bluuebunny/crossref_metadata_2025 huggingface dataset:
Using among-year variation to assess maternal effects inPinus aristataandPinus flexilis
Authors: Borgman Erin M. , Schoettle Anna W. , Angert Amy L.
Published: September 2014

Maternal effects, the effect of the maternal environment during development on offspring growth, can complicate the interpretation of common garden studies. Growing one or more generations in a common environment can help minimize maternal effects, but is often not practical with long-lived species. In Pinus aristata Engelm. and Pinus flexilis James, we assessed maternal effects by growing offspring sourced over multiple years from the same mother trees, comparing growth traits between source years. Additionally, we explored the effect of maternal environment on seed characteristics by collecting five twig clippings from each mother tree and measuring characteristics indicative of the relative vigor of the tree during each seed source year. The effect of year was significant for twig growth characteristics, seed size, and seedling performance. For both species, there were significant relationships between the relative inter-annual (RIA) variation in seed mass and the RIA variation in numerous seedling traits including cotyledon length, seedling total dry mass, and needle length. Variation in seed mass was not predicted by yearly variation in the maternal plant’s phenotypic traits. These results support the hypothesis that maternal effects translate into variation in early seedling growth and suggest possibilities to statistically account for them in common garden studies involving long-lived species.
Partial diel vertical migration of sympatric vendace (Coregonus albula) and Fontane cisco (Coregonus fontanae) is driven by density dependence
Authors: Mehner Thomas
Published: September 2014

Recent studies have indicated that in fish populations performing diel vertical migrations (DVM), some individuals do not migrate but reflect a resident phenotype, a pattern named as partial DVM. I present data on fish densities and the proportion of residents in Lake Stechlin (Germany) as obtained by annual midwater trawling over four discrete depths during nighttime over 8 years. The lake is inhabited by the sympatric vendace (Coregonus albula) and Fontane cisco (Coregonus fontanae). The proportion of vendace residents increased with the density of vendace, whereas the proportion of Fontane cisco residents declined with increasing density, indicating that density plays a role in the migration patterns for both species, but in opposite directions. There were almost no differences in mean size, size-frequency distributions, or Fulton condition factor between resident or migrant parts of the populations in both species. However, the proportion of dry mass in wet mass, which indicates individual nutritional status, had a tendency to be lower in migrants than in residents in both species in the years 2011, 2012, and 2013. These data suggest that density dependence may be an important factor that modifies the proportion of residents in vertically migrating fish populations. In contrast, length-dependent predation vulnerability or systematic individual differences in nutritional status were not strongly supported as potential predictors of the proportion of residents. It needs to be discussed whether partial DVM is conceptually similar to partial seasonal migrations of fish, or whether DVM reflects variants of the ideal free distribution, which are inherently density-dependent.
THE SUPER-TURING COMPUTATIONAL POWER OF PLASTIC RECURRENT NEURAL NETWORKS
Authors: CABESSA JÉRÉMIE , SIEGELMANN HAVA T.
Published: September 2014

We study the computational capabilities of a biologically inspired neural model where the synaptic weights, the connectivity pattern, and the number of neurons can evolve over time rather than stay static. Our study focuses on the mere concept of plasticity of the model so that the nature of the updates is assumed to be not constrained. In this context, we show that the so-called plastic recurrent neural networks (RNNs) are capable of the precise super-Turing computational power — as the static analog neural networks — irrespective of whether their synaptic weights are modeled by rational or real numbers, and moreover, irrespective of whether their patterns of plasticity are restricted to bi-valued updates or expressed by any other more general form of updating. Consequently, the incorporation of only bi-valued plastic capabilities in a basic model of RNNs suffices to break the Turing barrier and achieve the super-Turing level of computation. The consideration of more general mechanisms of architectural plasticity or of real synaptic weights does not further increase the capabilities of the networks. These results support the claim that the general mechanism of plasticity is crucially involved in the computational and dynamical capabilities of biological neural networks. They further show that the super-Turing level of computation reflects in a suitable way the capabilities of brain-like models of computation.
Constructing analytical solutions of linear perturbations of inflation with modified dispersion relations
Authors: Zhu Tao , Wang Anzhong , Cleaver Gerald , Kirsten Klaus , Sheng Qin
Published: September 2014

We develop a technique to construct analytical solutions of the linear perturbations of inflation with a nonlinear dispersion relation, due to quantum effects of the early universe. Error bounds are given and studied in detail. The analytical solutions describe the evolution of the perturbations extremely well even when only the first-order approximations are considered.
ANALYTICAL MODELING OF SQUEEZE FILM DAMPING IN DUAL AXIS TORSION MICROACTUATORS
Authors: MOEENFARD HAMID
Published: September 2014

In this paper, problem of squeeze film damping in dual axis torsion microactuators is modeled and closed form expressions are provided for damping torques around tilting axes of the actuator. The Reynolds equation which governs the pressure distribution underneath the actuator is linearized. The resulting equation is then solved analytically. The obtained pressure distribution is used to calculate the normalized damping torques around tilting axes of the actuator. Dependence of the damping torques on the design parameters of the dual axis torsion actuator is studied. It is observed that with proper selection of the actuator's aspect ratio, damping torque along one of the tilting directions can be eliminated. It is shown that when the tilting angles of the actuator are small, squeeze film damping would act like a linear viscous damping. The results of this paper can be used for accurate dynamical modeling and control of torsion dual axis microactuators.
New criteria for a ring to have a semisimple left quotient ring
Authors: Bavula V. V.
Published: September 2014

Goldie's Theorem (1960), which is one of the most important results in Ring Theory, is a criterion for a ring to have a semisimple left quotient ring. The aim of the paper is to give four new criteria (using a completely different approach and new ideas). The first one is based on the recent fact that for an arbitrary ring R the set ℳ of maximal left denominator sets of R is a non-empty set [V. V. Bavula, The largest left quotient ring of a ring, preprint (2011), arXiv:math.RA:1101.5107]:

Theorem (The First Criterion). A ring R has a semisimple left quotient ring Q iff ℳ is a finite set, ⋂S∈ℳ ass (S) = 0 and, for each S ∈ ℳ, the ring S-1R is a simple left Artinian ring. In this case, Q ≃ ∏S∈ℳ S-1R.

