Implementation of network entropy algorithms on hpc machines, with application to high-dimensional experimental data

Network Theory is a prolific and lively field, especially when it approaches Biology. New concepts from this theory find application in areas where extensive datasets are already available for analysis, without the need to invest money to collect them. The only tools that are necessary to accomplish an analysis are easily accessible: a computing machine and a good algorithm. As these two tools progress, thanks to technology advancement and human efforts, wider and wider datasets can be analysed. The aim of this paper is twofold. Firstly, to provide an overview of one of these concepts, which originates at the meeting point between Network Theory and Statistical Mechanics: the entropy of a network ensemble. This quantity has been described from different angles in the literature. Our approach tries to be a synthesis of the different points of view. The second part of the work is devoted to presenting a parallel algorithm that can evaluate this quantity over an extensive dataset. Eventually, the algorithm will also be used to analyse high-throughput data coming from biology.

The development and deployment of FOTOS: a fast observation of trace organics system

Flüchtige organische Bestandteile (engl.: VOC) sind in der Atmosphäre in Spuren vorhanden, spielen aber trotzdem eine wichtige Rolle in der Luftchemie: sie beeinflussen das Ozon der Troposphäre, städtischen Smog, Oxidationskapazität und haben direkte und indirekte Auswirkungen auf die globale Klimaveränderung. Eine wichtige Klasse der VOC sind die Nicht-Methan-Kohlenwasserstoffe (engl.: NMHC), die überwiegend von anthropogenen Quellen kommen. Aus diesem Grund ist für Luftchemiker ein Messinstrument nötig, das die VOC, die NMHC eingeschlossen, mit einer höheren Zeitauflösung misst, besonders für Echtzeitmessungen an Bord eines Forschungsflugzeuges. Dafür wurde das System zur schnellen Beobachtung von organischen Spuren (engl.: FOTOS) entworfen, gebaut für den Einsatz in einem neuen Wissenschaftlichen Flugzeug, das in großen Höhen und über weite Strecken fliegt, genannt HALO. In der Folge wurde FOTOS in zwei Messkampagnen am Boden getestet. FOTOS wurde entworfen und gebaut mit einem speziell angefertigten, automatisierten, kryogenen Probensystem mit drei Fallen und einem angepassten, erworbenen schnellen GC-MS. Ziel dieses Aufbaus war es, die Vielseitigkeit zu vergrößern und das Störungspotential zu verringern, deshalb wurden keine chemischen Trocknungsmittel oder adsorbierenden Stoffe verwendet. FOTOS erreichte eine Probenfrequenz von 5.5 Minuten, während es mindestens 13 verschiedene C2- bis C5-NMHC maß. Die Drei-Sigma-Detektionsgrenze für n- und iso-Pentan wurde als 2.6 und 2.0 pptv ermittelt, in dieser Reihenfolge. Labortests bestätigten, dass FOTOS ein vielseitiges, robustes, hochautomatisiertes, präzises, genaues, empfindliches Instrument ist, geeignet für Echtzeitmessungen von VOC in Probenfrequenzen, die angemessen sind für ein Forschungsflugzeug wie HALO. Um die Leistung von FOTOS zu bestätigen, wurde vom 26. Januar bis 4. Februar 2010 ein Zwischenvergleich gemacht mit dem GC-FID-System am Meteorologischen Observatorium Hohenpeißenberg, einer WMO-GAW-globalen Station. Dreizehn verschiedene NMHC wurden innerhalb des Rahmens der GWA Data Quality Objectives (DQO) analysiert und verglichen. Mehr als 80% der Messungen von sechs C3- bis C5-NMHC erfüllten diese DQO. Diese erste Messkampagne im Feld hob die Robustheit und Messgenauigkeit von FOTOS hervor, zusätzlich zu dem Vorteil der höheren Probenfrequenz, sogar in einer Messung am Boden. Um die Möglichkeiten dieses Instrumentes im Feld zu zeigen, maß FOTOS ausgewählte leichte NMHC während einer Messkampagne im Borealen Waldgebiet, HUMPPA-COPEC 2010. Vom 12. Juli bis zum 12. August 2010 beteiligte sich eine internationale Gruppe von Instituten und Instrumenten an Messungen physikalischer und chemischer Größen der Gas- und Partikelphasen der Luft über dem Borealen Wald an der SMEAR II-Station nahe Hyyttiälä, Finnland. Es wurden mehrere Hauptpunkte von Interesse im Mischungsverhältnis der Alkane und im Isomerenverhätnis von Pentan identifiziert, insbesondere sehr unterschiedliche Perioden niedriger und hoher Variabilität, drei Rauchschwaden von Biomassen-Verbrennung von russischen Waldbränden und zwei Tage mit extrem sauberer Luft aus der Polarregion. Vergleiche der NMHC mit anderen anthropogenen Indikatoren zeigten mehrere Quellen anthropogener Einflüsse am Ort auf und erlaubten eine Unterscheidung zwischen lokalen und weiter entfernten Quellen. Auf einen minimalen natürlichen Beitrag zum 24h-Kreislauf von NOx wurde geschlussfolgert aus der Korrelation von NOx mit Alkanen. Altersschätzungen der Luftmassen durch das Isomerenverhältnis von Pentan wurden erschwert durch sich verändernde Verhältnisse der Quellen und durch Besonderheiten der Photochemie während des Sommers im hohen Norden. Diese Messungen zeigten den Wert des Messens leichter NMHC, selbst in abgelegenen Regionen, als einen zusätzlichen spezifischen Marker von anthropogenem Einfluss.

