11,434 research outputs found

    Scaling up integrated photonic reservoirs towards low-power high-bandwidth computing

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    Food biodiversity: Quantifying the unquantifiable in human diets

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    Dietary diversity is an established public health principle, and its measurement is essential for studies of diet quality and food security. However, conventional between food group scores fail to capture the nutritional variability and ecosystem services delivered by dietary richness and dissimilarity within food groups, or the relative distribution (i.e., evenness or moderation) of e.g., species or varieties across whole diets. Summarizing food biodiversity in an all-encompassing index is problematic. Therefore, various diversity indices have been proposed in ecology, yet these require methodological adaption for integration in dietary assessments. In this narrative review, we summarize the key conceptual issues underlying the measurement of food biodiversity at an edible species level, assess the ecological diversity indices previously applied to food consumption and food supply data, discuss their relative suitability, and potential amendments for use in (quantitative) dietary intake studies. Ecological diversity indices are often used without justification through the lens of nutrition. To illustrate: (i) dietary species richness fails to account for the distribution of foods across the diet or their functional traits; (ii) evenness indices, such as the Gini-Simpson index, require widely accepted relative abundance units (e.g., kcal, g, cups) and evidence-based moderation weighting factors; and (iii) functional dissimilarity indices are constructed based on an arbitrary selection of distance measures, cutoff criteria, and number of phylogenetic, nutritional, and morphological traits. Disregard for these limitations can lead to counterintuitive results and ambiguous or incorrect conclusions about the food biodiversity within diets or food systems. To ensure comparability and robustness of future research, we advocate food biodiversity indices that: (i) satisfy key axioms; (ii) can be extended to account for disparity between edible species; and (iii) are used in combination, rather than in isolation

    Identifizierung prädiktiver und prognostischer Biomarker in unterschiedlichen Tumorkompartimenten des ösophagealen Adenokarzinoms

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    Das ösophageale Adenokarzinom zeigt eine global steigende Inzidenz und hat mit einer 5-Jahres-Überlebensrate von weniger als 25% eine schlechte Prognose. Personalisierte Therapieansätze sind selten und prognostische/prädiktive Biomarker des Tumormikromilieus sind unzureichend charakterisiert. Die kumulative Promotion nähert sich dieser Problematik in drei unterschiedlichen Schwerpunkten. 1. Zur Identifizierung Kompartiment-spezifischer Biomarker wurde eine Methode entwickelt, welche als kostengünstige Alternative zum sc-Seq Expressionsprofile individueller Zelltypen generiert. Dabei erfolgt die Extraktion der RNA nicht aus Einzelzellen, sondern aus flowzytometrisch-getrennten Zellkompartimenten. Die Separation der Proben in Epithelzellen, Immunzellen und Fibroblasten wurde durch verschiedene Verfahren validiert und eine suffiziente Ausbeute an RNA auch für kleine Gewebemengen gezeigt. 2. Biomarker des Immunzellkompartiments als therapeutische Angriffspunkte wurden in einem Patientenkollektiv von bis zu 551 Patienten auf ihre Bedeutung beim EAC überprüft. Es zeigte sich eine Expression der Immuncheckpoints LAG3, VISTA und IDO auf TILs durch IHC und RNA-Sonden basierte Verfahren in einem relevanten Anteil (LAG3: 11,4%, VISTA: 29%, IDO: 52,6%). Es konnte eine prognostisch günstige Bedeutung der VISTA, LAG3 und IDO Expression gezeigt werden. Durch den Vergleich von Genexpressionsprofilen aus therapienaiven und vorbehandelten Tumoren konnte zudem ein immunsuppressiver Effekt von neoadjuvanten Therapiekonzepten auf das Tumormikromilieu des EACs gezeigt werden. Dabei kam es zur verminderten Expression von Checkpoints und Anzahl TILs nach (Radio-) Chemotherapie. 3. Im Tumorzellkompartiment wurde die Rolle von Amplifikationen in ErbB-Rezeptor abhängigen Signalwegen durch FISH-Technik und Immunhistochemie evaluiert. Es fanden sich KRAS Amplifikationen in 17,1%, PIK3CA Amplifikationen in 5% sowie eine HER2/neu-Überexpression in 14,9% der untersuchten Tumore

    Norsk rå kumelk, en kilde til zoonotiske patogener?

