bluuebunny/crossref_metadata_2025 huggingface dataset:
Parotid Dermoid Cyst
Authors: Birsan Christina , Raza Anwar , Cobb Camilla
Published: August 2012

A dermoid cyst arising in the parotid is rare and usually represents the rare first branchial cleft type II anomaly, which can have morphology similar to a dermoid cyst. This study reports the case of a 20-year-old woman who presented with a parotid mass, which on histologic review was consistent with a dermoid cyst. This appears to be the first case report of a parotid dermoid cyst with focus on the gross and histopathologic findings and to be presented in a histopathology focused journal. The discussion includes the clinical presentation, imaging findings, gross pathology, histologic features, and differential diagnosis of parotid dermoid cysts. Although there was no prior fine needle aspiration (FNA) of the lesion in this case, parotid masses are commonly subject to FNA prior to excision. Therefore, a brief review of the FNA findings in dermoid cysts is also included.
Adaptive closed-loop control of a single-link flexible manipulator
Authors: Shaheed Mohammad Hasan , Tokhi Osman
Published: August 2012

An investigation into the development of a closed-loop vibration control strategy for flexible manipulator systems is presented in this paper. Development of the controller is carried out in two phases. A collocated position controller on the basis of a proportional-derivative feedback control technique is developed first and then a command-filter vibration controller is developed based on the dominant vibration modes of the system and placed inside the position control loop. While the purpose of the position controller is to place the end-point of the manipulator at a position of demand, the objective of the vibration controller is to reduce motion-induced vibration of the manipulator arising from structural flexibility of the system during fast maneuvers. Low-pass and band-stop elliptic filters are used in designing the vibration controller to filter out input energy at dominant vibration modes of the manipulator so that it is not excited at its natural frequencies. The performances of the controllers are assessed within a simulation environment of a single-link flexible manipulator. It is demonstrated that while the performance of the position controller in controlling the rigid body motion of the manipulator is as expected, significant reduction in the level of structural vibration of the system is achieved with the help of the vibration controller.
Lower Heart Rate Variability Associated With Military Sexual Trauma Rape and Posttraumatic Stress Disorder
Authors: Lee Elizabeth Ann Davis , Theus Sue A.
Published: August 2012

Low heart rate variability (HRV) can occur with psychological disorders such as posttraumatic stress disorder (PTSD). The purpose of this study was to examine the association between PTSD by trauma type and decreased HRV measures in female veterans with cardiac symptoms. This secondary analysis utilized data from a previous study of female veterans ( n = 125) examined for cardiac symptoms by Holter and electrocardiogram recordings at a Veterans Affairs medical center. The mean HRV measure from three 10-s data segments with spontaneous respirations was obtained for each subject. PTSD diagnosis and type of trauma exposure were collected from mental health consult notes. Chi-square was used for frequency of subject characteristics; independent t tests and one-way analysis of variance (ANOVA) compared means of HRV measures between trauma types. Statistical significance was set at p < .05 a priori. By ANOVA, significantly lower log-transformed standard deviation of all normal sinus rhythm R-R intervals (SDNN) and log-transformed square root of the mean of the sum of the squares of differences between adjacent normal sinus rhythm R-R intervals (RMSSD) were found in the PTSD group with documented rape military sexual trauma (MST) compared to other groups including no PTSD, PTSD following MST with rape not specified, combat exposure, and nonmilitary-related trauma; lower HRV measures were not found with other PTSD types of trauma. This study suggests rape MST with concomitant PTSD may be a risk factor for decreased HRV in female veterans examined for cardiac symptoms.
Thermodynamic sweet spot for high-efficiency, dilute, boosted gasoline engines
Authors: Lavoie George A , Ortiz-Soto Elliott , Babajimopoulos Aristotelis , Martz Jason B , Assanis Dennis N
Published: August 2012

Recent developments in ignition, boosting, and control systems have opened up new opportunities for highly dilute, high-pressure combustion regimes for gasoline engines. This study analytically explores the fundamental thermodynamics of operation in these regimes under realistic burn duration, heat loss, boosting, and friction constraints. The intent is to identify the benefits of this approach and the path to achieving optimum engine and vehicle-level fuel economy. A simple engine/turbocharger model in GT-Power is used to perform a parametric study exploring the conditions for best engine efficiency. These conditions are found in the mid-dilution range, a result of the tradeoff between fluid property benefits of lean mixtures and friction benefits of higher loads. Dilution with exhaust gas is nearly as effective as air dilution when compared using a ‘fuel-to-charge’ equivalence ratio defined as Φ′≡Φ (1-RGF) where RGF is the total residual gas fraction. Optimal brake efficiencies are obtained over a range 0.45 ≤ Φ′ ≤ 0.65 for operation up to 3 bar manifold pressure, yielding peak temperatures under 2100 K and peak pressures under 150 bar. These conditions are intermediate between homogeneous charge compression ignition and spark-ignition regimes, and are the subject of much current research on advanced combustion modes. An engine–vehicle drive train simulation shows that accessing this thermodynamic sweet spot has the potential for vehicle fuel economy gains between 23% and 58%.
Antenatal maternal protein deprivation: sexually dimorphic programming of the pancreatic renin-angiotensin system
Authors: Goyal Ravi , Wong Christine , Van Wickle Jonathan , Longo Lawrence D
Published: August 2012

