Three-dimensional, in-silico breast phantom for multimodality image simulations

We report on the construction of anatomically realistic three-dimensional in-silico breast phantoms with adjustable sizes, shapes and morphologic features. The concept of multiscale spatial resolution is implemented for generating breast tissue images from multiple modalities. Breast epidermal boundary and subcutaneous fat layer is generated by fitting an ellipsoid and 2nd degree polynomials to reconstructive surgical data and ultrasound imaging data. Intraglandular fat is simulated by randomly distributing and orienting adipose ellipsoids within a fibrous region immediately within the dermal layer. Cooper’s ligaments are simulated as fibrous ellipsoidal shells distributed within the subcutaneous fat layer. Individual ductal lobes are simulated following a random binary tree model which is generated based upon probabilistic branching conditions described by ramification matrices, as originally proposed by Bakic et al [3, 4]. The complete ductal structure of the breast is simulated from multiple lobes that extend from the base of the nipple and branch towards the chest wall. As lobe branching progresses, branches are reduced in height and radius and terminal branches are capped with spherical lobular clusters. Biophysical parameters are mapped onto the complete anatomical model and synthetic multimodal images (Mammography, Ultrasound, CT) are generated for phantoms of different adipose percentages (40%, 50%, 60%, and 70%) and are analytically compared with clinical examples. Results demonstrate that the in-silico breast phantom has applications in imaging performance evaluation and, specifically, great utility for solving image registration issues in multimodality imaging.

Is there still a role for intraoperative enteroscopy in patients with obscure gastrointestinal bleeding?

BACKGROUND: in 21st century, endoscopic study of the small intestine has undergone a revolution with capsule endoscopy and balloon-assisted enteroscopy. The difficulties and morbidity associated with intraoperative enteroscopy, the gold-standard in the 20th century, made this technique to be relegated to a second level. AIMS: evaluate the actual role and assess the diagnostic and therapeutic value of intraoperative enteroscopy in patients with obscure gastrointestinal bleeding. PATIENTS AND METHODS: we conducted a retrospective study of 19 patients (11 males; mean age: 66.5 ± 15.3 years) submitted to 21 IOE procedures for obscure GI bleeding. Capsule endoscopy and double balloon enteroscopy had been performed in 10 and 5 patients, respectively. RESULTS: with intraoperative enteroscopy a small bowel bleeding lesion was identified in 79% of patients and a gastrointestinal bleeding lesion in 94%. Small bowel findings included: angiodysplasia (n = 6), ulcers (n = 4), small bowel Dieulafoy´s lesion (n = 2), bleeding from anastomotic vessels (n = 1), multiple cavernous hemangiomas (n = 1) and bleeding ectopic jejunal varices (n = 1). Agreement between capsule endoscopy and intraoperative enteroscopy was 70%. Endoscopic and/or surgical treatment was used in 77.8% of the patients with a positive finding on intraoperative enteroscopy, with a rebleeding rate of 21.4% in a mean 21-month follow-up period. Procedure-related mortality and postoperative complications have been 5 and 21%, respectively. CONCLUSIONS: intraoperative enteroscopy remains a valuable tool in selected patients with obscure GI bleeding, achieving a high diagnostic yield and allowing an endoscopic and/or surgical treatment in most of them. However, as an invasive procedure with relevant mortality and morbidity, a precise indication for its use is indispensable.

Probabilistic Models for Scalable Knowledge Graph Construction

In the past decade, systems that extract information from millions of Internet documents have become commonplace. Knowledge graphs -- structured knowledge bases that describe entities, their attributes and the relationships between them -- are a powerful tool for understanding and organizing this vast amount of information. However, a significant obstacle to knowledge graph construction is the unreliability of the extracted information, due to noise and ambiguity in the underlying data or errors made by the extraction system and the complexity of reasoning about the dependencies between these noisy extractions. My dissertation addresses these challenges by exploiting the interdependencies between facts to improve the quality of the knowledge graph in a scalable framework. I introduce a new approach called knowledge graph identification (KGI), which resolves the entities, attributes and relationships in the knowledge graph by incorporating uncertain extractions from multiple sources, entity co-references, and ontological constraints. I define a probability distribution over possible knowledge graphs and infer the most probable knowledge graph using a combination of probabilistic and logical reasoning. Such probabilistic models are frequently dismissed due to scalability concerns, but my implementation of KGI maintains tractable performance on large problems through the use of hinge-loss Markov random fields, which have a convex inference objective. This allows the inference of large knowledge graphs using 4M facts and 20M ground constraints in 2 hours. To further scale the solution, I develop a distributed approach to the KGI problem which runs in parallel across multiple machines, reducing inference time by 90%. Finally, I extend my model to the streaming setting, where a knowledge graph is continuously updated by incorporating newly extracted facts. I devise a general approach for approximately updating inference in convex probabilistic models, and quantify the approximation error by defining and bounding inference regret for online models. Together, my work retains the attractive features of probabilistic models while providing the scalability necessary for large-scale knowledge graph construction. These models have been applied on a number of real-world knowledge graph projects, including the NELL project at Carnegie Mellon and the Google Knowledge Graph.

