bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of relationship between the synthesis/process parameters and properties of a sol–gel‐derived polymer nanocomposite system
Authors: Çopuroğlu Mehmet , Şen Murat
Published: March 2013

A Ti‐containing silicate‐based epoxy‐functional polymer nanocomposite system was synthesized by a sol–gel route with or without the introduction of a reflux process, which was followed by UV‐induced epoxy polymerization. Influences of synthesis and process parameters, including Ti content, sol ageing, reflux process, and UV‐irradiation on various properties of the system were detailed. It was demonstrated that the introduction of a reflux process during the sol–gel synthesis could significantly modify the chemical and physical properties of the resultant material system along with other parameters such as Ti content. Overall results showed that the synthesis and process parameters examined could be employed to modify the microstructure, and to tune the final properties of this polymer nanocomposite system. The technique described herein, therefore, could be used to develop a new process regime to obtain materials of this type with desired properties, which might potentially be employed in certain applications such as dental restoration. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Clinical Response, Drug Survival, and Predictors Thereof Among 548 Patients With Psoriatic Arthritis Who Switched Tumor Necrosis Factor α Inhibitor Therapy: Results from the Danish Nationwide DANBIO Registry
Authors: Glintborg Bente , Østergaard Mikkel , Krogh Niels Steen , Andersen Martin Dehn , Tarp Ulrik , Loft Anne Gitte , Lindegaard Hanne M. , Holland‐Fischer Mette , Nordin Henrik , Jensen Dorte Vendelbo , Olsen Christian Holkmann , Hetland Merete Lund
Published: March 2013

Objective

To describe the frequency of treatment switching and outcomes among patients with psoriatic arthritis (PsA) who switched tumor necrosis factor α inhibitor (TNFi) agents in routine care.

Methods

We conducted an observational cohort study based on the Danish nationwide DANBIO registry. Treatment outcomes were evaluated using the American College of Rheumatology criteria for 20% improvement (ACR20)/ACR50/ACR70, European League Against Rheumatism (EULAR) response criteria for good response, and the 28‐joint count Disease Activity Score (DAS28) (remission). Kaplan‐Meier and regression analyses were used for drug survival analyses and to identify predictors of outcome after treatment switching.

Results

Of 1,422 patients starting TNFi agents, 548 patients (39%) switched to a second biologic drug during up to 10 years of followup. Median followup was 2.3 years (interquartile range [IQR] 1.0–4.3 years). Switchers were more frequently women (56% versus 45%), had a shorter disease duration (3 versus 4 years), a higher median Health Assessment Questionnaire (HAQ) score (1.1 [IQR 0.6–1.6] versus 0.9 [IQR 0.5–1.4]), DAS28 (4.8 [4.0–5.7] versus 4.4 [3.6–5.2]), pain score on a visual analog scale (VAS) (65 mm [46–77] versus 62 mm [40–75]), and fatigue score on a VAS (69 mm [50–83] versus 64 mm [42–80] mm) (all P < 0.05 at start of first TNFi). During the first and second treatment, HAQ, DAS28, and VAS scores and C‐reactive protein levels had decreased after 6 months (all P < 0.05), and median drug survival was 2.2 versus 1.3 years (P < 0.001). Lower fatigue score increased survival of the second TNFi. After switching, the proportions of patients achieving a sustained ACR20, ACR50, ACR70, EULAR good response, and DAS28 remission after 3–6 months were 22% (number needed to treat [NNT] 4.5), 13% (NNT 7.9), 5% (NNT 20), 19% (NNT 5.3), and 34% (NNT 2.9), respectively. Response rates were lower during the second treatment (all P < 0.01 versus first TNFi). At the 2‐year visit, 47% of switchers had achieved an ACR20 response. No differences between drug–drug combinations were found.

Conclusion

Thirty‐nine percent of the patients with PsA switched TNFi agents. Response rates and drug survival were lower after switching; however, half of the switchers had an ACR20 response 2 years after starting the first TNFi.
Rheumatoid Arthritis in Latin Americans Enriched for Amerindian Ancestry Is Associated With Loci in Chromosomes 1, 12, and 13, and the HLA Class II Region
Authors: Herráez David López , Martínez‐Bueno Manuel , Riba Laura , de la Torre Ignacio García , Sacnún Mónica , Goñi Mario , Berbotto Guillermo A. , Paira Sergio , Musuruana Jorge Luis , Graf César E. , Alvarellos Alejandro J. , Messina Osvaldo D. , Babini Alejandra M. , Strusberg Ingrid , Marcos Juan Carlos , Scherbarth Hugo , Spindler Alberto J. , Quinteros Ana , Toloza Sergio M. A. , Moreno José Luis C. , Catoggio Luis J. , Tate Guillermo , Eimon Alicia , Citera Gustavo , Catalán Pellet Antonio , Nasswetter Gustavo G. , Cardiel Mario H. , Miranda Pedro , Ballesteros Francisco , Esquivel‐Valerio Jorge A. , Maradiaga‐Ceceña Marco A. , Acevedo‐Vásquez Eduardo M. , García García Conrado , Tusié‐Luna Teresa , Pons‐Estel Bernardo A. , Alarcón‐Riquelme Marta E.
Published: March 2013

Objective

To identify susceptibility loci for rheumatoid arthritis (RA) in Latin American individuals with admixed European and Amerindian genetic ancestry.

Methods

Genotyping was performed in 1,475 patients with RA and 1,213 control subjects, using a customized BeadArray containing 196,524 markers covering loci previously associated with various autoimmune diseases. Principal components analysis (EigenSoft package) and Structure software were used to identify outliers and define the population substructure. REAP software was used to define cryptic relatedness and duplicates, and genetic association analyses were conducted using Plink statistical software.

