bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporating work zone configuration factors into speed‐flow and capacity models
Authors: Weng Jinxian , Meng Qiang
Published: June 2014

This study aims to develop work zone speed‐flow and capacity models, which incorporate work zone configuration factors including the number of work zones, geometrical alignment, work zone speed limit, and work zone length. On the basis of the traffic data from six work zone sites with various work zone configurations, two nonlinear traffic speed and flow models including work zone configuration factors are developed for the uncongested and congested traffic conditions, respectively. A work zone capacity model is proposed on the basis of the two models. The three models can further be used to examine the effects of work zone configuration factors on the speed‐flow relationship and capacity at work zones. Results show that traffic speed, traffic flow, and work zone capacity increase with the posted speed limit. Traffic speed under uncongested conditions decreases with the geometric alignment, the number of work zones, work zone length, and heavy vehicle percentage. Under congested conditions, the increase of the number of work zones is found to exhibit a larger negative impact on the traffic flow than the increase of geometric alignment. The number of work zones is also found to have the largest negative impacts on work zone capacity, followed by the geometric alignment. Short work zone length exhibits a relatively minor contribution to increasing work zone capacity. Copyright © 2014 John Wiley & Sons, Ltd.
Zum Einfluss von Atrien auf die Gebäudeenergieeffizienz – eine Fallanalyse mit Betriebsoptimierung eines Atriumgebäudes
Authors: Zargari Mani
Published: June 2014

Der Einfluss von Atrien auf die Energieeffizienz und den thermischen Komfort eines Gebäudes kann sehr unterschiedlich ausfallen. Entscheidend hierfür sind die konstruktiven Randbedingungen und das Energiekonzept eines Atriumgebäudes. Anhand der erfolgreichen Umsetzung von Optimierungsmaßnahmen am Hauptgebäude der LBS Nord Hannover Kronsberg mit einem begleitenden messtechnischen Monitoring wird demonstriert, wie sich unterschiedliche Energiekonzepte auf die Energieeffizienz und den thermischen Komfort des Gesamtgebäudes auswirken. Die Belüftung der zwischen den Gebäuderiegeln liegenden verglasten Grünhöfe wird so angepasst, dass die jeweils geltenden Konditionierungsanforderungen des Kerngebäudes unterstützt werden. Durch eine verbesserte Integration der Grünhöfe in das Belüftungskonzept der Kerngebäude werden die Lüftungswärmeverluste und der Energieaufwand für die mechanische Belüftung verringert. Im Beobachtungszeitraum ist daher eine signifikante Reduzierung des Energieverbrauchs für Wärme, Kälte und Strom zu verzeichnen. Darüber hinaus hat sich das sommerliche Raumklima in den Grünhöfen und den Büros deutlich verbessert. Zudem wird aufgezeigt, wie diese Maßnahmen unter Berücksichtigung der thermischen Anforderungen der winterlichen Vegetationsruhe der Bepflanzung umgesetzt werden können.

The effect of atria to the energy efficiency of buildings – a case study with the re‐commissioning of an atria building. The influence of an atrium on the energy efficiency and the thermal comfort of a building can be different. Decisive are construction boundaries and the energy design of the building. On the basis of an successful optimization of the headquarter building of LBS Nord in Hannover Kronsberg with an accompanying measurement based monitoring it can be shown, what kind of impact different energy concepts of the integrated atria have on the energy efficiency and thermal comfort of the whole building. The ventilation of the unconditioned atrium in the analyzed building has been adapted to the heating and cooling requirements of the core building in a way that these demands are actively supported. Due to this improved integration of the atrium in the whole building the ventilation heat loss and the electric power consumption for the air handling systems are lowered. In the observation period the energy demand of the building for heating, cooling and lighting had been reduced. The thermal comfort in the atria and the adjacent offices during the summer period has been improved. Additionally it has been shown how the changes in the energy concept can be achieved by considering the thermal requirements of the winter dormancy of the plants inside the atria.
Passivhaustauglichkeit von Fensteranschlüssen entsprechend ift‐Richtlinie WA‐15/2‐Bauanschlussfugen Teil 1: Bewertung der energetischen Qualität und Dauerhaftigkeit
Authors: Leimer Hans‐Peter , Schneider Jan
Published: June 2014

Jedes Gebäude verfügt über eine Vielzahl unterschiedlicher Bauanschlussfugen. In Anbetracht der geforderten energetischen Qualität der Gebäudehülle müssen diese Bauanschlussfugen dauerhaft luftdicht hergestellt werden und über entsprechende wärmetechnische Eigenschaften verfügen, um die Einflussnahme auf das energetische Verhalten des Gebäudes zu reduzieren. Gerade die energetische Optimierung von Bauteilanschlüssen bzw. Wärmebrücken wurde in den letzten Jahren daher stark thematisiert. Die Bewertung und Untersuchung der Dauerhaftigkeit von Abdichtungssystemen hingegen hat noch nicht Einzug in die aktuelle Normung gehalten. Die hier vorgestellte Untersuchung beschäftigt sich daher mit der Bewertung der energetischen Qualität von Fensteranschlüssen einerseits sowie mit der Dauerhaftigkeit von marktgängigen Systemen andererseits.

