bluuebunny/crossref_metadata_2025 huggingface dataset:
Type I Interferon Released by Myeloid Dendritic Cells Reversibly Impairs Cytomegalovirus Replication by Inhibiting Immediate Early Gene Expression
Authors: Holzki Julia Katharina , Dağ Franziska , Dekhtiarenko Iryna , Rand Ulfert , Casalegno-Garduño Rosaely , Trittel Stephanie , May Tobias , Riese Peggy , Čičin-Šain Luka
Published: July 2015

Cytomegalovirus (CMV) is a ubiquitous beta-herpesvirus whose reactivation from latency is a major cause of morbidity and mortality in immunocompromised hosts. Mouse CMV (MCMV) is a well-established model virus to study virus-host interactions. We showed in this study that the CD8-independent antiviral function of myeloid dendritic cells (mDC) is biologically relevant for the inhibition of MCMV replication
in vivo
and
in vitro. In vivo
ablation of CD11c
+
DC resulted in higher viral titers and increased susceptibility to MCMV infection in the first 3 days postinfection. We developed
in vitro
coculture systems in which we cocultivated MCMV-infected endothelial cells or fibroblasts with T cell subsets and/or dendritic cells. While CD8 T cells failed to control MCMV replication, bone marrow-derived mDC reduced viral titers by a factor of up to 10,000. Contact of mDC with the infected endothelial cells was crucial for their antiviral activity. Soluble factors secreted by the mDC blocked MCMV replication at the level of immediate early (IE) gene expression, yet the viral lytic cycle reinitiated once the mDC were removed from the cells. On the other hand, the mDC did not impair MCMV replication in cells deficient for the interferon (IFN) alpha/beta receptor (IFNAR), arguing that type I interferons were critical for viral control by mDC. In light of our recent observation that type I IFN is sufficient for the induction of latency immediately upon infection, our results imply that IFN secreted by mDC may play an important role in the establishment of CMV latency.

IMPORTANCE
Numerous studies have focused on the infection of DC with cytomegaloviruses and on the establishment of latency within them. However, almost all of these studies have relied on the infection of DC monocultures
in vitro
, whereas DC are just one among many cell types present in an infection site
in vivo
. To mimic this aspect of the
in vivo
situation, we cocultured DC with infected endothelial cells or fibroblasts. Our data suggest that direct contact with virus-infected endothelial cells activates CD11c
+
DC, which leads to reversible suppression of MCMV replication at the level of IE gene expression by a mechanism that depends on type I IFN. The effect matches the formal definition of viral latency. Therefore, our data argue that the interplay of dendritic cells and infected neighboring cells might play an important role in the establishment of viral latency.
The Epstein-Barr Virus BDLF4 Gene Is Required for Efficient Expression of Viral Late Lytic Genes
Authors: Watanabe Takahiro , Narita Yohei , Yoshida Masahiro , Sato Yoshitaka , Goshima Fumi , Kimura Hiroshi , Murata Takayuki
Published: July 2015

Epstein-Barr virus (EBV) is a gammaherpesvirus, associated with infectious mononucleosis and various types of malignancy. We focused here on the BDLF4 gene of EBV and identified it as a lytic gene, expressed with early kinetics. Viral late gene expression of the BDLF4 knockout strain was severely restricted; this could be restored by an exogenous supply of BDLF4. These results indicate that BDLF4 is important for the EBV lytic replication cycle, especially in late gene expression.
Adhesins Involved in Attachment to Abiotic Surfaces by Gram-Negative Bacteria
Authors: Berne Cécile , Ducret Adrien , Hardy Gail G. , Brun Yves V.
Published: July 2015

During the first step of biofilm formation, initial attachment is dictated by physicochemical and electrostatic interactions between the surface and the bacterial envelope. Depending on the nature of these interactions, attachment can be transient or permanent. To achieve irreversible attachment, bacterial cells have developed a series of surface adhesins promoting specific or nonspecific adhesion under various environmental conditions. This article reviews the recent advances in our understanding of the secretion, assembly, and regulation of the bacterial adhesins during biofilm formation, with a particular emphasis on the fimbrial, nonfimbrial, and discrete polysaccharide adhesins in Gram-negative bacteria.
What diseases are causally linked to vitamin D deficiency?
Authors: Reid Ian R
Published: July 2015

The classical clinical consequence of vitamin D deficiency is osteomalacia, presenting as rickets in children. This remains a common problem in parts of the Middle East and the Indian subcontinent, and occurs when serum 25-hydroxyvitamin D levels are <25 nmol/L. Osteomalacia remains the only problem that is unequivocally a consequence of vitamin D deficiency. Low levels of 25-hydroxyvitamin D are observed in a wide range of conditions, but consistent trial evidence of amelioration of these conditions with vitamin D is lacking. Monotherapy with vitamin D has not been found to be effective in meta-analyses of trials assessing its effects on bone density, fractures or falls. At present, supplements should be advised for individuals at risk of having serum 25-hydroxyvitamin D levels in the 25–40 nmol/L range, or below, with a view to prevention of osteomalacia.
A hitherto unrecognised case of progressive multifocal leukoencephalopathy
Authors: Tan Huey Kuan , Tang Chun Hong
Published: July 2015

