bluuebunny/crossref_metadata_2025 huggingface dataset:
Singlet Oxygen Generation and Photoinduced Charge Separation of Tetra Polyethyleneglycol Functionalized Zinc Phthalocyanine‐Fullerene Dyad
Authors: Gobeze Habtom B. , Tram Ta , KC Chandra B. , Cantu Robert R. , Karr Paul A. , D'Souza Francis
Published: September 2016

Utilization of polyethyleneglycol (PEG) functionalized zinc phthalocyanine, (PEG)4ZnPc in (i) singlet oxygen generation, and (ii) in building energy harvesting donor‐acceptor systems using fullerene, C60 as an acceptor via the well‐known metal‐ligand axial coordination approach is reported. The (PEG)4ZnPc was found to be capable of producing singlet oxygen with a quantum yield, ΦΔ of 0.77 in toluene, a value higher than that obtained for pristine (t‐bu)4ZnPc (ΦΔ=0.54) carrying no PEG groups, revealing its usefulness in photodynamic therapy applications. Spectroscopic studies revealed efficient binding of phenylimidazole functionalized fullerene, C60Im with 1:1 stoichiometry to (PEG)4ZnPc. Binding constant K for the formation of (PEG)4ZnPc:ImC60 dyad was found to be 6×103 M−1 revealing moderate stability. Geometric and electronic studies of the dyad was arrived by B3LYP/3‐21G(∗︁) method. The HOMO level was found to be on zinc phthalocyanine entity while the LUMO level was found to be on the C60 entity suggesting formation of (PEG)4ZnPc·+:ImC60· − charge separated state during the process of electron transfer reaction. Redox studies on the (PEG)4ZnPc:ImC60 dyad enabled accurate determination of the oxidation and reduction potentials of the donor‐acceptor system, and to evaluate free‐energy changes associated for the charge separation process. Kinetics of photoinduced charge separation and recombination in the (PEG)4ZnPc:ImC60 dyad was investigated using femtosecond transient absorption studies. Relatively long‐lived charge separated states were confirmed for the dyad suggesting their potential usefulness in energy harvesting applications.
Gene expression profiling of granule cells and Purkinje cells in the zebrafish cerebellum
Authors: Takeuchi Miki , Yamaguchi Shingo , Sakakibara Yoshimasa , Hayashi Takuto , Matsuda Koji , Hara Yuichiro , Tanegashima Chiharu , Shimizu Takashi , Kuraku Shigehiro , Hibi Masahiko
Published: September 2016

The structure of the neural circuitry of the cerebellum, which functions in some types of motor learning and coordination, is generally conserved among vertebrates. However, some cerebellar features are species specific. It is not clear which genes are involved in forming these conserved and species‐specific structures and functions. This study uses zebrafish transgenic larvae expressing fluorescent proteins in granule cells, Purkinje cells, or other cerebellar neurons and glial cells to isolate each type of cerebellar cells by fluorescence‐activated cell sorting and to profile their gene expressions by RNA sequencing and in situ hybridization. We identify genes that are upregulated in granule cells or Purkinje cells, including many genes that are also expressed in mammalian cerebella. Comparison of the transcriptomes in granule cells and Purkinje cells in zebrafish larvae reveals that more developmental genes are expressed in granule cells, whereas more neuronal‐function genes are expressed in Purkinje cells. We show that some genes that are upregulated in granule cells or Purkinje cells are also expressed in the cerebellum‐like structures. Our data provide a platform for understanding the development and function of the cerebellar neural circuits in zebrafish and the evolution of cerebellar circuits in vertebrates. J. Comp. Neurol. 525:1558–1585, 2017. © 2016 Wiley Periodicals, Inc.
H2 Formation on Cosmic Grain Siliceous Surfaces Grafted with Fe+: A Silsesquioxanes‐Based Computational Model
Authors: Fioroni Marco , DeYonker Nathan J.
Published: September 2016

Cosmic siliceous dust grains are involved in the synthesis of H2 in the inter‐stellar medium. In this work, the dust grain siliceous surface is represented by a hydrogen Fe‐metalla‐silsesquioxane model of general formula: [Fe(H7Si7O12−n)(OH)n]+ (n=0,1,2) where Fe+ behaves like a single‐site heterogeneous catalyst grafted on a siliceous surface synthesizing H2 from H. A computational analysis is performed using two levels of theory (B3LYP‐D3BJ and MP2‐F12) to quantify the thermodynamic driving force of the reaction: [Fe‐T7H7]++4H→[Fe‐T7H7(OH)2]++H2. The general outcomes are: 1) H2 synthesis is thermodynamically strongly favored; 2) Fe‐H / Fe‐H2 barrier‐less formation potential; 3) chemisorbed H‐Fe leads to facile H2 synthesis at 20≤T≤100 K; 4) relative spin energetics and thermodynamic quantities between the B3LYP‐D3BJ and MP2‐F12 levels of theory are in qualitative agreement. The metalla‐silsesquioxane model shows how Fe+ fixed on a siliceous surface can potentially catalyze H2 formation in space.
Template‐free synthesis of hierarchical zinc oxide with improved photocatalytic properties
Authors: Wang X. J. , Han Y. J. , Song Y.Q. , Chen X.N.
Published: September 2016