The Second Criterion is given via the minimal primes of R and goes further than the First one in the sense that it describes explicitly the maximal left denominator sets S via the minimal primes of R. The Third Criterion is close to Goldie's Criterion but it is easier to check in applications (basically, it reduces Goldie's Theorem to the prime case). The Fourth Criterion is given via certain left denominator sets.
Facile synthesis of CuO nanoparticles as anode for lithium ion batteries with enhanced performance
Authors: Wang Linlin , Tang Kaibin , Zhang Min , Zhang Xiaozhu , Xu Jingli
Published: September 2014

Particle size effects on the electrochemical performance of the CuO particles toward lithium are essential. In this work, a low-cost, large-scale production but simple approach has been developed to fabricate CuO nanoparticles with an average size in ~ 130 nm through thermolysis of Cu ( OH )2 precursors. As anode materials for lithium ion batteries (LIBs), the CuO nanoparticles deliver a high reversible capacity of 540 mAh g-1 over 100 cycles at 0.5 C. It also exhibits a rate capacity of 405 mAh g-1 at 2 C. These results suggest that the facile synthetic method of producing the CuO nanoparticles can enhance cycle performance, superior to that of some different sizes of the CuO nanoparticles and many reported CuO -based anodes.
Some new results on strong integer additive set-indexers of graphs
Authors: Sudev N. K. , Germina K. A.
Published: September 2014

Let ℕ0 be the set of all non-negative integers. An integer additive set-indexer (IASI) of a graph G is an injective function f : V(G) → 2ℕ0 such that the induced function gf : E(G) → 2ℕ0 defined by f+(uv) = f(u) + f(v) is also injective. An IASI is said to be k-uniform if |f+(e)| = k for all e ∈ E(G). In this paper, we introduce the notions of strong IASIs and initiate a study of the graphs which admit strong IASIs.
The microstructure and dielectric properties of titanium oxide doped with nano CuO
Authors: Li Juan , Fu Renli , Xu Yue , Fu Zhenxiao , Su Hongjuan
Published: September 2014

The TiO 2 ceramics doped with nano CuO were fabricated by the conventional solid-state reaction method. The crystal structure, microstructure, microwave dielectric properties and lattice vibrations of TiO 2 ceramics doped with nano CuO have been investigated. Nano CuO with higher sintering capability worked as flux former and effectively improved the sintering process of TiO 2 ceramics. The microwave dielectric properties of TiO 2 doped with nano CuO were much better than that doped with micron CuO at the same doping content. Raman spectra showed that the full width at half maximum of Eg mode of TiO 2 doped with micron CuO was larger than nano CuO doped ones, which indicated a poor crystalline and a short phonon lifetime. TiO 2 doped with 1 wt.% nano CuO , sintered at 950°C for 2 h had compact and homogeneous microstructure and possessed the following dielectric properties: εr = 106, Q × f = 24808, τf = 371 ppm/°C.
Irreversible information loss: Fundamental notions and entropy costs
Authors: Anderson Neal G.
Published: September 2014

Landauer's Principle (LP) associates an entropy increase with the irreversible loss of information from a physical system. Clear statement, unambiguous interpretation, and proper application of LP requires precise, mutually consistent, and sufficiently general definitions for a set of interlocking fundamental notions and quantities (entropy, information, irreversibility, erasure). In this work, we critically assess some common definitions and quantities used or implied in statements of LP, and reconsider their definition within an alternative “referential” approach to physical information theory that embodies an overtly relational conception of physical information. We prove an inequality on the entropic cost of irreversible information loss within this context, as well as “referential analogs” of LP and its more general restatement by Bennett. Advantages of the referential approach for establishing fundamental limits on the physical costs of irreversible information loss in communication and computing systems are discussed throughout.
Allison mixtures: Where random digits obey thermodynamic principles
Authors: Gunn Lachlan J. , Allison Andrew , Abbott Derek
Published: September 2014

Parrondo's paradox is a well-known situation where losing strategies can be combined to win, and is based on a thermodynamic Brownian ratchet principle. We demonstrate a new extension of Parrondo's paradox called the Allison mixture where it is possible to paradoxically generate random sequences with nonzero autocovariance, out of sub-sequences of zero autocovariance. We explain the effect with a ratchet analogy and show the behavior of random digits follows a thermodynamic analogy. As Kish-based cipher techniques rely on the Second Law for their security, this raises the tantalizing open question of whether the Allison mixture can be exploited for new Kish-inspired digital security schemes.
Demons: Maxwell's demon, Szilard's engine and Landauer's erasure–dissipation
Authors: Kish Laszlo B. , Granqvist Claes G. , Khatri Sunil P. , Wen He
Published: September 2014

