9,509 research outputs found

    The Type 2 Diabetes Knowledge Portal: an open access genetic resource dedicated to type 2 diabetes and related traits

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    Associations between human genetic variation and clinical phenotypes have become a foundation of biomedical research. Most repositories of these data seek to be disease-agnostic and therefore lack disease-focused views. The Type 2 Diabetes Knowledge Portal (T2DKP) is a public resource of genetic datasets and genomic annotations dedicated to type 2 diabetes (T2D) and related traits. Here, we seek to make the T2DKP more accessible to prospective users and more useful to existing users. First, we evaluate the T2DKP's comprehensiveness by comparing its datasets with those of other repositories. Second, we describe how researchers unfamiliar with human genetic data can begin using and correctly interpreting them via the T2DKP. Third, we describe how existing users can extend their current workflows to use the full suite of tools offered by the T2DKP. We finally discuss the lessons offered by the T2DKP toward the goal of democratizing access to complex disease genetic results

    Role of Molecular, Crystal, and Surface Chemistry in Directing the Crystallization of Entacapone Polymorphs on the Au(111) Template Surface

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    The pharmaceutical compound entacapone ((E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide) is important in the treatment of Parkinson’s disease, exhibiting interesting polymorphic behavior upon crystallization from solution. It consistently produces its stable form A with a uniform crystal size distribution on the surface of an Au(111) template while concomitantly forming its metastable form D within the same bulk solution. Molecular modeling using empirical atomistic force-fields reveals more complex molecular and intermolecular structures for form D compared to form A, with the crystal chemistry of both polymorphs being dominated by van der Waals and π–π stacking interactions with lower contributions (ca. 20%) from hydrogen bonding and electrostatic interactions. Comparative lattice energies and convergence for the polymorphs are consistent with the observed concomitant polymorphic behavior. Synthon characterization reveals an elongated needle-like morphology for form D crystals in contrast to the more equant form A crystals with the surface chemistry of the latter exposing the molecules’ cyano groups on its {010} and {011} habit faces. Density functional theory modeling of surface adsorption reveals preferential interactions between Au and the synthon GA interactions of form A on the Au surface. Molecular dynamics modeling of the entacapone/gold interface reveals the entacapone molecular structure within the first adsorbed layer to show nearly identical interaction distances, for both the molecules within form A or D with respect to the Au surface, while in the second and third layers when entacapone molecule–molecule interactions overtake the interactions between those of molecule–Au, the intermolecular structures are found to be closer to the form A structure than form D. In these layers, synthon GA (form A) could be reproduced with just two small azimuthal rotations (5° and 15°) whereas the closest alignment to a form D synthon requires larger azimuthal rotations (15° and 40°). The cyano functional group interactions with the Au template dominate interfacial interactions with these groups being aligned parallel to the Au surface and with nearest neighbor distances to Au atoms more closely matching those in form A than form D. The overall polymorph direction pathway thus encompasses consideration of molecular, crystal, and surface chemistry factors

    Challenges in the Design and Implementation of IoT Testbeds in Smart-Cities : A Systematic Review

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    Advancements in wireless communication and the increased accessibility to low-cost sensing and data processing IoT technologies have increased the research and development of urban monitoring systems. Most smart city research projects rely on deploying proprietary IoT testbeds for indoor and outdoor data collection. Such testbeds typically rely on a three-tier architecture composed of the Endpoint, the Edge, and the Cloud. Managing the system's operation whilst considering the security and privacy challenges that emerge, such as data privacy controls, network security, and security updates on the devices, is challenging. This work presents a systematic study of the challenges of developing, deploying and managing urban monitoring testbeds, as experienced in a series of urban monitoring research projects, followed by an analysis of the relevant literature. By identifying the challenges in the various projects and organising them under the V-model development lifecycle levels, we provide a reference guide for future projects. Understanding the challenges early on will facilitate current and future smart-cities IoT research projects to reduce implementation time and deliver secure and resilient testbeds

    Evaluation Methodologies in Software Protection Research

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    Man-at-the-end (MATE) attackers have full control over the system on which the attacked software runs, and try to break the confidentiality or integrity of assets embedded in the software. Both companies and malware authors want to prevent such attacks. This has driven an arms race between attackers and defenders, resulting in a plethora of different protection and analysis methods. However, it remains difficult to measure the strength of protections because MATE attackers can reach their goals in many different ways and a universally accepted evaluation methodology does not exist. This survey systematically reviews the evaluation methodologies of papers on obfuscation, a major class of protections against MATE attacks. For 572 papers, we collected 113 aspects of their evaluation methodologies, ranging from sample set types and sizes, over sample treatment, to performed measurements. We provide detailed insights into how the academic state of the art evaluates both the protections and analyses thereon. In summary, there is a clear need for better evaluation methodologies. We identify nine challenges for software protection evaluations, which represent threats to the validity, reproducibility, and interpretation of research results in the context of MATE attacks