As an underlying mechanism of antenatal maternal malnutrition-induced type 2 diabetes mellitus (T2DM), alterations in the local pancreatic renin-angiotensin system (RAS) may play a significant role. We tested the hypothesis that antenatal maternal protein deprivation (AMPD) leads to increased activity of the local pancreatic RAS, with associated hyperglycemia in the adult progeny. Mice dams were fed either control or 50% protein restricted diet (AMPD) starting one week before conception and maintained during complete gestation. Our results demonstrate low birth weight (control 1.5 ± 0.03 and AMPD 1.3 ± 0.03) and sexually dimorphic programming of the pancreatic RAS, with development of hyperglycemia only in the female mice offspring as a consequence of AMPD. No significant difference in serum insulin concentration was observed; however, AMPD was associated with increased mRNA and protein expression of angiotensinogen, renin and angiotensin-converting enzyme (ACE)-1 in male and female offspring. Of importance, mRNA and protein expression of ACE 2 and angiotensin II receptors was up-regulated only in the male offspring, as a consequence of AMPD. We conclude that sexually dimorphic programming of the pancreatic RAS expression is associated with AMPD diet-mediated development of hyperglycemia.
A unified approach for the structural health monitoring of waveguides
Authors: Zhu Xuan , Rizzo Piervincenzo
Published: August 2012

In this article, the simultaneous use of ultrasonic testing and impedance-based technique to monitor the health of structural waveguides is proposed. Methods based on the propagation of guided waves are increasingly used in all those structural health monitoring applications that benefit from built-in transduction, moderately large inspection ranges, and high sensitivity to small flaws. In the meantime, impedance-based method promises to adequately assess the structural integrity of simple and complex structures that include welds and bolts. As both wave-based and impedance-based approaches can utilize piezoelectric transducers (lead zirconate titanate) bonded or embedded to the structure being monitored, this article describes a unified structural health monitoring paradigm where these techniques are employed simultaneously, driven by the same sensing/hardware/software unit. Specifically, we propose to use two lead zirconate titanates controlled by a National Instruments–PXI running in LabVIEW. An ad hoc LabVIEW Virtual Instrument controls signal output and input as well as processing and storage. To assess the feasibility of this unified system, an aluminum plate and a steel pipe were monitored. Damage was simulated by changing the boundary conditions of each structure. The results show that the proposed system is robust and can be developed further to address the challenges associated with the structural health monitoring of complex structures.
On assessing the robustness of structural health monitoring technologies
Authors: Stull Christopher J , Hemez François M , Farrar Charles R
Published: August 2012

As structural health monitoring continues to gain popularity, both as an area of research and as a tool for use in industrial applications, the number of technologies associated with structural health monitoring will also continue to grow. As a result, the engineer tasked with developing a structural health monitoring system is faced with myriad hardware and software technologies from which to choose, often adopting an ad hoc qualitative approach based on physical intuition or past experience to making such decisions, and offering little in the way of justification for a particular decision. This article offers a framework that aims to provide the engineer with a quantitative approach for choosing from among a suite of candidate structural health monitoring technologies. The framework is outlined for the general case, where a supervised learning approach to structural health monitoring is adopted and is then demonstrated on two problems commonly encountered when developing structural health monitoring systems: (a) selection of damage-sensitive features, where the engineer must determine the appropriate order of an autoregressive model for modeling of time-history data, and (b) selection of a damage classifier, where the engineer must select from among a suite of candidate classifiers, the one most appropriate for the task at hand. The data employed for these problems are taken from a preliminary study that examined the feasibility of applying structural health monitoring technologies to the RAPid Telescopes for Optical Response observatory network.
Baseline-free pipeline monitoring using optical fiber–guided laser ultrasonics
Authors: Lee Hyeonseok , Yang Jinyeol , Sohn Hoon
Published: August 2012

This study develops an optical fiber–guided laser ultrasonic system and baseline-free damage detection method that enables structural health monitoring of pipelines employed under a high-temperature environment of nuclear power plants. First, this study designs embeddable optical fibers and fixing devices, so that the laser beams used for ultrasonic excitation and sensing could be transmitted between laser sources and target pipe surfaces through the optical fibers. All devices are specially designed for a high-temperature environment up to 300°C. Then, a damage detection method is developed to identify typical pipe defects without any previous baseline data. This technique is based on the premise that multiple identical wave paths exist in an intact axisymmetric pipe, but the similarity among the ultrasonic signals obtained from these identical wave paths breaks down when there is a nonaxisymmetric defect. The feasibility of the proposed technique has been experimentally verified using a stainless steel pipe specimen under a high-temperature environment.
Fiber optic method for health assessment of pipelines subjected to earthquake-induced ground movement
Authors: Glisic Branko , Yao Yao
Published: August 2012

