bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Analysis of Periodically Heterogenous Beams
Authors: Han Shilei , Bauchau Olivier
Published: June 2016

Based on the symplectic transfer-matrix method, this paper develops a novel approach for the analysis of beams presenting periodic heterogeneities along their span. The approach, rooted in the Hamiltonian formalism, generalizes developments presented earlier by the authors for spanwise uniform beams. Starting from the kinematics of a unit cell, the approach proceeds through a set of structure-preserving symplectic transformations and decomposes the solution into its central and extremity components. The geometric configuration and material properties of the unit cell may be arbitrarily complex as long as the cell's two end cross sections are identical. The proposed approach identifies an equivalent, homogenized beam with uniform curvatures and sectional stiffness characteristics along its span. Numerical examples are presented to demonstrate the capabilities of the analysis. Predictions are found to be in excellent agreement with those obtained by full finite-element analysis.
Massively Parallel Discrete Element Method Simulations on Graphics Processing Units
Authors: Steuben John , Mustoe Graham , Turner Cameron
Published: June 2016

This paper outlines the development and implementation of large-scale discrete element method (DEM) simulations on graphics processing hardware. These simulations, as well as the topic of general-purpose graphics processing unit (GPGPU) computing, are introduced and discussed. We proceed to cover the general software design choices and architecture used to realize a GPGPU-enabled DEM simulation, driven primarily by the massively parallel nature of this computing technology. Further enhancements to this simulation, namely, a more advanced sliding friction model and a thermal conduction model, are then addressed. This discussion also highlights some of the finer points and issues associated with GPGPU computing, particularly surrounding the issues of parallelization, synchronization, and approximation. Qualitative comparison studies between simple and advanced sliding friction models demonstrate the effectiveness of the friction model. A test problem and an application problem in the area of wind turbine blade icing demonstrate the capabilities of the thermal model. We conclude with remarks regarding the simulations developed, future work needed, and the general suitability of GPGPU architectures for DEM computations.
On Global Convergence in Design Optimization Using the Particle Swarm Optimization Technique
Authors: Flocker Forrest W. , Bravo Ramiro H.
Published: June 2016

The particle swarm optimization (PSO) method is becoming a popular optimizer within the mechanical design community because of its simplicity and ability to handle a wide variety of objective functions that characterize a proposed design. Typical examples arising in mechanical design are nonlinear objective functions with many constraints, which typically arise from the various design specifications. The method is particularly attractive to mechanical design because it can handle discontinuous functions that occur when the designer must choose from a discrete set of standard sizes. However, as in other optimizers, the method is susceptible to converging to a local rather than global minimum. In this paper, convergence criteria for the PSO method are investigated and an algorithm is proposed that gives the user a high degree of confidence in finding the global minimum. The proposed algorithm is tested against five benchmark optimization problems, and the results are used to develop specific guidelines for implementation.
Failure Experiments on Pipes With Local Wall Thinning Subjected to Multi-Axial Loads
Authors: Li Yinsheng , Hasegawa Kunio , Miura Naoki , Hoshino Katsuaki
Published: June 2016

Piping lines in nuclear power plants may experience multi-axial loads including tensile force, bending, and torsion moments during operation. There is a lack of guidance for failure evaluation of locally wall-thinned pipes under the multi-axial loads including torsion moment. The ASME B&PV Code Section XI Working Group is currently developing fully plastic failure evaluation procedures for pressurized piping items containing local wall thinning subjected to multi-axial loads. A failure estimation method for locally wall-thinned pipes subjected to multi-axial loads including torsion moment has been proposed through numerical analyses. In this study, in order to investigate the failure behavior of the pipes with local wall thinning subjected to multi-axial loads including the torsion, failure experiments were performed on 20 mm diameter carbon steel pipes with a local wall thinning. Based on the experimental results, the proposed failure estimation method is confirmed to be applicable to pipes with local wall thinning.
The Association Between Internal and External Measures of Training Load in Batsmen and Medium-Fast Bowlers During Net-Based Cricket Training
Authors: Vickery Will , Dascombe Ben , Duffield Rob
Published: June 2016

Purpose:

To examine the relationship between session rating of perceived exertion (sRPE) and measures of internal and external training load (TL) in cricket batsmen and medium-fast bowlers during net-based training sessions.

Methods:

The internal (heart rate), external (movement demands, PlayerLoad), and technical (cricket-specific skills) loads of 30 male cricket players (age 21.2 ± 3.8 y, height 1.82 ± 0.07 m, body mass 79.0 ± 8.7 kg) were determined from net-based cricket-training sessions (n = 118). The relationships between sRPE and measures of TL were quantified using Pearson product–moment correlations respective to playing position. Stepwise multiple-regression techniques provided key internal- and external-load determinants of sRPE in cricket players.

Results:

Significant correlations were evident (r = -.34 to .87, P < .05) between internal and external measures of TL and sRPE, with the strongest correlations (r ≥ .62) for GPS-derived measures for both playing positions. In batsmen, stepwise multiple-regression analysis revealed that 67.8% of the adjusted variance in sRPE could be explained by PlayerLoad and high-intensity distance (y = 27.43 + 0.81 PlayerLoad + 0.29 high-intensity distance). For medium-fast bowlers, 76.3% of the adjusted variance could be explained by total distance and mean heart rate (y = 101.82 + total distance 0.05 + HRmean – 0.48).

