bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating UK perennial energy crop supply using farm‐scale models with spatially disaggregated data
Authors: Alexander Peter , Moran Dominic , Smith Pete , Hastings Astley , Wang Shifeng , Sünnenberg Gilla , Lovett Andrew , Tallis Matthew J. , Casella Eric , Taylor Gail , Finch Jon , Cisowska Iwona
Published: November 2013

To achieve the UK Government's aim of expansion in the growth of perennial energy crops requires farmers to select these crops in preference to conventional rotations. Existing studies estimating the total potential resource have either only simplistically considered the farmer decision‐making and opportunity costs, for example using an estimate of annual land rental charge; or have not considered spatial variability, for example using representative farm types. This paper attempts to apply a farm‐scale modelling approach with spatially specific data to improve understanding of potential perennial energy crop supply. The model main inputs are yield maps for the perennial energy crops, Miscanthus and willow grown as short‐rotation coppice (SRC), and regional yields for conventional crops. These are used to configure location specific farm‐scale models, which optimize for profit maximization with risk aversion. Areas that are unsuitable or unavailable for energy crops, due to environmental or social factors, are constrained from selection. The results are maps of economic supply, assuming a homogenous farm‐gate price, allowing supply cost curves for the UK market to be derived. The results show a high degree of regional variation in supply, with different patterns for each energy crop. Using estimates of yields under climate change scenarios suggests that Miscanthus supply may increase under future climates while the opposite effect is suggested for SRC willow. The results suggest that SRC willow is only likely to able to supply a small proportion of the anticipated perennial energy crop target, without increases in market prices. Miscanthus appears to have greater scope for supply, and its dominance may be amplified over time by the effects of climate change. Finally, the relationship to the demand side of the market is discussed, and work is proposed to investigate the factors impacting how the market as a whole may develop.
Moderate physical exercise reduces parasitaemia and protects colonic myenteric neurons in mice infected with Trypanosoma cruzi
Authors: Moreira Neide M. , Santos Franciele d. N. , Toledo Max Jean d. O. , Moraes Solange M. F. d. , Araujo Eduardo J. d. A. , Sant'Ana Debora d. M. G. , Araujo Silvana M. d.
Published: November 2013

This study evaluated the influence of moderate physical exercise on the myenteric neurons in the colonic intestinal wall of mice that had been infected with Trypanosoma cruzi. Parasitology and immunological aspects of the mice were considered. Forty‐day‐old male Swiss mice were divided into four groups: Trained Infected (TI), Sedentary Infected (SI), Trained Control (TC), and Sedentary Control (SC). The TC and TI were subjected to a moderate physical exercise program on a treadmill for 8 weeks. Three days after finishing exercise, the TI and SI groups were inoculated with 1,300 blood trypomastigotes of the Y strain‐T. cruzi. After 75 days of infection results were obtained. Kruskal‐Wallis or Analyze of variance (Tukey post hoc test) at 5% level of significance was performed. Moderate physical exercise reduced both the parasite peak (day 8 of infection) and total parasitemia compared with the sedentary groups (P < 0.05). This activity also contributed to neuronal survival (P < 0.05). Exercise caused neuronal hypertrophy (P < 0.05) and an increase in the total thickness of the intestinal wall (P < 0.05). The TI group exhibited an increase in the number of intraepithelial lymphocytes (P > 0.05). In trained animals, the number of goblet cells was reduced compared with sedentary animals (P < 0.05). Physical exercise prevented the formation of inflammatory foci in the TI group (P < 0.05) and increased the synthesis of TNF‐α (P < 0.05) and TGF‐β (P > 0.05). The present results demonstrated the benefits of moderate physical exercise, and reaffirmed the possibility of that it may contribute to improving clinical treatment in Chagas' disease patients.
Capturing the Stories behind the Numbers: The Auckland Regional Community Stroke Study (ARCOS IV), a Qualitative Study
Authors: Rutherford Sandy J. , Theadom Alice , Jones Amy , Hocking Clare , Feigin Valery , Krishnamurthi Rita , Kent Bruce , Barker-Collo Suzanne , McPherson Kathryn M.
Published: November 2013

Background

Qualitative data can add value and understanding to more traditional epidemiological studies. This study was designed to complement the quantitative data from the incidence study the Auckland Regional Community Stroke Study or ARCOS-IV by using qualitative methods to uncover the richer detail of life as a stroke survivor, thereby extending our understanding of the impact of stroke.

Aims

The aims of the study were to identify how the experience of recovery and adaptation changes over time after stroke; and to elicit the strategies people with stroke and their whānau/family use and find helpful in living life after stroke. The aim of this paper is to describe the methodology and also the challenges and advantages of embedding qualitative research into a large epidemiological study.

Methods

Longitudinal study utilizing a Qualitative Description design in a subset of those taking part in the incidence study. Participants will be interviewed at 6, 12, 24, and 36 months after stroke. Semistructured interviews will explore three key areas: ( 1 ) issues of importance to people following a stroke and their whānau/family; ( 2 ) the perceived impact on people's sense of recovery, adaptation, and hopes; and ( 3 ) key strategies that people with stroke and their whānau/family use and find most helpful in living life after stroke. Thematic analysis will be conducted using iterative constant comparative methods.