Natural disasters, in particular earthquakes, can cause damage to pipelines with disastrous humanitarian, social, economic, and ecologic consequences. Thus, real-time, automatic, or on-demand assessment of damage to pipelines after the earthquake is essential for early emergency response, efficient preparation of rescue plans, and mitigation of these disastrous consequences. This article presents the development of a method for buried pipelines health assessment based on distributed fiber optic sensors, which are sensitive to strain at every point along their lengths. The sensors are both bonded to pipeline and embedded in the soil, in the proximity of the pipeline. The research includes determination of sensor topology, identification of required sensor properties, selection of sensors, development of installation procedures, implementation, and validation. The validation of the method was made through a large-scale testing: a 13-m-long real-size concrete segmented pipeline was assembled in a large test basin filled with soil and was tested under simulated permanent ground displacement. The basin consisted of two parts: the movable north part and the fixed south part. The movable north part of the test basin was attached to four hydraulic actuators, which were used to apply controlled displacement of the basin, and it induced damage to the pipeline by crushing the joints between adjacent pipeline segments. As a part of validation, the results obtained from distributed sensors were compared with resistive strain gauges. Two validation tests were performed: the first in 2010 and the second in 2011. The method is presented in detail, and the most significant results of both tests are analyzed, compared, and discussed. The validation tests confirmed the capacity of the method to reliably detect and localize the damage on pipeline and the displacement in the soil.
On the Digital Playing Field
Authors: Witkowski Emma
Published: August 2012

In the following article, the author explores the notion of playing computer games as sports by sketching out the labors and sensations of Counter-Strike teams playing at pro/am e-sports local area network (LAN) tournaments. How players are engaged physically in practice and play is described in this qualitative study through the core themes of movement, haptic engagement, and the balanced body. Furthermore, the research describes how technologies in play are laboring actors too; the players and technologies in this study are rendered as networked, extended, and acting in and on the same fields of play. In asking is there a “sport” in e-sports, this study questions the legitimacy of a traditional sports ontology and simultaneously tackles the notion of engagement with computer game play as a legitimate sporting endeavor.
A probabilistic approach for estimating defect size and density considering detection uncertainties and measurement errors
Authors: Chatterjee Kaushik , Modarres Mohammad
Published: August 2012

Every structural component has some form and amount of hidden defects, however small it might be. These defects should be detected and characterized in order to ensure reliability of safety-critical structures. Test equipment is often used to inspect and gather data from probable defect sites in structural components during in-service inspections for maintenance purposes. This data is then analyzed and processed to measure the defect size and density. In-service inspection data may be highly uncertain in nature owing to detection uncertainties and measurement errors typically associated with the testing and evaluation process. These uncertainties and errors, if not properly accounted for, can result in defect size and density estimates not representative of the true state of degradations. In this article we first provide a description of the detection uncertainties and measurement errors in the context of nondestructive testing and evaluation. We then propose a Bayesian approach that updates prior knowledge of defect size and density with uncertain nondestructive evaluation data, accounting for detection uncertainties, measurement errors, and other associated uncertainties, to infer the posterior estimates of true size and number of defects. An example application of the proposed approach is then presented for estimating true defect size and density in nuclear reactor piping welds using ultrasonic evaluation data. The Bayesian approach presented in this article fills a critical gap in health management and reliability prognosis of structures, thereby enhancing the overall structural safety and operability.
Tyrosine phosphorylation of DEP-1/CD148 as a mechanism controlling Src kinase activation, endothelial cell permeability, invasion, and capillary formation
Authors: Spring Kathleen , Chabot Catherine , Langlois Simon , Lapointe Line , Trinh Nguyen Thu Ngan , Caron Christine , Hebda Jagoda K. , Gavard Julie , Elchebly Mounib , Royal Isabelle
Published: August 2012

DEP-1/CD148 is a receptor-like protein tyrosine phosphatase with antiproliferative and tumor-suppressive functions. Interestingly, it also positively regulates Src family kinases in hematopoietic and endothelial cells, where we showed it promotes VE-cadherin–associated Src activation and endothelial cell survival upon VEGF stimulation. However, the molecular mechanism involved and its biologic functions in endothelial cells remain ill-defined. We demonstrate here that DEP-1 is phosphorylated in a Src- and Fyn-dependent manner on Y1311 and Y1320, which bind the Src SH2 domain. This allows DEP-1–catalyzed dephosphorylation of Src inhibitory Y529 and favors the VEGF-induced phosphorylation of Src substrates VE-cadherin and Cortactin. Accordingly, RNA interference (RNAi)–mediated knockdown of DEP-1 or expression of DEP-1 Y1311F/Y1320F impairs Src-dependent biologic responses mediated by VEGF including permeability, invasion, and branching capillary formation. In addition, our work further reveals that above a threshold expression level, DEP-1 can also dephosphorylate Src Y418 and attenuate downstream signaling and biologic responses, consistent with the quiescent behavior of confluent endothelial cells that express the highest levels of endogenous DEP-1. Collectively, our findings identify the VEGF-dependent phosphorylation of DEP-1 as a novel mechanism controlling Src activation, and show this is essential for the proper regulation of permeability and the promotion of the angiogenic response.
The interplay between the Rab27A effectors Slp4-a and MyRIP controls hormone-evoked Weibel-Palade body exocytosis
Authors: Bierings Ruben , Hellen Nicola , Kiskin Nikolai , Knipe Laura , Fonseca Ana-Violeta , Patel Bijal , Meli Athina , Rose Marlene , Hannah Matthew J. , Carter Tom
Published: August 2012