This talk addressed the following questions in the public debate at HoTPI: (i) energy dissipation limits of switches, memories and control; (ii) whether reversible computers are possible, or does their concept violate thermodynamics; (iii) Szilard's engine, Maxwell's demon and Landauer's principle: corrections to their exposition in the literature; (iv) whether Landauer's erasure–dissipation principle is valid, if the same energy dissipation holds for writing information, or if it is invalid; and (v) whether (non-secure) erasure of memories, or the writing of the same amount of information, dissipates most heat.
Mapping suitability for open-loop ground source heat pump systems: a screening tool for England and Wales, UK
Authors: Abesser Corinna , Lewis Melinda A. , Marchant Andrew P. , Hulbert Andrew G.
Published: September 2014

The UK Government expects that, by 2020, 12% of the UK’s heat demand will come from renewable sources, and is providing incentives to help achieve this. Open-loop ground source heat pumps (GSHP) could make a substantial contribution. A web-based screening tool has been developed that highlights areas where conditions may be suitable for installing commercial-scale (>100 kW heating or cooling demand) open-loop GSHP systems in England and Wales. In addition to the basic requirements for open-loop GSHP (i.e. the availability of a sufficiently productive aquifer within a reasonable depth beneath the surface) the tool provides information on existing abstractions, water chemistry and the location of protected areas. Validation and tool application show that it produces reliable results and provides an effective method for the initial assessment of subsurface conditions and suitability for GSHP installations. Hence, the tool can help to reduce uncertainty at the early planning stage, and also to promote GSHP technology to a variety of audiences.
Modified Electroconvulsive Therapy in a Patient with Gastric Adenocarcinoma and Metastases to Bone and Liver
Authors: Wang Gennie , Milne Brian , Rooney Rachel , Saha Tarit
Published: September 2014

Background. In addition to general anesthesia, muscle relaxants are given prior to electroconvulsive therapy (ECT) in order to prevent musculoskeletal injury. Higher doses of muscle relaxants have been suggested for patients at high risk for bone fractures; however, there are adverse side effects associated with these higher doses.Aims. We present a successful case of ECT to treat chronic major depressive disorder in a 62-year-old woman at high risk of bone fracture due to gastric adenocarcinoma with metastases to bone and liver.Case. Increasing doses of the muscle relaxant succinylcholine (0.45–0.74 mg/kg) were sufficient to prevent musculoskeletal complications throughout the course of 9 bifrontal ECT treatments. Following treatment, the patient reported and demonstrated markedly improved mood and functionality, enabling her transfer to a palliative care facility.Conclusion. Standard doses of succinylcholine were sufficient to mitigate the risk of pathological fractures in this patient with metastatic bone lesions. As there are established risks to using high doses of succinylcholine, with no evidence that higher doses reduce the incidence of fractures in high-risk populations, we suggest taking a conservative approach, using clinical observation and periodic plain radiography to dictate succinylcholine dose titration in such high-risk patients.
Coating of Mesh Grafts for Prolapse and Urinary Incontinence Repair with Autologous Plasma: Exploration Stage of a Surgical Innovation
Authors: Barski Dimitri , Gerullis Holger , Georgas Evangelos , Bär Andreas , Lammers Bernhard , Ramon Albert , Ysebaert Dirk , Klosterhalfen Bernd , Boros Mihaly , Otto Thomas
Published: September 2014

Purpose. Optimized biocompatibility is a major requirement for alloplastic materials currently applied for stress urinary incontinence (SUI) and pelvic organ prolapse (POP) repair. In the preliminary studies the mesh modification by coating with autologous plasma resulted in the increased adherence scorein vitroand improved biocompatibility in an animal model. The first use of plasma coated meshes in human is presented.Materials and Methods. Between 04/2013 and 05/2014, 20 patients with the indication for SUI and POP repair were selected in a single institution. The applied meshes were modified by autologous plasma coating prior to implantation. A retrospective chart review for peri- and early postoperative complications was performed. Functional outcome and QoL were evaluated pre- and postoperatively.Results. The functional outcome and QoL improved significantly in all groups. Two reoperations (Grade IIIB) with the release of TVT-mesh in anesthesia due to the obstruction were needed. No other severe complications were registered.Conclusion. For the first time we applied a mesh modification in a human setting according toIDEALcriteria of surgical innovations. The procedure of mesh coating with autologous plasma is safe and a prospective randomized trial proving a positive effect of plasma coating on the biocompatibility and morbidity outcome with long-term registry is planned.
Design of High-Gain and Beam Steering Antennas Using a New Planar Folded-Line Metamaterial Structure
Authors: Le Minh Thuy , Nguyen Quoc Cuong , Vuong Tan Phu
Published: September 2014

In the last few years, there has been growing interest in employing metamaterials (MTMs) to enhance antenna gain. In this paper we proposed a novel structure of planar folded-line left-handed metamaterial (FL-LHM) and applied it to improve the gain of three 5.8 GHz microstrip antenna types: a circularly polarized patch antenna, an antenna array, and a beam steering antenna. The planar FL-LHM structure was designed based on transmission line analysis. Their scattering parameters were obtained using a numerical model; the negative effective permittivity and permeability were then calculated from these parameters for the assessment of negative refraction index region. The S11and radiation patterns of three fabricated antennas were measured; these results matched well with the simulation. We observed that the gain was increased up to 3 dBi for all the antennas. In addition, we were also able to maintain the circular polarization as well as the steering of the antenna without changing its dimensions.
A Three-Step Approach with Adaptive Additive Magnitude Selection for the Sharpening of Images
Authors: Kau Lih-Jen , Lee Tien-Lin
Published: September 2014