Results

A strong genetic association between RA and the major histocompatibility complex region was observed, localized within BTNL2/DRA–DQB1– DQA2 (P = 7.6 × 10−10), with 3 independent effects. We identified an association in the PLCH2‐HES5‐TNFRSF14‐MMEL1 region of chromosome 1 (P = 9.77 × 10−6), which was previously reported in Europeans, Asians, and Native Canadians. We identified one novel putative association in ENOX1 on chromosome 13 (P = 3.24 × 10−7). Previously reported associations were observed in the current study, including PTPN22, SPRED2, STAT4, IRF5, CCL21, and IL2RA, although the significance was relatively moderate. Adjustment for Amerindian ancestry improved the association of a novel locus in chromosome 12 at C12orf30 (NAA25) (P = 3.9 × 10−6). Associations with the HLA region, SPRED2, and PTPN22 improved in individuals positive for anti–cyclic citrullinated peptide antibodies.

Conclusion

Our data define, for the first time, the contribution of Amerindian ancestry to the genetic architecture of RA in an admixed Latin American population by confirming the role of the HLA region and supporting the association with a locus in chromosome 1. In addition, we provide data for novel putative loci in chromosomes 12 and 13.
Neointimal tissue component assessed by tissue characterization with 40 MHz intravascular ultrasound imaging: Comparison of drug‐eluting stents and bare‐metal stents
Authors: Tsujita Kenichi , Takaoka Naoko , Kaikita Koichi , Hokimoto Seiji , Horio Eiji , Sato Koji , Mizobe Michio , Nakayama Naoki , Kojima Sunao , Tayama Shinji , Sugiyama Seigo , Nakamura Sunao , Ogawa Hisao
Published: March 2013

Objectives

The present study used iMap IVUS system to compare neointimal tissue components between DES and bare‐metal stents (BMSs).

Background

Drug‐eluting stents (DESs) can cause impaired arterial healing, which constitutes the most important pathological substrate underlying late DES thrombosis. Intravascular ultrasound (IVUS)‐based tissue characterization allows for the in vivo identification of neointimal tissue components.

Methods and Results

Follow‐up IVUS data after coronary stenting (9.8 ± 9.4 months from index procedures) was obtained from consecutive 61 lesions (34 in DES, 27 in BMS). The iMap tissue components (fibrotic, lipidic, necrotic, and calcified) were measured in every recorded frame and expressed as percentages of mean neointimal cross‐sectional area for the stented segment. Patients' characteristics were comparable between DES and BMS. When compared with BMSs, smaller (2.9 ± 0.4 mm vs. 3.2 ± 0.4 mm, P = 0.004) and longer (34 ± 18 mm vs. 26 ± 14 mm, P = 0.03) DESs were implanted. When compared with BMS group, minimum lumen area at follow‐up was significantly greater in DES group (3.9 ± 1.8 mm2 vs. 3.1 ± 1.5 mm2, P < 0.04), mainly attributable to suppression of neointimal hyperplasia (1.7 ± 0.8 mm2 vs. 3.1 ± 1.5 mm2, P < 0.0001). The iMap analyses showed that neointima after DES placement was composed of smaller fibrotic component (67 ± 8% vs. 78 ± 7%, P < 0.0001), larger necrotic (14 ± 4% vs. 9 ± 3%, P < 0.0001) and calcified (15 ± 6% vs. 7 ± 4%, P < 0.0001) components compared with BMS. Logistic regression analysis showed that only intra‐DES neointima was a significant predictor of necrotic neointima at follow‐up.

Conclusions

DES implantation would be associated with iMap‐derived necrotic and less‐fibrotic neointimal formation. In vivo iMap evaluation of neointimal tissue may provide useful information in detecting impaired healing after stenting. © 2013 Wiley Periodicals, Inc.
Tuning the Photoisomerization of a N^C‐Chelate Organoboron Compound with a MetalAcetylide Unit
Authors: Wang Nan , Ko Soo‐Byung , Lu Jia‐Sheng , Chen Leanne D. , Wang Suning
Published: March 2013

To examine the impact of metal moieties that have different triplet energies on the photoisomerization of B(ppy)Mes2 compounds (ppy=2‐phenyl pyridine, Mes=mesityl), three metal‐functionalized B(ppy)Mes2 compounds, Re‐B, Au‐B, and Pt‐B, have been synthesized and fully characterized. The metal moieties in these three compounds are Re(CO)3(tert‐Bu2bpy)(CC), Au(PPh3)(CC), and trans‐Pt(PPh3)2(CC)2, respectively, which are connected to the ppy chelate through the alkyne linker. Our investigation has established that the ReI unit completely quenches the photoisomerization of the boron unit because of a low‐lying intraligand charge transfer/MLCT triplet state. The AuI unit, albeit with a triplet energy that is much higher than that of B(ppy)Mes2, upon conjugation with the ppy chelate unit, substantially increases the contribution of the π→π* transition, localized on the conjugated chelate backbone in the lowest triplet state, thereby leading to a decrease in the photoisomerization quantum efficiency (QE) of the boron chromophore when excited at 365 nm. At higher excitation energies, the photoisomerization QE of Au‐B is comparable to that of the silyl–alkyne‐functionalized B(ppy)Mes2 (TIPS‐B), which was attributable to a triplet‐state‐sensitization effect by the AuI unit. The PtII unit links two B(ppy)Mes2 together in Pt‐B, thereby extending the π‐conjugation through both chelate backbones and leading to a very low QE of the photoisomerization. In addition, only one boron unit in Pt‐B undergoes photoisomerization. The isomerization of the second boron unit is quenched by an intramolecular energy transfer of the excitation energy to the low‐energy absorption band of the isomerized boron unit. TD‐DFT computations and spectroscopic studies of the three metal‐containing boron compounds confirm that the photoisomerization of the B(ppy)Mes2 chromophore proceeds through a triplet photoactive state and that metal units with suitable triplet energies can be used to tune this system.
Biofuel Cells for Biomedical Applications: Colonizing the Animal Kingdom
Authors: Falk Magnus , Narváez Villarrubia Claudia W. , Babanova Sofia , Atanassov Plamen , Shleev Sergey
Published: March 2013

