bluuebunny/crossref_metadata_2025 huggingface dataset:
The Addition of Nitriles to Tetramesityldisilene: A Comparison of the Reactivity between Surface and Molecular Disilenes
Authors: Hardwick Julie A. , Baines Kim M.
Published: December 2014

The addition of acetonitrile, propionitrile, and phenylacetonitrile to tetramesityldisilene (Mes2SiSiMes2) was examined. In general, 1,2,3‐azadisiletines and the tautomeric enamines were formed, although a ketenimine was formed as the major product in the addition of phenylacetonitrile to the disilene. In the presence of LiCl, the mode of addition changed for both acetonitrile and propionitrile: insertion into the α‐CH bond of acetonitrile and/or formation of the formal HCN adduct was observed. Preliminary investigations of the reactivity of the nitrile adducts are also reported. A comparison between the reactivity of nitriles with Mes2SiSiMes2 and the Si(100)‐2×1 surface was made both in terms of the types of adducts formed and their reactivity. Some insights into the surface chemistry are offered.
Marital status and head and neck cancer outcomes
Authors: Inverso Gino , Mahal Brandon A. , Aizer Ayal A. , Donoff R. Bruce , Chau Nicole G. , Haddad Robert I.
Published: December 2014

BACKGROUND

The objective of this study was to examine the effects of marital status on stage at presentation, receipt of treatment, and survival in patients with head and neck cancer (HNC).

METHODS

The Surveillance, Epidemiology, and End Results database was used to analyze 51,272 patients who were diagnosed with HNC from 2007 to 2010. The impact of marital status on cancer stage at presentation, receipt of definitive treatment, and HNC‐specific mortality (HNCSM) was determined using multivariable logistic and Fine and Gray competing‐risks regression models, as appropriate.

RESULTS

Marriage had a protective effect against metastatic presentation of oral and laryngeal cancers (oral cancer: adjusted odds ratio [AOR], 0.72; 95% confidence interval [CI], 0.60‐0.87; P < .001; laryngeal cancer: AOR, 0.53; 95% CI, 0.42‐0.67; P < .001) but not against oropharyngeal, hypopharyngeal, or nasopharyngeal cancers. Among patients with nonmetastatic disease, married patients were more likely to receive definitive treatment (overall AOR, 1.77; 95% CI, 1.60‐1.95; P < .001) and had a lower risk of HNCSM (overall adjusted hazard ratio, 0.72; 95% CI, 0.68‐0.77; P < .001); these associations remained significant across all HNC sites.

CONCLUSIONS

Among patients with oral and laryngeal cancers, those who are married are less likely to present with metastatic disease. In addition, married patients are more likely to receive definitive treatment and less likely to die from HNC across all HNC sites. This suggests that spousal support may have a role in the surveillance of visual and symptomatic HNC types and leads to higher rates of treatment and better survival across all HNC sites. Cancer 2015;121:1273–1278. © 2014 American Cancer Society.
Phase 2 trial of the cyclin‐dependent kinase 4/6 inhibitor palbociclib in patients with retinoblastoma protein‐expressing germ cell tumors
Authors: Vaughn David J. , Hwang Wei‐Ting , Lal Priti , Rosen Mark A. , Gallagher Maryann , O'Dwyer Peter J.
Published: December 2014

BACKGROUND

Alterations in the retinoblastoma pathway in germ cell tumors (GCTs) have been described. In the phase 1 trials of the selective cyclin‐dependent kinase 4/6 inhibitor palbociclib, 3 patients with unresectable, growing, mature teratoma syndrome achieved prolonged disease stabilization. The authors conducted an open‐label, phase 2 study to determine the efficacy and safety of palbociclib in patients with incurable, refractory, retinoblastoma protein (pRB)‐expressing GCTs.

METHODS

Patients who had incurable, refractory GCTs that demonstrated pRB expression by immunohistochemistry received oral palbociclib 125 mg daily for 21 days followed by a 7‐day break. The primary endpoint was the 24‐week progression‐free survival (PFS) rate. A 24‐week PFS rate ≥15% was considered promising, and a PFS rate ≤5% was not considered promising.

RESULTS

Thirty patients received treatment, and 29 were evaluable for the primary endpoint. The estimated 24‐week PFS rate was 28% (90% exact confidence interval, 15%‐44%). Patients who had teratoma and teratoma with malignant transformation had significantly better PFS than patients who had nonteratomatous GCTs. Toxicity was manageable and was principally hematologic.

CONCLUSIONS

Treatment with palbociclib was associated with a favorable 24‐week PFS rate in patients with refractory, pRB‐expressing GCTs. Benefit was mainly observed in patients who had unresectable teratomas and teratomas with malignant transformation. Cancer 2015;121:1463–1468. © 2014 American Cancer Society.
Biospecimen repositories and cytopathology
Authors: Krishnamurthy Savitri
Published: December 2014

Biospecimen repositories are important for the advancement of biomedical research. Literature on the potential for biobanking of fine‐needle aspiration, gynecologic, and nongynecologic cytology specimens is very limited. The potential for biobanking of these specimens as valuable additional resources to surgically excised tissues appears to be excellent. The cervicovaginal specimens that can be used for biobanking include Papanicolaou‐stained monolayer preparations and residual material from liquid‐based cytology preparations. Different types of specimen preparations of fine‐needle aspiration and nongynecologic specimens, including Papanicolaou‐stained and Diff‐Quik–stained smears, cell blocks. and dedicated passes/residual material from fine‐needle aspiration stored frozen in a variety of solutions, can be used for biobanking. Because of several gaps in knowledge regarding the standard of operative procedures for the procurement, storage, and quality assessment of cytology specimens, further studies as well as national conferences and workshops are needed not only to create awareness but also to facilitate the use of cytopathology specimens for biobanking. Cancer (Cancer Cytopathol) 2015;123:152–161. © 2014 American Cancer Society.
A Visible‐Light Harvesting System for CO2 Reduction Using a RuII–ReI Photocatalyst Adsorbed in Mesoporous Organosilica
Authors: Ueda Yutaro , Takeda Hiroyuki , Yui Tatsuto , Koike Kazuhide , Goto Yasutomo , Inagaki Shinji , Ishitani Osamu
Published: December 2014