    Investigating neural differentiation capacity in Alzheimer’s disease iPSC-derived neural stem cells

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    Neurodegeneration in Alzheimer’s disease (AD) may be exacerbated by dysregulated hippocampal neurogenesis. Neural stem cells (NSC) maintain adult neurogenesis and depletion of the NSC niche has been associated with age-related cognitive decline and dementia. We hypothesise that familial AD (FAD) mutations bias NSC toward premature neural specification, reducing the stem cell niche over time and accelerating disease progression. Somatic cells derived from patients with FAD (PSEN1 A246E and PSEN1 M146L heterozygous mutations) and healthy controls were reprogrammed to generate induced pluripotent stem cells (iPSC). Pluripotency for patient and control iPSC lines was confirmed, then cells were amplified and cryopreserved as stores. iPSC were subjected to neural specification to rosette-forming SOX2+/nestin+ NSCs for comparative evaluations between FAD and age-matched controls. FAD patient and control NSC were passaged under defined steady state culture conditions to assess stem cell maintenance using quantitative molecular markers (SOX2, nestin, NeuN, MAP2 and βIII-tubulin). We observed trends towards downregulated expression of the nestin coding gene NES (p=0.051) and upregulated expression of MAP2 (p=0.16) in PSEN1 NSC compared with control NSC, indicative of a premature differentiation phenotype induced by presence of the PSEN1 mutation. Cell cycle analysis of PSEN1 NSC showed that compared with controls, a greater number of PSEN1 NSC were retained in G0/G1 phase of the cell cycle (p=0.39), fewer progressed to S-phase (p=0.11) and fewer still reached G2 phase (p=0.23), suggesting cell cycle progression may be impaired in PSEN1 NSC. Nuclear DNA fragmentation was increased (p=0.10) in FAD NSC compared with controls, indicative of elevated cell death/apoptosis. Flow cytometry-based analysis of live, nestin+ NSC and NPC indicated increased apoptosis (p=0.14) in FAD NSC compared with controls, as well as increasing levels of apoptosis (p=0.33) in FAD NSC as they specified to neural progenitor cells. Global RNA sequencing was used to identify transcriptomic changes occurring during both disease and control neural specification. GO analysis of DEGs between PSEN1 and control NSC at P3 revealed significant upregulation (FDR<0.0000259) of 5 biological processes related to transcription and gene expression as well as significant upregulation (FDR<0.000000725) of 12 molecular functions related to DNA binding and transcription factor activity. These data suggest significant changes in gene expression were occurring in PSEN1 NSC at P3 compared with control NSC at the same stage in neural specification. The number of DEGs (p<0.05) between PSEN1 and control NSC at P3 was 9.92-fold higher than the number of DEGs between PSEN1 and control NSC at P2, suggesting transcriptomic differences between PSEN1 and control NSC become more pronounced as cells specify further down the neural lineage. Gene ontology (GO) analysis of differentially expressed genes (DEGs) specific to AD neural differentiation revealed significant dysregulation (FDR p<0.05) of genes related to neurogenesis, apoptosis, cell cycle, transcriptional control, and cell growth/maintenance as PSEN1 NSC matured from P2 to P3. The number of DEGs (p<0.05) in PSEN1 neural differentiation was 4.7-fold higher than the number of DEGs seen in control neural differentiation, indicating more transcriptional changes occurred in PSEN1 NSC than in controls at the same time point in neural specification. Dysregulation of Notch signalling was specific to PSEN1 neural differentiation and Notch related DEGs significantly upregulated (p<0.05) in PSEN1 NSC at P3 compared with P2 included NCOR2, JAG2, CHAC1 and RFNG. qPCR based validation displayed significant upregulation of RFNG (p=0.04) in PSEN1 NSC at P3 compared with PSEN1 NSC at P2, and indicated a trend towards upregulation of JAG2 expression, correlating with RNA sequencing data. Data generated in this study indicate that presence of the PSEN1 mutation significantly increases the number of transcriptional changes occurring during neural differentiation. It is plausible that transcriptional changes to Notch signalling cause dysregulated neural specification and increased apoptosis in PSEN1 NSC, ultimately resulting in depletion of the NSC niche

    Isolation and Characterization of Rhizospheric Bacteria Associated with Canna Plant for Production of Maltooligosaccharide Amylase