Conclusions

This methodology paper demonstrates the application of mixed methods in epidemiology. It also considers some of the practical and methodological issues that have emerged and may provide a useful framework for other qualitative projects in population-based studies.
Pericardioscopic imaging findings in cadaveric dogs: Comparison of an apical pericardial window and sub‐phrenic pericardectomy
Authors: Skinner Owen T. , Case J. Brad , Ellison Gary W. , Monnet Eric L.
Published: November 2013

Objective

To compare the pericardioscopic cardiovascular anatomy visible between apical pericardial window (PW) and sub‐phrenic pericardectomy (SPP).

Study Design

Experimental study.

Animals

Canine cadavers (n = 5).

Methods

Thoracoscopy was performed using a transdiaphragmatic subxyphoid and right and left intercostal portals. A 4 cm × 4 cm apical PW was created with endoscopic scissors. The intra‐pericardiac structures were then pericardioscopically assessed using a subjective ordinal scale (0: not visible, 1: <50% seen, 2: >50% seen) before SPP. Assessment was repeated after SPP.

Results

An apical PW provided limited access to the cardiac structures, with only the right ventricle >50% visible in all cadavers. The right atrium, right auricle, left ventricle, right coronary artery, and interventricular paraconal branch of the left coronary artery were observed but were typically <50% visible after apical PW. The left atrium and auricle, and heart base could not be consistently seen through an apical PW. Sub‐phrenic pericardectomy significantly improved observation of all intrapericardiac structures assessed, except for the right atrium and right ventricle.

Conclusions

PW centered over the cardiac apex limits evaluation of the pericardial space during pericardioscopy compared to SPP in cadaveric dogs.
Analysis of quantitative trait loci in mice suggests a role of Enoph1 in stress reactivity
Authors: Barth Alexander , Bilkei‐Gorzo Andras , Drews Eva , Otte David M. , Diaz‐Lacava Amalia , Varadarajulu Jeeva , Turck Christoph W. , Wienker Thomas F. , Zimmer Andreas
Published: November 2013

Significant progress in elucidating the genetic etiology of anxiety and depression has been made during the last decade through a combination of human and animal studies. In this study, we aimed to discover genetic loci linked with anxiety as well as depression in order to reveal new candidate genes. Therefore, we initially tested the behavioral sensitivity of 543 F2 animals derived from an intercross of C57BL/6J and C3H/HeJ mice in paradigms for anxiety and depression. Next, all animals were genotyped with 269 microsatellite markers with a mean distance of 5.56 cM. Finally, a Quantitative Trait Loci (QTL) analysis was carried out, followed by selection of candidate genes. The QTL analysis revealed several new QTL on chromosome 5 with a common core interval of 19 Mb. We further narrowed this interval by comparative genomics to a region of 15 Mb. A database search and gene prioritization revealed Enoph1 as the most significant candidate gene on the prioritization list for anxiety and also for depression fulfilling our selection criteria. The Enoph1 gene, which is involved in polyamine biosynthesis, is differently expressed in parental strains, which have different brain spermidine levels and show distinct anxiety and depression‐related phenotype. Our result suggests a significant role in polyamines in anxiety and depression‐related behaviors.

image

Enoph1, an enzyme of the methionine salvage pathway involved in polyamine biosynthesis, was identified by QTL analysis as a candidate gene contributing to stress‐sensitivity in a F2 population of mice derived from C57BL/6J × C3H/HeJ intercrosses. The parental strains express two different protein variants of Enoph1, show different Enoph1 expression levels, and have different brain spermidine levels. These findings suggest that Enoph1 modulates stress sensitivity in these strains.
Understanding the distributed cognitive processes of intensive care patient discharge
Authors: Lin Frances , Chaboyer Wendy , Wallis Marianne
Published: November 2013

Aims and objectives

To better understand and identify vulnerabilities and risks in the ICU patient discharge process, which provides evidence for service improvement.

Background

Previous studies have identified that ‘after hours’ discharge and ‘premature’ discharge from ICU are associated with increased mortality. However, some of these studies have largely been retrospective reviews of various administrative databases, while others have focused on specific aspects of the process, which may miss crucial components of the discharge process.

Design

This is an ethnographic exploratory study.

Methods

Distributed cognition and activity theory were used as theoretical frameworks. Ethnographic data collection techniques including informal interviews, direct observations and collecting existing documents were used. A total of 56 one‐to‐one interviews were conducted with 46 participants; 28 discharges were observed; and numerous documents were collected during a five‐month period. A triangulated technique was used in both data collection and data analysis to ensure the research rigour.

Results

Under the guidance of activity theory and distributed cognition theoretical frameworks, five themes emerged: hierarchical power and authority, competing priorities, ineffective communication, failing to enact the organisational processes and working collaboratively to optimise the discharge process. Issues with teamwork, cognitive processes and team members' interaction with cognitive artefacts influenced the discharge process.

Conclusion

Strategies to improve shared situational awareness are needed to improve teamwork, patient flow and resource efficiency. Tools need to be evaluated regularly to ensure their continuous usefulness.