A photocatalytic system for CO2 reduction exhibiting visible‐light harvesting was developed by preparing a hybrid consisting of a supramolecular metal complex as photocatalyst and periodic mesoporous organosilica (PMO) as light harvester. A RuIIReI binuclear complex (RuRe) with methylphosphonic acid anchor groups was adsorbed on acridone or methylacridone embedded in the walls of PMO mesochannels to yield the hybrid structure. The embedded organic groups absorbed visible light, and the excitation energy was funneled to the Ru units. The energy accumulation was followed by electron transfer and catalytic reduction of CO2 to CO on the Re unit. The light harvesting of these hybrids enhanced the photocatalytic CO evolution rate by a factor of up to ten compared with that of RuRe adsorbed on mesoporous silica without a light harvester.
Barrier Strain and Carbon Incorporation‐Engineered Performance Improvements for AlGaN/GaN High Electron Mobility Transistors**
Authors: Luong Tien Tung , Ho Yen Teng , Tran Binh Tinh , Woong Yuen Yee , Chang Edward Yi
Published: December 2014

The improvements in electrical characteristics of AlGaN/GaN high electron mobility transistors (HEMTs) grown using metal‐organic (MO)CVD by engineering structure, barrier strain, and unintentional carbon incorporation, are demonstrated in this work. Both normal HEMT structure (with a high temperature (HT) AlN buffer) and advanced HEMT structure (with a high‐low‐high temperature (HLHT) AlN buffer, and a HT AlN interlayer (IL)) present a breakdown voltage higher than 200 V, while a much smaller breakdown voltage of 17 V is measured on the conventional structure using a low‐temperature GaN buffer. The HT AlN IL inserted in the middle of the conventional HEMT structure introduces a reduction in the tension of the AlGaN barrier, which results in an improvement of the surface morphology (0.46 nm). As a consequence, the two‐dimensional electron gas (2DEG) mobility increases by remarkable 46% (1900 cm2 V−1 s−1). The HLHT AlN buffer, substituting for the HT AlN buffer, leads to the enhancement of GaN crystalline quality, which contributes to the performance improvement for HEMTs. The advanced HEMT, using both an AlN IL and an HLHT AlN buffer, produces increases in the DC maximum drain current by 35.5% (∼680 A mm−1), and in the transconductance by 15% (114 mS mm−1) in comparison with the normal HEMT with an AlN buffer. The very low leakage current in the advanced HEMTs is caused by optimizing the design of the buffer and modifying growth parameters. Lastly, the reduction of AlGaN barrier tensile strain by inserting the HT AlN IL is promising for an improvement in AlGaN/GaN HEMT reliability.
A low‐complexity resource allocation algorithm in OFDMA‐based cooperative cognitive radio networks
Authors: Tang Yi , Wang Lijie , Zhao Haitao , Wei Jibo
Published: December 2014

In this paper, we propose a low‐complexity resource allocation algorithm for the orthogonal frequency division multiplexing cooperative cognitive radio networks, where multiple primary users (PUs) and multiple secondary users (SUs) coexist. Firstly, we introduce a new concept of ‘efficiency capacity’ to represent the channel conditions of SUs by considering both of the interference caused by the PUs and the channel gains of the SUs with the assist of the relays. Secondly, we allocate the relay, subcarrier and transmission power jointly under the constraint of limiting interference caused to the PUs. Simulation results show that the proposed algorithm can achieve a high data rate with a relative low power level. Copyright © 2014 John Wiley & Sons, Ltd.
An appraisal of how the vitamin A‐redox hypothesis can maintain honesty of carotenoid‐dependent signals
Authors: Simons Mirre J. P. , Groothuis Ton G. G. , Verhulst Simon
Published: December 2014

The vitamin A‐redox hypothesis provides an explanation for honest signaling of phenotypic quality by carotenoid‐dependent traits. A key aspect of the vitamin A‐redox hypothesis, applicable to both yellow and red coloration, is the hypothesized negative feedback of tightly regulated Vitamin A plasma levels on the enzyme responsible for sequestering both Vitamin A and carotenoids from the gut. We performed a meta‐analysis and find that vitamin A levels are positively related to carotenoid plasma levels (r = 0.50, P = 0.0002). On the basis of this finding and further theoretical considerations, we propose that the vitamin A‐redox hypothesis is unlikely to explain carotenoid‐dependent honest signaling.
Bioaccumulation kinetics of the conventional energetics TNT and RDX relative to insensitive munitions constituents DNAN and NTO in Rana pipiens tadpoles
Authors: Lotufo Guilherme R. , Biedenbach James M. , Sims Jerre G. , Chappell Pornsawan , Stanley Jacob K. , Gust Kurt A.
Published: December 2014

