bluuebunny/crossref_metadata_2025 huggingface dataset:
On the biogeochemical response of a glacierized High Arctic watershed to climate change: revealing patterns, processes and heterogeneity among micro‐catchments
Authors: Nowak Aga , Hodson Andy
Published: June 2014

Our novel study examines landscape biogeochemical evolution following deglaciation and permafrost change in Svalbard by looking at the productivity of various micro‐catchments existing within one watershed. It also sheds light on how moraine, talus and soil environments contribute to solute export from the entire watershed into the downstream marine ecosystem.

We find that solute dynamics in different micro‐catchments are sensitive to abiotic factors such as runoff volume, water temperature, geology, geomorphological controls upon hydrological flowpaths and landscape evolution following sea level and glacial changes. Biotic factors influence the anionic composition of runoff because of the importance of microbial SO42− and NO3− production. The legacy of glaciation and its impact upon sea level changes is shown to influence local hydrochemistry, allowing Cl− to be used as a tracer of thawing permafrost that has marine origins. However, we show that a ‘glacial signal’ dominates solute export from the watershed. Therefore, although climatically driven change in the proglacial area has an influence on local ecosystems, the biogeochemical response of the entire watershed is dominated by glacially derived products of rapid chemical weathering. Consequently, only the study of micro‐catchments existing within watersheds can uncover the landscape response to contemporary climate change. Copyright © 2014 John Wiley & Sons, Ltd.
Effects of Neonatal Enzyme Replacement Therapy and Simvastatin Treatment on Cervical Spine Disease in Mucopolysaccharidosis I Dogs
Authors: Chiaro Joseph A , O'Donnell Patricia , Shore Eileen M , Malhotra Neil R , Ponder Katherine P , Haskins Mark E , Smith Lachlan J
Published: June 2014

Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease characterized by deficient α-L-iduronidase activity, leading to the accumulation of poorly degraded glycosaminoglycans (GAGs). Children with MPS I exhibit high incidence of spine disease, including accelerated disc degeneration and vertebral dysplasia, which in turn lead to spinal cord compression and kyphoscoliosis. In this study we investigated the efficacy of neonatal enzyme replacement therapy (ERT), alone or in combination with oral simvastatin (ERT + SIM) for attenuating cervical spine disease progression in MPS I, using a canine model. Four groups were studied: normal controls; MPS I untreated; MPS I ERT-treated; and MPS I ERT + SIM–treated. Animals were euthanized at age 1 year. Intervertebral disc condition and spinal cord compression were evaluated from magnetic resonance imaging (MRI) images and plain radiographs, vertebral bone condition and odontoid hypoplasia were evaluated using micro–computed tomography (µCT), and epiphyseal cartilage to bone conversion was evaluated histologically. Untreated MPS I animals exhibited more advanced disc degeneration and more severe spinal cord compression than normal animals. Both treatment groups resulted in partial preservation of disc condition and cord compression, with ERT + SIM not significantly better than ERT alone. Untreated MPS I animals had significantly lower vertebral trabecular bone volume and mineral density, whereas ERT treatment resulted in partial preservation of these properties. ERT + SIM treatment demonstrated similar, but not greater, efficacy. Both treatment groups partially normalized endochondral ossification in the vertebral epiphyses (as indicated by absence of persistent growth plate cartilage), and odontoid process size and morphology. These results indicate that ERT begun from a very early age attenuates the severity of cervical spine disease in MPS I, particularly for the vertebral bone and odontoid process, and that additional treatment with simvastatin does not provide a significant additional benefit over ERT alone. © 2014 American Society for Bone and Mineral Research.
Prediction of Incident Hip Fracture with the Estimated Femoral Strength by Finite Element Analysis of DXA Scans in the Study of Osteoporotic Fractures
Authors: Yang Lang , Palermo Lisa , Black Dennis M , Eastell Richard
Published: June 2014

A bone fractures only when loaded beyond its strength. The purpose of this study was to determine the association of femoral strength, as estimated by finite element (FE) analysis of dual-energy X-ray absorptiometry (DXA) scans, with incident hip fracture in comparison to hip bone mineral density (BMD), Fracture Risk Assessment Tool (FRAX), and hip structure analysis (HSA) variables. This prospective case-cohort study included a random sample of 1941 women and 668 incident hip fracture cases (295 in the random sample) during a mean ± SD follow-up of 12.8 ± 5.7 years from the Study of Osteoporotic Fractures (n = 7860 community-dwelling women ≥67 years of age). We analyzed the baseline DXA scans (Hologic 1000) of the hip using a validated plane-stress, linear-elastic finite element (FE) model of the proximal femur and estimated the femoral strength during a simulated sideways fall. Cox regression accounting for the case-cohort design assessed the association of estimated femoral strength with hip fracture. The age–body mass index (BMI)-adjusted hazard ratio (HR) per SD decrease for estimated strength (2.21; 95% CI, 1.95–2.50) was greater than that for total hip (TH) BMD (1.86; 95% CI, 1.67–2.08; p < 0.05), FN BMD (2.04; 95% CI, 1.79–2.32; p > 0.05), FRAX scores (range, 1.32–1.68; p < 0.0005), and many HSA variables (range, 1.13–2.43; p < 0.005), and the association was still significant (p < 0.05) after further adjustment for hip BMD or FRAX scores. The association of estimated strength with incident hip fracture was strong (Harrell's C index 0.770), significantly better than TH BMD (0.759; p < 0.05) and FRAX scores (0.711–0.743; p < 0.0001), but not FN BMD (0.762; p > 0.05). Similar findings were obtained for intracapsular and extracapsular fractures. In conclusion, the estimated femoral strength from FE analysis of DXA scans is an independent predictor and performs at least as well as FN BMD in predicting incident hip fracture in postmenopausal women. © 2014 American Society for Bone and Mineral Research.
Dose response of umeclidinium administered once or twice daily in patients with COPD: A pooled analysis of two randomized, double‐blind, placebo‐controlled studies
Authors: Donohue James F. , Kalberg Christopher , Shah Palvi , Beerahee Misba , Mehta Rashmi , Gunawan Rudy , Church Alison
Published: June 2014