Weibel-Palade body (WPB) exocytosis underlies hormone-evoked VWF secretion from endothelial cells (ECs). We identify new endogenous components of the WPB: Rab3B, Rab3D, and the Rab27A/Rab3 effector Slp4-a (granuphilin), and determine their role in WPB exocytosis. We show that Rab3B, Rab3D, and Rab27A contribute to Slp4-a localization to WPBs. siRNA knockdown of Slp4-a, MyRIP, Rab3B, Rab3D, Rab27A, or Rab3B/Rab27A, or overexpression of EGFP-Slp4-a or EGFP-MyRIP showed that Slp4-a is a positive and MyRIP a negative regulator of WPB exocytosis and that Rab27A alone mediates these effects. We found that ECs maintain a constant amount of cellular Rab27A irrespective of the WPB pool size and that Rab27A (and Rab3s) cycle between WPBs and a cytosolic pool. The dynamic redistribution of Rab proteins markedly decreased the Rab27A concentration on individual WPBs with increasing WPB number per cell. Despite this, the probability of WPB release was independent of WPB pool size showing that WPB exocytosis is not determined simply by the absolute amount of Rab27A and its effectors on WPBs. Instead, we propose that the probability of release is determined by the fractional occupancy of WPB-Rab27A by Slp4-a and MyRIP, with the balance favoring exocytosis.
Multiple functionally divergent and conserved copies of alpha tubulin in bdelloid rotifers
Authors: Eyres Isobel , Frangedakis Eftychios , Fontaneto Diego , Herniou Elisabeth A , Boschetti Chiara , Carr Adrian , Micklem Gos , Tunnacliffe Alan , Barraclough Timothy G
Published: August 2012

Background

Bdelloid rotifers are microscopic animals that have apparently survived without sex for millions of years and are able to survive desiccation at all life stages through a process called anhydrobiosis. Both of these characteristics are believed to have played a role in shaping several unusual features of bdelloid genomes discovered in recent years. Studies into the impact of asexuality and anhydrobiosis on bdelloid genomes have focused on understanding gene copy number. Here we investigate copy number and sequence divergence in alpha tubulin. Alpha tubulin is conserved and normally present in low copy numbers in animals, but multiplication of alpha tubulin copies has occurred in animals adapted to extreme environments, such as cold-adapted Antarctic fish. Using cloning and sequencing we compared alpha tubulin copy variation in four species of bdelloid rotifers and four species of monogonont rotifers, which are facultatively sexual and cannot survive desiccation as adults. Results were verified using transcriptome data from one bdelloid species, Adineta ricciae.

Results

In common with the typical pattern for animals, monogonont rotifers contain either one or two copies of alpha tubulin, but bdelloid species contain between 11 and 13 different copies, distributed across five classes. Approximately half of the copies form a highly conserved group that vary by only 1.1% amino acid pairwise divergence with each other and with the monogonont copies. The other copies have divergent amino acid sequences that evolved significantly faster between classes than within them, relative to synonymous changes, and vary in predicted biochemical properties. Copies of each class were expressed under the laboratory conditions used to construct the transcriptome.

Conclusions

Our findings are consistent with recent evidence that bdelloids are degenerate tetraploids and that functional divergence of ancestral copies of genes has occurred, but show how further duplication events in the ancestor of bdelloids led to proliferation in both conserved and functionally divergent copies of this gene.
Failure of delayed nonsynaptic neuronal plasticity underlies age-associated long-term associative memory impairment
Authors: Watson Shawn N , Risling Tara E , Hermann Petra M , Wildering Willem C
Published: August 2012

Background

Cognitive impairment associated with subtle changes in neuron and neuronal network function rather than widespread neuron death is a feature of the normal aging process in humans and animals. Despite its broad evolutionary conservation, the etiology of this aging process is not well understood. However, recent evidence suggests the existence of a link between oxidative stress in the form of progressive membrane lipid peroxidation, declining neuronal electrical excitability and functional decline of the normal aging brain. The current study applies a combination of behavioural and electrophysiological techniques and pharmacological interventions to explore this hypothesis in a gastropod model (Lymnaea stagnalisfeeding system) that allows pinpointing the molecular and neurobiological foundations of age-associated long-term memory (LTM) failure at the level of individual identified neurons and synapses.

Results

Classical appetitive reward-conditioning induced robust LTM in mature animals in the first quartile of their lifespan but failed to do so in animals in the last quartile of their lifespan. LTM failure correlated with reduced electrical excitability of two identified serotonergic modulatory interneurons (CGCs) critical in chemosensory integration by the neural network controlling feeding behaviour. Moreover, while behavioural conditioning induced delayed-onset persistent depolarization of the CGCs known to underlie appetitive LTM formation in this model in the younger animals, it failed to do so in LTM-deficient senescent animals. Dietary supplementation of the lipophilic anti-oxidant α-tocopherol reversed the effect of age on CGCs electrophysiological characteristics but failed to restore appetitive LTM function. Treatment with the SSRI fluoxetine reversed both the neurophysiological and behavioural effects of age insenioranimals.