Relevance to clinical practice

Health care professionals need to be aware of the impact of their competing priorities and ensure discharges occur in a timely manner. Activity theory and distributed cognition are useful theoretical frameworks to support healthcare organisational research.
Living at home with eating difficulties following stroke: a phenomenological study of younger people's experiences
Authors: Klinke Marianne E , Hafsteinsdóttir Thóra B , Thorsteinsson Björn , Jónsdóttir Helga
Published: November 2013

Aims and objectives

To explore and describe the experience of eating and eating‐related difficulties in stroke survivors living at home.

Background

The ability to consume food and to take pleasure in eating is an essential part of life. For people with stroke, eating difficulties are frequent. A phenomenological perspective of stroke survivors' experience of eating difficulties exceeding the acute stroke event and in‐hospital rehabilitation is missing.

Design

A qualitative study founded on the Husslarian descriptive phenomenology.

Methods

Colaizzi's seven phases of data analysis provided a systematic approach to explore 17 in‐depth interviews from seven participants and how eating difficulties influenced their daily lives.

Results

Eating difficulties revealed themselves in participants' relationship with the outer world in far‐reaching disruptions of habits, capacities and actions. Four key themes illuminating the eating difficulties emerged: (1) preserving dignity by not conveying serious problems, (2) staying vigilant to bodily limitations, (3) stepping out of the security zone and (4) moving on without missing out. The findings exposed that eating difficulties might not only lead to serious consequences such as malnutrition but also, and equally importantly, lead to losses in the existential, social and cultural lifeworld.

Conclusions

The experience of eating difficulties entails an ongoing readjustment process, which is strongly influenced by interactions with other people. The findings suggest that individualised long‐term support is needed to facilitated the use of helpful strategies to manage eating difficulties.

Relevance to clinical practice

The long‐term losses that people with eating difficulties experience are not reflected in conventional screening tools and interventions. To avoid haphazard identification presupposes professional knowledge of how eating difficulties are woven into daily life. This knowledge may inform innovative nursing strategies reaching beyond immediate rehabilitation. Partnership‐based practice may provide an important framework to establish unique needs and to mobilise relevant actions and resources.
Bioequivalence of Orally Administered Generic, Compounded, and Innovator‐Formulated Itraconazole in Healthy Dogs
Authors: Mawby D.I. , Whittemore J.C. , Genger S. , Papich M.G.
Published: November 2013

Background

Itraconazole is commonly used to treat systemic fungal infections in dogs, but problems exist with absorption and cost.

Objective

To determine oral bioequivalence of generic and compounded itraconazole compared to original innovator (brand name) itraconazole in healthy dogs.

Animals

Nine healthy, adult research Beagle dogs.

Methods

A randomized, 3‐way, 3‐period, crossover design with an 8‐day washout period. After a 12‐hour fast, each dog received 100 mg (average: 10.5 mg/kg) of either innovator itraconazole, an approved human generic capsule, or compounded itraconazole (compounded using a commercially available compounding vehicle) with a small meal. Plasma was collected at predetermined intervals for high pressure liquid chromatography analysis. Concentration data were analyzed using noncompartmental pharmacokinetics to determine area under the curve (AUC), peak concentration (CMAX), and terminal half‐life. Bioequivalence tests compared generic and compounded itraconazole to the reference formulation.

Results

Average ratios of compounded and generic formulations to the reference formulation of itraconazole for AUC were 5.52% and 104.2%, respectively, and for CMAX were 4.14% and 86.34%, respectively. A test of bioequivalence using 2 one‐sided tests and 90% confidence intervals did not meet bioequivalence criteria for either formulation.

Conclusion and Clinical Importance

Neither generic nor compounded itraconazole is bioequivalent to the reference formulation in dogs. However, pharmacokinetic data for generic formulation were similar enough that therapeutic concentrations could be achieved. Compounded itraconazole produced such low plasma concentrations, it is unlikely to be effective; therefore, compounded itraconazole should not be used in dogs.
Signalment, Clinical Presentation, and Diagnostic Findings in 122 Dogs with Spinal Arachnoid Diverticula
Authors: Mauler D.A. , De Decker S. , De Risio L. , Volk H.A. , Dennis R. , Gielen I. , Van der Vekens E. , Goethals K. , Van Ham L.
Published: November 2013

Background

Most information about spinal arachnoid diverticula (SADs) in dogs has been retrieved from relatively small case series. The aim of this study was to describe this disease in a larger number of dogs.

Objectives

Description of the signalment, clinical presentation, and imaging findings of a large number of dogs withSADs.

Animals

One hundred and twenty‐two dogs withSADs.

Methods

Retrospective case series study. All medical records were searched for a diagnosis ofSAD. The diagnosis was made based on myelography, computed tomography myelography (CT‐m), or magnetic resonance imaging (MRI).

Results

In the 122 dogs, 125SADs were identified. Sixty‐five were located in the cervical region and 60 in the thoracolumbar region. A higher body weight was significantly associated with a cervical localization of theSAD(P < .001). Ninety‐five dogs were male and 27 dogs were female. Male dogs were significantly overrepresented (P < .0001). The most commonly affected breed was the Pug dog. Previous or concurrent spinal disorders, in the near proximity of the diagnosedSAD, were seen in 26 dogs. Eight of 13 French Bulldogs and 7 of 21 Pug dogs withSADs had a previous or concurrent spinal disease, whereas other spinal disorders occurred in only 1 of 17 Rottweilers withSADs.

