bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of Interleukin‐22 in Myasthenia Gravis
Authors: Zheng S. , Dou C. , Xin N. , Wang J. , Wang J. , Li P. , Fu L. , Shen X. , Cui G. , Dong R. , Lu J. , Zhang Y.
Published: April 2013

IL‐17 and IL‐22 are implicated in the pathogenesis of autoimmune diseases. The roles of IL‐22 in the pathophysiology of myasthenia gravis (MG) remain unsettled. The aim of this study was to investigate the possible relationship between serum IL‐22, IL‐17 levels, anti‐acetylcholine receptor antibody (anti‐AChR Ab) titres and clinical parameters in patients with MG. The serum IL‐22, IL‐17 levels and anti‐AChR Ab titres were tested by enzyme‐linked immunosorbent assay (ELISA), while the expression of IL‐22 and IL‐17 mRNAs in peripheral blood mononuclear cells (PBMC) from healthy and MG subjects were detected by quantitative real‐time PCR (qRT‐PCR). Furthermore, PBMC from 12 patients with generalized MG were purified and treated with recombinant human IL‐22 (rhIL‐22), the IL‐17 levels of supernatant were detected by ELISA. We found that the IL‐17 levels were significantly increased, but IL‐22 levels were significantly decreased in the serum of patients with MG compared with healthy controls. Consistantly, a significant decrease in IL‐22 mRNA levels and an increase in IL‐17 mRNA levels were detected in PBMC collected from patients with MG, compared with healthy controls. A negative correlation between IL‐22 mRNA in PBMC, serum IL‐22 and serum anti‐AChR Ab levels was found in patients with MG. Moreover, in cultured MG PBMC treated with recombinant human IL‐22 (rhIL‐22), the IL‐17 levels were decreased in a dose‐dependent manner. Our findings indicated a possible role of IL‐22 as a protective factor in MG.
Characterization of a novel allele, HLA‐DQB1*06:47
Authors: He J. ‐J. , Zhang W. , He J. , Zhu F. ‐M. , Lv H. ‐J.
Published: April 2013

HLA‐DQB1*06:47 has one base substitution at position 618C>A in exon 3 from HLA‐DQB1*06:02:01.
Multicultural learning: parent encounters with difference in a Birmingham primary school
Authors: Wilson Helen F
Published: April 2013

In the UK, schools are considered vital to the realisation of intercultural cities, to the strengthening of community relations and to the development of new forms of social learning. This paper brings work on the geographies of education and learning together with work on the challenges of living with difference, to examine how the routines and repetitive interactions of everyday school life shape the capacities of parents to live with difference. Utilising research with white British parents at a multicultural primary school in Birmingham, UK, the paper builds on the growing interest in the spaces and theories of urban encounter to extend work that has examined the value of shared school spaces. While attending to the (re)production of social difference and the problematic accounts of anxiety, hierarchy and belonging that fracture the school community, the paper also examines the shared parental commitments and aspirations that underpin the motivations for intercultural dialogue and learning. In so doing, the paper details how existing knowledges and ways of living are called into question and gradually altered through personal work, pragmatic negotiation and the development of practical competencies and calls for much greater emphasis on these small and incremental changes in future work.
Comparison of complication rates in dogs with nasoesophageal versus nasogastric feeding tubes
Authors: Yu Melissa K. , Freeman Lisa M. , Heinze Cailin R. , Parker Valerie J. , Linder Deborah E.
Published: April 2013

Abstract

Objective

To compare complication rates between nasoesophageal (NE) and nasogastric (NG) feeding tubes in dogs.

Design

Retrospective study.

Setting

University referral veterinary hospital.

Animals

A total of 46 dogs that were fed through a NE (n= 28) or NG (n= 18) tube between January 2007 and December 2011 and that also had either thoracic radiography or computed tomography performed so that location of the distal tip of the tube in either the esophagus or stomach could be confirmed.

Interventions

None.

Measurements and Main Results

The medical record of each eligible case was reviewed and data recorded included signalment, underlying disease, body weight, body condition score, medications, duration of feeding, diet used, and complications observed (ie, vomiting, regurgitation, diarrhea, early tube removal, clogged tube, epistaxis, pulmonary aspiration, hyperglycemia, and refeeding syndrome). Dogs with NE tubes were significantly younger than dogs with NG tubes (P= 0.03) but there were no other significant differences in signalment, underlying disease, medications, duration of anorexia, percent of resting energy requirement achieved, or change in weight during tube feeding. There also was no significant difference between the NE and NG groups for any of the recorded complications. Significantly fewer dogs in the NE group died or were euthanized (3/28) compared to the NG group (7/18;P= 0.02) but outcome was not associated with age, underlying disease, or any of the recorded tube complications.

Conclusions

This study did not identify a difference in complication rate between NE and NG feeding tubes in dogs. Additional studies are required to determine the optimal terminal location of feeding tubes in dogs.
Preliminary evaluation of the utility of comparing SpO2/FiO2and PaO2/FiO2ratios in dogs
Authors: Calabro Janine M. , Prittie Jennifer E. , Palma Douglas A.
Published: April 2013

Objective

To determine whether the ratio of pulse oximetry saturation/fraction of inspired oxygen (SpO2/FiO2, [SF]) correlates with the ratio of partial pressure of oxygen in arterial blood/FiO2(PaO2/FiO2, [PF]) in dogs.

Design

Prospective, observational pilot study.

Setting

Urban tertiary veterinary referral center.

Animals

Thirty‐eight client‐owned dogs requiring assessment of oxygenation.

Interventions

None.

