bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular farming of human cytokines and blood products from plants: Challenges in biosynthesis and detection of plant‐produced recombinant proteins
Authors: da Cunha Nicolau B. , Vianna Giovanni R. , da Almeida Lima Thaina , Rech Elíbio
Published: December 2013

Plants have emerged as an attractive alternative to the traditional mammalian cell cultures or microbial cell‐based systems system for the production of valuable recombinant proteins. Through recombinant DNA technology, plants can be engineered to produce large quantities of pharmaceuticals and industrial proteins of high quality at low costs. The recombinant production, by transgenic plants, of therapeutic proteins normally present in human plasma, such as cytokines, coagulation factors, anticoagulants, and immunoglobulins, represents a response to the ongoing challenges in meeting the demand for therapeutic proteins to treat serious inherited or acquired bleeding and immunological diseases. As the clinical utilization of fractionated plasma molecules is limited by high production costs, using recombinant biopharmaceuticals derived from plants represents a feasible alternative to provide efficient treatment. Plant‐derived pharmaceuticals also reduce the potential risks to patients of infection with pathogens or unwanted immune responses due to immunogenic antigens. In this review, we summarize the recent advances in molecular farming of cytokines. We also examine the technological basis, upcoming challenges, and perspectives for the biosynthesis and detection of these molecules in different plant production platforms.
Randomized clinical trial comparing survival after D1 or D2 gastrectomy for gastric cancer
Authors:   the Italian Gastric Cancer Study Group, Degiuli M , Sasako M , Ponti A , Vendrame A , Tomatis M , Mazza C , Borasi A , Capussotti L , Fronda G , Morino M , Ferri V , Rebecchi F , Garino M , Viganò L , Scaglione D , Locatelli L , Teggia P Mello
Published: December 2013

Background

It is still unclear whether D2 lymphadenectomy improves the survival of patients with gastric cancer and should therefore be performed routinely or selectively. The aim of this multicentre randomized trial was to compare D2 and D1 lymphadenectomy in the treatment of gastric cancer.

Methods

Between June 1998 and December 2006, patients with gastric adenocarcinoma were assigned randomly to either D1 or D2 gastrectomy. Intraoperative randomization was implemented centrally by telephone. Primary outcome was overall survival; secondary endpoints were disease-specific survival, morbidity and postoperative mortality.

Results

A total of 267 eligible patients were allocated to either D1 (133 patients) or D2 (134) resection. Morbidity (12·0 versus 17·9 per cent respectively; P = 0·183) and operative mortality (3·0 versus 2·2 per cent; P = 0·725) rates did not differ significantly between the groups. Median follow-up was 8·8 (range 4·5–13·1) years for surviving patients and 2·4 (0·2–11·9) years for those who died, and was not different in the two treatment arms. There was no difference in the overall 5-year survival rate (66·5 versus 64·2 per cent for D1 and D2 lymphadenectomy respectively; P = 0·695). Subgroup analyses showed a 5-year disease-specific survival benefit for patients with pathological tumour (pT) 1 disease in the D1 group (98 per cent versus 83 per cent for the D2 group; P = 0·015), and for patients with pT2–4 status and positive lymph nodes in the D2 group (59 per cent versus 38 per cent for the D1 group; P = 0·055).

Conclusion

No difference was found in overall 5-year survival between D1 and D2 resection. Subgroup analyses suggest that D2 lymphadenectomy may be a better choice in patients with advanced disease and lymph node metastases. Registration number: ISRCTN11154654 (http://www.controlled-trials.com).
Lentiviral‐mediated overexpression of Akt1 reduces anoxia–reoxygenation injury in cardiomyocytes
Authors: Du Yanyan , Zhu Hong , Li Dongye , Wang Lele , Zhang Lin , Luo Yuanyuan , Pan Defeng , Huang Manman
Published: December 2013

Activated PI3K/Akt signalling exerts a protective effect after myocardial ischemia by phosphorylating various substrates; however, the precise mechanism by which this occurs remains to be elucidated. We have constructed the recombinant lentiviral vector pLVX‐Akt1‐EGFP‐ 3FLAG (LV‐Akt1) to determine the efficiency of LV‐Akt1 infection, explore the protective role of Akt1, and investigate the possible mechanism by which Akt1 signalling acts during anoxia/reoxygenation (A/R) of cardiomyocytes in primary culture. Akt1 gene transfection increased cardiomyocyte pulsation, reduced cell mortality, and decreased the concentration of lactate dehydrogenase (LDH) in myocardial cells supernatants. Akt1 transfection increased the levels of intracellular p‐Akt, enhanced the expression of the anti‐apoptosis protein Bcl‐2, and reduced that of the apoptosis protein Bax (thereby increasing the Bcl‐2/Bax ratio), and caused some increase in hypoxia‐inducible factor1α (HIF‐1α) and vascular endothelial growth factor (VEGF) expression after A/R. The protective role of Akt1 was partly suppressed by adding a phosphoinositide 3‐kinase/Akt inhibitor (LY294002). In conclusion, LV‐Akt1 was successfully constructed and neonatal rat cardiomyocytes were transfected efficiently. Akt1 overexpression significantly reduced A/R injury in cardiomyocytes, and this could be related to its effects on various targets of the PI3K/Akt signalling pathway, such as Bcl‐2, Bax, HIF‐1α and VEGF.
Concomitant activation of the PI3K/Akt and ERK1/2 signalling is involved in cyclic compressive force‐induced IL‐6 secretion in MLO‐Y4 cells
Authors: Yin Jian , Hao Zhichao , Ma Yuanyuan , Liao Shuang , Li Xianxian , Fu Jing , Wu Yeke , Shen Jiefei , Zhang Ping , Li Xiaoyu , Wang Hang
Published: December 2013