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    The worldwide emerging trend of eating “natural” foods, that has not been processed, also applies for beverages. According to Norwegian legislation, all milk must be pasteurized before commercial sale but drinking milk that has not been heat-treated, is gaining increasing popularity. Scientist are warning against this trend and highlights the risk of contracting disease from milkborne microorganisms. To examine potential risks associated with drinking unpasteurized milk in Norway, milk- and environmental samples were collected from dairy farms located in south-east of Norway. The samples were analyzed for the presence of specific zoonotic pathogens; Listeria monocytogenes, Campylobacter spp., and Shiga toxin-producing Escherichia coli (STEC). Cattle are known to be healthy carriers of these pathogens, and Campylobacter spp. and STEC have a low infectious dose, meaning that infection can be established by ingesting a low number of bacterial cells. L. monocytogenes causes one of the most severe foodborne zoonotic diseases, listeriosis, that has a high fatality rate. All three pathogens have caused milk borne disease outbreaks all over the world, also in Norway. During this work, we observed that the prevalence of the three examined bacteria were high in the environment at the examined farms. In addition, 7% of the milk filters were contaminated by STEC, 13% by L. monocytogenes and 4% by Campylobacter spp. Four of the STEC isolates detected were eaepositive, which is associated with the capability to cause severe human disease. One of the eae-positive STEC isolates were collected from a milk filter, which strongly indicate that Norwegian raw milk may contain potential pathogenic STEC. To further assess the possibilities of getting ill by STEC after consuming raw milk, we examined the growth of the four eae-positive STEC isolates in raw milk at different temperatures. All four isolates seemed to have ability to multiply in raw milk at 8°C, and one isolate had significant growth after 72 hours. Incubation at 6°C seemed to reduce the number of bacteria during the first 24 hours before cell death stopped. These findings highlight the importance of stable refrigerator temperatures, preferable < 4°C, for storage of raw milk. The L. monocytogenes isolates collected during this study show genetic similarities to isolates collected from urban and rural environmental locations, but different clones were predominant in agricultural environments compared to clinical and food environments. However, the results indicate that the same clone can persist in a farm over time, and that milk can be contaminated by L. monocytogenes clones present in farm environment. Despite testing small volumes (25 mL) of milk, we were able to isolate both STEC and Campylobacter spp. directly from raw milk. A proportion of 3% of the bulk tank milk and teat milk samples were contaminated by Campylobacter spp. and one STEC was isolated from bulk tank milk. L monocytogenes was not detected in bulk tank milk, nor in teat milk samples. The agricultural evolvement during the past decades have led to larger production units and new food safety challenges. Dairy cattle production in Norway is in a current transition from tie-stall housing with conventional pipeline milking systems, to modern loose housing systems with robotic milking. The occurrence of the three pathogens in this project were higher in samples collected from farms with loose housing compared to those with tiestall housing. Pasteurization of cow’s milk is a risk reducing procedure to protect consumers from microbial pathogens and in most EU countries, commercial distribution of unpasteurized milk is legally restricted. Together, the results presented in this thesis show that the animal housing may influence the level of pathogenic bacteria in the raw milk and that ingestion of Norwegian raw cow’s milk may expose consumers to pathogenic bacteria which can cause severe disease, especially in children, elderly and in persons with underlying diseases. The results also highlight the importance of storing raw milk at low temperatures between milking and consumption.Å spise mat som er mindre prosessert og mer «naturlig» er en pågående trend i Norge og i andre deler av verden. Interessen for å drikke melk som ikke er varmebehandlet, såkalt rå melk, er også økende. I Norge er det påbudt å pasteurisere melk før kommersielt salg for å beskytte forbrukeren mot sykdomsfremkallende mikroorganismer. Fagfolk advarer mot å drikke rå melk, og påpeker risikoen for å bli syk av patogene bakterier som kan finnes i melken. I denne avhandlingen undersøker vi den potensielle risikoen det medfører å drikke upasteurisert melk fra Norge. I tillegg til å samle inn tankmelk- og speneprøver fra melkegårder i sørøst Norge, samlet vi også miljøprøver fra de samme gårdene for å kartlegge forekomst og for å identifisere potensielle mattrygghetsrisikoer i melkeproduksjonen. Alle prøvene ble analysert for de zoonotiske sykdomsfremkallende bakteriene Listeria monocytogenes, Campylobacter spp., og Shiga toksin-produserende Escherichia coli (STEC). Kyr kan være friske smittebærere av disse bakteriene, som dermed kan etablere et reservoar på gårdene. Bakteriene kan overføres fra gårdsmiljøet til melkekjeden og dermed utfordre mattryggheten. Disse bakteriene har forårsaket melkebårne sykdomsutbrudd over hele verden, også i Norge. Campylobacter spp. og STEC har lav infeksiøs dose, som vil si at man kan bli syk selv om man bare inntar et lavt antall bakterieceller. L. monocytogenes kan gi sykdommen listeriose, en av de mest alvorlige matbårne zoonotiske sykdommene vi har i den vestlige verden. Resultater fra denne oppgaven viser en høy forekomst av de tre patogenene i gårdsmiljøet. I tillegg var 7% av melkefiltrene vi testet positive for STEC, 13% positive for L. monocytogenes og 4% positive for Campylobacter spp.. Fire av STEC isolatene bar genet for Intimin, eae, som er ansett som en viktig virulensfaktor som øker sjansen for alvorlig sykdom. Ett av de eae-positive isolatene ble funnet i et melkefilter, noe som indikerer at norsk rå melk kan inneholde patogene STEC. For å videre vurdere risikoen for å bli syk av STEC fra rå melk undersøkte vi hvordan de fire eae-positive isolatene vokste i rå melk lagret ved forskjellige temperaturer. For alle isolatene økte antall bakterier etter lagring ved 8°C, og for et isolat var veksten signifikant. Etter lagring ved 6°C ble antallet bakterier redusert de første 24 timene, deretter stoppet reduksjonen i antall bakterier. Disse resultatene viser hvor viktig det er å ha stabil lav lagringstemperatur for rå melk, helst < 4°C. L. monocytogenes isolatene som ble samlet inn fra melkegårdene viste genetiske likheter med isolater samlet inn fra urbane og rurale miljøer rundt omkring i Norge. Derimot var kloner som dominerte i landbruksmiljøet forskjellige fra kliniske isolater og isolater fra matproduksjonslokaler. Videre så man at en klone kan persistere på en gård over tid og at melk kan kontamineres av L. monocytogenes kloner som er til stede i gårdsmiljøet. Til tross for små testvolum av tankmelken (25 mL) fant vi både STEC og Campylobacter spp. i melkeprøvene. 3% av tankmelkprøvene og speneprøvene var positive for Campylobacter spp. og ett STEC isolat ble funnet i tankmelk. L. monocytogenes ble ikke funnet direkte i melkeprøvene. Landbruket i Norge er i stadig utvikling der besetningene blir større, men færre. Melkebesetningene er midt i en overgang der tradisjonell oppstalling med melking på bås byttes ut med løsdriftssystemer og melkeroboter. Forekomsten av de tre patogenene funnet i denne studien var høyere i besetningene med løsdrift sammenliknet med besetningene som hadde melkekyrne oppstallet på bås. Pasteurisering er et viktig forebyggende tiltak for å beskytte konsumenter fra mikrobielle patogener, og i de fleste EU-land er kommersielt salg av rå melk juridisk begrenset. Denne studien viser at oppstallingstype kan påvirke nivåene av patogene bakterier i gårdsmiljøet og i rå melk. Inntak av rå melk kan eksponere forbruker for patogene bakterier som kan gi alvorlig sykdom, spesielt hos barn, eldre og personer med underliggende sykdommer. Resultatene underbygger viktigheten av å pasteurisere melk for å sikre mattryggheten, og at det er avgjørende å lagre rå melk ved kontinuerlig lave temperaturer for å forebygge vekst av zoonotiske patogener