Passive house suitability of window connections according to the German ift guideline WA‐15/2 on component connections. Part 1: Evaluation of the energy performance and durability. Buildings have various component connections. In view of the required energetic quality of the building envelope component connections shall be durably airtight and have appropriate thermal properties to reduce the influence on the energy performance of the building. Especially the energy optimization of component connections or thermal bridges was discussed in recent years. The evaluation and analysis of the durability of joint seals did not enter the current standards yet. The presented study refers to the evaluation of the energetically quality of window connections and to the durability of marketable joint seals.
Fez family transcription factors: Controlling neurogenesis and cell fate in the developing mammalian nervous system
Authors: Eckler Matthew J. , Chen Bin
Published: June 2014

Fezf1 and Fezf2 are highly conserved transcription factors that were first identified by their specific expression in the anterior neuroepithelium of Xenopus and zebrafish embryos. These proteins share an N‐terminal domain with homology to the canonical engrailed repressor motif and a C‐terminal DNA binding domain containing six C2H2 zinc‐finger repeats. Over a decade of study indicates that the Fez proteins play critical roles during nervous system development in species as diverse as fruit flies and mice. Herein we discuss recent progress in understanding the functions of Fezf1 and Fezf2 in neurogenesis and cell fate specification during mammalian nervous system development. Going forward we believe that efforts should focus on understanding how expression of these factors is precisely regulated, and on identifying target DNA sequences and interacting partners. Such knowledge may reveal the mechanisms by which Fezf1 and Fezf2 accomplish both independent and redundant functions across diverse tissue and cell types.
The intermediates take it all: Asymptotics of higher criticism statistics and a powerful alternative based on equal local levels
Authors: Gontscharuk Veronika , Landwehr Sandra , Finner Helmut
Published: June 2014

The higher criticism (HC) statistic, which can be seen as a normalized version of the famous Kolmogorov–Smirnov statistic, has a long history, dating back to the mid seventies. Originally, HC statistics were used in connection with goodness of fit (GOF) tests but they recently gained some attention in the context of testing the global null hypothesis in high dimensional data. The continuing interest for HC seems to be inspired by a series of nice asymptotic properties related to this statistic. For example, unlike Kolmogorov–Smirnov tests, GOF tests based on the HC statistic are known to be asymptotically sensitive in the moderate tails, hence it is favorably applied for detecting the presence of signals in sparse mixture models. However, some questions around the asymptotic behavior of the HC statistic are still open. We focus on two of them, namely, why a specific intermediate range is crucial for GOF tests based on the HC statistic and why the convergence of the HC distribution to the limiting one is extremely slow. Moreover, the inconsistency in the asymptotic and finite behavior of the HC statistic prompts us to provide a new HC test that has better finite properties than the original HC test while showing the same asymptotics. This test is motivated by the asymptotic behavior of the so‐called local levels related to the original HC test. By means of numerical calculations and simulations we show that the new HC test is typically more powerful than the original HC test in normal mixture models.
Spectroscopic and molecular simulation studies on the interaction of di‐(2‐ethylhexyl) phthalate and human serum albumin
Authors: Wang Yaping , Zhang Guowen
Published: June 2014

Di‐(2‐ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in industrial production, but may have a potential health risk. In this study, the binding characteristics of DEHP with human serum albumin (HSA) in aqueous solution at pH 7.4 were determined using UV/vis absorption, fluorescence, Fourier transform infrared (FTIR) spectroscopy and circular dichroism (CD), along with a molecular simulation technique. Analysis of the fluorescence titration data at different temperatures suggested that the fluorescence quenching mechanism of HSA by DEHP was static. The calculated thermodynamic parameters indicated that hydrophobic forces played a predominant role in formation of the DEHP–HSA complex, but hydrogen bonds could not be omitted. Site marker competitive experiments and denaturation studies showed that the binding of DEHP to HSA primarily took place in subdomain IIA of HSA, and molecular docking results further corroborated the binding sites. The synchronous fluorescence, UV/vis absorption, FTIR and CD spectra revealed that the addition of DEHP induced changes in the secondary structure of HSA. Protein surface hydrophobicity (PSH) tests indicated that DEHP binding to HSA caused an increase in the PSH. Moreover, the effects of some metal ions on the binding constant of DEHP − HSA interaction were also investigated. Copyright © 2014 John Wiley & Sons, Ltd.
Effect of regional trauma centralization on volume, injury severity and outcomes of injured patients admitted to trauma centres
Authors: Metcalfe D , Bouamra O , Parsons N R , Aletrari M-O , Lecky F E , Costa M L
Published: June 2014

Background

Centralization of complex healthcare services into specialist high-volume centres is believed to improve outcomes. For injured patients, few studies have evaluated the centralization of major trauma services. The aim of this study was to evaluate how a regional trauma network affected trends in admissions, case mix, and outcomes of injured patients.

Methods

A retrospective before–after study was undertaken of severely injured patients attending four hospitals that became major trauma centres (MTCs) in March 2012. Consecutive patients with major trauma were identified from a national registry and divided into two groups according to injury before or after the launch of a new trauma network. The two cohorts were compared for differences in case mix, demand on hospital resources, and outcomes.

Results

Patient volume increased from 442 to 1326 (200 per cent), operations from 349 to 1231 (253 per cent), critical care bed-days from 1100 to 3704 (237 per cent), and total hospital bed-days from 7910 to 22 772 (188 per cent). Patient age increased on MTC designation from 45·0 years before March 2012 to 48·2 years afterwards (P = 0·021), as did the proportion of penetrating injuries (1·8 versus 4·1 per cent; P = 0·025). Injury severity fell as measured by median Injury Severity Score (16 versus 14) and Revised Trauma Score (4·1 versus 7·8). Fewer patients required secondary transfer to a MTC from peripheral hospitals (19·9 versus 16·1 per cent; P = 0·100). There were no significant differences in total duration of hospital stay, critical care requirements or mortality. However, there was a significant increase, from 55·5 to 62·3 per cent (P < 0·001), in the proportion of patients coded as having a ‘good recovery’ at discharge after institution of the trauma network.