Context sensitive design of provincial road Galliera SP4.

In the past centuries and before the invention of automobile, roads consisted mainly of unpaved paths connecting only few cities. Later, in the beginning of the twentieth century, the automobile was introduced and a new type of the transportation system was born. Therefore, it was necessary to change the condition of roads to fit with the automobiles. With the spread and the development of the automobiles, roads also have developed and increased all over the world. That caused negative effects on the environment and humans’ life quality. Thus, highways associations and communities had to take some steps to reduce these effects and care about environmental and cultural issues with the traditional commitment to safety and mobility, and that is known as context sensitive design. The aim of this thesis is to use the concepts of context sensitive design to reduce the negative environmental impacts of provincial road Galliera, which connects via Colombo in city of Bologna to provincial road 3 in Argelato city. Some solutions were proposed in this thesis to reduce traffic noise, fragmentation, fauna mortality and to improve the aesthetics of the road.

Identification of stock units of Mullus barbatus (Linnaeus, 1758) in the Italian seas: development of genomic 2b-RAD markers and biological variation analysis.

This thesis is settled within the STOCKMAPPING project, which represents one of the studies that were developed in the framework of RITMARE Flagship project. The main goals of STOCKMAPPING were the creation of a genomic mapping for stocks of demersal target species and the assembling of a database of population genomic, in order to identify stocks and stocks boundaries. The thesis focuses on three main objectives representing the core for the initial assessment of the methodologies and structure that would be applied to the entire STOCKMAPPING project: individuation of an analytical design to identify and locate stocks and stocks boundaries of Mullus barbatus, application of a multidisciplinary approach to validate biological methods and an initial assessment and improvement for the genotyping by sequencing technique utilized (2b-RAD). The first step is the individuation of an analytical design that has to take in to account the biological characteristics of red mullet and being representative for STOCKMAPPING commitments. In this framework a reduction and selection steps was needed due to budget reduction. Sampling areas were ranked according the individuation of four priorities. To guarantee a multidisciplinary approach the biological data associated to the collected samples were used to investigate differences between sampling areas and GSAs. Genomic techniques were applied to red mullet for the first time so an initial assessment of molecular protocols for DNA extraction and 2b-RAD processing were needed. At the end 192 good quality DNAs have been extracted and eight samples have been processed with 2b-RAD. Utilizing the software Stacks for sequences analyses a great number of SNPs markers among the eight samples have been identified. Several tests have been performed changing the main parameter of the Stacks pipeline in order to identify the most explicative and functional sets of parameters.

Stock boundaries of Parapenaeus longirostris (Lucas, 1846) populations in the Italian seas: Development of genomic 2b-RAD markers and biological variation analysis.

