bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly Efficient Yellow Organic Light Emitting Diode with a Novel Wet‐ and Dry‐Process Feasible Iridium Complex Emitter
Authors: Jou Jwo‐Huei , Lin You‐Xing , Peng Shiang‐Hau , Li Chieh‐Ju , Yang Yu‐Min , Chin Chih‐Lung , Shyue Jing‐Jong , Sun Shih‐Sheng , Lee Mandy , Chen Chien‐Tien , Liu Ming‐Chung , Chen Cheng‐Chang , Chen Guan‐Yu , Wu Jin‐Han , Li Cheng‐Hung , Sung Chao‐Feng , Lee Mei‐Ju , Hu Je‐Ping
Published: August 2013

Yellow emission is crucial in RGBY display technology and in fabricating physiologically friendly, low color‐temperature lighting sources. Emitters with both wet‐ and dry‐process feasibility are highly desirable to fabricate, respectively, high‐quality devices via vapor deposition and cost‐effective, large‐area devices via roll‐to‐roll fabrication. Here, high‐efficiency organic light‐emitting diodes with a novel wet‐ and dry‐process feasible yellow‐emitting iridium complex, bis[5‐methyl‐7‐fluoro‐5H‐benzo(c)(1,5) naphthyridin‐6‐one]iridium (picolinate), are demonstrated. By spin coating, the device shows, at 1000 cd m−2, an external quantum efficiency (EQE) of 18.5% with an efficacy of 52.3 lm W−1, the highest among all reported yellow devices via wet‐process, while using vapor deposition, the EQE is 22.6% with a 75.1 lm W−1 efficacy, the highest among all dry‐processed counterparts. The high efficiency may be attributed to the replacement of the hydrogen atom with a fluorine atom on a 2‐substitutional site in the emitter to prevent dense molecular packing‐caused self‐quenching and to reduce radiationless deactivation rates, leading to a high quantum yield (71%).
Numerical and analytical modeling of solid–liquid expression from soft plant materials
Authors: Petryk Mykhaylo , Vorobiev Eugene
Published: August 2013

A physical model of solid–liquid expression from liquid containing plant materials is presented in one‐dimensional (1‐D) formulation. The layer of sliced cellular material is conceptualized as a double porosity system with extraparticle and intraparticle networks for liquid flow. Filtration‐consolidation equations with corresponding initial and boundary conditions were formulated for both extraparticle and intraparticle networks. It was supposed for the sliced plant material that the extraparticle network forms the first porosity with low‐storage capacity, while the intraparticle network forms a second porosity with high storage capacity. Computational modeling of pressure profiles in macro‐ and micropores versus time for different layer sections was done for real plant material (sugar beet tissue) with two different compressibility‐permeability characteristics corresponding to different degrees of tissue disruption. Results demonstrate the delayed pressure drop in the intraparticle network and retardation of consolidation kinetics for the less destroyed plant tissue. © 2013 American Institute of Chemical Engineers AIChE J, 59: 4762–4771, 2013
Second family with the boston‐type craniosynostosis syndrome: Novel mutation and expansion of the clinical spectrum
Authors: Janssen Alexander , Hosen Mohammad J. , Jeannin Philippe , Coucke Paul J. , De Paepe Anne , Vanakker Olivier M.
Published: August 2013

Craniosynostosis, caused by early fusion of one or more cranial sutures, can affect the coronal or lambdoid sutures, or include premature fusion of the sagittal (scaphocephaly) or metopic suture (trigonocephaly). Often occurring as isolated finding, their co‐existence in a craniosynostosis syndrome is infrequent. We describe a four‐generation family with variable expression of a craniosynostosis phenotype with scaphocephaly and a particularly severe trigonocephaly. Molecular analysis revealed a missense mutation in the MSX2—associated with the Boston‐type craniosynostosis syndrome—affecting the same amino‐acid residue as in the original Boston family. Besides unique features such as the cranial sutures involved, minor limb abnormalities and incomplete penetrance, our patients share with the original family autosomal dominant inheritance and the presence of multiple endocranial erosions on CT imaging. Though these findings appear to be important diagnostic clues for MSX2‐related craniosynostosis, it is noteworthy that the first affected generation in this family presented merely with isolated sagittal or unicoronal craniosynostosis and cutaneous syndactyly. Molecular analysis of MSX2 should therefore be considered in patients with isolated scaphocephaly/unicoronal synostosis, especially in the presence of a family history for craniosynostosis or syndactyly. © 2013 Wiley Periodicals, Inc.
De novo complex X chromosome rearrangement unmasking maternally inherited CSF2RA deletion in a girl with pulmonary alveolar proteinosis
Authors: Auger Julie , Bonnet Céline , Valduga Mylène , Philippe Christophe , Bertolo‐Houriez Emmanuelle , Beri‐Dexheimer Mylène , Schweitzer Cyril , Leheup Bruno , Jonveaux Philippe
Published: August 2013

