bluuebunny/crossref_metadata_2025 huggingface dataset:
Greenhouse-gas emissions from stockpiled and composted dairy-manure residues and consideration of associated emission factors
Authors: Biala J. , Lovrick N. , Rowlings D. , Grace P.
Published: July 2016

Emissions from stockpiled pond sludge and yard scrapings were compared with composted dairy-manure residues blended with shredded vegetation residues and chicken litter over a 5-month period at a farm in Victoria (Australia). Results showed that methane emissions occurred primarily during the first 30–60 days of stockpiling and composting, with daily emission rates being highest for stockpiled pond sludge. Cumulated methane (CH4) emissions per tonne wet feedstock were highest for stockpiling of pond sludge (969 g CH4/t), followed by composting (682 g CH4/t) and stockpiling of yard scrapings (120 g CH4/t). Sizeable nitrous oxide (N2O) fluxes were observed only when temperatures inside the compost windrow fell below ~45−50°C. Cumulated N2O emissions were highest for composting (159 g N2O/t), followed by stockpiling of pond sludge (103 g N2O/t) and yard scrapings (45 g N2O/t). Adding chicken litter and lime to dairy-manure residues resulted in a very low carbon-to-nitrogen ratio (13 : 1) of the composting mix, and would have brought about significant N2O losses during composting. These field observations suggested that decisions at composting operations, as in many other businesses, are driven more by practical and economic considerations rather than efforts to minimise greenhouse-gas emissions. Total greenhouse-gas emissions (CH4 + N2O), expressed as CO2-e per tonne wet feedstock, were highest for composting (64.4 kg), followed by those for stockpiling of pond sludge (54.5 kg) and yard scraping (16.3 kg). This meant that emissions for composting and stockpiling of pond sludge exceeded the new Australian default emission factors for ‘waste composting’ (49 kg). This paper proposes to express greenhouse-gas emissions from secondary manure-management systems (e.g. composting) also as emissions per tonne wet feedstock, so as to align them with the approach taken for ‘waste composting’ and to facilitate the development of emission-reduction methodologies for improved manure management at the farm level.
Methods for causal inference from gene perturbation experiments and validation
Authors: Meinshausen Nicolai , Hauser Alain , Mooij Joris M. , Peters Jonas , Versteeg Philip , Bühlmann Peter
Published: July 2016

Inferring causal effects from observational and interventional data is a highly desirable but ambitious goal. Many of the computational and statistical methods are plagued by fundamental identifiability issues, instability, and unreliable performance, especially for large-scale systems with many measured variables. We present software and provide some validation of a recently developed methodology based on an invariance principle, called invariant causal prediction (ICP). The ICP method quantifies confidence probabilities for inferring causal structures and thus leads to more reliable and confirmatory statements for causal relations and predictions of external intervention effects. We validate the ICP method and some other procedures using large-scale genome-wide gene perturbation experiments in
Saccharomyces cerevisiae
. The results suggest that prediction and prioritization of future experimental interventions, such as gene deletions, can be improved by using our statistical inference techniques.
Improving massive experiments with threshold blocking
Authors: Higgins Michael J. , Sävje Fredrik , Sekhon Jasjeet S.
Published: July 2016

Inferences from randomized experiments can be improved by blocking: assigning treatment in fixed proportions within groups of similar units. However, the use of the method is limited by the difficulty in deriving these groups. Current blocking methods are restricted to special cases or run in exponential time; are not sensitive to clustering of data points; and are often heuristic, providing an unsatisfactory solution in many common instances. We present an algorithm that implements a widely applicable class of blocking—threshold blocking—that solves these problems. Given a minimum required group size and a distance metric, we study the blocking problem of minimizing the maximum distance between any two units within the same group. We prove this is a nondeterministic polynomial-time hard problem and derive an approximation algorithm that yields a blocking where the maximum distance is guaranteed to be, at most, four times the optimal value. This algorithm runs in
O
(
n
log
n
) time with
O
(
n
) space complexity. This makes it, to our knowledge, the first blocking method with an ensured level of performance that works in massive experiments. Whereas many commonly used algorithms form pairs of units, our algorithm constructs the groups flexibly for any chosen minimum size. This facilitates complex experiments with several treatment arms and clustered data. A simulation study demonstrates the efficiency and efficacy of the algorithm; tens of millions of units can be blocked using a desktop computer in a few minutes.
Dative Case Marking in Vafsi within the OT Framework
Authors: Mirdehghan Mahinnaz , Yousefi Saeed Reza
Published: July 2016

The dative case in Vafsi appears in three structures: (a) the case of the experiencer in sensory verbs, (b) the case of the indirect object (IO), and (c) the case of the object of the preposition /da/ (to), or the preposition /az/ (to), or the enclitic /-o/ (to), or the object of the postposition /rā/ (for). In Vafsi, as in many other Indo-European languages, sensory verbs necessitate the emergence of quirky subjects which have the experiencer function and are dative case marked. In order to analyze the dative case marking in Vafsi using optimality theory, this article uses the faithfulness constraint of faith-lex and the markedness constraint hierarchy of *ERG≫*DAT≫*ACC≫*NOM. Vafsi always allocates the dative case to the IO of the ditransitive verbs. This phenomenon is illustrated by use of an optimality theory (OT) tableau. Some Vafsi ditransitive verbs dative case mark the IOs using adpositions. If so, Vafsi differential adpositional case marking (DACM) will rule, as the IOs are objects of adposition (OAs) simultaneously.
Preparation of MAO coatings doped with graphene oxide
Authors: Yang W. , Xu D. P. , Wang J. L. , Jiang B. L.
Published: July 2016