Umeclidinium (UMEC) is an inhaled long‐acting muscarinic antagonist approved in the US and EU for the once‐daily (QD) treatment of chronic obstructive pulmonary disease (COPD); it is not indicated for the treatment of asthma. To fully characterize the dose–response relationship of UMEC in patients with COPD, a pooled analysis of data from two randomized, placebo‐controlled, cross‐over, dose‐ranging studies was performed, evaluating UMEC at doses of 15.6–1000 mcg QD and 15.6–250 mcg twice daily (BID). The primary endpoint was trough forced expiratory volume in one second (FEV1) at the end of each study's treatment period (Day 8/Day 15). A population model‐based analysis using total daily UMEC dose was used for the primary analysis comparing QD and BID dosing. A physiological effect (Emax) model was optimal in defining the relationship between UMEC dose and the primary endpoint, demonstrating a clear monotonic dose response over QD and BID dosing regimens. UMEC doses ≥62.5 mcg QD were differentiated from lower doses and BID dosing did not provide benefit over QD dosing. The potency (ED50) estimate was 33 mcg with QD dosing. These data indicate that UMEC 62.5 mcg and 125 mcg QD provide lung function benefits that warrant further investigation for the treatment of COPD.
Doppler evaluation of ocular vessels in patients with primary open angle glaucoma
Authors: Suprasanna K. , Shetty Chandrakant M. , Charudutt S. , Kadavigere Rajagopal
Published: June 2014

Purpose

To assess ocular blood flow in patients with primary open angle glaucoma (POAG) with or without progressive visual field loss in comparison with controls.

Methods

Color Doppler imaging was performed on 78 eyes with established POAG (25 with progressive visual field loss and 53 with stable visual field) and 78 control eyes. Peak systolic velocity, end diastolic velocity (EDV), and resistance index (RI) were measured in the ophthalmic (OA), central‐retinal, and medial and lateral posterior ciliary arteries.

Results

Peak systolic velocity and EDV were lower and RI was higher in the ocular vessels of eyes with POAG (p < .01). The OA and medial posterior ciliary arteries RI was higher, and the OA EDV was lower in glaucomatous eyes with progressive than with stable visual field loss. The receiver operating characteristic curve showed the optimal cutoff RI to be 0.847.

Conclusions

Ocular blood flow appears compromised in eyes with POAG, particularly in those with progressive visual field loss. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 42:486–491, 2014
Usefulness of intracardiac echocardiography with a mechanical probe for catheter‐based interventions: A 10‐year prospective registry
Authors: Rigatelli Gianluca , Dell'Avvocata Fabio , Giordan Massimo , Viceconte Nicola , Osanna Rocco Aldo , Braggion Gabriele , Aggio Silvio , Cardaioli Paolo , Chen Jack P.
Published: June 2014

Background

The clinical outcome benefit of intracardiac echocardiography (ICE) with a mechanical probe during congenital heart disease interventions has not been fully investigated. We reported the long‐term results of a prospective registry of interatrial shunt closure guided by mechanical ICE.

Methods

We enrolled 537 patients (mean age 48 ± 19.0 years, 378 females) submitted to ICE‐aided procedures in a prospective registry over a 10‐year period (September 2003‐September 2013). All patients underwent transesophageal echocardiography (TEE) before the planned procedure. We evaluated (1) structure identification capability, (2) fossa ovale and interatrial septum component measurement, (3) procedure monitoring capability, (4) procedural and fluoroscopy times, and radiograph dose, (5) probe‐related complications.

Results

ICE was successfully performed and was able to correctly identify the structures previously assessed by TEE in all patients. In 24 patients (4.5%), ICE allowed better anatomy definition than TEE. In 35 other patients (6.5%), ICE identified structures not observed by TEE, which led to change indications to interventions or the operative technique to be used. In 131 patients (24.4%), ICE evaluation led to change the planned device to be implanted. There was only one probe‐related complication (0.2%).