    Procedure-Aware Pretraining for Instructional Video Understanding

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    Our goal is to learn a video representation that is useful for downstream procedure understanding tasks in instructional videos. Due to the small amount of available annotations, a key challenge in procedure understanding is to be able to extract from unlabeled videos the procedural knowledge such as the identity of the task (e.g., 'make latte'), its steps (e.g., 'pour milk'), or the potential next steps given partial progress in its execution. Our main insight is that instructional videos depict sequences of steps that repeat between instances of the same or different tasks, and that this structure can be well represented by a Procedural Knowledge Graph (PKG), where nodes are discrete steps and edges connect steps that occur sequentially in the instructional activities. This graph can then be used to generate pseudo labels to train a video representation that encodes the procedural knowledge in a more accessible form to generalize to multiple procedure understanding tasks. We build a PKG by combining information from a text-based procedural knowledge database and an unlabeled instructional video corpus and then use it to generate training pseudo labels with four novel pre-training objectives. We call this PKG-based pre-training procedure and the resulting model Paprika, Procedure-Aware PRe-training for Instructional Knowledge Acquisition. We evaluate Paprika on COIN and CrossTask for procedure understanding tasks such as task recognition, step recognition, and step forecasting. Paprika yields a video representation that improves over the state of the art: up to 11.23% gains in accuracy in 12 evaluation settings. Implementation is available at https://github.com/salesforce/paprika.Comment: CVPR 202