Micro arc oxidation (MAO) coatings doped with graphene oxide (GO) were prepared on the 6061 Al alloy substrates in the electrolyte composed of an aqueous solution of sodium silicate (Na2SiO3·9H2O, 20 g L−1) and 100 mg L−1 GO. The microstructure, mechanical property and tribological behaviour of the MAO + GO composite coatings were comparatively investigated. Results indicated that GO was easily dispersed into the solution for MAO coatings preparation. Little of GO in the composite coating was observed by field-emission scanning electron microscopy and energy dispersive spectrometer. This composite coating with increased proportion of α-Al2O3 phase still exhibited a porous microstructure like MAO coating but with an improved binding force, mechanical property and tribological behaviour. Furthermore, the tribological behaviour of this composite coating sliding against with hard alloy steel (YG6), silicon nitride (Si3N4) and High-carbon chromium bearing steel (GCr15) had been analysed.
Effect of post-deposition heat treatment on electrodeposited NiCoCrAlY coatings
Authors: Zhang L. Z. , Bates B. L. , Zhang Y.
Published: July 2016

An electrolytic process was utilised to fabricate NiCoCrAlY coatings, involving deposition of a composite coating consisting of the (Ni,Co) matrix and CrAlY particles, followed by a diffusion heat treatment to convert the composite coating to the desired NiCoCrAlY microstructure. This study focused on the effects of the post-deposition heat-treating conditions (temperature and atmosphere) on the final coating microstructure and composition. The (Ni,Co)–CrAlY composite coatings were heat-treated for 2 h at 1000, 1100 and 1200°C in vacuum and Ar, respectively. Phase constituents and concentrations of the major elements in the coating after heat treatment were examined. Vacuum heat treatment at temperatures ≥1100°C resulted in a significant decrease in Cr content at the coating surface due to Cr evaporation. Heat treatment at 1200°C also caused outward diffusion of Ti from the substrate alloy to the coating layer.
Microstructure and mechanical properties of pulsed laser cladded IN718 alloy coating
Authors: Zhang Y. , Yang L. , Dai J. , Liu J. , Zhang W. , Chen H. , Wang Z. , Shi K.
Published: July 2016

The pulsed laser cladded IN718 coatings were fabricated with different scanning speeds of laser cladding, the microstructure and Nb segregation in Laves phase were analysed, the microhardness and the wear resistance of the cladded coatings were investigated. The results showed that the microstructure in the pulsed laser cladded IN718 coating consisted of austenite and interdendritic Laves with Nb concentration over 27 wt-%. The microstructure was refined and Nb concentration in Laves phase was decreased by increasing scanning speed. The microhardness of the as-deposited and the heat-treated coatings was increased with increasing scanning speed due to more Nb dissolving in the austenite during the solidification and increasing main strengthening phase γ″-Ni3Nb precipitation amount during the heat treatment, respectively. The wear resistance of the pulsed laser cladded IN718 coating was improved by heat treatment and increasing scanning speed, and the wear mechanism was mainly the fatigue wear associated with the abrasive wear.
Non-monotonic growth rates of sawtooth precursors evidenced with a new method on ASDEX Upgrade
Authors: Vezinet D. , Igochine V. , Weiland M. , Yu Q. , Gude A. , Meshcheriakov D. , Sertoli M.
Published: July 2016

This paper describes a new method to derive, from soft x-ray (SXR) tomography, robust estimates of the core displacement, growth rate and frequency of a 1/1 sawtooth crash precursor. The method is valid for very peaked SXR profiles and is robust against both the inversion algorithm and the presence of tungsten in a rotating plasma. Three typical ASDEX Upgrade crashes are then analysed. In all cases a postcursor is observed, suggesting incomplete reconnection. Despite different dynamics, in all three cases the growth rate of the core displacement shows similar features. First, it is not constant, supporting the idea of non-linear growth. Second, it can be divided into clearly identified phases with quasi-constant growth rates, suggesting sudden change of growth regime rather than smooth transitions. Third, its evolution is non-monotonic, with phases of accelerated growth followed by damped phases. This damping is interpreted for two cases respectively as an effect of fast ions and of mode coupling, based on the result of a MHD simulation. The mode frequency is observed in all cases to be closely related to the plasma bulk rotation profile, with little or no visible effect of the electron diamagnetic drift frequency. The onset criterion could not be clearly identified and it is shown that the role of the pressure gradient is not as expected from a naive extrapolation of the linear stability theory.
Non-axisymmetric ideal equilibrium and stability of ITER plasmas with rotating RMPs
Authors: Ham C.J. , Cramp R.G.J. , Gibson S. , Lazerson S.A. , Chapman I.T. , Kirk A.
Published: July 2016