IL‐6 has a dual role in bone remodelling. The ERK1/2 pathway partially upregulated IL‐6 secretion in osteocyte‐like MLO‐Y4 cells exposed to CCF. We have now investigated the possible role of phosphatidylinositol 3‐kinase (PI3K)/Akt signalling pathway in the CCF‐induced IL‐6 expression. MLO‐Y4 cells were treated with CCF 2,000 µstrain, 2 Hz, or 10, 30 min, 1, 3 and 6 h. IL‐6 expression, Akt and ERK1/2 and PI3K/Akt phosphorylation were determined by RT‐PCR, ELISA and Western blotting. Inhibition of PI3K/Akt with LY294002 or ERK1/2 with PD98059 significantly attenuated IL‐6 upregulation, and IL‐6 expression was abolished by inhibiting both pathways. Inhibition of one pathway downregulated the other's phosphorylation level. In conclusion, concomitant activation of PI3K/Akt and ERK1/2 pathways mediated IL‐6 expression in MLO‐Y4 cells under CCF.
Simvastatin promotes cardiac microvascular endothelial cells proliferation, migration and survival by phosphorylation of p70 S6K and FoxO3a
Authors: Pan Qiao , Xie Xiaobo , Guo Yan , Wang Haichang
Published: December 2013

Restenosis severely limits the overall efficacy of interventions. One of the reasons is the lack of reendothelialization related to inhibition of endothelial cell proliferation and migration since drug is delivered to the luminal surface. Statins can promote angiogenic processes by improving endothelial function, proliferation and migration in cardiac microvascular endothelial cells (CMECs). This study clarified the effect of simvastatin on Akt/mTOR/p70 S6K and FoxO3a signalling pathways in rat CMECs following pretreated with rapamycin. Rapamycin treatment for 24 h inhibited CMECs' proliferation, migration and NO (nitric oxide) secretion, but with increased cell apoptosis and reactive oxygen species (ROS) production. In contrast, simvastatin pretreatment significantly improved proliferation, migration and NO secretion, and inhibited CMECs' apoptosis and ROS production in rapamycin‐induced CMECs. Western blot assay showed that, after treatment with simvastatin, the phosphorylation of Akt/mTOR/p70 S6K and FoxO3a were up‐regulated in rapamycin‐induced CMECs, which was significantly reversed by pretreatment with LY294002. The data suggest that simvastatin inhibits rapamycin‐induced CMECs dysfunction and apoptosis, probably through activation of PI3K/Akt/mTOR/p70 S6K and mTOR/FoxO3a signalling pathway in a sequential manner and this pathway may be important in some of the pleiotropic effects of statins.
Alteration of human umbilical vein endothelial cell gene expression in different biomechanical environments
Authors: Shoajei Shahrokh , Tafazzoli‐Shahdpour Mohammad , Shokrgozar Mohammad Ali , Haghighipour Nooshin
Published: December 2013

Biomechanical environments affect the function of cells. In this study we analysed the effects of five mechanical stimuli on the gene expression of human umbilical vein endothelial cells (HUVECs) in mRNA level using real‐time PCR. The following loading regimes were applied on HUVECs for 48 h: intermittent (0–5 dyn/cm2, 1 Hz) and uniform (5 dyn/cm2) shear stresses concomitant by 10% intermittent equiaxial stretch (1 Hz), uniform shear stress alone (5 dyn/cm2), and intermittent uniaxial and equiaxial stretches (10%, 1 Hz). A new bioreactor was made to apply uniform/cyclic shear and tensile loadings. Three endothelial suggestive specific genes (vascular endothelial growth factor receptor‐2 (VEGFR‐2, also known as FLK‐1), von Willebrand Factor (vWF) and vascular endothelial‐cadherin (VE‐cadherin)), and two smooth muscle genes (α‐smooth muscle actin (α‐SMA) and smooth muscle myosin heavy chain (SMMHC)) were chosen for assessment of alteration in gene expression of endothelial cells and transdifferentiation toward smooth cells following load applications.

Shear stress alone enhanced the endothelial gene expression significantly, while stretching alone was identified as a transdifferentiating factor. Cyclic equiaxial stretch contributed less to elevation of smooth muscle genes compared to uniaxial stretch. Cyclic shear stress in comparison to uniform shear stress concurrent with cyclic stretch was more influential on promotion of endothelial genes expression. Influence of different mechanical stimuli on gene expression may open a wider horizon to regulate functions of cell for tissue engineering purposes.
Non‐aqueous, surfactant‐free antifoam emulsions: Properties and triggered release
Authors: Dimitrova Tatiana D. , Cauvin Severine , Lecomte Jean‐Paul , Colson Annick
Published: December 2013

Processing convenience and formulation flexibility frequently require the delivery of the silicone oils as emulsions. The shelf life of the latter is achieved kinetically, in the most cases via the addition of surfactants. On the other hand, surfactants are the subject of increasing scrutiny with regard to their environmental impact. The goal of this study is to formulate silicone oils in surfactant‐free emulsions and to demonstrate the controlled release of the active silicone material.