Conclusions

Mechanical ICE may offer a valid alternative to conventional TEE in guiding congenital heart disease interventional procedures. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 42:534–543, 2014
Challenges Faced by Patients With Progressive Supranuclear Palsy and their Families
Authors: Moore Theresa , Guttman Mark
Published: June 2014

The literature is inadequate for understanding the challenges experienced by people with PSP and their families. Therefore, the aim of this study was to understand the challenges of people with PSP and their caregivers and identify their priority need. In this qualitative study, five focus groups were conducted with people with PSP and/or their family caregivers, one group with long‐term care staff, and one with community caregivers. Data were analyzed using fundamental qualitative description. Four themes were identified: knowledge, services, research, and symptoms. Knowledge challenges were identified as the priority need, with the most common challenges in this category being lack of knowledge of PSP among community workers, physicians, patients, and family members. Service challenges involved service access and interactions with physicians, community workers, private caregivers, and long‐term care staff. Research challenges related to the lack of research and the failure of health care providers or PSP organizations to communicate research findings. Symptoms most often identified as challenging were falls, mobility, vision, mood or thinking, speech, and swallowing. Participants identified their priority need as dissemination of information about PSP. This has not been captured in previous research. This information needs to reach doctors, long‐term care staff, community workers, patients, families, and the general public. Subsequent activities to meet this need are summarized. These activities resulted in three new resources: a brochure for patients and families; an information packet for physicians; and a webinar for staff in long‐term care and community.
Existence results for a nonlinear version of Rotenberg model with infinite maturation velocities
Authors: Boumhamdi Mounir , Latrach Khalid , Zeghal Ahmed
Published: June 2014

In this paper, we present some existence results on L1 spaces of a nonlinear boundary value problem derived from a model introduced by Rotenberg (1983) describing the growth of a cell population. Each cell of this population is distinguished by its degree of maturity μ ∈ [0,1] and its maturation velocity v. The biological boundary at μ = 0 and μ = 1 are fixed and tightly coupled through the mitosis. At mitosis, daughter cells and mother cells are related by a general reproduction rule, which covers all known biological ones. In this work, the maturation velocity is allowed to be infinite, that is, v ∈ [0, + ∞ ). This hypothesis introduce some mathematical difficulties, which are overcomed by using a measure of weak noncompactness adapted to the problem and a recent fixed point theorem (Theorem 3.2) involving weakly compact operators on nonreflexive Banach spaces. Copyright © 2014 John Wiley & Sons, Ltd.
Bifurcation analysis of amathematical model for the growth of solid tumors in the presence of external inhibitors
Authors: Wu Junde , Cui Shangbin
Published: June 2014

We study bifurcations from radial solution of a free boundary problem modeling the dormant state of nonnecrotic solid tumors in the presence of external inhibitors. This problem consists in three linear elliptic equations with two Dirichlet and one Neumann boundary conditions and a fourth boundary condition coupling surface tension effects on free boundary. In this paper, surface tension coefficient γ plays the role of bifurcation parameter. We prove that in certain situations there exists a positive null point sequence for γ where bifurcation occurs from radial solution, while in the other situations, either bifurcation occurs at only finite many points of γ or even it does not occur for any γ > 0. Copyright © 2014 John Wiley & Sons, Ltd.
Gap formulas for closed linear relations
Authors: Álvarez Teresa
Published: June 2014

A classical formula for the gap between two densely defined closed operators in a Hilbert space is extended to the case of linear relations. Copyright © 2014 John Wiley & Sons, Ltd.
An Experimental and Analytical Study of an Asymmetric Capacitively Coupled Plasma Used for Plasma Polymerization
Authors: Michelmore Andrew , Whittle Jason D. , Short Robert D. , Boswell Rod W. , Charles Christine
Published: June 2014

Plasma processing is widely used to provide novel surface modifications to materials for a variety of applications. Typically, the systems used to carry out these modifications are poorly characterised. Here we describe the basics of a global model for a capacitively coupled asymmetric parallel plate radiofrequency plasma system routinely used to produce plasma polymers. An analytical global model was developed for argon, for which cross‐sections are known, at a constant pressure of 1 Pa, and includes an electrical model and a power balance. The main parameters of interest were ion flux and self‐bias voltages. The argon modelling results were then compared to experimental results for a range of operating gases (argon, oxygen, amines, acids, alcohols, ethers, siloxanes) including both saturated and unsaturated compounds with molecular weights ranging from 40 to 162 g · mol−1, for different inter‐electrode separations and from 2 to 50 W using an Impedans OctIV probe. Importantly, it is shown that the RF power transfer efficiency is dependent on the gas. The results show that the argon model results can be used to predict the plasma parameters for other gases when the RF power transfer efficiency is taken into account.
Crystal structures of ligand‐bound octaprenyl pyrophosphate synthase from Escherichia coli reveal the catalytic and chain‐length determining mechanisms
Authors: Han Xu , Chen Chun‐Chi , Kuo Chih‐Jung , Huang Chun‐Hsiang , Zheng Yingying , Ko Tzu‐Ping , Zhu Zhen , Feng Xinxin , Wang Ke , Oldfield Eric , Wang Andrew H.‐J. , Liang Po‐Huang , Guo Rey‐Ting , Ma Yanhe
Published: June 2014

Octaprenyl pyrophosphate synthase (OPPs) catalyzes consecutive condensation reactions of one allylic substrate farnesyl pyrophosphate (FPP) and five homoallylic substrate isopentenyl pyrophosphate (IPP) molecules to form a C40 long‐chain product OPP, which serves as a side chain of ubiquinone and menaquinone. OPPs belongs to the trans‐prenyltransferase class of proteins. The structures of OPPs from Escherichia coli were solved in the apo‐form as well as in complexes with IPP and a FPP thio‐analog, FsPP, at resolutions of 2.2–2.6 Å, and revealed the detailed interactions between the ligands and enzyme. At the bottom of the active‐site tunnel, M123 and M135 act in concert to form a wall which determines the final chain length. These results represent the first ligand‐bound crystal structures of a long‐chain trans‐prenyltransferase and provide new information on the mechanisms of catalysis and product chain elongation. Proteins 2015; 83:37–45. © 2014 Wiley Periodicals, Inc.
Light‐yield improvement trends in mixed scintillation crystals
Authors: Sidletskiy Oleg , Gektin Alexander , Belsky Andrei
Published: June 2014

The behavior of light yield in a wide range of inorganic scintillation crystals formed by isovalent substitution of anions or cations was investigated. The correlation between improvement of light yield in mixed crystals, and the ratios of volumes occupied by the competing atoms (ions) has been analyzed. A phenomenological approach to the prediction of light yield in mixed scintillation crystals allows us to predict the optimal combination of mixing components to reach the best scintillation performance.