Conclusion

MTC designation leads to an increased case volume with considerable implications for operating theatre capacity and bed occupancy. Although no mortality benefit was demonstrated within 6 months of establishing this trauma network, early detectable advantages included improved functional outcome at discharge.
Multiparametric magnetic resonance imaging outperforms the Prostate Cancer Prevention Trial risk calculator in predicting clinically significant prostate cancer
Authors: Salami Simpa S. , Vira Manish A. , Turkbey Baris , Fakhoury Mathew , Yaskiv Oksana , Villani Robert , Ben‐Levi Eran , Rastinehad Ardeshir R.
Published: June 2014

BACKGROUND

The Prostate Cancer Prevention Trial risk calculator for high‐grade (PCPTHG) prostate cancer (CaP) was developed to improve the detection of clinically significant CaP. In this study, the authors compared the performance of the PCPTHG against multiparametric magnetic resonance imaging (MP‐MRI) in predicting men at risk of CaP.

METHODS

Men with an abnormal prostate‐specific antigen (PSA) level or digital rectal examination (DRE) and a suspicious lesion on a 3‐Tesla MP‐MRI were enrolled prospectively. Three radiologists reviewed and graded all lesions on a 5‐point Likert scale. Biopsy of suspicious lesion(s) was performed using a proprietary MRI/transrectal ultrasound fusion‐guided prostate biopsy system, after which 12‐core biopsy was performed. A genitourinary pathologist reviewed all pathology slides. The performance of PCPTHG was compared with that of MP‐MRI in predicting clinically significant CaP.

RESULTS

Of 175 men who were eligible for analysis, 64.6% (113 of 175 men) were diagnosed with CaP, including 93 of 113 men (82.3%) who had clinically significant disease. Age, abnormal DRE, PSA, PSA density, prostate size, extraprostatic extension on MRI, apparent diffusion coefficient value, and MRI lesion size were identified as significant predictors of high‐grade CaP (all P < .05). The area under the receiver operating characteristic curve of PCPTHG for predicting high‐grade CaP was 0.676 (95% confidence interval [CI], 0.592‐0.751). By using a risk cutoff of ≥15% for biopsy as, proposed previously for high‐grade CaP, sensitivity was 96.4%, specificity was 7.6%, and the false‐positive rate was 51.1%. In contrast, the area under the receiver operating characteristic curve of MP‐MRI for high‐grade CaP was 0.769 (95% CI, 0.703‐0.834), and it was 0.812 (95% CI, 0.754‐0.869) for clinically significant CaP.

CONCLUSIONS

MP‐MRI outperforms PCPTHG in predicting clinically significant CaP, and its application may help select patients who will benefit from CaP diagnosis and treatment. Cancer 2014;120:2876–2882. © 2014 American Cancer Society.
Effects of metformin on endometrial cancer cell growth in vivo: A preoperative prospective trial
Authors: Mitsuhashi Akira , Kiyokawa Takako , Sato Yasunori , Shozu Makio
Published: June 2014

BACKGROUND

Metformin, an antidiabetic drug, decreases the incidence of various cancers in diabetic patients. Metformin‐induced inhibition of cancer cell proliferation has been confirmed in vitro but not in humans. Because endometrial cancer is associated with insulin resistance, the authors investigated whether a diabetes‐therapeutic metformin dose inhibits cancer cell growth in patients with endometrial cancer.

METHODS

A dose of metaformin was administered (1500‐2250 mg/day) to 31 patients with endometrial cancer preoperatively for 4 to 6 weeks. Cell proliferation was assessed in patient tissues using immunohistochemical and Western blot analyses and DNA synthesis was measured in serum using a thymidine uptake assay. All statistical tests were 2‐sided. P values of < .05 were considered statistically significant.

RESULTS

Preoperative metformin treatment decreased DNA synthesis in sera and significantly reduced the Ki‐67 (mean proportional decrease, 44.2%; 95% confidence interval [95% CI], 35.4‐53.0 [P < .001]) and topoisomerase IIα (mean proportional decrease, 36.4%; 95% CI, 26.7‐46.0 [P < .001]) labeling indices. Levels of phospho‐ribosomal protein S6 and phospho‐extracellular signal‐regulated kinase 1/2 (ERK1/2) were found to be significantly decreased and phospho‐adenosine monophosphate‐activated protein kinase and p27 levels were significantly increased. Preoperative metformin use caused significant decreases in circulating factors, including insulin, glucose, insulin‐like growth factor 1, and leptin. DNA synthesis‐stimulating activity in patient sera was significantly decreased during metformin administration.