A 65-year-old man presented with a 6-week history of increasing confusion with associated cognitive decline. Empirical antibiotic cover for a urinary tract infection was prescribed with no response. After exhaustive radiological and pathological investigations were carried out, a diagnosis of John Cunningham virus encephalopathy was made. This case report describes the varied clinical presentation of symptoms and their management options, along with the latest clinical opinions behind them.
Van der Knaap disease: a rare disease with atypical features
Authors: Roy Ujjawal , Joshi Bhushan , Ganguly Goutam
Published: July 2015

Megalencephalic leukoencephalopathy with subcortical cysts (MLC), or Van der Knaap disease, is a rare autosomal recessive disorder. It is characterised by macrocephaly that either presents at birth or develops during infancy. It occurs more commonly in some ethnicities where consanguinity is common, such as in the Agrawal community in India. This disease typically presents with a history of delayed motor milestones in affected children. MRI findings including leukodystrophy and subcortical cysts are hallmarks of the disease and yield the diagnostic clue in most cases. Several cases of Van der Knaap disease with classical features have been reported in the literature. We present a case of Van der Knaap disease with classical MRI features, including a few distinctly atypical characteristics in its epidemiological, clinical and electrophysiological attributes.
Fungal endophthalmitis: an unusual complication of GI surgery and endoluminal vacuum therapy
Authors: Wood Megan , Wright David , Witherspoon Paul
Published: July 2015

We present a case of endogenous fungal endophthalmitis arising as a complication of fungal septicaemia following gastrointestinal surgery, and subsequent treatment with endoluminal vacuum therapy (Endo-SPONGE, B Braun Medical Ltd). Our patient developed a pre-sacral collection due to an anastomotic leak post ileoanal pouch formation. Despite treatment with Endo-sponges and antibiotics, the patient suffered recurrent sepsis and the cavity failed to reduce in size. He developed red eyes and blurred vision, leading to the diagnosis of fungal endophthalmitis. Extended fungal cultures of the Endo-sponges and pouch effluent revealedCandidaspp. This case is the first report of fungal endophthalmitis associated with Endo-sponge use and highlights the importance of fungal cultures in patients with ongoing sepsis.
Colistin neurotoxicity: revisited
Authors: Nigam Aruna , Kumari Archana , Jain Reena , Batra Swaraj
Published: July 2015

The revival of polymyxin antibiotics with the advent of multidrug resistant gram–negative bacteria in the recent decade has led to renewed interest in toxicity of this indispensable drug. We report a postoperative case of burst abdomen where colistin was started in view ofPseudomonasorganism sensitive to colistin. Subsequently, the patient went into respiratory depression and encephalopathy after starting the treatment. She recovered promptly after stopping the drug.
Screening for Lynch syndrome and referral to clinical genetics by selective mismatch repair protein immunohistochemistry testing: an audit and cost analysis
Authors: Colling Richard , Church David N , Carmichael Juliet , Murphy Lucinda , East James , Risby Peter , Kerr Rachel , Chetty Runjan , Wang Lai Mun
Published: July 2015

Lynch syndrome (LS) accounts for around 3% of colorectal cancers (CRCs) and is caused by germline mutations in mismatch repair (MMR) genes. Recently, screening strategies to identify patients with LS have become popular. We audited CRCs screened with MMR immunohistochemistry (IHC) in 2013. 209 tumours had MMR IHC performed at a cost of £12 540. 47/209 (21%) cases showed IHC loss of expression in at least one MMR protein. 28/44 cases with loss of MLH1 had additionalBRAF V600Etesting, at a cost of £5040. MMR IHC reduced the number of potential clinical genetics referrals from 209 to 47.BRAFmutation testing, performed in a subset of cases with MLH1 loss, further reduced this to 21. At a cost of £1340 per referral, this model of LS screening for clinical genetics referral had significant potential savings (£234 340) and can be easily implemented in parallel with MMR IHC done for prognostication in CRCs.
Place of death in the population dying from diseases indicative of palliative care need: a cross-national population-level study in 14 countries
Authors: Pivodic Lara , Pardon Koen , Morin Lucas , Addington-Hall Julia , Miccinesi Guido , Cardenas-Turanzas Marylou , Onwuteaka-Philipsen Bregje , Naylor Wayne , Ruiz Ramos Miguel , Van den Block Lieve , Wilson Donna M , Loucka Martin , Csikos Agnes , Rhee Yong Joo , Teno Joan , Deliens Luc , Houttekier Dirk , Cohen Joachim
Published: July 2015

Background

Studying where people die across countries can serve as an evidence base for health policy on end-of-life care. This study describes the place of death of people who died from diseases indicative of palliative care need in 14 countries, the association of place of death with cause of death, sociodemographic and healthcare availability characteristics in each country and the extent to which these characteristics explain country differences in the place of death.

Methods

Death certificate data for all deaths in 2008 (age ≥1 year) in Belgium, Canada, the Czech Republic, England, France, Hungary, Italy, Mexico, the Netherlands, New Zealand, South Korea, Spain (Andalusia), the USA and Wales caused by cancer, heart/renal/liver failure, chronic obstructive pulmonary disease, diseases of the nervous system or HIV/AIDS were linked with national or regional healthcare statistics (N=2 220 997).