We report on a 3‐year‐old girl with a de novo complex X chromosome rearrangement associated with congenital pulmonary alveolar proteinosis (PAP) and short stature. Array comparative genome hybridization and FISH analyses contributed to characterize the complex rearrangement consisting of a 7.37 Mb terminal deletion of Xp22.33p22.2, a 17.3 Mb interstitial inverted duplication of Xp22.2p21.3, and a 10.14 Mb duplication of Xq27.3q28. PCR analysis of microsatellite markers supported a paternal origin of the X chromosome rearrangement. A pre‐meiotic two‐step mechanism may explain the occurrence of this complex X rearrangement: an inverted duplication deletion event on Xp, and duplication of the Xq27.3qter region through a telomere capture event stabilizing the broken chromosome Xp end. The girl has also inherited from her healthy mother an X chromosome with a colony stimulating factor 2 receptor, alpha (CSF2RA) gene deletion. Consistent with the recessive mode of inheritance, the de novo paternal Xp22.33p22.2 deletion combined to the maternally inherited CSF2RA gene deletion led to homozygous deletion of CSF2RA and PAP diagnosis in the girl. The Xp deletion encompasses the pseudoautosomal region 1 (PAR1) which contains genes that escape X inactivation. Short stature homeobox (SHOX) haploinsufficiency explains growth retardation. Absence of other symptoms in relation to the X deletion/amplification is most probably due to skewed X inactivation. Finally, inherited deletions may unmask rare pathogenic genomic rearrangement and contribute to clinical phenotypes by a recessive mode of gene action. © 2013 Wiley Periodicals, Inc.
Multiple Lupus‐Associated ITGAM Variants Alter Mac‐1 Functions on Neutrophils
Authors: Zhou Yebin , Wu Jianming , Kucik Dennis F. , White Nathan B. , Redden David T. , Szalai Alexander J. , Bullard Daniel C. , Edberg Jeffrey C.
Published: August 2013

Objective

Multiple studies have demonstrated that single‐nucleotide polymorphisms (SNPs) in the ITGAM locus (including the nonsynonymous SNPs rs1143679, rs1143678, and rs1143683) are associated with systemic lupus erythematosus (SLE). ITGAM encodes the protein CD11b, a subunit of the β2 integrin Mac‐1. The purpose of this study was to determine the effects of ITGAM genetic variation on the biologic functions of neutrophil Mac‐1.

Methods

Neutrophils from ITGAM‐genotyped and ‐sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement‐coated erythrocytes, serum‐treated zymosan, heat‐treated zymosan, and IgG‐coated erythrocytes. The adhesion capacity of ITGAM variants, in adhering to either purified intercellular adhesion molecule 1 or tumor necrosis factor α–stimulated endothelial cells, was assessed in a flow chamber. Expression levels of total CD11b and activation of CD11b were assessed by flow cytometry.

Results

Mac‐1–mediated neutrophil phagocytosis, determined in cultures with 2 different complement‐coated particles, was significantly reduced in individuals with nonsynonymous variant alleles of ITGAM. This reduction in phagocytosis was related to variation at either rs1143679 (in the β‐propeller region) or rs1143678/rs1143683 (highly linked SNPs in the cytoplasmic/calf‐1 regions). Phagocytosis mediated by Fcγ receptors was also significantly reduced in donors with variant ITGAM alleles. Similarly, firm adhesion of neutrophils was significantly reduced in individuals with variant ITGAM alleles. These functional alterations were not attributable to differences in total receptor expression or activation.

Conclusion

The nonsynonymous ITGAM variants rs1143679 and rs1143678/rs113683 contribute to altered Mac‐1 function on neutrophils. These results underscore the need to consider multiple nonsynonymous SNPs when assessing the functional consequences of ITGAM variation on immune cell processes and the risk of SLE.
Association of Paraoxonase 1 Gene Polymorphism and Enzyme Activity With Carotid Plaque in Rheumatoid Arthritis
Authors: Charles‐Schoeman Christina , Lee Yuen Yin , Shahbazian Ani , Gorn Alan H. , FitzGerald John , Ranganath Veena K. , Taylor Mihaela , Ragavendra Nagesh , McMahon Maureen , Elashoff David , Reddy Srinivasa T.
Published: August 2013

Objective

To investigate the relationship of genetic and biochemical determinants of paraoxonase 1 activity to carotid plaque as a surrogate marker of cardiovascular (CV) risk in patients with rheumatoid arthritis (RA).

Methods

The relationships between paraoxonase 1 activity, PON1 genotype (for the functional polymorphism at position 192), and carotid plaque presence were determined in 168 RA patients. After an overnight fast, blood was collected for lipoprotein analysis, and paraoxonase 1 activity was measured using paraoxon as the substrate. The PON1 Q192R genotype was determined for all patients. Lipoprotein cholesterol levels, traditional CV risk factors, medication use, and RA disease characteristics were assessed for all patients.

Results

Paraoxonase 1 activity values in the RA patients were highest for the RR genotype, intermediate for the QR genotype, and lowest for the QQ genotype (P < 0.0001). Compared to patients with either the QQ genotype or the QR genotype, patients with the RR genotype demonstrated decreased risk of carotid plaque on multivariate analysis, controlling for traditional CV risk factors, high‐sensitivity C‐reactive protein levels, prednisone use, and cholesterol‐lowering medication use (P < 0.05). Additional multivariate logistic regression analysis controlling for the above factors also revealed a significant association of plasma paraoxonase 1 activity with carotid plaque in RA patients. Lower plasma paraoxonase 1 activity was associated with increased risk of carotid plaque (P < 0.05).

