bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimalarial Activity of Tulathromycin in a Murine Model of Malaria
Authors: Villarino Nicolas , Denny Joshua E. , Schmidt Nathan W.
Published: April 2015

There is an urgent need for new antimalarial agents and strategies to treat and control malaria. This study shows an antiplasmodium effect of tulathromycin in mice infected with
Plasmodium yoelii
. The administration of tulathromycin around the time of infection prevented the progression of disease in 100% of the animals. In addition, highly parasitized mice treated with tulathromycin showed a decreased parasite burden and cleared the parasite faster than did untreated infected mice.
Blocking Hsp70 Enhances the Efficiency of Amphotericin B Treatment against Resistant Aspergillus terreus Strains
Authors: Blatzer Michael , Blum Gerhard , Jukic Emina , Posch Wilfried , Gruber Peter , Nagl Markus , Binder Ulrike , Maurer Elisabeth , Sarg Bettina , Lindner Herbert , Lass-Flörl Cornelia , Wilflingseder Doris
Published: April 2015

The polyene antifungal amphotericin B (AmB) is widely used to treat life-threatening fungal infections. Even though AmB resistance is exceptionally rare in fungi, most
Aspergillus terreus
isolates exhibit an intrinsic resistance against the drug
in vivo
and
in vitro
. Heat shock proteins perform a fundamental protective role against a multitude of stress responses, thereby maintaining protein homeostasis in the organism. In this study, we elucidated the role of heat shock protein 70 (Hsp70) family members and compared resistant and susceptible
A. terreus
clinical isolates. The upregulation of cytoplasmic Hsp70 members at the transcriptional as well as translational levels was significantly higher with AmB treatment than without AmB treatment, particularly in resistant
A. terreus
isolates, thereby indicating a role of Hsp70 proteins in the AmB response. We found that Hsp70 inhibitors considerably increased the susceptibility of resistant
A. terreus
isolates to AmB but exerted little impact on susceptible isolates. Also, in
in vivo
experiments, using the
Galleria mellonella
infection model, cotreatment of resistant
A. terreus
strains with AmB and the Hsp70 inhibitor pifithrin-μ resulted in significantly improved survival compared with that achieved with AmB alone. Our results point to an important mechanism of regulation of AmB resistance by Hsp70 family members in
A. terreus
and suggest novel drug targets for the treatment of infections caused by resistant fungal isolates.
Genome Sequence of Aspergillus flavus NRRL 3357, a Strain That Causes Aflatoxin Contamination of Food and Feed
Authors: Nierman William C. , Yu Jiujiang , Fedorova-Abrams Natalie D. , Losada Liliana , Cleveland Thomas E. , Bhatnagar Deepak , Bennett Joan W. , Dean Ralph , Payne Gary A.
Published: April 2015

Aflatoxin contamination of food and livestock feed results in significant annual crop losses internationally.
Aspergillus flavus
is the major fungus responsible for this loss. Additionally,
A. flavus
is the second leading cause of aspergillosis in immunocompromised human patients. Here, we report the genome sequence of strain NRRL 3357.
Complete Genome Sequence of Bifidobacterium kashiwanohense JCM 15439
T
, Isolated from Feces from a Healthy Japanese Infant
Authors: Morita Hidetoshi , Toh Hidehiro , Nakano Akiyo , Oshima Kenshiro , Takagi Misako , Suda Wataru , Tanabe Soichi , Hattori Masahira
Published: April 2015

We isolated
Bifidobacterium kashiwanohense
JCM 15439 from the feces of a healthy Japanese infant and proposed it as the type strain of a novel species within the genus
Bifidobacterium
. Here, we report the complete genome sequence of this organism.
Draft Genome Sequences of Eight Type Strains of the Genus
Demequina
Authors: Hamada Moriyuki , Ichikawa Natsuko , Oguchi Akio , Komaki Hisayuki , Tamura Tomohiko , Fujita Nobuyuki
Published: April 2015

Here, we report the draft genome sequences of the type strains of
Demequina aestuarii
,
Demequina aurantiaca
,
Demequina flava
,
Demequina globuliformis
,
Demequina lutea
,
Demequina oxidasica
,
Demequina salsinemoris
, and
Demequina sediminicola
. The genome sequences presented here will facilitate taxonomical, ecological, and functional studies of members of the genus
Demequina
.
Draft Genome Sequence of Enterobacter aerogenes, a DDE-Degrading and Plant Growth-Promoting Strain Isolated from
Cucurbita pepo
Authors: Eevers Nele , Van Hamme Jonathan D. , Bottos Eric M. , Weyens Nele , Vangronsveld Jaco
Published: April 2015

We report here the draft genome of
Enterobacter aerogenes
, a Gram-negative bacterium of the
Enterobacteriaceae
isolated from
Cucurbita pepo
root tissue. This bacterium shows 2,2-
bis
(
p
-chlorophenyl)-1,1-dichloroethylene (DDE)-degrading potential and plant growth-promoting capacity. An analysis of its 4.5-Mb draft genome will enhance the understanding of DDE degradation pathways and phytoremediation applications for DDE-contaminated soils.
Phenotypic Heterogeneity in Expression of the K1 Polysaccharide Capsule of Uropathogenic Escherichia coli and Downregulation of the Capsule Genes during Growth in Urine
Authors: King Jane E. , Aal Owaif Hasan A. , Jia Jia , Roberts Ian S.
Published: April 2015