Conclusions and Clinical Importance

Pug dogs and French Bulldogs might have a predisposition forSADdevelopment. In a large percentage of these dogs, a concurrent spinal disorder, which might predispose toSADformation, was diagnosed. The high prevalence in male dogs warrants further investigation.
Psychosocial functioning is correlated with activation in the anterior cingulate cortex and left lateral prefrontal cortex during a verbal fluency task in euthymic bipolar disorder: A preliminary fMRI study
Authors: Yoshimura Yasushi , Okamoto Yasumasa , Onoda Keiichi , Okada Go , Toki Shigeru , Yoshino Atsuo , Yamashita Hidehisa , Yamawaki Shigeto
Published: November 2013

Aim

Cognitive impairment may account for functional and occupational disability in patients with bipolar disorder even during periods of euthymia. While imaging suggests structural, neurochemical, and functional abnormalities in bipolar disorder patients, the pathophysiology of these deficits has not been elucidated. It was hypothesized that euthymic bipolar patients would have different cortical activation during a verbal fluency task compared to healthy controls, and that psychosocial functioning would be associated with prefrontal cortical activation during the task in the bipolar group.

Methods

Ten euthymic bipolar patients and 10 healthy control participants (matched for age, gender, and years of education) underwent functional magnetic resonance imaging (fMRI) during a verbal fluency task, tapping task and visual task. Correlational analysis between the fMRI brain activation and clinical variables of the participants, including Global Assessment of Functioning (GAF) score, was performed.

Results

Compared to the controls, euthymic bipolar patients had significantly greater activation in the bilateral precuneus with similar behavioral performance during the verbal fluency task. There were no significant differences between the groups for the visual task or the simple motor task. Activation in both the left anterior cingulate cortex (ACC) and the left dorsolateral prefrontal cortex (PFC) were significantly positively correlated with GAF score in the euthymic bipolar patients.

Conclusion

Both the ACC and lateral PFC regions are components of a neural network that plays a critical role in psychosocial functioning, and are often found to be affected in bipolar patients.
Differences in the gut microbiota of healthy children and those with type 1 diabetes
Authors: Soyucen Erdogan , Gulcan Aynur , Aktuglu‐Zeybek Ayse Cigdem , Onal Hasan , Kiykim Ertugrul , Aydin Ahmet
Published: November 2013

Background

Intestinal barriers, intestinal flora, and mucosal immunity are the main factors responsible for the development of various allergic and autoimmune diseases. The aim of this study was to investigate the relationship between the intestinal flora of children and the presence of type 1 diabetes, and to determine if gut microbiota could partly explain the etiology of the disease.

Methods

Fecal flora analysis was done using quantitative cultures on selective and non‐selective media with different thermal and atmospheric conditions for bacterial and fungal growth. The study group consisted of 35 patients (16 female, 19 male; mean age, 10.73 ± 4.16 years), who had been followed by the University of Istanbul, Cerrahpasa Medical Faculty, Department of Pediatrics, and were newly diagnosed with type 1 diabetes. The control group consisted of 35 healthy subjects (15 female, 20 male; mean age, 9.96 ± 4.09 years), who were randomly selected and had similar demographics.

Results

Bifidobacterium colonization was lower in patients with type 1 diabetes compared to the control group, whereas Candida albicans and Enterobacteriaceae other than Echerichia coli colonization was increased.

Conclusion

A decrease in beneficial anaerobic bacteria levels and a concomitant increase in Enterobacteriaceae other than E. coli and C. albicans colonization may lead to a disturbance in the ecological balance of intestinal flora, which could be a triggering factor in type 1 diabetes etiology.
Multiparametric MEMS Biosensors With Integrated Impedance Spectroscopy and Gravimetric Measurements for Water Toxicity Sensing
Authors: Liu Fei , Li Fang , Khademhosseini Ali , Voiculescu Ioana
Published: November 2013

This paper presents the design, fabrication and characterization of a novel multiparametric microelectromechanical (MEMS) biosensor based on live mammalian cells with capabilities of sensing the toxicity of field water with minimized false-positive rate. This biosensor combines two biosensing techniques, resonant frequency measurements and electric cell-substrate impedance sensing (ECIS) on a single chip. The sensor is based on the innovative placement of the working microelectrode for ECIS technique as the upper electrode of a quartz crystal microbalance (QCM) resonator. This multiparametric biosensor was characterized with bovine aortic endothelial cells (BAECs). Toxicity tests to study BAECs responsiveness to health-threatening concentrations of ammonia in de-ionized water as a toxicant model will also be presented. The increase of the resonant frequency and decrease of impedance of the biosensor indicated the detachment of cells as a result of toxicant stimulation of ammonia solution. These gravimetric and impedimetric measurements on the same cell monolayer demonstrate that the multiparametric biosensor is able to perform two types of measurements simultaneously and this sensor can successfully be tested with drinking water containing toxicants.
Study of Long Term Viability of Endothelial Cells on Biochip for Rapid and Reliable Water Toxicity Measurements
Authors: Liu Fei , Chen Tingting , Zhang Xudong , Li Fang , Voiculescu Ioana
Published: November 2013