Measurements and Main Results

Arterial blood gas analysis with co‐oximetry was performed on samples obtained from the dorsal pedal artery. Median SpO2was 91.5% (range 80–97%) and median PaO2was 70.1 mmHg (range 44.5–103.8 mmHg). Hypoventilation was uncommon and venous admixture was the predominant cause of hypoxemia in this population. Median SF was 435.7 (range 381.0–461.9) and median PF was 334.0 (range 211.9–494.3). Nine dogs (23.6%) had PF <300; no dogs had PF below 200. SF and PF were correlated (ρ = 0.618,P< 0.01).

Conclusions

SF and PF in dogs spontaneously breathing room air have good correlation, suggesting that SF may be a useful, noninvasive surrogate for PF when assessing oxygenation in canine patients. Further studies are warranted to confirm and validate this relationship in spontaneously breathing and mechanically ventilated dogs on varying levels of FiO2and to assess the ability of SF to predict outcome.
Investigation of the time evolution of STM-tip temperature during electron bombardment
Authors: Hellmann David , Worbes Ludwig , Kloppstech Konstantin , Könne Nils , Kittel Achim
Published: April 2013

In the field of scanning probe microscopy, great attention must be paid to the state of sample and probe with respect to unintentionally adsorbed molecules. There are many techniques for cleaning tips described in literature, among them the use of accelerated electrons as an energy source. So far, all of the setups described yielded either no or only indirect information about the probe's temperature reached during the cleaning procedure. The Near-Field Scanning Thermal Microscopy probe not only serves as scanning tunneling microscope tip, but also includes a thermosensor in the vicinity of the probe's apex. Since the tip's body mainly consists of glass, which has a softening point of 1100 K, it must not be heated excessively in order to prevent its destruction. The authors use electron bombardment for cleaning these unique sensors, while the thermosensor is used as feedback for an automated device which is controlling the procedure. Our findings reveal that probe temperatures of up to 1220 K can be reached for short periods of time without causing any damage. In this article, the authors describe the device as well as experimental data concerning the relation between the energies used for cleaning and the resulting temperature of the probe. The presented data might serve as an indicator for other setups where a direct measurement of the temperature of the apex is impossible.
The Cross-Bridge Spring: Can Cool Muscles Store Elastic Energy?
Authors: George N. T. , Irving T. C. , Williams C. D. , Daniel T. L.
Published: April 2013

Lock and Load in the Cold

Muscle extensibility can act as an energy storage vehicle, like springs bouncing back after being compressed.

George
et al.

(p.
1217
, published online 25 April) now show that energy can also be stored within muscles as a function of their natural temperature gradient. In hawkmoth muscle myofilaments, reduced cross-bridge cycling regionally constrains myofilaments, resulting in a "lock-spring lattice" that enables elastic energy storage as both the myofilaments and cross-bridges deform. Elastic energy stored in cross-bridges that remain bound and elastically deformed at the end of the first half of a contraction cycle can be released during the second half, thus serving as an additional elastic force. Such "bonus" energy may be especially important given the high energetic demands of flight, but because temperature gradients are a natural result of energy generation and heat dissipation in muscle, this mechanism could be more broadly important in locomotion systems.
Role of Tissue Protection in Lethal Respiratory Viral-Bacterial Coinfection
Authors: Jamieson Amanda M. , Pasman Lesley , Yu Shuang , Gamradt Pia , Homer Robert J. , Decker Thomas , Medzhitov Ruslan
Published: April 2013

Tolerance Needed

It's a common enough occurrence: You're sick as a dog with a cold, but the person in the office next door just has a few sniffles. What accounts for this difference? Most commonly, these sorts of differences are chalked up to differences in resistance—perhaps you have higher viral loads than your office mate. But such differences can also involve differences in the ability to tolerate the same amount of virus. Deciphering the contribution of resistance versus tolerance, however, is difficult.

Jamieson
et al.

(p.
1230
, published online 25 April) studied a mouse model of viral and bacterial co-infection where tolerance and resistance could be separated. Mice infected with influenza virus were more likely to succumb to a secondary infection with
Legionella pneumophila
as a result of impaired tolerance to tissue damage, rather than because of a difference in bacterial burden.
Draft Genome Sequence of MKD8, a Conjugal Recipient Mycobacterium smegmatis Strain
Authors: Gray Todd A. , Palumbo Michael J. , Derbyshire Keith M.
Published: April 2013

We report an annotated draft genome sequence of the
Mycobacterium smegmatis
strain MKD8. This strain acts as a recipient during conjugation with the reference
M. smegmatis
strain mc
2
155. While the genomes of the two strains are colinear and have similar sizes, extensive genome-wide sequence variation suggests rich diversity within the
M. smegmatis
clade.
Genome Sequence of a Novel Archaeal Fusellovirus Assembled from the Metagenome of a Mexican Hot Spring
Authors: Servín-Garcidueñas Luis E. , Peng Xu , Garrett Roger A. , Martínez-Romero Esperanza
Published: April 2013

The consensus genome sequence of a new member of the family
Fuselloviridae
designated as SMF1 (
Sulfolobales
Mexican fusellovirus 1) is presented. The complete circular genome was recovered from a metagenomic study of a Mexican hot spring. SMF1 exhibits an exceptional coding strand bias and a reduced set of fuselloviral core genes.
Management of mandibular deviation after mandibulectomy by simplified approach
Authors: Arora Varuni , Singh Kamleshwar , Agrawal Kaushal Kishor , Alvi Habib Ahmed
Published: April 2013