Results

13% (Canada) to 53% (Mexico) of people died at home and 25% (the Netherlands) to 85% (South Korea) died in hospital. The strength and direction of associations between home death and cause of death, sociodemographic and healthcare availability factors differed between countries. Differences between countries in home versus hospital death were only partly explained by differences in these factors.

Conclusions

The large differences between countries in and beyond Europe in the place of death of people in potential need of palliative care are not entirely attributable to sociodemographic characteristics, cause of death or availability of healthcare resources, which suggests that countries’ palliative and end-of-life care policies may influence where people die.
Development and validation of a feline abdominal palpation model and scoring rubric
Authors: Williamson J. A. , Hecker K. , Yvorchuk K. , Artemiou E. , French H. , Fuentealba C.
Published: July 2015

Simulation in veterinary education enables clinical skills practice without animal use. A feline abdominal palpation model was created that allows practice in this fractious species. This study assessed the model and rubric using a validation framework of content evidence, internal structure and relationship with level of training. Content Evidence: Veterinarians accepted this model as a helpful training tool for students (median=4 on five‐point Likert scale). Internal Structure Evidence: G‐coefficients were low for first‐ and second‐year students (0.28 and 0.23), but were acceptable for veterinarians (0.61). Internal consistency values (0.24, 0.42 and 0.67) followed a similar pattern. Thus, scores were more reliable for veterinarians than for the students. Evidence of Relationship with Level of Training: Although level of training impacted reliability, its effect on performance scores was inconsistent. Analysis of variance (ANOVA) identified no differences among the groups of students and veterinarians. However, effect size between first‐ and third‐year students was medium to large (0.62). Effect sizes between the veterinarians and student groups were small. Although the model and rubric appeared valid for experts, modifications would be necessary to generate reliable scores for students. These results allow greater understanding of the needs of students utilising a low‐fidelity model.
Reliability-based geotechnical design in 2014 Canadian Highway Bridge Design Code
Authors: Fenton Gordon A. , Naghibi Farzaneh , Dundas David , Bathurst Richard J. , Griffiths D.V.
Published: July 2015

Canada has two national civil codes of practice that include geotechnical design provisions: the National Building Code of Canada and the Canadian Highway Bridge Design Code. For structural designs, both of these codes have been employing a load and resistance factor format embedded within a limit states design framework since the mid-1970s. Unfortunately, limit states design in geotechnical engineering has been lagging well behind that in structural engineering for the simple fact that the ground is by far the most variable (and hence uncertain) of engineering materials. Although the first implementation of a geotechnical limit states design code appeared in Denmark in 1956, it was not until 1979 that the concept began to appear in Canadian design codes, i.e., in the Ontario Highway Bridge Design Code, which later became the Canadian Highway Bridge Design Code (CHBDC). The geotechnical design provisions in the CHBDC have evolved significantly since their inception in 1979. This paper describes the latest advances appearing in the CHBDC along with the steps taken to calibrate its recent geotechnical resistance and consequence factors.
Yeast microbiota of natural cavities of manatees (Trichechus inunguis and Trichechus manatus) in Brazil and its relevance for animal health and management in captivity
Authors: Sidrim José Júlio Costa , Carvalho Vitor Luz , Castelo-Branco Débora de Souza Collares Maia , Brilhante Raimunda Sâmia Nogueira , Bandeira Tereza de Jesus Pinheiro Gomes , Cordeiro Rossana de Aguiar , Guedes Gláucia Morgana de Melo , Barbosa Giovanna Riello , Lazzarini Stella Maris , Oliveira Daniella Carvalho Ribeiro , de Meirelles Ana Carolina Oliveira , Attademo Fernanda Löffler Niemeyer , Freire Augusto Carlos da Bôaviagem , Moreira José Luciano Bezerra , Monteiro André Jalles , Rocha Marcos Fábio Gadelha
Published: July 2015

The aim of this study was to characterize the yeast microbiota of natural cavities of manatees kept in captivity in Brazil. Sterile swabs from the oral cavity, nostrils, genital opening, and rectum of 50 Trichechus inunguis and 26 Trichechus manatus were collected. The samples were plated on Sabouraud agar with chloramphenicol and incubated at 25 °C for 5 days. The yeasts isolated were phenotypically identified by biochemical and micromorphological tests. Overall, 141 strains were isolated, of which 112 were from T. inunguis (Candida albicans, Candida parapsilosis sensu stricto, Candida orthopsilosis, Candida metapsilosis, Candida guilliermondii, Candida pelliculosa, Candida tropicalis, Candida glabrata, Candida famata, Candida krusei, Candida norvegensis, Candida ciferri, Trichosporon sp., Rhodotorula sp., Cryptococcus laurentii) and 29 were from T. manatus (C. albicans, C. tropicalis, C. famata, C. guilliermondii, C. krusei, Rhodotorula sp., Rhodotorula mucilaginosa, Rhodotorula minuta, Trichosporon sp.). This was the first systematic study to investigate the importance of yeasts as components of the microbiota of sirenians, demonstrating the presence of potentially pathogenic species, which highlights the importance of maintaining adequate artificial conditions for the health of captive manatees.
Size does not matter for male Marbled Salamanders (Ambystomaopacum)
Authors: Croshaw D.A. , Pechmann J.H.K.
Published: July 2015