The manufacturing of explosives and their loading, assembling, and packing into munitions for use in testing on training sites or battlefields has resulted in contamination of terrestrial and aquatic sites that may pose risk to populations of sensitive species. The bioaccumulative potential of the conventional explosives 2,4,6-trinitrotoluene (TNT) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and of the insensitive munitions (i.e., less shock sensitive) compound 2,4-dinitroanisole (DNAN) were assessed using the Northern leopard frog, Rana pipiens. Trinitrotoluene entering the organism was readily biotransformed to aminodinitrotoluenes, whereas no transformation products were measured for RDX or DNAN. Uptake clearance rates were relatively slow and similar among compounds (1.32–2.19 L kg−1 h−1). Upon transfer to uncontaminated water, elimination rate was very fast, resulting in the prediction of fast time to approach steady state (5 h or less) and short elimination half-lives (1.2 h or less). A preliminary bioconcentration factor of 0.25 L kg−1 was determined for the insensitive munitions compound 3-nitro-1,2,4-trizole-5-one (NTO) indicating negligible bioaccumulative potential. Because of the rapid elimination rate for explosives, tadpoles inhabiting contaminated areas are expected to experience harmful effects only if under constant exposure conditions given that body burdens can rapidly depurate preventing tissue concentrations from persisting at levels that may cause detrimental biological effects. Environ Toxicol Chem 2015;34:880–886. © 2014 SETAC
Test Rig for Hybrid System Emulation: New Real‐Time Transient Model Validated in a Wide Operative Range
Authors: Damo U. M. , Ferrari M. L. , Turan A. , Massardo A. F.
Published: December 2014

This paper reports an entirely new simulation tool for a hybrid system emulator facility built by the Thermochemical Power Group (TPG) at the University of Genoa, Italy. This new software was developed with the following targets: real‐time performance, good stability level and high calculation reliability. In details, to obtain real‐time performance a new approach based on 0‐D technique was chosen also for components usually analysed with 1‐D or 2‐D tools (e.g. the recuperator). These are essential key aspects to operate it in hardware‐in‐the‐loop mode or to evaluate predictive results for long transient operations. This work was based on collaboration between the University of Manchester, UK and the University of Genoa, Italy.

The activity was carried out with a test rig composed of the following technology: a microturbine package able to produce up to 100 kWe and modified for external connections, external pipes designed for several purposes (by‐pass, measurement or bleed), and a high temperature modular vessel necessary to emulate the dimension of an SOFC stack. The real‐time transient model of this facility was developed inside the Matlab‐Simulink environment with the following modelling approach: a library of components allows to reach a high level of flexibility and an user‐friendly approach. This model includes the machine control system as an essential device to analyse further layouts (new components in the rig) and hardware‐in‐the‐loop operations.

The experimental data collected in the laboratory by TPG were used to validate the simulation tool. The results calculated with the model were satisfactory compared with experimental data considering both steady‐state and transient operations. The most important innovative aspects of this work are related to this wide validation range (not only small power steps, but the whole operative range was considered) obtaining real‐time performance and considering microturbine conditions different from standard operations (additional pressure and temperature losses and unusual thermal capacitance). The modelling simplified approach used for such a complex system is an important innovative aspect, because usually the model reliability performance is obtained with more complex (and not real‐time) tools. This work is based on an innovative modelling approach based on 0‐D tools able to operate in real‐time mode (as necessary for hardware‐in‐the‐loop tests) with an accuracy level comparable with more complex and more time consuming software.

This validated tool is an important base for future calculations to study innovative hybrid system layouts. For instance, TPG is planning to analyse the option of increasing fuel cell pressure and performance with a booster system (e.g. a turbocharger).
Clinical activity of androgen deprivation therapy in patients with metastatic/relapsed androgen receptor–positive salivary gland cancers
Authors: Locati Laura D. , Perrone Federica , Cortelazzi Barbara , Lo Vullo Salvatore , Bossi Paolo , Dagrada Gianpaolo , Quattrone Pasquale , Bergamini Cristiana , Potepan Paolo , Civelli Enrico , Fallai Carlo , Pilotti Silvana , Licitra Lisa
Published: December 2014

Background

Androgen deprivation therapy has some clinical activity in selected salivary gland cancer histotypes, with androgen receptor expression.

Methods

We retrospectively analyzed patients with androgen receptor‐expressing recurrent/metastatic salivary gland cancer, treated with androgen deprivation therapy. Protein expression of androgen receptor and ErbB family members was investigated. Progression‐free survival (PFS) and overall survival (OS) were the main endpoints.

Results

Seventeen patients were identified. No significant toxicities were reported. Overall response rate was 64.7%; 3‐year PFS and 5‐year OS were 11.8% and 19.3%, respectively. Androgen receptor overexpression may be sustained by gain of chromosome X (58%) and TP53 mutation (44%). No association between response to androgen deprivation therapy and epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2, HER3 expression, PIK3CA mutations, or phosphatase and tensin homolog (PTEN) deletion was identified.

Conclusion

We confirm the activity of androgen deprivation therapy in androgen receptor‐expressing recurrent/metastatic salivary gland cancers. The hypothesis that an androgen receptor increased gene copy number may represent a possible mechanism of primary resistance should be further investigated. © 2015 Wiley Periodicals, Inc. Head Neck 38: 724–731, 2016
Rising prevalence of human papillomavirus–related oropharyngeal cancer in Australia over the last 2 decades
Authors: Hong Angela , Lee C. Soon , Jones Deanna , Veillard Anne‐Sophie , Zhang Mei , Zhang Xiaoying , Smee Robert , Corry June , Porceddu Sandro , Milross Christopher , Elliott Michael , Clark Jonathan , Rose Barbara
Published: December 2014

Background

This study provides Australian data on the characteristics of human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (SCC) over the last 2 decades.