Conclusions

The results identify the CGCs as cellular loci of age-associated appetitive learning and memory impairment inLymnaeaand buttress the hypothesis that lipid peroxidation-dependent depression of intrinsic excitability is a hallmark of normal neuronal aging. The data implicate both lipid peroxidation-dependent non-synaptic as well as apparently lipid peroxidation-independent synaptic mechanisms in the age-dependent decline in behavioural plasticity in this model system.
Differential effects of the changes of LDL cholesterol and systolic blood pressure on the risk of carotid artery atherosclerosis
Authors: Chien Kuo-Liong , Tu Yu-Kang , Hsu Hsiu-Ching , Su Ta-Chen , Lin Hung-Ju , Chen Ming-Fong , Lee Yuan-Teh
Published: August 2012

Background

The effects of baseline and changes in blood pressure and low density lipoprotein (LDL) cholesterol on the carotid intima media thickness (IMT) have not been well documented.

Methods

A total of 2572 adults (mean age 53.8 years, 54.6% women) in a Taiwanese community undertook three blood pressure and LDL cholesterol examinations over 6 years. Latent growth curve modeling was used to investigate the effects of baseline and change in blood pressure and LDL cholesterol on IMT.

Results

Greater baseline LDL and blood pressure were associated with an increase in IMT (0.005 ± 0.002 mm per 1 mg/dL [p = 0.006] and 0.041 ± 0.004 mm mmHg [p <0.0001], respectively. Change in blood pressure was associated with a significant increase in IMT (0.047±0.016, P = 0.004), whilst the association between change in LDL and change in IMT was not statistically significant (0.008±0.006, P = 0.20).

Conclusions

Carotid IMT was associated with baseline blood pressure and LDL cholesterol, yet only changes of blood pressure, not LDL cholesterol, were related to carotid IMT during the 6-year observation.
The effect of hospital volume on patient outcomes in severe acute pancreatitis
Authors: Shen Hsiu-Nien , Lu Chin-Li , Li Chung-Yi
Published: August 2012

Background

We investigated the relation between hospital volume and outcome in patients with severe acute pancreatitis (SAP). The determination is important because patient outcome may be improved through volume-based selective referral.

Methods

In this cohort study, we analyzed 22,551 SAP patients in 2,208 hospital-years (between 2000 and 2009) from Taiwan’s National Health Insurance Research Database. Primary outcome was hospital mortality. Secondary outcomes were hospital length of stay and charges. Hospital SAP volume was measured both as categorical and as continuous variables (per one case increase each hospital-year). The effect was assessed using multivariable logistic regression models with generalized estimating equations accounting for hospital clustering effect. Adjusted covariates included patient and hospital characteristics (model 1), and additional treatment variables (model 2).

Results

Irrespective of the measurements, increasing hospital volume was associated with reduced risk of hospital mortality after adjusting the patient and hospital characteristics (adjusted odds ratio [OR] 0.995, 95% confidence interval [CI] 0.993-0.998 for per one case increase). The patients treated in the highest volume quartile (≥14 cases per hospital-year) had 42% lower risk of hospital mortality than those in the lowest volume quartile (1 case per hospital-year) after adjusting the patient and hospital characteristics (adjusted OR 0.58, 95% CI 0.40-0.83). However, an inverse relation between volume and hospital stay or hospital charges was observed only when the volume was analyzed as a categorical variable. After adjusting the treatment covariates, the volume effect on hospital mortality disappeared regardless of the volume measures.

Conclusions

These findings support the use of volume-based selective referral for patients with SAP and suggest that differences in levels or processes of care among hospitals may have contributed to the volume effect.
Neutrophil necrosis and annexin 1 degradation associated with airway inflammation in lung transplant recipients with cystic fibrosis
Authors: Tsao Francis H C , Xiang Zhuzai , Abbasi Adnan , Meyer Keith C
Published: August 2012

Background

Neutrophils sequestered in lower respiratory tract secretions in the inflamed lung may undergo apoptosis and/or necrosis and release toxic cellular contents that can injure airways or parenchyma. This study examined the viability of neutrophils retrieved from the proximal airways of lung transplant recipients with bacterial tracheobronchitis.

Methods

Integrity and stability of intracellular proteins in neutrophils from proximal airways and peripheral blood from lung transplant recipients with bacterial tracheobronchitis were analyzed via Western blot analysis and determination of neutrophil viability by morphologic appearance and flow cytometry.

Results

Neutrophils in tracheobronchial secretions from lung transplant recipients with cystic fibrosis who had normal chest radiographic imaging but bronchoscopic evidence of purulent tracheobronchitis post-transplant were necrotic and associated with degradation of intracellular protein annexin 1. The neutrophil influx was compartmentalized to large airways and not detected in peripheral bronchoalveolar airspaces sampled via bronchoalveolar lavage. Peripheral blood neutrophils from healthy subjects culturedin vitrodemonstrated that annexin 1 degradation, particularly to a 33 kDa annexin 1 breakdown product (A1-BP), was associated with neutrophil necrosis, but not apoptosis. Although annexin 1 degradation was not specific to neutrophil necrosis, it was a sensitive marker of intracellular protein degradation associated with neutrophil necrosis. Annexin 1 degradation to 33 kDa A1-BP was not observed in peripheral blood neutrophils from healthy subjects, but annexin 1 appeared to be degraded in peripheral blood neutrophils of lung transplant recipients despite a normal morphologic appearance of these cells.