Relation between the rate of light‐yield improvement and ratio of the volumes occupied by the substituted atoms.
EPR study of the hydrogen center in HPHT diamonds grown in carbonate medium
Authors: Komarovskikh Andrey , Nadolinny Vladimir , Palyanov Yuri , Kupriyanov Igor , Sokol Alexander
Published: June 2014

An electron paramagnetic resonance (EPR) study of synthetic diamond crystals grown at HTHP conditions in the carbonate medium Na2CO3CO2H2OC has revealed a hydrogen‐containing center (VOH) along with centers OX1, OX2, and OX3 tentatively associated with oxygen. In the X‐band EPR spectra, the forbidden transitions of the center are superimposed on the allowed HFS lines of one hydrogen atom. We have succeeded in analysis of the allowed transitions in Q‐band experiments. On the basis of the obtained experimental data a hypothetical model of the center has been proposed as a vacancy–oxygen complex with incorporated hydrogen atom. The occurrence of hydrogen in the studied diamond crystals is supported by the presence of CH vibrations in the IR spectra in the range of 3000 cm−1.
Pomegranate Juice and Prostate Cancer: Importance of the Characterisation of the Active Principle
Authors: Chrubasik‐Hausmann Sigrun , Vlachojannis Christian , Zimmermann Benno
Published: June 2014

Two exploratory clinical studies investigating proprietary pomegranate products showed a trend of effectiveness in increasing prostate‐specific antigen doubling time in patients with prostate cancer. A recent clinical study did not support these results. We therefore analysed a lot of the marketed pomegranate blend for co‐active pomegranate compounds. The high‐performance liquid chromatography method was used to detect punicalagin, ellagic acid and anthocyanins. Total polyphenoles were determined by the Folin–Ciocalteu method using gallic acid as reference. The results show that the co‐active compounds in the daily dose of the pomegranate blend were far below those previously tested and that the photometric assessment is not reliable for the standardisation of study medications. Not pomegranate but the low amount of co‐active compounds in the proprietary pomegranate blend was responsible for its clinical ineffectiveness. Copyright © 2014 John Wiley & Sons, Ltd.
Black Tea Extract and its Thearubigins Relieve the Sildenafil‐Induced Delayed Gut Motility in Mice: A Possible Role of Nitric Oxide
Authors: Murad Hussam A. S. , Abdallah Hossam M.
Published: June 2014

In this study we hypothesize that a standardized black tea aqueous extract (BTE) and thearubigins, its main polyphenolic pigments, will improve sildenafil‐induced delay in gastric emptying (GE) and small intestinal transit (SIT) in mice. Twenty groups of mice (n = 8) were given a phenol red meal, and three sets of experiments were performed. In the first and second sets, effects of different concentrations of BTE, thearubigins (TRs), and sildenafil (SLD), alone and in combinations, on GE and SIT were measured. In the third set, influence of nω‐Nitro‐l‐arginine methyl ester hydrochloride (l‐NAME) pretreatment on effects of these treatments was tested.

Black tea extract (3% and 4.5%) and thearubigins (50 and 60 mg/kg) dose‐dependently increased GE and SIT, whereas BTE 6% and thearubigins 70 mg/kg did not affect them. Sildenafil dose‐dependently reduced both GE and SIT. Combination of metoclopramide, BTE 4.5%, thearubigins 60, or l‐NAME with sildenafil (5 mg/kg) reversed its motility‐delaying effects. Pretreatment with l‐NAME followed by BTE 4.5%, thearubigins 60, BTE 4.5% + sildenafil 5, or thearubigins 60 + sildenafil 5 only partially affected the accelerating effects of BTE 4.5% and thearubigins 60. In conclusion, a standardized BTE and its thearubigins improve the sildenafil‐induced delayed gut motility in mice. This improvement was partially blocked by l‐NAME suggesting a possible role of nitric oxide. Thus, BTE 4.5% or TRs 60 mg/kg solution could be considered a reliever therapy for the sildenafil‐induced dyspepsia. Copyright © 2014 John Wiley & Sons, Ltd.
Electron attachment to some naphthoquinone derivatives: long‐lived molecular anion formation
Authors: Asfandiarov N. L. , Pshenichnyuk S. A. , Vorob'ev A. S. , Nafikova E. P. , Elkin Y. N. , Pelageev D. N. , Koltsova E. A. , Modelli A.
Published: June 2014

RATIONALE

Electron Affinity (EA) is one of the fundamental properties of a molecule. EA values can be measured with various experimental methods, although their availability is still relatively limited. We make an attempt to use Dissociative Electron Attachment Spectroscopy (DEAS) data for evaluation of the EAs of twelve naphthoquinone (NQ) derivatives.