Understanding the phenotypic attributes that contribute to variance in mating and reproductive success is crucial in the study of evolution by sexual selection. In many animals, body size is an important trait because larger individuals enjoy greater fitness due to the ability to secure more mates and produce more offspring. Among males, this outcome is largely mediated by greater success in competition with rival males and (or) advantages in attractiveness to females. Here we tested the hypothesis that large male Marbled Salamanders (Ambystoma opacum (Gravenhorst, 1807)) mate with more females and produce more offspring than small males. In experimental breeding groups, we included males chosen specifically to represent a range of sizes. After gravid females mated and nested freely, we collected egg clutches and genotyped all adults and samples of hatchlings with highly variable microsatellite markers to assign paternity. Size had little effect on male mating and reproductive success. Breeding males were not bigger than nonbreeding males, mates of polyandrous females were not smaller than those of monogamous females, and there was no evidence for positive assortative mating by size. Although body size did not matter for male Marbled Salamanders, we documented considerable fitness variation and discuss alternative traits that could be undergoing sexual selection.
Using morphology to infer physiology: case studies on rorqual whales (Balaenopteridae)
Authors: Goldbogen Jeremy A. , Shadwick Robert E. , Lillie Margo A. , Piscitelli Marina A. , Potvin Jean , Pyenson Nicholas D. , Vogl A. Wayne
Published: July 2015

Whales are important model systems for understanding the physiological and ecological consequences of extreme body size. However, whales are also some of the most difficult animals to study because their large size precludes experimental studies under controlled conditions. Here we review a wide range of morphological studies that enable greater inference of physiological processes. In particular, we focus on baleen whales that exhibit extensive diving and foraging adaptations. Using morphological data, we (i) explore the biomechanics and sensory physiology of lunge-feeding rorqual whales (Balaenopteridae), (ii) determine the effects of scale and diving pressures on the circulatory physiology of fin whales (Balaenoptera physalus (L., 1758)), and (iii) better understand the adaptations of the cetacean respiratory system that facilitate a fully aquatic life history. These studies underscore the value of understanding functional morphology in animals that cannot be studied using traditional laboratory techniques.
Regionally widespread parasitic water mites have relatively broad host-species ranges
Authors: Mlynarek Julia J. , Knee Wayne , Smith Bruce P. , Forbes Mark R.
Published: July 2015

Certain parasite species have free-living stages, so habitat range may influence host-species range. We tested whether regional occurrence and habitat use of parasitic water mites were related to their host-species range. We collected 7445 Arrenurus Dugès, 1834 mites from 7107 coenagrionid damselflies, representing 11 host species from 13 sites in southeastern Ontario and southwestern Quebec. Because larval water mites are difficult to identify morphologically to species, we chose to amplify the barcode fragment of cytochrome oxidase subunit I to explore host-species ranges. Fifteen operational taxonomic units or clades were identified based on the amplification from 217 larval mites. The Arrenurus clades that were present in both bog and marsh habitats had a broader host-species range than clades found only in marshes (the comparison with one clade found only in bogs lacked statistical power). As predicted, host-species range increased with the regional occurrence of an Arrenurus clade. Additionally, the most commonly barcoded species also have high host-species ranges. This result could be because species with broader host-species ranges are more common and were more likely to be sampled and barcoded (an explanation we favor), or due to sampling bias. Although this is the first study exploring whether habitat range affects host-species range, further investigation is needed to tease apart which habitat factors influence host-species ranges the most.
Generating Majorana neutrino masses with loops
Authors: Geng Chao-Qiang
Published: July 2015

We give a review on neutrino models in which Majorana neutrino masses are generated radiatively through loop diagrams. In particular, we concentrate on the two-loop models which contain extra doubly charged singlet [Formula: see text] and triplet [Formula: see text] scalars beyond the Standard Model so that the new Yukawa [Formula: see text] and effective [Formula: see text] couplings can be induced. In these two-loop models, we find that the neutrino mass spectrum is a normal hierarchy and the rate of the neutrinoless double beta decay [Formula: see text] can be large as it is dominated by the short-distance tree contribution. In addition, by using the neutrino oscillation data and comparing with the global fitting result in the literature, we find a unique neutrino mass matrix and predict the Dirac and two Majorana CP phases to be [Formula: see text], [Formula: see text] and [Formula: see text] with [Formula: see text], respectively.
Counterfactual quantum cryptography network with untrusted relay
Authors: Chen Yuanyuan , Gu Xuemei , Jiang Dong , Xie Ling , Chen Lijun
Published: July 2015

Counterfactual quantum cryptography allows two remote parties to share a secret key even though a physical particle is not in fact transmitted through the quantum channel. In order to extend the scope of counterfactual quantum cryptography, we use an untrusted relay to construct a multi-user network. The implementation issues are discussed to show that the scheme can be realized with current technologies. We also prove the practical security advantages of the scheme by eliminating the probability that an eavesdropper can directly access the signal or an untrusted relay can perform false operations.
An Efficient Flash Translation Layer for Large Block NAND Flash Devices
Authors: Chung Tae-Sun , Park Dong-Joo , Kim Jongik
Published: July 2015