Uropathogenic
Escherichia coli
(UPEC) is the major causative agent of uncomplicated urinary tract infections (UTI). The K1 capsule on the surface of UPEC strains is a key virulence factor, and its expression may be important in the onset and progression of UTI. In order to understand capsule expression in more detail, we analyzed its expression in the UPEC strain UTI89 during growth in rich medium (LB medium) and urine and during infection of a bladder epithelial cell line. Comparison of capsule gene transcription using a chromosomal
gfp
reporter fusion showed a significant reduction in transcription during growth in urine compared to that during growth in LB medium. When examined at the single-cell level, following growth in both media, capsule gene expression appears to be heterogeneous, with two distinct green fluorescent protein (GFP)-expressing populations. Using anti-K1 antibody, we showed that this heterogeneity in gene expression results in two populations of encapsulated and unencapsulated cells. We demonstrated that the capsule hinders attachment to and invasion of epithelial cells and that the unencapsulated cells within the population preferentially adhere to and invade bladder epithelial cells. We found that once internalized, UTI89 starts to produce capsule to aid in its intracellular survival and spread. We propose that this observed phenotypic diversity in capsule expression is a fitness strategy used by the bacterium to deal with the constantly changing environment of the urinary tract.
Acupuncture versus Usual Care for Postoperative Nausea and Vomiting in Children after Tonsillectomy/Adenoidectomy: A Pragmatic, Multicentre, Double-Blinded, Randomised Trial
Authors: Liodden Ingrid , Sandvik Leiv , Valeberg Berit Taraldsen , Borud Einar , Norheim Arne Johan
Published: April 2015

Objectives

To investigate the effect of a standardised acupuncture on nausea and vomiting in children after tonsillectomy with or without adenoidectomy when possible placebo effects were precluded.

Methods

A pragmatic, multicentre, double-blinded, randomised controlled trial. The study was conducted over 10 months in 2012–2013 at three ambulatory clinics. Two hundred and eighty-two children, age 1–11 years, American Society of Anesthesiologists grade ≤II, were included. To equalise expectancy effects, all parents were told that their child would receive acupuncture. However, children were randomly allocated to perioperative bilateral needling acupuncture at PC6, depth 7 mm, mean time 17 min (SD 5–45) during anaesthesia plus usual care, or to usual care only. The regional ethics committee approved this approach. Primary endpoints were nausea and vomiting 24 h postoperatively.

Results

This study did not demonstrate any effect of acupuncture (95% CI) compared with standard care. The overall vomiting in the acupuncture and usual-care groups was 44.2% and 47.9%, respectively. Nausea was experienced by 31.7% in the acupuncture group and by 32.6% in the usual-care group. The test power was acceptable for comparisons of vomiting.

Conclusions

The findings suggest that when controlling for possible placebo effects standardised PC6 acupuncture needling during anaesthesia without further stimulation of PC6 is not effective in reducing nausea and vomiting in children after tonsillectomy with or without adenoidectomy. Future studies should investigate acupuncture treatment which balances adequate dose and technique and a feasible, child-friendly acupuncture treatment.

Trial Registration Number

ClinicalTrials.gov NCT01729052.
Reduced keratin expression in colorectal neoplasia and associated fields is reversible by diet and resection
Authors: Evans Caroline A , Rosser Ria , Waby Jennifer S , Noirel Josselin , Lai Daphne , Wright Phillip C , Williams Elizabeth A , Riley Stuart A , Bury Jonathan P , Corfe Bernard M
Published: April 2015

Background

Patients with adenomatous colonic polyps are at increased risk of developing further polyps suggesting field-wide alterations in cancer predisposition. The current study aimed to identify molecular alterations in the normal mucosa in the proximity of adenomatous polyps and to assess the modulating effect of butyrate, a chemopreventive compound produced by fermentation of dietary residues.

Methods

A cross-sectional study was undertaken in patients with adenomatous polyps: biopsy samples were taken from the adenoma, and from macroscopically normal mucosa on the contralateral wall to the adenoma and from the mid-sigmoid colon. In normal subjects biopsies were taken from the mid-sigmoid colon. Biopsies were frozen for proteomic analysis or formalin-fixed for immunohistochemistry. Proteomic analysis was undertaken using iTRAQ workflows followed by bioinformatics analyses. A second dietary fibre intervention study arm used the same endpoints and sampling strategy at the beginning and end of a high-fibre intervention.

Results

Key findings were that keratins 8, 18 and 19 were reduced in expression level with progressive proximity to the lesion. Lesional tissue exhibited multiple K8 immunoreactive bands and overall reduced levels of keratin. Biopsies from normal subjects with low faecal butyrate also showed depressed keratin expression. Resection of the lesion and elevation of dietary fibre intake both appeared to restore keratin expression level.

Conclusion

Changes in keratin expression associate with progression towards neoplasia, but remain modifiable risk factors. Dietary strategies may improve secondary chemoprevention.