A non‐aqueous silicone emulsion comprising of a continuous phase of a polar organic liquid, having droplets of silicone antifoam compound dispersed therein, have been developed. These systems are stabilised by (fractal) waxy particles which play a dual role. They act as Pickering stabilisers and in the same time they form an elastic network in the continuous phase, providing a creaming stability of more than a year. A triggered release of the (antifoam) silicone active can be achieved via heating above the melting temperature of the waxy particles. This is demonstrated by the fact that no antifoam activity has been observed at temperatures below ca. 60°C, while at temperature of above 65–70°C a strong antifoam effect has been obtained.
Hartley Transform for Reduction to the Pole
Authors: Yao LUO
Published: December 2013

As an integral transform similar to the Fourier transform, the Hartley transform is more efficient and economical than its progenitor. This work attempts to use it to process magnetic data based on the general properties of the Hartley transform. A practical method for reduction to the pole (RTP) in the Hartley domain is presented. The problems of reduction to the pole (RTP) processing at low magnetic latitudes are also discussed, and a filtering operator is introduced in the algorithm, modified by slightly increasing the inclination of the normal magnetic field at low latitudes to suppress north‐south trending features. Calculations on theoretical models indicate that RTP in the Hartley domain is accurate and reliable. Real data processing demonstrates that this RTP algorithm is applicable.
Establishment of the Medial‐Hotspot Reference Datum and Study of the Westward Drift of Lithosphere
Authors: Xin‐Hui ZHU , Fu‐Ping SUN , Ren WANG
Published: December 2013

Now as to geodetic application, the constrain condition of no‐net‐rotation (NNR) has been recommended and adopted by IERS organization in defining the Earth reference system. While to geophysical application, the absolute plate motion model and data relative to NNR reference datum may bring misguide to mantle convection and other research. Considering hotspot relative motion, a medial hotspot (MHS) reference datum is proposed, of which the constraint rule is presented. Two absolute plate motion models designated as MHS‐NUVEL1A and MHS‐ITRF2005 are constructed using a set of hotspot data globally distributed in conjunction with the plate motion models NNR‐NUVEL1A and ITRF2005VEL, respectively, which are compared and analyzed with other absolute plate motion models based on the hotspots reference frame. The lithosphere's westward drift is discussed. The results show that the lithosphere has a net rotation relative to the hotspots with a rate 0.26°/Ma, about a pole of 50°S, 62°E with respect to the deep mantle, which is closer to that from the plate forced model in the direction, faster in the rate by 10%.
Mineral Magnetic Properties and Late Quaternary Transgressions Recorded by the Borehole WJ in the Taihu Plain, China
Authors: Ting CHEN , Zhang‐Hua WANG , Xiao‐Ke QIANG , Chun‐Yan MA , Qing ZHAN
Published: December 2013

With paleomagnetism and AMS14C dating results, we reconstructed the depositional environmental evolution and marine transgression events during the Late Quaternary by examining the lithology, grain size, magnetic properties, and foraminifera of sediments from a borehole WJ in the Taihu plain of southern Yangtze Delta, China. We also investigated the application of magnetic proxies to distinguishing depositional environments in the estuarine‐deltaic area. The results show that the sediment sequence of borehole WJ could be divided into four periods including Mid‐Pleistocene stage I, Mid‐Pleistocene stage II, Late Pleistocene, and Holocene. Their depositional geomorphological conditions were fluvial‐lacustrine plain, coast‐terrace, mouth bar‐estuary‐tidal flat‐terrace, and lacustrine plain, respectively. Three transgression events were revealed by the borehole WJ, which happened during the late stage of Mid‐Pleistocene, marine isotope stage (MIS) 5 and MIS3 of Late‐Pleistocene. The MIS5e transgression was the strongest one and the transgression in the late stage of MIS3 intensified significantly. Magnetic properties were strongest in the tidal flat and mouth bar sediments, with notably high values of χlf, SIRM and HIRM.
Employing Response Surface Methodology for Optimization of Mercury Bioremediation by Vibrio parahaemolyticus PG02 in Coastal Sediments of Bushehr, Iran
Authors: Jafari Seyed Ali , Cheraghi Sama , Mirbakhsh Maryam , Mirza Roozbeh , Maryamabadi Ammar
Published: December 2013

Three bacterial species of PG01, PG02, and PG03 were isolated from coastal sediments of Bushehr (Iran) as mercury‐resistant bacteria. According to 16S ribosomal DNA gene sequence, the strains were identified as Vibrio natriegens, Vibrio parahaemolyticus, and Oceanimonas baumannii, respectively. Minimum inhibitory concentration test in the presence of HgCl2 revealed that the strain PG02 was the most resistant one, which tolerated up to 45 mg L−1 Hg2+. Tracing the growth curves for the PG02 showed that when it is initially exposed to 5 mg L−1 Hg2+ in the medium, only 10% of its natural growth is reduced, while it simultaneously succeeds to remove 90% of mercury. However, initially 10 mg L−1 Hg2+ in the medium led to 30% growth inhibition and 80% mercury removal. According to a linear relationship between the growth inhibition percentage and the initial mercury concentrations, the median effective concentration was calculated as 21.84 mg L−1 for PG02. Central composite design under response surface methodology well proposed a model with high values of R2 = 0.999 and adjusted R2 = 0.998 which predicted the maximum mercury removal of 89.47% by PG02 under optimum pH of 7.2, temperature of 37.5°C and the initial mercury concentration of 5 mg L−1.
Multiple paternity in wild house mice (Mus musculus musculus): effects on offspring genetic diversity and body mass
Authors: Thonhauser Kerstin E. , Thoß Michaela , Musolf Kerstin , Klaus Teresa , Penn Dustin J.
Published: December 2013