Conclusion:

These results suggest that sRPE is a valid method of reporting TL among cricket batsmen and medium-fast bowlers. Position-specific responses are evident and should be considered when monitoring the TL of cricket players.
Risk of Neurological Insult in Competitive Deep Breath-Hold Diving
Authors: Tetzlaff Kay , Schöppenthau Holger , Schipke Jochen D.
Published: June 2016

Context:

It has been widely believed that tissue nitrogen uptake from the lungs during breath-hold diving would be insufficient to cause decompression stress in humans. With competitive free diving, however, diving depths have been ever increasing over the past decades.

Methods:

A case is presented of a competitive free-diving athlete who suffered stroke-like symptoms after surfacing from his last dive of a series of 3 deep breath-hold dives. A literature and Web search was performed to screen for similar cases of subjects with serious neurological symptoms after deep breath-hold dives.

Case Details:

A previously healthy 31-y-old athlete experienced right-sided motor weakness and difficulty speaking immediately after surfacing from a breathhold dive to a depth of 100 m. He had performed 2 preceding breath-hold dives to that depth with surface intervals of only 15 min. The presentation of symptoms and neuroimaging findings supported a clinical diagnosis of stroke. Three more cases of neurological insults were retrieved by literature and Web search; in all cases the athletes presented with stroke-like symptoms after single breath-hold dives of depths exceeding 100 m. Two of these cases only had a short delay to recompression treatment and completely recovered from the insult.

Conclusions:

This report highlights the possibility of neurological insult, eg, stroke, due to cerebral arterial gas embolism as a consequence of decompression stress after deep breath-hold dives. Thus, stroke as a clinical presentation of cerebral arterial gas embolism should be considered another risk of extreme breath-hold diving.
Improvement of Long-Jump Performance During Competition Using a Plyometric Exercise
Authors: Bogdanis Gregory C. , Tsoukos Athanasios , Veligekas Panagiotis
Published: June 2016

Purpose:

To examine the acute effects of a conditioning plyometric exercise on long-jump performance during a simulated long-jump competition.

Methods:

Eight national-level track and field decathletes performed 6 long-jump attempts with a full approach run separated by 10-min recoveries. In the experimental condition subjects performed 3 rebound vertical jumps with maximal effort 3 min before the last 5 attempts, while the 1st attempt served as baseline. In the control condition the participants performed 6 long jumps without executing the conditioning exercise.

Results:

Compared with baseline, long-jump performance progressively increased only in the experimental condition, from 3.0%, or 17.5 cm, in the 3rd attempt (P = .046, d = 0.56), to 4.8%, or 28.2 cm, in the 6th attempt (P = .0001, d = 0.84). The improvement in long-jump performance was due to a gradual increase in vertical takeoff velocity from the 3rd (by 8.7%, P = .0001, d = 1.82) to the 6th jump (by 17.7%, P = .0001, d = 4.38). Horizontal-approach velocity, takeoff duration, and horizontal velocity at takeoff were similar at all long-jump attempts in both conditions (P = .80, P = .36, and P = .15, respectively).

Conclusions:

Long-jump performance progressively improved during a simulated competition when a plyometric conditioning exercise was executed 3 min before each attempt. This improvement was due to a progressive increase in vertical velocity of takeoff, while there was no effect on the horizontal velocity.
A Review of the Internal and External Physiological Demands Associated With Batting in Cricket
Authors: Scanlan Aaron T. , Berkelmans Daniel M. , Vickery William M. , Kean Crystal O.
Published: June 2016

Cricket is a popular international team sport with various game formats ranging from long-duration multiday tests to short-duration Twenty20 game play. The role of batsmen is critical to all game formats, with differing physiological demands imposed during each format. Investigation of the physiological demands imposed during cricket batting has historically been neglected, with much of the research focusing on bowling responses and batting technique. A greater understanding of the physiological demands of the batting role in cricket is required to assist strength and conditioning professionals and coaches with the design of training plans, recovery protocols, and player-management strategies. This brief review provides an updated synthesis of the literature examining the internal (eg, metabolic demands and heart rate) and external (eg, activity work rates) physiological responses to batting in the various game formats, as well as simulated play and small-sided-games training. Although few studies have been done in this area, the summary of data provides important insight regarding physiological responses to batting and highlights that more research on this topic is required. Future research is recommended to combine internal and external measures during actual game play, as well as comparing different game formats and playing levels. In addition, understanding the relationship between batting technique and physiological responses is warranted to gain a more holistic understanding of batting in cricket, as well as to develop appropriate coaching and training strategies.
Repurposing of Aspirin and Ibuprofen as Candidate Anti-Cryptococcus Drugs
Authors: Ogundeji Adepemi O. , Pohl Carolina H. , Sebolai Olihile M.
Published: June 2016

The usage of fluconazole and amphotericin B in clinical settings is often limited by, among other things, drug resistance development and undesired side effects. Thus, there is a constant need to find new drugs to better manage fungal infections. Toward this end, the study described in this paper considered the repurposing of aspirin (acetylsalicylic acid) and ibuprofen as alternative drugs to control the growth of cryptococcal cells.
In vitro
susceptibility tests, including a checkerboard assay, were performed to assess the response of
Cryptococcus neoformans
and
Cryptococcus gattii
to the above-mentioned anti-inflammatory drugs. Next, the capacity of these two drugs to induce stress as well as their mode of action in the killing of cryptococcal cells was determined. The studied fungal strains revealed a response to both aspirin and ibuprofen that was dose dependent, with ibuprofen exerting greater antimicrobial action. More importantly, the MICs of these drugs did not negatively (i) affect growth or (ii) impair the functioning of macrophages; rather, they enhanced the ability of these immune cells to phagocytose cryptococcal cells. Ibuprofen was also shown to act in synergy with fluconazole and amphotericin B. The treatment of cryptococcal cells with aspirin or ibuprofen led to stress induction via activation of the high-osmolarity glycerol (HOG) pathway, and cell death was eventually achieved through reactive oxygen species (ROS)-mediated membrane damage. The presented data highlight the potential clinical application of aspirin and ibuprofen as candidate anti-
Cryptococcus
drugs.
Dimethyl Sulfoxide Protects Escherichia coli from Rapid Antimicrobial-Mediated Killing
Authors: Mi Hongfei , Wang Dai , Xue Yunxin , Zhang Zhi , Niu Jianjun , Hong Yuzhi , Drlica Karl , Zhao Xilin
Published: June 2016