Trial registration number

ISRCTN90852168.
Single-Machine Scheduling with Learning Effect, Deteriorating Jobs and Convex Resource Dependent Processing Times
Authors: Li Xin-Jun , Wang Jian-Jun , Wang Xue-Ru
Published: April 2015

This paper considers single-machine scheduling with learning effect, deteriorating jobs and convex resource dependent processing times, i.e., the processing time of a job is a function of its starting time, its position in a sequence and its convex resource allocation. The objective is to find the optimal sequence of jobs and the optimal convex resource allocation separately to minimize a cost function containing makespan, total completion (waiting) time, total absolute differences in completion (waiting) times and total resource cost. It is proved that the problem can be solved in polynomial time.
Detection prospects of the cosmic neutrino background
Authors: Li Yu-Feng
Published: April 2015

The existence of the cosmic neutrino background (CνB) is a fundamental prediction of the standard Big Bang cosmology. Although current cosmological probes provide indirect observational evidence, the direct detection of the CνB in a laboratory experiment is a great challenge to the present experimental techniques. We discuss the future prospects for the direct detection of the CνB, with the emphasis on the method of captures on beta-decaying nuclei and the PTOLEMY project. Other possibilities using the electron-capture (EC) decaying nuclei, the annihilation of extremely high-energy cosmic neutrinos (EHECνs) at the Z-resonance, and the atomic de-excitation method are also discussed in this review (talk given at the International Conference on Massive Neutrinos, Singapore, 9–13 February 2015).
Variations in the structural, electronic and optical properties of N-doped TiO2 with increasing N doping concentration
Authors: Khan Matiullah , Gul Sahar Ramin , Li Jing , Cao Wenbin
Published: April 2015

Based on density functional theory, calculations were performed for geometrically optimized N -doped TiO 2 models. The effect of N dopant and its increasing doping concentration on the band structure are elucidated. N doping narrowed the band gap of TiO 2 and introduced isolated N 2p states within the band gap. The location of N 2p states within the band gap can be optimized by N doping concentration. All N -doped TiO 2 models shifted the absorption edge of TiO 2 toward visible light region and increasing N doping concentration improved the visible light absorption. N -doped TiO 2 model having reduced band gap without any isolated states will improve the photocatalytic response. Our results provide strong theoretical background for existing experiments.
Mean field dynamics of interaction processes with duplication, loss and copy
Authors: Bassetti Federico , Toscani Giuseppe
Published: April 2015

We present and analyze kinetic models for the size evolution of a huge number of populations subject to interactions which describe both birth and death in a single population, and migration between them. If the mean size of the population is preserved, we prove that the solution to the underlying kinetic equation converges to equilibrium as time goes to infinity, and in various relevant cases we recover its main properties. In addition, by considering a suitable asymptotic procedure (the limit of quasi-invariant interactions) a simpler kinetic description of the model is derived. This procedure allows to describe the evolution process in terms of a linear kinetic transport-type equation. Among the various processes that can be described in this way, one recognizes a process which is closely related to the Lea–Coulson model of mutation processes in bacteria, a variation of the original model proposed by Luria and Delbrück, and a model recently proposed to describe evolution of the cross-genomic family abundance (i.e. the number of genes of a given family found in different genomes).
Generalized impedance boundary conditions for strongly absorbing obstacle: The full wave equation
Authors: Nguyen Hoai-Minh , Nguyen Linh Viet
Published: April 2015

This paper is devoted to the study of the generalized impedance boundary conditions (GIBCs) for a strongly absorbing obstacle in the time regime in two and three dimensions. The GIBCs in the time domain are heuristically derived from the corresponding conditions in the time harmonic regime. The latter is frequency-dependent except the one of order 0; hence the formers are non-local in time in general. The error estimates in the time regime can be derived from the ones in the time harmonic regime when the frequency dependence is well controlled. This idea is originally due to Nguyen and Vogelius [Approximate cloaking for the full wave equation via change of variables, SIAM J. Math. Anal.44 (2012) 769–807] for the cloaking context. In this paper, we present the analysis to the GIBCs of orders 0 and 1. To implement the ideas in [H.-M. Nguyen and M. S. Vogelius, Approximate cloaking for the full wave equation via change of variables, SIAM J. Math. Anal.44 (2012) 769–807], we revise and extend the work of Haddar, Joly, and Nguyen, [Generalized impedance boundary condition for scattering by strongly absorbing obstacles: the scalar case, Math. Models Methods Appl. Sci.15 (2005) 1273–1300], where the GIBCs were investigated for a fixed frequency in three dimensions. Even though we heavily follow the strategy in [H.-M. Nguyen and M. S. Vogelius, Approximate cloaking for the full wave equation via change of variables, SIAM J. Math. Anal.44 (2012) 769–807], our analysis on the stability contains new ingredients and ideas. First, instead of considering the difference between solutions of the exact model and the approximate model, we consider the difference between their derivatives in time. This simple idea helps us to avoid the machinery used in [H.-M. Nguyen and M. S. Vogelius, Approximate cloaking for the full wave equation via change of variables, SIAM J. Math. Anal.44 (2012) 769–807] concerning the integrability with respect to frequency in the low frequency regime. Second, in the high frequency regime, the Morawetz multiplier technique used in [H.-M. Nguyen and M. S. Vogelius, Approximate cloaking for the full wave equation via change of variable, SIAM J. Math. Anal.44 (2012) 769–807] does not fit directly in our setting. Our proof makes use of a result by Hörmander in [Lp estimates for (pluri-) subharmonic functions, Math. Scand.20 (1967) 65–78]. Another important part of the analysis in this paper is the well-posedness in the time domain for the approximate problems imposed with GIBCs on the boundary of the obstacle, which are non-local in time.
Supercoiled tangles and stick numbers of 2-Bridge links
Authors: Insko Erik , Trapp Rolland
Published: April 2015