The magnetic perturbations produced by the resonant magnetic perturbation (RMP) coils will be rotated in ITER so that the spiral patterns due to strike point splitting which are locked to the RMP also rotate. This is to ensure even power deposition on the divertor plates. VMEC equilibria are calculated for different phases of the RMP rotation. It is demonstrated that the off harmonics rotate in the opposite direction to the main harmonic. This is an important topic for future research to control and optimize ITER appropriately. High confinement mode (H-mode) is favourable for the economics of a potential fusion power plant and its use is planned in ITER. However, the high pressure gradient at the edge of the plasma can trigger periodic eruptions called edge localized modes (ELMs). ELMs have the potential to shorten the life of the divertor in ITER (Loarte et al 2003 Plasma Phys. Control. Fusion
45 1549) and so methods for mitigating or suppressing ELMs in ITER will be important. Non-axisymmetric RMP coils will be installed in ITER for ELM control. Sampling theory is used to show that there will be significant a

n

c
o
i
l
s

−

n

r
m
p

harmonic sideband. There are nine coils toroidally in ITER so

n

c
o
i
l
s

=
9

. This results in a significant n  =  6 component to the

n

r
m
p

=
3

applied field and a significant n  =  5 component to the

n

r
m
p

=
4

applied field. Although the vacuum field has similar amplitudes of these harmonics the plasma response to the various harmonics dictates the final equilibrium. Magnetic perturbations with toroidal mode number n  =  3 and n  =  4 are applied to a 15 MA,

q

95

≈
3

burning ITER plasma. We use a three-dimensional ideal magnetohydrodynamic model (VMEC) to calculate ITER equilibria with applied RMPs and to determine growth rates of infinite n ballooning modes (COBRA). The

n

r
m
p

=
4

case shows little change in ballooning mode growth rate as the RMP is rotated, however there is a change with rotation for the

n

r
m
p

=
3

case.
Unbiased classification of spatial strategies in the Barnes maze
Authors: Illouz Tomer , Madar Ravit , Clague Charlotte , Griffioen Kathleen J. , Louzoun Yoram , Okun Eitan
Published: July 2016

Motivation: Spatial learning is one of the most widely studied cognitive domains in neuroscience. The Morris water maze and the Barnes maze are the most commonly used techniques to assess spatial learning and memory in rodents. Despite the fact that these tasks are well-validated paradigms for testing spatial learning abilities, manual categorization of performance into behavioral strategies is subject to individual interpretation, and thus to bias. We have previously described an unbiased machine-learning algorithm to classify spatial strategies in the Morris water maze.

Results: Here, we offer a support vector machine—based, automated, Barnes-maze unbiased strategy (BUNS) classification algorithm, as well as a cognitive score scale that can be used for memory acquisition, reversal training and probe trials. The BUNS algorithm can greatly benefit Barnes maze users as it provides a standardized method of strategy classification and cognitive scoring scale, which cannot be derived from typical Barnes maze data analysis.

Availability and Implementation: Freely available on the web at http://okunlab.wix.com/okunlab as a MATLAB application.

Contact:  eitan.okun@biu.ac.il

Supplementary information:  Supplementary data are available at Bioinformatics online.
ChAsE: chromatin analysis and exploration tool
Authors: Younesy Hamid , Nielsen Cydney B. , Lorincz Matthew C. , Jones Steven J.M. , Karimi Mohammad M. , Möller Torsten
Published: July 2016

Summary : We present ChAsE, a cross-platform desktop application developed for interactive visualization, exploration and clustering of epigenomic data such as ChIP-seq experiments. ChAsE is designed and developed in close collaboration with several groups of biologists and bioinformaticians with a focus on usability and interactivity. Data can be analyzed through k-means clustering, specifying presence or absence of signal in epigenetic data and performing set operations between clusters. Results can be explored in an interactive heat map and profile plot interface and exported for downstream analysis or as high quality figures suitable for publications.

Availability and Implementation: Software, source code (MIT License), data and video tutorials available at http://chase.cs.univie.ac.at .

Contact : mkarimi@brc.ubc.ca or torsten.moeller@univie.ac.at

Supplementary information:  Supplementary data are available at Bioinformatics online.
ConsPred: a rule-based (re-)annotation framework for prokaryotic genomes
Authors: Weinmaier Thomas , Platzer Alexander , Frank Jeroen , Hellinger Hans-Jörg , Tischler Patrick , Rattei Thomas
Published: July 2016

Motivation: The rapidly growing number of available prokaryotic genome sequences requires fully automated and high-quality software solutions for their initial and re-annotation. Here we present ConsPred, a prokaryotic genome annotation framework that performs intrinsic gene predictions, homology searches, predictions of non-coding genes as well as CRISPR repeats and integrates all evidence into a consensus annotation. ConsPred achieves comprehensive, high-quality annotations based on rules and priorities, similar to decision-making in manual curation and avoids conflicting predictions. Parameters controlling the annotation process are configurable by the user. ConsPred has been used in the institutions of the authors for longer than 5 years and can easily be extended and adapted to specific needs.