METHODS

Naphthoquinone (NQ) and eleven of its hydroxyl derivatives were investigated by means of DEAS. A combined investigation of NQ and juglone by means of the Electron Transmission Spectroscopy (ETS) and DEAS techniques, with the support of density functional theory (DFT) calculations, allowed us to elucidate the empty‐level structures of NQ and its hydroxyl derivatives.

RESULTS

All molecules under investigation form extremely long‐lived molecular anions associated with three resonant states (except for NQ, where only two long‐lived resonances were observed). The hydroxyl substituents of NQ cause an increase in EA and number of internal degrees of freedom (N), and, as a result, an increase in the mean electron autodetachment lifetimes of the molecular negative ions (NIs). Evaluation of the EAs from the measured lifetimes of the molecular NIs through a simple Arrhenius approximation gives results in reasonable agreement with those obtained with DFT calculations.

CONCLUSIONS

NI lifetime measurements by means of a modified DEAS instrumentation can provide quantitative data of EA. A simple Arrhenius approximation seems to be adequate to describe the process of electron detachment from molecular anions. Copyright © 2014 John Wiley & Sons, Ltd.
Reversible platypnea‐orthodeoxia syndrome induced by rapidly progressive interstitial pneumonia in a patient with polymyositis
Authors: Yamakawa Hideaki , Yoshida Masahiro , Baba Yuri , Ishikawa Takeo , Takagi Masamichi , Kuwano Kazuyoshi
Published: June 2014

We report a case of platypnea‐orthodeoxia that developed in a 64‐year‐old Japanese woman during an episode of rapidly progressive interstitial pneumonia with polymyositis. Pulmonary infiltrates were predominant in the bilateral lower lobes. The patient was treated successfully with early administration of immunosuppressive therapies and polymyxin B‐immobilized fiber column‐direct hemoperfusion, and her platypnea‐orthodeoxia improved with resolution of the underlying parenchymal lung disease. Reports of platypnea‐orthodeoxia syndrome with interstitial pneumonia are extremely rare. The recognition that platypnea‐orthodeoxia syndrome may occur in multiple disease states, including interstitial pneumonia, is crucial to the understanding of this perplexing disorder.
Cannibalization and option value effects of secondary markets: Evidence from the US concert industry
Authors: Bennett Victor M. , Seamans Robert , Zhu Feng
Published: June 2014

We examine how reducing search frictions in secondary markets affects the value appropriated by firms in primary markets. We characterize two effects on primary‐market firms caused by intermediaries entering secondary markets: the “cannibalization” and “option value” effects. Separation between primary and secondary markets can drive which of the two effects dominates. Firms selling valuable and scarce products are more likely to have separate primary and secondary markets, and will therefore appropriate more value when secondary markets thicken. Firms selling products that are not valuable and scarce will be hurt. Further, we hypothesize that firms have incentives to engineer scarcity by limiting supply when secondary markets thicken to separate primary and secondary markets. We find support for these hypotheses in the U.S. concert ticket industry. Copyright © 2014 John Wiley & Sons, Ltd.
Bio‐Hybrid Cell‐Based Actuators for Microsystems
Authors: Carlsen Rika Wright , Sitti Metin
Published: June 2014

As we move towards the miniaturization of devices to perform tasks at the nano and microscale, it has become increasingly important to develop new methods for actuation, sensing, and control. Over the past decade, bio‐hybrid methods have been investigated as a promising new approach to overcome the challenges of scaling down robotic and other functional devices. These methods integrate biological cells with artificial components and therefore, can take advantage of the intrinsic actuation and sensing functionalities of biological cells. Here, the recent advancements in bio‐hybrid actuation are reviewed, and the challenges associated with the design, fabrication, and control of bio‐hybrid microsystems are discussed. As a case study, focus is put on the development of bacteria‐driven microswimmers, which has been investigated as a targeted drug delivery carrier. Finally, a future outlook for the development of these systems is provided. The continued integration of biological and artificial components is envisioned to enable the performance of tasks at a smaller and smaller scale in the future, leading to the parallel and distributed operation of functional systems at the microscale.
Molecular Aspects of Adipoepithelial Transdifferentiation in Mouse Mammary Gland
Authors: Prokesch A. , Smorlesi A. , Perugini J. , Manieri M. , Ciarmela P. , Mondini E. , Trajanoski Z. , Kristiansen K. , Giordano A. , Bogner-Strauss J.G. , Cinti Saverio
Published: June 2014

The circular, reversible conversion of the mammary gland during pregnancy and involution is a paradigm of physiological tissue plasticity. The two most prominent cell types in mammary gland, adipocytes and epithelial cells, interact in an orchestrated way to coordinate this process. Previously, we showed that this conversion is at least partly achieved by reciprocal transdifferentiation between mammary adipocytes and lobulo-alveolar epithelial cells. Here, we aim to shed more light on the regulators of mammary transdifferentiation. Using immunohistochemistry with cell type-specific lipid droplet-coating markers (Perilipin1 and 2), we show that cells with an intermediate adipoepithelial phenotype exist during and after pregnancy. Nuclei of cells with similar transitional structural characteristics are highly positive for Elf5, a master regulator of alveologenesis. In cultured adipocytes, we could show that transient and stable ectopic expression of Elf5 induces expression of the milk component whey acidic protein, although the general adipocyte phenotype is not affected suggesting that additional pioneering factors are necessary. Furthermore, the lack of transdifferentiation of adipocytes during pregnancy after clearing of the epithelial compartment indicates that transdifferentiation signals must emanate from the epithelial part. To explore candidate genes potentially involved in the transdifferentiation process, we devised a high-throughput gene expression study to compare cleared mammary fat pads with developing, contralateral controls at several time points during pregnancy. Incorporation of bioinformatic predictions of secretory proteins provides new insights into possible paracrine signaling pathways and downstream transdifferentiation factors. We discuss a potential role for osteopontin (secreted phosphoprotein 1 [Spp1]) signaling through integrins to induce adipoepithelial transdifferentiation. Stem Cells  2014;32:2756–2766
Elevated O-GlcNAc Levels Activate Epigenetically Repressed Genes and Delay Mouse ESC Differentiation Without Affecting Naïve to Primed Cell Transition
Authors: Speakman Christopher M. , Domke Tanja C.E. , Wongpaiboonwattana Wikrom , Sanders Kelly , Mudaliar Manikhandan , van Aalten Daan M.F. , Barton Geoffrey J. , Stavridis Marios P.
Published: June 2014