Methods

The HPV status of 515 patients with oropharyngeal SCC diagnosed between 1987 and 2010 was determined by HPV E6‐targeted multiplex real time polymerase chain reaction assay (PCR) and p16 immunohistochemistry.

Results

The HPV positivity rate increased from 20.2% (1987–1995) to 63.5% (2006–2010). Among HPV‐positive oropharyngeal SCC over the study period, the median age increased from 55.4 years to 59.8 years (p = .004) and there was a trend of an increasing proportion of never smokers (19.2% to 34.0%). The use of radiation therapy (RT) in patients with HPV‐positive oropharyngeal cancer increased from 26.9% to 68.1% (p = .007) and we also observed a trend of improved outcomes.

Conclusion

Our data show a rising prevalence of HPV‐positive oropharyngeal SCC in Australia over the last 2 decades. These patients with HPV‐positive oropharyngeal SCC are now presenting at an older age and about one third have never smoked. © 2015 Wiley Periodicals, Inc. Head Neck 38: 743–750, 2016
Surgical molecular navigation with ratiometric activatable cell penetrating peptide for intraoperative identification and resection of small salivary gland cancers
Authors: Hussain Timon , Savariar Elamprakash N. , Diaz–Perez Julio A. , Messer Karen , Pu Minya , Tsien Roger Y. , Nguyen Quyen T.
Published: December 2014

Background

We evaluated the use of intraoperative fluorescence guidance by enzymatically cleavable ratiometric activatable cell‐penetrating peptide (RACPPPLGC(Me)AG) containing Cy5 as a fluorescent donor and Cy7 as a fluorescent acceptor for salivary gland cancer surgery in a mouse model.

Methods

Surgical resection of small parotid gland cancers in mice was performed with fluorescence guidance or white light (WL) imaging alone. Tumor identification accuracy, operating time, and tumor‐free survival were compared.

Results

RACPP guidance aided tumor detection (positive histology in 90% [27/30] vs 48% [15/31] for WL; p < .001). An approximate 25% ratiometric signal increase as the threshold to distinguish between tumor and adjacent tissue, yielded >90% detection sensitivity and specificity. Operating time was reduced by 54% (p < .001), and tumor‐free survival was increased with RACPP guidance (p = .025).

Conclusion

RACPP provides real‐time intraoperative guidance leading to improved survival. Ratiometric signal thresholds can be set according to desired detection accuracy levels for future RACPP applications. © 2015 Wiley Periodicals, Inc. Head Neck 38: 715–723, 2016
Comorbidity and performance status as independent prognostic factors in patients with head and neck squamous cell carcinoma
Authors: Wang Jennifer R. , Habbous Steven , Espin–Garcia Osvaldo , Chen Duoduo , Huang Shao Hui , Simpson Colleen , Xu Wei , Liu Fei‐Fei , Brown Dale H. , Gilbert Ralph W. , Gullane Patrick J. , Irish Jonathan C. , Goldstein David P. , Liu Geoffrey
Published: December 2014

Background

The purpose of this study was to evaluate the individual and combined relationship of comorbidity and performance status (PS) on head and neck squamous cell carcinoma (HNSCC) survival.

Methods

Six hundred patients with HNSCC were prospectively recruited. Comorbidity and PS were measured using the Charlson Comorbidity Index (CCI) and the Eastern Cooperative Oncology Group (ECOG) Scale. Outcomes were overall survival (OS) and cancer‐specific survival (CSS).

Results

A total of 48.3% of the patients had at least 1 comorbidity, and 42.3% had impaired PS at baseline. There was no correlation between CCI and ECOG (Spearman's ρ = 0.033; p = .42). In multivariate analysis, CCI score was significantly associated with OS (p = .01). ECOG was not associated with OS, but seems to act as an effect modifier in the association between comorbidity and OS. CCI and ECOG were not associated with CSS.

Conclusion

CCI and ECOG scores both provide prognostic information in predicting OS in HNSCC, but a significant association with CSS was not observed. © 2015 Wiley Periodicals, Inc. Head Neck 38: 736–742, 2016
Osteoradionecrosis of mandible bone in patients with oral cancer—associated factors and treatment outcomes
Authors: Chen Jyun‐An , Wang Chen‐Chi , Wong Yong‐Kie , Wang Ching‐Ping , Jiang Rong‐San , Lin Jin‐Ching , Chen Chien‐Chih , Liu Shih‐An
Published: December 2014

Background

The purpose of this study was to investigate factors associated with osteoradionecrosis (ORN) of the mandible bone in a large cohort of patients with oral cancer.

Methods

We reviewed the medical records of patients with oral cancer and identified those with ORN of the mandible bone. Variables of patients with and without ORN were compared and associated factors were investigated by logistic regression model.

Results

A total of 1692 patients were included in the final analysis and 105 patients (6.2%) developed ORN in the mandible bone. Primary site, including mouth floor, buccal mucosa, retromolar trigone, or gum, segmental mandibulectomy, and total radiation dose to the primary site ≥75 Gy were independent factors associated with ORN. After aggressive treatment using surgical intervention with/without hyperbaric oxygen, 93.3% of the patients healed completely.