Summary: The ConsPred algorithm for producing a consensus from the varying scores of multiple gene prediction programs approaches manual curation in accuracy. Its rule-based approach for choosing final predictions avoids overriding previous manual curations.

Availability and implementation: ConsPred is implemented in Java, Perl and Shell and is freely available under the Creative Commons license as a stand-alone in-house pipeline or as an Amazon Machine Image for cloud computing, see https://sourceforge.net/projects/conspred/.

Contact:  thomas.rattei@univie.ac.at

Supplementary information:  Supplementary data are available at Bioinformatics online.
Recognizing metal and acid radical ion-binding sites by integrating
ab initio
modeling with template-based transferals
Authors: Hu Xiuzhen , Dong Qiwen , Yang Jianyi , Zhang Yang
Published: July 2016

Motivation: More than half of proteins require binding of metal and acid radical ions for their structure and function. Identification of the ion-binding locations is important for understanding the biological functions of proteins. Due to the small size and high versatility of the metal and acid radical ions, however, computational prediction of their binding sites remains difficult.

Results: We proposed a new ligand-specific approach devoted to the binding site prediction of 13 metal ions (Zn 2+ , Cu 2+ , Fe 2+ , Fe 3+ , Ca 2+ , Mg 2+ , Mn 2+ , Na + , K + ) and acid radical ion ligands (CO3 2− , NO2 − , SO4 2− , PO4 3− ) that are most frequently seen in protein databases. A sequence-based ab initio model is first trained on sequence profiles, where a modified AdaBoost algorithm is extended to balance binding and non-binding residue samples. A composite method IonCom is then developed to combine the ab initio model with multiple threading alignments for further improving the robustness of the binding site predictions. The pipeline was tested using 5-fold cross validations on a comprehensive set of 2,100 non-redundant proteins bound with 3,075 small ion ligands. Significant advantage was demonstrated compared with the state of the art ligand-binding methods including COACH and TargetS for high-accuracy ion-binding site identification. Detailed data analyses show that the major advantage of IonCom lies at the integration of complementary ab initio and template-based components. Ion-specific feature design and binding library selection also contribute to the improvement of small ion ligand binding predictions.

Availability and Implementation : http://zhanglab.ccmb.med.umich.edu/IonCom

Contact:  hxz@imut.edu.cn or zhng@umich.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
The SMAL web server: global multiple network alignment from pairwise alignments
Authors: Dohrmann Jakob , Singh Rahul
Published: July 2016

Motivation: Alignments of protein-protein interaction networks (PPIN) can be used to predict protein function, study conserved aspects of the interactome, and to establish evolutionary correspondences. Within this problem context, determining multiple network alignments (MNA) is a significant challenge that involves high computational complexity. A limited number of public MNA implementations are available currently and the majority of the pairwise network alignment (PNA) algorithms do not have MNA counterparts. Furthermore, current MNA algorithms do not allow choosing a specific PPIN relative to which an MNA could be constructed. Also, once an MNA is obtained, it cannot easily be modified, such as through addition of a new network, without expensive re-computation of the entire MNA.

Results: SMAL (Scaffold-Based Multiple Network Aligner) is a public, open-source, web-based application for determining MNAs from existing PNAs that addresses all the aforementioned challenges. With SMAL, PNAs can be combined rapidly to obtain an MNA. The software also supports visualization and user-data interactions to facilitate exploratory analysis and sensemaking. SMAL is especially useful when multiple alignments relative to a particular PPIN are required; furthermore, SMAL alignments are persistent in that existing correspondences between networks (obtained during PNA or MNA) are not lost as new networks are added. In comparative studies alongside existent MNA techniques, SMAL MNAs were found to be superior per a number of measures, such as the total number of identified homologs and interologs as well as the fraction of all identified correspondences that are functionally similar or homologous to the scaffold. While directed primarily at PPIN-alignment, SMAL is a generic network aligner and may be applied to arbitrary networks.

Availability information: The SMAL web server and source code is available at: http://haddock6.sfsu.edu/smal/

Contact:  rahul@sfsu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
MetaCycle: an integrated R package to evaluate periodicity in large scale data
Authors: Wu Gang , Anafi Ron C. , Hughes Michael E. , Kornacker Karl , Hogenesch John B.
Published: July 2016

Summary: Detecting periodicity in large scale data remains a challenge. While efforts have been made to identify best of breed algorithms, relatively little research has gone into integrating these methods in a generalizable method. Here, we present MetaCycle, an R package that incorporates ARSER, JTK_CYCLE and Lomb-Scargle to conveniently evaluate periodicity in time-series data. MetaCycle has two functions, meta2d and meta3d, designed to analyze two-dimensional and three-dimensional time-series datasets, respectively. Meta2d implements N-version programming concepts using a suite of algorithms and integrating their results.

Availability and implementation: MetaCycle package is available on the CRAN repository ( https://cran.r-project.org/web/packages/MetaCycle/index.html ) and GitHub ( https://github.com/gangwug/MetaCycle ).

