bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cost‐effectiveness of a successful community‐based obesity prevention program: The be active eat well program
Authors: Moodie Marjory L. , Herbert Jessica K. , de Silva‐Sanigorski Andrea M. , Mavoa Helen M. , Keating Catherine L. , Carter Robert C , Waters Elizabeth , Gibbs Lisa , Swinburn Boyd A. 
Published: March 2013

ObjectiveTo examine the cost‐effectiveness of Be Active Eat Well (BAEW), a large, multifaceted, community‐based capacity‐building demonstration program that promoted healthy eating and physical activity for Australian children aged 4‐12 years between 2003 and 2006.Design and MethodsA quasi‐experimental, longitudinal design was used with anthropometric data collected at baseline (1001 children—intervention; 1183—comparator) and follow‐up. A societal perspective was employed, with intervention resource use measured retrospectively based on process evaluation reports, school newsletters, reports, and key stakeholder interviews, and valued in 2006 Australian dollars (AUD). Outcomes were measured as Body Mass Index (BMI) units saved and Disability Adjusted Life Years (DALYs) averted over the predicted cohort lifetime, and reported as incremental cost‐effectiveness ratios (with 95% uncertainty intervals).ResultsThe intervention cost AUD0.34M ($0.31M; $0.38M) annually, and resulted in savings of 547 (−104; 1209) BMI units and 10.2 (−0.19; 21.6) DALYs. This translated to modest cost offsets of AUD27 311 (−$1803; $58 242) and a net cost per DALY saved of AUD29 798 (dominated; $0.26M).ConclusionsBAEW was affordable and cost‐effective, and generated substantial spin‐offs in terms of activity beyond funding levels. Elements fundamental to its success and any potential cost efficiencies associated with scaling‐up now require identification.
Membrane phospholipid bilayer as a determinant of monoacylglycerol lipase kinetic profile and conformational repertoire
Authors: Nasr Mahmoud L. , Shi Xiaomeng , Bowman Anna L. , Johnson Michael , Zvonok Nikolai , Janero David R. , Vemuri V. Kiran , Wales Thomas E. , Engen John R. , Makriyannis Alexandros 
Published: March 2013

AbstractThe membrane‐associated serine hydrolase, monoacylglycerol lipase (MGL), is a well‐recognized therapeutic target that regulates endocannabinoid signaling. Crystallographic studies, while providing structural information about static MGL states, offer no direct experimental insight into the impact of MGL's membrane association upon its structure–function landscape. We report application of phospholipid bilayer nanodiscs as biomembrane models with which to evaluate the effect of a membrane system on the catalytic properties and conformational dynamics of human MGL (hMGL). Anionic and charge‐neutral phospholipid bilayer nanodiscs enhanced hMGL's kinetic properties [apparent maximum velocity (Vmax) and substrate affinity (Km)]. Hydrogen exchange mass spectrometry (HX MS) was used as a conformational analysis method to profile experimentally the extent of hMGL–nanodisc interaction and its impact upon hMGL structure. We provide evidence that significant regions of hMGL lid‐domain helix α4 and neighboring helix α6 interact with the nanodisc phospholipid bilayer, anchoring hMGL in a more open conformation to facilitate ligand access to the enzyme's substrate‐binding channel. Covalent modification of membrane‐associated hMGL by the irreversible carbamate inhibitor, AM6580, shielded the active site region, but did not increase solvent exposure of the lid domain, suggesting that the inactive, carbamylated enzyme remains intact and membrane associated. Molecular dynamics simulations generated conformational models congruent with the open, membrane‐associated topology of active and inhibited, covalently‐modified hMGL. Our data indicate that hMGL interaction with a phospholipid membrane bilayer induces regional changes in the enzyme's conformation that favor its recruiting lipophilic substrate/inhibitor from membrane stores to the active site via the lid, resulting in enhanced hMGL catalytic activity and substrate affinity.
Structure‐based network analysis of an evolved G protein‐coupled receptor homodimer interface
Authors: Nichols Sara E. , Hernández Carlos X. , Wang Yi , McCammon James Andrew 
Published: March 2013