Conclusion

Among patients with oral cancer after radiation, ORN is an uncommon and dreaded complication. Recognition of associated factors can help physicians to identify those at risk. © 2015 Wiley Periodicals, Inc. Head Neck 38: 762–768, 2016
Photodamage in deep tissue two‐photon optical biopsy of human skin
Authors: Dalbosco Luca , Zanini Giulia , D'Amato Elvira , Tessarolo Francesco , Boi Sebastiana , Bauer Paolo , Haase Albrecht , Antolini Renzo
Published: December 2014

Photodamage, induced by femtosecond laser radiation, was studied in thick samples of human skin tissue (healthy skin and neoplastic lesions). Photobleaching, photoionization, and thermomechanical damage effects were characterized comparatively. The laser power dependence of the damage rates allowed to connect macroscopic effects to underlying molecular processes. Optical effects were correlated to histopathological changes. Tissue alterations were found only from thermomechanical cavitation and limited to superficial layers of the epidermis. From the depth‐dependencies of all damage thresholds a depth‐dependent power‐compensation scheme was defined allowing for damage‐free deep tissue optical biopsy.

Damage‐induced luminescence pattern for different excitation powers and a corresponding threshold analysis.

magnified image

Damage‐induced luminescence pattern for different excitation powers and a corresponding threshold analysis.
Electrospun biomaterial scaffolds with varied topographies for neuronal differentiation of human‐induced pluripotent stem cells
Authors: Mohtaram Nima Khadem , Ko Junghyuk , King Craig , Sun Lin , Muller Nathan , Jun Martin Byung‐Guk , Willerth Stephanie M.
Published: December 2014

In this study, we investigated the effect of micro and nanoscale scaffold topography on promoting neuronal differentiation of human induced pluripotent stem cells (iPSCs) and directing the resulting neuronal outgrowth in an organized manner. We used melt electrospinning to fabricate poly (ε‐caprolactone) (PCL) scaffolds with loop mesh and biaxial aligned microscale topographies. Biaxial aligned microscale scaffolds were further functionalized with retinoic acid releasing PCL nanofibers using solution electrospinning. These scaffolds were then seeded with neural progenitors derived from human iPSCs. We found that smaller diameter loop mesh scaffolds (43.7 ± 3.9 µm) induced higher expression of the neural markers Nestin and Pax6 compared to thicker diameter loop mesh scaffolds (85 ± 4 µm). The loop mesh and biaxial aligned scaffolds guided the neurite outgrowth of human iPSCs along the topographical features with the maximum neurite length of these cells being longer on the biaxial aligned scaffolds. Finally, our novel bimodal scaffolds also supported the neuronal differentiation of human iPSCs as they presented both physical and chemical cues to these cells, encouraging their differentiation. These results give insight into how physical and chemical cues can be used to engineer neural tissue. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 2591–2601, 2015.
Safety, pharmacokinetics, and pharmacodynamics of TV‐1380, a novel mutated butyrylcholinesterase treatment for cocaine addiction, after single and multiple intramuscular injections in healthy subjects
Authors: Cohen‐Barak Orit , Wildeman Jacqueline , van de Wetering Jeroen , Hettinga Judith , Schuilenga‐Hut Petra , Gross Aviva , Clark Shane , Bassan Merav , Gilgun‐Sherki Yossi , Mendzelevski Boaz , Spiegelstein Ofer
Published: December 2014

Human plasma butyrylcholinesterase (BChE) contributes to cocaine metabolism and has been considered for use in treating cocaine addiction and cocaine overdose. TV‐1380 is a recombinant protein composed of the mature form of human serum albumin fused at its amino terminus to the carboxy‐terminus of a truncated and mutated BChE. In preclinical studies, TV‐1380 has been shown to rapidly eliminate cocaine in the plasma thus forestalling entry of cocaine into the brain and heart. Two randomized, blinded phase I studies were conducted to evaluate the safety, pharmacokinetics, and pharmacodynamics of TV‐1380, following single and multiple administration in healthy subjects. TV‐1380 was found to be safe and well tolerated with a long half‐life (43–77 hours) and showed a dose‐proportional increase in systemic exposure. Consistent with preclinical results, the ex vivo cocaine hydrolysis, TV‐1380 activity clearly increased upon treatment in a dose‐dependent manner. In addition, there was a direct relationship between ex vivo cocaine hydrolysis (kel) and TV‐1380 serum concentrations. There was no evidence that TV‐1380 affected heart rate, the uncorrected QT interval, or the heart‐rate‐corrected QTcF interval. TV‐1380, therefore, offers a safe once‐weekly therapy to increase cocaine hydrolysis.
Nonseparating Cycles Avoiding Specific Vertices
Authors: Hong Yanmei , Kang Liying , Yu Xingxing
Published: December 2014

Thomassen proved that every ‐connected graph G contains an induced cycle C such that is k‐connected, establishing a conjecture of Lovász. In general, one could ask the following question: For any positive integers , does there exist a smallest positive integer such that for any ‐connected graph G, any with , and any , there is an induced cycle C in such that and is l‐connected? The case when is a well‐known conjecture of Lovász that is still open for . In this article, we prove and . We also consider a weaker version: For any positive integers , is there a smallest positive integer such that for every ‐connected graph G and any with , there is an induced cycle C in such that is l‐connected? The case when was studied by Thomassen. We prove and .
On the Decay of Crossing Numbers of Sparse Graphs
Authors: Balogh József , Leaños Jesus , Salazar Gelasio
Published: December 2014

Richter and Thomassen proved that every graph has an edge e such that the crossing number of is at least . Fox and Cs. Tóth proved that dense graphs have large sets of edges (proportional in the total number of edges) whose removal leaves a graph with crossing number proportional to the crossing number of the original graph; this result was later strenghthened by Černý, Kynčl, and G. Tóth. These results make our understanding of the decay of crossing numbers in dense graphs essentially complete. In this article we prove a similar result for large sparse graphs in which the number of edges is not artificially inflated by operations such as edge subdivisions. We also discuss the connection between the decay of crossing numbers and expected crossing numbers, a concept recently introduced by Mohar and Tamon.
Different protective and reparative effects of olmesartan in stroke according to time of administration and withdrawal
Authors: Gutiérrez‐Fernández María , Fuentes Blanca , Rodríguez‐Frutos Berta , Ramos‐Cejudo Jaime , Otero‐Ortega Laura , Díez‐Tejedor Exuperio
Published: December 2014

