitrary degree. We demonstrate the relationship with both the conventional vector version of the Bianchi identities and to the exterior covariant derivative approach. Contact manifolds, codimension one foliations and the Cartan form of classical mechanics are studied as examples of its flexibility and utility.
China and the Middle Income Trap
Authors: WONG John
Published: September 2016

Is China falling into the “middle-income trap” (MIT) with its current economic slowdown? Extrapolating from its 2015 per capita income of US$8,300 and benchmarking a developed economy at US$16,000, China would become a developed economy within 10 years with a reasonably strong growth of around 6%. China’s impressive R&D efforts and industrial upgrading towards “intensive manufacturing” could help it cross the MIT; however, it may run into a new kind of trap, the “low-income developed-economy trap”.
The End of Nihilism: Systemic Therapy of Advanced Non–Small Cell Lung Cancer
Authors: Ernani Vinicius , Steuer Conor E. , Jahanzeb Mohammad
Published: September 2016

Lung cancer is the leading cause of cancer death in the United States and many other parts of the world. Non–small cell lung cancer (NSCLC) comprises 85–90% of lung cancers. Historically, the expected survival of patients with advanced disease has been estimated in months. In recent years, however, lung cancer has come to be seen as a treatable disease with multiple therapeutic options. Enormous advances in the understanding of its pathways and mechanisms have enabled personalized therapy in NSCLC. The evolving approach to therapy focuses on genomic profiling of the tumors to find molecular targets and develop specific agents for individualized therapy. In addition, maintenance therapy has emerged as a valid approach, and the choice of chemotherapy now varies by histology. Most recently, immunotherapy with checkpoint inhibitors has shown promising results, with impressive durations of response and a tolerable toxicity profile. Together, these discoveries have improved overall survival substantially in patient populations that have access to these advancements. We review the clinical data surrounding these impressive improvements.
Management of Rectal Cancer Without Radical Resection
Authors: Beets Geerard L. , Figueiredo Nuno F. , Beets-Tan Regina G.H.
Published: September 2016

The basis of the current treatment of rectal cancer is a radical total mesorectal excision of the rectum, and although this provides excellent oncological control, it is associated with morbidity and functional problems in cancer survivors. Organ-preservation alternatives are local excision alone for very early tumors, chemoradiation followed by either local excision of a small tumor remnant or, when there is a complete clinical response, a nonoperative watch-and-wait approach. The functional advantage of these alternatives is clear, but there is some concern about the oncological risk. Although the available studies suggest that with adequate selection and follow-up this risk is small, the evidence is still weak. Because of patients' high interest in preserving quality of life, clinicians should cautiously move ahead and offer the option of organ preservation to patients in a controlled setting while awaiting further evidence.
Health Behavior Change: Moving from Observation to Intervention
Authors: Sheeran Paschal , Klein William M.P. , Rothman Alexander J.
Published: September 2016

How can progress in research on health behavior change be accelerated? Experimental medicine (EM) offers an approach that can help investigators specify the research questions that need to be addressed and the evidence needed to test those questions. Whereas current research draws predominantly on multiple overlapping theories resting largely on correlational evidence, the EM approach emphasizes experimental tests of targets or mechanisms of change and programmatic research on which targets change health behaviors and which techniques change those targets. There is evidence that engaging particular targets promotes behavior change; however, systematic studies are needed to identify and validate targets and to discover when and how targets are best engaged. The EM approach promises progress in answering the key question that will enable the science of health behavior change to improve public health: What strategies are effective in promoting behavior change, for whom, and under what circumstances?
Integrative Genomic Analysis Identifies the Core Transcriptional Hallmarks of Human Hepatocellular Carcinoma
Authors: Allain Coralie , Angenard Gaëlle , Clément Bruno , Coulouarn Cédric
Published: September 2016

Integrative genomics helped characterize molecular heterogeneity in hepatocellular carcinoma (HCC), leading to targeted drug candidates for specific HCC subtypes. However, no consensus was achieved for genes and pathways commonly altered in HCC. Here, we performed a meta-analysis of 15 independent datasets (n = 784 human HCC) and identified a comprehensive signature consisting of 935 genes commonly deregulated in HCC as compared with the surrounding nontumor tissue. In the HCC signature, upregulated genes were linked to early genomic alterations in hepatocarcinogenesis, particularly gains of 1q and 8q. The HCC signature covered well-established cancer hallmarks, such as proliferation, metabolic reprogramming, and microenvironment remodeling, together with specific hallmarks associated with protein turnover and epigenetics. Subsequently, the HCC signature enabled us to assess the efficacy of signature-relevant drug candidates, including histone deacetylase inhibitors that specifically reduced the viability of six human HCC cell lines. Overall, this integrative genomics approach identified cancer hallmarks recurrently altered in human HCC that may be targeted by specific drugs. Combined therapies targeting common and subtype-specific cancer networks may represent a relevant therapeutic strategy in liver cancer. Cancer Res; 76(21); 6374–81. ©2016 AACR.
Interleukin-17–Producing Neutrophils Link Inflammatory Stimuli to Disease Progression by Promoting Angiogenesis in Gastric Cancer
Authors: Li Tuan-Jie , Jiang Yu-Ming , Hu Yan-Feng , Huang Lei , Yu Jiang , Zhao Li-Ying , Deng Hai-Jun , Mou Ting-Yu , Liu Hao , Yang Yang , Zhang Qi , Li Guo-Xin
Published: September 2016

Purpose: Elevated levels of neutrophils have been associated with poor survival in various cancers, but direct evidence supporting a role for neutrophils in the immunopathogenesis of human cancers is lacking.