Spatial behavior of two coral reef fishes within a Caribbean Marine Protected Area

A better understanding of the key ecological processes of marine organisms is fundamental to improving design and effective implementation of marine protected areas (MPAs) and marine biodiversity. The movement behavior of coral reef fish is a complex mechanism that is highly linked to species life-history traits, predation risk and food resources. We used passive acoustic telemetry to study monthly, daily and hourly movement patterns and space use in two species, Schoolmaster snapper (Lutjanus apodus) and Stoplight parrotfish (Sparisoma viride). We investigated the spatial overlap between the two species and compared intra-specific spatial overlap between day and night. Presence-absence models showed different diel presence and habitat use patterns between the two species. We constructed a spatial network of the movement patterns, which showed that for both species when fish were detected by the array of receivers most movements were made around the coral reef habitat while occasionally moving to silt habitats. Our results show that most individuals made predictable daily crepuscular migrations between different locations and habitat types, although individual behavioral changes were observed for some individuals across time. Our study also highlights the necessity to consider multiple species during MPA implementation and to take into account the specific biological and ecological traits of each species. The low number of fish detected within the receiver array, as well as the intraspecific variability observed in this study, highlight the need to compare results across species and individuals to be used for MPA management.

Development of computer application for determination of chemical diffusion properties in biological tissues

The main objective of this work was to develop an application capable of determining the diffusion times and diffusion coefficients of optical clearing agents and water inside a known type of muscle. Different types of chemical agents can also be used with the method implemented, such as medications or metabolic products. Since the diffusion times can be calculated, it is possible to describe the dehydration mechanism that occurs in the muscle. The calculation of the diffusion time of an optical clearing agent allows to characterize the refractive index matching mechanism of optical clearing. By using both the diffusion times and diffusion of water and clearing agents not only the optical clearing mechanisms are characterized, but also information about optical clearing effect duration and magnitude is obtained. Such information is crucial to plan a clinical intervention in cooperation with optical clearing. The experimental method and equations implemented in the developed application are described in throughout this document, demonstrating its effectiveness. The application was developed in MATLAB code, but the method was personalized so it better fits the application needs. This process significantly improved the processing efficiency, reduced the time to obtain he results, multiple validations prevents common errors and some extra functionalities were added such as saving application progress or export information in different formats. Tests were made using glucose measurements in muscle. Some of the data, for testing purposes, was also intentionally changed in order to obtain different simulations and results from the application. The entire project was validated by comparing the calculated results with the ones found in literature, which are also described in this document.

Bioanalytical applications of microfluidic devices

The first part of the thesis describes a new patterning technique--microfluidic contact printing--that combines several of the desirable aspects of microcontact printing and microfluidic patterning and addresses some of their important limitations through the integration of a track-etched polycarbonate (PCTE) membrane. Using this technique, biomolecules (e.g., peptides, polysaccharides, and proteins) were printed in high fidelity on a receptor modified polyacrylamide hydrogel substrate. The patterns obtained can be controlled through modifications of channel design and secondary programming via selective membrane wetting. The protocols support the printing of multiple reagents without registration steps and fast recycle times. The second part describes a non-enzymatic, isothermal method to discriminate single nucleotide polymorphisms (SNPs). SNP discrimination using alkaline dehybridization has long been neglected because the pH range in which thermodynamic discrimination can be done is quite narrow. We found, however, that SNPs can be discriminated by the kinetic differences exhibited in the dehybridization of PM and MM DNA duplexes in an alkaline solution using fluorescence microscopy. We combined this method with multifunctional encoded hydrogel particle array (fabricated by stop-flow lithography) to achieve fast kinetics and high versatility. This approach may serve as an effective alternative to temperature-based method for analyzing unamplified genomic DNA in point-of-care diagnostic.