Unfavourable sequelae from mandibular surgeries include malocclusion and temporomandibular joint dysfunction. The management of the situation before these complications arise is largely based on experience. This report presents a case where mandibular deviation is decreased through an additional row of teeth in the maxillary removable partial denture, and by decreasing scar contracture in the surgical site by means of a simple exercise.
Chronic eosinophilic pneumonia: a paediatric case
Authors: Tassinari Davide , Di Silverio Carulli Chiara , Visciotti Francesca , Petrucci Roberta
Published: April 2013

Chronic eosinophilic pneumonia (CEP) is a rare disorder in children, characterised by respiratory and systemic symptoms, with a generally good prognosis. A 11-year-old asthmatic girl was admitted to our clinic with a 3-month history of progressive cough, dyspnoea, weight loss and asthenia. Peripheral blood eosinophilia, multiple bilateral pulmonary infiltrates to the x-ray, multiple nodules with a surrounding ground-glass halo and peripheral predominance to the chest CT suggested the diagnosis of eosinophilic lung disease (ELD). Further investigations ruled out other ELD and supported diagnosis of CEP. The response to oral corticosteroids was dramatic, no relapses were reported in 2-year follow-up while the patient was under inhaled corticosteroids for pre-existing asthma.
Splenic abcess owing to brucellosis
Authors: Jamil Gohar , Jamil Mujgan , Saif Al Nuaimi Noura , Taha Mazen
Published: April 2013

Brucellosis, caused by aerobic Gram-negative coccabacilli, is prevalent worldwide. It occurs mainly because of the consumption of unpasteurised milk and contact with animals. The disease is particularly hyperendemic in the Mediterranean region and Arabian Peninsula. Its high prevalence in the UAE continues to be a major health problem, causing significant morbidity and mortality. According to the Ministry of Health, 119 cases were reported in 2010, and most of those cases were patients aged over 45. Even though an effective treatment is available for this disease, treatment failure frequently occurs owing to delay in diagnosis, relapses and its prolonged clinical course. We present a 33-year-old man who was admitted to our internal medicine teaching unit service with non-specific symptoms. A workup revealedBrucellain the blood cultures. An abdominal ultrasound showed multiple splenic abscesses. After treatment with triple therapy, the patient has remained asymptomatic at 2 years follow-up.
Cryptococcal sternal osteomyelitis in a healthy woman: a review ofCryptococcus neoformans
Authors: Jain Deepali , Najjar Mazen , Azher Qazi , Bachuwa Ghassan
Published: April 2013

Cryptococcus, an opportunistic yeast, known to afflict immune-compromised patients is often overlooked in immune-competent patients. This has led to increasing morbidity and mortality worldwide. We present a case ofCryptococcuscausing sternal osteomyelitis in an immune-competent individual. Till date no case ofCryptococcuscausing sternal osteomyelitis in an immune-competent patient has been reported in the English literature since 1946–2011. With the rising incidence ofCryptococcusinfection it should be included among the list of infections causing osteomyelitis. Early detection and prompt treatment can decrease both morbidity and mortality.
Pneumothorax necessitans in a patient with trapped lung and rheumatoid arthritis
Authors: Ahmed Rumman , Ahmed Usama , Syed Imran
Published: April 2013

The authors report the case of a patient with a background of trapped lung following thoracocentesis who developed an anterolateral intercostal pneumothoracocele resulting in a pneumothorax necessitans (PN). Our purpose is to highlight the pathophysiology and interesting radiological features associated with PN in trapped lung. Our case is particularly unique due to the subacute nature of its presentation in a patient with rheumatoid arthritis and unusual pre-existing lung pathology.
The Newport eye: design and initial evaluation of a novel foreign body training phantom
Authors: Marson Ben A , Sutton Lynne J
Published: April 2013

To improve SHO confidence in corneal foreign body removal, a novel training phantom is proposed. This phantom is a polyvinyl and gelatine-based model, easily fabricated in the emergency department (ED). Use of the phantom results in a significant improvement in SHO confidence, and therefore, makes a useful, cost-effective adjunct for ED training.
Aberrant anaplastic lymphoma kinase expression in high-grade pulmonary neuroendocrine carcinoma
Authors: Nakamura Harumi , Tsuta Koji , Yoshida Akihiko , Shibata Tatsuhiro , Wakai Susumu , Asamura Hisao , Furuta Koh , Tsuda Hitoshi
Published: April 2013

Aims

In lung cancer with anaplastic lymphoma kinase (ALK) gene rearrangement, accurate diagnosis is essential to identify patients who can be treated with a specific kinase inhibitor. Sensitive ALK immunostaining can provide nearly complete concordance with gene rearrangement status and is expected to serve as a surrogate biomarker for tailored treatment with an ALK inhibitor. In the present report, we describe aberrant ALK expression in a small proportion of pulmonary neuroendocrine carcinomas (NECs) that do not haveALKgene alteration.

Methods

A total of 227 pulmonary NECs were assembled on tissue microarrays and were subjected to highly sensitive ALK staining methods.

Results

We observed focal positivity with heterogeneous intensity in 2 (2.9%) of 69 small-cell carcinomas and 1 (0.9%) of 106 large-cell NECs. In contrast, 52 carcinoid tumours were all negative for ALK expression. NeitherALKrearrangement nor amplification was observed using fluorescence in situ hybridisation, and no somatic mutation was detected in three ALK positive NECs.