The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). In EBs, expression of mesodermal and endodermal markers is also delayed. However, the transition of naïve cells to primed pluripotency indicated by Rex1 (Zfp42), Nanog, Esrrb, and Dppa3 downregulation and Fgf5 upregulation remains unchanged. Finally, we demonstrate that increased O-GlcNAcylation results in upregulation of genes normally epigenetically silenced in ESCs, supporting the emerging role for this protein modification in the regulation of histone modifications and DNA methylation. Stem Cells  2014;32:2605–2615
Notch1 Stimulation Induces a Vascularization Switch With Pericyte-Like Cell Differentiation of Glioblastoma Stem Cells
Authors: Guichet Pierre-Olivier , Guelfi Sophie , Teigell Marisa , Hoppe Liesa , Bakalara Norbert , Bauchet Luc , Duffau Hugues , Lamszus Katrin , Rothhut Bernard , Hugnot Jean-Philippe
Published: June 2014

Glioblastoma multiforms (GBMs) are highly vascularized brain tumors containing a subpopulation of multipotent cancer stem cells. These cells closely interact with endothelial cells in neurovascular niches. In this study, we have uncovered a close link between the Notch1 pathway and the tumoral vascularization process of GBM stem cells. We observed that although the Notch1 receptor was activated, the typical target proteins (HES5, HEY1, and HEY2) were not or barely expressed in two explored GBM stem cell cultures. Notch1 signaling activation by expression of the intracellular form (NICD) in these cells was found to reduce their growth rate and migration, which was accompanied by the sharp reduction in neural stem cell transcription factor expression (ASCL1, OLIG2, and SOX2), while HEY1/2, KLF9, and SNAI2 transcription factors were upregulated. Expression of OLIG2 and growth were restored after termination of Notch1 stimulation. Remarkably, NICD expression induced the expression of pericyte cell markers (NG2, PDGFRβ, and α-smooth muscle actin [αSMA]) in GBM stem cells. This was paralleled with the induction of several angiogenesis-related factors most notably cytokines (heparin binding epidermal growth factor [HB-EGF], IL8, and PLGF), matrix metalloproteinases (MMP9), and adhesion proteins (vascular cell adhesion molecule 1 [VCAM1], intercellular adhesion molecule 1 [ICAM1], and integrin alpha 9 [ITGA9]). In xenotransplantation experiments, contrasting with the infiltrative and poorly vascularized tumors obtained with control GBM stem cells, Notch1 stimulation resulted in poorly disseminating but highly vascularized grafts containing large vessels with lumen. Notch1-stimulated GBM cells expressed pericyte cell markers and closely associated with endothelial cells. These results reveal an important role for the Notch1 pathway in regulating GBM stem cell plasticity and angiogenic properties. Stem Cells  2015;33:21–34
The impacts of white‐tailed deer browsing and distance from the forest edge on soybean yield
Authors: Rogerson Joseph E. , Bowman Jacob L. , Tymkiw Elizabeth L. , Colligan Gregory M. , Vasilas Bruce L.
Published: June 2014

Many soybean (Glycine max) producers consider white‐tailed deer (Odocoileus virginianus) to be costly crop pests, and chemical repellants are an option for reducing deer damage. To cost‐effectively utilize repellants, it is crucial to know the spatial and temporal aspects of deer‐browsing patterns. During 2003–2006 in Delaware, USA, we investigated where and when browsing was most intense within crop fields and subsequently had the greatest effect on yield of soybeans at an estimated deer density of 21 deer/km2. We systematically placed plots (n = 1,340) at 10‐m intervals from the forest edge. We designed protection treatments to mimic the effect of chemical repellents. We systematically assigned types of protection treatments to plots and protected plots using fencing. Protection did not affect the yield of double‐crop soybeans in any year. In 2 years of the study (2003 and 2006), protection did not affect full‐season soybean yield. In the other 2 years (2004 and 2005), plots protected from deer browse yielded less than plots that were not protected. Yield tended to be the lowest in the first 20 m from the forest edge, but there was no interaction effect between deer browsing and distance from the forest edge for any year or crop type. We found that deer browsing increased yield, possibly because browsing increases branching of individual plants, and thus the number of bean pods. We also found that the distance from the forest edge affected yield, but independently of deer browsing. Deer damage to soybeans, at a deer density of 21 deer/km2, may be more of a perceptual issue and the use of a chemical repellant would not be justified. © 2014 The Wildlife Society.
Reconstruction of focal cartilage defects in the talus with miniarthrotomy and collagen matrix
Authors: Walther M. , Altenberger S. , Kriegelstein S. , Volkering C. , Röser A.
Published: June 2014

Surgical principal and objective

Treatment of focal cartilage defects (traumatic or osteochondrosis dissecans) of the talus using a collagen matrix. The goal is to stabilize the superclot formed after microfracturing to accommodate cartilage repair. The procedure can be carried out via miniarthrotomy, without medial malleolus osteotomy.