The challenge of sales competitions.

Universities in the United Kingdom do not make provision to deliver sales-ready graduates to the economy. One means of delivering sales education is participation in university sales competitions that bring together commercial sponsors, the higher education establishment and those students who may be interested in embarking upon a sales career. This paper explores the views of a sample of Edinburgh Napier University undergraduate students who completed a survey, with both multiple choice and open-ended questions, that detailed their experience in taking part in the Russ Berrie Institute (RBI) Sales Challenge competition between 2009-2014 at the Cotsakos Business Faculty of William Paterson University, New Jersey, in the United States. Ten categories of questions were asked relating to students' sales working experience, sales education, sales jobs, skills and knowledge, their preparation for the sales challenge competition process, observations during the event, post-competition reflection, and overall benefits of taking part in the sales competition process. The findings suggest that there are multiple benefits to students, business and universities from sales challenge competitions, which deliver an overall win-win-win outcome for all stakeholders.

Asiakasarvon kehittäminen B2B-palveluyrityksessä

Yritysten välisen yhteistyön toimittajavalinta perustuu asiakasarvon määrittämiseen ja vertailuun. Tämä tutkimus tehtiin yritys A:lle asiakasarvon ymmärtämiseksi, kehittämiseksi ja asiakaspääoman kasvattamiseksi. Teoreettisesti keskeisiä käsiteltäviä teemoja ovat asiakasarvon luonti, toimittaminen ja kasvattaminen. Tutkimus on toteutettu pääasiassa kvalitatiivisesti teemahaastattelun kautta, jossa haastateltiin viittä yritys A:n asiakasyritystä. Tutkimus suunniteltiin yhdessä työn tilanneen yrityksen kanssa suhteessa aiempiin tutkimuksiin ja tavoitteisiin. Tutkimuksen tuloksissa havaittiin selviä vahvuuksia liittyen yritys A:n asiakasyritysten asiakasarvon teemoihin. Vahvuudet liittyivät muun muassa suoriin kustannuksiin, erillisiin lisäpalveluihin ja asiakaspalveluun. Kehitettävät teemat liittyivät pääasiassa työn suorittamiseen ja markkinointiin. Tulokset ovat käsitelty niin numeerisesti kuin tärkeimpinä teemoina. Asiakasarvoon ja –pääomaan liittyvistä teemoista esitetään lopuksi ratkaisuehdotus työn tilanneelle yritykselle, jota voidaan hyödyntää jatkossa ko. johtamisessa. Asiakasarvosta tulisi tehdä niin yrityskohtaisesti kuin tieteen kannalta lisää tutkimusta, sillä siinä on onnistuessaan merkittävä liiketoiminnallinen potentiaali.

Playing for Real: Designing Alternate Reality Games in Learning Contexts

Alternate Reality Game (ARG) represent a new genre of transmedia practice where players hunt for scattered clues, make sense of disparate information, and solve puzzles to advance an ever-evolving storyline. Players participate in ARGs using multiple communications technologies, ranging from print materials to mobile devices. However, many interaction design challenges must be addressed to weave these everyday communication tools together into an immersive, participatory experience. Transmedia design is not an everyday process. Designers must create and connect story bits across multiple media (video, audio, text) and multiple platforms (phones, computers, physical spaces). Furthermore, they must engage with players of varying skill levels. Few studies to-date have explored the design process of ARGs in learning contexts. Fewer still have focused on challenges involved in designing for youth (13-17 years old). In this study, I explore the process of designing ARGs as vehicles for promoting information literacy and participatory culture for adolescents (13-17 years old). Two ARG design scenarios, distinguished by target learning environment (formal and informal context) and target audience (adolescents), comprise the two cases that I examine. Through my analysis of these two design cases, I articulate several unique challenges faced by designers who create interactive, transmedia stories for – and with – youth. Drawing from these design challenges, I derive a repertoire of design strategies that future designers and researchers may use to create and implement ARGs for teens in learning contexts. In particular, I propose a narrative design framework that allows for the categorization of ARGs as storytelling constructs that lie along a continuum of participation and interaction. The framework can serve as an analytic tool for researchers and a guide for designers. In addition, I establish a framework of social roles that designers may employ to craft transmedia narratives before live launch and to promote and scaffold player participation after play begins. Overall, the contributions of my study include theoretical insights that may advance our understanding of narrative design and analysis as well as more practical design implications for designers and practitioners seeking to incorporate transmedia features into learning experiences that target youth.