Conclusions

Thus, this aberrant expression is probably of a wild-type ALK and a potential pitfall when implementing sensitive ALK immunohistochemistry in the molecular diagnosis of lung cancer.
Seeing-off of dead bodies at death discharges in Japan
Authors: Masaki Sakiko , Asai Atsushi
Published: April 2013

For most death discharge (‘shibou tai-in’) patients, hospitals in Japan offer seeing-off (‘omiokuri’) services, a practice characteristic of Japanese culture. When a patient dies, nurses usually perform after-death procedures before transferring the body to the mortuary, where the nurses and doctors gather to provide the seeing-off service. This study was carried out to determine differences between the nurses’ and bereaved families’ opinions and thoughts regarding the seeing-off service. Semi-structured interviews were conducted with 17 nurses (focus group interviews) and 6 bereaved families (personal interviews). The interviews assessed: (1) the reasons why nurses provided seeing-off services; (2) thoughts during the seeing-off service; (3) impressions of the mortuary rituals; and (4) the necessity for the seeing-off service. The results indicated that nurses expressed their courtesy and sense of appreciation during the seeing-off service, which was recognised as an important nursing role. In contrast, bereaved families felt thankful but also doubtful, particularly as regards the mortuary rituals. In light of the differences in perspective between nurses and families, it may be that the level of satisfaction with the seeing-off service is largely affected by the relationship between the family and the medical professionals before the patient's death. Our study also notes that Japanese people respect the dead body and treat it with care, reflecting the unique culture and customs of Japan.
The Art and the Science of Equine Surgery
Authors: Greet Tim
Published: April 2013

The horse was the primary consideration for veterinarians when Veterinary Record was first published in 1888. Here, Tim Greet describes the scientific developments in equine surgery since then, while also highlighting the need to employ the art.
Synthesis and Electrochemical Properties of Novel Co2+/Co3+ Layered Ordered Rock-Salt Structure Type Li0.75Ca0.25CoO¬2
Authors: Blakely Colin K. , Bruno Shaun R. , Davis Joshua D. , Poltavets Viktor V.
Published: April 2013

New layered transition metal oxide cathode material, Li0.75Ca0.25CoO2 (Space Group = P63/mmc; a = 2.817 Å, b = 2.817 Å, c = 10.79 Å ß = 120{degree sign}) was prepared by a multistep synthetic technique. Electrochemical cycling of 0.75 Li+ per formula unit utilizes both the Co3+/Co4+ and Co2+/Co3+ redox couples. The presence of Ca2+ between CoO2 layers results in low volume difference (~0.8%) between fully lithiated and delithiated materials.
Processing of Silicon Anodes by Aerosol Jet Printing
Authors: Schmerling Marcus , Wirth Ingo , Kügeler Carsten
Published: April 2013

Aerosol Jet® Printing is investigated as deposition technique for silicon as anode material for lithium-ion batteries. Binder free structures with silicon particles were deposited and galvanostaticly cycled. The morphological changes of the electrode were examined with SEM, Raman spectroscopy and x-ray photon spectroscopy (XPS). The fast degradation is explained with the huge amount of side reactions building LiF and the low conductivity of the intrinsic silicon particles. The addition of conducting carbon did not affect cycling stability.
High Performance and Safe Electrolyte Development
Authors: Xing Weibing , Buettner-Garrett Josh , Kelly Joseph , Krysiak Mike , Zhang Jian
Published: April 2013

We report efforts at ADA Technologies, Inc. to tackle the challenges conventional Li-ion electrolytes are facing using design-of-experiment (DOE) approach to systematically study the role of electrolyte components and their interactions in Li-ion cells operated at a wide range of temperatures and near 5V cell voltage. The role of room temperature ionic liquids (IL) as an electrolyte component on performance and safety was studied. Lithium salts with good stability characteristics, such as LiTFSI, LiBOB, LiBF4, were evaluated along with LiPF6 used in conventional electrolytes. The role of individual carbonate and ester solvents on performance was also studied.
Applying Lumped Capacitance Method to Calculate Heat Rates in the Charge/Discharge of Prismatic Lithium Cells in Natural Convection
Authors: Bazinski Stephen , Wang Xia
Published: April 2013

To determine heat rates is very critical in designing thermal management of the lithium-ion battery under different rates of charge and discharge. The objective of this research is to determine heat rates in charge/discharge of a prismatic lithium ion battery under natural condition by applying the lumped capacitance method. A prismatic lithium cell is treated as a lumped capacitance model during natural convection cooling and is found to have extremely good correlation to measured data. This is due in large part to the high area-to-volume ratio. As a result, the average convection coefficient (that was found from a best-fitting curve exercise) was used in an energy balance equation. This made it possible to determine the rate of heat generated by the cell under different C-rates of discharge. It was found that the average rate of heat generation during an entire discharge cycle has a linear relationship with the C-rate.
A Novel Sodium-Ion Rechargeable Battery
Authors: Minakshi Manickam , Ralph David
Published: April 2013

Energy storage is always an important issue and will be far more important in the future than at any time in the past. Storing large amounts of electricity cheaply, something that will be essential for making renewable energy the primary source, rather than just the supplemental source it is a current challenge. Such storage will make it practical to store energy from wind turbines and solar farms for later use. To achieve these, sodium-based energy storage systems have been identified as a key technology for the future as the lithium technology is more expensive. Existing sodium technologies work at high temperature, where molten sodium and molten sulphur are the anode and cathode respectively and they have never found widespread use. An alternative strategic approach used in this study is water-based sodium-ion intercalation cell (MnO2|NaOH|NaCo1/3Ni1/3Mn1/3PO4) for a promising low temperature energy storage device.
All-Solid Thin-Filmed Li-Ion Rechargeable Battery with Aligned Carbon Nanotube Anode
Authors: Baba Mamoru , Izumida Fukunori , Ye Rongbin , Yoshida Jun , Ushirokawa Tomohito , Ohta Koji , Kusunoki Michiko
Published: April 2013