Conclusion

The current findings suggest a relationship of the genetic determinants and activity of paraoxonase 1 to CV risk in RA patients, as assessed by the presence or absence of carotid plaque. Further CV outcome studies are warranted to validate the utility of paraoxonase 1 as a biomarker of CV risk in patients with RA.
Trial and error method for optimal tradable credit schemes: The network case
Authors: Wang Xiaolei , Yang Hai , Han Deren , Liu Wei
Published: August 2013

Recent studies on the new congestion reduction method―tradable credit scheme rely on the full information of speed‐flow relationship, demand function, and generalized cost. As analytical travel demand, functions are difficult to establish in practice. This paper develops a trial and error method for selecting optimal credit schemes for general networks in the absence of demand functions. After each trial of tradable credit scheme, the credit charging scheme and total amount of credits to be distributed are updated by both observed link flows at traffic equilibrium and revealed credit price at market equilibrium. The updating strategy is based on the method of successive averages and its convergence is established theoretically. Our numerical experiments demonstrate that the method of successive averages based trial and error method for tradable credit schemes has a lower convergence speed in comparison with its counterpart for congestion pricing and could be enhanced by exploring more efficient methods that make full use of credit price information. Copyright © 2013 John Wiley & Sons, Ltd.
Influence of calcium alginate on peripheral nerve regeneration: In vivo study
Authors: Szarek Dariusz , Marycz Krzysztof , Bednarz Paulina , Tabakow Paweł , Jarmundowicz Włodzimierz , Laska Jadwiga
Published: August 2013

Recently, we described the influence of sodium alginate on the inflammatory infiltrate during neuroregeneration in tube nerve grafts. It was noticeable that there was the coexistence of inflammatory cells, including neutrophils, plasma cells, and macrophages with Schwann cells and axons. This may indicate a beneficial interaction between alginates and the infiltrate and the additional beneficial effect of the cells on the neuroregeneration process in the inflammatory infiltrates. In this study, we have performed in vivo evaluation of our novel tubular implant prepared by a polyurethane/polylactide blend filled with alginate fibers. The influence of filling the lumen of the tubes with sodium and calcium alginates on the regeneration process of the rat sciatic nerve was investigated. The neuroregeneration process was assessed by detailed histomorphometric studies, axon counting, and calculating the regenerative indexes. It was observed that calcium alginate had a supportive effect on nerve regeneration similar to nerve autotransplant.
Re‐engineering the μ‐conotoxin SIIIA scaffold
Authors: Akondi K. B. , Lewis R. J. , Alewood P. F.
Published: August 2013

Voltage‐gated sodium (Nav) channels are responsible for generation and propagation of action potentials throughout the nervous system. Their malfunction causes several disorders and chronic conditions including neuropathic pain. Potent subtype specific ligands are essential for deciphering the molecular mechanisms of Nav channel function and development of effective therapeutics. µ‐Conotoxin SIIIA is a potent mammalian Nav1.2 channel blocker that exhibits analgesic activity in rodents. We undertook to reengineer loop 1 through a strategy involving charge alterations and truncations which led to the development of µ‐SIIIA mimetics with novel selectivity profiles. A novel [N5K/D15A]SIIIA(3–20) mutant with enhanced net positive charge showed a dramatic increase in its Nav1.2 potency (IC50 of 0.5 nM vs. 9.6 nM for native SIIIA) though further truncations led to loss of potency. Unexpectedly, it appears that SIIIA loop 1 significantly influences its Nav channel interactions despite loop 2 and 3 residues constituting the pharmacophore. This minimal functional conotoxin scaffold may allow further development of selective NaV blockers. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 347–354, 2014.
Molecular and Crystal Structure Diversity, and Physical Properties of Tetrathiafulvalene Derivatives Substituted with Various Aryl Groups through Sulfur Bridges
Authors: Sun Jibin , Lu Xiaofeng , Shao Jiafeng , Li Xuexiang , Zhang Shangxi , Wang Baolin , Zhao Jinlian , Shao Yongliang , Fang Ran , Wang Zhaohui , Yu Wei , Shao Xiangfeng
Published: August 2013

A library of tetrathiafulvalene (TTF) derivatives (TTF‐1–TTF‐47) bearing aryl groups attached through sulfur bridges has been created. The peripheral aryl groups exert a significant influence on both the electronic and crystallographic properties of the resulting TTFs. These TTFs display broad absorption bands at 400–500 nm caused by intramolecular charge‐transfer transitions between the aryl groups and central TTF core, and their first redox potentials increase with increasing electron‐withdrawing ability of the aryl groups. In their crystal structures (22 examples), the central TTF cores adopt various conformations, including chair, half‐chair, boat, and planar conformations. Moreover, the peripheral aryl groups exhibit multiple alignment modes with respect to the central TTF core, caused by their rotation about the two CS bonds of the sulfur bridges. The packing motifs of these TTFs depend on both the nature of the aryl groups and their spatial alignment modes. Driven by intermolecular van der Waals forces and π–π interactions between the aryl groups and between the aryl groups and the TTF core, these TTFs adopt various packing structures. As a typical example, TTF‐14, an achiral molecule, adopts a helical chain stack through intermolecular atomic close contacts. Moreover, the molecular geometries and packing motifs of these TTFs are sensitive to environmental variation, as exemplified by TTF‐28, which adopts three distinct crystal modifications with diverse molecular geometries and stacking modes under different crystallization conditions. This work indicates that these TTFs are potential candidates as electronic materials, as well as functional building blocks for supramolecular assembly.
Prognostic value of rapid response to enhanced cognitive behavioral therapy in a routine clinic sample of eating disorder outpatients
Authors: Raykos Bronwyn C. , Watson Hunna J. , Fursland Anthea , Byrne Susan M. , Nathan Paula
Published: August 2013

Objective

This study examined whether rapid response to enhanced cognitive behavioral therapy (CBT‐E) was associated with superior treatment outcomes in a transdiagnostic sample of patients with an eating disorder.