Aimed to find the additive magnitude automatically and adaptively, we propose a three-step and model-based approach for the sharpening of images in this paper. In the first pass, a Grey prediction model is applied to find a global maximal additive magnitude so that the condition of oversharpening in images to be sharpened can be avoided. During the second pass, edge pixels are picked out with our previously proposed edge detection mechanism. In this pass, a low-pass filter is also applied so that isolated pixels will not be regarded as around an edge. In the final pass, those pixels detected as around an edge are adjusted adaptively based on the local statistics, and those nonedge pixels are kept unaltered. Extensive experiments on natural images as well as medical images with subjective and objective evaluations will be given to demonstrate the usefulness of the proposed approach.
Neurenteric Cyst of the Area Postrema
Authors: Miller Claire M. , Wang Bonnie H. , Moon Seong-Jin , Chen Eric , Wang Huan
Published: September 2014

Neurenteric cysts are CNS lesions most frequently occurring in the spinal cord. Intracranial neurenteric cysts are rarer, typically presenting with headache, mass effect, or location-specific symptoms. The area postrema is known as the emetic center of the brain; lesions can cause nausea and vomiting. Our case, featuring a neurenteric cyst of the area postrema, illustrates the importance of considering a neurological etiology for nonspecific symptoms that otherwise elude explanation. Our patient presented with acute decompensated hydrocephalus upon exploratory abdominal laparoscopy for unresolving abdominal pain. The patient had an eight-month history of unexplained intermittent nausea, vomiting, and abdominal pain. These bouts increased in frequency during the weeks before acute presentation, prompting exploratory abdominal laparoscopy. The acute decompensation was managed by ventriculostomy, and cranial MRI revealed a cystic mass by the floor of the fourth ventricle. After the patient stabilized and returned to neurological baseline, suboccipital craniectomy and resection were performed. The mass was histologically identified as a neurenteric cyst. The patient was free from neurological complaints at one-year follow-up, indicating that the successful resection of the area postrema-associated neurenteric cyst resolved her previous symptoms. Thus, some intracranial lesions can masquerade as nonspecific symptoms, presenting a challenge to accurate diagnosis.
Quantifying Proteinuria in Hypertensive Disorders of Pregnancy
Authors: Amin Sapna V. , Illipilla Sireesha , Hebbar Shripad , Rai Lavanya , Kumar Pratap , Pai Muralidhar V.
Published: September 2014

Background.Progressive proteinuria indicates worsening of the condition in hypertensive disorders of pregnancy and hence its quantification guides clinician in decision making and treatment planning.Objective.To evaluate the efficacy of spot dipstick analysis and urinary protein-creatinine ratio (UPCR) in hypertensive disease of pregnancy for predicting 24-hour proteinuria.Subjects and Methods.A total of 102 patients qualifying inclusion criteria were evaluated with preadmission urine dipstick test and UPCR performed on spot voided sample. After admission, the entire 24-hour urine sample was collected and analysed for daily protein excretion. Dipstick estimation and UPCR were compared to the 24-hour results.Results.Seventy-eight patients (76.5%) had significant proteinuria of more than 300 mg/24 h. Dipstick method showed 59% sensitivity and 67% specificity for prediction of significant proteinuria. Area under curve for UPCR was 0.89 (95% CI: 0.83 to 0.95,P<0.001) showing 82% sensitivity and 12.5% false positive rate for cutoff value of 0.45. Higher cutoff values (1.46 and 1.83) predicted heavy proteinuria (2 g and 3 g/24 h, resp.).Conclusion.This study suggests that random urinary protein : creatine ratio is a reliable investigation compared to dipstick method to assess proteinuria in hypertensive pregnant women. However, clinical laboratories should standardize the reference values for their setup.
Tumor-Suppressive miR148a Is Silenced by CpG Island Hypermethylation in IDH1-Mutant Gliomas
Authors: Li Sichen , Chowdhury Reshmi , Liu Fei , Chou Arthur P. , Li Tie , Mody Reema R. , Lou Jerry J. , Chen Weidong , Reiss Jean , Soto Horacio , Prins Robert , Liau Linda M. , Mischel Paul S. , Nghiemphu Phioanh L. , Yong William H. , Cloughesy Timothy F. , Lai Albert
Published: September 2014

Purpose: IDH1/2-mutant gliomas harbor a distinct glioma-CpG island methylation phenotype (G-CIMP) that may promote the initiation and progression of secondary pathway gliomas by silencing tumor-suppressive genes. The potential role of tumor-suppressive microRNAs (miRNA; miR) in this process is not understood.

Experimental Design: To identify potential tumor-suppressive miRNA hypermethylated in glioma, the methylation profiles of IDH1/2WT gliomas (n = 11) and IDH1MUT glioma (n = 20) were compared by using massively parallel reduced representation bisulfite sequencing (RRBS). The methylation status of selected miRNA was validated by using targeted bisulfite sequencing (BiSEQ) in a large cohort of glioma tissue samples including 219 IDH1WT and 72 IDH1/2MUT samples. The expression of selected miRNAs was determined by using the TaqMan qPCR. Functional analyses of miR148a were conducted and target genes were identified.

Results: We identify miR148a as a novel, G-CIMP–associated miRNA whose methylation is tightly correlated with IDH1 mutation and associated with improved survival in patients with malignant glioma. We confirm that downregulation of miR148a can occur via DNA methylation. We demonstrate that IDH1 mutation provides a mechanism of miR148a methylation and downregulation, and that restoration of miR148a reduced tumorigenic properties of glioma cells, possibly by targeting DNMT1.