A thin-filmed Li-ion rechargeable battery using a carbon nanotube (CNT) anode was realized for the first time. The CNT anode suitable for the thin-filmed battery was successfully fabricated on a SiC surface by using both the SiC surface decomposition technique for growth of an aligned CNT film and the Ar-sputter etching technique for a smooth surface of the CNT film. The present CNT anode battery showed good cell characteristics of a high cell voltage between 3 and 4 V, a large capacity, and long cycle performance over 2000 cycles. Especially, the maximum capacity obtained here reached roughly 1460 mAh/cm3 over the theoretical value of graphite anode.
Investigation of Fuel Cell Materials and Liquid Water Transport by Means of Synchrotron Imaging
Authors: Markötter Henning , Haußmann Jan , Alink Robert , Dittmann Katja , Tötzke Christian , Krüger Philipp , Klages Merle , Arlt Tobias , Müller Bernd , Riesemeier Heinrich , Scholta Joachim , Gerteisen Dietmar , Manke Ingo , Banhart John
Published: April 2013

Synchrotron imaging allows addressing various important issues in fuel cell research, for example water distribution and transport. The water distribution in polymer electrolyte membrane fuel cells (PEMFCs) was observed quasi in-situ directly after operation by means of synchrotron tomography. The 3D data set was compared with the tomogram of a dry cell in order to separate the water distribution from cell materials. Engineered transport pathways realized by perforating holes through the gas diffusion layer (GDL) are a recent approach to optimize water transport and cell performance. For some parameter sets a cell performance increase and an improvement of stabilization have already been proven. We present high resolution investigations of the water distribution in perforated GDLs of operating PEMFCs by means of in-situ synchrotron radiography. The surrounding areas of the holes exhibited a distinct hydrophilic character.
Study Thermal Stability of Silicate Olivine Cathode Materials with and without Coating
Authors: Wei Qiang , Zheng Haixing , Huang Yuhong
Published: April 2013

In this research, oxygen release from Li2MnSiO4, Li2Mn0.5Fe0.5SiO4, and chemically delithiated Li2Mn0.5Fe0.5SiO4 at temperatures up to 800{degree sign}C was studied by thermogravimetric analysis (TGA). The results show that the silicate cathode materials release less oxygen (< 4 % weight loss up to 800{degree sign}C) at high temperatures than other cathode materials including LiFePO4, 5%; LiMnPO4, 7%; LiCoO2, 6%, and NCA, 22%. Limited DSC studies on carbon-coated Li2Mn0.5Fe0.5SiO4 show that after 45 cycles at 1/16C rate, the fully charged Li2-xMn0.5Fe0.5SiO4 in presence of electrolyte releases more heat at lower temperatures in comparison to published data on Li2-xMnSiO4 and Li2-xFeSiO4.
Electrochemical Applications of Electrolytes based on Ionic Liquids
Authors: Neto M.J. , Leones R. , Sentanin F. , Esperança J.M. S. S. , Medeiros Maria Jose , Pawlicka A. , Silva Maria Manuela
Published: April 2013

The potential utility of room temperature ionic liquids as electrolytes in current electrochemical applications has been explored. Hence, the electrochemical behavior of [Ni(tmc)]Br2 complex at a glassy carbon electrode in the absence or in the presence of unsaturated halides in the ionic liquids, 1-ethyl-3-methylimidazolium ethylsulfate, [C2mim][C2SO4] and N,N,N-trimethyl-N-(2-hydroxyethyl) ammonium bis(trifluoromethylsulfonyl)imide, [N1 1 1 2(OH)][NTf2], has been examined by cyclic voltammetry. It was observed that [Ni(tmc)]2+ complex is reduced in a reversible one-electron step and the electrogenerated [Ni(tmc)]+ complex catalytically reduces the carbon-halogen bond of unsaturated halides. The potencial use of natural ionic conducting polymer matrixes was also investigated. Samples of natural macromolecules-based electrolytes with the ionic liquid 1-ethyl-3-methylimidazolium ethylsulfate, [C2mim][C2SO4], were prepared and characterized. The preliminary studies carried out with electrochromic devices (ECDs) incorporating optimized compositions have confirmed that these materials may perform as satisfactory multifunctional component layers in the field of ECD-based devices.
Physical Models of the Conductivity in Glucose Alkaline Fuel Cell
Authors: Rubin Z. , Mor Lea
Published: April 2013

The research is using simple physical models, considering either the empirical behavior of the solution's viscosity, or the consideration of ions and molecules colliding in solutions in a membraneless glucose-fueled alkaline fuel cell. The conductivity is expressed as a function of KOH and glucose concentrations. The equilibrium constant was determined for the reaction that glucose undergoes in the alkaline conditions in a glucose -fuelled alkaline fuel cell . The equilibrium constant was estimated for different KOH and glucose concentrations . The physical properties of the species (i.e. radii, thermal velocity) in an alkaline solution can be estimate by comparing the experimental results with the theory. The solution's viscosity, an empirical characteristic of the solution, is basically a function of parameters influencing the collision in the solution and is linear with the solute (glucose) concentration. This explains the mechanism by which the viscosity influences the solution conductivity
ZnO Nanostructures Prepared on LiAlO2 Substrates by Chemical Vapor Deposition
Authors: Tu Ya-Ting , Chen Cheng-Huan , Lu Cheng-Ying James , Huang Teng Hsing , Yan Tao , Wu Jih-Jen , Chou Mitch M.C. , Chang Liuwen
Published: April 2013