CONCLUSIONS

An antidiabetic dose of metformin inhibited endometrial cancer cell growth in vivo, an effect likely due to its effect on humoral factor(s). This translational study provides considerable rationale to initiate large clinical trials. Cancer 2014;120:2986–2995. © American Cancer Society.
Shh‐proteoglycan interactions regulate maturation of olfactory glomerular circuitry
Authors: Persson Laura , Witt Rochelle M. , Galligan Meghan , Greer Paul L. , Eisner Adriana , Pazyra‐Murphy Maria F. , Datta Sandeep R. , Segal Rosalind A.
Published: June 2014

The olfactory system relies on precise circuitry connecting olfactory sensory neurons (OSNs) and appropriate relay and processing neurons of the olfactory bulb (OB). In mammals, the exact correspondence between specific olfactory receptor types and individual glomeruli enables a spatially precise map of glomerular activation that corresponds to distinct odors. However, the mechanisms that govern the establishment and maintenance of the glomerular circuitry are largely unknown. Here we show that high levels of Sonic Hedgehog (Shh) signaling at multiple sites enable refinement and maintenance of olfactory glomerular circuitry. Mice expressing a mutant version of Shh (ShhAla/Ala), with impaired binding to proteoglycan co‐receptors, exhibit disproportionately small olfactory bulbs containing fewer glomeruli. Notably, in mutant animals the correspondence between individual glomeruli and specific olfactory receptors is lost, as olfactory sensory neurons expressing different olfactory receptors converge on the same glomeruli. These deficits arise at late stages in post‐natal development and continue into adulthood, indicating impaired pruning of erroneous connections within the olfactory bulb. In addition, mature ShhAla/Ala mice exhibit decreased proliferation in the subventricular zone (SVZ), with particular reduction in neurogenesis of calbindin‐expressing periglomerular cells. Thus, Shh interactions with proteoglycan co‐receptors function at multiple locations to regulate neurogenesis and precise olfactory connectivity, thereby promoting functional neuronal circuitry. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1255–1267, 2014
Estimation Methods of Short Circuit Current Using Normal PMU Measurements and Field Testing
Authors: Verma Suresh Chand , Nakachi Yoshiki , Wazawa Yoshihiko , Kosaka Yoko , Kobayashi Takenori , Omata Kazuya , Takabayashi Yoshiki
Published: June 2014

This paper proposes estimation methods for short circuit currents using phasor measurement unit (PMU) measurements (phasors). The methods follow the basic notion of representing the source side of a power system by an equivalent circuit with a voltage behind a back impedance, and employ a set of voltage and current phasors measured at substations during the normal variation of loads in their estimation. In order to improve the estimation accuracy of the proposed methods, the concept of using the changes between consecutive phasors is introduced. Furthermore, to make the methods applicable to a real‐world system, the concept of a reference phasor, used to remove the effects of system‐wide frequency variations and a filtering process to filter out the outlier phasors, is proposed and implemented. The validity and effectiveness of the proposed methods were checked and confirmed through experiments and field tests.
Copper‐Assisted Hemiacetal Synthesis: A CuII Chain Obtained by a One‐Step in situ Reaction of Picolinaldehyde
Authors: Dhal Piu , Sasmal Ashok , Gómez‐García Carlos J. , Bauzá Antonio , Frontera Antonio , Pilet Guillaume , Mitra Samiran
Published: June 2014

The 1D polymer complex [Cu2(L)2(SCN)2]n (1) has been synthesised in a one‐step in situ reaction of picolinaldehyde with sodium thiocyanate. The complex 1 was characterised by FTIR spectroscopy, UV/Vis spectrophotometry and elemental analysis. The crystal structure of complex 1 shows that chains of dimer complexes are formed with tetra‐ and pentacoordinate copper centres alternately linked by one thiocyanato and two alkoxido bridges. Variable‐temperature magnetic measurements showed a strong antiferromagnetic interaction between the copper centres within the dimer mediated by the two alkoxido bridges with a J value of –374 cm–1, which is in agreement with the DFT‐calculated value of –284 cm–1. EPR and cyclic voltammetric analyses were also carried out, as well as DFT calculations to evaluate the packing forces and their energies.
Substituted Benzo[a]carbazoles and Indoleacetic Acids from Arylglyoxals and Enamines through Domino Condensation, Thermal Cyclization, and Aromatization
Authors: Maity Subhendu , Pathak Sudipta , Pramanik Animesh
Published: June 2014

A two‐step method has been developed in which cyclohexanone‐fused 2‐(3‐pyrrolyl)‐2‐cyanoacetamides, the condensation products of enamines, arylglyoxals, and malononitrile, are converted into highly substituted benzo[a]carbazoles through a one‐step thermal cyclization and palladium‐catalyzed aromatization. The biologically important indoleacetic acid derivatives are also obtained in good yields from the hydrolysis and aromatization of the same cyanoacetamides.
Autoxidation as a trigger for the slow release of volatile perfumery chemicals
Authors: Indradas Brinda , Hansen Christopher , Palmer Michael , Womack Gary B.
Published: June 2014

Finding suitable precursor molecules that extend the lifetime of perfumes by decomposing and releasing fragrant chemicals under relatively mild, ambient conditions remains a significant challenge. Although the majority of effort in this regard has been directed toward using hydrolysis reactions as the release event, autoxidation and subsequent fragmentation reactions also would appear to be well suited for this purpose given the constant exposure of deposited perfumes to atmospheric oxygen. Divinyl ethers, prepared from enolizable perfume aldehydes, have two olefin functions adjacent to the ether oxygen and were found to provide prolonged release of fragrant carbonyl compounds by an autoxidative fragmentation process. After deposition onto cotton terry cloth from a liquid fabric softener, dynamic headspace analysis showed the liberation of the parent aldehyde along with a one‐carbon smaller carbonyl compound and the enol formate ester of the parent aldehyde. Depending on the structure of the divinyl ether both liberated carbonyl compounds can be perfumery materials and both always were released from the cotton at significantly higher levels than the unmodified parent aldehydes used to prepare reference samples. Autoxidation of the divinyl ethers initiated by peroxy‐radical addition to alkene functions would account for the oxidative cleavage reactions yielding the smaller carbonyl compounds and the enol formates. Hydrolysis of the enol formate could generate the parent aldehyde. The liberation of volatile carbonyl compounds from divinyl ethers demonstrates the potential usefulness of autoxidation as a trigger for the sustained release of fragrant compounds from suitably designed precursors. Copyright © 2014 John Wiley & Sons, Ltd.
Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis
Authors: Smagris Eriks , BasuRay Soumik , Li John , Huang Yongcheng , Lai Ka‐man V. , Gromada Jesper , Cohen Jonathan C. , Hobbs Helen H.
Published: June 2014