Utilizing both twisting and writhing, we construct integral tangles with few sticks, leading to an efficient method for constructing polygonal 2-bridge links. Let L be a two-bridge link with crossing number c, stick number s, and n tangles. It is shown that [Formula: see text]. We also show that if c > 12n + 3, then minimal stick representatives do not admit minimal crossing projections.
Use of Measured Vibration ofIn-SituSleeper for Detecting Underlying Railway Ballast Damage
Authors: Hu Q. , Lam H. F. , Alabi S. A.
Published: April 2015

The identification of railway ballast damage under a concrete sleeper is investigated by following the Bayesian approach. The use of a discrete modeling method to capture the distribution of ballast stiffness under the sleeper introduces artificial stiffness discontinuities between different ballast regions. This increases the effects of modeling errors and reduces the accuracy of the ballast damage detection results. In this paper, a continuous modeling method was developed to overcome this difficulty. The uncertainties induced by modeling error and measurement noise are the major difficulties of vibration-based damage detection methods. In the proposed methodology, Bayesian probabilistic approach is adopted to explicitly address the uncertainties associated with the identified model parameters. In the model updating process, the stiffness of the ballast foundation is assumed to be continuous along the sleeper by using a polynomial of order N. One of the contributions of this paper is to calculate the order N conditional on a given set of measurement utilizing the Bayesian model class selection method. The proposed ballast damage detection methodology was verified with vibration data obtained from a segment of full-scale ballasted track under laboratory conditions, and the experimental verification results are very encouraging showing that it is possible to use the Bayesian approach along with the newly developed continuous modeling method for the purpose of ballast damage detection.
Analytical Solution for Vibration of a Rotating Delaminated Composite Beam with End Mass
Authors: Jafari-Talookolaei Ramazan-Ali
Published: April 2015

In this paper, the free vibration of rotating laminated composite beams (LCBs) with general lay-ups and single through-the-width delamination is analytically investigated. The Hamilton’s principle is used to derive the coupled governing differential equations and boundary conditions for the rotating delaminated beam, considering the effects of shear deformation, rotary inertia, material couplings (bending–tension, bending–twist and tension–twist couplings), and Poisson’s effect. Both the free mode and constrained mode assumptions are adopted. Analytical solution for the natural frequencies and mode shapes are presented by incorporating the constraint conditions using the Lagrange multipliers method. The accuracy is assured by the convergence of the natural frequencies, as well as by comparison with published results. The effects of various factors such as delamination parameter, fiber angle, hub radius, material anisotropy, end mass and rotating speed are studied in detail. The difference between the results based on the free mode and constrained mode assumptions is also investigated.
RELATIONSHIP BETWEEN WEIGHT CHANGE AND CHANGES IN 3D ACCELERATION SIGNALS GENERATED BY WALKING
Authors: VIHRIÄLÄ ERKKI , RINTA-PAAVOLA ANNELI , SORVOJA HANNU , JÄMSÄ TIMO , MYLLYLÄ RISTO
Published: April 2015

This study set out to investigate if a relationship exists between weight change and changes in 3D acceleration signals associated with walking. In addition to giving biomechanical information, this relationship could be applied in conjunction with new weight management solutions to address the excess weight problem currently plaguing the world. The study was conducted with 15 subjects. For a period of two months, they were weighed every morning and carried a 3D accelerometer during the working day. Daily accelerometric signals were recorded and signals recognized as walking were analyzed. To obtain information in a more controlled situation and higher weight change, a separate follow-up study was carried out involving one test subject performing controlled walking exercises. Our results show that a relationship does exist between weight change and 3D acceleration signals. The obtained correlation coefficient between weight change and the acceleration-related parameter was 0.21 for the combined result of all test subjects (n = 147, p = 0.01). Higher correlations were recorded for individual subjects (r = 0.97, p < 0.001). Also the follow-up with controlled walking exercises showed a high correlation (r = 0.89, p < 0.001). On the other hand, statistically significant results were not obtained for all subjects, and identical signal parameters did not always produce similar results.
Calculation of free energy changes due to mutations from alchemical free energy simulations
Authors: Rashid M. Harunur , Heinzelmann Germano , Kuyucak Serdar
Published: April 2015

How a mutation affects the binding free energy of a ligand is a fundamental problem in molecular biology/biochemistry with many applications in pharmacology and biotechnology, e.g. design of drugs and enzymes. Free energy change due to a mutation can be determined most accurately by performing alchemical free energy calculations in molecular dynamics (MD) simulations. Here we discuss the necessary conditions for success of free energy calculations using toxin peptides that bind to ion channels as examples. We show that preservation of the binding mode is an essential requirement but this condition is not always satisfied, especially when the mutation involves a charged residue. Otherwise problems with accuracy of results encountered in mutation of charged residues can be overcome by performing the mutation on the ligand in the binding site and bulk simultaneously and in the same system. The proposed method will be useful in improving the affinity and selectivity profiles of drug leads and enzymes via computational design and protein engineering.
Theoretical calculations of stability, mechanical and thermodynamic properties of IVA group Willemite-II nitrides
Authors: Ding Ying-Chun , Chen Min , Wu Wen-Juan
Published: April 2015

The structural stability and mechanical and thermodynamic properties of WII- A 3 N 4 ( A=C , Si , Ge and Sn ) are calculated by first-principles calculations based on the density functional theory. The calculated lattice parameters and elastic constants of WII- A 3 N 4 ( A=C , Si , Ge and Sn ) are in good agreement with the experimental data and previously calculated values. WII- A 3 N 4 ( A=C , Si , Ge and Sn ) compounds are also found to be thermodynamically and mechanically stable. The results suggest that hardness of WII- C 3 N 4 is the hardest of these C 3 N 4 polymorphs. The hardness of WII- Sn 3 N 4 is the smallest among WII- A 3 N 4 ( A=C , Si , Ge and Sn ).