Multiple mating is common in many species, but it is unclear whether multiple paternity enhances offspring genetic diversity or fitness. We conducted a survey on wild house mice (Mus musculus musculus), and we found that in 73 pregnant females, 29% of litters had multiple sires, which is remarkably similar to the 23–26% found in feral populations of Mus musculus domesticus in the USA and Australia, respectively. The question is: How has selection maintained multiple mating in these subspecies since the evolutionary divergence, ca. 2800–6000 years ago? We found no evidence that multiple paternity enhanced females’ litter size, contrary to the fertility assurance or genetic benefits hypotheses. Multiple paternity was associated with reduced mean and variance in offspring body mass, which suggests that females allocate fewer resources or that there is increased intrauterine conflict in multiple‐ versus single‐sired litters. We found increased allelic diversity (though not heterozygosity) in multiple‐sired litters, as predicted by the genetic diversity hypothesis. Finally, we found that the dams’ heterozygosity was correlated with the mean heterozygosity of their offspring in single‐ and multiple‐sired litters, suggesting that outbred, heterozygous females were more likely to avoid inbreeding than inbred, homozygous females. Future studies are needed to examine how increased genetic diversity of litters and smaller mean (and variance) offspring body mass associated with multiple paternity affect offspring fitness.
The spectral karyotype of L5178Y TK+/− mouse lymphoma cells clone 3.7.2C and factors affecting mutant frequency at the thymidine kinase (tk) locus in the microtitre mouse lymphoma assay
Authors: Fellows Mick D. , McDermott Angela , Clare Katie R. , Doherty Ann , Aardema Marilyn J.
Published: December 2013

There has been much discussion on acceptable spontaneous mutant frequencies in the mouse lymphoma assay (MLA). This culminated in the International Workshop on Genotoxicity Testing (IWGT) recommended control limits for the microtitre version of 50–170 mutants/106 viable cells, which has now been included in the draft Organization for Economic Co‐Operation and Development guideline for assays investigating mammalian cell gene mutation at the tk locus. Some of the factors affecting mutant frequency have been investigated. It was shown that when culturing methotrexate cleansed TK+/− cells, a spontaneous mutant frequency of ∼100 mutants/106 viable cells was achieved after only 26 doublings. However, after further culturing for ∼6 months the spontaneous mutant frequency only gradually increased. Culturing for this time did not affect the karyotype of the cell in so much as the modal chromosome number remained stable. The spontaneous mutant frequency could effectively be manipulated by cleansing with various concentrations of methotrexate. The necessity for using appropriately heat‐inactivated horse serum was confirmed. Finally, following treatment with 4‐nitroquinoline‐N‐oxide, cells did not preferentially survive when plated at high cell densities (1.6 cells plus 2,000 feeder cells/well) versus cells at low density (1.6 cells/well). It was considered that these findings confirm that the dynamics of spontaneous mutant formation in the MLA are complex. However, the karyotype of L5178Y cells is remarkably stable and assuming investigators are using cells with appropriate provenance and good culturing technique, it is clear that the IWGT recommendations are achievable. Environ. Mol. Mutagen. 55:35–42, 2014. © 2013 Wiley Periodicals, Inc.
Evaluation of thermal fire hazard of 10 polymeric building materials and proposing a classification method based on cone calorimeter results
Authors: Bakhtiyari Saeed , Taghi‐Akbari Leila , Ashtiani Masoud Jamali
Published: December 2013

The use of polymeric building materials has been grown in many countries of Middle East in recent years. However, there are only a few fire testing laboratories in this region. Therefore, development of a method for controlling the reaction to fire of materials with bench scale tests is necessary. Providing a framework for classification of thermal fire hazard of materials based on bench scale heat release rate results was attempted. The fire behavior of 10 polymeric building materials was tested with cone calorimeter. The relationship between reaction to fire variables and physical properties of tested samples was examined. The thermal fire hazards of materials were assessed using methods presented by different researchers and with Conetools software. The results revealed that time to ignition, peak rate of heat release, and total heat release are essential variables for determining the fire hazard of materials. A classification method is proposed, which can be used in building codes in countries where the full‐scale test facilities are not available. The method also can be used for quality control purpose and evaluation of fire behavior of materials in bench scale by manufacturers. An example of potential requirements for interior finishes for some occupancy types is also presented. Copyright © 2013 John Wiley & Sons, Ltd.
Erodibility of low‐compaction steep‐sloped reclaimed surface mine lands in the southern Appalachian region, USA
Authors: Hoomehr Siavash , Schwartz John S. , Yoder Daniel , Drumm Eric C. , Wright Wesley
Published: December 2013

The use of loose spoils on steep slopes for surface coal mining reclamation sites has been promoted by the US Department of Interior, Office of Surface Mining for the establishment of native forest, as prescribed by the Forest Reclamation Approach (FRA). Although low‐compaction spoils improve tree survival and growth, erodibility on steep slopes was suspected to increase. This study quantified a combined KC factor (combining the effects of the soil erodibility K factor and cover management C) for low compaction, steep‐sloped (>20°) reclaimed mine lands in the Appalachian region, USA. The combined KC factor was used because standard Unit Plot conditions required to separate these factors, per Revised Universal Soil Loss Equation (RUSLE) experimental protocols, were not followed explicitly. Three active coal mining sites in the Appalachian region of East Tennessee, each containing four replicate field plots, were monitored for rainfall and sediment yields during a 14‐month period beginning June 2009. Average cumulative erosivity for the study sites during the monitoring period was measured as 5248.9 MJ·mm·ha−1·h−1. The KC ranged between 0.001 and 0.05 t·ha·h·ha−1·MJ−1·mm−1, with the highest values occurring immediately following reclamation site construction as rills developed (June – August 2009). The KC for two study sites with about an 18–20 mm spoil D84 were above 0.01 t·ha·h·ha−1·MJ−1·mm−1 during rill development, and below 0.003 t·ha·h·ha−1·MJ−1·mm−1 after August 2009 for the post‐rill development period. The KC values for one site with a 40 mm spoil D84 were never above 0.008 t·ha·h·ha−1·MJ−1·mm−1 and also on average were lower, being more similar to the other two sites after the rill development period. Based on an initial KC factor (Ke) measured during the first few storm events, the average C factor (Ce) was estimated as 0.58 for the rill development period and 0.13 for the post‐rill development period. It appears that larger size fractions of spoils influence KC and Ce factors on low‐compaction steep slopes reclamation sites. Copyright © 2013 John Wiley & Sons, Ltd.
Photonic crystal enhancement of a homogeneous fluorescent assay using submicron fluid channels fabricated by E‐jet patterning
Authors: Tan Yafang , Sutanto Erick , Alleyne Andrew G. , Cunningham Brian T.
Published: December 2013