This thesis is developed in the contest of Ritmare project WP1, which main objective is the development of a sustainable fishery through the identification of populations boundaries in commercially important species in Italian Seas. Three main objectives are discussed in order to help reach the main purpose of identification of stock boundaries in Parapenaeus longirostris: 1 -Development of a representative sampling design for Italian seas; 2 -Evaluation of 2b-RAD protocol; 3 -Investigation of populations through biological data analysis. First of all we defined and accomplished a sampling design which properly represents all Italian seas. Then we used information and data about nursery areas distribution, abundance of populations and importance of P. longirostris in local fishery, to develop an experimental design that prioritize the most important areas to maximize the results with actual project funds. We introduced for the first time the use of 2b-RAD on this species, a genotyping method based on sequencing the uniform fragments produced by type IIB restriction endonucleases. Thanks to this method we were able to move from genetics to the more complex genomics. In order to proceed with 2b-RAD we performed several tests to identify the best DNA extraction kit and protocol and finally we were able to extract 192 high quality DNA extracts ready to be processed. We tested 2b-RAD with five samples and after high-throughput sequencing of libraries we used the software “Stacks” to analyze the sequences. We obtained positive results identifying a great number of SNP markers among the five samples. To guarantee a multidisciplinary approach we used the biological data associated to the collected samples to investigate differences between geographical samples. Such approach assures continuity with other project, for instance STOCKMED, which utilize a combination of molecular and biological analysis as well.

Design and optimization of turbo-expanders for organic rankine cycles

In a world focused on the need to produce energy for a growing population, while reducing atmospheric emissions of carbon dioxide, organic Rankine cycles represent a solution to fulfil this goal. This study focuses on the design and optimization of axial-flow turbines for organic Rankine cycles. From the turbine designer point of view, most of this fluids exhibit some peculiar characteristics, such as small enthalpy drop, low speed of sound, large expansion ratio. A computational model for the prediction of axial-flow turbine performance is developed and validated against experimental data. The model allows to calculate turbine performance within a range of accuracy of ±3%. The design procedure is coupled with an optimization process, performed using a genetic algorithm where the turbine total-to-static efficiency represents the objective function. The computational model is integrated in a wider analysis of thermodynamic cycle units, by providing the turbine optimal design. First, the calculation routine is applied in the context of the Draugen offshore platform, where three heat recovery systems are compared. The turbine performance is investigated for three competing bottoming cycles: organic Rankine cycle (operating cyclopentane), steam Rankine cycle and air bottoming cycle. Findings indicate the air turbine as the most efficient solution (total-to-static efficiency = 0.89), while the cyclopentane turbine results as the most flexible and compact technology (2.45 ton/MW and 0.63 m3/MW). Furthermore, the study shows that, for organic and steam Rankine cycles, the optimal design configurations for the expanders do not coincide with those of the thermodynamic cycles. This suggests the possibility to obtain a more accurate analysis by including the computational model in the simulations of the thermodynamic cycles. Afterwards, the performance analysis is carried out by comparing three organic fluids: cyclopentane, MDM and R245fa. Results suggest MDM as the most effective fluid from the turbine performance viewpoint (total-to-total efficiency = 0.89). On the other hand, cyclopentane guarantees a greater net power output of the organic Rankine cycle (P = 5.35 MW), while R245fa represents the most compact solution (1.63 ton/MW and 0.20 m3/MW). Finally, the influence of the composition of an isopentane/isobutane mixture on both the thermodynamic cycle performance and the expander isentropic efficiency is investigated. Findings show how the mixture composition affects the turbine efficiency and so the cycle performance. Moreover, the analysis demonstrates that the use of binary mixtures leads to an enhancement of the thermodynamic cycle performance.

Computer aided design and finite element modeling to predict bulk mechanical properties of bone scaffolds using triply periodic minimal surfaces (progettazione assistita al calcolatore ed analisi con il metodo degli elementi finiti per predire il comportamento meccanico di scaffolds ossei creati con l'uso di superfici minime periodiche in tre direzioni)

The aim of Tissue Engineering is to develop biological substitutes that will restore lost morphological and functional features of diseased or damaged portions of organs. Recently computer-aided technology has received considerable attention in the area of tissue engineering and the advance of additive manufacture (AM) techniques has significantly improved control over the pore network architecture of tissue engineering scaffolds. To regenerate tissues more efficiently, an ideal scaffold should have appropriate porosity and pore structure. More sophisticated porous configurations with higher architectures of the pore network and scaffolding structures that mimic the intricate architecture and complexity of native organs and tissues are then required. This study adopts a macro-structural shape design approach to the production of open porous materials (Titanium foams), which utilizes spatial periodicity as a simple way to generate the models. From among various pore architectures which have been studied, this work simulated pore structure by triply-periodic minimal surfaces (TPMS) for the construction of tissue engineering scaffolds. TPMS are shown to be a versatile source of biomorphic scaffold design. A set of tissue scaffolds using the TPMS-based unit cell libraries was designed. TPMS-based Titanium foams were meant to be printed three dimensional with the relative predicted geometry, microstructure and consequently mechanical properties. Trough a finite element analysis (FEA) the mechanical properties of the designed scaffolds were determined in compression and analyzed in terms of their porosity and assemblies of unit cells. The purpose of this work was to investigate the mechanical performance of TPMS models trying to understand the best compromise between mechanical and geometrical requirements of the scaffolds. The intention was to predict the structural modulus in open porous materials via structural design of interconnected three-dimensional lattices, hence optimising geometrical properties. With the aid of FEA results, it is expected that the effective mechanical properties for the TPMS-based scaffold units can be used to design optimized scaffolds for tissue engineering applications. Regardless of the influence of fabrication method, it is desirable to calculate scaffold properties so that the effect of these properties on tissue regeneration may be better understood.