Furthermore, the mechanical anisotropy, Debye temperature, the minimum thermal conductivity and thermodynamic properties of WII- A 3 N 4 ( A=C , Si , Ge and Sn ) compounds can be investigated.
Stability and convergence of relaxation schemes to hyperbolic balance laws via a wave operator
Authors: Miroshnikov Alexey , Trivisa Konstantina
Published: April 2015

This paper deals with relaxation approximations of nonlinear systems of hyperbolic balance laws. We introduce a class of relaxation schemes and establish their stability and convergence to the solution of hyperbolic balance laws before the formation of shocks, provided that we are within the framework of the compensated compactness method. Our analysis treats systems of hyperbolic balance laws with source terms satisfying a special mechanism which induces weak dissipation in the spirit of Dafermos [Hyperbolic systems of balance laws with weak dissipation, J. Hyp. Diff. Equations 3 (2006) 505–527.], as well as hyperbolic balance laws with more general source terms. The rate of convergence of the relaxation system to a solution of the balance laws in the smooth regime is established. Our work follows in spirit the analysis presented by [Ch. Arvanitis, Ch. Makridakis and A. E. Tzavaras, Stability and convergence of a class of finite element schemes for hyperbolic conservation laws, SIAM J. Numer. Anal. 42(4) (2004) 1357–1393]; [S. Jin and X. Xin, The relaxation schemes for systems of conservation laws in arbitrary space dimensions, Comm. Pure Appl. Math. 48 (1995) 235–277] for systems of hyperbolic conservation laws without source terms.
The Interpolating Complex Variable Element-Free Galerkin Method for Temperature Field Problems
Authors: Deng Yajie , Liu Chao , Peng Miaojuan , Cheng Yumin
Published: April 2015

In this paper, an interpolating complex variable moving least-squares (ICVMLS) method is presented. In the ICVMLS method, the trial function of a two-dimensional problem is formed with a one-dimensional basis function, and the shape function of the ICVMLS method satisfies the property of Kronecker δ function. The ICVMLS method has greater computational efficiency than the moving least-squares (MLS) approximation. Then combining the ICVMLS method with the Galerkin weak form of temperature field problems, an interpolating complex variable element-free Galerkin (ICVEFG) method is proposed. In the ICVEFG method, we can obtain the equation system by applying the essential boundary conditions directly. Compared with the element-free Galerkin (EFG) method and the complex variable element-free Galerkin (CVEFG) method, the ICVEFG method in this paper has higher accuracy and efficiency.
Anti-tumor response induced by immunologically modified carbon nanotubes and laser irradiation using rat mammary tumor model
Authors: Acquaviva Joseph T. , Bahavar Cody F. , Zhou Feifan , Li Xiaosong , Howard Eric W. , Bullen Liz C. , Silvy Ricardo P. , Chen Wei R.
Published: April 2015

The ideal treatment modality for metastatic cancer would be a local treatment that can destroy primary tumors while inducing an effective systemic anti-tumor response. To this end, we developed laser immunotherapy, combining photothermal laser application with an immunoadjuvant for the treatment of metastatic cancer. Additionally, to enhance the selective photothermal effect, we integrated light-absorbing nanomaterials into this innovative treatment. Specifically, we developed an immunologically modified carbon nanotube combining single-walled carbon nanotubes (SWNTs) with the immunoadjuvant glycated chitosan (GC). To determine the effectiveness of laser irradiation, a series of experiments were performed using two different irradiation durations — 5 and 10 min. Rats were inoculated with DMBA-4 cancer cells, a metastatic cancer cell line. The treatment group of rats receiving laser irradiation for 10 min had a 50% long-term survival rate without residual primary or metastatic tumors. The treatment group of rats receiving laser irradiation for 5 min had no long-term survivors; all rats died with multiple metastases at several distant sites. Therefore, Laser+SWNT–GC treatment with 10 min of laser irradiation proved to be effective at reducing tumor size and inducing long-term anti-tumor immunity.
High vibration damping in in situ In–Zn composites
Authors: Balch Samuel P. , Lakes Roderic S.
Published: April 2015

Indium–zinc in situ composites were fabricated and their viscoelastic properties studied over 8.5 decades of frequency. Material with 5% indium by weight was found to have a stiffness damping product (the figure of merit for damping layers) of 1.9 GPa at 10 Hz; 3 times better than the peak of polymer damping layers and over a wider frequency range. Material with 15% indium had a stiffness damping product of 1.8 GPa. The indium segregated in a platelet morphology, particularly favorable for attaining high damping from a small concentration, as predicted by viscoelastic composite theory.
Calibration, Validation, and Prediction in Random Simulation Models
Authors: Yuan Jun , Ng Szu Hui
Published: April 2015