Measuring water toxicity is a lengthy process, and rapid analytical methods are limited. A complementary approach is to measure water toxicity on live cells via electric cell-substrate impedance sensing (ECIS) using a field portable device. This paper presents a study of the longevity of bovine aortic endothelial cell (BAECs VEC Technologies, Rensselaer, NY) by integrating a microfluidic device onto the ECIS sensors. This microfluidic chamber with a network of tree-like perfusion microfluidic channels for cell media delivery to the culturing chamber was fabricated from a biocompatible polymer and tested for longevity studies. This perfusion microchannels were designed as a symmetric arbor with binary splitting to provide equal flow in all the perfusion channels. The microdimensions of the perfusion channels provide high flow resistance, thus carrying low flow rates for a given head pressure and generating low shear stress to the cells during the long-time cell attachment and proliferation period. With such a microfluidic device, cell media can be automatically and evenly perfused into the culturing chamber and no significant shear stress produced by media perfusion was observed. During the longevity study, the BAECs were able to survive in good health for longer than one month. Toxicity tests to study the BAECs responsiveness to health-threatening concentrations of ammonia using the microfluidic ECIS sensor will be also presented. Using impedance spectroscopy technique we demonstrated the BAECs can rapidly respond to ammonia concentrations between the military exposure guideline of 2mM and human lethal concentration of 55mM.

The BAECs monolayer represent the most important component of a biosensor for testing water toxicity in the field. This research concluded that the BAECs could resist at least 34 days on the microfluidic chip and demonstrate high values of cell membrane impedance during long period of time.
Multiscale Modeling and Simulation of a Microbead in an Optical Trapping Process
Authors: Haghshenas-Jaryani Mahdi , Tran Nguyen T. , Bowling Alan P. , Drake James A. , Mohanty Samarendra
Published: November 2013

The purpose of this work is to generate a theoretical model for the dynamics of a polystyrene microsphere under the influence of Gaussian beam optical tweezers (OTs) in the ray-optics regime. OTs use the radiation pressure from a focused laser beam to manipulate microscopic objects as small as atoms [1]. They have been used in the biological sciences to measure nanometer-range displacements, apply picoNewton-range forces, and determine the mechanical properties of DNA, cell membranes, whole cells, and microtubules. The proposed model takes into account the forces and moments imparted onto the microbead by the OTs beam, and uses a Newton-Euler Dynamics framework to generate the equations of motion. Although examination of dimensionless numbers and other indicators including, Reynolds number 10−9 ≤ Re ≤ 10−4, Knudsen number 0.0001875, and the disproportionality between the mass and the viscous drag co-efficients O(10−4), does not clearly indicate whether this is a multiscale problem or not; but, a numerical integration of the original model leads to a long simulation run-time, a few days. Moreover, investigation of the step size showed that the adaptive numerical integrator was proceeding with a picosecond step size in order to achieve the requested accuracy. This situation implies a multiscale feature involved in the dynamics of optical trapping process of the small bead. To address this issue, a multiscale model is developed that helps to significantly reduce the simulation run-time and reveals underdamped behavior of the bead. In order to verify the theoretical model, experiments were carried out on a microsphere bead with 1.6μm diameter. A comparison of experimental data and simulation data indicate that this approach closely models microparticle behavior to the accuracy of the experiment under Gaussian beam optical tweezers.
Development of a Dynamic Testing Device for Predicting the Enhanced Permeation and Retention (EPR) Effect of Different Nanoparticles in Tumor Vessels
Authors: Baek Sungchul , Taylor Robert A. , Barber Tracie J.
Published: November 2013

A microfluidic device was developed to simulate the dynamic conditions of the transvascular transport of nanoparticles. The device utilizes a microfluidic channel, filter paper, collagen gel—which represent the blood vessel, porous vessel wall, and interstitial matrix of the tumor, respectively. By controlling these components, the fluid-dynamic conditions of the tumor blood vessels can be simulated.

For the initial study, Durapore® filters with the nominal diameter of 0.22 μm and 5 mg/ml type 1 collagen gel were used. The transvascular transport parameters of the membrane for a model particle, 20 nm gold spheres, were similar to those of rabbit VX2 carcinoma model. Overall, this design allows for fundamental research into the fluid dynamic transport of particles inside different organs, cancer types and stages. To investigate the physiological conditions of cancer, future studies will include modification of the filter membranes with proteins as well as subsequent culturing of endothelial cells on the filter and tumor cells in the gel matrix. Through this device, we will be able to prescribe nanoparticle fluids for to obtain enhanced permeation and retention.
A Robust Framework for Adaptive Multiscale Modeling of Biopolymers Using Highly Parallelizable Methods
Authors: Khan Imad M. , Anderson Kurt S.
Published: November 2013