Conclusions: We identify miR148a as a novel G-CIMP–associated miRNA, and provide results suggesting that miR148a restoration may have therapeutic implications. Clin Cancer Res; 20(22); 5808–22. ©2014 AACR.
Alteration of Cell–Cell and Cell–Matrix Adhesion in Urothelial Cells: An Oncogenic Mechanism for Mutant FGFR3
Authors: di Martino Erica , Kelly Gavin , Roulson Jo-An , Knowles Margaret A.
Published: September 2014

Activating mutations of FGFR3 are a common and early event in bladder cancer. Ectopic expression of mutant FGFR3 in normal urothelial cells has both pro-proliferative and antiapoptotic effects at confluence, suggesting that mutant cells are insensitive to cell–cell contact inhibition. Herein, detailed analysis revealed that these cells have reduced cell–cell adhesion, with large intercellular spaces observable at confluence, and diminished cell–substrate adhesion to collagen IV, collagen I, and fibronectin. These phenotypic alterations are accompanied by changes in the expression of genes involved in cell adhesion and extracellular matrix remodeling. Silencing of endogenous mutant FGFR3 in bladder cancer cells induced converse changes in transcript levels of CDH16, PLAU, MMP10, EPCAM, TNC, and HAS3, confirming them as downstream gene targets of mutant FGFR3. Overexpression of EPCAM, HAS3, and MMP10 transcripts was found in a large fraction of primary bladder tumors analyzed, supporting their key role in bladder tumorigenesis in vivo. However, no correlation was found between their protein and/or mRNA expression and FGFR3 mutation status in tumor specimens, indicating that these genes may be targeted by several converging oncogenic pathways. Overall, these results indicate that mutant FGFR3 favors the development and progression of premalignant bladder lesions by altering key genes regulating the cell–cell and cell–matrix adhesive properties of urothelial cells.

Implications: The ability of mutant FGFR3 to drive transcriptional expression profiles involved in tumor cell adhesion suggests a mechanism for expansion of premalignant urothelial lesions. Mol Cancer Res; 13(1); 138–48. ©2014 AACR.
Human Fecal Microbiome–Based Biomarkers for Colorectal Cancer
Authors: Narayanan Vilvapathy , Peppelenbosch Maikel P. , Konstantinov Sergey R.
Published: September 2014

Colorectal cancer may develop slowly over years from precursor lesions, and thus screening combined with early diagnosis is the key to disease prevention. Recent studies have elucidated specific traits in the gut microbiome associated with colorectal cancer and suggested that the microbiome may be useful in screening for colorectal cancer purposes but failed to provide protocols that can be applied in a practical situation. A recent study by Zackular and colleagues, presented on page 1112, provides an important way forward here in showing that specific analysis of multiple aspects of the microbiome composition in toto provides reliable detection of both precancerous and cancerous lesions. This important achievement when combined with other noninvasive techniques promises to provide highly effective tools for early colorectal cancer diagnosis and its prevention. Cancer Prev Res; 7(11); 1108–11. ©2014 AACR.
Genomic Landscape of Ewing Sarcoma Defines an Aggressive Subtype with Co-Association of STAG2 and TP53 Mutations
Authors: Tirode Franck , Surdez Didier , Ma Xiaotu , Parker Matthew , Le Deley Marie Cécile , Bahrami Armita , Zhang Zhaojie , Lapouble Eve , Grossetête-Lalami Sandrine , Rusch Michael , Reynaud Stéphanie , Rio-Frio Thomas , Hedlund Erin , Wu Gang , Chen Xiang , Pierron Gaelle , Oberlin Odile , Zaidi Sakina , Lemmon Gordon , Gupta Pankaj , Vadodaria Bhavin , Easton John , Gut Marta , Ding Li , Mardis Elaine R. , Wilson Richard K. , Shurtleff Sheila , Laurence Valérie , Michon Jean , Marec-Bérard Perrine , Gut Ivo , Downing James , Dyer Michael , Zhang Jinghui , Delattre Olivier
Published: September 2014

Ewing sarcoma is a primary bone tumor initiated by EWSR1–ETS gene fusions. To identify secondary genetic lesions that contribute to tumor progression, we performed whole-genome sequencing of 112 Ewing sarcoma samples and matched germline DNA. Overall, Ewing sarcoma tumors had relatively few single-nucleotide variants, indels, structural variants, and copy-number alterations. Apart from whole chromosome arm copy-number changes, the most common somatic mutations were detected in STAG2 (17%), CDKN2A (12%), TP53 (7%), EZH2, BCOR, and ZMYM3 (2.7% each). Strikingly, STAG2 mutations and CDKN2A deletions were mutually exclusive, as confirmed in Ewing sarcoma cell lines. In an expanded cohort of 299 patients with clinical data, we discovered that STAG2 and TP53 mutations are often concurrent and are associated with poor outcome. Finally, we detected subclonal STAG2 mutations in diagnostic tumors and expansion of STAG2-immunonegative cells in relapsed tumors as compared with matched diagnostic samples.

Significance: Whole-genome sequencing reveals that the somatic mutation rate in Ewing sarcoma is low. Tumors that harbor STAG2 and TP53 mutations have a particularly dismal prognosis with current treatments and require alternative therapies. Novel drugs that target epigenetic regulators may constitute viable therapeutic strategies in a subset of patients with mutations in chromatin modifiers. Cancer Discov; 4(11); 1342–53. ©2014 AACR.