Model calibration and validation are important processes in the development of stochastic computer models of real complex systems. This article introduces an integrated approach for model calibration, validation, and prediction based on Gaussian process metamodels and a Bayesian approach. Within this integrated approach, a sequential approach is further proposed for stochastic computer model calibration. Several design criteria for this sequential stage are proposed and studied, including an entropy-based criterion and one based on minimizing prediction error. To further use the data resources to improve the performance of both calibration and prediction, an adaptive procedure that combines these criteria is introduced to balance the resource allocation between the calibration and prediction. The accuracy and efficiency of the proposed sequential calibration approach and the integrated approach are illustrated with several numerical examples.
Antihypertensive Peptides from Food Proteins
Authors: Aluko Rotimi E.
Published: April 2015

Bioactive peptides are encrypted within the primary structure of food proteins where they remain inactive until released by enzymatic hydrolysis. Once released from the parent protein, certain peptides have the ability to modulate the renin-angiotensin system (RAS) because they decrease activities of renin or angiotensin-converting enzyme (ACE), the two main enzymes that regulate mammalian blood pressure. These antihypertensive peptides can also enhance the endothelial nitric oxide synthase (eNOS) pathway to increase nitric oxide (NO) levels within vascular walls and promote vasodilation. The peptides can block the interactions between angiotensin II (vasoconstrictor) and angiotensin receptors, which can contribute to reduced blood pressure. This review focuses on the methods that are involved in antihypertensive peptide production from food sources, including fractionation protocols that are used to enrich bioactive peptide content and enhance peptide activity. It also discusses mechanisms that are believed to be involved in the antihypertensive activity of these peptides.
Modern Statistical Challenges in High-Resolution Fluorescence Microscopy
Authors: Aspelmeier Timo , Egner Alexander , Munk Axel
Published: April 2015

Conventional light microscopes have been used for centuries for the study of small length scales down to approximately 250 nm. Images from such a microscope are typically blurred and noisy, and the measurement error in such images can often be well approximated by Gaussian or Poisson noise. In the past, this approximation has been the focus of a multitude of deconvolution techniques in imaging. However, conventional microscopes have an intrinsic physical limit of resolution. Although this limit remained unchallenged for a century, it was broken for the first time in the 1990s with the advent of modern superresolution fluorescence microscopy techniques. Since then, superresolution fluorescence microscopy has become an indispensable tool for studying the structure and dynamics of living organisms. Current experimental advances go to the physical limits of imaging, where discrete quantum effects are predominant. Consequently, this technique is inherently of a non-Gaussian statistical nature, and we argue that recent technological progress also challenges the long-standing Poisson assumption. Thus, analysis and exploitation of the discrete physical mechanisms of fluorescent molecules and light, as well as their distributions in time and space, have become necessary to achieve the highest resolution possible. This article presents an overview of some physical principles underlying modern fluorescence microscopy techniques from a statistical modeling and analysis perspective. To this end, we develop a prototypical model for fluorophore dynamics and use it to discuss statistical methods for image deconvolution and more complicated image reconstruction and enhancement techniques. Several examples are discussed in more detail, including variational multiscale methods for confocal and stimulated emission depletion (STED) microscopy, drift correction for single marker switching (SMS) microscopy, and sparse estimation and background removal for superresolution by polarization angle demodulation (SPoD). We illustrate that such methods benefit from advances in large-scale computing, for example, from recent tools from convex optimization. We argue that in the future, even higher resolutions will require more detailed models that delve into sub-Poissonian statistics.
A method for long-term live imaging of tissue macrophages in adipose tissue explants
Authors: Gericke Martin , Weyer Ulrike , Braune Julia , Bechmann Ingo , Eilers Jens
Published: April 2015

Obesity is frequently associated with a chronic low-grade inflammation within adipose tissue (AT). Although classical signs of inflammation are missing in AT inflammation, there is a significant increase in macrophages and, to a lesser extent, other immune cells, such as T cells, B cells, mast cells, and neutrophils. The spatial and temporal activation of these cells as well as their accumulation in the AT seem to be tightly linked to so-called crown-like structures (CLS). CLS are accumulations of adipose tissue macrophages (ATMs) around dead adipocytes and are thought to reflect a scavenger response. At present, data on the life cycle of CLS are missing. To better understand the cellular events underlying AT inflammation, we developed an approach that allows long-term imaging of ATMs, adipocytes, and CLS within live AT explants. We tested three putative reporter mouse lines for myeloid cells in regard to their suitability for live imaging. Thereby, we identified ATMs from CSF1R-eGFP mice to exhibit the most robust expression of eGFP. AT explants from these mice allowed stable live imaging for more than 7 days without significant phototoxicity. Long-term imaging thus revealed the accumulation of ATMs around dying adipocytes, migration of ATMs within AT, and also the degradation of the lipid remnants of perishing adipocytes. The observed behavior of ATMs in the context of AT inflammation is in line with previous studies but for the first time provides data on the specific behavior of individual ATMs and on the life cycle of CLS with unprecedented spatiotemporal resolution.
Deciphering the pathogenesis of NSAID enteropathy using proton pump inhibitors and a hydrogen sulfide-releasing NSAID
Authors: Blackler Rory W. , De Palma Giada , Manko Anna , Da Silva Gabriela J. , Flannigan Kyle L. , Bercik Premysl , Surette Michael G. , Buret Andre G. , Wallace John L.
Published: April 2015