Indications

International Cartilage Repair Society (ICRS) grade III and IV focal cartilage defects of the talus > 1.5 cm2.

Contraindications

Generalized osteoarthritis, inflammatory joint disease, gout, neuroarthropathy.

Surgical technique

Miniarthrotomy to open the ankle joint. Debridement of unstable cartilage and necrotic bone, curettage of cysts. Filling of the bone defects with autologous cancellous bone. Sealing of reconstructed bone with fibrin glue and attachment of a collagen matrix shaped to precisely fit the defect.

Postoperative regimen

Immobilization for 48 h. Partial weight bearing of 10 kg for 6 weeks, with continuous passive motion. Increasing weight bearing from 7 weeks onwards.

Results

Follow-up of at least 30 months in 14 patients showed improvement in the Score of the American Orthopedic Foot and Ankle Society (AOFAS) from 50 to 89 points, with equal mobility on both sides of the upper ankle joint.
First 100 Laparoscopic Surgeries in a Predominantly Rural Nigerian Population: A Template for Future Growth
Authors: Ekwunife Christopher N. , Nwobe Ogechukwu
Published: June 2014

Background

Minimal access surgery has revolutionized surgery practice. Its proven advantages, such as reduced postoperative pain, early return to unrestricted activities, and better cosmesis, have become important drivers for its rapid development. In sub‐Saharan Africa this development has been slow. The aim of the current study was to describe the challenges and outcomes of laparoscopic procedures in a public hospital that caters to a predominantly rural population.

Material and methods

The first 100 patients who underwent laparoscopic procedure in the Department of Surgery at Federal Medical Centre, Owerri, Nigeria were retrospectively analyzed. Data were retrieved from the medical records department as well as the surgical theater procedure register. The focus of the study was on patient demographics, indication for surgery, procedure performed, length of hospital stay, and morbidity and mortality data. Staff training was done locally and abroad.

Results

Altogether, 100 patients had laparoscopic surgery in our general surgery unit from September 2007 through July 2013. The ages of the patients was 5–75 years (median 36.5 years). The three main procedures were cholecystectomy (36 %), diagnostic laparoscopy (29 %), and appendectomy (21 %). The other operations performed included liver abscess drainage (7 %), adhesiolysis (3 %), hernia repair (1 %), and Heller’s myotomy (1 %). Four cases were converted to open surgery. There were no deaths. There were 14 grades I and II postoperative complications in nine patients.

Conclusions

Our study suggests that basic laparoscopic procedures could be offered safely to our resource‐poor rural population. It is a platform on which we can hopefully introduce advanced laparoscopic surgical operations.
Evaluation of the Patient-Specific Functional Scale in hand Fractures and Dislocations
Authors: Novak Christine B. , Williams Marianne M. , Conaty Kathleen
Published: June 2014

Background

Generic upper extremity disability questionnaires utilize standardized items. The Patient-Specific Functional Scale (PSFS) allows the patient to identify specific self-reported items. This study evaluated the validity of the PSFS to assess outcome in patients with hand fractures or dislocations.

Methods

Adults with hand fractures or dislocations, who completed hand therapy between January 2012 and January 2013, were eligible for inclusion. At the initial and final assessment, each patient was asked to complete the PSFS. Each patient identified three items that were difficult or they were unable to perform, and the degree of difficulty was ranked from 0 to 10 (able to perform at pre-injury level). We excluded patients with an incomplete PSFS. Statistical analyses evaluated the relationships between the PSFS and the independent variables.

Results

There were 63 patients (37 men, 26 women); 21 of the 63 patients underwent surgery for fracture fixation. The mean duration of hand therapy treatment was 2.2±1.4 months. The mean PSFS scores were as follows: initial 3.2±2.2; final 8.1± 2.2. There was a significant improvement in PSFS scores from initial to final assessment ( p<0.001) and a moderate correlation ( r=0.3, p=0.02). There was no statistical difference in PSFS scores between men and women or surgery and no surgery.

Conclusions

In these patients with hand fractures or dislocations, the PSFS indicated significant improvement in function. Using items identified by the patient, the PSFS provides a valuable perspective of outcome and may be used in conjunction with generic disease-specific questionnaire for assessment of the upper extremity.
What do Belarusians think about the EU and what can the EU do for Belarus?
Authors: Melyantsou Dzianis
Published: June 2014

This article focuses on Belarusians’ attitudes towards integration, the EU and Russia, as well as on their motives for choosing foreign allies. To judge by its values, Belarusian society is closer to the Customs Union of Russia, Belarus and Kazakhstan than to the EU. Nevertheless, Belarusians’ geopolitical preference is not the result of political or social values but is based on pragmatic calculations, according to which Europe successfully competes with Russia. Further growth of pro-European attitudes is limited by the frosty relations between Minsk and Brussels, difficulties with Schengen visas, and a general lack of knowledge about the EU.
Responding to the Russian Invasion of Crimea: Policy Recommendations for US and European Leaders
Authors: Nix Stephen B.
Published: June 2014