Method

Participants were 105 patients with a primary eating disorder diagnosis who received individual CBT‐E at a community‐based outpatient clinic. Patients completed measures of eating disorder and related pathology at baseline and post‐treatment. The Eating Disorder Examination‐Questionnaire (EDE‐Q) was administered at baseline and again, on average, 4.6 weeks after commencing treatment to assess rapid response to CBT‐E. Patients achieving reliable change on the EDE‐Q at this point were classified as rapid responders.

Results

No baseline differences distinguished rapid and nonrapid responders. Rapid responders had significantly lower scores on EDE‐Q global at post‐treatment, were more likely to achieve full remission, and required significantly fewer treatment sessions than nonrapid responders. One‐quarter of the nonrapid responders went on to achieve full remission. There were no group differences on measures of anxiety and depression symptoms at the end of treatment.

Discussion

Early change in treatment is encouraged to achieve the best possible prognosis in CBT‐E. Those who did not achieve rapid response still had an overall significant improvement in symptoms from pretreatment to post‐treatment, but a lower rate of full remission. Nonrapid responders are an important group of patients to study because they offer researchers an opportunity to improve clinical decision‐making and treatment outcomes for patients who are at risk of suboptimal response. © 2013 Wiley Periodicals, Inc.(Int J Eat Disord 2013; 46:764–770)
Novel mutations and expression alterations in SMAD3/TGFBR2 genes in oral carcinoma correlate with poor prognosis
Authors: Sivadas Vadakke Peringode , George Nebu Abraham , Kattoor Jayasree , Kannan S.
Published: August 2013

Transforming growth factor beta (TGF‐β) signaling is a pleiotropic cytokine signaling pathway, which controls cellular activities ranging from embryogenesis to apoptosis. Although many molecular alterations in this pathway have been described in cancers, the central point of concern, that is how these alterations influence the treatment outcome, has been addressed to a lesser extent. In this study, we have characterized the alterations of TGF‐β‐SMAD signaling in 97 oral squamous cell carcinoma (OSCC) samples and assessed the association between these alterations and the outcome of the treatment. Genomic level alteration analysis using reverse transcriptase polymerase chain reaction‐single‐strand conformation polymorphism/sequencing revealed that there were 25% samples harboring genomic level alterations in this pathway. Altogether, 21% samples showed TGFBR2 mutations, whereas three cases were found to harbor novel SMAD3 mutations. Notably, 14 out of 24 TGFBR2 mutations are of one type (c.*6C>A), which supplemented complementarity for hsa‐miR‐3189‐5p. These samples showed significantly low TGFBR2 transcript levels (P = 0.026). In addition, transcript level studies using quantitative real‐time PCR revealed a strong association between low TGFBR2 transcript levels and poor disease‐free survival (P = 0.028) as well as poor overall survival (P = 0.013). In brief, our results showed that oral cancers with TGFBR2 downregulation comprise a different group with more aggressive nature. These results suggest that in OSCCs, TGFBR2 transcript levels may be developed as a promising prognostic biomarker. Furthermore, for the first time, this study reports SMAD3 mutations in oral carcinoma. © 2013 Wiley Periodicals, Inc.
Head and neck fascia and compartments: No space for spaces
Authors: Guidera Alice K. , Dawes Patrick J. D. , Fong Amy , Stringer Mark D.
Published: August 2013

An accurate understanding of the arrangement of cervical fascia and its associated compartments is essential for differential diagnosis, predicting the spread of disease, and surgical management. The purpose of this detailed review is to summarize the anatomic, clinical, and radiological literature to determine what is known about the arrangement of cervical fascia and to highlight controversies and consensus. The current terminology used to describe cervical fascia and compartments is replete with confusing synonyms and inconsistencies, creating important interdisciplinary differences in understanding. The term “spaces” is inappropriate. A modified nomenclature underpinned by evidence‐based anatomic and radiologic findings is proposed. This should not only enhance our understanding of cervical anatomy but also facilitate clearer interdisciplinary communication. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1058–1068, 2014
Predicted no effect concentration derivation as a significant source of variability in environmental hazard assessments of chemicals in aquatic systems: An international analysis
Authors: Hahn Thorsten , Diamond Jerry , Dobson Stuart , Howe Paul , Kielhorn Janet , Koennecker Gustav , Lee-Steere Chris , Mangelsdorf Inge , Schneider Uwe , Sugaya Yoshio , Taylor Ken , Dam Rick Van , Stauber Jenny L
Published: August 2013