The small intestine is a significant site of ulceration and bleeding induced by nonsteroidal anti-inflammatory drugs (NSAIDs). The pathogenesis is poorly understood. The present study explored the roles of bile, bacteria, and enterohepatic circulation to NSAID enteropathy, using both a conventional NSAID (naproxen) and a gastrointestinal-safe naproxen derivative (ATB-346), as well as proton pump inhibitors (PPIs). Rats were treated orally with naproxen or equimolar doses of ATB-346 over a 5-day period, with or without PPI administration, and intestinal damage was quantified. The cytotoxicity of bile from the rats was evaluated in vitro. Biliary excretion of naproxen and ATB-346 was determined. The impact of the NSAIDs and of PPIs on the composition of the intestinal microbiota was examined by deep sequencing of 16s rRNA. Naproxen caused significant intestinal damage and inflammation, whereas ATB-346 did not. Naproxen, but not ATB-346, dose dependently increased the cytotoxicity of bile, and it was further increased by PPI coadministration. Whereas biliary excretion of naproxen was significant in naproxen-treated rats, it was greatly reduced in rats treated with ATB-346. The enteric microbiota of naproxen-treated rats was distinct from that in vehicle- or ATB-346-treated rats, and PPI administration caused significant intestinal dysbiosis. The increase in cytotoxicity of bile induced by naproxen and PPIs may contribute significantly to intestinal ulceration and bleeding. Some of these effects may occur secondary to significant changes in the jejunal microbiota induced by both naproxen and PPIs.
Cardiac mTOR rescues the detrimental effects of diet-induced obesity in the heart after ischemia-reperfusion
Authors: Aoyagi Toshinori , Higa Jason K. , Aoyagi Hiroko , Yorichika Naaiko , Shimada Briana K. , Matsui Takashi
Published: April 2015

Diet-induced obesity deteriorates the recovery of cardiac function after ischemia-reperfusion (I/R) injury. While mechanistic target of rapamycin (mTOR) is a key mediator of energy metabolism, the effects of cardiac mTOR in ischemic injury under metabolic syndrome remains undefined. Using cardiac-specific transgenic mice overexpressing mTOR (mTOR-Tg mice), we studied the effect of mTOR on cardiac function in both ex vivo and in vivo models of I/R injury in high-fat diet (HFD)-induced obese mice. mTOR-Tg and wild-type (WT) mice were fed a HFD (60% fat by calories) for 12 wk. Glucose intolerance and insulin resistance induced by the HFD were comparable between WT HFD-fed and mTOR-Tg HFD-fed mice. Functional recovery after I/R in the ex vivo Langendorff perfusion model was significantly lower in HFD-fed mice than normal chow diet-fed mice. mTOR-Tg mice demonstrated better cardiac function recovery and had less of the necrotic markers creatine kinase and lactate dehydrogenase in both feeding conditions. Additionally, mTOR overexpression suppressed expression of proinflammatory cytokines, including IL-6 and TNF-α, in both feeding conditions after I/R injury. In vivo I/R models showed that at 1 wk after I/R, HFD-fed mice exhibited worse cardiac function and larger myocardial scarring along myofibers compared with normal chow diet-fed mice. In both feeding conditions, mTOR overexpression preserved cardiac function and prevented myocardial scarring. These findings suggest that cardiac mTOR overexpression is sufficient to prevent the detrimental effects of diet-induced obesity on the heart after I/R, by reducing cardiac dysfunction and myocardial scarring.
Ganglion Cell Complex Evaluation in Exudative Age-Related Macular Degeneration after Repeated Intravitreal Injections of Ranibizumab
Authors: Perdicchi Andrea , Peluso Giacomo , Iacovello Daniela , Balestrieri Marco , Delle Fave Martina , Abdolrahimzadeh Solmaz , Scuderi Gian Luca , Fenicia Vito , Recupero Santi Maria
Published: April 2015

Purpose. To detect the effects of intravitreal ranibizumab injections on GCC in patients with wet AMD.Methods. 32 wet AMD eyes were selected and submitted at three ranibizumab injections. RTVue-OCT GCC and MM5 protocol were performed before treatment and twenty days after each injection.Results. At baseline mean GCC thickness was 93.9 ± 18.5 μm. Twenty days after each intravitreal injection it was, respectively, 85.8 ± 10.1, 86.5 ± 9.3, and 91.1 ± 11.5 μm, without statistical significance. A significant improvement in visual acuity (P= 0.031) and a reduction of mean foveal (P= 0.001) and macular thickness (P= 0.001) were observed.Conclusion. The clinical results confirm therapeutic efficacy of intravitreal injections of ranibizumab in wet AMD. A contemporary not statistically significant reduction of GCC thickness suggests that the loading phase of ranibizumab does not have any toxic effects on ganglion cell complex.
Ocular Rigidity and Outflow Facility in Nonproliferative Diabetic Retinopathy
Authors: Panagiotoglou Theonitsa , Tsilimbaris Miltiadis , Ginis Harilaos , Karyotakis Nikos , Georgiou Vaggelis , Koutentakis Pavlos , Pallikaris Ioannis
Published: April 2015