Brand formative design - development and assessment of product design from a future, brand and consumer perspective

With this dissertation research we investigate intersections between design and marketing and in this respect, which factors do contribute that a product design becomes brand formative. We have developed a Brand Formative Design (BFD) framework, which investigates individual design features in a holistic, comparable, brand relevant, and consumer specific context. We discuss what kinds of characteristics contribute to BFD but also illuminate how they should be applied and examine: rnA holistic framework leading to Brand Formative Design. Identification and assessment of BFD Drivers. The dissection of products into three Distinctive Design Levels. The detection of surprising design preferences. The appropriate degree of scheme deviation with evolutionary design. Simulated BFD development processes with three different products and the integration of consumers. Future oriented objectification, comparability and assessment of design. Recommendations for the management of design in a brand specific context. Design is a product feature, which contributes significantly to the success of products. However, the development of new design contains challenges. Design can hardly be objectified; many people have an opinion concerning the attractiveness of new products but cannot formulate their future preferences. Product design is widely developed based on intuition, which can be difficult for the management of design. Here the concept of Brand Formative Design can provide a framework which contributes to structure, objectify, develop and assess new evolutionary design in brand and future relevant contexts, but also integrates consumers and their preferences without restricting creativity too much.

Comparative Study of Informal Health Care Networks and Elderly Health Status in Argentina and Cuba

The objective of this study is to evaluate the impact of informal care support networks on the health status, life satisfaction, happiness and anxiety of elderly individuals in Argentina and Cuba. Recent economic changes, demographic changes, the structure of families and changes in women?s labor participation have affected the availability of informal care. Additionally, the growing number of elderly as a percentage of total population has significant implications for both formal and informal care in Argentina and Cuba. Methods: The SABE - Survey on Health, Well-Being, and Aging in Latin America and the Caribbean, 2000 was used as the data source. The survey has a sample of 10,656 individuals aged 60 years and older residing in private households occupied by permanent dwellers in 7 cities in the Latin American and Caribbean region. My study will focus on the Buenos Aires and Havana samples in which there were 1043 individuals and 1905 individuals respectively. General sampling design was used to establish comparability between countries. Individuals requiring assistance are surveyed on their source of help and the relative impact of informal versus paid help is measured for this group. Other measures of social support (number of living children, companionship and number of individuals living in the same dwelling) are used to measure networks for the full sample. Multivariate probit regression analyses were run separately for Cuba and for Argentina to evaluate the marginal impacts of the types of social support on health status, life satisfaction, happiness and anxiety. Results: For Argentina, almost all of the family help variables positively impact good health. Getting help from most other members of the family negatively impacts satisfaction with life. Happiness is affected differently by each of the family help variables but community support increases the likelihood of being happy. Although none of the family or community help variables show statistical significance, most negatively affect anxiety levels. In Cuba, all of the social support variables have a positive marginal impact on the health status of the elderly. In this case, some of the family and community help variables have a negative marginal impact on life satisfaction; however, it appears that having those closest to the elderly, children, spouse, or other family, positively impacts life satisfaction. Most of the support variables negatively impact happiness. Receiving help from a child, spouse or parent is associated with a marginal increase in anxiety, whereas receiving help from a grandchild, another family member or a friend actually reduces anxiety. Discussion: The study highlights the necessity for enhancing the coordination of various care networks in order to provide adequate care and reduce the burdens of old age on the individual, family and society and the need for consistent support for the caregivers. More qualitative work should be done to identify how support is given and what comprises the support. The constant change and advancement of the world, and the growth of the Latin American and Caribbean region, suggests that more updates studies need to be done.