Contact:  hogenesch@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
AMIGO2, a toolbox for dynamic modeling, optimization and control in systems biology
Authors: Balsa-Canto Eva , Henriques David , Gábor Attila , Banga Julio R.
Published: July 2016

Motivation: Many problems of interest in dynamic modeling and control of biological systems can be posed as non-linear optimization problems subject to algebraic and dynamic constraints. In the context of modeling, this is the case of, e.g. parameter estimation, optimal experimental design and dynamic flux balance analysis. In the context of control, model-based metabolic engineering or drug dose optimization problems can be formulated as (multi-objective) optimal control problems. Finding a solution to those problems is a very challenging task which requires advanced numerical methods.

Results: This work presents the AMIGO2 toolbox: the first multiplatform software tool that automatizes the solution of all those problems, offering a suite of state-of-the-art (multi-objective) global optimizers and advanced simulation approaches.

Availability and Implementation: The toolbox and its documentation are available at: sites.google.com/site/amigo2toolbox .

Contact:  ebalsa@iim.csic.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
Changes in the distribution and function of leukocytes after whole-body iron ion irradiation
Authors: Gridley Daila S. , Pecaut Michael J.
Published: July 2016

High-energy particle radiation could have a considerable impact on health during space missions. This study evaluated C57BL/6 mice on Day 40 after total-body 56 Fe 26+ irradiation at 0, 1, 2 and 3 gray (Gy). Radiation consistently increased thymus mass (one-way ANOVA: P  < 0.005); spleen, liver and lung masses were similar among all groups. In the blood, there was no radiation effect on the white blood cell (WBC) count or major leukocyte types. However, the red blood cell count, hemoglobin, hematocrit and the CD8+ T cytotoxic (Tc) cell count and percentage all decreased, while both the CD4:CD8 (Th:Tc) cell ratio and spontaneous blastogenesis increased, in one or more irradiated groups compared with unirradiated controls ( P  < 0.05 vs 0 Gy). In contrast, splenic WBC, lymphocyte, B cell and T helper (Th) counts, %B cells and the CD4:CD8 ratio were all significantly elevated, while Tc percentages decreased, in one or more of the irradiated groups compared with controls ( P  < 0.05 vs 0 Gy). Although there were trends for minor, radiation-induced increases in %CD11b+ granulocytes in the spleen, cells double-labeled with adhesion markers (CD11b+CD54+, CD11b+CD62E+) were normal. Splenocyte spontaneous blastogenesis and that induced by mitogens (PHA, ConA, LPS) was equivalent to normal. In bone marrow, the percentage of cells expressing stem cell markers, Sca-1 and CD34/Sca-1, were low in one or more of the irradiated groups ( P  < 0.05 vs 0 Gy). Collectively, the data indicate that significant immunological abnormalities still exist more than a month after 56 Fe irradiation and that there are differences dependent upon body compartment.
Smart Buyers
Authors: Burkart Mike , Lee Samuel
Published: July 2016

We study transactions in which sellers fear being underpaid because their outside option is better known to the buyer. We rationalize various observed contracts as solutions to such smart buyer problems. Key to these solutions is granting the seller upside participation. In contrast, the lemons problem calls for granting the buyer downside protection. But, in either case, the seller (buyer) receives a convex (concave) claim. Thus, contracts usually associated with the lemons problem, such as debt or cash-equity offers, can be equally well manifestations of the smart buyer problem, although the two information asymmetries have opposite cross-sectional implications.

Received December 23, 2014; accepted May 23, 2016 by Editor Uday Rajan.
Home-Based HIV Testing Among Pregnant Couples Increases Partner Testing and Identification of Serodiscordant Partnerships
Authors: Krakowiak Daisy , Kinuthia John , Osoti Alfred O. , Asila Victor , Gone Molly A. , Mark Jennifer , Betz Bourke , Parikh Saloni , Sharma Monisha , Barnabas Ruanne , Farquhar Carey
Published: July 2016

Introduction:

Male partner HIV testing has been recognized as an important component of prevention of mother-to-child HIV transmission. Scheduled home-based couple HIV testing may be an effective strategy to reach men.

Methods:

Women attending their first antenatal visit at Kisumu County Hospital in Kenya were randomized to home-based education and HIV testing within 2 weeks of enrollment (HOPE) or to written invitations for male partners to attend clinic (INVITE). Male partner HIV testing and maternal child health outcomes were compared at 6 months postpartum.

Results:

Of 1101 women screened, 620 were eligible and 601 were randomized to HOPE (n = 306) or INVITE (n = 295). At 6 months postpartum, male partners were more than twice as likely [relative risk (RR) = 2.10; 95% CI (CI): 1.81 to 2.42] to have been HIV tested in the HOPE arm [233 (87%)] compared with the INVITE arm [108 (39%)]. Couples in the HOPE arm [192 (77%)] were 3 times as likely (RR = 3.17; 95% CI: 2.53 to 3.98) to have been tested as a couple as the INVITE arm [62 (24%)] and women in the HOPE arm [217 (88%)] were also twice as likely (RR = 2.27; 95% CI: 1.93 to 2.67) to know their partner's HIV status as the INVITE arm [98 (39%)]. More serodiscordant couples were identified in the HOPE arm [33 (13%)] than in the INVITE arm [10 (4%)] (RR = 3.38; 95% CI: 1.70 to 6.71). Maternal child health outcomes of facility delivery, postpartum family planning, and exclusive breastfeeding did not vary by arm.