Interdisciplinary research has combined the efforts of many scientists and engineers to gain an understanding of biotic and abiotic electrochemical processes, materials properties, biomedical, and engineering approaches for the development of alternative power‐generating and/or energy‐harvesting devices, aiming to solve health‐related issues and to improve the quality of human life. This review intends to recapitulate the principles of biofuel cell development and the progress over the years, thanks to the contribution of cross‐disciplinary researchers that have combined knowledge and innovative ideas to the field. The emergence of biofuel cells, as a response to the demand of electrical power devices that can operate under physiological conditions, are reviewed. Implantable biofuel cells operating inside living organisms have been envisioned for over fifty years, but few reports of implanted devices have existed up until very recently. The very first report of an implanted biofuel cell (implanted in a grape) was published only in 2003 by Adam Heller and his coworkers. This work was a result of earlier scientific efforts of this group to “wire” enzymes to the electrode surface. The last couple of years have, however, seen a multitude of biofuel cells being implanted and operating in different living organisms, including mammals. Herein, the evolution of the biofuel concept, the understanding and employment of catalyst and biocatalyst processes to mimic biological processes, are explored. These potentially green technology biodevices are designed to be applied for biomedical applications to power nano‐ and microelectronic devices, drug delivery systems, biosensors, and many more.
Asymmetric Synthesis of Structurally Diverse Aminophosphonic Acids by Using Enantiopure N‐(p‐Tolylsulfinyl)cinnamaldimines as Reagents
Authors: Łyżwa Piotr , Błaszczyk Jarosław , Sieroń Lesław , Mikołajczyk Marian
Published: March 2013

We have developed new approaches to diverse enantiopure aminophosphonic acids by using enantiomeric (S)‐N‐(p‐tolylsulfinyl)cinnamaldimine (1) as a single starting material. The synthetic strategy is based on a highly diastereoselective addition reaction of phosphite anion or α‐phosphonate carbanion to a sulfinimine followed by isolation of the major diastereoisomeric α‐amino‐ or β‐amino adducts and their further conversion to the desired targets through proper transformation of the cinnamylidene moiety. Both diastereoisomerically pure (SS,RC)‐ and (SS,SC)‐α‐amino adducts 2 and 4 obtained were converted under acidic conditions into the unknown enantiomerically pure (R)‐ and (S)‐α‐amino‐β,γ‐propenylphosphonic acids 3. In the same way, the enantiopure (R)‐ and (S)‐β‐amino‐γ,δ‐butenylphosphonic acids were synthesized from the corresponding (SS,RC)‐ and (SS,SC)‐β‐amino adducts. Starting from the (SS,RC)‐β‐amino adduct a new stereoselective synthesis of (R)‐2‐amino‐3‐phosphonopropanoic acid (9) has been accomplished in three simple steps (tandem ozonolysis/reduction reaction, oxidation reaction and acidic hydrolysis) in an overall 40 % yield. The 3‐amino regioisomer of 9 has been prepared from the (SS,RC)‐α‐amino adduct 2 through a two‐reaction sequence involving a tandem ozonolysis/reduction reaction and a Mitsunobu cyanation/acidic hydrolysis. The overall yield of this conversion to 11 was 52.5 %. According to our strategy, we have been able to complete the first synthesis of the enantiopure (R)‐phosphoemeriamine 15, which is an unknown phosphonic analogue of emeriamine (aminocarnitine). The conversion of the (SS,RC)‐β‐amino adduct 5 into (R)‐phosphoemeriamine has been accomplished in five simple synthetic steps (ozonolysis/reduction reaction, mesylation reaction, amination reaction, methylation reaction and acidic hydrolysis) in 24 % overall yield. The stereochemistry of the addition of PIII‐nucleophiles and α‐phosphonate carbanion to a chiral sulfinimine is also discussed.
A Selective Catalytic Oxidation of Ascorbic Acid at the Aminopyrimidyl Functionalized‐Conductive Polymer Electrode
Authors: Abdelwahab Adel A. , Kim Dong‐Min , Halappa Naveen M. , Shim Yoon‐Bo
Published: March 2013

A simple detection method of ascorbic acid (AA) through selective catalytic oxidation has been developed using a novel conducting polymer poly‐3′‐(2‐aminopyrimidyl)‐2,2′:5′,2“‐terthiophene (pAPTT). The pAPTT electrode showed an excellent selectivity in facilitating the electron transfer of AA and blocked the interferences of cationic species due to the positively charged pAPTT film. This method proved to be effective in the determination of AA in the presence of various biological interfering species. The dynamic range of AA detection was from 10 to 200 µM and the detection limit was 1.4±0.06 µM.
The formation of supraglacial debris covers by primary dispersal from transverse englacial debris bands
Authors: Kirkbride Martin P. , Deline Philip
Published: March 2013