Community Genetics Reveal Elevated Levels of Sympatric Gene Flow among Morphologically Similar but Not among Morphologically Dissimilar Species of Lake Victoria Cichlid Fish

We examined genetic structure among five species of Lake Victoria haplochromine cichlids in four island communities, using a full factorial sampling design that compared genetic differentiation between pairs of species and populations of varying morphological similarity and geographical proximity. We found that allopatric conspecific populations were on average significantly more strongly differentiated than sympatric heterospecific populations of morphologically similar species. Allopatric heterospecific populations of morphologically dissimilar species were most differentiated. Our work demonstrates that phenotypic divergence can be maintained and perhaps even evolve in sympatry despite considerable gene flow between species. Conversely, phenotypic resemblance among conspecific populations can be maintained despite geographical isolation. Additionally we show that anthropogenically increased hybridization does not affect all sympatric species evenly but predominantly affects morphologically similar and closely related species. This has important implications for the evolution of reproductive isolation between species These findings are also consistent with the hypothesis of speciation reversal due to weakening of divergent selection and reproductive isolation as a consequence of habitat homogenization and offers an evolutionary mechanistic explanation for the observation that species poor assemblages in turbid areas of the lake are characterized by just one or two species in each of a few morphologically distinct genera.

Evaluation of the Design of Komendant's Cycloidal, Thin Shell Roofs At the Kimbell Art Museum Using Finite Element Analysis

The analysis of Komendant's design of the Kimbell Art Museum was carried out in order to determine the effectiveness of the ring beams, edge beams and prestressing in the shells of the roof system. Finite element analysis was not available to Komendant or other engineers of the time to aid them in the design and analysis. Thus, the use of this tool helped to form a new perspective on the Kimbell Art Museum and analyze the engineer's work. In order to carry out the finite element analysis of Kimbell Art Museum, ADINA finite element analysis software was utilized. Eight finite element models (FEM-1 through FEM-8) of increasing complexity were created. The results of the most realistic model, FEM-8, which included ring beams, edge beams and prestressing, were compared to Komendant's calculations. The maximum deflection at the crown of the mid-span surface of -0.1739 in. in FEM-8 was found to be larger than Komendant's deflection in the design documents before the loss in prestressing force (-0.152 in.) but smaller than his prediction after the loss in prestressing force (-0.3814 in.). Komendant predicted a larger longitudinal stress of -903 psi at the crown (vs. -797 psi in FEM-8) and 37 psi at the edge (vs. -347 psi in FEM-8). Considering the strength of concrete of 5000 psi, the difference in results is not significant. From the analysis it was determined that both FEM-5, which included prestressing and fixed rings, and FEM-8 can be successfully and effectively implemented in practice. Prestressing was used in both models and thus served as the main contribution to efficiency. FEM-5 showed that ring and edge beams can be avoided, however an architect might find them more aesthetically appropriate than rigid walls.

INTEGRATED ASSESSMENT OF ANTHROPOGENIC, CLIMATE, AND POLICY INDUCED CHANGES OF PHOSPHORUS EXPORT IN THE UNITED STATES LAURENTIAN GREAT LAKES WATERSHEDS

Anthropogenic activities have increased phosphorus (P) loading in tributaries to the Laurentian Great Lakes resulting in eutrophication in small bays to most notably, Lake Erie. Changes to surface water quality from P loading have resulted in billions of dollars in damage and threaten the health of the world’s largest freshwater resource. To understand the factors affecting P delivery with projected increasing urban lands and biofuels expansion, two spatially explicit models were coupled. The coupled models predict that the majority of the basin will experience a significant increase in urban area P sources while the agriculture intensity and forest sources of P will decrease. Changes in P loading across the basin will be highly variable spatially. Additionally, the impacts of climate change on high precipitation events across the Great Lakes were examined. Using historical regression relationships on phosphorus concentrations, key Great Lakes tributaries were found to have future changes including decreasing total loads and increases to high-flow loading events. The urbanized Cuyahoga watersheds exhibits the most vulnerability to these climate-induced changes with increases in total loading and storm loading , while the forested Au Sable watershed exhibits greater resilience. Finally, the monitoring network currently in place for sampling the amount of phosphorus entering the U.S. Great Lakes was examined with a focus on the challenges to monitoring. Based on these interviews, the research identified three issues that policy makers interested in maintaining an effective phosphorus monitoring network in the Great Lakes should consider: first, that the policy objectives driving different monitoring programs vary, which results in different patterns of sampling design and frequency; second, that these differences complicate efforts to encourage collaboration; and third, that methods of funding sampling programs vary from agency to agency, further complicating efforts to generate sufficient long-term data to improve our understanding of phosphorus into the Great Lakes. The dissertation combines these three areas of research to present the potential future impacts of P loading in the Great Lakes as anthropogenic activities, climate and monitoring changes. These manuscripts report new experimental data for future sources, loading and climate impacts on phosphorus.