Conclusions:

Home-based HIV testing for pregnant couples resulted in higher uptake of male partner and couple testing, as well as higher rates of HIV status disclosure and identification of serodiscordant couples. However, the intervention did not result in higher uptake of maternal child health outcomes, because facility delivery and postpartum family planning were high in both arms, whereas exclusive breastfeeding was low. The HOPE intervention was successful at its primary aim to increase HIV testing and disclosure among pregnant couples and was able to find more serodiscordant couples compared with the invitation-only strategy.

Trial Registration:

Clinicaltrials.gov registry: NCT01784783.
Mother Infant Retention for Health (MIR4Health): Study Design, Adaptations, and Challenges With PMTCT Implementation Science Research
Authors: Fayorsey Ruby N. , Chege Duncan , Wang Chunhui , Reidy William , Peters Zachary , Syengo Masila , Barasa Chrisostim , Owino Samuel O. , Sirengo Martin , Hawken Mark P. , Abrams Elaine J.
Published: July 2016

Background:

Effective retention of HIV-infected mothers and their infants is fraught with multiple challenges, resulting in loss across the continuum of prevention of mother-to-child HIV transmission (PMTCT) care and missed opportunities to offer life-saving HIV prevention and treatment.

Methods:

The Mother Infant Retention for Health study is an individual-randomized study evaluating the effectiveness of active patient follow-up compared with standard of care on the combined outcome of attrition of HIV-infected women and their infants at 6 months postpartum. Lay counselors administered the active patient follow-up package of interventions, including individualized health education, use of flip charts during clinic visits, and at home, phone and short message service appointment reminders, active phone and physical tracking of patients immediately after missed clinic visits, and individualized retention and adherence support.

Results:

Use of study visits to indicate participant progression along the PMTCT cascade highlights the nature of loss among women and infants in PMTCT care because of issues such as pregnancy complications, infant deaths, and transfer out. Delay in implementation of Option B+, unanticipated slow enrollment, a health-care worker strike, rapid HIV test kit shortages, and changes in national PMTCT guidelines necessitated several modifications to the protocol design and implementation to ensure successful completion of the study.

Conclusions:

Flexibility when operationalizing an implementation science study is critical in the context of the shifting landscape in a noncontrolled “real-world” setting.

Trial Registration:

Clinicaltrials.gov NCT01962220.
Cost-Effectiveness of Pre-exposure HIV Prophylaxis During Pregnancy and Breastfeeding in Sub-Saharan Africa
Authors: Price Joan T. , Wheeler Stephanie B. , Stranix-Chibanda Lynda , Hosek Sybil G. , Watts D. Heather , Siberry George K. , Spiegel Hans M. L. , Stringer Jeffrey S. , Chi Benjamin H.
Published: July 2016

Introduction:

Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition is cost-effective when delivered to those at substantial risk. Despite a high incidence of HIV infection among pregnant and breastfeeding women in sub-Saharan Africa (SSA), a theoretical increased risk of preterm birth on PrEP could outweigh the HIV prevention benefit.

Methods:

We developed a decision analytic model to evaluate a strategy of daily oral PrEP during pregnancy and breastfeeding in SSA. We approached the analysis from a health care system perspective across a lifetime time horizon. Model inputs were derived from existing literature and local sources. The incremental cost-effectiveness ratio (ICER) of PrEP versus no PrEP was calculated in 2015 U.S. dollars per disability-adjusted life year (DALY) averted. We evaluated the effect of uncertainty in baseline estimates through one-way and probabilistic sensitivity analyses.

Results:

PrEP administered to pregnant and breastfeeding women in SSA was cost-effective. In a base case of 10,000 women, the administration of PrEP averted 381 HIV infections but resulted in 779 more preterm births. PrEP was more costly per person ($450 versus $117), but resulted in fewer disability-adjusted life years (DALYs) (3.15 versus 3.49). The incremental cost-effectiveness ratio of $965/DALY averted was below the recommended regional threshold for cost-effectiveness of $6462/DALY. Probabilistic sensitivity analyses demonstrated robustness of the model.

Conclusions:

Providing PrEP to pregnant and breastfeeding women in SSA is likely cost-effective, although more data are needed about adherence and safety. For populations at high risk of HIV acquisition, PrEP may be considered as part of a broader combination HIV prevention strategy.
Concept Mapping of PMTCT Implementation Challenges and Solutions Across 6 sub-Saharan African Countries in the NIH-PEPFAR PMTCT Implementation Science Alliance
Authors: Aarons Gregory A. , Sommerfeld David H. , Chi Benjamin H. , Ezeanolue Echezona E. , Sturke Rachel , Guay Laura , Siberry George K.
Published: July 2016

Objective:

Although tremendous gains have been made to reduce mother-to-child HIV transmission (MTCT) globally, evidence-based practice implementation remains inconsistent in sub-Saharan Africa. We sought to identify the key domains for effective prevention of MTCT (PMTCT) implementation, using a participatory mixed-methods approach.