Environmental hazard assessments for chemicals are carried out to define an environmentally “safe” level at which, theoretically, the chemical will not negatively affect any exposed biota. Despite this common goal, the methodologies in use are very diverse across different countries and jurisdictions. This becomes particularly obvious when international scientists work together on documents with global scope, e.g., in the World Health Organization (WHO) International Program on Chemical Safety. In this article, we present a study that describes the extent of such variability and analyze the reasons that lead to different outcomes in deriving a “safe level” (termed the predicted no effect concentration [PNEC] throughout this article). For this purpose, we chose 5 chemicals to represent well-known substances for which sufficient high-quality aquatic effects data were available: ethylene glycol, trichloroethylene, nonylphenol, hexachlorobenzene, and copper (Cu). From these data, 2 data sets for each chemical were compiled: the full data set, that contained all information from selected peer-review sources, and the base data set, a subsample of the full set simulating limited data. Scientists from the European Union (EU), United States, Canada, Japan, and Australia independently carried out hazard assessments for each of these chemicals using the same data sets. Their reasoning for key study selection, use of assessment factors, or use of probabilistic methods was comprehensively documented. The observed variation in the PNECs for all chemicals was up to 3 orders of magnitude, and this was not simply due to obvious factors such as the size of the data set or the methodology used. Rather, this was due to individual decisions of the assessors within the scope of the methodology used, especially key study selection, acute versus chronic definitions, and size of assessment factors. Awareness of these factors, together with transparency of the decision-making process, would be necessary to minimize confusion and uncertainty related to different hazard assessment outcomes, particularly in international documents. The development of a “guideline on transparency in decision-making” ensuring the decision-making process is science-based, understandable, and transparent, may therefore be a promising way forward. Integr Environ Assess Manag 2014;10:30–36. © 2013 SETAC
Using sparse dose–response data for wildlife risk assessment
Authors: Hill Ryan A , Pyper Brian J , Lawrence Gary S , Mann Gary S , Allard Patrick , Mackintosh Cheryl E , Healey Norm , Dwyer James , Trowell Jennifer
Published: August 2013

Hazard quotients based on a point-estimate comparison of exposure to a toxicity reference value (TRV) are commonly used to characterize risks for wildlife. Quotients may be appropriate for screening-level assessments but should be avoided in detailed assessments, because they provide little insight regarding the likely magnitude of effects and associated uncertainty. To better characterize risks to wildlife and support more informed decision making, practitioners should make full use of available dose–response data. First, relevant studies should be compiled and data extracted. Data extractions are not trivial—practitioners must evaluate the potential use of each study or its components, extract numerous variables, and in some cases, calculate variables of interest. Second, plots should be used to thoroughly explore the data, especially in the range of doses relevant to a given risk assessment. Plots should be used to understand variation in dose–response among studies, species, and other factors. Finally, quantitative dose–response models should be considered if they are likely to provide an improved basis for decision making. The most common dose–response models are simple models for data from a particular study for a particular species, using generalized linear models or other models appropriate for a given endpoint. Although simple models work well in some instances, they generally do not reflect the full breadth of information in a dose–response data set, because they apply only for particular studies, species, and endpoints. More advanced models are available that explicitly account for variation among studies and species, or that standardize multiple endpoints to a common response variable. Application of these models may be useful in some cases when data are abundant, but there are challenges to implementing and interpreting such models when data are sparse. Integr Environ Assess Manag 2014;10:3–11. © 2013 SETAC
Selecting surrogate endpoints for estimating pesticide effects on avian reproductive success
Authors: Bennett Richard S , Etterson Matthew A
Published: August 2013

A Markov chain nest productivity model (MCnest) has been developed for projecting the effects of a specific pesticide-use scenario on the annual reproductive success of avian species of concern. A critical element in MCnest is the use of surrogate endpoints, defined as measured endpoints from avian toxicity tests that represent specific types of effects possible in field populations at specific phases of a nesting attempt. In this article, we discuss the attributes of surrogate endpoints and provide guidance for selecting surrogates from existing avian laboratory tests as well as other possible sources. We also discuss some of the assumptions and uncertainties related to using surrogate endpoints to represent field effects. The process of explicitly considering how toxicity test results can be used to assess effects in the field helps identify uncertainties and data gaps that could be targeted in higher-tier risk assessments. Integr Environ Assess Manag 2013;9:600–609. © 2013 SETAC
Loss of prolyl hydroxylase‐2 in myeloid cells and T‐lymphocytes impairs tumor development
Authors: Mamlouk Soulafa , Kalucka Joanna , Singh Rashim Pal , Franke Kristin , Muschter Antje , Langer Anika , Jakob Christiane , Gassmann Max , Baretton Gustavo B. , Wielockx Ben
Published: August 2013

The tumor microenvironment plays a pivotal role during cancer development and progression. The balance between suppressive and cytotoxic responses of the tumor immune microenvironment has been shown to have a direct effect on the final outcome in various human and experimental tumors. Recently, we demonstrated that the oxygen sensor HIF‐prolyl hydroxylase‐2 (PHD2) plays a detrimental role in tumor cells, stimulating systemic growth and metastasis in mice. In our current study, we show that the conditional ablation of PHD2 in the hematopoietic system also leads to reduced tumor volume, intriguingly generated by an imbalance between enhanced cell death and improved proliferation of tumor cells. This effect seems to rely on the overall downregulation of protumoral as well as antitumoral cytokines. Using different genetic approaches, we were able to confine this complex phenotype to the crosstalk of PHD2‐deficient myeloid cells and T‐lymphocytes. Taken together, our findings reveal a multifaceted role for PHD2 in several hematopoietic lineages during tumor development and might have important implications for the development of tumor therapies in the future.
The interplay between HPV and host immunity in head and neck squamous cell carcinoma
Authors: Andersen Anne Skou , Koldjær Sølling Anne Sophie , Ovesen Therese , Rusan Maria
Published: August 2013