In February 2014, Russia invaded Crimea, Ukraine. Two weeks later it annexed the region. This gross violation of international laws and agreements cannot be tolerated–-and it is up to the international community to deliver a decisive, punitive response that seeks to limit Russian influence in Europe and the rest of the world over time. In order to counter Russian expansionism, US and European leaders must work to bolster the democracies of the Eastern Partnership states, develop a safe and secure energy supply for European countries, strengthen the defences of the front-line NATO states of Central and Eastern Europe, and re-evaluate the exchange of goods between Europe and Russia. In addition, international support for the new Ukrainian government will be essential in the coming years. Failure to deliver an appropriate response will have grave consequences for the future world order.
Dual role of cerebral blood flow in regional brain temperature control in the healthy newborn infant
Authors: Iwata Sachiko , Tachtsidis Ilias , Takashima Sachio , Matsuishi Toyojiro , Robertson Nicola J. , Iwata Osuke
Published: June 2014

Small shifts in brain temperature after hypoxia–ischaemia affect cell viability. The main determinants of brain temperature are cerebral metabolism, which contributes to local heat production, and brain perfusion, which removes heat. However, few studies have addressed the effect of cerebral metabolism and perfusion on regional brain temperature in human neonates because of the lack of non‐invasive cot‐side monitors. This study aimed (i) to determine non‐invasive monitoring tools of cerebral metabolism and perfusion by combining near‐infrared spectroscopy and echocardiography, and (ii) to investigate the dependence of brain temperature on cerebral metabolism and perfusion in unsedated newborn infants.

Thirty‐two healthy newborn infants were recruited. They were studied with cerebral near‐infrared spectroscopy, echocardiography, and a zero‐heat flux tissue thermometer. A surrogate of cerebral blood flow (CBF) was measured using superior vena cava flow adjusted for cerebral volume (rSVC flow). The tissue oxygenation index, fractional oxygen extraction (FOE), and the cerebral metabolic rate of oxygen relative to rSVC flow (CMRO2 index) were also estimated.

A greater rSVC flow was positively associated with higher brain temperatures, particularly for superficial structures. The CMRO2 index and rSVC flow were positively coupled. However, brain temperature was independent of FOE and the CMRO2 index. A cooler ambient temperature was associated with a greater temperature gradient between the scalp surface and the body core.

Cerebral oxygen metabolism and perfusion were monitored in newborn infants without using tracers. In these healthy newborn infants, cerebral perfusion and ambient temperature were significant independent variables of brain temperature. CBF has primarily been associated with heat removal from the brain. However, our results suggest that CBF is likely to deliver heat specifically to the superficial brain. Further studies are required to assess the effect of cerebral metabolism and perfusion on regional brain temperature in low‐cardiac output conditions, fever, and with therapeutic hypothermia.
Changing the role of the traditional birth attendant in Somaliland
Authors: Pyone Thidar , Adaji Sunday , Madaj Barbara , Woldetsadik Tadesse , van den Broek Nynke
Published: June 2014

Objective

To explore the feasibility of changing the role of the traditional birth attendant (TBA) to act as birth companion and promoter of skilled birth attendance.

Methods

Between 2008 and 2012, 75 TBAs received 3 days of training and were paid US $5 for each patient brought to any of five healthcare facilities in Maroodi Jeex, Somaliland. Health facilities were upgraded (infrastructure, drugs and equipment, staff training, and incentivization). Eight key informant interviews (KIIs) and 10 focus group discussions (FGDs) involving 32 TBAs and 32 mothers were conducted. A framework approach was used for analysis.

Results

TBAs adopted their new role easily; instead of conducting home births and referring women to a facility only at onset of complications, they accompanied or referred mothers to a nearby facility for delivery, prenatal care, or postnatal care. Both TBAs and mothers accepted this new role, resulting in increased deliveries at health facilities. Facilitating factors included the creation of an enabling environment at the health facility, acceptance of the TBA by health facility staff, and monetary incentivization.

Conclusion

Changing the role of the TBA to support facility‐based delivery is feasible and acceptable. Further research is needed to see whether this is replicable and can be scaled‐up.
ARISTOPHANES VS TYPHON: CO(S)MIC RIVALRY, VOICE AND TEMPORALITY INKNIGHTS
Authors: Telò Mario
Published: June 2014

Recent studies have analysed the essential role of interpoetic rivalry in Aristophanes' comic imagination. Zachary Biles has shown that ‘festival agonistics provide an underlying logic for the overall thematic design of individual plays’ and that ‘the plays can be treated as creative responses to the competitions.’ Aristophanes' dramatisation of comic competition has been viewed as a reflection of the struggles of political factions in late-fifth-century Athens or as an expression of a ‘rhetoric of self-promotion’ that builds the comic plot through the mutual borrowing of comic material (jokes, running gags). This paper suggests thatKnightspresents interpoetic rivalry as a conflict of embodied aesthetic modes. In this play, Aristophanes' tendentious definition of his comic self against his predecessor Cratinus results in opposed ways of conceptualising the sonic quality of dramatic performance and its material effects on the audience. The nexus of voice and temporality, which, as I argue, shapes the play's agonistic plot, equates the intergenerational duelling of Aristophanes' and Cratinus' political counterparts (the Sausage Seller and the older Paphlagon, respectively) to a contrast of somatic experiences grounded in sound.