Glaciological controls on debris cover formation are investigated from the perspective of primary dispersal of supraglacial debris across a melting ice surface. This involves the migration of angled debris septa outcrops across a melting, thinning glacier ablation zone. Three measures of a glacier's ability to evacuate supraglacial debris are outlined: (1) a concentration factor describing the focusing of englacial debris into specific supraglacial mass loads; (2) the rate of migration of a septum outcrop relative to the local ice surface; and (3) a downstream velocity differential between a slower septum outcrop and the faster ice surface velocity. Measures (1) and (2) are inversely related, while measure (3) increases down‐glacier to explain why slow‐moving, thinning ice rapidly becomes debris covered. Data from Glacier d'Estelette (Italian Alps) are used to illustrate these processes, and to explore the potential for debris cover formation and growth in different glaciological environments. The transition from a ‘clean’, transport‐dominated to a debris‐covered ablation‐dominated glacier is explained by the melting out of more closely‐spaced debris septa, in combination with the geometric interactions of angled septa and ice surface in a field of reducing flow and increasing ablation. The growth and shrinkage of debris covers are most sensitive to glaciological changes at glaciers with gently‐dipping debris‐bearing foliation, but less sensitive at high‐compression glaciers whose termini are constrained by moraine dams and other forms of obstruction. These findings show that a variety of debris‐covered glacier types will show a spectrum of response characteristics to negative mass balance. Copyright © 2013 John Wiley & Sons, Ltd.
Amounts, isotopic character, and ages of organic and inorganic carbon exported from rivers to ocean margins: 2. Assessment of natural and anthropogenic controls
Authors: Hossler Katie , Bauer James E.
Published: March 2013

Riverine exports of carbon (C) and organic matter (OM) are regulated by a variety of natural and anthropogenic factors. Understanding the relationships between these various factors and C and OM exports can help to constrain global C budgets and allow assessment of current and future anthropogenic impacts on both riverine and global C cycles. We quantified the effects of multiple natural and anthropogenic controls on riverine export fluxes and compositions of particulate organic C, dissolved organic C, and dissolved inorganic C for a regional group of eight rivers in the northeastern U.S. Potential controls related to hydrogeomorphology and regional climate, soil order, soil texture, bedrock lithology, land use, and anthropogenic factors were analyzed individually, collectively, and at scales of both local and regional influence. Factors related to hydrogeomorphology and climate, followed in importance by land use and anthropogenic factors, exhibited the strongest impacts on riverine C exports and compositions, particularly at smaller localized scales. The effects of hydrogeomorphology and climate were primarily related to volumetric flow, which resulted in greater exports of terrestrial and total C. Principal anthropogenic factors included impacts of wastewater treatment plants (WWTPs) and river impoundments. The presence of WWTPs as well as anthropogenic use of carbonate‐based materials (e.g., limestone) may have substantially increased riverine C exports, particularly fossil C exports, in the study region. The presence of nuclear power plants in the associated watersheds is also discussed because of the potential for anthropogenic 14C inputs and subsequent biasing of aquatic C studies utilizing natural abundance 14C.
Eroding dynamic topography
Authors: Braun J. , Robert X. , Simon‐Labric T.
Published: March 2013

Geological observations of mantle flow‐driven dynamic topography are numerous, especially in the stratigraphy of sedimentary basins; on the contrary, when it leads to subaerial exposure of rocks, dynamic topography must be substantially eroded to leave a noticeable trace in the geological record. Here, we demonstrate that despite its low amplitude and long wavelength and thus very low slopes, dynamic topography is efficiently eroded by fluvial erosion, providing that drainage is strongly perturbed by the mantle flow driven surface uplift. Using simple scaling arguments, as well as a very efficient surface processes model, we show that dynamic topography erodes in direct proportion to its wavelength. We demonstrate that the recent deep erosion experienced in the Colorado Plateau and in central Patagonia is likely to be related to the passage of a wave of dynamic topography generated by mantle upwelling.
Inter‐annual changes of alpine inland lake water storage on the Tibetan Plateau: Detection and analysis by integrating satellite altimetry and optical imagery
Authors: Song Chunqiao , Huang Bo , Ke Linghong
Published: March 2013

The effects of climate change have a substantial influence on the extremely vulnerable hydrologic environment of the Tibetan Plateau. The estimation of alpine inland lake water storage variations is essential to modeling the alpine hydrologic process and evaluating water resources. Due to a lack of historical hydrologic observations in this remote and inaccessible region, such estimations also fill a gap in studies on the continuous inter‐annual and seasonal changes in the inland lake water budget. Using Lake Siling Co as a case study, we derived a time‐series of lake surface extents from MODIS imagery, and scarce lake water level data from the satellite altimetry of two sensors (ICESat/GLAS and ENVISAT RA‐2) between 2001 and 2011. Then, based on the fact that the rise in lake water levels is tightly dependent on the expansion of the lake extent, we established an empirical model to simulate a continuous lake water level dataset corresponding to the lake area data during the lake's unfreezing period. Consequently, from three dimensions, the lake surface area, water level and water storage variations consistently revealed that Lake Siling Co exhibited a dramatic trend to expand, particularly from 2001 to 2006. Based on the statistical model and lake area measurements from Landsat images since 1972, the extrapolated lake water level and water storage indicate that the lake has maintained a continual expansion process and that the cumulative water storage variations during 1999–2011 account for 66.84% of the total lake water budget (26.87 km3) from 1972 to 2011. Copyright © 2013 John Wiley & Sons, Ltd.
Nonlinear dynamics and recurrence analysis of extreme precipitation for observed and general circulation model generated climates
Authors: Panagoulia Dionysia , Vlahogianni Eleni I.
Published: March 2013