Angiotensin type 1 receptor blockers (ARBs) have induced improved functional recovery and reduced infarct volume in experimental animal models of stroke. Clinical data have indicated a positive correlation between prestroke treatment with ARBs and reduced stroke severity and better outcomes; however, the mechanisms of these beneficial effects are not yet well understood. This study compares the protective and possible reparative effects of continuous oral treatment with olmesartan (OLM) with OLM pretreatment and withdrawal after permanent middle cerebral artery occlusion (pMCAO) in rats. Fifty‐two Sprague‐Dawley rats were randomly assigned to five groups: MCAO–/OLM (OLM 10 mg/kg/day for 14 days after infarct), MCAOOLM/OLM (OLM 10 mg/kg/day for 7 days before and 14 days after infarct), MCAOOLM/– (OLM 10 mg/kg/day for 7 days before infarct), sham, and control. We analyzed functional recovery; lesion size; cell death; expression of the pro‐oxidant enzyme NADPH oxidase 4 (NOX‐4); isolectin‐B4; and repair markers such as glial fibrillary acidic protein, vascular endothelial growth factor (VEGF), and brain‐derived neurotrophic factor (BDNF). All of the OLM‐treated groups showed significantly better functional scores and reduced infarct sizes and cell death compared with the control group 14 days after pMCAO. Levels of NOX‐4, VEGF, and BDNF were significantly lower in the brains of the MCAOOLM/OLM and sham groups compared with the other groups. OLM treatment improved functional recovery and reduced lesion size and cell death after cerebral ischemia. Only the continuous administration of OLM before and after stroke reduced oxidative stress levels, with better tissue preservation, without triggering brain repair marker activation. © 2014 Wiley Periodicals, Inc.
Fimbriae‐mediated outer membrane vesicle production and invasion of Porphyromonas gingivalis
Authors: Mantri Chinmay K. , Chen Chin‐Ho , Dong Xinhong , Goodwin Jeffery Shawn , Pratap Siddharth , Paromov Victor , Xie Hua
Published: December 2014

Porphyromonas gingivalis is a keystone periopathogen that plays an essential role in the progress of periodontitis. Like other gram‐negative bacteria, the ability of P. gingivalis to produce outer membrane vesicles is a strategy used to interact with, and survive within its biological niches. Here we compared the protein components associated with vesicles derived from a fimbriated strain (33277) and an afimbriated strain (W83) of P. gingivalis using proteomic analyses. Some well‐known virulence factors were identified in vesicles from both strains, such as gingipains and hemagglutinin. In contrast, FimC, FimD, and FimE, minor components of long fimbriae were found exclusively in 33277 vesicles, while proteins with a tetratricopeptide repeat (TPR) domain were unique to W83 vesicles. We found that significantly more 33277 than W83 vesicles were internalized into human oral keratinocytes and gingival fibroblasts. Interestingly, FimA, a well‐known adhesin responsible for the attachment and invasion of P. gingivalis into host cells, was not essential for the invasive capabilities of P. gingivalis vesicles. Rather minor components of long fimbriae were required for an efficient invasive activity of vesicles. The most striking finding was that P. gingivalis strains lacking or having a reduced FimA expression showed a significant reduction in vesiculation. These results suggest that production and pathogenicity of P. gingivalis vesicles may largely depend on expression of the fim locus, and that the integration of vesicle production and pathogenicity with fimbrial expression may allow P. gingivalis to confer upon itself certain functional advantages.
Modeling the World Health Organization Disability Assessment Schedule II using non‐parametric item response models
Authors: Galindo‐Garre Francisca , Hidalgo María Dolores , Guilera Georgina , Pino Oscar , Rojo J. Emilio , Gómez‐Benito Juana
Published: December 2014

The World Health Organization Disability Assessment Schedule II (WHO‐DAS II) is a multidimensional instrument developed for measuring disability. It comprises six domains (getting around, self‐care, getting along with others, life activities and participation in society). The main purpose of this paper is the evaluation of the psychometric properties for each domain of the WHO‐DAS II with parametric and non‐parametric Item Response Theory (IRT) models. A secondary objective is to assess whether the WHO‐DAS II items within each domain form a hierarchy of invariantly ordered severity indicators of disability.

A sample of 352 patients with a schizophrenia spectrum disorder is used in this study. The 36 items WHO‐DAS II was administered during the consultation. Partial Credit and Mokken scale models are used to study the psychometric properties of the questionnaire.

The psychometric properties of the WHO‐DAS II scale are satisfactory for all the domains. However, we identify a few items that do not discriminate satisfactorily between different levels of disability and cannot be invariantly ordered in the scale.