Persistent infection with human papillomavirus (HPV) type 16 is a major risk factor for the development of head and neck squamous cell carcinoma (HNSCC), in particular oropharyngeal squamous cell carcinoma (OPSCC). The oropharyngeal epithelium differs from the mucosal epithelium at other commonly HPV16‐infected sites (i.e., cervix and anogenital region) in that it is juxtaposed with the underlying lymphatic tissue, serving a key immunologic function in the surveillance of inhaled and ingested pathogens. Therefore, the natural history of infection and immune response to HPV at this site may differ from that at other anatomic locations. This review summarizes the literature concerning the adaptive immune response against HPV in the context of HNSCC, with a focus on the T‐cell response. Recent studies have shown that a broad repertoire of tumor‐infiltrating HPV‐specific T‐cells are found in nearly all patients with HPV‐positive tumors. A systemic response is found in only a proportion of these. Furthermore, the local response is more frequent in OPSCC patients than in cervical cancer patients and HPV‐negative OPSCC patients. Despite this, tumor persistence may be facilitated by abnormalities in antigen processing, a skewed T‐helper cell response, and an increased local prevalence of T‐regulatory cells. Nonetheless, the immunologic profile of HPV‐positive vs. HPV‐negative HNSCC is associated with a significantly better outcome, and the HPV‐specific immune response is suggested to play a role in the significantly better response to therapy of HPV‐positive patients. Immunoprofiling may prove a valuable prognostic tool, and immunotherapy trials targeting HPV are underway, providing hope for decreasing treatment‐related toxicity.
Evaluation of the impact of a breast cancer awareness program in rural Ghana: A cross‐sectional survey
Authors: Mena Marisa , Wiafe‐Addai Beatrice , Sauvaget Catherine , Ali Ibrahim A. , Wiafe Seth A. , Dabis François , Anderson Benjamin O. , Malvy Denis , Sasco Annie J.
Published: August 2013

Community awareness is crucial to early detection of breast cancer in low‐ and middle‐income countries. In Ghana 60% of the cases are detected at late stages. Breast Care International (BCI) is a Ghanaian non‐governmental organization dedicated to raising breast cancer awareness. A cross‐sectional survey was designed to assess the impact of BCI program on knowledge, attitudes and practices (KAP) toward breast cancer among women from rural communities of Ghana. A total of 232 women were interviewed in June 2011 in the Ashanti region; of these 131 participants were from a community that received the BCI program in August 2010 (intervention group) and 101 from another community that received the program post‐survey (referent group). Data analysis was performed using Epi‐Info version 3.5.3. Knowledge about breast cancer among participants who received the program was better than among those who did not. Only 53.5% of participants from the referent group knew that breast cancer usually appears as painless breast lump when compared to 82.3% from the intervention group. Participants who attended the program were significantly more likely to obtain higher knowledge scores (odds ratio (OR) = 2.10, 95% confidence interval (CI) = 1.14–3.86) and to state practicing breast self‐examination (OR = 12.29, 95% CI = 5.31–28.48). The BCI program improved KAP toward breast cancer. Further research is warranted to provide stronger evidence that the program improves breast cancer early detection.
Expression of TLR9 in tumor‐infiltrating mononuclear cells enhances angiogenesis and is associated with a worse survival in lung cancer
Authors: Belmont Laure , Rabbe Nathalie , Antoine Martine , Cathelin Dominique , Guignabert Christophe , Kurie Jonathan , Cadranel Jacques , Wislez Marie
Published: August 2013

Toll‐like receptors (TLRs) play a crucial role in the innate and adaptive immune responses against microbial infection, tissue injury and cancer. Ligands of TLR9 have been developed as therapy in non‐small‐cell lung carcinoma (NSCLC). However, phase III clinical trials in metastatic NSCLC were negative. Our objective was to determine whether TLR9 affects tumor growth. We generated a mouse model of lung adenocarcinoma (ADC) mutated for K‐ras (K‐rasLA1), with and without TLR9 inactivation (K‐rasLA1TLR9−/− and K‐rasLA1TLR9+/+, respectively). TLR9 was functionally expressed only in mononuclear cells of K‐rasLA1TLR9+/+ mice. These mice had significantly worse survival and a higher tumor burden than K‐rasLA1TLR9−/− mice. Lung tumors were analyzed for 24 cytokines/growth factors using Bio‐Plex multiplex bead‐based assays. Factor VIII was assessed by immunochemistry. Tumors from K‐rasLA1TLR9+/+ mice were characterized by an angiogenic phenotype with higher concentrations of vascular endothelial growth factor (VEGF) and higher microvessel density than from K‐rasLA1TLR9−/− mice. LKR13 cells, an ADC cell line derived from K‐rasLA1 mice, were subcutaneously injected into TLR9−/− and TLR9+/+ mice. Syngeneic tumors regressed in TLR9−/− but not in TLR9+/+ mice. Peripheral blood mononuclear cells from TLR9−/− mice released less VEGF than those from TLR9+/+ mice. In 61 patients with early‐stage NSCLC, TLR9 was expressed in mononuclear cells that infiltrated tumors, as assessed by immunochemistry, and contributed to worse survival. Our results suggest that TLR9 expression in mononuclear cells was associated with an angiogenic phenotype and promoted lung cancer progression. These findings may aid clinical development of TLR9 ligands to treat cancers.
Adhesive protein‐free synthetic hydrogels for retinal pigment epithelium cell culture with low ROS level
Authors: Chen Yong Mei , Liu Zhen Qi , Feng Zhi Hui , Xu Feng , Liu Jian Kang
Published: August 2013