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Porphyromonas gingivalis Gingipains Selectively Reduce CD14 Expression, Leading to Macrophage Hyporesponsiveness to Bacterial Infection
Authors: Wilensky Asaf , Tzach-Nahman Rinat , Potempa Jan , Shapira Lior , Nussbaum Gabriel
Published: September 2014

Cysteine proteases (gingipains) from Porphyromonas gingivalis are key virulence factors in chronic periodontitis. Innate immune receptors CD14, Toll-like receptor (TLR) 2 and TLR4 are important in P. gingivalis recognition. We examined the ability of gingipains to cleave CD14, TLR2 and TLR4, and the consequences for the cellular response to bacterial challenge. Macrophages were exposed to Arg (RgpA and RgpB)- and Lys (Kgp)-gingipains, and residual expression of TLR2, TLR4 and CD14 was determined by flow cytometry. The cellular response to live bacteria following exposure to purified gingipains was evaluated by TNFα production and bacterial phagocytosis. RgpA and Kgp decreased CD14 detection in a concentration (p = 0.0000002)- and time (p = 0.03)-dependent manner, whereas RgpB had no significant effect. TLR2 and TLR4 expression were unaffected. Reduction in CD14 expression was more efficient with Lys-gingipain than with Arg-gingipain. A reduced CD14 surface level correlated with decreased TNFα secretion and bacterial phagocytosis following challenge with live P. gingivalis, but the response to heat-killed bacteria was unaffected. Therefore, gingipains reduce CD14 expression without affecting expression of the bacterial-sensing TLRs. Reduced CD14 expression depends on the gingipain hemagglutinin/adhesion site and results in macrophage hyporesponsiveness to bacterial challenge. Further studies are needed to determine if reduced CD14 expression is linked to periodontitis induced by P. gingivalis.
Stent Placement for Severe Stenosis of the Left Common Carotid Artery with Internal-to-External Carotid Steal
Authors: Kimura Ryota , Takayama Katsutoshi , Myouchin Kaoru , Wada Takeshi , Kurokawa Shinichiro , Kichikawa Kimihiko
Published: September 2014

We report the case of a 64-year-old male with internal carotid artery (ICA)-to-external carotid artery (ECA) steal due to severe stenosis of the common carotid artery (CCA). Left CCA occlusion was initially diagnosed on 3-dimensional time-of-flight magnetic resonance angiography, but digital subtraction angiography revealed severe stenosis of the left CCA and retrograde flow through the left ICA feeding the left ECA. Diverted blood flow from ECA to ICA in cases with occlusion or severe stenosis of the CCA represents a well-known alternative collateral flow pattern called ECA-to-ICA steal. However, collateral flow from ICA to ECA is rarely observed and may be termed ICA-to-ECA steal. We treated CCA stenosis in our patient by carotid artery stenting (CAS) because his CCA stenosis had been gradually progressing since the initial ischaemic attack. Antegrade ICA flow subsequently recovered. To the best of our knowledge, this is the first report of ICA-to-ECA steal normalised by the treatment of CCA stenosis using CAS. i 2014 S. Karger AG, Basel
Long-Term Clinical Outcome of Major Adverse Cardiac Events in Survivors of Infective Endocarditis
Authors: Shih Chia-Jen , Chu Hsi , Chao Pei-Wen , Lee Yi-Jung , Kuo Shu-Chen , Li Szu-Yuan , Tarng Der-Cherng , Yang Chih-Yu , Yang Wu-Chang , Ou Shuo-Ming , Chen Yung-Tai
Published: September 2014

Background—

Substantial infective endocarditis (IE)–related morbidity and mortality may occur even after successful treatment. However, no previous study has explored long-term hard end points (ie, stroke, myocardial infarction, heart failure, cardiovascular death) in addition to all-cause mortality in IE survivors.

Methods and Results—

A nationwide population-based cohort study was conducted among IE survivors identified with the use of the Taiwan National Health Insurance Research Database during 2000 to 2009. IE survivors were defined as those who survived after discharge from first hospitalization with a diagnosis of IE. A total of 10 116 IE survivors were identified. IE survivors were matched to control subjects without IE at a 1:1 ratio through the use of propensity scores. The primary outcomes were stroke, myocardial infarction, readmission for heart failure, and sudden cardiac death or ventricular arrhythmia. The secondary outcomes were repeat IE and all-cause mortality. Compared with the matched cohort, IE survivors had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.59; 95% confidence interval [CI], 1.40–1.80), hemorrhagic stroke (aHR, 2.37; 95% CI, 1.90–2.96), myocardial infarction (aHR, 1.44; 95% CI, 1.17–1.79), readmission for heart failure (aHR, 2.24; 95% CI, 2.05–2.43), sudden death or ventricular arrhythmia (aHR, 1.69; 95% CI, 1.44–1.98), and all-cause death (aHR, 2.27; 95% CI, 2.14–2.40). Risk factors for repeat IE were older age, male sex, drug abuse, and valvular replacement after an initial episode of IE.