We demonstrate the enhancement of a liquid‐based homogenous fluorescence assay using the resonant electric fields from a photonic crystal (PC) surface. Because evanescent fields are confined to the liquid volume nearest to the photonic crystal, we developed a simple approach for integrating a PC fabricated on a silicon substrate within a fluid channel with submicron height, using electrohydrodynamic jet (e‐jet) printing of a light‐curable epoxy adhesive to define the fluid channel pattern. The PC is excited by a custom‐designed compact instrument that illuminates the PC with collimated light that precisely matches the resonant coupling condition when the PC is covered with aqueous media. Using a molecular beacon nucleic acid fluorescence resonant energy transfer (FRET) probe for a specific miRNA sequence, we demonstrate an 8× enhancement of the fluorescence emission signal, compared to performing the same assay without exciting resonance in the PC detecting a miRNA sequence at a concentration of 62 nM from a liquid volume of only ∼20 nL. The approach may be utilized for any liquid‐based fluorescence assay for applications in point‐of‐care diagnostics, environmental monitoring, or pathogen detection. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Existence of Five MOLS of Orders 18 and 60
Authors: Abel R. Julian R.
Published: December 2013

In this article, we provide direct constructions for five mutually orthogonal Latin squares (MOLS) of orders and 60. For , these come from a new (60, 6, 1) difference matrix. For , the required construction is obtained by combining two different methods that were used in the constructions of four MOLS(14) and eight MOLS(36).
Creative Imagination is Stable Across Technological Media: The Spore Creature Creator Versus Pencil and Paper
Authors: Cockbain Jessica , Vertolli Michael O. , Davies Jim
Published: December 2013

T. B. Ward (1994) investigated creativity by asking participants to draw alien creatures that they imagined to be from a planet very different from Earth. He found that participant drawings reliably contained features typical of common Earth animals. As a consequence, Ward concluded that creativity is structured. The present investigation predicts that this limitation on creativity is not restricted to drawings: the use of different technology will not change creative output. To investigate this question, participants performed Ward's task twice: once using pencil and paper and once using software made to design creatures (the Spore Creature Creator). Only minor significant differences were found. This preliminarily suggests that changing tools does not affect the overall rigidity of the creative process. This lends further support to Ward's thesis on the structural rigidity of creativity. We conclude by suggesting an elaboration to Ward's thesis that will be explored in future work. We suggest that aesthetics might be one of the factors that contribute to creative constraint, in that creatures that are too unusual would be less interesting.
Cost‐effectiveness of simultaneous resection and RFA versus 2‐stage hepatectomy for bilobar colorectal liver metastases
Authors: Abbott Daniel E. , Sohn Vance Y. , Hanseman Dennis , Curley Steven A.
Published: December 2013

Background and Objectives

The current healthcare climate demands evaluation of treatment modalities in terms of costs and benefits. We compared the cost‐effectiveness of two different strategies for bilobar colorectal liver metastases (bCRLM).

Methods

Patients with bCRLM treated with either resection/RFA or planned 2‐stage hepatectomy at our institution between 1999 and 2011 were reviewed. A decision analysis model was populated with treatment probabilities, outcomes, survival, and costs (Medicare payment, 2011 US$).

Results

Two hundred fourteen patients underwent resection/RFA. Eighty‐two patients were treated with planned 2‐stage hepatectomy; 26 (32%) patients never completed a 2nd resection. In the 2‐stage cohort, 50 patients underwent portal vein embolization (PVE). Overall complication rate and 90‐day mortality for resection/RFA was 36% and 3.7%, and for 2‐stage hepatectomy (both procedures combined) was 44% and 7.3%, respectively. Cost‐effectiveness analysis revealed that resection/RFA cost $37,120 for 46.2‐month survival, while planned 2‐stage resection cost $62,198 for 35.9‐month survival. If, hypothetically, all 2‐stage patients completed both stages of resection, the per‐patient cost was $72,644 for 40.3‐month survival.

Conclusions

Resection/RFA is associated with lower costs and longer survival when compared to 2‐stage resection. This 1‐stage approach for bCRLM should be viewed as an efficient use of resources for this challenging clinical scenario. J. Surg. Oncol. 2014 109:516–520. © 2013 Wiley Periodicals, Inc.
Management Effects on Soil Organic Carbon Stock in Mediterranean Open Rangelands—Treeless Grasslands
Authors: Parras‐Alcántara Luis , Díaz‐Jaimes Luisa , Lozano‐García Beatriz
Published: December 2013

Soil organic carbon (SOC) is subject to relatively rapid changes. In grasslands soils, the management system influences these changes. Therefore, these soils play a crucial role in climate change mitigation. Current research has developed strategies and methodologies to help us understand their role as a carbon sink.