Conclusions

Neutrophils were necrotic from the proximal airways of lung transplant recipients with bacterial tracheobronchitis, and this process may begin when neutrophils are still in the systemic circulation prior to sequestration in inflamed airways. Annexin 1 degradation to 33 kDa A1-BP may be useful as a sensitive marker to detect neutrophil necrosis.
Oncolytic vaccinia virus GLV-1h68 strain shows enhanced replication in human breast cancer stem-like cells in comparison to breast cancer cells
Authors: Wang Huiqiang , Chen Nanhai G , Minev Boris R , Szalay Aladar A
Published: August 2012

Background

Recent data suggest that cancer stem cells (CSCs) play an important role in cancer, as these cells possess enhanced tumor-forming capabilities and are responsible for relapses after apparently curative therapies have been undertaken. Hence, novel cancer therapies will be needed to test for both tumor regression and CSC targeting. The use of oncolytic vaccinia virus (VACV) represents an attractive anti-tumor approach and is currently under evaluation in clinical trials. The purpose of this study was to demonstrate whether VACV does kill CSCs that are resistant to irradiation and chemotherapy.

Methods

Cancer stem-like cells were identified and separated from the human breast cancer cell line GI-101A by virtue of increased aldehyde dehydrogenase 1 (ALDH1) activity as assessed by the ALDEFLUOR assay and cancer stem cell-like features such as chemo-resistance, irradiation-resistance and tumor-initiating were confirmed in cell culture and in animal models. VACV treatments were applied to both ALDEFLUOR-positive cells in cell culture and in xenograft tumors derived from these cells. Moreover, we identified and isolated CD44+CD24+ESA+cells from GI-101A upon an epithelial-mesenchymal transition (EMT). These cells were similarly characterized both in cell culture and in animal models.

Results

We demonstrated for the first time that the oncolytic VACV GLV-1h68 strain replicated more efficiently in cells with higher ALDH1 activity that possessed stem cell-like features than in cells with lower ALDH1 activity. GLV-1h68 selectively colonized and eventually eradicated xenograft tumors originating from cells with higher ALDH1 activity. Furthermore, GLV-1h68 also showed preferential replication in CD44+CD24+ESA+cells derived from GI-101A upon an EMT induction as well as in xenograft tumors originating from these cells that were more tumorigenic than CD44+CD24-ESA+cells.

Conclusions

Taken together, our findings indicate that GLV-1h68 efficiently replicates and kills cancer stem-like cells. Thus, GLV-1h68 may become a promising agent for eradicating both primary and metastatic tumors, especially tumors harboring cancer stem-like cells that are resistant to chemo and/or radiotherapy and may be responsible for recurrence of tumors.
Genetic, environmental and stochastic factors in monozygotic twin discordance with a focus on epigenetic differences
Authors: Czyz Witold , Morahan Julia M , Ebers George C , Ramagopalan Sreeram V
Published: August 2012

Genetic-epidemiological studies on monozygotic (MZ) twins have been used for decades to tease out the relative contributions of genes and the environment to a trait. Phenotypic discordance in MZ twins has traditionally been ascribed to non-shared environmental factors acting after birth, however recent data indicate that this explanation is far too simple. In this paper, we review other reasons for discordance, including differences in thein uteroenvironment, genetic mosaicism, and stochastic factors, focusing particularly on epigenetic discordance. Epigenetic differences are gaining increasing recognition. Although it is clear that in specific cases epigenetic alterations provide a causal factor in disease etiology, the overall significance of epigenetics in twin discordance remains unclear. It is also challenging to determine the causality and relative contributions of environmental, genetic, and stochastic factors to epigenetic variability. Epigenomic profiling studies have recently shed more light on the dynamics of temporal methylation change and methylome heritability, yet have not given a definite answer regarding their relevance to disease, because of limitations in establishing causality. Here, we explore the subject of epigenetics as another component in human phenotypic variability and its links to disease focusing particularly on evidence from MZ twin studies.
High throughput phenotyping for aphid resistance in large plant collections
Authors: Chen Xi , Vosman Ben , Visser Richard GF , van der Vlugt René AA , Broekgaarden Colette
Published: August 2012

Background

Phloem-feeding insects are among the most devastating pests worldwide. They not only cause damage by feeding from the phloem, thereby depleting the plant from photo-assimilates, but also by vectoring viruses. Until now, the main way to prevent such problems is the frequent use of insecticides. Applying resistant varieties would be a more environmental friendly and sustainable solution. For this, resistant sources need to be identified first. Up to now there were no methods suitable for high throughput phenotyping of plant germplasm to identify sources of resistance towards phloem-feeding insects.