A statistical framework based on nonlinear dynamics theory and recurrence quantification analysis of dynamical systems is proposed to quantitatively identify the temporal characteristics of extreme (maximum) daily precipitation series. The methodology focuses on both observed and general circulation model (GCM) generated climates for present (1961–2000) and future (2061–2100) periods which correspond to 1xCO2 and 2xCO2 simulations. The daily precipitation has been modelled as a stochastic process coupled with atmospheric circulation. An automated and objective classification of daily circulation patterns (CPs) based on optimized fuzzy rules was used to classify both observed CPs and ECHAM4 GCM‐generated CPs for 1xCO2 and 2xCO2 climate simulations (scenarios). The coupled model ‘CP‐precipitation’ was suitable for precipitation downscaling. The overall methodology was applied to the medium‐sized mountainous Mesochora catchment in Central‐Western Greece. Results reveal substantial differences between the observed maximum daily precipitation statistical patterns and those produced by the two climate scenarios. A variable nonlinear deterministic behaviour characterizes all climate scenarios examined. Transitions’ patterns differ in terms of duration and intensity. The 2xCO2 scenario contains the strongest transitions highlighting an unusual shift between floods and droughts. The implications of the results to the predictability of the phenomenon are also discussed. Copyright © 2013 John Wiley & Sons, Ltd.
Comparison of three methods of hydrogeological parameter estimation in leaky aquifers using transient flow pumping tests
Authors: Li Peiyue , Qian Hui , Wu Jianhua
Published: March 2013

Accurate knowledge of hydrogeological parameters is essential for groundwater modeling, protection and remediation. Three methods (type curve fitting method, inflection point method and global curve‐fitting method (GCFM)) which are frequently applied in the estimation of leaky aquifer parameters were compared using synthetic pumping tests. The results revealed GCFM could provide best parameter estimation among the three methods with fewer uncertainties associated with the processes of parameter estimation. GCFM was also found to be both time saving and of low cost and is thus more preferable for hydrogeological parameter estimation than the other two methods. Copyright © 2013 John Wiley & Sons, Ltd.
DRAINAGE PERFORMANCE ASSESSMENT IN A MODERNIZED OASIS SYSTEM
Authors: Ben Aissa I. , Bouarfa S. , Vincent B. , Chaumont C. , Perrier A.
Published: March 2013

Saharan oases are frequently subjected to waterlogging due to the presence of shallow and salty groundwater and poor irrigation and drainage conditions. To overcome this problem in Tunisia, in 2002 an official modernization programme was implemented based on two operations: (i) increasing irrigation efficiency by building concrete irrigation canals to limit losses due to water percolation and (ii) controlling waterlogging and salinity by installing a subsurface drainage system in place of the traditional open‐ditch system. In this study, a salinity balance was performed in Fatnassa, a representative Saharan oasis in Tunisia. Two spatial levels were monitored over a period of two years: an irrigated and drained field (0.8 ha) and the northern part of the oasis covering 114 ha. Results showed an equilibrated salinity balance at the field level, whereas, at the oasis level, the drainage system was unable to evacuate more than 30% of the salts in the first year and 15% in the second. We consider the clogging effect detected in several locations in the oasis as the main cause of this dysfunction. For the future, we recommend a more participatory approach to designing drainage systems, probably moving toward mixed systems with traditional open ditches and modern subsurface pipes, both easy to maintain by the farmers themselves. Adequate envelopes to prevent clogging in mineral soils have to be tested in situ before extension of subsurface drainage. Copyright © 2013 John Wiley & Sons, Ltd.
The neurobiology of tetrahydrobiopterin biosynthesis: A model for regulation of GTP cyclohydrolase I gene transcription within nigrostriatal dopamine neurons
Authors: Kapatos Gregory
Published: March 2013

Within the brain, the reduced pteridine cofactor 6R‐L‐erythro‐5,6,7,8‐tetrahydrobiopterin (BH4) is absolutely required for the synthesis of the monoamine (MA) neurotransmitters dopamine (DA), norepinephrine, epinephrine (E), and serotonin (5‐HT), the novel gaseous neurotransmitter nitric oxide and the production of yet to be identified 1‐O‐alkylglycerol‐derived lipids. GTP cyclohydrolase I (GTPCH) catalyzes the first and limiting step in the BH4 biosynthetic pathway, which is now thought to involve up to eight different proteins supporting six alternate de novo and two alternate salvage pathways. Gene expression analysis across different regions of the human brain shows the abundance of transcripts coding for all eight of these proteins to be highly correlated with each other and to be enriched within human MA neurons. The potential for multiple routes for BH4 synthesis therefore exists within the human brain. GTPCH expression is particularly heterogeneous across different populations of human and rodent MA‐containing neurons, with low expression levels and therefore BH4 being a characteristic of nigrostriatal DA (NSDA) neurons. Basic knowledge of how GCH1 gene transcription is controlled within NSDA neurons may explain the distinctive susceptibility of these neurons to human genetic mutations that result in BH4 deficiency. A model for cyclic adenosine monophosphate‐dependent GCH1 transcription is described that involves a unique combination of DNA regulatory sequences and transcription factors. This model proposes that low levels of GCH1 transcription within NSDA neurons are driven by their distinctive physiology, suggesting that pharmacological manipulation of GCH1 gene transcription can be used to modify BH4 levels and therefore DA synthesis in the basal ganglia. © 2013 IUBMB Life 65(4):323–333, 2013.
Phenylalanine hydroxylase: Function, structure, and regulation
Authors: Flydal Marte I. , Martinez Aurora
Published: March 2013