Recently, flash memory is widely used as a non-volatile storage for embedded applications such as smart phones, MP3 players, digital cameras and so on. The software layer called flash translation layer (FTL) becomes more important since it is a key factor in the overall flash memory system performance. Many researchers have proposed FTL algorithms for small block flash memory in which the size of a physical page of flash memory is equivalent to the size of a data sector of the file system. However, major flash vendors have now produced large block flash memory in which the size of a physical page is larger than the file system's data sector size. Since large block flash memory has new features, designing FTL algorithms specialized to large block flash memory is a challenging issue. In this paper, we provide an efficient FTL named LSTAFF* for large block flash memory. LSTAFF* is designed to achieve better performance by using characteristics of large block flash memory and to provide safety by abiding by restrictions of large block flash memory. Experimental results show that LSTAFF* outperforms existing algorithms on a large block flash memory.
Lescop's invariant and gauge theory
Authors: Poudel Prayat
Published: July 2015

Taubes proved that the Casson invariant of an integral homology 3-sphere equals half the Euler characteristic of its instanton Floer homology. We extend this result to all closed oriented 3-manifolds with positive first Betti number by establishing a similar relationship between the Lescop invariant of the manifold and its instanton Floer homology. The proof uses surgery techniques.
A new identity involving the classical Kloosterman sums and 2-dimensional Kloosterman sums
Authors: Zhang Wenpeng , Han Di
Published: July 2015

The main purpose of this paper is, using the properties of Gauss sums and the estimate for trigonometric sums, to study the relationships between the sixth power mean of the classical Kloosterman sums and the fourth power mean of the 2-dimensional Kloosterman sums, and give an interesting identity for them.
Numerical and Experimental Simulation of Two-Phase Tsunami Flow Through Buildings with Openings
Authors: Hartana  , Murakami Keisuke
Published: July 2015

During tsunami action on a structure, the structure is subjected to heavy loads with complex phenomena which include the interactions among tsunami, structure and air. In order to mitigate tsunami damages on structures, it is important to understand the characteristics of tsunami hydraulic loads acting on the structures with taking into account the above interactions. In the present study, the characteristics of tsunami forces on a building structure are investigated using a two-phase flow model. Two types of building models, a building without openings and with openings, were dealt with; and the effects of openings on the building under the tsunami hydraulic loads are examined. The simulation results were compared with the results obtained from one-phase flow simulation, and also verified with experimental data. The numerical results show good agreement with the measured ones. Furthermore, the effects of air taken into the flow and opening configuration on the characteristics of pressures and uplift forces were also discussed.
Antiplane Scattering of SH Waves by a Trapezoidal Valley with a Circular-Arc Alluvium in an Elastic Half Space
Authors: Zhang Chao , Liu Qijian , Deng Peng
Published: July 2015

Both lithologic and topographic irregularities may trigger significant scattering phenomenon of seismic waves. In this study, a series solution is presented for the analysis of scattering of SH waves induced by a trapezoidal valley during earthquakes. An appropriate region matching technique is utilized to divide the physical region into four computational subregions. The wave motions of each subregion are obtained as an infinite series of wave functions with unknown coefficients in the respective cylindrical coordinates through wave function expansion method. The Graf's addition theorem is applied to transform the wave potentials of each subregion into the global coordinate. The mixed boundary conditions are solved by truncating the obtained infinite equations into a finite set. The effects of geometrical topographies and sedimentary properties on the amplification are analyzed and discussed in terms of steady-state and transient response analysis.
Stability analysis of a discrete biological model
Authors: Khan A. Q. , Qureshi M. N.
Published: July 2015

In this paper, we investigate the equilibrium point, local and global behavior of the unique positive equilibrium point, and rate of convergence of positive solutions of following discrete biological model: [Formula: see text] where parameters [Formula: see text] and the initial conditions [Formula: see text] are positive real numbers. Some numerical examples are given to verify theoretical results.
CLT for linear spectral statistics of a rescaled sample precision matrix
Authors: Zheng Shurong , Bai Zhidong , Yao Jianfeng
Published: July 2015

Central limit theorems (CLTs) of linear spectral statistics (LSS) of general Fisher matrices [Formula: see text] are widely used in multivariate statistical analysis where [Formula: see text] with a deterministic complex matrix [Formula: see text] and two sample covariance matrices [Formula: see text] and [Formula: see text] from two independent samples with sample sizes [Formula: see text] and [Formula: see text]. As the first step to obtain the CLT, it is necessary to establish the CLT for LSS of the random matrix [Formula: see text], or equivalently that of [Formula: see text], that is a sample precision matrix rescaled by a general non-negative definite Hermitian matrix [Formula: see text]. Because the scaling matrix [Formula: see text] in many large-dimensional problems may not be invertible, the result does not simply follow from the celebrated CLT by Bai and Silverstein (2004). Thus, we have to alternatively derive the CLT of LSS of [Formula: see text] where the inverse of [Formula: see text] may not exist, thus extending Bai and Silverstein’s CLT. As a further innovation of the paper, general populations for the sample covariance matrix [Formula: see text] are covered requiring the existence a fourth-order moment of arbitrary value, that is not necessarily matching the values of the Gaussian case.
Simulating the area covered by lava flows using the DOWNFLOW code
Authors: Tarquini Simone , Favalli Massimiliano
Published: July 2015