In this study, the SOC and total nitrogen contents and stocks (SOC‐S) and their variation with depth were evaluated in annual crop rotations (cereal–fallow). Fifty soil profiles were sampled in the Los Pedroches Valley (southern Spain). This area consists of Mediterranean open rangelands—treeless grasslands with cereal–fallow rotation, under two management systems: long‐term (20 years) organic farming (OF) and conventional tillage (CT). The studied soils were Cambisols (CM), Leptosols (LP) and Luvisols (LV). The objective of this research was to determine any management system effects (OF vs CT) on SOC and total nitrogen contents and stocks and their variation with profile depth. It was observed that SOC concentration decreased with depth (Ah–Ap > Bw > C). The SOC concentration was higher in the top soil for all studied soils in OF compared with CT. The highest totals of SOC‐S were found in LV‐OF (66·01 Mg ha−1) and the lowest in LP‐CT (21·33 Mg ha−1). Significant differences (p < 0·05) between soils types and management practices were found in carbon stocks, increasing the SOC‐S in OF compared with that in CT in all studied soils; this increase was 75·25%, 85·73% and 234·88% for CM, LV and LP, respectively. The results indicated that management practices significantly influence SOC‐S in the Los Pedroches Valley and, consequently, OF in annual crop rotations (cereal–fallow) is an excellent alternative to CT that increases the SOC content in Mediterranean open rangelands—treeless grasslands environments. Copyright © 2013 John Wiley & Sons, Ltd.
The pan‐deacetylase inhibitor panobinostat suppresses the expression of oncogenic miRNAs in hepatocellular carcinoma cell lines
Authors: Henrici Alexander , Montalbano Roberta , Neureiter Daniel , Krause Michael , Stiewe Thorsten , Slater Emily Prentice , Quint Karl , Ocker Matthias , Di Fazio Pietro
Published: December 2013

Deacetylase inhibitors (DACi) are a new class of drugs with a broad spectrum of mechanisms that favor their application in cancer therapy. Currently, the exact mechanisms and cellular effects of DACi have not been fully elucidated. In addition to their effects on histone acetylation, DACi can interfere with gene expression via miRNA pathways. Treatment with panobinostat (LBH589), a novel potent DACi, led to the highly aberrant modulation of several miRNAs in hepatocellular carcinoma (HCC) cell lines as shown by miRNA array analysis. Among them, hsa‐miR‐19a, hsa‐miR‐19b1 and the corresponding precursors were down‐regulated by panobinostat in TP53−/− Hep3B and TP53+/+ HepG2 cell lines; hsa‐miR30a‐5p mature form only was suppressed in both HCC cell lines, as confirmed by further RT‐qPCR analysis. In HCC cell lines, panobinostat caused the upregulation of the predicted miRNA targets APAF1 and Beclin1 protein levels. Transfection with oligonucleotides mimicking these miRNAs led to an increase in the viability rate of both cell lines as analyzed by impedance‐based real‐time cell analysis. In addition, transfecting miRNA mimicking oligonucleotides resulted in the decrease of APAF1, Beclin1 and PAK6 at the protein level, proving the regulating influence of the investigated miRNAs on gene final products. The overexpression of the above mentioned oncomiRs in Hep3B and HepG2 cell lines leads to cell proliferation and downregulation of cell death associated proteins. In our model, panobinostat exerts its anti‐cancer effect by suppressing these miRNAs and restoring the expression of their corresponding tumor suppressor targets. © 2013 Wiley Periodicals, Inc.
In vitro transformation of chlorogenic acid by human gut microbiota
Authors: Tomas‐Barberan Francisco , García‐Villalba Rocío , Quartieri Andrea , Raimondi Stefano , Amaretti Alberto , Leonardi Alan , Rossi Maddalena
Published: December 2013

Scope

Chlorogenic acid (3‐O‐caffeoyl‐quinic acid, C‐QA), the caffeic ester of quinic acid, is one of the most abundant phenolic acids in Western diet. The majority of C‐QA escapes absorption in the small intestine and reaches the colon, where the resident microbiota transforms it into several metabolites. C‐QA conversion by the gut microbiota from nine subjects was compared to evaluate the variability of bacterial metabolism. It was investigated whether a potentially probiotic Bifidobacterium strain, capable of C‐QA hydrolysis, could affect C‐QA fate.

Methods and results

Bioconversion experiments exploiting the microbiota from diverse subjects revealed that C‐QA was metabolized through a succession of hydrogenation, dexydroxylation and ester hydrolysis, occurring in different order among the subjects. Transformation may proceed also through quinic acid residue breakdown, since caffeoyl‐glycerol intermediates were identified (HPLC‐MS/MS, Q‐TOF). All the pathways converged on 3‐(3‐hydroxyphenyl)‐propanoic acid, which was transformed to hydroxyphenyl‐ethanol and/or phenylacetic acid in few subjects. A strain of Bifidobacterium animalis able to hydrolyze C‐QA was added to microbiota cultures. It affected microbial composition but not to such an extent that C‐QA metabolism was modified.

Conclusion

A picture of the variability of microbiota C‐QA transformations among subjects is provided. The transformation route through caffeoyl‐glycerol intermediates is described for the first time.
Prebiotic oligosaccharides directly modulate proinflammatory cytokine production in monocytes via activation of TLR4
Authors: Capitán‐Cañadas Fermín , Ortega‐González Mercedes , Guadix Emilia , Zarzuelo Antonio , Suárez María Dolores , de Medina Fermín Sánchez , Martínez‐Augustin Olga
Published: December 2013

Scope

Prebiotic oligosaccharides are currently used in a variety of clinical settings for their effects on intestinal microbiota. Here, we have examined the direct, microbiota independent, effects of prebiotics on monocytes and T lymphocytes in vitro.

Methods and results

Prebiotics generally evoked cytokine secretion (TNF‐α, IL‐6, and IL‐10) by mouse splenocytes but inhibited LPS ‐induced IFN‐γ and IL‐17 release. Inulin was found to enhance LPS‐induced IL‐10 secretion. Splenocytes from TLR4−/− (where TLR is Toll‐like receptor) mice showed a markedly depressed response. Conversely, in both basal and LPS‐stimulated conditions, prebiotic inhibition of IFN‐γ levels was preserved. These results suggested a predominant effect on monocytes via TLR4 ligation and possible inhibition of T cells. Hence, we studied the modulation of primary rat monocytes and T lymphocytes, focusing on fructooligosaccharides (FOS) and inulin. In monocytes, FOS and inulin induced TNF‐α, growth‐regulated oncogene α, and IL‐10, but not IL‐1β release. The NF‐κB inhibitor Bay 11–7082 fully prevented these effects. Pharmacological evidence also indicated a significant involvement of mitogen‐activated protein kinase and phosphatidylinositol‐3‐kinase. There was little effect on T cells. FOS and inulin also generally increased TNF‐α, IL‐1β, and IL‐10, but not IL‐8, in human peripheral blood monocytes.

Conclusion

We conclude that prebiotics may act as TLR4 ligands or as indirect TLR4 modulators to upregulate cytokine secretion in monocytes.
Relationships of body composition and liver fat content with insulin resistance in obesity‐matched adolescents and adults
Authors: Linder Katarzyna , Springer Fabian , Machann Jürgen , Schick Fritz , Fritsche Andreas , Häring Hans‐Ulrich , Blumenstock Gunnar , Ranke Michael B. , Stefan Norbert , Binder Gerhard , Ehehalt Stefan
Published: December 2013

Objective

While in adults not total body‐ or visceral fat mass, but liver fat content was found to independently determine insulin resistance, it is unclear whether these relationships are already present in obese adolescents.

Methods

Thirty‐nine overweight/obese adolescents were matched for sex and BMI with 39 adults. To compare the age‐ and sex‐specific BMI values of adolescents and adults, the percentile value of each adolescent was projected to the age of 18. Body fat depots were quantified by whole‐body magnetic resonance (MR) imaging. Liver fat content was measured with 1H‐MR spectroscopy. Insulin resistance was estimated from the homeostasis model assessment of insulin resistance (HOMA‐IR).

Results

Compared to overweight and obese adults, adolescents had higher HOMA‐IR (P < 0.001) and lower lean body mass (P = 0.002). Furthermore, they had higher total body‐ (P = 0.02), but lower visceral‐ (P < 0.001) fat mass, while liver fat content was not significantly different between the groups (P = 0.16). In both groups liver fat content (both P ≤ 0.007), but not total body‐ or visceral fat mass (all P ≥ 0.64) was an independent predictor of insulin resistance.

Conclusions

Having lower visceral fat mass, overweight and obese adolescents are more insulin resistant than sex‐ and BMI‐matched adults. Liver fat content, but not total body‐ or visceral fat mass, is an independent determinant of insulin resistance in adolescents.
Gastroschisis – what should be told to parents?
Authors: Lepigeon Karine , Van Mieghem Tim , Vasseur Maurer Sabine , Giannoni Eric , Baud David
Published: December 2013

Gastroschisis is a common congenital abdominal wall defect. It is almost always diagnosed prenatally thanks to routine maternal serum screening and ultrasound screening programs. In the majority of cases, the condition is isolated (i.e. not associated with chromosomal or other anatomical anomalies). Prenatal diagnosis allows for planning the timing, mode and location of delivery. Controversies persist concerning the optimal antenatal monitoring strategy. Compelling evidence supports elective delivery at 37 weeks' gestation in a tertiary pediatric center. Cesarean section should be reserved for routine obstetrical indications.

Prognosis of infants with gastroschisis is primarily determined by the degree of bowel injury, which is difficult to assess antenatally. Prenatal counseling usually addresses gastroschisis issues. However, parental concerns are mainly focused on long‐term postnatal outcomes including gastrointestinal function and neurodevelopment. Although infants born with gastroschisis often endure a difficult neonatal course, they experience few long‐term complications.

This manuscript, which is structured around common parental questions and concerns, reviews the evidence pertaining to the antenatal, neonatal and long‐term implications of a fetal gastroschisis diagnosis and is aimed at helping healthcare professionals counsel expecting parents. © 2013 John Wiley & Sons, Ltd.
The cell‐free fetal DNA fraction in maternal blood decreases after physical activity
Authors: Schlütter Jacob Mørup , Hatt Lotte , Bach Cathrine , Kirkegaard Ida , Kølvraa Steen , Uldbjerg Niels
Published: December 2013

Objective

If noninvasive prenatal testing using next generation sequencing is to be effective for pregnant women, a cell‐free fetal DNA (cffDNA) fraction above 4% is essential unless the depth of sequencing is increased. This study's objective is to determine whether physical activity has an effect on the proportion of cell‐free DNA (cfDNA) arising from the fetus (fetal fraction).

Methods

Nine pregnant women carrying male fetuses at gestational age 12+0 weeks to 14+6 weeks were included. Plasma from nine pregnant women was drawn prior to, immediately after, and 30 min after 30 min of cycling with a pulse‐rate of 150 beats per minute. The concentrations of cffDNA (DYS14) and cfDNA (RASSF1A) were assessed using quantitative real‐time polymerase chain reaction.