Nuclear and plastid markers reveal the persistence of genetic identity: A new perspective on the evolutionary history of Petunia exserta

Recently divergent species that can hybridize are ideal models for investigating the genetic exchanges that can occur while preserving the species boundaries. Petunia exserta is an endemic species from a very limited and specific area that grows exclusively in rocky shelters. These shaded spots are an inhospitable habitat for all other Petunia species, including the closely related and widely distributed species P. axillaris. Individuals with intermediate morphologic characteristics have been found near the rocky shelters and were believed to be putative hybrids between P. exserta and P. axillaris, suggesting a situation where Petunia exserta is losing its genetic identity. In the current study, we analyzed the plastid intergenic spacers trnS/trnG and trnH/psbA and six nuclear CAPS markers in a large sampling design of both species to understand the evolutionary process occurring in this biological system. Bayesian clustering methods, cpDNA haplotype networks, genetic diversity statistics, and coalescence-based analyses support a scenario where hybridization occurs while two genetic clusters corresponding to two species are maintained. Our results reinforce the importance of coupling differentially inherited markers with an extensive geographic sample to assess the evolutionary dynamics of recently diverged species that can hybridize. (C) 2013 Elsevier Inc. All rights reserved.

Pharmacogenetics-based population pharmacokinetic analysis of etravirine in HIV-1 infected individuals

Objectives: Etravirine (ETV) is metabolized by cytochrome P450 (CYP) 3A, 2C9, and 2C19. Metabolites are glucuronidated by uridine diphosphate glucuronosyltransferases (UGT). To identify the potential impact of genetic and non-genetic factors involved in ETV metabolism, we carried out a two-step pharmacogenetics-based population pharmacokinetic study in HIV-1 infected individuals. Materials and methods: The study population included 144 individuals contributing 289 ETV plasma concentrations and four individuals contributing 23 ETV plasma concentrations collected in a rich sampling design. Genetic variants [n=125 single-nucleotide polymorphisms (SNPs)] in 34 genes with a predicted role in ETV metabolism were selected. A first step population pharmacokinetic model included non-genetic and known genetic factors (seven SNPs in CYP2C, one SNP in CYP3A5) as covariates. Post-hoc individual ETV clearance (CL) was used in a second (discovery) step, in which the effect of the remaining 98 SNPs in CYP3A, P450 cytochrome oxidoreductase (POR), nuclear receptor genes, and UGTs was investigated. Results: A one-compartment model with zero-order absorption best characterized ETV pharmacokinetics. The average ETV CL was 41 (l/h) (CV 51.1%), the volume of distribution was 1325 l, and the mean absorption time was 1.2 h. The administration of darunavir/ritonavir or tenofovir was the only non-genetic covariate influencing ETV CL significantly, resulting in a 40% [95% confidence interval (CI): 13–69%] and a 42% (95% CI: 17–68%) increase in ETV CL, respectively. Carriers of rs4244285 (CYP2C19*2) had 23% (8–38%) lower ETV CL. Co-administered antiretroviral agents and genetic factors explained 16% of the variance in ETV concentrations. None of the SNPs in the discovery step influenced ETV CL. Conclusion: ETV concentrations are highly variable, and co-administered antiretroviral agents and genetic factors explained only a modest part of the interindividual variability in ETV elimination. Opposing effects of interacting drugs effectively abrogate genetic influences on ETV CL, and vice-versa.

The Design of International Trade Agreements: Introducing a New Dataset

Preferential trade agreements (PTAs) have been proliferating for the last twenty years. A large literature has studied various aspects of this phenomenon. Until recently, however, many large-N studies have paid only scant attention to variation across PTAs in terms of content and design. Our contribution to this literature is a new dataset on the design of trade agreements that is the most comprehensive in terms of both variables coded and agreements covered. We illustrate the dataset’s usefulness in re-visiting the questions if and to what extent PTAs impact trade flows. The analysis shows that on average PTAs increase trade flows, but that this effect is largely driven by deep agreements. In addition, we provide evidence that provisions that tackle behind-the-border regulation matter for trade flows. The dataset’s contribution is not limited to the PTA literature, however. Broader debates on topics such as institutional design and the legalization of international relations will also benefit from the novel data.