DOWNFLOW is a probabilistic code for the simulation of the area covered by lava flows. This code has been used extensively for several basaltic volcanoes in the last decade, and a review of some applications is presented. DOWNFLOW is based on the simple principle that a lava flow tends to follow the steepest descent path downhill from the vent. DOWNFLOW computes the area possibly inundated by lava flows by deriving a number,
N
, of steepest descent paths, each path being calculated over a randomly perturbed topography. The perturbation is applied at each point of the topography, and ranges within the interval ±Δ
h
.
N
and Δ
h
are the two basic parameters of the code. The expected flow length is constrained by statistical weighting based on the past activity of the volcano. The strength of the code is that: (i) only limited volcanological knowledge is necessary to apply the code at a given volcano; (ii) there are only two (easily tunable) input parameters; and (iii) computational requirements are very low. However, DOWNFLOW does not provide the progression of the lava emplacement over time. The use of DOWNFLOW is ideal when a large number of simulations are necessary: for example, to compile maps for hazard and risk-assessment purposes.
Nonsteroidal anti-inflammatory drugs alter vasa recta diameter via pericytes
Authors: Kennedy-Lydon Teresa , Crawford Carol , Wildman Scott S. , Peppiatt-Wildman Claire M.
Published: July 2015

We have previously shown that vasa recta pericytes are known to dilate vasa recta capillaries in the presence of PGE2and contract vasa recta capillaries when endogenous production of PGE2is inhibited by the nonselective nonsteroidal anti-inflammatory drug (NSAID) indomethacin. In the present study, we used a live rat kidney slice model to build on these initial observations and provide novel data that demonstrate that nonselective, cyclooxygenase-1-selective, and cyclooxygenase -2-selective NSAIDs act via medullary pericytes to elicit a reduction of vasa recta diameter. Real-time images of in situ vasa recta were recorded, and vasa recta diameters at pericyte and nonpericyte sites were measured offline. PGE2and epoprostenol (a prostacyclin analog) evoked dilation of vasa recta specifically at pericyte sites, and PGE2significantly attenuated pericyte-mediated constriction of vasa recta evoked by both endothelin-1 and ANG II. NSAIDs (indomethacin > SC-560 > celecoxib > meloxicam) evoked significantly greater constriction of vasa recta capillaries at pericyte sites than at nonpericyte sites, and indomethacin significantly attenuated the pericyte-mediated vasodilation of vasa recta evoked by PGE2, epoprostenol, bradykinin, and S-nitroso- N-acetyl-l-penicillamine. Moreover, a reduction in PGE2was measured using an enzyme immune assay after superfusion of kidney slices with indomethacin. In addition, immunohistochemical techiques were used to demonstrate the population of EP receptors in the medulla. Collectively, these data demonstrate that pericytes are sensitive to changes in PGE2concentration and may serve as the primary mechanism underlying NSAID-associated renal injury and/or further compound-associated tubular damage.
Differential encoding of spatial information among retinal on cone bipolar cells
Authors: Purgert Robert J. , Lukasiewicz Peter D.
Published: July 2015

The retina is the first stage of visual processing. It encodes elemental features of visual scenes. Distinct cone bipolar cells provide the substrate for this to occur. They encode visual information, such as color and luminance, a principle known as parallel processing. Few studies have directly examined whether different forms of spatial information are processed in parallel among cone bipolar cells. To address this issue, we examined the spatial information encoded by mouse ON cone bipolar cells, the subpopulation excited by increments in illumination. Two types of spatial processing were identified. We found that ON cone bipolar cells with axons ramifying in the central inner plexiform layer were tuned to preferentially encode small stimuli. By contrast, ON cone bipolar cells with axons ramifying in the proximal inner plexiform layer, nearest the ganglion cell layer, were tuned to encode both small and large stimuli. This dichotomy in spatial tuning is attributable to amacrine cells providing stronger inhibition to central ON cone bipolar cells compared with proximal ON cone bipolar cells. Furthermore, background illumination altered this difference in spatial tuning. It became less pronounced in bright light, as amacrine cell-driven inhibition became pervasive among all ON cone bipolar cells. These results suggest that differential amacrine cell input determined the distinct spatial encoding properties among ON cone bipolar cells. These findings enhance the known parallel processing capacity of the retina.
Adaptation and aftereffects of split-belt walking in cerebellar lesion patients
Authors: Hoogkamer Wouter , Bruijn Sjoerd M. , Sunaert Stefan , Swinnen Stephan P. , Van Calenbergh Frank , Duysens Jacques
Published: July 2015

To walk efficiently and stably on different surfaces under various constrained conditions, humans need to adapt their gait pattern substantially. Although the mechanisms behind locomotor adaptation are still not fully understood, the cerebellum is thought to play an important role. In this study we aimed to address the specific localization of cerebellar involvement in split-belt adaptation by comparing performance in patients with stable focal lesions after cerebellar tumor resection and in healthy controls. We observed that changes in symmetry of those parameters that were most closely related to interlimb coordination (such as step length and relative double stance time) were similar between healthy controls and cerebellar patients during and after split-belt walking. In contrast, relative stance times (proportions of stance in the gait cycle) were more asymmetric for the patient group than for the control group during the early phase of the post-split-belt condition. Patients who walked with more asymmetric relative stance times were more likely to demonstrate lesions in vermal lobules VI and Crus II. These results confirm that deficits in gait adaptation vary with ataxia severity and between patients with different types of cerebellar damage.
Neural substrates of sensorimotor processes: letter writing and letter perception
Authors: Vinci-Booher Sophia A. , James Karin H.
Published: July 2015