For many biopolymers (RNA, DNA, enzymes and proteins) the nature of the molecules interaction within the cell has been determined to be highly a function of its conformational structure. Understanding how to influence and control this structure thus is of critical importance if one wishes to manipulate the intercellular processes of which these biopolymers play such a central role. In molecular dynamics (MD) simulations, a fully atomistic model represents the system at the finest scale and as such captures all the dynamics of the system. If the simulation is permitted to run sufficiently long important emergent behaviors can develop and show themselves. Such MD simulations represent a direct applications of Newton’s Laws of Motion to the individual atoms in the system, and are conceptually the easiest to implement. An advantage of this procedure is that the simulation yields important information not only about the intermediate states and the mechanisms which produced them, but also provides the rates at which these processes occur. These intermediate conformational states have repeatedly been implicated in many known biological function [1], [2]. Unfortunately, this albeit correct, but naive approach quickly leads to intractable models and prohibitive computational expense when applied to systems involving many atoms. As a result, researcher often grossly over simplify the system move to non-deterministic methods such as Monte Carlo, which effectively remove dynamics from the system, or use undesirably gross model simplification. Because of these forward dynamics performance difficulties, potentially important mechanisms governing biopolymer structure have not been adequately explored and/or identified. The methods and algorithms described in this paper are intended to extend the capabilities of the simulation techniques for such systems so that the forward dynamics can better predict the non-equilibrium behavior of these systems, thus complementing Monte Carlo, while retaining much useful intermediate process and temporal information.
Ultrasound Mediated Enhancement of Nanoparticle Uptake in PC-3 Cancer Cells
Authors: Thomas Antony , Baldwin Paige , Liu Yaling
Published: November 2013

Ultrasound in the presence of microbubbles brings in transient increase in cell membrane permeability, which allows the entry of foreign molecules into cells. This platform has been applied in in vitro and in vivo gene delivery studies in recent years[1–2]. The frequently used microbubbles are air or inert gas encapsulated in a protein, lipid or polymer which is commonly used as FDA approved contrast agents in diagnostic ultrasound. On exposure to ultrasound the microbubbles lead to formation of small pores on the cell membrane. This work concentrates on application of this platform to enhance cellular uptake of nanoparticles and thereby achieve enhanced drug delivery. Nanoparticles can be manipulated at the nano level and have been applied in the realm of cancer detection and treatment for imaging, targeting tumors, and drug delivery purposes [2].
Intrathecal Magnetic Drug Targeting: A New Approach to Treating Diseases of the Central Nervous System
Authors: Lueshen Eric , Venugopal Indu , Linninger Andreas
Published: November 2013

Intrathecal (IT) drug delivery is a standard technique which involves direct injection of drugs into the cerebrospinal fluid (CSF)-filled space within the spinal canal to treat many diseases of the central nervous system. Currently, in order to reach the therapeutic drug concentration at certain locations within the spinal canal, high drug doses are used. With no method to deliver the large drug doses locally, current IT drug delivery treatments are hindered with wide drug distributions throughout the central nervous system (CNS) which cause harmful side effects. In order to overcome the current limitations of IT drug delivery, we have developed the novel method of intrathecal magnetic drug targeting (IT-MDT). Gold-coated magnetite nanoparticles are infused into a physiologically and anatomically relevant in vitro human spine model and then targeted to a specific site using external magnetic fields, resulting in a substantial increase in therapeutic nanoparticle localization at the site of interest. Experiments aiming to determine the effect of key parameters such as magnet strength, duration of magnetic field exposure, location of magnetic field, and ferrous implants on the collection efficiency of our superparamagnetic nanoparticles in the targeting region were performed. Our experiments indicate that intrathecal magnetic drug targeting and implant-assisted IT-MDT are promising techniques for concentrating and localizing drug-functionalized nanoparticles at required target sites within the spinal canal for potential treatment of diseases affecting the central nervous system.
Magnetic Nanoparticle Hyperthermia Cancer Therapy Temperature Distribution Modeling and Validation
Authors: Stigliano Robert V. , Shubitidze Fridon , Hoopes P. Jack
Published: November 2013

The use of magnetic nanoparticles (mNP’s) in hyperthermia therapy for the treatment of cancer has been receiving increasing interest in the past few decades. It is known that heating cancerous tissues to temperatures above physiologically normal levels will cause cytotoxicity. In mNP hyperthermia, mNP’s are either injected intravenously or directly into the tumor site. In many tumor types the nanoparticles are invaginated into the cancer cells and aggregated into endosomes. Local temperature increases are achievable by exposing tumors containing mNP’s to an alternating magnetic field (AMF). The proximity of the mNP’s has a strong influence on their ability to generate heat due to inter-particle magnetic interaction effects [1, 2]. Taking this effect into account is important when modeling the heating characteristics of mNP’s.
Mechanism of Cell Lysis in Microfluidic Channel With Integrated Nanocomposite Electrodes
Authors: Mishra Madhusmita , Koduri Anil Krishna , Chandra Aman , Mahapatra D. Roy , Hegde G. M.
Published: November 2013

This paper reports on the characterization of an integrated micro-fluidic platform for controlled electrical lysis of biological cells and subsequent extraction of intracellular biomolecules. The proposed methodology is capable of high throughput electrical cell lysis facilitated by nano-composite coated electrodes. The nano-composites are synthesized using Carbon Nanotube and ZnO nanorod dispersion in polymer. Bacterial cells are used to demonstrate the lysis performance of these nanocomposite electrodes. Investigation of electrical lysis in the microchannel is carried out under different parameters, one with continuous DC application and the other under DC biased AC electric field. Lysis in DC field is dependent on optimal field strength and governed by the cell type. By introducing the AC electrical field, the electrokinetics is controlled to prevent cell clogging in the micro-channel and ensure uniform cell dispersion and lysis. Lysis mechanism is analyzed with time-resolved fluorescence imaging which reveal the time scale of electrical lysis and explain the dynamic behavior of GFP-expressing E. coli cells under the electric field induced by nanocomposite electrodes. The DNA and protein samples extracted after lysis are compared with those obtained from a conventional chemical lysis method by using a UV–Visible spectroscopy and fluorimetry. The paper also focuses on the mechanistic understanding of the nano-composite coating material and the film thickness on the leakage charge densities which lead to differential lysis efficiency.
In Vitro Cancer Metastasis Induced by Mechanical Force
Authors: Tang Xin , Saif Taher
Published: November 2013