Experimental Design: A total of 573 patients with gastric cancer were enrolled in this study. Immunohistochemistry and real-time PCR were performed to analyze the distribution and clinical relevance of neutrophils in different microanatomic regions. The regulation and function of neutrophils were assessed both in vitro and in vivo.

Results: Increased neutrophil counts in the peripheral blood were associated with poor prognosis in gastric cancer patients. In gastric cancer tissues, neutrophils were enriched predominantly in the invasive margin, and neutrophil levels were a powerful predictor of poor survival in patients with gastric cancer. IL17+ neutrophils constitute a large portion of IL17-producing cells in human gastric cancer. Proinflammatory IL17 is a critical mediator of the recruitment of neutrophils into the invasive margin by CXC chemokines. Moreover, neutrophils at the invasive margin were a major source of matrix metalloproteinase-9, a secreted protein that stimulates proangiogenic activity in gastric cancer cells. Accordingly, high levels of infiltrated neutrophils at the invasive margin were positively correlated with angiogenesis progression in patients with gastric cancer.

Conclusions: These data provide direct evidence supporting the pivotal role of neutrophils in gastric cancer progression and reveal a novel immune escape mechanism involving fine-tuned collaborative action between cancer cells and immune cells in the distinct tumor microenvironment. Clin Cancer Res; 23(6); 1575–85. ©2016 AACR.
Neubeurteilung des WINROP-Alarms erhöht die Spezifität des WINROP-Systems
Authors: Lorenz Birgit
Published: September 2016

Hintergrund: Die Frühgeborenen-Retinopathie (ROP; Retinopathia praematurorum) ist eine potenziell zur Erblindung führende Krankheit, die bei extrem verfrüht geborenen Säuglingen auftritt. Die Einführung neuer ROP-Vorsorgeuntersuchungssysteme mit höherer Sensitivität und Spezifität als bisherige Leitlinien für das ROP-Screening hat das Potenzial, die Zahl belastender Augenuntersuchung bei diesen Säuglingen zu verringern. Ziele: Erhöhung der Spezifizität des WINROP-Überwachungssystems (Weight, Insulin-like growth factor-I, Neonatal, ROP) zur Identifikation extrem frühgeborener Säuglinge mit behandlungsbedürftiger ROP. Methoden: Zwei Kohorten, die zuvor WINROP-Analysen unterzogen worden waren, wurden in die Studie eingeschlossen und erneut evaluiert. Das Körpergewicht bei WINROP-Alarm für extrem frühgeborene Säuglinge (Entbindung vor Schwangerschaftswoche 27) wurde reevaluiert, und durch Setzung «sicherer» WINROP-Alarmgrenzwerte für das Körpergewicht erfolgte eine Neubeurteilung der Stichproben nach WINROP-Alarm. Die folgenden beiden Kohorten wurden untersucht: (1) die Kohorte der EXPRESS-Studie (Extremely Preterm Infants in Sweden Study) mit 2004-2007 in Schweden geborenen Säuglingen (n = 407) und (2) die extrem frühgeborenen Säuglinge einer nordamerikanischen Kohorte, Geburtsjahrgänge 2006-2009 (n = 566). Ergebnisse: In der EXPRESS-Kohorte lag bei 12,5% (40/319) der Säuglinge, bei denen zuvor ein WINROP-Alarm erfolgt war, nun kein Alarm mehr vor; die Spezifität von WINROP in der EXPRESS-Kohorte stieg damit von 23,9% (86/360) auf 35,0% (126/360). In der nordamerikanischen Kohorte hatten nach der erneuten Beurteilung 15,4% (81/526) keinen Alarm mehr; die Spezifität stieg von 8,5% (38/447) auf 26,6% (119/447). Die Sensitivität betrug unverändert 97,5% in der EXPRESS-Kohorte (45/47) und 98,3% (117/119) in der nordamerikanischen Kohorte. Schlussfolgerungen: Die Spezifität des WINROP-Überwachungssystems für extrem frühgeborene Säuglinge kann durch erneute Evaluierung anhand des Gewichts bei WINROP-Alarm signifikant verbessert werden. Neonatology 2015;108:152-156 (DOI:10.1159/000435770)
Diagnosis of Jejunal Metastases from Lung Cancer Using Capsule Endoscopy
Authors: Leduc Charlotte , Prim Nathalie , Mennecier Bertrand , Delvaux Michel , Gangi Afshin , Quoix Elisabeth
Published: September 2016

Gastrointestinal metastases from lung cancer are rare and usually asymptomatic. We report a case of small bowel metastases from primary lung cancer revealed by abdominal pain and severe recurrent anaemia. The diagnosis was obtained with capsule endoscopy. This non-invasive procedure thus represents a valuable method contributing to a rapid and detailed diagnosis while reducing underdiagnosis, and it should thus be considered for lung cancer patients complaining of abdominal symptoms, which may indeed be related to gastrointestinal metastases.