A sequence polymorphism (rs738409, I148M) in patatin‐like phospholipid domain containing protein 3 (PNPLA3) is strongly associated with nonalcoholic fatty liver disease (NAFLD), but the mechanistic basis for this association remains enigmatic. Neither ablation nor overexpression of wild‐type PNPLA3 affects liver fat content in mice, whereas hepatic overexpression of the human 148M transgene causes steatosis. To determine whether the 148M allele causes fat accumulation in the liver when expressed at physiological levels, we introduced a methionine codon at position 148 of the mouse Pnpla3 gene. Knockin mice had normal levels of hepatic fat on a chow diet, but when challenged with a high‐sucrose diet their liver fat levels increased 2 to 3‐fold compared to wild‐type littermates without any associated changes in glucose homeostasis. The increased liver fat in the knockin mice was accompanied by a 40‐fold increase in PNPLA3 on hepatic lipid droplets, with no increase in hepatic PNPLA3 messenger RNA (mRNA). Similar results were obtained when the catalytic dyad of PNPLA3 was inactivated by substituting the catalytic serine with alanine (S47A). Conclusion: These data provide the first direct evidence that physiological expression of PNPLA3 148M variant causes NAFLD, and that the accumulation of catalytically inactive PNPLA3 on the surfaces of lipid droplets is associated with the accumulation of TG in the liver. (Hepatology 2015;61:108–118)
Proposals to Establish a Partnership Bankruptcy Regime in China: With Lessons from the UK and USA
Authors: Chuyi Wei
Published: June 2014

Following in the steps of the USA and UK, China introduced partnerships with limited liability in 2006, the same year that a market‐oriented bankruptcy statute was enacted. Although the bankruptcy statute enshrines basic elements of modern bankruptcy law, it fails to stipulate specific rules for partnership bankruptcy. As partnership with limited liability acquires increasing importance, especially limited partnerships as a popular form of private equity firms, a partnership bankruptcy regime becomes indispensable. This article considers the experience of the UK and USA in order to make proposals to establish a partnership bankruptcy regime in China. Although partnership bankruptcy law can be formulated by analogy to corporate bankruptcy law, special considerations must be given to the characteristics of partnership such as unlimited liability and lack of separation of management from ownership. Further, as partnership bankruptcy may lead to partner bankruptcy and vice versa, conflicts between partnership creditors and partners' personal creditors must also be considered. Copyright © 2014 INSOL International and John Wiley & Sons, Ltd
MC1R variants increased the risk of sporadic cutaneous melanoma in darker‐pigmented Caucasians: A pooled‐analysis from the M‐SKIP project
Authors: Pasquali Elena , García‐Borrón José C. , Fargnoli Maria Concetta , Gandini Sara , Maisonneuve Patrick , Bagnardi Vincenzo , Specchia Claudia , Liu Fan , Kayser Manfred , Nijsten Tamar , Nagore Eduardo , Kumar Rajiv , Hansson Johan , Kanetsky Peter A. , Ghiorzo Paola , Debniak Tadeusz , Branicki Wojciech , Gruis Nelleke A. , Han Jiali , Dwyer Terry , Blizzard Leigh , Landi Maria Teresa , Palmieri Giuseppe , Ribas Gloria , Stratigos Alexander , Council M. Laurin , Autier Philippe , Little Julian , Newton‐Bishop Julia , Sera Francesco , Raimondi Sara ,   for the M‐SKIP Study Group
Published: June 2014

The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M‐SKIP project, an international pooled‐analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random‐effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17–1.84) for V60L to 2.74 (1.53–4.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared with wild‐type subjects (SOR; 95%CI: 1.66; 1.41–1.96) and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R‐associated melanoma risk increased only for darker‐pigmented Caucasians: SOR (95%CI) was 3.14 (2.06–4.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker‐pigmented Caucasians with MC1R variants as well as to lightly pigmented, fair‐skinned subjects.
On Dimensionality of Halogen‐Bonded Thiophene Solid‐State Assemblies
Authors: Barrès Anne‐Lise , Allain Magali , Frère Pierre , Batail Patrick
Published: June 2014

We report on the structures of three dibromothiophene compounds (4, 5, and 12) and the analysis of the patterns of self‐assembly in the solid state by CBr⋅⋅⋅BrC halogen bonds of a selected set of 16 di‐ or poly‐bromine(poly)thiophene monomers sorted according to the dimensionality of their halogen‐bonded, extended frameworks thereby identifying syn‐ or anti‐strings and layers. We conclude that in 1, 2, 9, and 10, the antiparallel orientation of successive CBr⋅⋅⋅BrC halogen‐bonded dibromothiophene units along extended anti‐strings is linked to the occurrence of solid‐state polymerization.
Increasing the repeating units of ethylene glycol‐based dimethacrylates directed toward reduced oxidative stress and co‐stimulatory factors expression in human monocytic cells
Authors: Tamura Atsushi , Fukumoto Izumi , Yui Nobuhiko , Matsumura Mitsuaki , Miura Hiroyuki
Published: June 2014

