bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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 &lt; 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 &lt; 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 &lt; 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 &lt; 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

Abstract
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’.
Hot-wiring clathrin-mediated endocytosis in human cells
Authors: Wood Laura A. , Clarke Nicholas I. , Sarkar Sourav , Royle Stephen J. 
Published: July 2016

AbstractClathrin-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

AbstractH2 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

AbstractSpatial 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.
Exploring the interrelationship between public service motivation and corruption theories
Authors: Kim Young Jong , Kim Eun Sil 
Published: July 2016

Purpose– The purpose of this paper is to investigate the interrelationship between public service motivation (PSM) and corruption theory. This paper further explores the possibility of integrating two theories in order to prevent corruption.Design/methodology/approach– Existing theories on PSM and corruption were briefly reviewed in finding the connection between the two theories. The discussions primarily focus on finding the theoretical and empirical interrelationship between PSM theories and corruption theories.Findings– This paper suggests applying PSM theories in preventing corruption by adding ethical dimension of PSM to corruption theories. In other words, the PSM constructs can be incorporated in developing an anti-corruption strategy. In the context of public administration, the authors find the importance of PSM theory in developing an effective anti-corruption strategy.Practical implications– Public officials should be encouraged to possess strong ethical standards in public service; highly motivated candidates for public service positions should be sought in order to create a clean and reliable government; and PSM educational programs in the early stages of schooling should be adopted to stimulate ethics for young children.Originality/value– This study adds contributions to the understanding of theoretical relationship between PSM and corruption theory. The authors suggest that integrating PSM and corruption theory can be beneficial in building new paradigms to prevent corruption in a country such as Korea.
Community relations dealing with a not in my back yard (NIMBY) context
Authors: Chung Wonjun , Choi Jinbong , Woo Chang Wan , Lee Soobum , Saindon Christina E. 
Published: July 2016

Purpose
This paper investigates whether building a nuclear power plant in a community would inherently bring local conflict phenomena such as “not in my back yard (NIMBY)”, focusing especially on the interactive effect between different types of local publics and their exposure to either a supportive or opposing message about a hypothetical local governmental plan to build a nuclear power plant on community participation intentions.

Design/methodology/approach
Applying the two theoretical frameworks (situational theory of publics and social exchange theory) to NIMBY, this study used a quantitative approach by using 471 participants in a 4 (publics: active, aware, aroused or inactive) × 2 (advocacy message type: supportive or opposing message) experimental design.

Findings
The results showed that regardless of message types, active publics were more likely to participate in community activities than any other public, but this group strongly opposed the harmful facility, while inactive publics continued to be inactive. However, aware and aroused publics were significantly influenced by messages.

Originality/value
The rationale and findings of this research are original, as they have not been published previously, and are not being simultaneously submitted elsewhere. This research should contribute to the broad body of knowledge and practices in community-based conflict issues in terms of risk management. It is believed that the discussion and implications of the findings should raise interesting areas for further research.