The contribution of reactive oxygen species (ROS) to antimicrobial lethality was examined by treatingEscherichia coliwith dimethyl sulfoxide (DMSO), an antioxidant solvent frequently used in antimicrobial studies. DMSO inhibited killing by ampicillin, kanamycin, and two quinolones and had little effect on MICs. DMSO-mediated protection correlated with decreased ROS accumulation and provided evidence for ROS-mediated programmed cell death. These data support the contribution of ROS to antimicrobial lethality and suggest caution when using DMSO-dissolved antimicrobials for short-time killing assays.
Characterization of the Neisseria gonorrhoeae Iron and Fur Regulatory Network
Authors: Yu Chunxiao , McClure Ryan , Nudel Kathleen , Daou Nadine , Genco Caroline Attardo
Published: June 2016

The
Neisseria gonorrhoeae
f
erric
u
ptake
r
egulator (Fur) protein controls expression of iron homeostasis genes in response to intracellular iron levels. In this study, using transcriptome sequencing (RNA-seq) analysis of an
N. gonorrhoeae
fur
strain, we defined the gonococcal Fur and iron regulons and characterized Fur-controlled expression of an ArsR-like DNA binding protein. We observed that 158 genes (8% of the genome) showed differential expression in response to iron in an
N. gonorrhoeae
wild-type or
fur
strain, while 54 genes exhibited differential expression in response to Fur. The Fur regulon was extended to additional regulators, including NrrF and 13 other small RNAs (sRNAs), and two transcriptional factors. One transcriptional factor, coding for an ArsR-like regulator (ArsR), exhibited increased expression under iron-replete conditions in the wild-type strain but showed decreased expression across iron conditions in the
fur
strain, an effect that was reversed in a
fur
-complemented strain. Fur was shown to bind to the promoter region of the
arsR
gene downstream of a predicted σ
70
promoter region. Electrophoretic mobility shift assay (EMSA) analysis confirmed binding of the ArsR protein to the
norB
promoter region, and sequence analysis identified two additional putative targets, NGO1411 and NGO1646. A gonococcal
arsR
strain demonstrated decreased survival in human endocervical epithelial cells compared to that of the wild-type and
arsR
-complemented strains, suggesting that the ArsR regulon includes genes required for survival in host cells. Collectively, these results demonstrate that the
N. gonorrhoeae
Fur functions as a global regulatory protein to repress or activate expression of a large repertoire of genes, including additional transcriptional regulatory proteins.

IMPORTANCE
Gene regulation in bacteria in response to environmental stimuli, including iron, is of paramount importance to both bacterial replication and, in the case of pathogenic bacteria, successful infection. Bacterial DNA binding proteins are a common mechanism utilized by pathogens to control gene expression under various environmental conditions. Here, we show that the DNA binding protein Fur, expressed by the human pathogen
Neisseria gonorrhoeae
, controls the expression of a large repertoire of genes and extends this regulon by controlling expression of additional DNA binding proteins. One of these proteins, an ArsR-like regulator, was required for
N. gonorrhoeae
survival within host cells. These results show that the Fur regulon extends to additional regulatory proteins, which together contribute to gonococcal mechanisms of pathogenesis.
CodY-Dependent Regulation of Sporulation in Clostridium difficile
Authors: Nawrocki Kathryn L. , Edwards Adrianne N. , Daou Nadine , Bouillaut Laurent , McBride Shonna M.
Published: June 2016

Clostridium difficile
must form a spore to survive outside the gastrointestinal tract. The factors that trigger sporulation in
C. difficile
remain poorly understood. Previous studies have suggested that a link exists between nutritional status and sporulation initiation in
C. difficile
. In this study, we investigated the impact of the global nutritional regulator CodY on sporulation in
C. difficile
strains from the historical 012 ribotype and the current epidemic 027 ribotype. Sporulation frequencies were increased in both backgrounds, demonstrating that CodY represses sporulation in
C. difficile
. The 027
codY
mutant exhibited a greater increase in spore formation than the 012
codY
mutant. To determine the role of CodY in the observed sporulation phenotypes, we examined several factors that are known to influence sporulation in
C. difficile
. Using transcriptional reporter fusions and quantitative reverse transcription-PCR (qRT-PCR) analysis, we found that two loci associated with the initiation of sporulation,
opp
and
sinR
, are regulated by CodY. The data demonstrate that CodY is a repressor of sporulation in
C. difficile
and that the impact of CodY on sporulation and expression of specific genes is significantly influenced by the strain background. These results suggest that the variability of CodY-dependent regulation is an important contributor to virulence and sporulation in current epidemic isolates. This report provides further evidence that nutritional state, virulence, and sporulation are linked in
C. difficile
.