A two-step process of chemical vapor deposition for growing ZnO nanostructures on gamma-LiAlO2 (100) substrate was proposed. By taking advantage of the dual orientation characteristic of the substrate, scattered islands with a {10-10} azimuth orientation were first grown at 650oC to serve as a mask followed by a second-step process at relatively low temperatures of 450-500oC to grow {0001} oriented nanostructures. Two examples were given in this paper. Nanorods of 50-200 nm in size were prepared at a high growing pressure of 200 torr, and nanocones were obtained at 50 torr. The density of the nanostructures can be controlled by the growing time of the first-step process. Both nanostructures were free from threading dislocations and showed good luminescence characteristics.
Effect of androgenic-anabolic steroids and heavy strength training on patellar tendon morphological and mechanical properties
Authors: Seynnes Olivier R. , Kamandulis Sigitas , Kairaitis Ramutis , Helland Christian , Campbell Emma-Louise , Brazaitis Marius , Skurvydas Albertas , Narici Marco V.
Published: April 2013

Combined androgenic-anabolic steroids (AAS) and overloading affects tendon collagen metabolism and ultrastructure and is often associated with a higher risk of injury. The aim of this prospective study was to investigate whether such effects would be reflected in the patellar tendon properties of individuals with a history of long-term resistance training and AAS abuse (RTS group), compared with trained (RT) and untrained (CTRL) nonsteroids users. Tendon cross-sectional area (CSA), stiffness, Young's modulus, and toe limit strain were measured in vivo, from synchronized ultrasonography and dynamometry data. The patellar tendon of RT and RTS subjects was much stiffer and larger than in the CTRL group. However, stiffness and modulus were higher in the RTS group (26%, P < 0.05 and 30%, P < 0.01, respectively) than in the RT group. Conversely, tendon CSA was 15% ( P < 0.05) larger in the RT group than in RTS, although differences disappeared when this variable was normalized to quadriceps maximal isometric torque. Yet maximal tendon stress was higher in RTS than in RT (15%, P < 0.05), without any statistical difference in maximal strain and toe limit strain between groups. The present lack of difference in toe limit strain does not substantiate the hypothesis of changes in collagen crimp pattern associated with AAS abuse. However, these findings indicate that tendon adaptations from years of heavy resistance training are different in AAS users, suggesting differences in collagen remodeling. Some of these adaptations (e.g., higher stress) could be linked to a higher risk of tendon injury.
The gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung
Authors: Henderson A. Cortney , Sá Rui Carlos , Theilmann Rebecca J. , Buxton Richard B. , Prisk G. Kim , Hopkins Susan R.
Published: April 2013

The gravitational gradient of intrapleural pressure is suggested to be less in prone posture than supine. Thus the gravitational distribution of ventilation is expected to be more uniform prone, potentially affecting regional ventilation-perfusion (V̇a/Q̇) ratio. Using a novel functional lung magnetic resonance imaging technique to measure regional V̇a/Q̇ ratio, the gravitational gradients in proton density, ventilation, perfusion, and V̇a/Q̇ ratio were measured in prone and supine posture. Data were acquired in seven healthy subjects in a single sagittal slice of the right lung at functional residual capacity. Regional specific ventilation images quantified using specific ventilation imaging and proton density images obtained using a fast gradient-echo sequence were registered and smoothed to calculate regional alveolar ventilation. Perfusion was measured using arterial spin labeling. Ventilation (ml·min−1·ml−1) images were combined on a voxel-by-voxel basis with smoothed perfusion (ml·min−1·ml−1) images to obtain regional V̇a/Q̇ ratio. Data were averaged for voxels within 1-cm gravitational planes, starting from the most gravitationally dependent lung. The slope of the relationship between alveolar ventilation and vertical height was less prone than supine (−0.17 ± 0.10 ml·min−1·ml−1·cm−1supine, −0.040 ± 0.03 prone ml·min−1·ml−1·cm−1, P = 0.02) as was the slope of the perfusion-height relationship (−0.14 ± 0.05 ml·min−1·ml−1·cm−1supine, −0.08 ± 0.09 prone ml·min−1·ml−1·cm−1, P = 0.02). There was a significant gravitational gradient in V̇a/Q̇ ratio in both postures ( P < 0.05) that was less in prone (0.09 ± 0.08 cm−1supine, 0.04 ± 0.03 cm−1prone, P = 0.04). The gravitational gradients in ventilation, perfusion, and regional V̇a/Q̇ ratio were greater supine than prone, suggesting an interplay between thoracic cavity configuration, airway and vascular tree anatomy, and the effects of gravity on V̇a/Q̇ matching.
Monoclonal Antibody against the Ectodomain of E-Cadherin (DECMA-1) Suppresses Breast Carcinogenesis: Involvement of the HER/PI3K/Akt/mTOR and IAP Pathways
Authors: Brouxhon Sabine M. , Kyrkanides Stephanos , Teng Xiaofei , Raja Veena , O'Banion M. Kerry , Clarke Robert , Byers Stephen , Silberfeld Andrew , Tornos Carmen , Ma Li
Published: April 2013

Purpose: Although targeted therapies against HER2 have been one of the most successful therapeutic strategies for breast cancer, patients eventually developed acquired resistance from compensatory upregulation of alternate HERs and mitogen-activated protein kinase–phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling. As we and others have shown that the soluble ectodomain fragment of E-cadherin exerts prooncogenic effects via HER1/2–mediated binding and activation of downstream prosurvival pathways, we explored whether targeting this ectodomain [DECMA-1 monoclonal antibody (mAb)] was effective in the treatment of HER2-positive (HER2+) breast cancers.