In conclusion the WHO‐DAS II can be used to assess overall disability in patients with schizophrenia, but some domains are too general to assess functionality in these patients because they contain items that are not applicable to this pathology. Copyright © 2014 John Wiley & Sons, Ltd.
Effects of tail suspension on serum testosterone and molecular targets regulating muscle mass
Authors: De Naeyer Hélène , Lamon Séverine , Russell Aaron P. , Everaert Inge , De Spaey Annelies , Jamart Cécile , Vanheel Bert , Taes Youri , Derave Wim
Published: December 2014

Introduction: The contribution of reduced testosterone levels to tail suspension (TS)‐induced muscle atrophy remains equivocal. The molecular mechanism by which testosterone regulates muscle mass during TS has not been investigated. Methods: Effects of TS on serum testosterone levels, muscle mass, and expression of muscle atrophy‐ and hypertrophy‐inducing targets were measured in soleus (SOL) and extensor digitorum longus (EDL) muscles after testosterone administration during 1, 5, and 14 days of TS in male mice. Results: TS produced an increase followed by a transient drop in testosterone levels. Muscle atrophy was associated with downregulation of Igf1 and upregulation of Mstn, Redd1, Atrogin‐1, and MuRF1 mRNA with clear differences in Igf1, Mstn, and MAFbx/Atrogin‐1 gene expression between SOL and EDL. Testosterone supplementation did not affect muscle mass or protein expression levels during TS. Conclusions The known anabolic effects of testosterone are not sufficient to ameliorate loss of muscle mass during TS. Muscle Nerve 52: 278–288, 2015
Corticosteroid injection in patients with ulnar neuropathy at the elbow: A randomized, double‐blind, placebo‐controlled trial
Authors: vanVeen Kiril E.B. , Alblas Kees (C) L. , Alons Imanda M.E. , Kerklaan Joost P. , Siegersma Marry C. , Wesstein Michel , Visser Leo H. , vankasteel Viviane , Jellema Korné
Published: December 2014

Introduction

We conducted a randomized, double‐blind, placebo‐controlled trial to evaluate the effect of ultrasound‐guided corticosteroid injection in patients with ulnar neuropathy at the elbow (UNE).

Methods

Fifty‐five patients were randomized between an ultrasound‐guided injection of 1 ml containing 40 mg methylprednisolone acetate and 10 mg lidocaine hydrochloride or a placebo injection. The primary outcome was the subjective change of symptoms after 3 months. The secondary outcomes were change in electrodiagnostic studies and ultrasonography findings.

Results

A success rate of 30% was found in the corticosteroid injection group versus 28% in the placebo injection group. Only the nerve cross‐sectional area changed significantly in the intervention group, from a mean of 11.9 mm2 to 10.9 mm2.

Conclusions

We could not demonstrate a positive effect of ultrasound‐guided corticosteroid injection in UNE compared with placebo. Favorable outcomes may be attributed to the natural course of UNE or the effect of patient education. Muscle Nerve 52:380–385, 2015
Dynamic finite element formulation for Cosserat elastic plates
Authors: Godio Michele , Stefanou Ioannis , Sab Karam , Sulem Jean
Published: December 2014

A displacement and rotation‐based dynamic finite element formulation for Cosserat plates is discussed in detail in this paper. Special attention is given to the validation of the element through adequate benchmarks and patch tests. The choice of the interpolation functions and the order of integration of the stiffness and the mass matrices are extensively argued. The possibility of local system deficiencies is explored, and a shear locking investigation specifically elaborated for Cosserat plates is carried out. It is shown how the present formulation has interesting computational properties as compared to a classical continuum‐based formulation and how it can provide suitable results despite the use of reduced integration. An example of application of the finite element is given, in which the natural frequencies of a masonry panel modelled by means of discrete elements are computed and compared with the finite elements solution. Copyright © 2014 John Wiley & Sons, Ltd.
Solution processing of polymer semiconductor: Insulator blends—Tailored optical properties through liquid–liquid phase separation control
Authors: Hellmann Christoph , Treat Neil D. , Scaccabarozzi Alberto D. , Razzell Hollis Joseph , Fleischli Franziska D. , Bannock James H. , de Mello John , Michels Jasper J. , Kim Ji‐Seon , Stingelin Natalie
Published: December 2014

It has been demonstrated that the 0‐0 absorption transition of poly(3‐hexylthiophene) (P3HT) in blends with poly(ethylene oxide) (PEO) could be rationally tuned through the control of the liquid–liquid phase separation process during solution deposition. Pronounced J‐like aggregation behavior, characteristic for systems of a low exciton band width, was found for blends where the most pronounced liquid–liquid phase separation occurred in solution, leading to domains of P3HT and PEO of high phase purity. Since liquid–liquid phase separation could be readily manipulated either by the solution temperature, solute concentration, or deposition temperature, to name a few parameters, our findings promise the design from the out‐set of semiconductor:insulator architectures of pre‐defined properties by manipulation of the interaction parameter between the solutes as well as the respective solute:solvent system using classical polymer science principles. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015, 53, 304–310
Discovering cancer biomarkers from clinical samples by protein microarrays
Authors: Hu Bin , Niu Xin , Cheng Li , Yang Li‐Na , Li Qing , Wang Yang , Tao Sheng‐Ce , Zhou Shu‐Min
Published: December 2014

Cancer biomarkers are of potential use in early cancer diagnosis, anticancer therapy development, and monitoring the responses to treatments. Protein‐based cancer biomarkers are major forms in use, as they are much easier to be monitored in body fluids or tissues. For cancer biomarker discovery, high‐throughput techniques such as protein microarrays hold great promises, because they are capable of global unbiased monitoring but with a miniaturized format. In doing so, novel and cancer type specific biomarkers can be systematically discovered at an affordable cost. In this review, we give a relatively complete picture on protein microarrays applied to clinical samples for cancer biomarker discovery, and conclude this review with the future perspectives.
K114 (trans, trans)‐bromo‐2,5‐bis(4‐hydroxystyryl)benzene is an efficient detector of cationic amyloid fibrils
Authors: Selmani Veli , Robbins Kevin J. , Ivancic Valerie A. , Lazo Noel D.
Published: December 2014