Results

The fetal fraction decreased significantly in all participants after physical activity (p < 0.01), a decrease varying from 1–17 percentage points. This was due to a significant increase in the concentration of cfDNA (p < 0.01), whereas the concentration of cffDNA remained the same. This alteration of the fetal fraction was not present 30 min after physical activity.

Conclusion

When planning the timing of noninvasive prenatal diagnosis based on the fetal fraction, physical activity prior to sampling should be avoided. © 2013 John Wiley & Sons, Ltd.
Improved resistive switching phenomena observed in SiNx‐based resistive switching memory through oxygen doping process
Authors: Park Ju Hyun , Kim Hee‐Dong , Hong Seok Man , Yun Min Ju , Jeon Dong Su , Kim Tae Geun
Published: December 2013

The improvement of resistive switching (RS) phenomena of silicon‐nitride (SiNx)‐based resistive random access memory (ReRAM) cells through oxygen doping process was investigated. As a result, compared to un‐doped SiNx films, the oxygen doped SiNx (SiNx:O2)‐based ReRAM cells show a lower current (∼0.3 μA) level at a high resistance state and a smaller variation of operating voltage through the reduction of leakage current in the SiNx:O2 film by combining silicon dangling bonds and doped oxygen ions. Therefore, we believe that the oxygen doping process in SiNx films can effectively improve the RS characteristics of SiNx‐based ReRAM cells. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Spatial language and abstract concepts
Authors: Casasanto Daniel , Bottini Roberto
Published: December 2013

What is the relationship between spatial language and abstract concepts? When people talk about abstract things that they can never see or touch, they often use spatial metaphors (e.g., alongvacation, ahighprice, aclosefriendship). According to theories of metaphorical mental representation, linguistic metaphors reflect underlying mental metaphors. Yet, behavioral experiments show that this is only one of the possible relationships between spatial metaphors in language and our spatial conceptualizations of abstract domains. In some cases, linguistic metaphors not only reflect speakers' thoughts, they also change those thoughts, such that people who use different linguistic metaphors rely on correspondingly different mental metaphors. Alternatively, spatial metaphors in language may reflect the way people conceptualize an abstract domainin some circumstances, but not in others. Finally, spatial language may reflect the way an abstract domain is typically conceptualizedby some people, but not by others. There is no single relationship between spatial language and abstract concepts. Discovering whether (and under what conditions) a linguistic metaphor corresponds to a mental metaphor can illuminate the ways in which our interactions with the physical and social environment shape our mental lives.WIREs Cogn Sci2014, 5:139–149. doi: 10.1002/wcs.1271

This article is categorized under:

Linguistics > Language in Mind and Brain

Psychology > Perception and Psychophysics

Psychology > Language
Self‐organizing maps for latent semantic analysis of free‐form text in support of public policy analysis
Authors: Till Bernie C. , Longo Justin , Dobell A. Rod , Driessen Peter F.
Published: December 2013

The huge amount of free‐form unstructured text in the blogosphere, its increasing rate of production, and its shrinking window of relevance, present serious challenges to the public policy analyst who seeks to take public opinion into account. Most of the tools which address this problem use XML tagging and other Web 3.0 approaches, which do not address the actual content of blog posts and the associated commentary. We give a tutorial review of latent semantic analysis and the self‐organizing maps, as considered in this context, and show how to apply the self‐organizing map over a probabilistic latent semantic space to the problem of completely unsupervised clustering of unstructured text in such a way as to be entirely independent of spelling, grammar, and even source language. This provides an algorithm suitable for clustering free‐form commentary with a well‐structured test environment. The algorithm is applied to academic paper abstracts instead, treated as unstructured text as though they were blog posts, because this set of documents has a known ground truth. The algorithm constructs a word category map and a document map in which words with similar meaning and documents with similar content are clustered together. WIREs Data Mining Knowl Discov 2014, 4:71–86. doi: 10.1002/widm.1112

This article is categorized under:

Algorithmic Development > Web Mining

Application Areas > Government and Public Sector

Technologies > Structure Discovery and Clustering
Spatiotemporal change footprint pattern discovery: an inter‐disciplinary survey
Authors: Zhou Xun , Shekhar Shashi , Ali Reem Y.
Published: December 2013

Given a definition of change and a dataset about spatiotemporal (ST) phenomena,STchange footprint discovery is the process of identifying the location and/or time of such changes from the dataset. Change footprint discovery is fundamentally important for the study of climate change, the tracking of disease, and many other applications. Methods for detecting change footprints have emerged from a diverse set of research areas, ranging from time series analysis and remote sensing to spatial statistics. Researchers have much to learn from one another, but are stymied by inconsistent use of terminology and varied definitions of change across disciplines. Existing reviews focus on discovery methods for only one or a few types of change footprints (e.g., point change in a time series). To facilitate sharing of insights across disciplines, we conducted a multi‐disciplinary review ofSTchange patterns and their respective discovery methods. We developed a taxonomy of possibleSTchange footprints and classified our review findings accordingly. This exercise allowed us to identify gaps in the research that we consider ripe for exploration, most notably change pattern discovery in vectorSTdatasets. In addition, we illustrate how such pattern discovery might proceed using two case studies from historicalGIS.WIREs Data Mining Knowl Discov2014, 4:1–23. doi: 10.1002/widm.1113

This article is categorized under:

Algorithmic Development > Spatial and Temporal Data Mining

Fundamental Concepts of Data and Knowledge > Motivation and Emergence of Data Mining

Technologies > Structure Discovery and Clustering