Engineering of human retinal pigment epithelium (RPE) cell monolayer with low level of reactive oxygen species (ROS) is important for regenerative RPE‐based therapies. However, it is still challenging to culture RPE monolayer with low ROS level on soft substratesin vitro. To address this, we developed cytocompatible hydrogels to culture human RPE cell monolayer for future use in regenerative RPE‐based therapies. The cell adhesion, proliferation, monolayer formation, morphology, survival, and ROS level of human ARPE‐19 cells cultured on the surfaces of negatively charged poly (2‐acrylamido‐2‐methyl propane sulfonic sodium) (PNaAMPS) and neutral poly(N,N‐dimethylacrylamide) (PDMAAm) hydrogels with different stiffness were investigated. The importance of hydrogel stiffness on the cell function was firstly highlighted on the base of determined optimal Young's modulus for cultivation of RPE cell monolayer with relatively low ROS level. The construction of RPE cell monolayer with low ROS level on the PNaAMPS hydrogel may hold great potential as promising candidates for transplantation of RPE cell monolayer‐hydrogel construct into the subretinal space to repair retinal functions. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2258–2267, 2014.
A theory of ionospheric response to upward‐propagating tides: Electrodynamic effects and tidal mixing effects
Authors: Yamazaki Yosuke , Richmond Arthur D.
Published: August 2013

The atmospheric tide at ionospheric heights is composed of those locally generated and those propagated from below. The role of the latter in producing the variability of the daytime ionosphere is examined using the National Center for Atmospheric Research Thermosphere‐Ionosphere‐Electrodynamics General Circulation Model. The impact of upward‐propagating tides is evaluated by running simulations with and without tidal forcing at the lower boundary (approximately 96 km), which imitates the effect of tides from below. When migrating diurnal and semidiurnal tides at the lower boundary is switched on, the intensity of E region currents and the upward velocity of the equatorial F region vertical plasma drift rapidly increase. The low‐latitude ionospheric total electron content (TEC) first increases, then gradually decreases to below the initial level. The initial increase in the low‐latitude TEC is caused by an enhanced equatorial plasma fountain while the subsequent decrease is due to changes in the neutral composition, which are characterized by a global‐scale reduction in the mass mixing ratio of atomic oxygen O1. The results of further numerical experiments indicate that the mean meridional circulation induced by dissipating tides in the lower thermosphere is mainly responsible for the O1 reduction; it acts like an additional turbulent eddy and produces a “mixing effect” that enhances net downward transport and loss of O1. It is stressed that both electrodynamic effects and mixing effects of upward‐propagating tides can be important in producing the variability of ionospheric plasma density. Since the two mechanisms act in different ways on different time scales, the response of the actual ionosphere to highly variable upward‐propagating tides is expected to be complex.
On the generation of ion beamlets in the magnetotail: Resonant acceleration versus stochastic acceleration
Authors: Dolgonosov M. S. , Zimbardo G. , Perri S. , Greco A.
Published: August 2013

In the Earth plasma sheet boundary layer, two types of ion beams (so‐called beamlets of type I and of type II) were investigated for more then two decades. Type I beamlets have energies <20 keV and small velocity dispersion, while type II beamlets have energies up to 100 keV and large velocity dispersion. It is believed that beamlets of type I result from nonadiabatic and resonant acceleration by the cross‐tail electric field Ey at the fulfillment of the resonant condition in the current sheet, while beamlets type II could be generated by sufficiently large level of electromagnetic fluctuations in the magnetotail. The resonant condition is very sensitive to the presence of the perturbation and eventually should be destroyed by growing “noise.” We performed test particle simulation taking into account two possible acceleration mechanisms, cross‐tail electric field Ey and stochastic acceleration due to electromagnetic perturbations. Electromagnetic perturbation were generated by a set of oscillating clouds in the plasma sheet. We obtained that type I beamlets could be observed even in the presence of moderate levels of perturbation δB∼Bz(z=0), where Bz is a magnetic field component perpendicular to the current sheet plane. Increasing the perturbation level, beamlets of higher energy are obtained. The interplay of ion resonant acceleration and magnetic perturbation in the magnetotail leads to a continuous transition from beamlets of type I to beamlets of type II. A comparison of the numerical results with the observation of ion populations in magnetotail is also discussed.
Polar motion excitations for an Earth model with frequency‐dependent responses: 1. A refined theory with insight into the Earth's rheology and core‐mantle coupling
Authors: Chen Wei , Ray Jim , Li JianCheng , Huang ChengLi , Shen WenBin
Published: August 2013

This study aims to improve the polar motion theory by developing refined frequency‐dependent transfer functions with the most current models for ocean tides, the Earth's rheology, and core‐mantle coupling. First, we present a power law for mantle anelasticity constrained by the Chandler period TCW and quality factor QCW and an empirical quasi‐fluid rheology model with a linear dependence on frequency, which is suitable for a period as long as ~18.6 years. Then we adopt the diurnal ocean tides from the International Earth Rotation and Reference Systems Service Conventions (2010), the long‐period ocean model of Dickman and Gross (2010), and the equilibrium ocean pole tide model of Desai (2002) to calculate the oceanic corrections to the Love numbers. Further, we present discussions on the geophysical and observational aspects of the Chandler period TCW and quality factor QCW, and provide preferred values and intervals for TCW and QCW, which allow us to place some constraints on the mantle anelasticity and core‐mantle coupling ratio ηCW. Although ηCW is affected by uncertainties in TCW and QCW, we find its real part should be around 2%–3% while its imaginary part might be only a few thousandths. Finally, the frequency‐dependent polar motion transfer functions T L and T NL are determined based on the models of frequency‐dependent Love numbers and core‐mantle coupling discussed above. Our transfer functions are related to the values of TCW and QCW, however, our analyses demonstrate that our transfer functions are rather stable and not sensitive to perturbations in TCW and QCW.
Bathymetry and geological structures beneath the Ross Ice Shelf at the mouth of Whillans Ice Stream, West Antarctica, modeled from ground‐based gravity measurements
Authors: Muto Atsuhiro , Christianson Knut , Horgan Huw J. , Anandakrishnan Sridhar , Alley Richard B.
Published: August 2013