Is there a health risk concerning the children´s consumption of cereal-based products? A cumulative mycotoxin risk assessment approach

Historically, the health risk of mycotoxins had been evaluated on the basis of single-chemical and single-exposure pathway scenarios. However, the co-contamination of foodstuffs with these compounds is being reported at an increasing rate and a multiple-exposure scenario for humans and vulnerable population groups as children is urgently needed. Cereals are among the first solid foods eaten by child and thus constitute an important food group of their diet. Few data are available relatively to early stages child´s exposure to mycotoxins through consumption of cereal-based foods. The present study aims to perform the cumulative risk assessment of mycotoxins present in a set of cereal-based foods including breakfast cereals (BC), processed cereal-based foods (PCBF) and biscuits (BT), consumed by children (1 to 3 years old, n=75) from Lisbon region, Portugal. Children food consumption and occurrence of 12 mycotoxins (aflatoxins, ochratoxin A, fumonisins and trichothecenes) in cereal-based foods were combined to estimate the mycotoxin daily intake, using deterministic and probabilistic approaches. Different strategies were used to treat the left censored data. For aflatoxins, as carcinogenic compounds, the margin of exposure (MoE) was calculated as a ratio of BMDL (benchmark dose lower confidence limit) and aflatoxin daily exposure. For the remaining mycotoxins, the output of exposure was compared to the dose reference values (TDI) in order to calculate the hazard quotients (HQ, ratio between exposure and a reference dose). The concentration addition (CA) concept was used for the cumulative risk assessment of multiple mycotoxins. The combined margin of exposure (MoET) and the hazard index (HI) were calculated for aflatoxins and the remaining mycotoxins, respectively. Main results revealed a significant health concern related to aflatoxins and especially aflatoxin M1 exposure according to the MoET and MoE values (below 10000), respectively. HQ and HI values for the remaining mycotoxins were below 1, revealing a low concern from a public health point of view. These are the first results on cumulative risk assessment of multiple mycotoxins present in cereal-based foods consumed by children. Considering the present results, more research studies are needed to provide the governmental regulatory bodies with data to develop an approach that contemplate the human exposure and, particularly, children, to multiple mycotoxins in food. The last issue is particularly important considering the potential synergistic effects that could occur between mycotoxins and its potential impact on human and, mainly, children health.

Paths to peace: conflict management trajectories in militarized interstate disputes

When multiple third-parties (states, coalitions, and international organizations) intervene in the same conflict, do their efforts inform one another? Anecdotal evidence suggests such a possibility, but research to date has not attempted to model this interdependence directly. The current project breaks with that tradition. In particular, it proposes three competing explanations of how previous intervention efforts affect current intervention decisions: a cost model (and a variant on it, a limited commitments model), a learning model, and a random model. After using a series of Markov transition (regime-switching) models to evaluate conflict management behavior within militarized interstate disputes in the 1946-2001 period, this study concludes that third-party intervention efforts inform one another. More specifically, third-parties examine previous efforts and balance their desire to manage conflict with their need to minimize intervention costs (the cost and limited commitments models). As a result, third-parties intervene regularly using verbal pleas and mediation, but rely significantly less frequently on legal, administrative, or peace operations strategies. This empirical threshold to the intervention costs that third-parties are willing to bear has strong theoretical foundations and holds across different time periods and third-party actors. Furthermore, the analysis indicates that the first third-party to intervene in a conflict is most likely to use a strategy designed to help the disputants work toward a resolution of their dispute. After this initial intervention, the level of third-party involvement declines and often devolves into a series of verbal pleas for peace. Such findings cumulatively suggest that disputants hold the key to effective conflict management. If the disputants adopt and maintain an extreme bargaining position or fail to encourage third-parties to accept greater intervention costs, their dispute will receive little more than verbal pleas for negotiations and peace.