    Machine Learning Research Trends in Africa: A 30 Years Overview with Bibliometric Analysis Review

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    In this paper, a critical bibliometric analysis study is conducted, coupled with an extensive literature survey on recent developments and associated applications in machine learning research with a perspective on Africa. The presented bibliometric analysis study consists of 2761 machine learning-related documents, of which 98% were articles with at least 482 citations published in 903 journals during the past 30 years. Furthermore, the collated documents were retrieved from the Science Citation Index EXPANDED, comprising research publications from 54 African countries between 1993 and 2021. The bibliometric study shows the visualization of the current landscape and future trends in machine learning research and its application to facilitate future collaborative research and knowledge exchange among authors from different research institutions scattered across the African continent

    The determinants of value addition: a crtitical analysis of global software engineering industry in Sri Lanka

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    It was evident through the literature that the perceived value delivery of the global software engineering industry is low due to various facts. Therefore, this research concerns global software product companies in Sri Lanka to explore the software engineering methods and practices in increasing the value addition. The overall aim of the study is to identify the key determinants for value addition in the global software engineering industry and critically evaluate the impact of them for the software product companies to help maximise the value addition to ultimately assure the sustainability of the industry. An exploratory research approach was used initially since findings would emerge while the study unfolds. Mixed method was employed as the literature itself was inadequate to investigate the problem effectively to formulate the research framework. Twenty-three face-to-face online interviews were conducted with the subject matter experts covering all the disciplines from the targeted organisations which was combined with the literature findings as well as the outcomes of the market research outcomes conducted by both government and nongovernment institutes. Data from the interviews were analysed using NVivo 12. The findings of the existing literature were verified through the exploratory study and the outcomes were used to formulate the questionnaire for the public survey. 371 responses were considered after cleansing the total responses received for the data analysis through SPSS 21 with alpha level 0.05. Internal consistency test was done before the descriptive analysis. After assuring the reliability of the dataset, the correlation test, multiple regression test and analysis of variance (ANOVA) test were carried out to fulfil the requirements of meeting the research objectives. Five determinants for value addition were identified along with the key themes for each area. They are staffing, delivery process, use of tools, governance, and technology infrastructure. The cross-functional and self-organised teams built around the value streams, employing a properly interconnected software delivery process with the right governance in the delivery pipelines, selection of tools and providing the right infrastructure increases the value delivery. Moreover, the constraints for value addition are poor interconnection in the internal processes, rigid functional hierarchies, inaccurate selections and uses of tools, inflexible team arrangements and inadequate focus for the technology infrastructure. The findings add to the existing body of knowledge on increasing the value addition by employing effective processes, practices and tools and the impacts of inaccurate applications the same in the global software engineering industry

    Targeting Fusion Proteins of HIV-1 and SARS-CoV-2

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    Viruses are disease-causing pathogenic agents that require host cells to replicate. Fusion of host and viral membranes is critical for the lifecycle of enveloped viruses. Studying viral fusion proteins can allow us to better understand how they shape immune responses and inform the design of therapeutics such as drugs, monoclonal antibodies, and vaccines. This thesis discusses two approaches to targeting two fusion proteins: Env from HIV-1 and S from SARS-CoV-2. The first chapter of this thesis is an introduction to viruses with a specific focus on HIV-1 CD4 mimetic drugs and antibodies against SARS-CoV-2. It discusses the architecture of these viruses and fusion proteins and how small molecules, peptides, and antibodies can target these proteins successfully to treat and prevent disease. In addition, a brief overview is included of the techniques involved in structural biology and how it has informed the study of viruses. For the interested reader, chapter 2 contains a review article that serves as a more in-depth introduction for both viruses as well as how the use of structural biology has informed the study of viral surface proteins and neutralizing antibody responses to them. The subsequent chapters provide a body of work divided into two parts. The first part in chapter 3 involves a study on conformational changes induced in the HIV-1 Env protein by CD4-mimemtic drugs using single particle cryo-EM. The second part encompassing chapters 4 and 5 includes two studies on antibodies isolated from convalescent COVID-19 donors. The former involves classification of antibody responses to the SARS-CoV-2 S receptor-binding domain (RBD). The latter discusses an anti-RBD antibody class that binds to a conserved epitope on the RBD and shows cross-binding and cross-neutralization to other coronaviruses in the sarbecovirus subgenus.</p
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