Methods:

Participants were members of the NIH-PEPFAR PMTCT Implementation Science Alliance (ISA), a platform of researchers, public-health practitioners, policymakers, and donors supported through NIH/PEPFAR. We used concept mapping to identify priority areas for PMTCT implementation science. Participants responded to the focus question: “In your experience, what factors have facilitated or hindered implementation of PMTCT interventions?” Responses were consolidated into discrete statements, grouped together based on similarity, and rated for importance, changeability, and extent to which ISA participation enhanced the capacity to influence/change the factor.

Results:

Using multidimensional scaling and cluster analysis, we identified 12 key domains of PMTCT implementation. Two domains (Governmental Commitment and Data Measurement & Collection) were consistently ranked at or near the top for overall importance, perceived changeability, and enhanced ability to address through ISA participation.

Discussion:

Through a stakeholder-based, participatory approach, we identified key domains for that should be considered for future PMTCT implementation research in sub-Saharan Africa.
Short- and long-term (trophic) purinergic signalling
Authors: Burnstock Geoffrey
Published: July 2016

There is long-term (trophic) purinergic signalling involving cell proliferation, differentiation, motility and death in the development and regeneration of most systems of the body, in addition to fast purinergic signalling in neurotransmission, neuromodulation and secretion. It is not always easy to distinguish between short- and long-term signalling. For example, adenosine triphosphate (ATP) can sometimes act as a short-term trigger for long-term trophic events that become evident days or even weeks after the original challenge. Examples of short-term purinergic signalling during sympathetic, parasympathetic and enteric neuromuscular transmission and in synaptic transmission in ganglia and in the central nervous system are described, as well as in neuromodulation and secretion. Long-term trophic signalling is described in the immune/defence system, stratified epithelia in visceral organs and skin, embryological development, bone formation and resorption and in cancer. It is likely that the increase in intracellular Ca2+in response to both P2X and P2Y purinoceptor activation participates in many short- and long-term physiological effects.

This article is part of the themed issue ‘Evolution brings Ca2+and ATP together to control life and death’.
Ca2+toxicity and mitochondrial damage in acute pancreatitis: translational overview
Authors: Maléth József , Hegyi Péter
Published: July 2016

Acute pancreatitis (AP) is a leading cause of hospitalization among non-malignant gastrointestinal disorders. The mortality of severe AP can reach 30–50%, which is most probably owing to the lack of specific treatment. Therefore, AP is a major healthcare problem, which urges researchers to identify novel drug targets. Studies from the last decades highlighted that the toxic cellular Ca2+overload and mitochondrial damage are key pathogenic steps in the disease development affecting both acinar and ductal cell functions. Moreover, recent observations showed that modifying the cellular Ca2+signalling might be beneficial in AP. The inhibition of Ca2+release from the endoplasmic reticulum or the activity of plasma membrane Ca2+influx channels decreased the severity of AP in experimental models. Similarly, inhibition of mitochondrial permeability transition pore (MPTP) opening also seems to improve the outcome of AP inin vivoanimal models. At the moment MPTP blockers are under detailed clinical investigation to test whether interventions in MPTP openings and/or Ca2+homeostasis of the cells can be specific targets in prevention or treatment of cell damage in AP.

This article is part of the themed issue ‘Evolution brings Ca2+and ATP together to control life and death’.
Impairments of neural circuit function in Alzheimer's disease
Authors: Busche Marc Aurel , Konnerth Arthur
Published: July 2016

An essential feature of Alzheimer's disease (AD) is the accumulation of amyloid-β (Aβ) peptides in the brain, many years to decades before the onset of overt cognitive symptoms. We suggest that during this very extended early phase of the disease, soluble Aβ oligomers and amyloid plaques alter the function of local neuronal circuits and large-scale networks by disrupting the balance of synaptic excitation and inhibition (
E
/
I
balance) in the brain. The analysis of mouse models of AD revealed that an Aβ-induced change of the
E
/
I
balance caused hyperactivity in cortical and hippocampal neurons, a breakdown of slow-wave oscillations, as well as network hypersynchrony. Remarkably, hyperactivity of hippocampal neurons precedes amyloid plaque formation, suggesting that hyperactivity is one of the earliest dysfunctions in the pathophysiological cascade initiated by abnormal Aβ accumulation. Therapeutics that correct the
E
/
I
balance in early AD may prevent neuronal dysfunction, widespread cell loss and cognitive impairments associated with later stages of the disease.

This article is part of the themed issue ‘Evolution brings Ca
2+
and ATP together to control life and death’.
Effect of knockout of α
2
δ-1 on action potentials in mouse sensory neurons
Authors: Margas Wojciech , Ferron Laurent , Nieto-Rostro Manuela , Schwartz Arnold , Dolphin Annette C.
Published: July 2016

Gene deletion of the voltage-gated calcium channel auxiliary subunit α
2
δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α
2
δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α
2
δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α
2
δ-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca
2+
entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in α
2
δ-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca
2+
buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of α
2
δ-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca
2+
-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca
2+
elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in α
2
δ-1 knockout sensory neurons.