Cryopreservation of somatic embryos for avocado germplasm conservation

Presently avocado germplasm is conserved ex situ in the form of field repositories across the globe including Australia. The maintenance of germplasm in the field is costly, labour and land intensive, exposed to natural disasters and always at the risk of abiotic and biotic stresses. The aim of this study was to overcome these problems using cryopreservation to store avocado (Persea americana Mill.) somatic embryos (SE). Two vitrification-based methods of cryopreservation were optimised (cryovial and droplet-vitrification) using four avocado cultivars (‘A10′, ‘Reed’, ‘Velvick’ and ‘Duke-7′). SE of the four cultivars were stored for short-term (one hour) in liquid nitrogen using the cryovial-vitrification method and showed a viability of 91%, 73%, 86% and 80% respectively. While when using the droplet vitrification method viabilities of 100%, 85% and 93% were recorded for ‘A10′, ‘Reed’ and ‘Velvick’. For long-term storage, SE of cultivars ‘A10′, ‘Reed’ and ‘Velvick’ were successfully recovered with viability of 65–100% after 3 months of LN storage. For cultivar ‘Reed’ and ‘Velvick’ SE were recovered after 12 months of LN storage with viability of 67% and 59%, respectively. The outcome of this work contributes towards the establishment of a cryopreservation protocol that is applicable across multiple avocado cultivars.

RestrictionDigest: A powerful Perl module for simulating genomic restriction digests

Background: Reduced-representation sequencing technology iswidely used in genotyping for its economical and efficient features. A popular way to construct the reduced-representation sequencing libraries is to digest the genomic DNA with restriction enzymes. A key factor of this method is to determine the restriction enzyme(s). But there are few computer programs which can evaluate the usability of restriction enzymes in reduced-representation sequencing. SimRAD is an R package which can simulate the digestion of DNA sequence by restriction enzymes and return enzyme loci number as well as fragment number. But for linkage mapping analysis, enzyme loci distribution is also an important factor to evaluate the enzyme. For phylogenetic studies, comparison of the enzyme performance across multiple genomes is important. It is strongly needed to develop a simulation tool to implement these functions. Results: Here, we introduce a Perl module named RestrictionDigest with more functions and improved performance. It can analyze multiple genomes at one run and generate concise comparison of enzyme performance across the genomes. It can simulate single-enzyme digestion, double-enzyme digestion and size selection process and generate comprehensive information of the simulation including enzyme loci number, fragment number, sequences of the fragments, positions of restriction sites on the genome, the coverage of digested fragments on different genome regions and detailed fragment length distribution. Conclusions: RestrictionDigest is an easy-to-use Perl module with flexible parameter settings.With the help of the information produced by the module, researchers can easily determine the most appropriate enzymes to construct the reduced-representation libraries to meet their experimental requirements.

Tackling health inequalities in primary care: an exploration of GPs’ experience at the frontline

In Scotland, life expectancy and health outcomes are strongly tied to socioeconomic status. Specifically, socioeconomically deprived areas suffer disproportionately from high levels of premature multimorbidity and mortality. To tackle these inequalities in health, challenges in the most deprived areas must be addressed. One avenue that merits attention is the potential role of general medical practitioners (GPs) in helping to address health inequalities, particularly due to their long-term presence in deprived communities, their role in improving patient and population health, and their potential advocacy role on behalf of their patients. GPs can be seen as what Lipsky calls ‘street-level bureaucrats’ due to their considerable autonomy in the decisions they make surrounding individual patient needs, yet practising under the bureaucratic structure of the NHS. While previous research has examined the applicability of Lipsky’s framework to the role of GPs, there has been very little research exploring how GPs negotiate between the multiple identities in their work, how GPs ‘socially construct’ their patients, how GPs view their potential role as ‘advocate’, and what this means in terms of the contribution of GPs to addressing existing inequalities in health. Using semi-structured interviews, this study explored the experience and views of 24 GPs working in some of Scotland’s most deprived practices to understand how they might combat this growing health divide via the mitigation (and potential prevention) of existing health inequalities. Participants were selected based on several criteria including practice deprivation level and their individual involvement in the Deep End project, which is an informal network comprising the 100 most deprived general practices in Scotland. The research focused on understanding GPs’ perceptions of their work including its broader implications, within their practice, the communities within which they practise, and the health system as a whole. The concept of street-level bureaucracy proved to be useful in understanding GPs’ frontline work and how they negotiate dilemmas. However, this research demonstrated the need to look beyond Lipsky’s framework in order to understand how GPs reconcile their multiple identities, including advocate and manager. As a result, the term ‘street-level professional’ is offered to capture more fully the multiple identities which GPs inhabit and to explain how GPs’ elite status positions them to engage in political and policy advocacy. This study also provides evidence that GPs’ social constructions of patients are linked not only to how GPs conceptualise the causes of health inequalities, but also to how they view their role in tackling them. In line with this, the interviews established that many GPs felt they could make a difference through advocacy efforts at individual, community and policy/political levels. Furthermore, the study draws attention to the importance of practitioner-led groups—such as the Deep End project—in supporting GPs’ efforts and providing a platform for their advocacy. Within this study, a range of GPs’ views have been explored based on the sample. While it is unclear how common these views are amongst GPs in general, the study revealed that there is considerable scope for ‘political GPs’ who choose to exercise discretion in their communities and beyond. Consequently, GPs working in deprived areas should be encouraged to use their professional status and political clout not only to strengthen local communities, but also to advocate for policy change that might potentially affect the degree of disadvantage of their patients, and levels of social and health inequalities more generally.