Conclusion—

Despite treatment, the risk of long-term major adverse cardiac events was substantially increased in IE survivors.
Angiotensin II Mediates Angiotensin Converting Enzyme Type 2 Internalization and Degradation Through an Angiotensin II Type I Receptor–Dependent Mechanism
Authors: Deshotels Matthew R. , Xia Huijing , Sriramula Srinivas , Lazartigues Eric , Filipeanu Catalin M.
Published: September 2014

Angiotensin-converting enzyme type 2 (ACE2) is a pivotal component of the renin–angiotensin system, promoting the conversion of angiotensin II (Ang-II) to Ang-(1-7). We previously reported that decreased ACE2 expression and activity contributes to the development of Ang-II–mediated hypertension in mice. The present study aimed to investigate the mechanisms involved in ACE2 downregulation during neurogenic hypertension. In ACE2-transfected Neuro-2A cells, Ang-II treatment resulted in a significant attenuation of ACE2 enzymatic activity. Examination of the subcellular localization of ACE2 revealed that Ang-II treatment leads to ACE2 internalization and degradation into lysosomes. These effects were prevented by both the Ang-II type 1 receptor (AT
1
R) blocker losartan and the lysosomal inhibitor leupeptin. In contrast, in HEK293T cells, which lack endogenous AT
1
R, Ang-II failed to promote ACE2 internalization. Moreover, this effect could be induced after AT
1
R transfection. Furthermore, coimmunoprecipitation experiments demonstrated that AT
1
R and ACE2 form complexes, and these interactions were decreased by Ang-II treatment, which also enhanced ACE2 ubiquitination. In contrast, ACE2 activity was not changed by transfection of AT
2
or Mas receptors. In vivo, Ang-II–mediated hypertension was blunted by chronic infusion of leupeptin in wildtype C57Bl/6, but not in ACE2 knockout mice. Overall, this is the first demonstration that elevated Ang-II levels reduce ACE2 expression and activity by stimulation of lysosomal degradation through an AT
1
R-dependent mechanism.
Biophysical Characterization of the Underappreciated and Important Relationship Between Heart Rate Variability and Heart Rate
Authors: Monfredi Oliver , Lyashkov Alexey E. , Johnsen Anne-Berit , Inada Shin , Schneider Heiko , Wang Ruoxi , Nirmalan Mahesh , Wisloff Ulrik , Maltsev Victor A. , Lakatta Edward G. , Zhang Henggui , Boyett Mark R.
Published: September 2014

Heart rate (HR) variability (HRV; beat-to-beat changes in the R-wave to R-wave interval) has attracted considerable attention during the past 30+ years (PubMed currently lists >17 000 publications). Clinically, a decrease in HRV is correlated to higher morbidity and mortality in diverse conditions, from heart disease to fetal distress. It is usually attributed to fluctuation in cardiac autonomic nerve activity. We calculated HRV parameters from a variety of cardiac preparations (including humans, living animals, Langendorff-perfused heart, and single sinoatrial nodal cell) in diverse species, combining this with data from previously published articles. We show that regardless of conditions, there is a universal exponential decay-like relationship between HRV and HR. Using 2 biophysical models, we develop a theory for this and confirm that HRV is primarily dependent on HR and cannot be used in any simple way to assess autonomic nerve activity to the heart. We suggest that the correlation between a change in HRV and altered morbidity and mortality is substantially attributable to the concurrent change in HR. This calls for re-evaluation of the findings from many articles that have not adjusted properly or at all for HR differences when comparing HRV in multiple circumstances.
Oral Delivery of Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7) Bioencapsulated in Plant Cells Attenuates Pulmonary Hypertension
Authors: Shenoy Vinayak , Kwon Kwang-Chul , Rathinasabapathy Anandharajan , Lin Shina , Jin Guiying , Song Chunjuan , Shil Pollob , Nair Anand , Qi Yanfei , Li Qiuhong , Francis Joseph , Katovich Michael J. , Daniell Henry , Raizada Mohan K.
Published: September 2014

Emerging evidences indicate that diminished activity of the vasoprotective axis of the renin–angiotensin system, constituting angiotensin-converting enzyme 2 (ACE2) and its enzymatic product, angiotensin-(1-7) [Ang-(1-7)] contribute to the pathogenesis of pulmonary hypertension (PH). However, long-term repetitive delivery of ACE2 or Ang-(1-7) would require enhanced protein stability and ease of administration to improve patient compliance. Chloroplast expression of therapeutic proteins enables their bioencapsulation within plant cells to protect against gastric enzymatic degradation and facilitates long-term storage at room temperature. Besides, fusion to a transmucosal carrier helps effective systemic absorption from the intestine on oral delivery. We hypothesized that bioencapsulating ACE2 or Ang-(1-7) fused to the cholera nontoxin B subunit would enable development of an oral delivery system that is effective in treating PH. PH was induced in male Sprague Dawley rats by monocrotaline administration. Subset of animals was simultaneously treated with bioencapsulaed ACE2 or Ang-(1-7) (prevention protocol). In a separate set of experiments, drug treatment was initiated after 2 weeks of PH induction (reversal protocol). Oral feeding of rats with bioencapsulated ACE2 or Ang-(1-7) prevented the development of monocrotaline-induced PH and improved associated cardiopulmonary pathophysiology. Furthermore, in the reversal protocol, oral ACE2 or Ang-(1-7) treatment significantly arrested disease progression, along with improvement in right heart function, and decrease in pulmonary vessel wall thickness. In addition, a combination therapy with ACE2 and Ang-(1-7) augmented the beneficial effects against monocrotaline-induced lung injury. Our study provides proof-of-concept for a novel low-cost oral ACE2 or Ang-(1-7) delivery system using transplastomic technology for pulmonary disease therapeutics.
Acutihumerus patagoniensis (Sieg, 1986) (Tanaidacea: Kalliapseudidae): supplementary description and remarks on its taxonomic status
Authors: GIACHETTI CLARA BELEN , ROCCATAGLIATA DANIEL
Published: September 2014