IMPORTANCE
This study sought to examine the relationship between nutrition and sporulation in
C. difficile
by examining the global nutritional regulator CodY. CodY is a known virulence and nutritional regulator of
C. difficile
, but its role in sporulation was unknown. Here, we demonstrate that CodY is a negative regulator of sporulation in two different ribotypes of
C. difficile
. We also demonstrate that CodY regulates known effectors of sporulation, Opp and SinR. These results support the idea that nutrient limitation is a trigger for sporulation in
C. difficile
and that the response to nutrient limitation is coordinated by CodY. Additionally, we demonstrate that CodY has an altered role in sporulation regulation for some strains.
Temporal Regulation of the Bacillus subtilis Acetylome and Evidence for a Role of MreB Acetylation in Cell Wall Growth
Authors: Carabetta Valerie J. , Greco Todd M. , Tanner Andrew W. , Cristea Ileana M. , Dubnau David
Published: June 2016

The past decade highlighted
N
ε
-lysine acetylation as a prevalent posttranslational modification in bacteria. However, knowledge regarding the physiological importance and temporal regulation of acetylation has remained limited. To uncover potential regulatory roles for acetylation, we analyzed how acetylation patterns and abundances change between growth phases in
B. subtilis
. To demonstrate that the identification of cell growth-dependent modifications can point to critical regulatory acetylation events, we further characterized MreB, the cell shape-determining protein. Our findings led us to propose a role for MreB acetylation in controlling cell width by restricting cell wall growth.
Interassociation consensus statement on cardiovascular care of college student-athletes
Authors: Hainline Brian , Drezner Jonathan , Baggish Aaron , Harmon Kimberly G , Emery Michael S , Myerburg Robert J , Sanchez Eduardo , Molossi Silvana , Parsons John T , Thompson Paul D
Published: June 2016

Cardiovascular evaluation and care of college student-athletes is gaining increasing attention from both the public and medical communities. Emerging strategies include screening of the general athlete population, recommendations of permissible levels of participation by athletes with identified cardiovascular conditions and preparation for responding to unanticipated cardiac events in athletic venues. The primary focus has been sudden cardiac death and the usefulness of screening with or without advanced cardiac screening. The National Collegiate Athletic Association convened a multidisciplinary task force to address cardiovascular concerns in collegiate student-athletes, and to develop consensus for an interassociation statement. This document summarises the task force deliberations and follow-up discussions, and includes available evidence on cardiovascular risk, preparticipation evaluation and the recognition of and response to cardiac arrest. Future recommendations for cardiac research initiatives, education and collaboration are also provided.
Design and Implementation of Gain-Offset Correction Algorithm Hardware Architecture for Grayscale and Color Images Contrast Enhancement
Authors: Nnolim Uche A.
Published: June 2016

This paper describes the design and implementation of a novel, high-speed hardware (HW) architecture for the gain-offset correction (GOC) image contrast enhancement algorithm on an FPGA fabric. The design is extremely fast and has been shown to process megapixel image frames at frame rates greatly exceeding real-time requirements. The design is small and compact enough to fit on small FPGAs to form a low-cost image processing solution. The automated nature of the contrast enhancement operation is due to the computation of global image statistics for each image. The architecture does not store any image frames to perform this task, heavily reducing memory requirements.
An Approximate Analytical Solution of the Problem of Fluid Filtration in the Multilayer Porous Medium
Authors: Ravshanov Normakhmad , Kurbonov Nozim , Mukhamadiev Abduvali
Published: June 2016

This paper deals with a mathematical problem statement of unsteady fluid flow in heterogeneous porous media with various hydrogeological characteristics. In order to solve the problem the authors developed an approximate analytical method. The method allows multidimensional differential equation in partial derivatives describing the process of fluid filtration in layered porous media to become one-dimensional differential equation. There was obtained a calculation formula for determining the process of mass transfer between the layers, depending on the operating modes of production wells and hydrogeological parameters of filtration layers. The model and the algorithm can be used as a mathematical support for the processes of development of oil and gas fields.
Lingdingyang Bay, Pearl River Estuary (China): geomorphological evolution and hydrodynamics
Authors: Jia Peihong , Xia Zhen , Yin Yong , Xue Qiao
Published: June 2016

The Pearl River is the largest river in southern China; it has eight outlets flowing into the South China Sea, four of which (Humen, Jiaomen, Hongqili and Hengmen) empty via Lingdingyang Bay. Tides, discharge strength and the presence of islands control sediments within these four outlets. Sediments are deposited, and form three shoals and two channels. The shoreline and its seabed topography have changed dramatically with increasing human impact.

In order to understand the geomorphological evolution of Lingdingyang Bay and its hydrodynamics, we integrated data obtained from two marine environment investigations conducted by the Guangzhou Marine Geological Survey (GMGS) in 2003 and in 2012, together with remote sensing multi-temporal images and historical materials, and analysed them using a geographical information system (GIS).

The results obtained show that the outlets are becoming narrower; the surface water area of Lingdingyang Bay is diminishing. Meanwhile, the sediment flux is reducing and becoming finer grained because the currents are being blocked by shoals and islands. Some parts of the bay are becoming deeper (27–37 m in the Chuanbi Channel). Correspondingly, the hydrodynamics in the bay are becoming weaker and sediments easier to deposit. Water exchange between the inner and outer sea is decreasing under the influence of unrestricted anthropogenic activities.