Based on the American Cancer Society’s report at 2004, after 50-year’s efforts in bio-chemical medicine development, the U.S.A. cancer mortality is 193.9 per 100,000 persons, which is not significantly reduced from that at 1950, 185.8 per 100,000 persons. One critical reason for the clinical inefficacy is that it is not identified what signals trigger the onset of metastasis. 90% of cancer deaths are caused by metastases (1–6). During metastasis, malignant cancer cells detach from the parent cancer tumor to invade new organs (5–7). Although the primary tumor can be readily removed by surgery if detected in time, metastasis cannot be cured effectively due to the presence of numerous secondary tumors. Here we present, for the first time, that cancer cells can exhibit metastasis like phenotype (MLP) in vitro when they are experiencing appropriate mechanical stimuli.
In Vivo Delivery of IL-1ra From PLGA Microspheres Prevents IL-1β Induced Glycosaminoglycan Loss in the Rat Caudal Intervertebral Disc
Authors: Gorth Deborah J. , Martin John T. , Dodge George R. , Hebela Nader M. , Malhotra Neil R. , Mauck Robert L. , Elliott Dawn M. , Smith Lachlan J.
Published: November 2013

Inflammation plays a central role in the progression of disc degeneration, which is strongly implicated as a cause of low back pain. The objectives of this in vivo study were: first to investigate whether PLGA microspheres could be retained in the disc, and second to test whether IL-1ra delivered from those microspheres could effectively inhibit IL-1β induced extracellular matrix loss using a rat caudal disc model. Three caudal disc levels (C6–7 to C8–9) of 6 Sprague-Dawley rats were exposed via a dorsal midline incision for treatment. Fluorescently labeled microspheres were clearly visible in the disc at all time points except 8 weeks. The GAG content of discs injected with IL-1β alone was significantly lower than that of the intact controls and the microsphere treatment group. For discs injected with both IL-1β and IL-1ra microspheres, GAG content was not different from the intact control. In this study we demonstrated for the first time that IL-1ra delivered from microspheres prevents IL-1β induced GAG loss in vivo, and that microspheres are retained in the disc space for at least 4 weeks.
Rapid In Vivo Assessment of the Nano/Bio Interface
Authors: Tanguay Robert L. , Truong Lisa , Zaikova Tatiana , Hutchison James E.
Published: November 2013

Recent advances in nanoscience offer great promise for the nanomedicine sector. These advances in the nanotechnology field will undoubtedly increase both human and environmental exposures to engineered nanomaterials. Whether these exposures pose a significant risk remains uncertain. Despite recent collective progress there remain gaps in our understanding of the nanomaterials physiochemical properties that drive or dictate biological compatibility. The development and implementation of rapid relevant and efficient testing strategies to assess these emerging materials prior to large-scale exposures could help advance this exciting field. I will present a powerful approach that utilizes a dynamic in vivo zebrafish embryonic assay to rapidly define the biological responses to nanomaterial exposures. Early developmental life stages are often uniquely sensitive to environmental insults, due in part to the enormous changes in cellular differentiation, proliferation and migration required to form the required cell types, tissues and organs. Molecular signaling underlies all of these processes. Most toxic responses result from disruption of proper molecular signaling, thus, early developmental life stages are perhaps the ideal life stage to determine if nanomaterials perturb normal biological pathways. Through automation and rapid throughput approaches, a systematic and iterative strategy has been deployed to help elucidate the nanomaterials properties that drive biological responses.
Development of a Biomimetic Electrospun Microfibrous Scaffold With Multiwall Carbon Nanotubes for Cartilage Regeneration
Authors: Holmes Benjamin , Castro Nathan J. , Li Jian , Zhang Lijie Grace
Published: November 2013

Cartilage defects, which are caused by a variety of reasons such as traumatic injuries, osteoarthritis, or osteoporosis, represent common and severe clinical problems. Each year, over 6 million people visit hospitals in the U.S. for various knee, wrist, and ankle problems. As modern medicine advances, new and novel methodologies have been explored and developed in order to solve and improve current medical problems. One of the areas of investigation that has thus far proven to be very promising is tissue engineering [1, 2]. Since cartilage matrix is nanocomposite, the goal of the current work is to use nanomaterials and nanofabrication methods to create novel biologically inspired tissue engineered cartilage scaffolds for facilitating human bone marrow mesenchymal stem cell (MSC) chondrogenesis. For this purpose, through electrospinning techniques, we designed a series of novel 3D biomimetic nanostructured scaffolds based on carbon nanotubes and biocompatible poly(L-lactic acid) (PLLA) polymers. Specifically, a series of electrospun fibrous PLLA scaffolds with controlled fiber dimension were fabricated in this study. In vitro hMSC studies showed that stem cells prefer to attach in the scaffolds with smaller fiber diameter. More importantly, our in vitro differentiation results demonstrated that incorporation of the biomimetic carbon nanotubes and poly L-lysine coating can induce more chondrogenic differentiations of MSCs than controls, which make them promising for cartilage tissue engineering applications.
Fully Biodegradable Magnetic Micro-Nanoparticles: A New Platform for Tissue Regeneration and Theranostic
Authors: Sandri Monica , Iafisco Michele , Panseri Silvia , Savini Elisa , Tampieri Anna
Published: November 2013