New gravity data reveal important geologic controls on the location and behavior of the grounding zone of Whillans Ice Stream (WIS), West Antarctica. Grounding zones of ice sheets and contiguous ice shelves are important for understanding ice sheet dynamics, as key processes that influence the grounded ice and its discharge into the ocean occur in these regions. Here, we model the bathymetry and shallow geological structures beneath the Ross Ice Shelf in an embayment of the WIS grounding zone using gravity data collected on the ground, in conjunction with seismic and radar data. We find that the region of shallow ocean water (<~50 m) is extensive; oceanographic models suggest that grounding zones exhibiting thin ocean cavities with gently sloping ice‐ocean interfaces are likely to be tidally well mixed, leading to slower basal melting than would occur in a thicker, stratified water column. Beneath the ocean water column, we model a fault and a sedimentary basin in a half‐graben, filled with two layers of sediments. The total thickness of the sediment layer is 900 to 1250 m in the half‐graben, and 600 to 800 m on the upthrown block, and the basement depth is no more than 2000 m. We observe that the upper, softer sediment is thinnest near the modern grounding line and may possibly pinch out near our grid, and that the modeled fault is roughly parallel to part the grounding. We therefore hypothesize that the WIS grounding line stabilized in its current location in part due to the subglacial geology.
Observed frequency and intensity of tropical precipitation from instantaneous estimates
Authors: Biasutti Michela , Yuter Sandra E.
Published: August 2013

Negative societal impacts can result from intense individual downpours, the accumulation of rainfall over a day or more, or a combination of these. Accumulation is reasonably well captured by daily reporting rain gauges, but rainfall intensity is not. Ten years of data from the Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR) are used to describe the spatial and seasonal distributions of instantaneous rainfall intensity with an emphasis on how these differ from the distributions of mean daily accumulation. Over tropical land, the rainy season, when rainfall is most frequent, does not coincide with the highest mean intensity. Rather, intensity peaks just before the rainy season. This offset is most obvious in the pre‐onset and post‐onset months in monsoon regions and it is also evident in equatorial regions without a well‐defined dry and rainy season. Most seasonal variations in rainfall intensity can be explained as parallel variations in the occurrence of convective, relative to stratiform, precipitation. However, regional differences in rainfall intensity are related to differences in the intensity of convection itself. Compared with seasonal changes in intensity over land, variations in convective precipitation fraction over tropical oceans are trivial, and the modest seasonal changes in the intensity of rainfall parallel those of frequency. These findings suggest that studies of precipitation extremes under global warming should (1) explicitly tackle the question of changes in the intensity of rainfall separately from changes in daily rainfall accumulation and (2) consider the different qualities of extreme precipitation events over ocean and over land.
A validation study for GPS radio occultation data with moist thermodynamic structure of tropical cyclones
Authors: Vergados Panagiotis , Mannucci Anthony J. , Su Hui
Published: August 2013

We exploit the cloud‐penetrating capability and insensitivity to precipitation of the Global Positioning System radio occultation (GPSRO) technique to study the humidity environment of tropical cyclones (TCs). We focus in regions within and around the vicinity of TCs' eye, where infrared and microwave observations are difficult to acquire due to cloudiness and heavy precipitation. We use data from the National Hurricane Center TC Best Tracks to identify the location of North Atlantic TCs. The Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) Data Analysis and Archive Center provides concurrent refractivity, temperature, and humidity measurements from the Challenging Minisatellite Payload and COSMIC missions and the European Centre for Medium‐Range Weather Forecasts (ECMWF). The distribution of GPSRO‐derived humidity profiles as functions of altitude and distance from the storms' center identifies a pronounced low‐level inflow, characteristic of mature TCs, at distances between 50 and 90 km, which coincide with the area where the eyewall of TCs forms. We also capture wavelike structures resembling spiral rainbands beyond the eyewall. The distribution of water vapor as functions of altitude and TC intensity shows a decrease at all altitudes when a tropical system matures from a tropical depression to a Category 1 (Cat 1) hurricane. The water vapor gradually increases from Cat 2 to Cat 5 hurricanes—a result that is also identified in ECMWF data sets and Atmospheric Infrared Sounder observations. We conclude that GPSRO data can contribute significantly to the understanding and modeling of the vertical structures of TCs.
Another Way to the Synthesis of 1,2,3‐Triazoles
Authors: Xu Beihua , Hu Yongzhou
Published: August 2013

The reactions of α‐bromoacetophenones with methylhydrazine in refluxing acetic acid generated 2‐methyl‐4‐aryl‐2H‐[1,2,3]triazoles in good yields. The method was developed by the reactions of α‐bromoacetophenones with phenylhydrazines in the presence of cupric ion, leading to 2,4‐diary‐2H‐[1,2,3]triazoles. The structures were established on the basis of corresponding IR, 1H NMR, and elemental analysis data.