Mammalian phenylalanine hydroxylase (PAH) catalyzes the rate‐limiting step in the phenylalanine catabolism, consuming about 75% of the phenylalanine input from the diet and protein catabolism under physiological conditions. In humans, mutations in the PAH gene lead to phenylketonuria (PKU), and most mutations are mainly associated with PAH misfolding and instability. The established treatment for PKU is a phenylalanine‐restricted diet and, recently, supplementation with preparations of the natural tetrahydrobiopterin cofactor also shows effectiveness for some patients. Since 1997 there has been a significant increase in the understanding of the structure, catalytic mechanism, and regulation of PAH by its substrate and cofactor, in addition to improved correlations between genotype and phenotype in PKU. Importantly, there has also been an increased number of studies on the structure and function of PAH from bacteria and lower eukaryote organisms, revealing an additional anabolic role of the enzyme in the synthesis of melanin‐like pigments. In this review, we discuss these recent studies, which contribute to define the evolutionary adaptation of the PAH structure and function leading to sophisticated regulation for effective catabolic processing of phenylalanine in mammalian organisms. © 2013 IUBMB Life 65(4):341–349, 2013.
A distal forearm fracture in childhood is associated with an increased risk for future fragility fractures in adult men, but not women
Authors: Amin Shreyasee , Melton L Joseph , Achenbach Sara J , Atkinson Elizabeth J , Dekutoski Mark B , Kirmani Salman , Fischer Philip R , Khosla Sundeep
Published: March 2013

Distal forearm fractures are among the most common fractures during childhood, but it remains unclear whether they predict an increased fracture risk later in life. We studied a population-based cohort of 1776 children ≤18 years of age, from Olmsted County, MN, USA, who had a distal forearm fracture in 1935–1992. Incident fractures occurring at age ≥35 years were identified through review of complete medical records using the linkage system of the Rochester Epidemiology Project. Observed nonpathologic fractures resulting from no more than moderate trauma (fragility fractures) were compared with expected numbers estimated from fracture site–specific incidence rates, based on age, sex, and calendar year, for Olmsted County (standardized incidence ratios [SIR]). In 1086 boys (mean ± SD age; 11 ± 4 years) and 690 girls (10 ± 4 years) followed for 27,292 person-years after the age of 35 years, subsequent fragility fractures were observed in 144 (13%) men and 74 (11%) women. There was an increased risk for future fragility fractures in boys who had a distal forearm fracture (SIR, 1.9; 95% CI, 1.6–2.3) but not girls (SIR, 1.0; 95% CI, 0.8–1.2). Fragility fractures at both major osteoporotic (hip, spine, wrist, and shoulder) sites (SIR, 2.6; 95% CI, 2.1–3.3) and remaining sites (SIR, 1.7; 95% CI, 1.3–2.0) were increased in men, irrespective of age at distal forearm fracture as boys. A distal forearm fracture in boys, but not girls, is associated with an increased risk for fragility fractures as older adults. It is necessary to determine whether the increased fractures observed in men is due to persistent deficits of bone strength, continued high fracture risk activity, or both. Until then, men should be asked about a childhood distal forearm fracture and, if so, warrant further screening and counseling on measures to optimize bone health and prevent fractures.
C-Reactive Protein, Bone Strength, and Nine-Year Fracture Risk: Data From the Study of Women's Health Across the Nation (SWAN)
Authors: Ishii Shinya , Cauley Jane A , Greendale Gail A , Crandall Carolyn J , Danielson Michelle E , Ouchi Yasuyoshi , Karlamangla Arun S
Published: March 2013

Higher levels of C-reactive protein (CRP), an inflammatory marker, are associated with increased fracture risk, although previous studies on CRP and bone mineral density (BMD) have yielded conflicting results. We aimed to test the hypotheses that composite indices of femoral neck strength relative to load, which are inversely associated with fracture risk, would also be inversely associated with CRP, and would explain part of the association between CRP and fracture risk. We analyzed data from a multisite, multiethnic prospective cohort of 1872 community-dwelling women, premenopausal or early perimenopausal at baseline. Femoral neck composite strength indices in three failure modes were calculated using dual-energy X-ray absorptiometry (DXA)-derived femoral neck width (FNW), femoral neck axis length (FNAL), femoral neck BMD and body size at baseline, as BMD*FNW/weight for compression strength, BMD*(FNW)2/(FNAL*weight) for bending strength, and BMD*FNW*FNAL/(height*weight) for impact strength. Incident nondigital, noncraniofacial fractures were ascertained annually over a median follow-up of 9 years. In analyses adjusted for age, race/ethnicity, diabetes, menopause transition stage, body mass index, smoking, alcohol use, physical activity, medications, prior fracture, and study site, CRP was associated inversely with each composite strength index (0.035–0.041 SD decrement per doubling of CRP, all p < 0.001), but not associated with femoral neck or lumbar spine BMD. During the follow-up, 194 women (10.4%) had fractures. In Cox proportional hazards analyses, fracture hazard increased linearly with loge(CRP), only for CRP levels ≥ 3 mg/L. Addition of femoral neck or lumbar spine BMD to the model did not attenuate the CRP-fracture association. However, addition of any of the composite strength indices attenuated the CRP-fracture association and made it statistically nonsignificant. We conclude that fracture risk increases with increasing CRP, only above the threshold of 3 mg/L. Unlike BMD, composite strength indices are inversely related to CRP levels, and partially explain the increased fracture risk associated with inflammation.
Serum IGF-1 Is Insufficient to Restore Skeletal Size in the Total Absence of the Growth Hormone Receptor
Authors: Wu Yingjie , Sun Hui , Basta-Pljakic Jelena , Cardoso Luis , Kennedy Oran D , Jasper Hector , Domené Horacio , Karabatas Liliana , Guida Clara , Schaffler Mitchell B , Rosen Clifford J , Yakar Shoshana
Published: March 2013