Cationic amyloid fibrils found in human semen enhance the transmission of the human immunodeficiency virus (HIV) and thus, are named semen‐derived enhancer of virus infection (SEVI). The mechanism for the enhancement of transmission is not completely understood but it has been proposed that SEVI neutralizes the repulsion that exists between the negatively charged viral envelope and host cell membrane. Consistent with this view, here we show that the fluorescence of cationic thioflavin T (ThT) in the presence of SEVI is weak, and thus ThT is not an efficient detector of SEVI. On the other hand, K114 ((trans, trans)‐bromo‐2,5‐bis(4‐hydroxystyryl)benzene) forms a highly fluorescent, phenolate‐like species on the cationic surface of SEVI. This species does not form in the presence of amyloid fibrils from insulin and amyloid‐β protein, both of which are efficiently detected by ThT fluorescence. Together, our results show that K114 is an efficient detector of SEVI.
Methodical assessment of the differences between the QNSE and MYJ PBL schemes for stable conditions
Authors: Tastula Esa‐Matti , Galperin Boris , Dudhia Jimy , LeMone Margaret A. , Sukoriansky Semion , Vihma Timo
Published: December 2014

The increasing number of physics parametrization schemes adopted in numerical weather forecasting models has resulted in a proliferation of intercomparison studies in recent years. Many of these studies concentrated on determining which parametrization yields results closest to observations rather than analyzing the reasons underlying the differences. In this work, we study the performance of two 1.5‐order boundary layer parameterizations, the quasi‐normal scale elimination (QNSE) and Mellor–Yamada–Janjić (MYJ) schemes, in the weather research and forecasting model. Our objectives are to isolate the effect of stability functions on the near‐surface values and vertical profiles of virtual temperature, mixing ratio and wind speed. The results demonstrate that the QNSE stability functions yield better error statistics for 2 m virtual temperature but higher up the errors related to QNSE are slightly larger for virtual temperature and mixing ratio. A surprising finding is the sensitivity of the model results to the choice of the turbulent Prandtl number for neutral stratification (Prt0): in the Monin–Obukhov similarity function for heat, the choice of Prt0 is sometimes more important than the functional form of the similarity function itself. There is a stability‐related dependence to this sensitivity: with increasing near‐surface stability, the relative importance of the functional form increases. In near‐neutral conditions, QNSE exhibits too strong vertical mixing attributed to the applied turbulent kinetic energy subroutine and the stability functions, including the effect of Prt0.
A dual‐observer approach for global output feedback stabilization of planar nonlinear systems with output‐dependent growth rates
Authors: Wang Xiangyu , Qian Chunjiang , Li Shihua
Published: December 2014

In this paper, we investigate the problem of global output feedback stabilization for a class of planar nonlinear systems under a more general growth condition, which encompasses both lower‐order and higher‐order state growths with output‐dependent rates. For more accurate estimation, two new observers with nonlinear gains are constructed to estimate the states on the lower‐order and higher‐order scales, respectively. The estimates produced from the dual‐observer are used delicately in the output feedback control law with both lower‐order and higher‐order modes. The overall stability of the system is guaranteed by rigorously choosing these nonlinear gains in the control law and the dual‐observer.
Adaptive fault‐tolerant control for a class of output‐constrained nonlinear systems
Authors: Jin Xu
Published: December 2014

In this work, by incorporating a tan‐type barrier Lyapunov function into the Lyapunov function design, we present a novel adaptive fault‐tolerant control (FTC) scheme for a class of output‐constrained multi‐input single‐output nonlinear systems with actuator failures under the perturbation of both parametric and nonparametric system uncertainties. We show that under the proposed adaptive FTC scheme, exponential convergence of the output tracking error into a small set around zero is guaranteed, while the constraint requirement on the system output will not be violated during operation. In the end, two illustrative examples are presented to demonstrate the effectiveness of the proposed FTC scheme. Copyright © 2015 John Wiley & Sons, Ltd.
Therapeutic gold, silver, and platinum nanoparticles
Authors: Yamada Miko , Foote Matthew , Prow Tarl W.
Published: December 2014

There are an abundance of nanoparticle technologies being developed for use as part of therapeutic strategies. This review focuses on a narrow class of metal nanoparticles that have therapeutic potential that is a consequence of elemental composition and size. The most widely known of these are gold nanoshells that have been developed over the last two decades for photothermal ablation in superficial cancers. The therapeutic effect is the outcome of the thickness and diameter of the gold shell that enables fine tuning of the plasmon resonance. When these metal nanoparticles are exposed to the relevant wavelength of light, their temperature rapidly increases. This in turn induces a localized photothermal ablation that kills the surrounding tumor tissue. Similarly, gold nanoparticles have been developed to enhance radiotherapy. The high‐Z nature of gold dramatically increases the photoelectric cross‐section. Thus, the photoelectric effects are significantly increased. The outcome of these interactions is enhanced tumor killing with lower doses of radiation, all while sparing tissue without gold nanoparticles. Silver nanoparticles have been used for their wound healing properties in addition to enhancing the tumor‐killing effects of anticancer drugs. Finally, platinum nanoparticles are thought to serve as a reservoir for platinum ions that can induce DNA damage in cancer cells. The future is bright with the path to clinical trials is largely cleared for some of the less complex therapeutic metal nanoparticle systems. WIREs Nanomed Nanobiotechnol 2015, 7:428–445. doi: 10.1002/wnan.1322

This article is categorized under:

Implantable Materials and Surgical Technologies > Nanomaterials and Implants

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery