bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using maximum entropy production to describe microbial biogeochemistry over time and space in a meromictic pond
Authors: Vallino Joseph J. , Huber Julie A. 
Published: February 2018

AbstractThe maximum entropy production (MEP) conjecture posits that systems with many degrees of freedom will likely organize to maximize the rate of free energy dissipation. Previous work indicates that biological systems can outcompete abiotic systems by maximizing free energy dissipation over time by utilizing temporal strategies acquired and refined by evolution, and over space via cooperation. In this study, we develop an MEP model to describe biogeochemistry observed in Siders Pond, a phosphate limited meromictic system located in Falmouth, MA that exhibits steep chemical gradients due to density-driven stratification that supports anaerobic photosynthesis as well as microbial communities that catalyze redox cycles involving O, N, S, Fe and Mn. The MEP model uses a metabolic network to represent microbial redox reactions, where biomass allocation and reaction rates are determined by solving an optimization problem that maximizes entropy production over time and a 1D vertical profile constrained by an advection-dispersion-reaction model. We introduce a new approach for modeling phototrophy and explicitly represent aerobic photoautotrophs, anoxygenic photoheterotrophs and anaerobic photoautotrophs. The metabolic network also includes reactions for heterotrophic bacteria, sulfate reducing bacteria, sulfide oxidizing bacteria and aerobic and anaerobic grazers. Model results were compared to observations of biogeochemical constituents collected over a 24 hour period at 8 depths at a single 15 m deep station in Siders Pond. Maximizing entropy production over long (3 d) intervals produced results more similar to field observations than short (0.25 d) interval optimizations, which support the importance of temporal strategies for maximizing entropy production over time. Furthermore, we found that entropy production must be maximized locally instead of globally where energy potentials are degraded quickly by abiotic processes, such as light absorption by water. This combination of field observations with modeling results show that microbial systems in nature can be accurately described by the maximum entropy production conjecture applied over time and space.
The clinician impact and financial cost to the NHS of litigation over pregabalin: a cohort study in English primary care
Authors: Croker Richard , Smyth Darren , Walker Alex J , Goldacre Ben 
Published: February 2018

AbstractObjectivesFollowing litigation over pregabalin’s second-use medical patent for neuropathic pain NHS England were required by the court to instruct GPs to prescribe the branded form (Lyrica) for pain. Pfizer’s patent was found invalid in 2015; a ruling subject to ongoing appeals. If the Supreme Court appeal in February 2018 is unsuccessful, the NHS can reclaim excess prescribing costs. We set out to describe the variation in prescribing of pregabalin as branded Lyrica, geographically and over time; to determine how clinicians responded to the NHS England instruction to GPs; and to model excess costs to the NHS attributable to the legal judgments.SettingEnglish primary careParticipantsEnglish general practicesPrimary and secondary outcome measuresVariation in prescribing of branded Lyrica across the country before and after the NHS England instruction, by practice and by Clinical Commissioning Group (CCG); excess prescribing costs.ResultsThe proportion of pregabalin prescribed as Lyrica increased, from 0.3% over six months before the NHS England instruction (September 2014-February 2015) to 25.7% afterwards (April - September 2015). Although 70% of pregabalin is estimated to be for neuropathic pain, only 11.6% of practices prescribed Lyrica at this level; the median proportion prescribed as Lyrica was 8.8% (IQR 1.1-41.9%). If pregabalin had come entirely off patent in September 2015, and Pfizer had not appealed, we estimate the NHS would have spent £502m less on pregabalin to July 2017.ConclusionNHS England instructions to GPs regarding branded prescription of pregabalin were widely ignored, and have created much debate around clinical independence in prescribing. Protecting revenue from “skinny labels” will pose a challenge. If Pfizer’s final appeal on the patent is unsuccessful the NHS can seek reimbursement of excess pregabalin prescribing costs, potentially £502m.
Stability of representational geometry across a wide range of fMRI activity levels
Authors: Arbuckle Spencer A. , Yokoi Atsushi , Pruszynski J. Andrew , Diedrichsen Jörn 
Published: February 2018

AbstractFine-grained activity patterns, as measured with functional magnetic resonance imaging (fMRI), are thought to reflect underlying neural representations. Multivariate analysis techniques, such as representational similarity analysis (RSA), can be used to test models of brain representation by quantifying the representational geometry (the collection of pair-wise dissimilarities between activity patterns). One important caveat, however, is that non-linearities in the coupling between neural activity and the fMRI signal may lead to significant distortions in the representational geometry estimated from fMRI activity patterns. Here we tested the stability of representational dissimilarity measures in primary sensory-motor (S1 and M1) and early visual regions (V1/V2) across a large range of activation levels. Subjects were visually cued with different letters to perform single finger presses with one of the 5 fingers at a rate of 0.3-2.6 Hz. For each stimulation frequency, we quantified the difference between the 5 activity patterns in M1, S1, and V1/V2. We found that the representational geometry remained stable, even though the average activity increased over a large dynamic range. These results indicate that the representational geometry of fMRI activity patterns can be reliably assessed, largely independent of the average activity in the region. This has important methodological implications for RSA and other multivariate analysis approaches that use the representational geometry to make inferences about brain representations.
BAX requires VDAC2 to mediate apoptosis and to limit tumor development
Authors: Chin Hui San , van Delft Mark F. , Ninnis Robert L. , Li Mark X. , Tan Iris K. L. , Reljic Boris , Scicluna Kristen , Dagley Laura F. , Sandow Jarrod J. , Kelly Gemma L. , Chappaz Stephane , Khaw Seong L. , Chang Catherine , Webb Andrew , Hockings Colin , Hall Cathrine M. , Kueh Andrew J. , Ryan Michael T. , Kluck Ruth M. , Bouillet Philippe , Herold Marco J. , Gray Daniel H. D. , Huang David C. S. , Dewson Grant 
Published: February 2018

AbstractIntrinsic apoptosis is critical for normal physiology including the prevention of tumor formation. BAX and BAK are essential for mediating this process and for the cytotoxic action of many anticancer drugs. BAX and BAK are thought to act in a functionally redundant manner and are considered to be regulated similarly. From an unbiased genome-wide CRISPR/Cas9 screen, we identified VDAC2 (voltage-dependent anion channel 2) as essential for BAX, but not BAK, to function. The genetic deletion of VDAC2 abrogated the association of BAX and BAK with mitochondrial complexes that contain VDAC1, VDAC2 and VDAC3. By disrupting its localization to mitochondria, BAX is rendered completely ineffective. Moreover, we defined an interface unique to VDAC2 that is required to drive BAX activity. Consequently, interfering with this interaction or deleting VDAC2 phenocopied the loss of BAX, including impairing the killing of tumor cells by anti-cancer agents such as the BCL-2 inhibitor venetoclax. Furthermore, the ability of BAX to prevent tumor formation was attenuated in the absence of VDAC2. Taken together, our studies show for the first time that BAX-mediated apoptosis, but not BAK-mediated apoptosis, is critically dependent on VDAC2, hence revealing the differential regulation of BAX and BAK.
A grow-and-lock model for the control of flagellum length in trypanosomes
Authors: Bertiaux Eloïse , Morga Benjamin , Blisnick Thierry , Rotureau Brice , Bastin Philippe 
Published: February 2018