Writing and perceiving letters are thought to share similar neural substrates; however, what constitutes a neural representation for letters is currently debated. One hypothesis is that letter representation develops from sensorimotor experience resulting in an integrated set of modality-specific regions, whereas an alternative account suggests that letter representations may be abstract, independent of modality. Studies reviewed suggest that letter representation consists of a network of modality-responsive brain regions that may include an abstract component.
Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance
Authors: Gurden Mark D. , Westwood Isaac M. , Faisal Amir , Naud Sébastien , Cheung Kwai-Ming J. , McAndrew Craig , Wood Amy , Schmitt Jessica , Boxall Kathy , Mak Grace , Workman Paul , Burke Rosemary , Hoelder Swen , Blagg Julian , Van Montfort Rob L.M. , Linardopoulos Spiros
Published: July 2015

Acquired resistance to therapy is perhaps the greatest challenge to effective clinical management of cancer. With several inhibitors of the mitotic checkpoint kinase MPS1 in preclinical development, we sought to investigate how resistance against these inhibitors may arise so that mitigation or bypass strategies could be addressed as early as possible. Toward this end, we modeled acquired resistance to the MPS1 inhibitors AZ3146, NMS-P715, and CCT251455, identifying five point mutations in the kinase domain of MPS1 that confer resistance against multiple inhibitors. Structural studies showed how the MPS1 mutants conferred resistance by causing steric hindrance to inhibitor binding. Notably, we show that these mutations occur in nontreated cancer cell lines and primary tumor specimens, and that they also preexist in normal lymphoblast and breast tissues. In a parallel piece of work, we also show that the EGFR p.T790M mutation, the most common mutation conferring resistance to the EGFR inhibitor gefitinib, also preexists in cancer cells and normal tissue. Our results therefore suggest that mutations conferring resistance to targeted therapy occur naturally in normal and malignant cells and these mutations do not arise as a result of the increased mutagenic plasticity of cancer cells. Cancer Res; 75(16); 3340–54. ©2015 AACR.
Aspirin Suppresses the Growth and Metastasis of Osteosarcoma through the NF-κB Pathway
Authors: Liao Dan , Zhong Li , Duan Tingmei , Zhang Ru-Hua , Wang Xin , Wang Gang , Hu Kaishun , Lv Xiaobin , Kang Tiebang
Published: July 2015

Purpose: Aspirin has recently been reported to reduce both the incidence and the risk of metastasis in colon cancer. However, there is no evidence at the cellular levels or in the animal models for such an effect of aspirin on cancer metastasis.

Experimental Design: MTT assay, colony formation assay, and apoptosis assay were employed to analyze the effects of aspirin on the osteosarcoma cell viability in vitro. The NF-κB activity was measured by the NF-κB p65 luciferase reporter. Western blotting was used to analyze the proteins in cells. The migration and invasion abilities of osteosarcoma cells in vitro were measured by the Transwell assay. Xenograft-bearing mice were used to assess the roles of aspirin in both tumor growth and metastasis of osteosarcoma in vivo (n = 5–8 mice/group). An unpaired Student t test or ANOVA with the Bonferroni post hoc test were used for the statistical comparisons.

Results: Aspirin reduced cell viability in a dose- and time-dependent manner in osteosarcoma cell lines, and aspirin synergistically sensitized osteosarcoma cells to cisplatin (DDP) in vitro and in vivo (P < 0.001). Moreover, aspirin markedly repressed the migration and invasion of osteosarcoma cells in vitro (P < 0.001), and dramatically diminished the occurrence of osteosarcoma xenograft metastases to the lungs in vivo (P < 0.001). Mechanistically, aspirin diminishes osteosarcoma migration, invasion, and metastasis through the NF-κB pathway.

Conclusions: Aspirin suppresses both the growth and metastasis of osteosarcoma through the NF-κB pathway at the cellular level and in the animal models. Clin Cancer Res; 21(23); 5349–59. ©2015 AACR.
Pleuropulmonary Blastoma in a Neonate Diagnosed Prenatally as Congenital Pulmonary Airway Malformation
Authors: Coleman Alan , Kline-Fath Beth , Stanek Jerzy , Lim Foong-Yen
Published: July 2015

Pleuropulmonary blastoma is an extremely rare lung neoplasm exclusive to children under 5 years of age. It presents a diagnostic challenge both prenatally and in early childhood due to its similarity to benign lung cysts, which are managed differently. We present the first case, to our knowledge, of a neonate with pleuropulmonary blastoma and myelomeningocele, though prenatally diagnosed as a congenital pulmonary airway malformation. We detail the prenatal imaging that facilitated counseling and delivery management in addition to the correlating postnatal imaging.
Behavioral Management of Feeding Disorders of Childhood
Authors: Silverman Alan H.
Published: July 2015

Feeding disorders, characterized by suboptimal intake and/or lack of age-appropriate eating habits, are common and may be seen in up to 45% of children. Feeding disorders are a significant concern to both the affected families and to the providers who treat them. Fortunately, there are well-established behavioral treatments which have been shown to be highly efficacious. This article provides an overview of behavioral assessment and treatment of pediatric feeding disorders, provides guidance in treatment planning, and provides information which may be useful in considering if additional psychological consultation may be beneficial.
Evaluation of Risk Minimisation Measures for Blood Components - Based on Reporting Rates of Transfusion-Transmitted Reactions (1997-2013)
Authors: Funk Markus B. , Heiden Margarethe , Volkers Peter , Lohmann Annette , Keller-Stanislawski Brigitte
Published: July 2015