Novel hierarchical nano materials possess tremendous latent force in many applications. In this paper, hierarchical flower‐like, spherical and bowl‐like zinc oxide was successfully synthesized by altering solvent ratio (absolute ethanol and diethylene glycol) via a simple and template‐free solvothermal synthetic route. The solvent ratio also plays a vital role in deciding the structure, crystalline, band gap energy and specific surface area of the as‐synthesized samples. The preparation mechanism of ZnO in mixed alcohols was discussed. The obtained samples were characterized by energy dispersive spectroscopy(EDS), X‐ray diffraction (XRD), field emission scanning electron microscope (FESEM), transmission electron microscopy (TEM), N2 adsorption‐desorption, UV–vis diffuse reflectance spectroscopy (DRS). Photocatalytic activity of the as‐prepared ZnO nanocrystals was evaluated by the degradation of MB under UV irradiation. Among, the most effective photocatalyst was synthesized when the diethylene glycol was 10 ml.
Hydrogen Production and Storage on a Formic Acid/Bicarbonate Platform using Water‐Soluble N‐Heterocyclic Carbene Complexes of Late Transition Metals
Authors: Jantke Dominik , Pardatscher Lorenz , Drees Markus , Cokoja Mirza , Herrmann Wolfgang A. , Kühn Fritz E.
Published: September 2016

The synthesis and characterization of two water‐soluble bis‐N‐heterocyclic carbene (NHC) complexes of rhodium and iridium is presented. Both compounds are active in H2 generation from formic acid and in hydrogenation of bicarbonate to formate. The rhodium derivative is most active in both reactions, reaching a TOF of 39 000 h−1 and a TON of 449 000 for H2 production. The catalytic hydrogenation reactions were carried out in an autoclave system and analyzed using the integrated peak areas in the 1H NMR spectra. Decomposition of formic acid was investigated using a Fisher–Porter bottle equipped with a pressure transducer. Long‐term stability for hydrogen evolution was tested by surveillance of the gas flow rate. The procedure does not require any additives like amines or inert gas conditions. Density functional theory calculations in agreement with experimental results suggest a bicarbonate reduction mechanism involving a second catalyst molecule, which provides an external hydride acting as reducing agent.
Ischemia reduces inter‐alpha inhibitor proteins in the brain of the ovine fetus
Authors: Spasova Mariya S. , Chen Xiaodi , Sadowska Grazyna B. , Horton Edward R. , Lim Yow‐Pin , Stonestreet Barbara S.
Published: September 2016

Hypoxic‐ischemic (HI) brain injury is a major cause of neurological abnormalities in the perinatal period. Inflammation contributes to the evolution of HI brain injury. Inter‐alpha inhibitor proteins (IAIPs) are a family of proteins that are part of the innate immune system. We have reported that endogenous IAIPs exhibit developmental changes in ovine brain and that exogenous IAIP treatment reduces neuronal death in HI neonatal rats. However, the effects of HI on endogenous IAIPs in brain have not been previously examined. In this study, we examined the effects of ischemia‐reperfusion on endogenous IAIPs levels in fetal sheep brain. Cerebral cortex, cerebellum, cervical spinal cord, choroid plexus, and CSF were snap frozen from sham control fetuses at 127 days gestation and after 30‐min of carotid occlusion and 4‐, 24‐, and 48‐h of reperfusion. IAIP levels were determined by Western immunoblot. IAIP expressions of the 250 kDa Inter‐alpha inhibitor (IaI) and 125 kDa Pre‐alpha inhibitor (PaI) in cerebral cortex and PaI in cerebellum were reduced (p < 0.05) 4‐h after ischemia compared with controls and returned toward control levels 24‐ and 48‐h after ischemia. CSF PaI and IaI were reduced 48 h after ischemia. We conclude that IAIPs in cerebral cortex and cerebellum are reduced by brain ischemia, and return toward control levels between 24 and 48 h after ischemia. However, changes in CSF IAIPs were delayed, exhibiting decreases 48 h after ischemia. We speculate that the decreases in endogenous IAIPs reflect increased utilization, potentially suggesting that they have endogenous neuroprotective properties. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 726–737, 2017
Characterization of a new Gsx2‐cre line in the developing mouse telencephalon
Authors: Qin Shenyue , Madhavan Mayur , Waclaw Ronald R. , Nakafuku Masato , Campbell Kenneth
Published: September 2016

In this study, we generated a transgenic mouse line driving Cre and EGFP expression with two putative cis‐regulatory modules (CRMs) (i.e., hs687 and hs678) upstream of the homeobox gene Gsx2 (formerly Gsh2), a critical gene for establishing lateral ganglionic eminence (LGE) identity. The combination of these two CRMs drives transgene expression within the endogenous Gsx2 expression domains along the anterior–posterior neuraxis. By crossing this transgenic line with the RosatdTomato (Ai14) reporter mouse line, we observed a unique recombination pattern in the lateral ventral telencephalon, namely the LGE and the dorsal half of the medial GE (MGE), but not in the septum. We found robust recombination in many cell types derived from these embryonic regions, including olfactory bulb and amygdala interneurons and striatal projection neurons from the LGE, as well as cortical interneurons from the MGE and caudal GE (CGE). In summary, this transgenic mouse line represents a new tool for genetic manipulation in the LGE/CGE and the dorsal half of MGE.
Vulnerability of Subarctic and Arctic breeding birds
Authors: Hof Anouschka R. , Rodríguez‐Castañeda Genoveva , Allen Andrew M. , Jansson Roland , Nilsson Christer
Published: September 2016

Recent research predicts that future climate change will result in substantial biodiversity loss associated with loss of habitat for species. However, the magnitude of the anticipated biodiversity impacts are less well known. Studies of species vulnerability to climate change through species distribution models are often limited to assessing the extent of species' exposure to the consequences of climate change to their local environment, neglecting species sensitivity to global change. The likelihood that species or populations will decline or go extinct due to climate change also depends on the general sensitivity and adaptive capacity of species. Hence, analyses should also obtain more accurate assessments of their vulnerability. We addressed this by constructing a vulnerability matrix for 180 bird species currently breeding in Subarctic and Arctic Europe that integrates a climatic exposure‐based vulnerability index and a natural‐history trait‐based vulnerability index. Species that may need extra conservation attention based on our matrix include the Great Snipe (Gallinago media), the Rough‐legged Buzzard (Buteo lagopus), the Red‐throated Pipit (Anthus cervinus), the Common Swift (Apus apus), the Horned Lark (Eremophila alpestris), and the Bar‐tailed Godwit (Limosa lapponica). Our vulnerability matrix stresses the importance of looking beyond exposure to climate change when species conservation is the aim. For the species that scored high in our matrix the future in the region looks grim and targeted conservation actions, incorporating macroecological and global perspectives, may be needed to alleviate severe population declines. We further demonstrate that climate change is predicted to significantly reduce the current breeding range of species adapted to cold climates in Subarctic and Arctic Europe. The number of incubation days and whether the species was a habitat specialist or not were also among the variables most strongly related to predicted contraction or expansion of species' breeding ranges. This approach may aid the identification of vulnerable bird species worldwide.
Cohort variation in individual body mass dissipates with age in large herbivores
Authors: Hamel S. , Gaillard J.‐M. , Yoccoz N. G. , Albon S. , Côté S. D. , Craine J. M. , Festa‐Bianchet M. , Garel M. , Lee P. , Moss C. , Nussey D. H. , Pelletier F. , Stien A. , Tveraa T.
Published: September 2016

Environmental conditions experienced during early growth and development markedly shape phenotypic traits. Consequently, individuals of the same cohort may show similar life‐history tactics throughout life. Conditions experienced later in life, however, could fine‐tune these initial differences, either increasing (cumulative effect) or decreasing (compensatory effect) the magnitude of cohort variation with increasing age. Our novel comparative analysis that quantifies cohort variation in individual body size trajectories shows that initial cohort variation dissipates throughout life, and that lifetime patterns change both across species with different paces of life and between sexes. We used longitudinal data on body size (mostly assessed using mass) from 11 populations of large herbivores spread along the “slow‐fast” continuum of life histories. We first quantified cohort variation using mixture models to identify clusters of cohorts with similar initial size. We identified clear cohort clusters in all species except the one with the slowest pace of life, revealing that variation in early size is structured among cohorts and highlighting typological differences among cohorts. Growth trajectories differed among cohort clusters, highlighting how early size is a fundamental determinant of lifetime growth patterns. In all species, among‐cohort variation in size peaked at the start of life, then quickly decreased with age and stabilized around mid‐life. Cohort variation was lower in species with a slower than a faster pace of life, and vanished at prime age in species with the slowest pace of life. After accounting for viability selection, compensatory/catch‐up growth in early life explained much of the decrease in cohort variation. Females showed less phenotypic variability and stronger compensatory/catch‐up growth than males early in life, whereas males showed more progressive changes throughout life. These results confirm that stronger selective pressures for rapid growth make males more vulnerable to poor environmental conditions early in life and less able to recover after a poor start. Our comparative analysis illustrates how variability in growth changes over time in closely related species that span a wide range on the slow‐fast continuum, the main axis of variation in life‐history strategies of vertebrates.
Unprecedented remote sensing data over King and Rim megafires in the Sierra Nevada Mountains of California
Authors: Stavros E. Natasha , Tane Zachary , Kane Van R. , Veraverbeke Sander , McGaughey Robert J. , Lutz James A. , Ramirez Carlos , Schimel David
Published: September 2016

Megafires have lasting social, ecological, and economic impacts and are increasing in the western contiguous United States. Because of their infrequent nature, there is a limited sample of megafires to investigate their unique behavior, drivers, and relationship to forest management practices. One approach is to characterize critical information pre‐, during, and post‐fire using remote sensing. In August 2013, the Rim Fire burned 104,131 ha and in September 2014, the King Fire burned 39,545 ha. Both fires occurred in California's Sierra Nevada. The areas burned by these fires were fortuitously surveyed by airborne campaigns, which provided the most recent remote sensing technologies not currently available from satellite. Technologies include an imaging spectrometer spanning the visible to shortwave infrared (0.38–2.5 μm), a multispectral, high‐spatial resolution thermal infrared (3.5–13 μm) spectroradiometer, and Light Detection and Ranging that provide spatial resolutions of pixels from 1 × 1 m to 35 × 35 m. Because of the unique information inherently derived from these technologies before the fires, the areas were subsequently surveyed after the fires. We processed and provide free dissemination of these airborne datasets as products of surface reflectance, spectral metrics and forest structural metrics ( http://dx.doi.org/10.3334/ORNLDAAC/1288). These data products provide a unique opportunity to study relationships among and between remote sensing observations and fuel and fire characteristics (e.g., fuel type, condition, structure, and fire severity). The novelty of these data is not only in the unprecedented types of information available from them before, during, and after two megafires, but also in the synergistic use of multiple state of the art technologies for characterizing the environment. The synergy of these data can provide novel information that can improve maps of fuel type, structure, abundance, and condition that may improve predictions of megafire behavior and effects, thus aiding management before, during, and after such events. Key questions that these data could address include: What drives, extinguishes, and results from megafires? How does megafire behavior relate to fire and fuel management? How does the size and severity of a megafire affect the ecological recovery of the system?
Individual and combined effects of two types of phenological shifts on predator–prey interactions
Authors: Rasmussen Nick L. , Rudolf Volker H. W.
Published: September 2016

Timing of phenological events varies among years with natural variation in environmental conditions and is also shifting in response to climate change. These phenological shifts likely have many effects on species interactions. Most research on the ecological consequences of phenological shifts has focused on variation in simple metrics such as phenological firsts. However, for a population, a phenological event exhibits a temporal distribution with many attributes that can vary (e.g., mean, variance, skewness), each of which likely has distinct effects on interactions. In this study, we manipulated two attributes of the phenological distribution of a prey species to determine their individual and combined effects on predator–prey interactions. Specifically, we studied how shifts in the mean and variation around the mean (i.e., synchrony) of hatching by tadpoles (Hyla cinerea) affected interactions with predatory dragonfly naiads (Tramea carolina). At the end of larval development, we quantified survival and growth of predator and prey. We found that both types of shifts altered demographic rates of the prey; that the effects of synchrony shifts, though rarely studied, were at least as strong as those due to mean shifts; and that the combined effects of shifts in synchrony and mean were additive rather than synergistic. By dissecting the roles of two types of shifts, this study represents a significant step toward a comprehensive understanding of the complex effects of phenological shifts on species interactions. Embracing this complexity is critical for predicting how climate change will alter community dynamics.
Tyrosine kinase 2 is not limiting human antiviral type III interferon responses
Authors: Fuchs Sebastian , Kaiser‐Labusch Petra , Bank Julia , Ammann Sandra , Kolb‐Kokocinski Anja , Edelbusch Christine , Omran Heymut , Ehl Stephan
Published: September 2016

Tyrosine kinase 2 (TYK2) associates with interferon (IFN) alpha receptor, IL‐10 receptor (IL‐10R) beta and other cytokine receptor subunits for signal transduction, in response to various cytokines, including type‐I and type‐III IFNs, IL‐6, IL‐10, IL‐12 and IL‐23. Data on TYK2 dependence on cytokine responses and in vivo consequences of TYK2 deficiency are inconsistent. We investigated a TYK2 deficient patient, presenting with eczema, skin abscesses, respiratory infections and IgE levels >1000 U/mL, without viral or mycobacterial infections and a corresponding cellular model to analyze the role of TYK2 in type‐III IFN mediated responses and NK‐cell function. We established a novel simple diagnostic monocyte assay to show that the mutation completely abolishes the IFN‐α mediated antiviral response. It also partly reduces IL‐10 but not IL‐6 mediated signaling associated with reduced IL‐10Rβ expression. However, we found almost normal type‐III IFN signaling associated with minimal impairment of virus control in a TYK2 deficient human cell line. Contrary to observations in TYK2 deficient mice, NK‐cell phenotype and function, including IL‐12/IL‐18 mediated responses, were normal in the patient. Thus, preserved type‐III IFN responses and normal NK‐cell function may contribute to antiviral protection in TYK2 deficiency leading to a surprisingly mild human phenotype.
Microbial oil production from various carbon sources by newly isolated oleaginous yeasts
Authors: Maina Sofia , Pateraki Chrysanthi , Kopsahelis Nikolaos , Paramithiotis Spiros , Drosinos Eleftherios H. , Papanikolaou Seraphim , Koutinas Apostolis
Published: September 2016

Microbial oil production has received significant attention as a potential precursor for the production of biofuels, oleochemicals and food products. In this study, six oleaginous yeasts, isolated from fruits, were selected based on their ability to accumulate high intracellular content of microbial oil (20–48% w/w of total dry weight). The highest content of saturated fatty acids was 68.7% (w/w), whereas the highest content of oleic acid was 62.7% (w/w). Furthermore, nutrient‐rich hydrolysates produced via enzymatic hydrolysis of flour‐rich waste streams generated by a confectionery industry were evaluated as fermentation media for microbial oil production via fed‐batch bioreactor cultures using one of the most promising isolates, namely VV_D4. A total dry weight of 40 g/L with a microbial oil content of 39% (w/w) was produced by isolate VV_D4. Critical biodiesel properties were estimated based on the fatty acid composition and correlated with the international standards. The microbial oil produced by the new isolates could be potentially used for biodiesel production.
Design of stirred digester with optimization of energy and power consumption
Authors: Mahmoodi‐Eshkaftaki Mahmood , Ebrahimi Rahim , Ghasemi‐Pirbaloti Abdollah
Published: September 2016

The goal of the present study was to design a new stirred digester according to laboratory experiments. For this purpose, amount of methane produced from co‐digestion of municipal waste, kitchen waste, and cow manure in different treatments was measured in laboratory conditions for 37°C. The substrate characteristics such as both total and volatile solids, pH, EC, amount of total carbon, nitrogen, phosphorus, potassium, and sulfate which can manage the methane production were measured. The results showed that the amounts of these characteristics were in suitable ranges for biogas production. The laboratory experiment results were then used to design an anaerobic digester for single‐family homes based on energy efficiency and mixing cost. As a result, the digester diameter, digester height, slurry height, baffle width, impeller diameter, blade width, blade length, and volume of designed stirred digester were determined as 57, 90, 60, 4.75, 25, 4, 10 cm, and 229 L, respectively. Furthermore, pitched blade turbine with six blades at 45° for speed of 300 rpm not only required a low power but also produced a high torque. Therefore, while the designed biogas plant consumes low energy, it has high mixing cost.

Nowadays, the researchers in bio‐system engineering focus on the designing biogas plant according to the direct relation among the power, torque, and energy. The novelty of the article is not only an evaluation of main substrate characteristics on methane production, but also design a new digester with high methane content at suitable pressure based on the best relation among the equipment dimensions of digester determined using shape factors. Furthermore study of impeller types and rotation speeds for providing high torque in low power and reducing energy consumption indirectly, and uses rule of thumb for power consumption to determine the best impeller type and rotation speed. © 2016 American Institute of Chemical Engineers Environ Prog, 36: 104–110, 2017
An in silico algal toxicity model with a wide applicability potential for industrial chemicals and pharmaceuticals
Authors: Önlü Serli , Saçan Melek Türker
Published: September 2016

The authors modeled the 72-h algal toxicity data of hundreds of chemicals with different modes of action as a function of chemical structures. They developed mode of action–based local quantitative structure–toxicity relationship (QSTR) models for nonpolar and polar narcotics as well as a global QSTR model with a wide applicability potential for industrial chemicals and pharmaceuticals. The present study rigorously evaluated the generated models, meeting the Organisation for Economic Co-operation and Development principles of robustness, validity, and transparency. The proposed global model had a broad structural coverage for the toxicity prediction of diverse chemicals (some of which are high–production volume chemicals) with no experimental toxicity data. The global model is potentially useful for endpoint predictions, the evaluation of algal toxicity screening, and the prioritization of chemicals, as well as for the decision of further testing and the development of risk-management measures in a scientific and regulatory frame. Environ Toxicol Chem 2017;36:1012–1019. © 2016 SETAC
Frequency of nuclear mutant huntingtin inclusion formation in neurons and glia is cell‐type‐specific
Authors: Jansen Anne H.P. , van Hal Maurik , op den Kelder Ilse C. , Meier Romy T. , de Ruiter Anna‐Aster , Schut Menno H. , Smith Donna L. , Grit Corien , Brouwer Nieske , Kamphuis Willem , Boddeke H.W.G.M. , den Dunnen Wilfred F.A. , van Roon Willeke M.C. , Bates Gillian P. , Hol Elly M. , Reits Eric A.
Published: September 2016

Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder that is caused by a CAG expansion in the Huntingtin (HTT) gene, leading to HTT inclusion formation in the brain. The mutant huntingtin protein (mHTT) is ubiquitously expressed and therefore nuclear inclusions could be present in all brain cells. The effects of nuclear inclusion formation have been mainly studied in neurons, while the effect on glia has been comparatively disregarded. Astrocytes, microglia, and oligodendrocytes are glial cells that are essential for normal brain function and are implicated in several neurological diseases. Here we examined the number of nuclear mHTT inclusions in both neurons and various types of glia in the two brain areas that are the most affected in HD, frontal cortex, and striatum. We compared nuclear mHTT inclusion body formation in three HD mouse models that express either full‐length HTT or an N‐terminal exon1 fragment of mHTT, and we observed nuclear inclusions in neurons, astrocytes, oligodendrocytes, and microglia. When studying the frequency of cells with nuclear inclusions in mice, we found that half of the population of neurons contained nuclear inclusions at the disease end stage, whereas the proportion of GFAP‐positive astrocytes and oligodendrocytes having a nuclear inclusion was much lower, while microglia hardly showed any nuclear inclusions. Nuclear inclusions were also present in neurons and all studied glial cell types in human patient material. This is the first report to compare nuclear mHTT inclusions in glia and neurons in different HD mouse models and HD patient brains. GLIA 2016;65:50–61
Pretreatment lymphocyte‐to‐monocyte ratio as an independent prognostic factor for head and neck cancer
Authors: Kano Satoshi , Homma Akihiro , Hatakeyama Hiromitsu , Mizumachi Takatsugu , Sakashita Tomohiro , Kakizaki Tomohiko , Fukuda Satoshi
Published: September 2016

Background

The purpose of this study was to analyze the relationship between pretreatment inflammatory markers and the prognosis of patients with oropharyngeal, hypopharyngeal, and laryngeal cancers.

Methods

The data for 285 patients treated with curative intent by concurrent chemoradiotherapy (CRT) were obtained and their pretreatment inflammatory markers, including neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and lymphocyte‐to‐monocyte ratio (LMR) were calculated.

Results

Significant relationships were observed between a high NLR and oropharyngeal or hypopharyngeal cancer, T3 to T4, N2b to N3, and clinical stage III to IV, whereas significant relationships were observed between a high LMR and laryngeal cancer, T1 to T2, and clinical stage I to II. With regard to survival outcomes, a high NLR, a high PLR, and a low LMR were all significantly associated with decreases in overall survival (OS) and disease‐free survival (DFS). Furthermore, multivariate analysis showed that LMR was an independent prognostic factor.

Conclusion

Pretreatment LMR was found to be an independent prognostic factor for patients with head and neck cancers treated by concurrent CRT. © 2016 Wiley Periodicals, Inc. Head Neck 39: 247–253, 2017
Current status and diagnostic values of the Bethesda system for reporting thyroid cytopathology in a papillary thyroid carcinoma–prevalent area
Authors: Lee You‐Bin , Cho Yoon Young , Jang Ju Young , Kim Tae Hyuk , Jang Hye Won , Chung Jae Hoon , Oh Young Lyun , Kim Sun Wook
Published: September 2016

Background

Most studies validating the Bethesda system for reporting thyroid cytopathology (TBSRTC) have been conducted in Western countries. We explored the current status of TBSRTC in an area where most thyroid malignancies are papillary carcinomas.

Methods

Fine‐needle aspirations (FNAs) of thyroid nodules performed in 2013 were retrospectively analyzed and the results were compared to final pathology on resection.

Results

Of 1947 FNAs, 1925 (98.9%) were reported using TBSRTC. Among 381 resected lesions, 27.3% of nondiagnostic, 19.6% of benign, 56.0% of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 33.3% of follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN), 97.7% of suspicious for malignancy, and 100.0% of malignant lesions were malignant on pathology. The sensitivity and specificity of FNA using TBSRTC were 96.7% and 84.1%, respectively.

Conclusion

TBSRTC works well in an area in which papillary thyroid cancer is prevalent; however, it may underestimate malignancy rates in AUS/FLUS, benign, and nondiagnostic categories. © 2016 Wiley Periodicals, Inc. Head Neck 39: 269–274, 2017
A critical assessment of the fibula flap donor site
Authors: Xu Zhong‐Fei , Bai Shuang , Zhang Zhi‐Qiang , Duan Wei‐Yi , Wang Zhi‐Qiang , Sun Chang‐Fu
Published: September 2016

Background

The free fibula flap has become popular for mandibular reconstruction. The purpose of this study was to propose comprehensive functional assessments of the donor site.

Methods

Thirty free fibula flaps for mandible reconstruction were prospectively enrolled in the study. Objective assessments included isokinetic testing of the ankle joint, electromyographic examination of the superficial peroneal nerve (SPN), and preoperative and postoperative foot scans. The Patient and Observer Scar Assessment Scale (POSAS) was used to subjectively assess the donor site.

Results

The isokinetic values of the donor side showed a significant decrease 1 year postoperatively. The results of the electromyographic test of the SPN were categorized as 3 types. The plantar center pressure shifted to the heel on the donor side 6 months postoperatively. The aesthetic outcome was satisfactory.

Conclusion

The functional parameters of the donor site indeed declined in our assessments. Further refinements in the surgical technique are needed to improve the donor site status. © 2016 Wiley Periodicals, Inc. Head Neck 39: 279–287, 2017
Incorporating Tactile Cues into Human‐Centered Virtual Product Design
Authors: Demirel H. Onan , Duffy Vincent G.
Published: September 2016

This study introduces a high‐fidelity tactile feedback mechanism to capture ergonomics attributes of users inside virtual product development cycle. The research question posed regards whether the tactile feedback mechanism in virtual experiment proposes high fidelity of ergonomics results when compared to physical experiment outcomes. This question was evaluated through an objective and a subjective study. Objective study was composed of an ergonomics product assessment experiment, where two different cart designs (a commercial cart and a prototype model) were evaluated for ergonomic adequacy (L4/L5 compression forces). Subjective evaluation was consisted of a questionnaire to assess subjects' preferences regarding which cart model they preferred in three different design categories; maneuverability, accessibility, and ergonomics. Results showed that tactile feedback mechanism was able to replicate the physical test conditions in virtual environment with high fidelity, and prototype cart model received higher mean ratings when compared to commercial cart model in each design category.
Forests and water in South America
Authors: Jones Julia , Almeida Auro , Cisneros Felipe , Iroumé Andres , Jobbágy Esteban , Lara Antonio , Lima Walter de Paula , Little Christian , Llerena Carlos , Silveira Luis , Villegas Juan Camilo
Published: September 2016

South America is experiencing rapid change in forest cover, of both native and planted forest. Forest cover loss is primarily attributable to fire, logging, and conversion of native forest to agriculture, pasture, and forest plantations, and types of change vary within and among the many diverse types of forests in South America. Major changes in forest cover and growing policy concerns underscore an urgent need for research on sustainable forest management and water ecosystem services in South America. Differences in land ownership and management objectives create trade‐offs between wood production and water ecosystem services from forests. Work is needed to quantify how forest change and management affect ecosystem services, such as wood production versus water provision. Current scientific understanding of forest management effects on water ecosystem services in South America has important limitations, including a scarcity of long‐term records and few long‐term integrated watershed studies. Industry, government, universities, and local communities should collaborate on integrated applied studies of forests and water. Data archiving and publically available data are required. The creation of national networks and a multi‐country South America network to identify and implement common water research protocols, share results, and explore their implications would promote common and well‐supported policies. Hydrologists working in South America are well placed to tackle the challenges and opportunities for collaborative research that will maintain the intrinsic values and water ecosystem services provided by South America's forests.
Recurrence‐free and overall survival among elderly stage III colon cancer patients treated with CAPOX or capecitabine monotherapy
Authors: van Erning F.N. , Janssen‐Heijnen M.L.G. , Creemers G.J. , Pruijt J.F.M. , Maas H.A.A.M. , Lemmens V.E.P.P.
Published: September 2016

The aim of this study is to investigate the effects of CAPOX and capecitabine on recurrence‐free survival (RFS) and overall survival (OS) among elderly stage III colon cancer patients and to evaluate the effect of (non‐)completion. Patients aged ≥70 years who underwent resection only or who were subsequently treated with CAPOX or capecitabine in 10 large non‐academic hospitals were included. RFS and OS were analyzed with Kaplan‐Meier curves and multivariable Cox regression adjusted for patient and tumor characteristics. 982 patients were included: 630 underwent surgery only, 191 received CAPOX and 161 received capecitabine. Five‐year RFS and OS did not differ between capecitabine and CAPOX (RFS: 63% vs. 60% (p = 0.91), adjusted HR = 0.99 (95%CI 0.68‐1.44); OS: 66% vs. 66% (p = 0.76), adjusted HR = 0.93 (95%CI 0.64–1.34)). After resection only, RFS was 38% and OS 37%. Completion rates were 48% for CAPOX and 68% for capecitabine. Three‐year RFS and OS did not differ between patients who discontinued CAPOX early and patients who completed treatment with CAPOX (RFS: 61% vs. 69% (p = 0.21), adjusted HR = 1.42 (95%CI 0.85–2.37); OS: 68% vs. 78% (p = 0.41), adjusted HR = 1.17 (95%CI 0.70–1.97)). Three‐year RFS and OS differed between patients who discontinued capecitabine early and patients who completed treatment with capecitabine (RFS: 54% vs. 72% (p = 0.01), adjusted HR = 2.07 (95%CI 1.11–3.84); OS: 65% vs. 80% (p = 0.01), adjusted HR = 2.00 (95%CI 1.12–3.59)). Receipt of CAPOX or capecitabine is associated with improved RFS and OS. The advantage does not differ by regimen. The addition of oxaliplatin might not be justified in elderly stage III colon cancer patients.
Deregulated matriptase activity in oral squamous cell carcinoma promotes the infiltration of cancer‐associated fibroblasts by paracrine activation of protease‐activated receptor 2
Authors: Kanemaru Ai , Yamamoto Koji , Kawaguchi Makiko , Fukushima Tsuyoshi , Lin Chen‐Yong , Johnson Michael D. , Camerer Eric , Kataoka Hiroaki
Published: September 2016

Cancer‐associated fibroblasts (CAFs) are known to contribute to cancer progression. We have reported that cell surface expression of hepatocyte growth factor activator inhibitor 1 (HAI‐1) is decreased in invasive oral squamous cell carcinoma (OSCC) cells. This study examined if HAI‐1‐insufficiency contributes to CAF recruitment in OSCC. Serum‐free conditioned medium (SFCM) from a human OSCC line (SAS) stimulated the migration of 3 human fibroblast cell lines, NB1RGB, MRC5 and KD. SFCM from HAI‐1‐knockdown SAS showed an additive effect on the migration of NB1RGB and MRC5, but not KD. SAS SFCM induced protease‐activated receptor‐2 (PAR‐2) expression in NB1RGB and MRC5, but not in KD, and a PAR‐2 antagonist blocked the stimulatory effect of HAI‐1 knockdown on migration of the PAR‐2 expressing cell lines. Moreover, HAI‐1‐deficient SFCM showed additive stimulatory effects on the migration of wild‐type but not PAR‐2‐deficient mouse fibroblasts. Therefore, the enhanced migration induced by HAI‐1‐insufficiency was mediated by PAR‐2 activation in fibroblasts. This activation resulted from the deregulation of the activity of matriptase, a PAR‐2 agonist protease. HAI‐1 may thus prevent CAF recruitment to OSCC by controlling matriptase activity. When HAI‐1 expression is reduced on OSCC, matriptase may contribute to CAF accumulation by paracrine activation of fibroblast PAR‐2. Immunohistochemical analysis of resected OSCC revealed increased PAR2‐positive CAFs in 35% (33/95) of the cases studied. The increased PAR‐2 positive CAFs tended to correlate with infiltrative histology of the invasion front and shorter disease‐free survival of the patients.
Longitudinal fluctuation in mammographic percent density differentiates between interval and screen‐detected breast cancer
Authors: Strand Fredrik , Humphreys Keith , Eriksson Mikael , Li Jingmei , Andersson Therese M. L. , Törnberg Sven , Azavedo Edward , Shepherd John , Hall Per , Czene Kamila
Published: September 2016

Interval breast cancer (IC) has a more aggressive phenotype and higher mortality than screen‐detected cancer (SDC). In this case‐case study, we investigated whether the size of longitudinal fluctuations in mammographic percent density (PD fluctuation) was associated with the ratio of IC versus SDC among screened women with breast cancer. The primary study population consisted of 1,414 postmenopausal breast cancer cases, and the validation population of 1,241 cases. We calculated PD fluctuation as the quadratic mean of deviations between actual PD and the long‐term trend estimated by a mixed effects model. In a logistic regression model we examined the association between PD fluctuation and IC versus SDC including adjustments for PD at last screening, age at diagnosis, BMI and hormone replacement therapy. All statistical tests were two‐sided. There were 385 IC and 1,029 SDC in the primary study population, with PD fluctuations of 0.44 and 0.41 respectively (p = 0.0309). After adjustments, PD fluctuation was associated with an increased ratio of IC versus SDC, with an estimated per‐standard deviation odds ratio of 1.17 (95% CI = 1.03–1.33), compared to 1.19 (95% CI = 1.04–1.38) in the validation population. In screened women with breast cancer, high fluctuation in mammographic percent density was associated with an increased ratio of IC versus SDC. Whether this is entirely related to a reduced mammographic detectability or to a biological phenotype promoting faster tumor growth remains to be elucidated.
Gene panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1/2
Authors: Kraus Cornelia , Hoyer Juliane , Vasileiou Georgia , Wunderle Marius , Lux Michael P. , Fasching Peter A. , Krumbiegel Mandy , Uebe Steffen , Reuter Miriam , Beckmann Matthias W. , Reis André
Published: September 2016