The ethylene glycol‐based dimethacrylates are commonly used in biomaterials and dental restorative materials as a cross‐linking agent. In this study, toxic effect of triethylene glycol dimethacrylate (TEGDMA) and poly(ethylene glycol) dimethacrylates (PEG‐DMAs) with various ethylene glycol repeating units was investigated in terms of cytotoxicity, oxidative stress, and the expression of co‐stimulatory factors in human leukemia cell line (THP‐1 cells) to verify the effect of ethylene glycol repeating units. Note that the 1‐octanol/water partition coefficient of PEG‐based dimethacrylates decreased with increasing the ethylene glycol repeating units, indicating that the hydrophilicity of PEG‐DMAs increased with ethylene glycol repeating units. The toxic effect of PEG‐DMAs such as cytotoxicity, oxidative stress, and the expression of CD86 in treated THP‐1 cells are reduced with increasing the ethylene glycol repeating units in PEG‐DMAs. However, the expression of CD54 in treated THP‐1 cells was not influenced with the ethylene glycol repeating units and the maximal expression level of CD54 was observed at the concentration range of 2–4 mM for all samples. Accordingly, hydrophilic character of PEG‐DMAs with long ethylene glycol chains definitely alleviates the some toxic aspect of PEG‐based DMAs. This finding would provide important insight into the design of new biomaterials and dental materials with superior biocompatibility. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1060–1066, 2015.
Can nanotechnology deliver the promised benefits without negatively impacting soil microbial life?
Authors: Dimkpa Christian O.
Published: June 2014

Nanotechnology exploits the enhanced reactivity of materials at the atomic scale to improve various applications for humankind. In agriculture, potential nanotechnology applications include crop protection and fertilization. However, such benefits could come with risks for the environment: non‐target plants, plant‐beneficial soil microbes and other life forms could be impacted if nanoparticles (nanomaterials) contaminate the environment. This review evaluates the impact of the major metallic nanoparticles (Ag, ZnO, CuO, CeO2, TiO2, and FeO‐based nanoparticles) on soil microbes involved in agricultural processes. The current literature indicate that in addition to population and organismal‐scale effects on microbes, other subtle impacts of nanoparticles are seen in the nitrogen cycle, soil enzyme activities, and processes involved in iron metabolism, phytohormone, and antibiotic production. These effects are negative or positive, the outcome being dependent on specific nanoparticles. Collectively, published results suggest that nanotechnology portends considerable, many negative, implications for soil microbes and, thus, agricultural processes that are microbially driven. Nonetheless, the potential of plant and soil microbial processes to mitigate the bioreactivity of nanoparticles also are observed. Whereas the roots of most terrestrial plants are associated with microbes, studies of nanoparticle interactions with plants and microbes are generally conducted separately. The few studies in actual microbe‐plant systems found effects of nanoparticles on the functioning of arbuscular mycorrhizal fungi, nitrogen fixation, as well as on the production of microbial siderophores in the plant rhizosphere. It is suggested that a better understanding of the agro‐ecological ramifications of nanoparticles would require more in‐depth interactive studies in combined plant‐microbe‐nanoparticle systems.
Treatment of spasmodic dysphonia with a neuromodulating electrical implant
Authors: Pitman Michael J.
Published: June 2014

Objectives/Hypothesis

To investigate the feasibility of an implantable electrical stimulation device to treat spasmodic dysphonia (SD) by neuromodulation of the muscle spindle gamma loop.

Study Design

Prospective case series.

Method

Five subjects underwent daily stimulation of the left thyroarytenoid muscle (TA) below the level of α‐motor neuron activation (AMNA) for 5 consecutive days. Professional and patient voice evaluations were performed. Transcartilagenous placement of an implantable stimulation device lead was investigated in anesthetized porcine and cadaveric human models.

Results

Three of 5 subjects improved in all categories of evaluation. One subject improved in three of four categories. These four subjects described significant carryover of effect after treatment. The fifth subject evidenced improvement until contracting an upper respiratory infection on day 3. Transcartilagenous electrode placement into the porcine TA with muscle stimulation was successful. The electrode lead was passed from the cadaveric larynx to the mastoid tip in the subplatysma layer with an absence of tension.

Conclusion

The symptoms of SD improve after electrical stimulation of the TA at levels below AMNA. This is likely through neuromodulation of the muscle spindle gamma loop. Implantation of an electrode into the TA with a postauricular implanted stimulator is feasible with modifications of an already existing device. With further investigation, such a device has the potential to deliver an alternative treatment for SD.

Level of Evidence

4, Laryngoscope, 124:2537–2543, 2014
Shoulder function following reconstruction with the supraclavicular artery island flap
Authors: Herr Marc W. , Bonanno Andrea , Montalbano Lisa A. , Deschler Daniel G. , Emerick Kevin S.
Published: June 2014

Objectives/Hypothesis

The supraclavicular artery island flap (SCAIF) is a pedicled fasciocutaneous flap used for head and neck reconstruction. In recent years, its use has significantly increased as a result of several advantageous characteristics, including pliability, an excellent color and texture match, ability to reconstruct a variety of skin and aerodigestive tract defects, and short harvest times. Clinical experience suggests that donor site complications are relatively infrequent and typically self‐limiting, and there have been no documented cases of prolonged or permanent shoulder dysfunction. However, formal studies have not been performed to assess this outcome. The goal of this study was to evaluate the effects of SCAIF flap harvest on postoperative shoulder strength and flexibility.