Purpose.To compare ocular rigidity (OR) and outflow facility (C) in patients with nonproliferative diabetic retinopathy (NPDR) and control subjects.Methods. Twenty-four patients with NPDR (NPDR group) and 24 controls (control group) undergoing cataract surgery were enrolled. NPDR group was further divided into patients with mild NPDR (NPDR1-group) and patients with moderate and/or severe NPDR (NPDR2-group). After cannulation of the anterior chamber, a computer-controlled device was used to infuse saline and increase the intraocular pressure (IOP) in a stepping procedure from 15 to 40 mmHg. Ocular rigidity and outflow facility coefficients were estimated from IOP and volume recordings.Results. Ocular rigidity was 0.0205 μL−1in NPDR group and 0.0202 μL−1in control group (P=0.942). In NPDR1-group, OR was 0.017 μL−1and in NPDR2-group it was 0.025μL−1(P=0.192). Outflow facility was 0.120 μL/min/mmHg in NPDR-group compared to 0.153 μL/min/mmHg in the control group at an IOP of 35 mmHg (P=0.151). There was no difference in C between NPDR1-group and NPDR2-group (P=0.709).Conclusions. No statistically significant differences in ocular rigidity and outflow facility could be documented between diabetic patients and controls. No difference in OR and C was detected between mild NPDR and severe NPDR.
Diagnostic Implications of an Elevated Troponin in the Emergency Department
Authors: Yiadom Maame Yaa , Jarolim Petr , Jenkins Cathy , Melanson Stacy E. F. , Conrad Michael , Kosowsky Joshua M.
Published: April 2015

Objective. To determine the proportion of initial troponin (cTn) elevations associated with Type I MI versus other cardiovascular and noncardiovascular diagnoses in an emergency department (ED) and whether or not a relationship exists between the cTn level and the likelihood of Type I MI.Background. In the ED, cTn is used as a screening test for myocardial injury. However, the differential diagnosis for an initial positive cTn result is not clear.Methods. Hospital medical records were retrospectively reviewed for visits associated with an initial positive troponin I-ultra (cTnI), ≥0.05 μg/L. Elevated cTnI levels were stratified into low (0.05–0.09), medium (0.1–0.99), or high (≥1.0). Discharge diagnoses were classified into 3 diagnostic groups (Type I MI, other cardiovascular, or noncardiovascular).Results. Of 23,731 ED visits, 4,928 (21%) had cTnI testing. Of those tested, 16.3% had initial cTnI ≥0.05. Among those with elevated cTn, 11% were classified as Type I MI, 34% had other cardiovascular diagnoses, and 55% had a noncardiovascular diagnosis. Type I MI was more common with high cTnI levels (41% incidence) than among subjects with medium (9%) or low (6%).Conclusion. A positive cTn is most likely a noncardiovascular diagnosis, but Type I MI is far more common with cTnI levels ≥1.0.
Relation between Body Structure and Hearing during Soft Tissue Auditory Stimulation
Authors: Adelman Cahtia , Kaufmann Yehezkely Michal , Chordekar Shai , Sohmer Haim
Published: April 2015

Hearing is elicited by applying the clinical bone vibrator to soft tissue sites on the head, neck, and thorax. Two mapping experiments were conducted in normal hearing subjects differing in body build: determination of thelowestsoft tissue stimulationsiteat which a 60 dB SL tone at 2.0 kHz was effective in eliciting auditory sensation and assessment of actualthresholdsalong the midline of the head, neck, and back. In males, a lower site for hearing on the back was strongly correlated with a leaner body build. A correlation was not found in females. In both groups, thresholds on the head were lower, and they were higher on the back, with a transition along the neck. This relation between the soft tissue stimulation site and hearing sensation is likely due to the different distribution of soft tissues in various parts of the body.
On Newton-Kantorovich Method for Solving the Nonlinear Operator Equation
Authors: Husam Hameed Hameed , Eshkuvatov Z. K. , Ahmedov Anvarjon , Nik Long N. M. A.
Published: April 2015

We develop the Newton-Kantorovich method to solve the system of2×2nonlinear Volterra integral equations where the unknown function is in logarithmic form. A new majorant function is introduced which leads to the increment of the convergence interval. The existence and uniqueness of approximate solution are proved and a numerical example is provided to show the validation of the method.
Molecularly Imprinted Nanomicrospheres as Matrix Solid-Phase Dispersant Combined with Gas Chromatography for Determination of Four Phosphorothioate Pesticides in Carrot and Yacon
Authors: Zhou Mengchun , Hu Nana , Shu Shaohua , Wang Mo
Published: April 2015

An efficient, rapid, and selective method for sample pretreatment, namely, molecularly imprinted matrix solid-phase dispersion (MI-MSPD) coupled with gas chromatography (GC), was developed for the rapid isolation of four phosphorothioate organophosphorus pesticides (tolclofos-methyl, phoxim, chlorpyrifos, and parathion-methyl) from carrot and yacon samples. New molecularly imprinted polymer nanomicrospheres were synthesized by using typical structural analogue tolclofos-methyl as a dummy template via surface grafting polymerization on nanosilica. Then, these four pesticides in carrot and yacon were extracted and adsorbed using the imprinted nanomicrospheres and further determined by gas chromatography. Under the optimized conditions, a good linearity of four pesticides was obtained in a range of 0.05–17.0 ng·g−1withRvarying from 0.9971 to 0.9996, and the detection limit of the method was 0.012~0.026 ng·g−1in carrot and yacon samples. The recovery rates at two spiked levels were in the range of 85.4–105.6% with RSD ≤9.6%. The presented MI-MSPD method combined the advantages of MSPD for allowing the extraction, dispersion, and homogenization in two steps and the advantages of MIPs for high affinity and selectivity towards four phosphorothioate pesticides, which could be applied to the determination of pesticide residues in complicated vegetal samples.