Acutihumerus patagoniensis (Sieg, 1986) was originally described based on a single specimen from Golfo Nuevo, northern Patagonia, Argentina. Over 3000 specimens referable to this species from just a few miles of its type locality are now available. Based on these specimens, the description of A. patagoniensis is completed and the ontogenetic changes of the male cheliped are described and illustrated. Acutihumerus patagoniensis has recently been considered a junior synonym of A. cavooreni (Băcescu & Absalao, 1985) from southern Brazil. However, these species can be distinguished mainly by the male chela: A. patagoniensis has a much wider notch palm than A. cavooreni. Furthermore, most of the males herein reported from off the Río de la Plata have a chela with a narrow notch, a fact that suggests that this area might be a zone of hybridization or contact between A. patagoniensis and A. cavooreni. Hence, we claim that the recently proposed synonymy has not been proven, and the resolution of this taxonomic problem must await additional specimens of A. cavooreni from its type locality (Rio Grande do Sul, Brazil).
One new species of the genus Kuzicus (Orthoptera: Tettigoniidae: Meconematinae) from Yunnan, China
Authors: HAN LI , SHI FU-MING
Published: September 2014

One new species is described, i.e. Kuzicus (Kuzicus) compressus Han & Shi sp. nov. The type species is preserved in the Museum of Hebei University.
Precipitation Estimates from MSG SEVIRI Daytime, Nighttime, and Twilight Data with Random Forests
Authors: Kühnlein Meike , Appelhans Tim , Thies Boris , Nauß Thomas
Published: September 2014

A new rainfall retrieval technique for determining rainfall rates in a continuous manner (day, twilight, and night) resulting in a 24-h estimation applicable to midlatitudes is presented. The approach is based on satellite-derived information on cloud-top height, cloud-top temperature, cloud phase, and cloud water path retrieved from Meteosat Second Generation (MSG) Spinning Enhanced Visible and Infrared Imager (SEVIRI) data and uses the random forests (RF) machine-learning algorithm. The technique is realized in three steps: (i) precipitating cloud areas are identified, (ii) the areas are separated into convective and advective-stratiform precipitating areas, and (iii) rainfall rates are assigned separately to the convective and advective-stratiform precipitating areas. Validation studies were carried out for each individual step as well as for the overall procedure using collocated ground-based radar data. Regarding each individual step, the models for rain area and convective precipitation detection produce good results. Both retrieval steps show a general tendency toward elevated prediction skill during summer months and daytime. The RF models for rainfall-rate assignment exhibit similar performance patterns, yet it is noteworthy how well the model is able to predict rainfall rates during nighttime and twilight. The performance of the overall procedure shows a very promising potential to estimate rainfall rates at high temporal and spatial resolutions in an automated manner. The near-real-time continuous applicability of the technique with acceptable prediction performances at 3–8-hourly intervals is particularly remarkable. This provides a very promising basis for future investigations into precipitation estimation based on machine-learning approaches and MSG SEVIRI data.
Orographic Signature on Extreme Precipitation of Short Durations
Authors: Avanzi Francesco , De Michele Carlo , Gabriele Salvatore , Ghezzi Antonio , Rosso Renzo
Published: September 2014

This paper investigates how atmospheric circulation and orography affect the spatial variability of extreme precipitation in terms of depth–duration–frequency (DDF) curve parameters. To this aim, the Italian territory was considered because it is characterized by a complex orography and different precipitation dynamics and regimes. A database of 1494 time series with more than 20 years of maximum annual precipitation data was collected for the durations of 1, 3, 6, 12, and 24 h. For each data series, the parameters of DDF curves were estimated using a statistical simple scale invariance model. Hence, the combined effect of orography and atmospheric fields on parameter variability was investigated considering the spatial distribution of the parameters and their relation with elevation. The vertically integrated atmospheric moisture flux J was used as a measurement of the principal direction of the vapor transport at a given location. The analysis highlights the variability of DDF parameters and quantiles according to orography and precipitation climatology. This is confirmed by the evaluation of J modal direction over the study area. The variability of DDF parameters with mere elevation shows that maxima at high elevations seem to be upper bounded and more variable than those at lower elevations. Moreover, the mean of maximum annual precipitation of unit duration decreases with elevation. This last phenomenon is defined as “reverse orographic effect” on extreme precipitation of short durations.
A 10-Year Study on the Characteristics of Thunderstorms in Belgium Based on Cloud-to-Ground Lightning Data
Authors: Poelman Dieter R.
Published: September 2014

Temporal and spatial distributions of cloud-to-ground (CG) lightning in Belgium are analyzed. Based on data from the European Cooperation for Lightning Detection (EUCLID) network, spanning a period of 10 years between 2004 and 2013, mean CG flash densities vary between 0.3 km−2 yr−1 in the west up to 2.4 km−2 yr−1 toward the east of Belgium, with an average flash density of 0.7 km−2 yr−1. The same behavior is found in terms of thunderstorm days and hours, where in the east most of the activity is observed, with a drop-off toward the coast. The majority of lightning activity takes place in the summer months between May and August, accounting for nearly 90% of the total activity. Furthermore, the thunderstorm season reaches its highest activity in July in terms of CG detections, while the diurnal cycle peaks between 1500 and 1600 UTC. A correlation is found between the estimated peak currents and altitude, with on average higher absolute peak currents at lower elevations and vice versa. In addition, a cell tracking algorithm is applied to the data to monitor the behavior of the individual cells. It is found that the lightning cells travel at an average speed of about 25 km h−1, with a preferred northeasterly direction of movement. At last, CG flash rates are strongly related to the cell area.