Nowadays, magnetic materials are receiving special attention due to their potential applications in different fields and in particular in medicine. Magnetic micro-nano-particles have been progressively employed as support materials for enzyme immobilization, and have been used as drug-delivery vehicles, contrast agents for magnetic resonance imaging as well as heat mediators for hyperthermia-based anti-cancer treatments and many other exciting biomedical applications. Magnetic materials have also attracted a big interest in the field of bone tissue regeneration because it has been demonstrated that magnetic nanoparticles have effect of osteoinduction even without external magnetic force. Therefore, one of the most big challenge in this field is the production of magnetic materials with good biocompatibility and biodegradability. In fact, the long-term effects in the human body of iron oxide (maghemite or magnetite), the most popular magnetic phase used in medicine and biotechnology, are not yet completely assessed. To this aim, in this work we developed an innovative biocompatible and bioresorbable superparamagnetic-like phase by doping nano-hydroxyapatite with Fe2+/Fe3+ ions (FeHA). Moreover the same magnetic nanoparticles were used as nano-particulate emulsifier for the preparation of hollow hybrid Fe-HA-poly(L-lactic) acid (PLLA) micro-nano-spheres. PLLA has been used because poly(α-hydroxy-esters) are the most frequently used synthetic polymers for biomedical applications owing to their biocompatibility, hydrolytic degradation process and proper mechanical properties. These micro-nanospheres could be used as new type of scaffold for hard tissue regeneration. In fact, spherical scaffold display several advantages respect to the monolithic counterpart e.g., (i) improving control over sustained delivery of therapeutic agents, signalling biomolecules and even pluripotent stem cells, (ii) serving as stimulus-sensitive delivery vehicles for triggered release, (iii) introducing porosity and/or improve the mechanical properties of bulk scaffolds by acting as porogen or reinforcement phase, (iv) supplying compartmentalized micro-reactors for dedicated biochemical processes, (v) functioning as cell delivery vehicle, and, finally, (vi) giving possibility of preparing injectable and/or mouldable formulations to be applied by using minimally invasive surgery. Moreover, the same magnetic materials could find applications in nanomedicine as a multifunctional carrier. Their magnetic functionality could be utilized to move them into the body towards target organs by an external magnetic field. Furthermore, the superparamagnetic feature of the nanoparticles could allow to tailor the release of the therapeutic agent by switching (on-off) the external magnetic field and/or to treat cancer cells by hyperthermia.
An Innovative Approach for Curcumin Delivery for Breast Cancer Using Albumin Nanoparticles
Authors: Soucy P. , Ehringer W. , Klinge C. , Frieboes H. , Gobin A.
Published: November 2013

Triple-negative breast cancer (TNBC) accounts for ∼25% of breast cancer among premenopausal African-American and Latino women1. Curcumin (diferuloylmethane; CCM), a natural polyphenol extracted from turmeric, has chemopreventive and chemotherapeutic activity in various cancers 2,3 and inhibits growth and invasion of TNBC/basal-like MDA-MB-231 human breast cancer cells 4. CCM has been reported to affect all stages of tumor progression and metastases due to its interactions with multiple targets. We employ a novel approach utilizing both computational and experimental modeling to characterize and analyze TNBC and the 3D tumor microenvironment responses to albumin bound CCM particles (ACP) versus CCM alone.
Tumor-on-Chip: Simulation of Complex Transport Around Tumor
Authors: Kwak Bongseop , Park Kinam , Han Bumsoo
Published: November 2013

Nanoparticles (NP) offer great potential as drug carriers for targeted delivery to tumor by increasing the delivery efficacy and reducing non-specific accumulation at non-targeted sites [1]. Despite these promising early outcomes [2], the NP delivery to target tumor site is still significantly limited due to complex in vivo transport barriers [3–5]. In order to improve the in vivo delivery efficacy, the NPs should be designed considering all these complex transport barriers beyond currently used enhanced permeation and retention (EPR) effect [6]. However, testing of NP delivery are primarily based on simple 2D or 3D in vitro cell cultures or animal models. However, these static 2D or 3D tumor models oversimplify the actual in vivo tumor environment including the absence of tissue-tissue interactions such as blood-endothelium, endothelium-intersititum, high interstitial fluid pressure, and interstitium-lymphatics [2, 3]. The animal models can provide the testbed with these tissue-tissue interactions, but it is very difficult to establish quantitative understanding of the NP transport at these tissue-tissue interfaces. To address these challenges and bridge the in vitro static models with the animal models, here we developed a 3D multi-layered microfluidic system that mimics the tissue-tissue interactions at tumor microenvironment is developed. The system is then used to investigate the transvascular and interstitial transport of NPs in tumor.