States of growth hormone (GH) resistance, such those observed in Laron dwarf patients, are characterized by mutations in the GH receptor (GHR), decreased serum and tissue IGF-1 levels, impaired glucose tolerance, and impaired skeletal acquisition. IGF-1 replacement therapy in such patients increases growth velocity but does not normalize growth. Herein we combined the GH-resistant (GHR knockout [GHRKO]) mouse model with mice expressing the hepatic Igf-1 transgene (HIT) to generate the GHRKO-HIT mouse model. In GHRKO-HIT mice, serum IGF-1 levels were restored via transgenic expression of Igf-1, allowing us to study how endocrine IGF-1 affects growth, metabolic homeostasis, and skeletal integrity. We show that in a GH-resistant state, normalization of serum IGF-1 improved body adiposity and restored glucose tolerance but was insufficient to support normal skeletal growth, resulting in an osteopenic skeletal phenotype. The inability of serum IGF-1 to restore skeletal integrity in the total absence of GHR likely resulted from reduced skeletal Igf-1 gene expression, blunted GH-mediated effects on the skeleton that are independent of serum or tissue IGF-1, and poor delivery of IGF-1 to the tissues. These findings are consistent with clinical data showing that IGF-I replacement therapy in patients with Laron syndrome does not achieve full skeletal growth.
Novel role of VMP1 as modifier of the pancreatic tumor cell response to chemotherapeutic drugs
Authors: Gilabert Marine , Vaccaro Maria Inés , Fernandez‐Zapico Martin E. , Calvo Ezequiel L. , Turrini Olivier , Secq Véronique , Garcia Stéphane , Moutardier Vincent , Lomberk Gwen , Dusetti Nelson , Urrutia Raul , Iovanna Juan L.
Published: March 2013

We hypothesized that inhibiting molecules that mediate the adaptation response to cellular stress can antagonize the resistance of pancreatic cancer cells to chemotherapeutic drugs. Toward this end, here, we investigated how VMP1, a stress‐induced autophagy‐associated protein, modulate stress responses triggered by chemotherapeutic agents in PDAC. We find that VMP1 is particularly over‐expressed in poorly differentiated human pancreatic cancer. Pharmacological studies show that drugs that work, in part, via the endoplasmic reticulum stress response, induce VMP1 expression. Similarly, VMP1 is induced by known endoplasmic reticulum stress activators. Genetic inactivation of VMP1 using RNAi‐based antagonize the pancreatic cancer stress response to antitumoral agents. Functionally, we find that VMP1 regulates both autophagy and chemotherapeutic resistance even in the presence of chloroquin, ATG5 or Beclin 1 siRNAs, or a Beclin 1‐binding VMP1 mutant. In addition, VMP1 modulates endoplasmic reticulum stress independently of its coupling to the molecular and cellular autophagy machinery. Preclinical studies demonstrate that xenografts expressing an inducible and tractable form of VMP1 show increased resistance to the gemcitabine treatment. These results underscore a novel role for VMP1 as a potential therapeutic target for combinatorial therapies aimed at sensitizing pancreatic cancer cells to chemotherapeutic agents as well as provide novel molecular mechanisms to better understand this phenomenon. J. Cell. Physiol. 228: 1834–1843, 2013. © 2013 Wiley Periodicals, Inc.
GRK2 negatively regulates IGF‐1R signaling pathway and cyclins' expression in HepG2 cells
Authors: Wei Zhengyu , Hurtt Reginald , Gu Tina , Bodzin Adam S. , Koch Walter J. , Doria Cataldo
Published: March 2013

G protein coupled receptor kinase 2 (GRK2) plays a central role in the regulation of a variety of important signaling pathways. Alternation of GRK2 protein level and activity casts profound effects on cell physiological functions and causes diseases such as heart failure, rheumatoid arthritis, and obesity. We have previously reported that overexpression of GRK2 has an inhibitory role in cancer cell growth. To further examine the role of GRK2 in cancer, in this study, we investigated the effects of reduced protein level of GRK2 on insulin‐like growth factor 1 receptor (IGF‐1R) signaling pathway in human hepatocellular carcinoma (HCC) HepG2 cells. We created a GRK2 knockdown cell line using a lentiviral vector mediated expression of GRK2 specific short hairpin RNA (shRNA). Under IGF‐1 stimulation, HepG2 cells with reduced level of GRK2 showed elevated total IGF‐1R protein expression as well as tyrosine phosphorylation of receptor. In addition, HepG2 cells with reduced level of GRK2 also demonstrated increased tyrosine phosphorylation of IRS1 at the residue 612 and increased phosphorylation of Akt, indicating a stronger activation of IGF‐1R signaling pathway. However, HepG2 cells with reduced level of GRK2 did not display any growth advantage in culture as compared with the scramble control cells. We further detected that reduced level of GRK2 induced a small cell cycle arrest at G2/M phase by enhancing the expression of cyclin A, B1, and E. Our results indicate that GRK2 has contrasting roles on HepG2 cell growth by negatively regulating the IGF‐1R signaling pathway and cyclins' expression. J. Cell. Physiol. 228: 1897–1901, 2013. © 2013 Wiley Periodicals, Inc.
Fibroblast cytoskeletal remodeling induced by tissue stretch involves ATP signaling
Authors: Langevin Helene M. , Fujita Takumi , Bouffard Nicole A. , Takano Takahiro , Koptiuch Cathryn , Badger Gary J. , Nedergaard Maiken
Published: March 2013