AbstractCrystallographic structures and experimental assays of human CXC chemokine receptor type 4 (CXCR4) provide strong evidence for the capacity to homodimerize, potentially as a means of allosteric regulation. Even so, how this homodimer forms and its biological significance has yet to be fully characterized. By applying principles from network analysis, sequence‐based approaches such as statistical coupling analysis to determine coevolutionary residues, can be used in conjunction with molecular dynamics simulations to identify residues relevant to dimerization. Here, the predominant coevolution sector lies along the observed dimer interface, suggesting functional relevance. Furthermore, coevolution scoring provides a basis for determining significant nodes, termed hubs, in the network formed by residues found along the interface of the homodimer. These node residues coincide with hotspots indicating potential druggability. Drug design efforts targeting such key residues could potentially result in modulation of binding and therapeutic benefits for disease states, such as lung cancers, lymphomas and latent HIV‐1 infection. Furthermore, this method may be applied to any protein–protein interaction.
Crystallographic analysis of the ENTH domain from yeast epsin Ent2 that induces a cell division phenotype
Authors: Costakes Gregory T. , Sen Arpita , Aguilar R. Claudio. , Stauffacher Cynthia V. 
Published: March 2013

AbstractEpsins are eukaryotic, endocytic adaptor proteins primarily involved in the early steps of clathrin mediated endocytosis. Two epsins exist inSaccharomyces cerevisiae, Ent1 and Ent2, with single epsin knockouts being viable, while the double knockout is not. These proteins contain a highly conserved Epsin N‐terminal homology (ENTH) domain that is essential for cell viability. In addition, overexpression of the ENTH domain of Ent2 (ENTH2) was shown to play a role in cell division by interacting with the septin organizing, Cdc42 GTPase activating protein, Bem3, leading to increased cytokinesis failure. In contrast, overexpression of the ENTH domain of Ent1 (ENTH1) does not affect cytokinesis, despite being 75% identical to ENTH2. An ENTH2N112D, S114E, E118Qmutant that switches residues in loop 7 to those found correspondingly in ENTH1 was incapable of inducing the cytokinesis phenotype. In order to better understand the role of loop 7 in the ENTH2‐induced phenotype at a molecular level, X‐ray crystallography was used to elucidate the structures of yeast ENTH2WTand ENTH2DEQ. Our results indicate that mutations did not affect the conformation of loop 7, but rather introduce an increased negative charge on a potential interaction interface. Morphological analysis of cells overexpressing ENTH2 loop 7 mutants showed that the cytokinesis failure phenotype was abolished by the single mutants N112D, E118Q, and to a lesser extent by S114E. Taken together, our results indicate that the interaction surface that contains loop 7 and the specific nature of these residues are crucial for ENTH2 involvement in cytokinesis. This research provides insight into a molecular mechanism by which ENTH2, but not ENTH1, overexpression in yeast leads to cell division defects. Structural data of WT and mutant ENTH2 domains along within vivophenotypic analysis of ENTH2 overexpressing cells indicate that the biochemical nature of three loop 7 residues is crucial for its role in cytokinesis.
Peptidyl cyclopropenones: Reversible inhibitors, irreversible inhibitors, or substrates of cysteine proteases?
Authors: Cohen Meital , Bretler Uriel , Albeck Amnon 
Published: March 2013

AbstractPeptidyl cyclopropenones were previously introduced as selective cysteine protease reversible inhibitors. In the present study we synthesized one such peptidyl cyclopropenone and investigated its interaction with papain, a prototype cysteine protease. A set of kinetics, biochemical, HPLC, MS, and 13C‐NMR experiments revealed that the peptidyl cyclopropenone was an irreversible inhibitor of the enzyme, alkylating the catalytic cysteine. In parallel, this cyclopropenone also behaved as an alternative substrate of the enzyme, providing a product that was tentatively suggested to be either a spiroepoxy cyclopropanone or a gamma‐lactone. Thus, a single family of compounds exhibits an unusual variety of activities, being reversible inhibitors, irreversible inhibitors and alternative substrates towards enzymes of the same family.
Copper‐chaperones with dicoordinated Cu(I)—Unique protection mechanism
Authors: Ansbacher Tamar , Chourasia Mukesh , Shurki Avital 
Published: March 2013

ABSTRACTCu(I) dicoordination with thiolate ligands is not common. Yet, different from its homologue proteins, human copper chaperone is known to bind Cu(I) using this low coordination number while binding Cu(I) only via the two conserved Cysteine residues, Cys12 and Cys15. Based on structural analysis, this work determines that the protein possesses two distinct conformations referred to as “in” and “out” due to the relative positioning of Cys12 (one of Cu(I) binding residues). The “out” conformation, with Cys12 pointing out, imposes a buried Cu(I) position, whereas the “in” conformation with Cys12 pointing inwards results in a more exposed Cu(I) thus, available for transfer. Using QM/MM methods along with thermodynamic cycles these two conformations are shown to exhibit different coordination preference, suggesting that the protein has evolved to have a unique Cu(I) protection mechanism. It is proposed that the “out” conformation with a preference to dicoordination prevents Cu(I) interaction with external ligands and/or Cu(I) release to the solvent, whereas the “in” conformation with preference to tricoordinated Cu(I), facilitates Cu(I) transfer to target proteins, where additional ligands are involved. Proteins 2013; 81:1411–1419. © 2013 Wiley Periodicals, Inc.
Why is Svalbard an island? Evidence for two‐stage uplift, magmatic underplating, and mantle thermal anomalies
Authors: Dörr N. , Clift P. D. , Lisker F. , Spiegel C. 
Published: March 2013

AbstractSvalbard is an anomalous, subaerial part of the Barents Shelf, Northeast Atlantic Ocean. In this study, we performed both, one‐ and two‐dimensional subsidence analyses based on basin structure, water depth, and thermochronology, to quantify and date the phases of uplift affecting Svalbard during the Cenozoic. Svalbard has experienced two phases of uplift, from >36 to ~10 Ma, and since ~10 Ma, similar in timing to uplift phases identified in Greenland, Scandinavia, and the Barents Shelf. Total uplift across much of the Central Tertiary Basin of Svalbard is >1.5 km and exceeds 2.5 km in parts of the West Spitsbergen Foldbelt (WSFB). Uplift from >36 to ~10 Ma accounts for the greatest part of the vertical motion and like the younger phase reduces in magnitude towards the east. Flexural rigidity of the lithosphere is estimated to be low (Te ≈ 5 km), so that post‐36 Ma erosion of the WSFB contributes little to the uplift, whose permanent nature and proximity to the synchronous Yermak Plateau favors a link to regional magmatic underplating. Plume dynamic support and flexural unloading along the western transform plate margin can be ruled out as influences on vertical motions. Since ~10 Ma renewed uplift, generating the modern topography may be linked to thermal erosion of the mantle lithosphere under Svalbard. We suggest that a likely cause of much of the surface uplift is the northward propagation of the Knipovich Ridge to establish continuous seafloor spreading through the Fram Strait after ~10 Ma.
Good Customers: The Value of Customers by Mode of Acquisition
Authors: Uncles Mark D. , East Robert , Lomax Wendy 
Published: March 2013

Are referred customers more valuable than customers recruited through advertising/promotion? This question is answered using data accumulated from surveys covering the satisfaction, recommendation, retention, spending and mode of acquisition of customers. The database comprises 6578 records and covers 15 product/service category groupings. Overall, referral customers are somewhat more satisfied, recommend their brand more, and have superior retention when compared to customers recruited through advertising/promotion. These findings suggest that referral customers are more profitable than advertising customers but, unexpectedly, their superiority over advertising customers rests mainly on their greater retention rather than their higher level of recommendation. On this evidence, referral customers bring somewhat more benefit to a firm than those recruited through advertising/promotion. Projections for a 7-year period illustrate the magnitude of these benefits. Also discussed and illustrated is a possible secondary outcome – social amplification.
Using a preclinical mouse model of high-grade astrocytoma to optimize p53 restoration therapy
Authors: Shchors Ksenya , Persson Anders I. , Rostker Fanya , Tihan Tarik , Lyubynska Natalya , Li Nan , Swigart Lamorna Brown , Berger Mitchel S. , Hanahan Douglas , Weiss William A. , Evan Gerard I. 
Published: March 2013

Significance
Glioblastoma is the most common and aggressive form of brain cancer. GBM patients typically respond poorly to conventional therapies. The tumor-suppressor protein 53 pathway is disrupted in a majority of GBM cases. Using a mouse model that mimics the progression of human GBM, we evaluate and optimize the therapeutic efficacy of functional p53 restoration in gliomas. We show that the efficacy of p53 restoration therapy in the animal model as well as in human GBM cells is improved markedly by an episodic dosing regimen that circumvents the selective pressure for adaptive resistance when p53 function is chronically restored.
Fishery Management Complexes: An Impediment or Aid to Sustainable Harvest? A Discussion Based on the Northeast Skate Complex
Authors: Hogan Fiona , Cadrin Steve , Haygood Alyssa 
Published: March 2013

Abstract
There are seven species of skates (family Rajidae) found along the East Coast of the USA. All seven species are currently managed by the New England Fisheries Management Council as a single management complex extending from the Gulf of Maine to Cape Hatteras. The objective of the management plan is to ensure the long-term sustainability of fishing for each species via a trip limit approach. Two species are harvested in two distinct commercial fisheries. Northeast Fisheries Science Center trawl survey data and published literature were examined to investigate differences between the individual species in the skate complex. Each species exhibited a unique thermal and geographic range in addition to vital life history traits (e.g., age at maturity, longevity, and maximum size). Thorny Skate Amblyraja radiata and Smooth Skate Malacoraja senta have narrow thermal ranges and maintain a more northern distribution. Barndoor Skate Dipturus laevis have a moderate thermal habitat. Little Skate Leucoraja erinacea and Winter Skate L. ocellata have broad thermal ranges and are distributed throughout the management area. Limited inferences can be made about the thermal preferences of Clearnose Skate Raja eglanteria without data from south of Cape Hatteras, but they appear to have a broad thermal range within the management area. Rosette Skate L. garmani have a narrow thermal range and tend to be found in the deep offshore mid-Atlantic region. The validity of managing multiple distinct species in a complex is questioned. This example shows that a mixed-stock management strategy may be inadequate to meet the sustainability needs of each species and the associated fisheries. A management strategy focused on individual species may lead to a more efficient harvest of targeted species while allowing for the rebuilding of overfished species.
Received November 8, 2011; accepted December 27, 2012
Ghost Fishing in the Southeast Alaska Commercial Dungeness Crab Fishery
Authors: Maselko Jacek , Bishop Gretchen , Murphy Peter 
Published: March 2013

Abstract
Entrapment of crabs by derelict crab pots (also known as ghost fishing) can be a significant consequence of commercial fishing. The prevalence of lost commercial pots and ghost-fishing entrapments was estimated for the commercial Dungeness crab Cancer magister fishery in southeastern Alaska during the 2009 and 2010 summer closures of the commercial season (16 August through 30 September). Teams of divers retrieved a random subsample of the derelict crab pots located using side-scan sonar. Altogether, we retrieved 123 derelict crab pots containing 215 entrapped Dungeness crabs. The densities of derelict crab pots varied from 1.5 to 10.1/km2, while the densities of entrapped Dungeness crabs ranged from 0 to 54.5/km2, depending on the area surveyed. Derelict crab pots were discovered to effectively ghost-fish for at least 7 years, indicating that there are long-term cumulative impacts on Dungeness crab populations. The number of derelict crab pots and entrapped Dungeness crabs at each of the surveyed areas was highly correlated with the number of fishermen, the number of pot lifts, and annual harvest in numbers, allowing for extrapolation to a regionwide estimate of crab entrapment and derelict crab pot abundance. Overall, our findings show instantaneous entrapment of less than 1% of the commercial crab harvest with a cumulative annual loss of less than 3% of the regional commercial crab harvest. We challenge the efficacy of the biodegradable escape mechanism currently employed in commercial Dungeness crab pots in southeastern Alaska and present alternatives which may require further in situ or laboratory verification of their effectiveness.
Received February 23, 2012; accepted December 27, 2012
Differences between Livestock and Crop Producers' Participation in Nutrient Trading
Authors: Sneeringer Stacy 
Published: March 2013

AbstractDescriptions of agricultural producers' participation in nutrient trading schemes generally refer to crop producers reducing nutrient run‐off from fields to generate credits. However, livestock producers may participate differently than crop producers because some are regulated as Concentrated Animal Feeding Operations (CAFOs), and because agricultural producers generating manure face different costs of reducing nutrient application (and therefore generating credits) from those only using fertilizer. These differences may affect nutrient reduction credit prices and the supply of agriculturally supplied credits, thereby raising the costs to non‐agricultural operations of meeting water quality goals. We examine how CAFO laws interact with nutrient trading requirements. We model trading participation by farm type and then simulate trading participation by applying the model to 2007 Census of Agriculture data.
Enabling interspecies epigenomic comparison with CEpBrowser
Authors: Cao Xiaoyi , Zhong Sheng 
Published: March 2013