SUMMARYSeveral models have been proposed to explain how eukaryotic cells control the length of their cilia and flagella. Here, we investigated this process in the protistTrypanosoma brucei, an excellent system for cells with stable cilia like photoreceptors or spermatozoa. We show that the total amount of intraflagellar transport material (IFT, the machinery responsible for flagellum construction) increases during flagellum elongation, consistent with constant delivery of precursors and the previously reported linear growth. Reducing the IFT frequency by RNAi knockdown of the IFT kinesin motors slows down the elongation rate and results in the assembly of shorter flagella. These keep on elongating after cell division but fail to reach the normal length. This failure is neither due to an absence of precursors nor to a morphogenetic control by the cell body. We propose that the flagellum is locked after cell division, preventing further elongation or shortening. This is supported by the fact that subsequent increase in the IFT rate does not lead to further elongation. The distal tip FLAM8 protein was identified as a marker for the locking event. It is initiated prior cell division, leading to an arrest of elongation in the daughter cell. Here, we propose a new model termed grow-and-lock where the flagellum elongates until a locking event takes place in a timely defined manner hence fixing length. Alteration in the growth rate and/or in the timing of the locking event would lead to the formation of flagella of different lengths.
DNA sequence context controls the binding and processivity of the T7 DNA primase
Authors: Afek Ariel , Ilic Stefan , Horton John , Lukatsky David B. , Gordan Raluca , Akabayov Barak 
Published: February 2018

SUMMARYPrimases are key enzymes involved in DNA replication. They act on single-stranded DNA, and catalyze the synthesis of short RNA primers used by DNA polymerases. Here, we investigate the DNA-binding and activity of the bacteriophage T7 primase using a new workflow calledHigh-ThroughputPrimaseProfiling (HTPP). Using a unique combination of high-throughput binding assays and biochemical analyses, HTPP reveals a complex landscape of binding specificity and functional activity for the T7 primase, determined by sequences flanking the primase recognition site. We identified specific features, such as G/T-rich flanks, which increase primase-DNA binding up to 10-fold and, surprisingly, also increase the length of newly formed RNA (up to 3-fold). To our knowledge, variability in primer length has not been reported for this primase. We expect that applying HTPP to additional enzymes will reveal new insights into the effects of DNA sequence composition on the DNA recognition and functional activity of primases.
Regulation of ATR activity by the RNA polymerase II phosphatase PNUTS-PP1
Authors: Landsverk Helga B. , Sandquist Lise E. , Rødland Gro Elise , Grallert Beata , Trinkle-Mulcahy Laura , Syljuåsen Randi G. 
Published: February 2018

AbstractAtaxia telangiectasia mutated and Rad3-related (ATR) kinase is a key factor activated by DNA damage and replication stress. Here, we show that ATR signaling is increased in human cells after depletion of the RNAPII phosphatase PNUTS-PP1, which dephosphorylates RNAPII on Ser 5 of its carboxy-terminal domain (CTD) (pRNAPII S5). Increased ATR signaling was observed in the presence and absence of ionizing radiation or replication stress and even in G1 phase after depletion of PNUTS. Vice versa, ATR signaling was reduced, in a PNUTS dependent manner, after inhibition of the CDK7 kinase mediating pRNAPII S5. Furthermore, CDC73, a well-known RNAPII-CTD binding protein, was required for the high ATR signaling after depletion of PNUTS and co-immunoprecipitated with RNAPII and ATR. These results suggest a novel pathway involving RNAPII, PNUTS-PP1 and CDC73 in ATR signaling and give new insight into the diverse functions of ATR.
Urban crisis change efforts: the NAB and NUC
Authors: Singleton Laura G. 
Published: February 2018

PurposeThis study aims to compare the National Alliance of Businessmen and the National Urban Coalition, two change efforts spawned during the 1960’s US Urban Crisis, in which businesses took a central role to address urban problems, particularly through expanding opportunities for African-Americans.Design/methodology/approachThis is a historical comparative case study developed through research utilizing published resources and archival material.FindingsNeither organization clearly achieved its initial goals, with each migrating toward the end of its existence away from business-related goals to focus on public education. Potential causes include economic obstacles, a heroic conception of change that fostered overcommitment, and conflicting institutional logics in the organization’s missions, both of which were intertwined with governmental objectives from their foundings. However, the period shows overall changes in social awareness by business, in which these organizations played a part, and efforts by today’s businesses to respond to racial tensions in cities display learning from these predecessor organizations.Research limitations/implicationsA significant dependence on published sources limits the depth of insight versus accessing organizational archives; however, it does offer a similar basis for information on both organizations to facilitate comparisons.Practical implicationsThe structural vulnerabilities of these organizations can present lessons for organizations hoping to pursue similar change through business partnerships today.Social implicationsThe racial tensions continuing in the USA today display parallel the challenges of the 1960s, making learning from these precedents valuable.Originality/valueThis study offers a comparative view of the NAB and NUC throughout their history, which has not previously been provided.
Continuity and change in the Sheffield armaments industry 1919-1930
Authors: Corker Chris 
Published: February 2018

Purpose
This article aims to explore the impact of the Great War on the Sheffield armaments industry through the use of four company case studies in Thomas Firth, John Brown, Cammell Laird and Hadfields. It charts the evolving situation the armaments companies found themselves in after the end of the conflict and the uncertain external environment they had to engage with. The article also examines the stagnant nature of armaments companies’ boards of directors in the 1920s and the ultimate rationalisation of the industry at the close of the decade.

Design/methodology/approach
The research design is based around a close examination of the surviving manuscript records of each of the companies included, the records of the speeches recorded by chairpersons at annual meetings and some governmental records.

Findings
The article concludes by outlining how the end of the Great War continued to affect the industry for the following decade and the complex evolving situation with a changing external environment and continuity of management internally ultimately leading to mergers in the industry.

Originality/value
This article uses a number of underused manuscript records to examine the Sheffield armaments industry and explores the effect of a global mega event in the Great War on one of the most technologically advanced industries of the period.
How Does Transfer Pricing Risk Affect Premiums in Cross‐Border Mergers and Acquisitions?
Authors: Mescall Devan , Klassen Kenneth J. 
Published: February 2018

ABSTRACTThis study investigates how transfer pricing risk affects the premiums in cross‐border mergers and acquisitions (M&A). Differences in the rigor of transfer pricing enforcement and the severity and clarity of rules across countries create differential risk of material costs for multinationals as they expand globally. We use 448 country‐level transfer pricing risk assessments by global transfer pricing partners and managers from two firms in 33 countries to develop a metric of country‐year transfer pricing risks. The resulting measure of transfer pricing risk is used to analyze the premiums of 3,103 cross‐border M&A from 2000 to 2012. We find that lower bid premiums are associated with higher transfer pricing risk in the target's country. We find the relation is stronger when expected future transfer pricing benefits are larger. Our results, consistent with the views of experts in the field, provide the first archival evidence that acquirers consider synergies created by future tax planning when estimating the value of a target.
Auditor Experience and the Timeliness of Litigation Loss Contingency Disclosures*
Authors: Chen Feng , Hou Yu , Richardson Gordon , Ye Minlei 
Published: February 2018

ABSTRACTThis paper hypothesizes and finds that firms audited by city‐industry specialists have more timely disclosures of contingent losses from litigation when there is no news coverage relating to the legal case prior to management disclosures. A closer examination reveals that this result is explained by the specialist auditors’ prior experience auditing clients in the same office and industry who are involved with litigation. In our setting, disclosures of litigation‐related contingent losses, we identify two kinds of knowledge generated from experience: industry knowledge and litigation knowledge. Industry knowledge helps auditors detect and correct poor implementation of guidance for litigation loss contingency disclosures. Auditors gain litigation knowledge from auditing clients in a given office and industry with previous involvement as defendants. Thus, the two types of knowledge interact in their effects on reporting outcomes.
How to measure capital investment efficiency: a literature synthesis
Authors: Gao Ru , Yu Xin 
Published: February 2018

AbstractThis article reviews and integrates the empirical literature on the measurement of investment efficiency in the areas of accounting and finance. We identify the theories behind the measures and provide a framework which organises the measures of investment efficiency into three groups: those based on neoclassical theories, agency theory and real options theory. Furthermore, the advantages and disadvantages of each type of measure are discussed, allowing researchers to compare and then ascertain the most appropriate measure for their research purpose and research context.
Psychotic experiences and religiosity: data from the WHO World Mental Health Surveys
Authors: Kovess‐Masfety V. , Saha S. , Lim C. C. W. , Aguilar‐Gaxiola S. , Al‐Hamzawi A. , Alonso J. , Borges G. , de Girolamo G. , de Jonge P. , Demyttenaere K. , Florescu S. , Haro J. M. , Hu C. , Karam E. G. , Kawakami N. , Lee S. , Lepine J. P. , Navarro‐Mateu F. , Stagnaro J. C. , ten Have M. , Viana M. C. , Kessler R. C. , McGrath J. J. ,   the WHO World Mental Health Survey Collaborators
Published: February 2018

ObjectivesReligiosity is often associated with better health outcomes. The aim of the study was to examine associations between psychotic experiences (PEs) and religiosity in a large, cross‐national sample.MethodsA total of 25 542 adult respondents across 18 countries from the WHO World Mental Health Surveys were assessed for PEs, religious affiliation and indices of religiosity, DSM‐IV mental disorders and general medical conditions. Logistic regression models were used to estimate the association between PEs and religiosity with various adjustments.ResultsOf 25 542 included respondents, 85.6% (SE = 0.3) (n = 21 860) respondents reported having a religious affiliation. Overall, there was no association between religious affiliation status and PEs. Within the subgroup having a religious affiliation, four of five indices of religiosity were significantly associated with increased odds of PEs (odds ratios ranged from 1.3 to 1.9). The findings persisted after adjustments for mental disorders and/or general medical conditions, as well as religious denomination type. There was a significant association between increased religiosity and reporting more types of PEs.ConclusionsAmong individuals with religious affiliations, those who reported more religiosity on four of five indices had increased odds of PEs. Focussed and more qualitative research will be required to unravel the interrelationship between religiosity and PEs.
An investigation of an open‐access model for scaling up methadone maintenance treatment
Authors: Madden Lynn M. , Farnum Scott O. , Eggert Kathryn F. , Quanbeck Andrew R. , Freeman Robert M. , Ball Samuel A. , Schottenfeld Richard S. , Shi Julia M. , Savage Mary Ellen , Barry Declan T. 
Published: February 2018

AbstractAimsTo examine retrospectively patient and programmatic outcomes following the development and implementation of an ‘open‐access’ model in which prospective patients were enrolled rapidly in methadone maintenance treatment, irrespective of ability to pay, and provided real‐time access to multiple voluntary treatment options.DesignMedical and administrative records were abstracted to compare data for 1 year before and 9 years after initiating the implementation of an open‐access treatment model in May 2007.SettingMethadone maintenance treatment center in Connecticut, USA.ParticipantsIndividuals with opioid use disorder entering treatment between July 2006 and June 2015. In June 2015, 64% (n = 2594) of the sample were men and 80% (n = 3133) reported that they were white.InterventionThe Network for the Improvement of Addiction Treatment‐informed open‐access treatment model uses process improvement strategies to improve treatment access and capacity.MeasurementsCensus, waiting time, retention, non‐medical opioid use, patient mortality and financial sustainability (net income and state‐block grants as proportions of revenue).FindingsIn the 9 years following the initial implementation of the open‐access model, patient census increased by 183% from 1431 to 4051, and average waiting‐time days decreased from 21 to 0.3 (same day) without apparent deleterious effects on rates of retention, non‐medical opioid use or mortality. Between fiscal years (FY) 06 and FY 15, net operating margin rose from 2 to 10%, while state‐block grant revenues declined 14% and the proportion of total revenue from state‐block grant revenue decreased from 49 to 24%.ConclusionsAn open‐access model for rapid enrolment of people with opioid use disorder in methadone treatment appears to improve treatment access, capacity, and financial sustainability without evidence of deleterious effects on treatment outcomes.