Fibroblasts in whole areolar connective tissue respond to static stretching of the tissue by expanding and remodeling their cytoskeleton within minutes both ex vivo and in vivo. This study tested the hypothesis that the mechanism of fibroblast expansion in response to tissue stretch involves extracellular ATP signaling. In response to tissue stretch ex vivo, ATP levels in the bath solution increased significantly, and this increase was sustained for 20 min, returning to baseline at 60 min. No increase in ATP was observed in tissue incubated without stretch or tissue stretched in the presence of the Rho kinase inhibitor Y27632. The increase in fibroblast cross sectional area in response to tissue stretch was blocked by both suramin (a purinergic receptor blocker) and apyrase (an enzyme that selectively degrades extracellular ATP). Furthermore, connexin channel blockers (octanol and carbenoxolone), but not VRAC (fluoxetine) or pannexin (probenecid) channel blockers, inhibited fibroblast expansion. Together, these results support a mechanism in which extracellular ATP signaling via connexin hemichannels mediate the active change in fibroblast shape that occurs in response to a static increase in tissue length. J. Cell. Physiol. 228: 1922–1926, 2013. © 2013 Wiley Periodicals, Inc.
EFFECTS OF REWARD BUNDLING ON MALE RATS' PREFERENCE FOR LARGER–LATER FOOD REWARDS
Authors: Stein Jeffrey S. , Smits Rochelle R. , Johnson Patrick S. , Liston Kennan J. , Madden Gregory J.
Published: March 2013

In both humans and nonhumans, prior research demonstrates increased preference for larger‐later over smaller‐sooner rewards when rewards are bundled together in a series (i.e., when an operant choice produces multiple discrete reward deliveries, as opposed to only a single delivery). These findings can be predicted using a traditional hyperbolic delay‐discounting model. The present study was designed to examine the parametric effects of the size of the reward bundle on larger‐later reward preference in male rats. During a reward‐bundling phase, rats were exposed to bundle‐sizes of either 1 (i.e., no bundling), 3, or 9 rewards. Rats in the Bundle‐size 9 group showed significantly greater larger‐later reward preference across a range of delays (0‐17.5 s) than rats in any other group, but no other significant differences in choice were observed between groups. In addition, when choice for unbundled rewards was assessed following the reward‐bundling phase, rats in the Bundle‐size 9 group showed a significant increase in larger‐later reward preference (compared to a pre‐test). Obtained data from the reward‐bundling phase are compared to model‐predicted data, and potential mechanisms of the observed increase in self‐control for unbundled rewards are discussed.
COMBINATIONS OF RESPONSE‐REINFORCER RELATIONS IN PERIODIC AND APERIODIC SCHEDULES
Authors: Kuroda Toshikazu , Cançado Carlos R. X. , Lattal Kennon A. , Elcoro Mirari , Dickson Chata A. , Cook James E.
Published: March 2013

Key pecking of 4 pigeons was studied under a two‐component multiple schedule in which food deliveries were arranged according to a fixed and a variable interfood interval. The percentage of response‐dependent food in each component was varied, first in ascending (0, 10, 30, 70 and 100%) and then in descending orders, in successive conditions. The change in response rates was positively related to the percentage of response‐dependent food in each schedule component. Across conditions, positively accelerated and linear patterns of responding occurred consistently in the fixed and variable components, respectively. These results suggest that the response–food dependency determines response rates in periodic and aperiodic schedules, and that the temporal distribution of food determines response patterns independently of the response–food dependency. Running rates, but not postfood pauses, also were positively related to the percentage of dependent food in each condition, in both fixed and variable components. Thus, the relation between overall response rate and the percentage of dependent food was mediated by responding that occurred after postfood pausing. The findings together extend previous studies wherein the dependency was either always present or absent, and increase the generality of the effects of variations in the response–food dependency from aperiodic to periodic schedules.
COCAINE VERSUS FOOD CHOICE PROCEDURE IN RATS: ENVIRONMENTAL MANIPULATIONS AND EFFECTS OF AMPHETAMINE
Authors: Thomsen Morgane , Barrett Andrew C. , Negus S. Stevens , Caine S. Barak
Published: March 2013

We have adapted a nonhuman primate model of cocaine versus food choice to the rat species. To evaluate the procedure, we tested cocaine versus food choice under a variety of environmental manipulations as well as pharmacological pretreatments. Complete cocaine‐choice dose‐effect curves (0–1.0 mg/kg/infusion) were obtained for each condition under concurrent fixed ratio schedules of reinforcement. Percentage of responding emitted on the cocaine‐reinforced lever was not affected significantly by removal of cocaine‐associated visual or auditory cues, but it was decreased after removal of response‐contingent or response‐independent cocaine infusions. Cocaine choice was sensitive to the magnitude and fixed ratio requirement of both the cocaine and food reinforcers. We also tested the effects of acute (0.32, 0.56, 1.0, 1.8 mg/kg) and chronic (0.1, 0.32 mg/kg/hr) d‐amphetamine treatment on cocaine choice. Acute and chronic d‐amphetamine had opposite effects, with acute increasing and chronic decreasing cocaine choice, similar to observations in humans and in nonhuman primates. The results suggest feasibility and utility of the choice procedure in rats and support its comparability to similar procedures used in humans and monkeys.
VALUING SOCIAL CAPITAL BY THE RESOURCES PEOPLE ALLOCATE TO ONE ANOTHER
Authors: Zischka Lorna
Published: March 2013

British Household Panel Survey data are used to show that individuals giving up resources for others are associated with communities with less social vices (higher levels of social capital). Analysing resource flows between people offers a new way of evaluating social capital and its determinant factors. Transfers between persons are further analysed using descriptive economic models. Social norms, networks, relative resource endowments and reciprocation all affect resource flows, but altruism determines whether relationships become mutually beneficial and supportive or else extractive and polarising. Positive social capital is characterised by individuals investing resources in people not better off than themselves. Copyright © 2013 John Wiley & Sons, Ltd.