Experimental Design: MMTV-PyMT transgenic mice and HER2+/E-cadherin–positive MCF-7 and BT474 trastuzumab-resistant (TtzmR) cells were treated with the DECMA-1 mAb. Antitumor responses were assessed by bromodeoxyuridine incorporation, apoptosis, and necrosis. The underlying intracellular prooncogenic pathways were explored using subcellular fractionation, immunoprecipitation, fluorescence microscopy, and immunoblotting.

Results: Treatment with DECMA-1 mAb significantly delayed tumor onset and attenuated tumor burden in MMTV-PyMT mice by reducing tumor cell proliferation and inducing apoptosis without any detectable cytotoxicity to mice or end-organs. In vitro treatment of MCF-7 and BT474 TtzmR cells reduced proliferation and induced cancer cell apoptosis. Importantly, this inhibition of breast tumorigenesis was due to concomitant downregulation, via ubiquitin-mediated degradation through the lysosome and proteasome pathways, of all HER family members, components of downstream PI3K/Akt/mTOR prosurvival signaling and suppression of inhibitor of apoptosis proteins.

Conclusions: Our results establish that the E-cadherin ectodomain-specific mAb DECMA-1 inhibits Ecad+/HER2+ breast cancers by hindering tumor growth and inducing apoptosis via downregulation of key oncogenic pathways involved in trastuzumab resistance, thereby establishing a novel therapeutic platform for the treatment of HER2+ breast cancers. Clin Cancer Res; 19(12); 3234–46. ©2013 AACR.
Japonicone A Suppresses Growth of Burkitt Lymphoma Cells through Its Effect on NF-κB
Authors: Li Xiaoguang , Yang Xinying , Liu Yanling , Gong Nuoxi , Yao Wenbo , Chen Peizhan , Qin Jiangjiang , Jin Huizi , Li Jingquan , Chu Ruiai , Shan Lei , Zhang Ruiwen , Zhang Weidong , Wang Hui
Published: April 2013

Purpose: NF-κB, a transcriptional regulator of diverse genes involved in cell survival, proliferation, adhesion, and apoptosis, has been implicated in various malignancies. We discovered a potent natural NF-κB inhibitor, Japonicone A, from the traditional herb Inula japonica Thunb, evaluated its preclinical pharmacology and therapeutic activity, and investigated the underlying mechanisms of action for its antitumor activity.

Experimental Design: Various types of cancer and normal cells were exposed to Japonicone A for cytotoxicity screening, followed by determination of cell apoptosis and cell-cycle arrest. Western blotting, immunostaining, and gene reporter assay were used to analyze NF-κB activity. Two xenograft models were used for therapeutic efficacy evaluation.

Results: Japonicone A killed cancer cells but had low cytotoxicity to normal cells. Burkitt lymphoma cells were particularly sensitive. Japonicone A inhibited the growth and proliferation of Raji, BJAB, and NAMALWA lymphoma cells and resulted in G2–M phase arrest and apoptosis. Furthermore, exposure of cells to Japonicone A caused inactivation of the TNF-α–TAK1–IKK-NF-κB axis and inhibition of TNF-α–stimulated NF-κB activity and nuclear translocation, followed by downregulation of NF-κB target genes involved in cell apoptosis (Bcl-2, Bcl-xL, XIAP, TRAF2) and in the cell cycle and growth (cyclin D, c-Myc). Moreover, Japonicone A inhibited local growth and dissemination of cancer cells to multiple organs in vivo.

Conclusion: Japonicone A exerts significant anticancer effects on Burkitt lymphoma cells in vitro and in vivo through targeting of the NF-κB signaling cascade. These results highlight the potential of Japonicone A as a chemotherapeutic agent and warrant its development as a therapy for lymphomas. Clin Cancer Res; 19(11); 2917–28. ©2013 AACR.
Receptor Affinity and Extracellular Domain Modifications Affect Tumor Recognition by ROR1-Specific Chimeric Antigen Receptor T Cells
Authors: Hudecek Michael , Lupo-Stanghellini Maria-Teresa , Kosasih Paula L. , Sommermeyer Daniel , Jensen Michael C. , Rader Christoph , Riddell Stanley R.
Published: April 2013

Purpose: The adoptive transfer of T cells modified to express a chimeric antigen receptor (CAR) comprised of an extracellular single-chain antibody (scFV) fragment specific for a tumor cell surface molecule, and linked to an intracellular signaling module, has activity in advanced malignancies. The receptor tyrosine kinase–like orphan receptor 1 (ROR1) is a tumor-associated molecule expressed in prevalent B-lymphoid and epithelial cancers and is absent on normal mature B cells and vital tissues, making it a candidate for CAR T-cell therapy.

Experimental Design: We constructed ROR1-CARs from scFVs with different affinities and containing extracellular IgG4-Fc spacer domains of different lengths, and evaluated the ability of T cells expressing each CAR to recognize ROR1+ hematopoietic and epithelial tumors in vitro, and to eliminate human mantle cell lymphoma (MCL) engrafted into immunodeficient mice.

Results: ROR1-CARs containing a short “Hinge-only” extracellular spacer conferred superior lysis of ROR1+ tumor cells and induction of T-cell effector functions compared with CARs with long “Hinge-CH2-CH3” spacers. CARs derived from a higher affinity scFV conferred maximum T-cell effector function against primary CLL and ROR1+ epithelial cancer lines in vitro without inducing activation-induced T-cell death. T cells modified with an optimal ROR1-CAR were equivalently effective as CD19-CAR–modified T cells in mediating regression of JeKo-1 MCL in immunodeficient mice.