Background: To assess the impact of safety measures, we compared reporting rates of transfusion-related reactions before and after the implementation of six measures in 1999, 2004, 2006, 2008 and 2009. Methods: Reporting rates of transfusion-transmitted bacterial infection (TTBI), viral infection (TTVI) and immune-mediated transfusion-related acute lung injury (TRALI) were calculated on the basis of confirmed annual reports and distributed blood components. Results: The introduction of HCV NAT testing caused a significant reduction of HCV reporting rate from 1:0.6 to 1:83.16 million administered blood components (p < 0.0001), donor screening for antibodies to hepatitis B core antigen caused a reduction of HBV reporting rate from 1:2.90 to 1:10.70 million units (p = 0.0168). A significant reduction from 1:0.094 to 1:2.42 million fresh frozen plasma (FFP) units could also be achieved by risk minimisation TRALI measures (p < 0.0001). Implementation of pre-donation sampling did not result in a significant decrease in TTBI, whereas limitation of shelf life for platelet concentrate (PC) minimised the TTBI reporting rate from 1:0.088 to 1:0.19 million PC units (p = 0.041). For HIV NAT pool testing, no significant reduction in HIV transmission was found due to very low reporting rates (1:10 million versus 1:27 million blood components, p = 0.422). Conclusion: On the basis of haemovigilance data, a significant benefit could be demonstrated for four of six implemented safety measures.
PRDX6 Protects ARPE-19 Cells from Oxidative Damage via PI3K/AKT Signaling
Authors: Zha Xu , Wu Guojiu , Zhao Xueying , Zhou Liqiong , Zhang Hong , Li Jinghua , Ma Linkun , Zhang Yuanping
Published: July 2015

Background/Aims: Oxidative stress that damages cells of the retinal pigment epithelium (RPE) can cause the development of hereditary retinal disease (HRD). PRDX6, which is a member of the PRDX family, is essential for removing metabolic free radicals from the body. However, the effect of PRDX6 on oxidative stress in HRD remains unknown. In this study, we sought to investigate the role of PRDX6 in oxidative stress-induced HRD in ARPE-19 cells and the molecular mechanism involved. Methods: ARPE-19 cells were used in the current study. Intracellular ROS levels were determined by flow cytometry. Lipid peroxidation was measured using a commercial MDA assay kit. Cellular variability was determined by MTT assay. Apoptosis was determined using an Annexin V-FITC Apoptosis Detection Kit. mRNA and protein expression levels were detected by real-time PCR and western blot analysis, respectively. Results: We found that H2O2 and blue light could induce significant oxidative stress damage and cell death in ARPE-19 cells. Furthermore, we found that PRDX6 levels significantly decreased after H2O2 treatment. PRDX6 overexpression protected ARPE-19 cells from H2O2- and blue light-induced oxidative damage, while PRDX6 knockdown enhanced oxidative damage in these cells. Mechanistically, we found that PRDX6 prevented oxidative damage and promoted ARPE-19 cell survival through the PI3K/AKT signaling pathway. Conclusions: Collectively, these results suggest that PRDX6 protects ARPE-19 cells from H2O2-induced oxidative stress and apoptosis and that this protection is mediated at least partially through the PI3K/AKT pathway.
Lumbar Disc Degeneration is Facilitated by MiR-100-Mediated FGFR3 Suppression
Authors: Yan Ning , Yu Shunzhi , Zhang Hailong , Hou Tiesheng
Published: July 2015

Background/Aims: The pathogenesis of lumbar disc degeneration (LDD) involved activation of matrix metalloproteinase 13 (MMP13) by differential expression of fibroblast growth factor receptor 1 (FGFR1) and FGFR3. Nevertheless, the molecular regulation of FGFR1 and FGFR3 in the lumber disc cells remains elusive. Methods: We examined the FGFR1 and FGFR3 levels and microRNAs (miRNAs) levels in the resected LDD discs, compared to the traumatized, non-LDD discs. We analyzed the binding of miR-100 to the 3′UTR of FGFR3 mRNA and its effects on FGFR3 translation by bioinformatics analysis and by luciferase-reporter assay, respectively. We modified miR-100 levels in a human nucleus pulposus SV40 cell line (HNPSV), and examined the effects on the expression of FGFR3 and MMP13, by RT-qPCR, Western blot and ELISA. Results: The levels of FGFR1 and miR-100 were significantly higher, while the levels of FGFR3 were significantly lower, in LDD discs, compared to the control non-LDD discs. The levels of FGFR3, but not the levels of FGFR1, inversely correlated with the levels of miR-100. Moreover, miR-100 was found to bind to the 3'UTR of FGFR3 mRNA to prevent its translation. In miR-100-modified HNPSV cells, we found that miR-100 decreased FGFR3 levels, and increased MMP13 levels. Conclusion: miR-100 may activate MMP13 through 3′UTR-suppressoin of FGFR3 mRNA to facilitate development of LDD.