Study Design

Prospective cohort pilot study.

Methods

Data was gathered prospectively during routine follow‐up and surveillance. The Penn Shoulder Score and Constant Shoulder Scale were used to measure subjective and objective outcomes. Physical therapists performed testing for strength and flexibility.

Results

Ten patients were evaluated from January to July, 2013. Subjective self‐reporting of shoulder function and satisfaction was good to excellent in most patients. The majority of patients demonstrated limitations in range of motion for one or more shoulder movements. Muscle strength was preserved postoperatively.

Conclusion

Harvest of the SCAIF appears to have limited postoperative morbidity. Postoperative shoulder strength and function appears to be very good; however, some limitation of range of motion was observed.

Level of Evidence

4 Laryngoscope, 124:2478–2483, 2014
Influence of continuous negative pressure in the rat middle ear
Authors: Akiyama Naotaro , Yamamoto‐Fukuda Tomomi , Takahashi Haruo
Published: June 2014

Objectives/Hypothesis

High negative pressure in the middle ear was thought to be closely related to the etiology of retraction‐type cholesteatoma. Recently, it has been detected that mechanical forces are important factors in epithelial turnover and affect cytoskeletal remodeling. Continuous negative pressure in the middle ear may possibly accelerate the proliferation and differentiation of epithelial cells of the tympanic membrane.

Study Design

Animal experimental study.

Methods

Eleven adult male Sprague‐Dawley rats were used, and continuous negative pressure was loaded by connecting a catheter from the rat's middle ear to the supply route of an implantable microinfusion pump, iPRECIO. At 7 days after implantation of the device, an otoendoscopic examination and micro‐computed tomography (CT) analysis of the temporal bone were performed; the temporal bones were then collected for histological and immunohistochemical analysis. The degree of proliferation and differentiation of epithelial cells of the tympanic membrane was investigated immunohistochemically using the anti–cytokeratin‐5 and anti–cytokeratin‐10 antibodies.

Results

Otoendoscopic examination revealed retraction of the pars flaccida in all of the ears under negative pressure. In the micro‐CT analysis, soft tissue density area in the hypotympanum was observed in all ears under negative pressure. Histological analysis revealed thickened epithelium of the pars flaccida. In this region, the thickness of layers with cytokeratin‐5–positive cells and cytokeratin‐10–positive cells were increased.

Conclusions

Continuous negative pressure in the middle ear can lead to thickening of the epithelium of the pars flaccida, and may accelerate the proliferation and differentiation of epithelial cells.

Level of Evidence

NA Laryngoscope 124:2404–2410, 2014
Systematic review and meta‐analysis of meniett therapy for Meniere‐s disease
Authors: Ahsan Syed F. , Standring Robert , Wang Yun
Published: June 2014

Objectives/Hypothesis

To perform a systematic review and meta‐analysis of micropressure treatment for Meniere's disease (MD).

Data Sources

Medline, Ovid, Web of Science, and Cochrane Library search of the literature from January 1996 to December 2012.

Review Methods

Systematic literature review followed Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Inclusion criteria required definitive diagnosis of unilateral MD, treatment with Meniett device, vertigo control results, and hearing results before and after treatment. Randomized controlled trials and other types of case‐control studies were included. Improvements in vertigo, American Academy of Otolaryngology–Head and Neck Surgery (AAO‐HNS) functional score, and pure tone average (PTA) were assessed. Funnel plots were used to detect bias and Q test was used to assess for heterogeneity. Random effects model was used for meta‐analysis. T test was used to assess for significance.

Results

Of 113 abstracts screened, 18 studies met criteria for review and 12 were used for meta‐analysis. Eight studies reported hearing evaluation and the improvement in PTA after Meniett treatment was significant (P = 0.0085). Data could not be combined for AAO‐HNS functional score due to heterogeneity. However, there was a trend toward improvement. Of six studies reporting frequency of vertigo, Meniett treatment significantly reduced frequency of vertigo (P = < .0001).

Limitations

Much of the data used in the analysis was derived from retrospective or level 4 studies. The average follow‐up was only 5 months, and there were low number of patients in the treatment and control groups.

Conclusion

The Meniett device is a safe, nondestructive treatment for patients' refractory to medical therapy for MD. Laryngoscope, 125:203–208, 2015
PDMS‐Containing Alternating Copolymers Obtained by Click Polymerization
Authors: Bretzler Victor , Grübel Matthias , Meister Simon , Rieger Bernhard
Published: June 2014

The copper(I)‐catalyzed alkine–azide cycloaddition (CuAAC) click polymerization is used for the synthesis of novel poly(dimethylsiloxane) (PDMS)‐containing alternating copolymers in a straightforward AA/BB polyaddition approach. The versatility of the CuAAC reaction allows incorporation of a series of different monomers varying in geometry, size, and functionality. A structure–property relation is revealed that shows that the polymer properties are dependent not only on the type of functionality incorporated but also on the size and geometry of the comonomer. The spectrum of properties that can be covered is highly interesting, ranging from viscous oils to brittle solids. Targeted application of monomers even gives access to properties that are typical for thermoplastic elastomers. Additional studies concerning the acceleration of the polymerization reaction support mechanistic considerations about a binuclear active species.