Lingdingyang Bay should be managed and protected continuously based on a scientific framework: otherwise, it will become narrower and, perhaps, even evolving eventually into a river, which may result in serious futures disasters through flooding and tides.
Low-dose testosterone protects against renal ischemia-reperfusion injury by increasing renal IL-10-to-TNF-α ratio and attenuating T-cell infiltration
Authors: Patil Chetan N. , Wallace Kedra , LaMarca Babbette D. , Moulana Mohadetheh , Lopez-Ruiz Arnaldo , Soljancic Andrea , Juncos Luis A. , Grande Joseph P. , Reckelhoff Jane F.
Published: June 2016

Renal ischemia-reperfusion (I/R) in male rats causes reductions in plasma testosterone, and infusion of testosterone 3 h postreperfusion is protective. We tested the hypotheses that acute high doses of testosterone promote renal injury after I/R, and that acute low-dose testosterone is protective by the following: 1) increasing renal IL-10 and reducing TNF-α; 2) its effects on nitric oxide; and 3) reducing intrarenal T-cell infiltration. Rats were subjected to renal I/R, followed by intravenous infusion of vehicle or testosterone (20, 50, or 100 μg/kg) 3 h postreperfusion. Low-dose testosterone (20 μg/kg) reduced plasma creatinine, increased nitrate/nitrite excretion, increased intrarenal IL-10, and reduced intrarenal TNF-α, whereas 50 μg/kg testosterone failed to reduce plasma creatinine, increased IL-10, but failed to reduce TNF-α. A higher dose of testosterone (100 mg/kg) not only failed to reduce plasma creatinine, but significantly increased both IL-10 and TNF-α compared with other groups. Low-dose nitro-l-arginine methyl ester (1 mg·kg−1·day−1), given 2 days before I/R, prevented low-dose testosterone (20 μg/kg) from protecting against I/R injury, and was associated with lack of increase in intrarenal IL-10. Intrarenal CD4+ and CD8+ T cells were significantly increased with I/R, but were attenuated with low-dose testosterone, as were effector T helper 17 cells. The present studies suggest that acute, low-dose testosterone is protective against I/R AKI in males due to its effects on inflammation by reducing renal T-cell infiltration and by shifting the balance to favor anti-inflammatory cytokine production rather than proinflammatory cytokines.
Rapid Resolution of Cholangitic Abscess and Biliary Sepsis in a Liver Transplant Recipient after Hepatic Artery Revascularization
Authors: Trakroo Sushrut , Qureshi Kamran
Published: June 2016

Hepatic arterial flow is paramount in preserving biliary integrity. We present an interesting clinical scenario of a liver transplant recipient with biliary anastomotic stricture who developed biliary abscess and sepsis after Endoscopic Retrograde Cholangiopancreatography. The abscess did not respond to maximal medical management, percutaneous drainage, and adequate endoscopic biliary drainage. Clinically, patient continued to deteriorate and imaging identified hepatic artery stenosis which was treated with percutaneous intra-arterial stenting. Revascularization and perfusion of infected area led to rapid resolution of abscess and sepsis. This case emphasizes the anatomic basis of biliary ductal pathology. An important educational point is to understand that interrupted hepatic arterial supply can lead to biliary complications in liver transplant recipients and early correction of perfusion deficit should be pursued in such cases. In nonresolving hepatobiliary infections after liver transplantation, hepatic arterial compromise should be looked for and if present promptly treated. Reperfusion of biliary system in our patient led to improved antibiotics penetration, resolution of abscess and sepsis, and healing of biliary stricture.
Modified Silica Nanofibers with Antibacterial Activity
Authors: Veverková Ivana , Lovětinská-Šlamborová Irena
Published: June 2016

This study is focused on development of functionalized inorganic-organic nanofibrous material with antibacterial activity for wound dressing applications. The nanofibers combining poly(vinyl alcohol) and silica were produced by electrospinning from the sol and thermally stabilized. The PVA/silica nanofibers surface was functionalized by silver and copper nanoparticles to ensure antibacterial activity. It was proven that quantity of adsorbed silver and copper nanoparticles depends on process time of adsorption. According to antibacterial tests results, this novel nanofibrous material shows a big potential for wound dressing applications due to its significant antibacterial efficiency.
A Fusion Protein Consisting of the Vaccine Adjuvant Monophosphoryl Lipid A and the Allergen Ovalbumin Boosts Allergen-Specific Th1, Th2, and Th17 ResponsesIn Vitro
Authors: Schülke Stefan , Vogel Lothar , Junker Ann-Christine , Hanschmann Kay-Martin , Flaczyk Adam , Vieths Stefan , Scheurer Stephan
Published: June 2016

Background. The detoxified TLR4-ligand Monophosphoryl Lipid A (MPLA) is the first approved TLR-agonist used as adjuvant in licensed vaccines but has not yet been explored as part of conjugated vaccines.Objective. To investigate the immune-modulating properties of a fusion protein consisting of MPLA and Ovalbumin (MPLA : Ova).Results. MPLA and Ova were chemically coupled by stable carbamate linkage. MPLA : Ova was highly pure without detectable product-related impurities by either noncoupled MPLA or Ova. Light scattering analysis revealed MPLA : Ova to be aggregated. Stimulation of mDC and mDC : DO11.10 CD4+TC cocultures showed a stronger activation of both mDC and Ova-specific DO11.10 CD4+TC by MPLA : Ova compared to the mixture of both components. MPLA : Ova induced both strong proinflammatory (IL-1β, IL-6, and TNF-α) and anti-inflammatory (IL-10) cytokine responses from mDCs while also boosting allergen-specific Th1, Th2, and Th17 cytokine secretion.Conclusion. Conjugation of MPLA and antigen enhanced the immune response compared to the mixture of both components. Due to the nonbiased boost of Ova-specific Th2 and Th17 responses while also inducing Th1 responses, this fusion protein may not be a suitable vaccine candidate for allergy treatment but may hold potential for the treatment of other diseases that require a strong stimulation of the host’s immune system (e.g., cancer).
Inhibition of Zymosan-Induced Inflammatory Factors Expression by ATRA Nanostructured Lipid Carriers
Authors: Zhou Hongyan , Zhang Wensong , Gao Xunyi , Zhang Hongguang , Kong Ning
Published: June 2016

Purpose. The study aimed to evaluate the effect of all-trans retinoic acid-loaded nanostructured lipid carriers (ATRA-NLCs) on the zymosan-induced expression of the cytokines IL-4, IL-10, and IFN-γand the matrix metalloproteinases/tissue inhibitor of metalloproteinases (MMPs/TIMPs) and TLR2in rabbit corneal fibroblasts (RCFs).Methods. ATRA-NLCs were prepared by emulsification. RCFs were isolated and harvested after four to seven passages in monolayer culture. Cytokine release (IL-4, IL-10, and IFN-γ) induced by zymosan was analyzed by cytokine release assay, reverse transcription, and real-time polymerase chain reaction (RT-PCR) analysis detection. MMP-1, MMP-3, and MMP-13, TIMP-1 and TIMP-2, and TLR2 expression were analyzed by immunoblotting.Results. ATRA-NLCs were resistant to light and physically stable, and the average size of the ATRA-NLCs was 200 nm. ATRA-NLCs increased the zymosan-induced release of IL-4 and IL-10 and decreased the release of IFN-γby RCFs. ATRA-NLCs decreased the levels of TLR2 and MMPs/TIMPs above.Conclusions. ATRA may be a potent anti-inflammatory agent for the therapy of fungal keratitis (FK).
Ex Vivo Apoptosis in CD8+ Lymphocytes Predicts Rectal Cancer Patient Outcome
Authors: Winkler Sebastian , Hoppe Philipp , Haderlein Marlen , Hecht Markus , Fietkau Rainer , Distel Luitpold V.
Published: June 2016

Background. Apoptotic rates in peripheral blood lymphocytes can predict radiation induced normal tissue toxicity. We studied whether apoptosis in lymphocytes has a prognostic value for therapy outcome.Methods. Lymphocytes of 87 rectal cancer patients were ex vivo irradiated with 2 Gy, 8 Gy, or a combination of 2 Gy ionizing radiation and Oxaliplatin. Cells were stained with Annexin V and 7-Aminoactinomycin D and apoptotic and necrotic rates were analyzed by multicolor flow cytometry.Results. After treatment, apoptotic and necrotic rates in CD8+ cells are consistently higher than in CD4+ cells, with lower corresponding necrotic rates. Apoptotic and necrotic rates of CD4+ cells and CD8+ cells correlated well within the 2 Gy, 8 Gy, and 2 Gy and Oxaliplatin arrangements (p≤0.009). High apoptotic CD8+ rates after 2 Gy, 8 Gy, and 2 Gy + Oxaliplatin treatment were prognostically favorable for metastasis-free survival (p=0.009,p=0.038,andp=0.009) and disease-free survival (p=0.013,p=0.098, andp=0.013).Conclusions. Ex vivo CD8+ apoptotic rates are able to predict the patient outcome in regard to metastasis-free or disease-free survival. Patients with higher CD8+ apoptotic rates in the peripheral blood have a more favorable prognosis. In addition to the prediction of late-toxicity by utilization of CD4+ apoptotic rates, the therapy outcome can be predicted by CD8+ apoptotic rates.
Pilot Study of Laser Doppler Measurement of Flow Variability in the Microcirculation of the Palatal Mucosa
Authors: Le Bars Pierre , Niagha Gaston , Kouadio Ayepa Alain , Demoersman Julien , Roy Elisabeth , Armengol Valérie , Soueidan Assem
Published: June 2016

Background.Histopathological alterations can arise when the denture-supporting mucosa experiences microbial and mechanical stress through the denture base and diagnosis of these diseases usually follows microvascular changes. Microcirculation measurement could allow for detection of such dysfunction and aid in the early diagnosis of palatal mucosa pathologies.Materials and Methods. We tested the sensitivity of laser Doppler for measuring the microcirculation of the palatal mucosa, assessing the median raphe (MR), Schroeder area (SA), and retroincisive papilla (RP). A Doppler PeriFlux 5000 System, containing a laser diode, was used. 54 healthy participants were recruited. We compare the measurements of PU (perfusion unit) using ANOVA test.Results.The numerical values for palatal mucosa blood flow differed significantly among the anatomical areas (p=0.0167). The mean value of Schroeder area was 92.6 (SD: 38.4) and was significantly higher than the retroincisive papilla (51.9) (SD: 20.2) (p<0.05), which in turn was higher than that of median raphe (31.9) (SD: 24.2) (p<0.0001).Conclusion.Schroeder area appeared to have the greatest sensitivity, and vascular flow variability among individuals was also greatest in this region. We suggest that analysis of blood stream modification with laser Doppler of the palatal mucosa can help to detect onset signs of pathological alterations.
Research on Coal Exploration Technology Based on Satellite Remote Sensing
Authors: Xiao Dong , Le Ba Tuan , Mao Yachun , Jiang Jinhong , Song Liang , Liu Shanjun
Published: June 2016

Coal is the main source of energy. In China and Vietnam, coal resources are very rich, but the exploration level is relatively low. This is mainly caused by the complicated geological structure, the low efficiency, the related damage, and other bad situations. To this end, we need to make use of some advanced technologies to guarantee the resource exploration is implemented smoothly and orderly. Numerous studies show that remote sensing technology is an effective way in coal exploration and measurement. In this paper, we try to measure the distribution and reserves of open-air coal area through satellite imagery. The satellite picture of open-air coal mining region in Quang Ninh Province of Vietnam was collected as the experimental data. Firstly, the ENVI software is used to eliminate satellite imagery spectral interference. Then, the image classification model is established by the improved ELM algorithm. Finally, the effectiveness of the improved ELM algorithm is verified by using MATLAB simulations. The results show that the accuracies of the testing set reach 96.5%. And it reaches 83% of the image discernment precision compared with the same image from Google.
Morphologic Damage of Rat Alveolar Epithelial Type II Cells Induced by Bile Acids Could Be Ameliorated by Farnesoid X Receptor Inhibitor Z-Guggulsterone In Vitro
Authors: Wang Jieqin , Huang Yaowei , Hou Xusheng , Wu Wenyu , Nie Lei , Tian Yinghong , Lu Yanmeng , Yin Yanru
Published: June 2016

Objective. To determine whether bile acids (BAs) affect respiratory functions through the farnesoid X receptor (FXR) expressed in the lungs and to explore the possible mechanisms of BAs-induced respiratory disorder.Methods. Primary cultured alveolar epithelial type II cells (AECIIs) of rat were treated with different concentrations of chenodeoxycholic acid (CDCA) in the presence or absence of FXR inhibitor Z-guggulsterone (GS). Then, expression of FXR in nuclei of AECIIs was assessed by immunofluorescence microscopy. And ultrastructural changes of the cells were observed under transmission electron microscope and analyzed by Image-Pro Plus software.Results. Morphologic damage of AECIIs was exhibited in high BAs group in vitro, with high-level expression of FXR, while FXR inhibitor GS could attenuate the cytotoxicity of BAs to AECIIs.Conclusions. FXR expression was related to the morphologic damage of AECIIs induced by BAs, thus influencing respiratory functions.
Outdoor Air Quality Level Inference via Surveillance Cameras
Authors: Zhang Zheng , Ma Huadong , Fu Huiyuan , Liu Liang , Zhang Cheng
Published: June 2016

Air pollution is a universal problem confronted by many developing countries. Because there are very few air quality monitoring stations in cities, it is difficult for people to know the exact air quality level anytime and anywhere. Fortunately, large amount of surveillance cameras have been deployed and can capture image densely and conveniently. In this case, this provides the possibility to utilize surveillance cameras as sensors to obtain data and predict the air quality level. To this end, we present a novel air quality level inference approach based on outdoor images. Firstly, we explore several features extracted from images as the robust representation for air quality prediction. Then, to effectively fuse these heterogeneous and complementary features, we adopt multikernel learning to learn an adaptive classifier for air quality level inference. In addition, to facilitate the research, we construct an Outdoor Air Quality Image Set (OAQIS) dataset, which contains high quality registered and calibrated images with rich labels, that is, concentration of particles mass (PM), weather, temperature, humidity, and wind. Extensive experiments on the OAQIS dataset demonstrate the effectiveness of the proposed approach.
Implications of Increase in Vascular Permeability in Tumors by VEGF: A Commentary on the Pioneering Work of Harold Dvorak
Authors: Dewhirst Mark W. , Ashcraft Kathleen A.
Published: June 2016

See related article by Senger et al., Cancer Res 1986;46:5629–32.

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Rendering the 3 + 3 Design to Rest: More Efficient Approaches to Oncology Dose-Finding Trials in the Era of Targeted Therapy
Authors: Nie Lei , Rubin Eric H. , Mehrotra Nitin , Pinheiro José , Fernandes Laura L. , Roy Amit , Bailey Stuart , de Alwis Dinesh P.
Published: June 2016

Selection of the maximum tolerated dose (MTD) as the recommended dose for registration trials based on a dose-escalation trial using variations of an MTD/3 + 3 design often occurs in the development of oncology products. The MTD/3 + 3 approach is not optimal and may result in recommended doses that are unacceptably toxic for many patients and in dose reduction/interruptions that might have an impact on effectiveness. Instead of the MTD/3 + 3 approach, the authors recommend an integrated approach. In this approach, typically an adaptive/Bayesian model provides a general framework to incorporate and make decisions for dose escalation based on nonclinical data, such as animal efficacy and toxicity data; clinical data, including pharmacokinetics/pharmacodynamics data; and dose/exposure–response data for efficacy and safety. To improve dose-ranging trials, model-based estimation, rather than hypothesis testing, should be used to maximize and integrate the information gathered across trials and doses. This approach may improve identification of optimal recommended doses, which can then be confirmed in registration trials. Clin Cancer Res; 22(11); 2623–9. ©2016 AACR.