Conclusions: Our results show that customizing spacer design and increasing affinity of ROR1-CARs enhances T-cell effector function and recognition of ROR1+ tumors. T cells modified with an optimized ROR1-CAR have significant antitumor efficacy in a preclinical model in vivo, suggesting they may be useful to treat ROR1+ tumors in clinical applications. Clin Cancer Res; 19(12); 3153–64. ©2013 AACR.
Human Anti-Macrophage Migration Inhibitory Factor Antibodies Inhibit Growth of Human Prostate Cancer Cells In Vitro and In Vivo
Authors: Hussain Filza , Freissmuth Michael , Völkel Dirk , Thiele Michael , Douillard Patrice , Antoine Gerhard , Thurner Patrick , Ehrlich Hartmut , Schwarz Hans-Peter , Scheiflinger Friedrich , Kerschbaumer Randolf J.
Published: April 2013

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine, originally discovered for its eponymous effect and now known for pleiotropic biologic properties in immunology and oncology. Circulating MIF levels are elevated in several types of human cancer including prostate cancer. MIF is released presumably by both stromal and tumor cells and enhances malignant growth and metastasis by diverse mechanisms, such as stimulating tumor cell proliferation, suppressing apoptotic death, facilitating invasion of the extracellular matrix, and promoting angiogenesis. Recently described fully human anti-MIF antibodies were tested in vitro and in vivo for their ability to influence growth rate and invasion of the human PC3 prostate cancer cell line. In vitro, the selected candidate antibodies BaxG03, BaxB01, and BaxM159 reduced cell growth and viability by inhibiting MIF-induced phosphorylation of the central kinases p44/42 mitogen-activated protein kinase [extracellular signal–regulated kinase-1 and -2 (ERK1/2)] and protein kinase B (AKT). Incubation of cells in the presence of the antibodies also promoted activation of caspase-3/7. The antibodies furthermore inhibited MIF-promoted invasion and chemotaxis as transmigration through Matrigel along a MIF gradient was impaired. In vivo, pharmacokinetic parameters (half-life, volume of distribution, and bioavailability) of the antibodies were determined and a proof-of-concept was obtained in a PC3-xenograft mouse model. Treatment with human anti-MIF antibodies blunted xenograft tumor growth in a dose-dependent manner. We therefore conclude that the anti-MIF antibodies described neutralize some of the key tumor-promoting activities of MIF and thus limit tumor growth in vivo. Mol Cancer Ther; 12(7); 1223–34. ©2013 AACR.
Integrative Genomic Characterization of Oral Squamous Cell Carcinoma Identifies Frequent Somatic Drivers
Authors: Pickering Curtis R. , Zhang Jiexin , Yoo Suk Young , Bengtsson Linnea , Moorthy Shhyam , Neskey David M. , Zhao Mei , Ortega Alves Marcus V. , Chang Kyle , Drummond Jennifer , Cortez Elsa , Xie Tong-xin , Zhang Di , Chung Woonbok , Issa Jean-Pierre J. , Zweidler-McKay Patrick A. , Wu Xifeng , El-Naggar Adel K. , Weinstein John N. , Wang Jing , Muzny Donna M. , Gibbs Richard A. , Wheeler David A. , Myers Jeffrey N. , Frederick Mitchell J.
Published: April 2013

The survival of patients with oral squamous cell carcinoma (OSCC) has not changed significantly in several decades, leading clinicians and investigators to search for promising molecular targets. To this end, we conducted comprehensive genomic analysis of gene expression, copy number, methylation, and point mutations in OSCC. Integrated analysis revealed more somatic events than previously reported, identifying four major driver pathways (mitogenic signaling, Notch, cell cycle, and TP53) and two additional key genes (FAT1, CASP8). The Notch pathway was defective in 66% of patients, and in follow-up studies of mechanism, functional NOTCH1 signaling inhibited proliferation of OSCC cell lines. Frequent mutation of caspase-8 (CASP8) defines a new molecular subtype of OSCC with few copy number changes. Although genomic alterations are dominated by loss of tumor suppressor genes, 80% of patients harbored at least one genomic alteration in a targetable gene, suggesting that novel approaches to treatment may be possible for this debilitating subset of head and neck cancers.

Significance: This is the first integrated genomic analysis of OSCC. Only through integrated multiplatform analysis was it possible to identify four key pathways. We also discovered a new disease subtype associated with CASP8 and HRAS mutation. Finally, many candidate targetable events were found and provide hope for future genomically driven therapeutic strategies. Cancer Discov; 3(7); 770–81. ©2013 AACR.

See related commentary by Iglesias-Bartolome et al., p. 722

This article is highlighted in the In This Issue feature, p. 705
Management of Pregnancies with Confirmed Cytomegalovirus Fetal Infection
Authors: Benoist Guillaume , Leruez-Ville Marianne , Magny Jean François , Jacquemard François , Salomon Laurent J. , Ville Yves
Published: April 2013

Systematic screening for cytomegalovirus (CMV) maternal infection is not recommended in most countries. Nevertheless, primary CMV infection will occur in around 1% of women. The vertical transmission rate is estimated to be around 30-50%. Newborns with congenital CMV infection remain asymptomatic in the majority of cases and around 10% will present with a wide range of abnormalities. Fetal infection can be diagnosed by amniocentesis with amplification of the viral genome in the amniotic fluid by polymerase chain reaction. This prenatal diagnosis is mainly performed when ultrasound abnormalities are observed. The purpose of this mini-review is to describe the management options when a fetus is known to be infected.