image
Raise Boring Rigs für bis zu 2.000 Meter tiefe Schächte
Authors: Künstle Benjamin , Frey Alexander
Published: June 2014

Die neu entwickelten Raise Boring Rigs von Herrenknecht haben sich weltweit in mehreren Projekteinsätzen bewährt. In der Summe wurden mit den Herrenknecht‐Rigs in Bergbau‐Projekten sowie in Wasserkraftwerks‐ und Straßenbauvorhaben bereits neun Schächte mit einer Gesamtlänge von 2.800 m erstellt. Bei der Entwicklung der Raise Boring Rigs kamen bewährte Elemente sowie umfassendes Know‐how aus dem maschinellen Tunnelvortriebstechnik zur Anwendung. Der Beitrag gibt eine kurze Übersicht über die Funktionsweise und den Aufbau der Raise Boring Rigs und stellt anschließend drei Praxiseinsätze vor.
EU‐Kennzeichnungsrichtlinie und die Herausforderungen bei der Auswahl einer geeigneten Nachweis‐Software
Authors: Ille Frank
Published: June 2014

Viele Unternehmen stehen erst am Anfang der Umsetzung der Richtlinie über die Rückverfolgbarkeit von Explosivstoffen. Da verschiedene Hersteller Track & Trace Lösungen anbieten, sollte sich jedes Unternehmen frühzeitig mit mehreren Anbietern auseinandersetzten, um für sich eine optimale Entscheidung treffen zu können. Neben vielen “harten” Kriterien für die Auswahl der passenden Lösung, wie Art der entsprechenden Geräte, Unterstützung bzw. Kompatibilität mit Sprengstofflieferanten, Art des Datenaustauschs und der zehnjährigen Datenspeicherung, Servicekonzept, Schulungsangeboten, Installations‐ und Einführungsaufwand und natürlich dem Preis, sind auch viele “weiche” Faktoren von großer Bedeutung. Letztlich muss jeder Anwender seinem Softwareanbieter vertrauen, dass dieser über viele Jahre den erforderlichen Service in akzeptabler Zeit zu vernünftigen Preisen bieten kann. Wirtschaftliche Unabhängigkeit und Leistungsfähigkeit, genügend Personal, langjährige Erfahrungen im Bereich Logistik und Track & Trace sowie ein nachvollziehbares langfristiges Preismodell sollten daher wichtige Auswahlkriterien sein. Ein Überblick über die Referenzen eines Anbieters kann hier eine wertvolle Hilfestellung sein.
In vivo MRI for effective non‐invasive detection and follow‐up of an orthotopic mouse model of lung cancer
Authors: Bianchi Andrea , Dufort Sandrine , Fortin Pierre‐Yves , Lux François , Raffard Gérard , Tassali Nawal , Tillement Olivier , Coll Jean‐Luc , Crémillieux Yannick
Published: June 2014

One of the main reasons for the dismal prognosis of lung cancer is related to the late diagnosis of this pathology. In this study, we evaluated the potential of optimized lung MRI techniques as a completely non‐invasive approach for non‐small‐cell lung cancer (NSCLC) MRI in vivo detection and follow‐up in a mouse model of lung adenocarcinoma expressing the luciferase gene.

Bioluminescent lung tumour cells were orthotopically implanted in immuno‐deficient mice. Ultra‐short echo‐time (UTE) MRI free‐breathing acquisitions were compared with standard gradient‐echo lung MRI (FLASH) using both respiratory‐gated and free‐breathing protocols. The MRI findings were validated against bioluminescence imaging (BLI) and gold‐standard histopathology analysis.

Adenocarcinoma‐like pathological tissue was successfully identified in all the mice with gated‐FLASH and non‐gated UTE MRI, and good tumour co‐localization was found between MRI, BLI and histological analyses. An excellent or good correlation was found between the measured bioluminescent signal and the total tumour volumes quantified with UTE MRI or gated‐FLASH MRI, respectively. No significant correlation was found when the tumours were segmented on non‐gated MR FLASH images.

MRI was shown to be a powerful imaging tool able to detect, quantify and longitudinally monitor the development of sub‐millimetric NSCLCs. To our knowledge, this is the first study which proves the feasibility of a completely non‐invasive MRI quantitative detection of lung adenocarcinoma in freely breathing mice. The absence of ionizing radiation and the high‐resolution of MRI, along with the complete non‐invasiveness and good reproducibility of the proposed non‐gated protocol, make this imaging tool ideal for direct translational applications. Copyright © 2014 John Wiley & Sons, Ltd.
Diagnosis Modelling for Dependability Assessment of Fault‐Tolerant Systems Based on Stochastic Activity Networks
Authors: Maza Samia
Published: June 2014

The growing demand for safety, reliability, availability and maintainability in modern technological systems has led these systems to become more and more complex. To improve their dependability, many features and subsystems are employed like the diagnosis system, control system, backup systems, and so on. These subsystems have all their own dynamic, reliability and performances and interact with each other in order to provide a dependable and fault‐tolerant system. This makes the dependability analysis and assessment very difficult. This paper proposes a method to completely model the diagnosis procedure in fault‐tolerant systems using stochastic activity networks. Combined with Monte Carlo simulation, this will allow the dependability assessment by including the diagnosis parameters and performances explicitly. Copyright © 2014 John Wiley & Sons, Ltd.