This article is part of the themed issue ‘Evolution brings Ca
2+
and ATP together to control life and death’.
Acid-sensing ion channels regulate spontaneous inhibitory activity in the hippocampus: possible implications for epilepsy
Authors: Ievglevskyi O. , Isaev D. , Netsyk O. , Romanov A. , Fedoriuk M. , Maximyuk O. , Isaeva E. , Akaike N. , Krishtal O.
Published: July 2016

Acid-sensing ion channels (ASICs) play an important role in numerous functions in the central and peripheral nervous systems ranging from memory and emotions to pain. The data correspond to a recent notion that each neuron and many glial cells of the mammalian brain express at least one member of the ASIC family. However, the mechanisms underlying the involvement of ASICs in neuronal activity are poorly understood. However, there are two exceptions, namely, the straightforward role of ASICs in proton-based synaptic transmission in certain brain areas and the role of the Ca
2+
-permeable ASIC1a subtype in ischaemic cell death. Using a novel orthosteric ASIC antagonist, we have found that ASICs specifically control the frequency of spontaneous inhibitory synaptic activity in the hippocampus. Inhibition of ASICs leads to a strong increase in the frequency of spontaneous inhibitory postsynaptic currents. This effect is presynaptic because it is fully reproducible in single synaptic boutons attached to isolated hippocampal neurons. In concert with this observation, inhibition of the ASIC current diminishes epileptic discharges in a low Mg
2+
model of epilepsy in hippocampal slices and significantly reduces kainate-induced discharges in the hippocampus
in vivo
. Our results reveal a significant novel role for ASICs.

This article is part of the themed issue ‘Evolution brings Ca
2+
and ATP together to control life and death’.
Hot-wiring clathrin-mediated endocytosis in human cells
Authors: Wood Laura A. , Clarke Nicholas I. , Sarkar Sourav , Royle Stephen J.
Published: July 2016

Clathrin-mediated endocytosis (CME) is the major route of receptor internalization at the plasma membrane. Analysis of constitutive CME is complicated by the fact that initiation of endocytic events is unpredictable. When and where a clathrin-coated pit will form and what cargo it will contain are difficult to foresee. Here we describe a series of genetically encoded reporters that allow the initiation of CME on demand. This is achieved by inducibly tethering a clathrin “hook” to a plasma membrane “anchor”. Our design incorporates temporal and spatial control of initiation using chemical and optical tools, and the cargo is defined. Since this system bypasses multiple steps in vesicle creation, we term it “hot-wiring”. In this paper, we use hot-wired endocytosis to define the functional interactions between clathrin and the β2 subunit of the AP2 complex. However, there are numerous applications for this new technology, which we hope will be broadly useful to the field.
HydDB: A web tool for hydrogenase classification and analysis
Authors: Dan Søndergaard , Christian N. S. Pedersen , Chris Greening
Published: July 2016

H2 metabolism is proposed to be the most ancient and diverse mechanism of energy-conservation. The metalloenzymes mediating this metabolism, hydrogenases, are encoded by over 60 microbial phyla and are present in all major ecosystems. We developed a classification system and web tool, HydDB, for the structural and functional analysis of these enzymes. We show that hydrogenase function can be predicted by primary sequence alone using an expanded classification scheme (comprising 29 [NiFe], 8 [FeFe], and 1 [Fe] hydrogenase classes) that defines 11 new classes with distinct biological functions. Using this scheme, we built a web tool that rapidly and reliably classifies hydrogenase primary sequences using a combination ofk-nearest neighbors’ algorithms and CDD referencing. Demonstrating its capacity, the tool reliably predicted hydrogenase content and function in 12 newly-sequenced bacteria, archaea, and eukaryotes. HydDB provides the capacity to browse the amino acid sequences of 3248 annotated hydrogenase catalytic subunits and also contains a detailed repository of physiological, biochemical, and structural information about the 38 hydrogenase classes defined here. The database and classifier are freely and publicly available athttp://services.birc.au.dk/hyddb/
Uncoupling of dysgranular retrosplenial “head direction” cells from the global head direction network
Authors: Jacob Pierre-Yves , Casali Giulio , Spieser Laure , Page Hector , Overington Dorothy , Jeffery Kate
Published: July 2016

Spatial cognition is an important model system with which to investigate how sensory signals are transformed into cognitive representations. Head direction cells, found in several cortical and subcortical regions, fire when an animal faces a given direction and express a global directional signal which is anchored by visual landmarks and underlies the “sense of direction”. We investigated the interface between visual and spatial cortical brain regions and report the discovery that a population of neurons in the dysgranular retrosplenial cortex, which we co-recorded with classic head direction cells in a rotationally symmetrical two-compartment environment, were dominated by a local visually defined reference frame and could be decoupled from the main head direction signal. A second population showed rotationally symmetric activity within a single sub-compartment suggestive of an acquired interaction with the head direction cells. These observations reveal an unexpected incoherence within the head direction system, and suggest that dysgranular retrosplenial cortex may mediate between visual landmarks and the multimodal sense of direction. Importantly, it appears that this interface supports a bi-directional exchange of information, which could explain how it is that landmarks can inform the direction sense while at the same time, the direction sense can be used to interpret landmarks.