See all articles in this CCR Focus section, “New Approaches for Optimizing Dosing of Anticancer Agents.”
Plasma 25-Hydroxyvitamin D, Vitamin D Binding Protein, and Risk of Colorectal Cancer in the Nurses' Health Study
Authors: Song Mingyang , Konijeti Gauree Gupta , Yuan Chen , Ananthakrishnan Ashwin N. , Ogino Shuji , Fuchs Charles S. , Giovannucci Edward L. , Ng Kimmie , Chan Andrew T.
Published: June 2016

Total circulating 25-hydroxyvitamin D [25(OH)D)] has been associated with lower risk of colorectal cancer. The physiologic mechanism, however, may be more directly related to the free or bioavailable fraction of 25(OH)D, which is influenced by levels of vitamin D binding protein (VDBP). We assessed the association of prediagnosis total, free, and bioavailable 25(OH)D and VDBP with colorectal cancer risk among predominantly white women in the Nurses' Health Study (NHS) who provided a blood specimen in 1989–1990. We documented 378 cases of colorectal cancer through 2011 and matched them to 689 controls according to age and time of blood draw. We genotyped two common polymorphisms in the gene coding VDBP and calculated free and bioavailable 25(OH)D levels based on total 25(OH)D, VDBP, albumin, and their estimated genotype-specific binding affinities. Total 25(OH)D was associated with lower colorectal cancer risk (P for trend = 0.01). Compared with women in the lowest quintile of total 25(OH)D, those in the highest quintile had a multivariable-adjusted odds ratio (OR) for colorectal cancer of 0.54 [95% confidence interval (CI), 0.33–0.87]. Comparing extreme quintiles, we did not find any significant association with risk of colorectal cancer for VDBP (OR, 0.98; 95% CI, 0.65–1.47), free 25(OH)D (OR, 0.71; 95% CI, 0.46–1.10), or bioavailable 25(OH)D (OR, 0.92; 95% CI, 0.60–1.42). In conclusion, prediagnosis levels of total, but not free or bioavailable 25(OH)D, were associated with lower colorectal cancer risk. Although our findings support an inverse association of vitamin D with colorectal cancer, this association does not appear to be due to the unbound or bioavailable fraction of circulating vitamin D. Cancer Prev Res; 9(8); 664–72. ©2016 AACR.
Identification of Serum Metabolites Associated With Incident Hypertension in the European Prospective Investigation Into Cancer and Nutrition–Potsdam Study
Authors: Dietrich Stefan , Floegel Anna , Weikert Cornelia , Prehn Cornelia , Adamski Jerzy , Pischon Tobias , Boeing Heiner , Drogan Dagmar
Published: June 2016

Metabolomics is a promising tool to gain new insights into early metabolic alterations preceding the development of hypertension in humans. We therefore aimed to identify metabolites associated with incident hypertension using measured data of serum metabolites of the European Prospective Investigation Into Cancer and Nutrition (EPIC)–Potsdam study. Targeted metabolic profiling was conducted on serum blood samples of a randomly drawn EPIC-Potsdam subcohort consisting of 135 cases and 981 noncases of incident hypertension, all of them being free of hypertension and not on antihypertensive therapy at the time of blood sampling. Mean follow-up was 9.9 years. A validated set of 127 metabolites was statistically analyzed with a random survival forest backward selection algorithm to identify predictive metabolites of incident hypertension taking into account important epidemiological hypertension risk markers. Six metabolites were identified to be most predictive for the development of hypertension. Higher concentrations of serine, glycine, and acyl-alkyl-phosphatidylcholines C42:4 and C44:3 tended to be associated with higher and diacyl-phosphatidylcholines C38:4 and C38:3 with lower predicted 10-year hypertension-free survival, although visualization by partial plots revealed some nonlinearity in the above associations. The identified metabolites improved prediction of incident hypertension when used together with known risk markers of hypertension. In conclusion, these findings indicate that metabolic alterations occur early in the development of hypertension. However, these alterations are confined to a few members of the amino acid or phosphatidylcholine metabolism, respectively.
Dietary Salt Intake Is a Determinant of Cardiac Changes After Treatment of Primary Aldosteronism
Authors: Catena Cristiana , Colussi GianLuca , Novello Marileda , Verheyen Nicolas D. , Bertin Nicole , Pilz Stefan , Tomaschitz Andreas , Sechi Leonardo A.
Published: June 2016

Primary aldosteronism is associated with increased left ventricular (LV) mass independently of blood pressure. Previous studies suggest that elevated aldosterone causes cardiac damage only in the presence of an inappropriate salt status. We examined the relevance of dietary salt intake on cardiac changes in patients with primary aldosteronism before and after treatment. Sixty-five patients with tumoral or idiopathic primary aldosteronism were recruited at a University medical center and followed after either surgical (n=30) or medical (n=35) treatment. At baseline and 1 year after treatment, cardiac morphology and functional variables were measured by echocardiography together with duplicate 24-hour urinary sodium collections. At baseline, LV mass index was associated with urinary sodium excretion and plasma aldosterone levels. During follow-up, blood pressure (from 167/102–135/83 mm Hg;
P
<0.001) and LV mass index (from 50.5±13.0–44.4±8.9 g/m
2.7
;
P
<0.001) decreased significantly with nonsignificant changes in LV geometry and functional properties. At the end of follow-up, percentage decrease in LV mass index was significantly greater in patients who had >10% reduction in urinary sodium excretion (15.0±12.5%) than in the remaining patients (5.5±9.3%;
P
<0.001). Changes in LV mass index induced by both surgical and medical treatment were directly and independently correlated with changes in blood pressure (β=0.419;
P
=0.009) and urinary sodium excretion (β=0.334;
P
=0.012) observed at follow-up. These findings strongly support the hypothesis that dietary salt intake has a crucial role in aldosterone-related LV changes and could contribute to cardiac damage in patients with primary aldosteronism.