Abstract
Summary: We developed the Comparative Epigenome Browser (CEpBrowser) to allow the public to perform multi-species epigenomic analysis. The web-based CEpBrowser integrates, manages and visualizes sequencing-based epigenomic datasets. Five key features were developed to maximize the efficiency of interspecies epigenomic comparisons.
Availability: CEpBrowser is a web application implemented with PHP, MySQL, C and Apache. URL: http://www.cepbrowser.org/.
Contact: szhong@ucsd.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Protective Mechanical Ventilation during General Anesthesia for Open Abdominal Surgery Improves Postoperative Pulmonary Function
Authors: Severgnini Paolo , Selmo Gabriele , Lanza Christian , Chiesa Alessandro , Frigerio Alice , Bacuzzi Alessandro , Dionigi Gianlorenzo , Novario Raffaele , Gregoretti Cesare , de Abreu Marcelo Gama , Schultz Marcus J. , Jaber Samir , Futier Emmanuel , Chiaranda Maurizio , Pelosi Paolo 
Published: March 2013

Abstract

Background:
The impact of intraoperative ventilation on postoperative pulmonary complications is not defined. The authors aimed at determining the effectiveness of protective mechanical ventilation during open abdominal surgery on a modified Clinical Pulmonary Infection Score as primary outcome and postoperative pulmonary function.

Methods:
Prospective randomized, open-label, clinical trial performed in 56 patients scheduled to undergo elective open abdominal surgery lasting more than 2 h. Patients were assigned by envelopes to mechanical ventilation with tidal volume of 9 ml/kg ideal body weight and zero-positive end-expiratory pressure (standard ventilation strategy) or tidal volumes of 7 ml/kg ideal body weight, 10 cm H2O positive end-expiratory pressure, and recruitment maneuvers (protective ventilation strategy). Modified Clinical Pulmonary Infection Score, gas exchange, and pulmonary functional tests were measured preoperatively, as well as at days 1, 3, and 5 after surgery.

Results:
Patients ventilated protectively showed better pulmonary functional tests up to day 5, fewer alterations on chest x-ray up to day 3 and higher arterial oxygenation in air at days 1, 3, and 5 (mmHg; mean ± SD): 77.1 ± 13.0 versus 64.9 ± 11.3 (P = 0.0006), 80.5 ± 10.1 versus 69.7 ± 9.3 (P = 0.0002), and 82.1 ± 10.7 versus 78.5 ± 21.7 (P = 0.44) respectively. The modified Clinical Pulmonary Infection Score was lower in the protective ventilation strategy at days 1 and 3. The percentage of patients in hospital at day 28 after surgery was not different between groups (7 vs. 15% respectively, P = 0.42).

Conclusion:
A protective ventilation strategy during abdominal surgery lasting more than 2 h improved respiratory function and reduced the modified Clinical Pulmonary Infection Score without affecting length of hospital stay.
Coadministration of the AMPAKINE CX717 with Propofol Reduces Respiratory Depression and Fatal Apneas
Authors: Ren Jun , Lenal Floriane , Yang Michael , Ding Xiuqing , Greer John J. 
Published: March 2013

Abstract

Background:
Propofol (2,6-diisopropylphenol) is used for the induction and maintenance of anesthesia in human and veterinary medicine. Propofol’s disadvantages include the induction of respiratory depression and apnea. Here, the authors report a clinically feasible pharmacological solution for reducing propofol-induced respiratory depression via a mechanism that does not interfere with anesthesia. Specifically, they test the hypothesis that the AMPAKINE CX717, which has been proven metabolically stable and safe for human use, can prevent and rescue from propofol-induced severe apnea.

Methods:
The actions of propofol and the AMPAKINE CX717 were measured via (1) ventral root recordings from newborn rat brainstem–spinal cord preparations, (2) phrenic nerve recordings from an adult mouse in situ working heart–brainstem preparation, and (3) plethysmographic recordings from unrestrained newborn and adult rats.

Results:

In vitro, respiratory depression caused by propofol (2 μm, n = 11, mean ± SEM, 41±5% of control frequency, 63±5% of control duration) was alleviated by CX717 (n = 4, 50–150 μm). In situ, a decrease in respiratory frequency (44±9% of control), phrenic burst duration (66±7% of control), and amplitude (78±5% of control) caused by propofol (2 μm, n = 5) was alleviated by coadministration of CX717 (50 μm, n = 5). In vivo, pre- or coadministration of CX717 (20–25mg/kg) with propofol markedly reduced propofol-induced respiratory depression (n = 7; 20mg/kg) and propofol-induced lethal apnea (n = 6; 30mg/kg).

Conclusions:
Administration of CX717 before or in conjunction with propofol provides an increased safety margin against profound apnea and death.