Results

In this paper we present a high throughput screening system to identify plants with an increased resistance against aphids. Its versatility is demonstrated using an Arabidopsis thaliana activation tag mutant line collection. This system consists of the green peach aphid Myzus persicae (Sulzer) and the circulative virus Turnip yellows virus (TuYV). In an initial screening, with one plant representing one mutant line, 13 virus-free mutant lines were identified by ELISA. Using seeds produced from these lines, the putative candidates were re-evaluated and characterized, resulting in nine lines with increased resistance towards the aphid.

Conclusions

This M. persicae-TuYV screening system is an efficient, reliable and quick procedure to identify among thousands of mutated lines those resistant to aphids. In our study, nine mutant lines with increased resistance against the aphid were selected among 5160 mutant lines in just 5 months by one person. The system can be extended to other phloem-feeding insects and circulative viruses to identify insect resistant sources from several collections, including for example genebanks and artificially prepared mutant collections.
Construction of a recombinant eukaryotic expression vector containing PHD3 gene and its expression in HepG2 cells
Authors: Liang Qi-Lian , Li Zhou-Yu , Zhou Yuan , Liu Qiu-Long , Ou Wen-Ting , Huang Zhi-Gang
Published: August 2012

Prolyl hydroxylase domain 3 (PHD3) is a hypoxia inducible factor-α (HIFα) regulator; it degrades HIFα in the presence of oxygen. Recently, there have been an increasing number of studies about the role of PHD3 in proliferation and apoptosis of cancer cells. However, most of the evidence for the role of PHD3 is observational, and little is known of the molecular mechanism. In our current study, we constructed a recombinant eukaryotic expression vector containing the PHD3 gene and detected its biological activity in human hepatoma cell line (HepG2 cells). We successfully constructed a recombinant pcDNA 3.1(+)-PHD3 plasmid; the results showed that PHD3 overexpression could inhibit the proliferation of HepG2 cells and induce apoptosis by activating caspase-3 activity. Our study has provided preliminary materials and data for further investigation of the effect of PHD3 on HepG2 cells.
Production of 1,3-PDO and butanol by a mutant strain of Clostridium pasteurianum with increased tolerance towards crude glycerol
Authors: Jensen Torbjørn Ølshøj , Kvist Thomas , Mikkelsen Marie Just , Westermann Peter
Published: August 2012

The production of biodiesel results in a concomitant production of crude glycerol (10% w/w). Clostridium pasteurianum can utilize glycerol as sole carbon source and converts it into 1,3-propanediol, ethanol, butanol, and CO2. Reduced growth and productivities on crude glycerol as compared to technical grade glycerol have previously been observed. In this study, we applied random mutagenesis mediated by ethane methyl sulfonate (EMS) to develop a mutant strain of C. pasteurianum tolerating high concentrations of crude glycerol. At an initial crude glycerol concentration of 25 g/l the amount of dry cell mass produced by the mutant strain was six times higher than the amount produced by the wild type. Growth of the mutant strain was even detected at an initial crude glycerol concentration of 105 g/l. A pH controlled reactor with in situ removal of butanol by gas-stripping was used to evaluate the performance of the mutant strain. Utilizing stored crude glycerol, the mutant strain showed significantly increased rates compared to the wild type. A maximum glycerol utilization rate of 7.59 g/l/h was observed along with productivities of 1.80 g/l/h and 1.21 g/l/h of butanol and 1,3-PDO, respectively. These rates are higher than what previously has been published for C. pasteurianum growing on technical grade glycerol in fed batch reactors. In addition, high yields of the main products (butanol and 1,3-PDO) were detected and these two products were efficiently separated in two steams using gas-stripping.
Fractional clearance of urate: validation of measurement in spot-urine samples in healthy subjects and gouty patients
Authors: Kannangara Diluk RW , Ramasamy Sheena N , Indraratna Praveen L , Stocker Sophie L , Graham Garry G , Jones Graham , Portek Ian , Williams Kenneth M , Day Richard O
Published: August 2012

Introduction

Hyperuricemia is the greatest risk factor for gout and is caused by an overproduction and/or inefficient renal clearance of urate. The fractional renal clearance of urate (FCU, renal clearance of urate/renal clearance of creatinine) has been proposed as a tool to identify subjects who manifest inefficient clearance of urate. The aim of the present studies was to validate the measurement of FCU by using spot-urine samples as a reliable indicator of the efficiency of the kidney to remove urate and to explore its distribution in healthy subjects and gouty patients.

Methods

Timed (spot, 2-hour, 4-hour, 6-hour, 12-hour, and 24-hour) urine collections were used to derive FCU in 12 healthy subjects. FCUs from spot-urine samples were then determined in 13 healthy subjects twice a day, repeated on 3 nonconsecutive days. The effect of allopurinol, probenecid, and the combination on FCU was explored in 11 healthy subjects. FCU was determined in 36 patients with gout being treated with allopurinol. The distribution of FCU was examined in 118 healthy subjects and compared with that from the 36 patients with gout.

Results

No substantive or statistically significant differences were observed between the FCUs derived from spot and 24-hour urine collections. Coefficients of variation (CVs) were both 28%. No significant variation in the spot FCU was obtained either within or between days, with mean intrasubject CV of 16.4%. FCU increased with probenecid (P < 0.05), whereas allopurinol did not change the FCU in healthy or gouty subjects. FCUs of patients with gout were lower than the FCUs of healthy subjects (4.8% versus 6.9%; P < 0.0001).