Breast and ovarian cancer (BC/OC) predisposition has been attributed to a number of high‐ and moderate to low‐penetrance susceptibility genes. With the advent of next generation sequencing (NGS) simultaneous testing of these genes has become feasible. In this monocentric study, we report results of panel‐based screening of 14 BC/OC susceptibility genes (BRCA1, BRCA2, RAD51C, RAD51D, CHEK2, PALB2, ATM, NBN, CDH1, TP53, MLH1, MSH2, MSH6 and PMS2) in a group of 581 consecutive individuals from a German population with BC and/or OC fulfilling diagnostic criteria for BRCA1 and BRCA2 testing including 179 with a triple‐negative tumor. Altogether we identified 106 deleterious mutations in 105 (18%) patients in 10 different genes, including seven different exon deletions. Of these 106 mutations, 16 (15%) were novel and only six were found in BRCA1/2. To further characterize mutations located in or nearby splicing consensus sites we performed RT‐PCR analysis which allowed confirmation of pathogenicity in 7 of 9 mutations analyzed. In PALB2, we identified a deleterious variant in six cases. All but one were associated with early onset BC and a positive family history indicating that penetrance for PALB2 mutations is comparable to BRCA2. Overall, extended testing beyond BRCA1/2 identified a deleterious mutation in further 6% of patients. As a downside, 89 variants of uncertain significance were identified highlighting the need for comprehensive variant databases. In conclusion, panel testing yields more accurate information on genetic cancer risk than assessing BRCA1/2 alone and wide‐spread testing will help improve penetrance assessment of variants in these risk genes.
Towards V&V suitable Domain Specific Modeling Languages for MBSE: A tooled approach
Authors: NASTOV Blazo , CHAPURLAT Vincent , DONY Christophe , PFISTER François
Published: September 2016

Considering Model‐Based Systems Engineering (MBSE) principles and needs, this article focuses on the design of Domain Specific Modeling Languages (DSMLs) aiming to link modeling, verification and validation (V&V) activities. The goal is to ease the work and increase the freedom and autonomy of experts from various domains in the process of creating and managing system models then to supply experts involved in analyses and decision making processes with models characterized by highest level of confidence. This paper introduces and illustrates a tool‐equipped approach, named “xviCore”, that provides MBSE experts with natively verifiable, executable and interoperable DSML named “xviDSML”, i.e., DSML that can be formally and directly checked and simulated requesting no huge efforts or skills.
Technology Update on the Unified Architecture Framework (UAF)
Authors: Hause Matthew , Bleakley Graham , Morkevicius Aurelijus
Published: September 2016

Architecture frameworks continue to evolve. The Unified Profile for the Department of Defense (DoD) Architecture Framework (DoDAF) and the UK's Ministry of Defence Architecture Framework (MODAF) (UPDM) provides a standard means of representing DoDAF, MODAF, and NATO Architecture Framework (NAF) conformant architectures using the Unified Modeling Language (UML), and Systems Modeling Language (SysML). Since the UPDM V2.0 publication, further information has emerged such as the June 2011 NATO study entitled: “Development of The AMN (Afghanistan Mission Network) Architecture In 2010 – Lessons Learned,” by Torsten Graeber of the NATO C3 Agency. This report identified the following in section 4.1‐ARCHITECTURE FRAMEWORKS, sub‐section 4.1.2 Observations (Need for a Unified Architecture Framework) and stated that:

• differences in DoDAF, MODAF, and NAF make it difficult to match the metamodel one to one.

• some of the concepts in the frameworks have the same name but different definitions, i.e. different semantics.

• difficult to cross‐walk the concepts between the different frameworks leads to miscommunication between architects using different frameworks.

Based on the above, the NATO Architecture Capability Team (Architecture CaT) meeting on Sept. 10‐11, 2012 committed to move to a single world‐wide Architecture Framework. Consequently, a new architecture framework profile supporting a unified framework is needed. It is intended that this framework bring the different architecture frameworks together. The UPDM V3.0 domain metamodel shall be derived from MODEM (the MODAF metamodel) and the DoDAF 2.0 metamodel (DM2), both of which are based upon the International Defence Enterprise Architecture Specification Foundation [IDEAS]. This paper will document the rationale behind the UPDM 3.0 as well as its new name of the Unified Architecture Framework (UAF).
Reliability Engineering: Value, Waste, and Costs
Authors: Barnard Albertyn
Published: September 2016

Several reliability engineering activities practised today cannot contribute to the primary objective of reliability engineering, which is the prevention of failure. Lean Thinking (or lean) is well‐known as management philosophy with the objective of maximising value by removal of waste from all activities. Can lean be applied to reliability engineering?

This paper starts with a brief discussion on the fundamentals of both reliability engineering and lean. It provides a definition of value in the context of reliability engineering, and applies this definition to identify categories of reliability engineering activities which can be considered as waste. The paper concludes with a discussion on reliability costs.
MBSE++ — Foundations for Extended Model‐Based Systems Engineering Across System Lifecycle
Authors: Bajaj Manas , Zwemer Dirk , Yntema Rose , Phung Alex , Kumar Amit , Dwivedi Anshu , Waikar Manoj
Published: September 2016

This paper presents an approach for next‐generation model‐based systems engineering across the system lifecycle, labelled MBSE++. This approach is based on the idea of a Total System Model that serves and evolves as the digital blueprint of a system through its lifecycle. The fundamental principles of MBSE++ are presented in this paper, including the use of decentralized and heterogeneous engineering models and repositories, spectrum of fine‐grained model‐based connections, unified representation of the system independent of the location of models, model transformations, comparisons, and synchronization to communicate between disciplines, and visualization and analytics for effective decision making. The motivation for each of the MBSE++ principles is presented, followed by a description of use cases. The use cases are exemplified using Syndeia, a MBE/MBSE platform developed by Intercax.