Filling in gaps of Drosophila melanogaster urate degradation metabolic pathway using metabolomics approaches: towards the core metabolome of the fruit fly

The primary goal of systems biology is to integrate complex omics data, and data obtained from traditional experimental studies in order to provide a holistic understanding of organismal function. One way of achieving this aim is to generate genome-scale metabolic models (GEMs), which contain information on all metabolites, enzyme-coding genes, and biochemical reactions in a biological system. Drosophila melanogaster GEM has not been reconstructed to date. Constraint-free genome-wide metabolic model of the fruit fly has been reconstructed in our lab, identifying gaps, where no enzyme was identified and metabolites were either only produced or consume. The main focus of the work presented in this thesis was to develop a pipeline for efficient gap filling using metabolomics approaches combined with standard reverse genetics methods, using 5-hydroxyisourate hydrolase (5-HIUH) as an example. 5-HIUH plays a role in urate degradation pathway. Inability to degrade urate can lead to inborn errors of metabolism (IEMs) in humans, including hyperuricemia. Based on sequence analysis Drosophila CG30016 gene was hypothesised to encode 5- HIUH. CG30016 knockout flies were examined to identify Malpighian tubules phenotype, and shortened lifespan might reflect kidney disorders in hyperuricemia in humans. Moreover, LC-MS analysis of mutant tubules revealed that CG30016 is involved in purine metabolism, and specifically urate degradation pathway. However, the exact role of the gene has not been identified, and the complete method for gap filling has not been developed. Nevertheless, thanks to the work presented here, we are a step closer towards the development of a gap-filling pipeline in Drosophila melanogaster GEM. Importantly, the areas that require further optimisation were identified and are the focus of future research. Moreover, LC-MS analysis confirmed that tubules rather than the whole fly were more suitable for metabolomics analysis of purine metabolism. Previously, Dow/Davies lab has generated the most complete tissue-specific transcriptomic atlas for Drosophila – FlyAtlas.org, which provides data on gene expression across multiple tissues of adult fly and larva. FlyAtlas revealed that transcripts of many genes are enriched in specific Drosophila tissues, and that it is possible to deduce the functions of individual tissues within the fly. Based on FlyAtlas data, it has become clear that the fly (like other metazoan species) must be considered as a set of tissues, each 2 with its own distinct transcriptional and functional profile. Moreover, it revealed that for about 30% of the genome, reverse genetic methods (i.e. mutation in an unknown gene followed by observation of phenotype) are only useful if specific tissues are investigated. Based on the FlyAtlas findings, we aimed to build a primary tissue-specific metabolome of the fruit fly, in order to establish whether different Drosophila tissues have different metabolomes and if they correspond to tissue-specific transcriptome of the fruit fly (FlyAtlas.org). Different fly tissues have been dissected and their metabolome elucidated using LC-MS. The results confirmed that tissue metabolomes differ significantly from each other and from the whole fly, and that some of these differences can be correlated to the tissue function. The results illustrate the need to study individual tissues as well as the whole organism. It is clear that some metabolites that play an important role in a given tissue might not be detected in the whole fly sample because their abundance is much lower in comparison to other metabolites present in all tissues, which prevent the detection of the tissue-specific compound.