Conclusions

The present studies indicate that the spot-FCU is a convenient, valid, and reliable indicator of the efficiency of the kidney in removing urate from the blood and thus from tissues. Spot-FCU determinations may provide useful correlates in studies investigating molecular mechanisms underpinning the observed range of efficiencies of the kidneys in clearing urate from the blood.

Trial Registration

ACTRN12611000743965
Magnitude of stimulation dictates the cannabinoid-mediated differential T cell response to HIVgp120
Authors: Chen Weimin , Kaplan Barbara L F , Pike Schuyler T , Topper Lauren A , Lichorobiec Nicholas R , Simmons Steven O , Ramabhadran Ram , Kaminski Norbert E
Published: August 2012

Cannabinoids differentially modulate T cell function with concomitant dysregulation of the NFAT-calcium signaling cascade.

Approximately 25% of immunocompromised HIV patients smoke marijuana for its putative therapeutic benefit. The goal of these studies was to test the hypothesis that marijuana-derived cannabinoids have immunomodulatory effects on HIV antigen-specific T cell effector function. A surrogate mouse model to induce polyclonal T cell responses against HIVgp120 was established. THC, a marijuana-derived cannabinoid, suppressed or enhanced mouse CD8+ T cell proliferation and the gp120-specific CTL response depending on the magnitude of the IFN-γ response. To determine the molecular mechanisms by which cannabinoids differentially modulate T cell responses, P/I or anti-CD3/CD28 antibodies were used for stimulation, and another marijuana-derived cannabinoid, CBD, was also investigated. THC or CBD suppressed or enhanced IFN-γ and IL-2 production by mouse splenocytes under optimal or suboptimal stimulation, respectively. Similar differential effects of cannabinoids on cytokine production were also observed on nuclear translocation of NFAT and with human PBMCs in response to P/I stimulation. However, THC and CBD elevated intracellular calcium, regardless of the stimulation level with P/I, suggesting that the cannabinoid-induced calcium increase provides an appropriate signal for activation in suboptimally stimulated T cells but an anergic-like signal as a result of excessive calcium in optimally stimulated T cells. Overall, these data demonstrate differential modulation by cannabinoids of a HIV antigen-specific response and identify a possible mechanism responsible for this effect.
Protecting Europe from Diseases: From the International Sanitary Conferences to the ECDC
Authors: Liverani Marco , Coker Richard
Published: August 2012

In the past few decades there has been increased integration of communicable disease policies in Europe. The historical roots of this process date back to the mid-nineteenth century, when national authorities realized that the cross-boundary spread of diseases cannot be only a matter of national governance but requires common agreements and regulations. In the early 1950s the structuring of the World Health Organization in regional offices further contributed to the definition of Europe as a unit for risk assessments and international health cooperation. More recently the consolidation of the European Union has provided new institutional bases for shaping communicable disease policies at the supranational level. This article reviews these different attempts to protect the European space from diseases. It is argued that changing modes of communicable disease control not only have reflected shifts in public health priorities and institutional contexts but have also been important loci where different understandings of Europe and European political identity emerged and were negotiated. Against this background the article then examines past achievements and future challenges of the current European framework and discusses implications for the wider process of European integration.
The Role of the European Court of Justice in the Europeanization of Communicable Disease Control: Driver or Irrelevance?
Authors: Hervey Tamara
Published: August 2012

What role(s) does the European Court of Justice (ECJ) play in the Europeanization of communicable disease control? Drawing on a review of the ECJ's case law, especially but not exclusively in public health fields, from the 1950s to 2009, this article argues that the ECJ's past and present role in the Europeanization of communicable disease control is neither that of a driver nor that of an irrelevance. Instead, the ECJ has been responsible for four important elements of the environment that over time led to the Europeanization of communicable disease control in general and the establishment of the European Centre for Disease Prevention and Control in particular: (1) the European Union itself has responsibility for public health; (2) agencies are a constitutionally permissible institutional arrangement in the EU; (3) EU legislation that inter alia protects public health is mandatory and justiciable; and (4) such EU legislation may not be undermined by liberalizing internal market law. A fifth idea, “mainstreaming” public health, could play a role in the future.
The European Centre for Disease Prevention and Control: Hub or Hollow Core?
Authors: Greer Scott L.
Published: August 2012

The European Centre for Disease Prevention and Control (ECDC) is the small agency established by the European Union (EU) to act as a hub for disease control, drawing on networks across the continent to achieve what other political systems do with large agencies. Despite this important task, the agency is largely unstudied. This article examines the ECDC from different angles, focusing on whether it can become the center of the networks that monitor, control, and prevent contagious diseases in Europe. The essay first retraces the events that led up to the ECDC's creation, focusing on the combination of policy debates about EU actions, political initiatives, and crises such as SARS that led to its creation. It then presents an overview of ECDC activities. The article concludes by examining the ECDC's prospects in light of its ability to secure its future through multiple political connections and a reputation for unique and useful advice. Insofar as it can do that, it will be able to contribute to the development of the EU and European public health.