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    The objectives of the study were to isolate amylolytic bacteria from the rhizosphere and plant tissue of Canna edulis Ker., as well as litter; to know oligosaccharide compounds produced from starch hydrolyzed by the bacterial enzymes, and to identify the amylolytic bacteria based on phenetic and 16S rRNA gene sequences. From the rhizosphere, Canna plant tissue, and litters obtained thirty-two amylolytic bacterial isolates. Eight isolates (TH6, TH7, T5, T10, D2, D3, A3, S1) produced high clear zone diameters ranging from 18-30 mm; especially an isolate T10, which was consistent in producing a total clear zone diameter of 20 mm. The hydrolysate of starch hydrolysed by the T10 amylase resulted in three oligosaccharide compounds maltotriose, maltotetraose, and maltopentose. The amylase activity of isolate T10 was optimal at a temperature of 40°C and pH at 0.801 U/mL. The isolate T10 was identified as a species member of Bacillus toyonensis based on phenotyphic characterization and 16S rDNA gene sequencing analysis with a similarity value of 99.93

    Desmuntant mites biològics a l'aula de ciències. Un recopilatori dels 70 més freqüents

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    La margarida és una flor? Només tenim 5 sentits? Els éssers humans es poden dividir en races? El fred causa els refredats? La selva amazònica és el pulmó del planeta? El desdejuni és el menjar més important del dia? Només utilitzem el 10% del nostre cervell? Totes aquestes idees formen part dels models mentals de gran part de la població. Idees que, o bé parteixen de conceptes correctes, però mal aplicats, o són totalment falses. Així, a pesar de la sobreabundància d’informació que existeix en l’actualitat, la falta d’educació informacional i la difusió de tota mena de desordres informatius creen un caldo de cultiu perfecte per a la transmissió i replicació d’informació errònia. Aquest llibre persegueix no només recopilar i desmuntar 70 mites biològics emprant informació científica actualitzada, sinó també aportar activitats per a treballar-los a l'aula (principalment en els nivells educatius d’ESO i Batxillerat), recopilar recursos accessoris per a continuar indagant en els mateixos i donar eines per a desenvolupar una perspectiva crítica amb la informació que rebem. D’aquesta manera, volem contribuir a l’alfabetització científica de la població, tenint com a eixos vertebradors, la interdisciplinarietat, la perspectiva de gènere, el respecte a la diversitat, la promoció de la salut, la sostenibilitat i la cura del medi ambient.UV-SFPIE_PID-2079949UVSFPIE_ PID-1642158Are daisies flowers? Do we only have 5 senses? Can human beings be divided into races? Can cold weather or being chilled cause a cold? Is the Amazon rainforest the lung of the planet? Is breakfast the most important meal of the day? Do we humans only use 10% of our cerebral capacity? All of these ideas belong to the collective mindset of our society. Ideas that either originate from hypotheses that are correct but are poorly applied, or are totally fake. Thus, despite the excessive amounts of information that is available nowadays, the lack of informational education and diffusion of all kinds of informational disorders create a breeding ground that is ideal for the transmission and reapplication for misinformation. The aim of this book is not only to compilate and dismantle 70 biological myths using up-to-date scientific information but also contribute with activities that can be used in class (mainly for secondary school levels), compilate complementary resources to keep an inquiring mindset towards the same and assist with tools to develop a critic perspective with the information that we come across. That way, we want to promote the scientific alphabetization of the population taking interdisciplinarity, gender perspective, respect for diversity, healthcare promotion and sustainability and care for the environment as its axis

    An empirical investigation of the relationship between integration, dynamic capabilities and performance in supply chains

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    This research aimed to develop an empirical understanding of the relationships between integration, dynamic capabilities and performance in the supply chain domain, based on which, two conceptual frameworks were constructed to advance the field. The core motivation for the research was that, at the stage of writing the thesis, the combined relationship between the three concepts had not yet been examined, although their interrelationships have been studied individually. To achieve this aim, deductive and inductive reasoning logics were utilised to guide the qualitative study, which was undertaken via multiple case studies to investigate lines of enquiry that would address the research questions formulated. This is consistent with the author’s philosophical adoption of the ontology of relativism and the epistemology of constructionism, which was considered appropriate to address the research questions. Empirical data and evidence were collected, and various triangulation techniques were employed to ensure their credibility. Some key features of grounded theory coding techniques were drawn upon for data coding and analysis, generating two levels of findings. These revealed that whilst integration and dynamic capabilities were crucial in improving performance, the performance also informed the former. This reflects a cyclical and iterative approach rather than one purely based on linearity. Adopting a holistic approach towards the relationship was key in producing complementary strategies that can deliver sustainable supply chain performance. The research makes theoretical, methodological and practical contributions to the field of supply chain management. The theoretical contribution includes the development of two emerging conceptual frameworks at the micro and macro levels. The former provides greater specificity, as it allows meta-analytic evaluation of the three concepts and their dimensions, providing a detailed insight into their correlations. The latter gives a holistic view of their relationships and how they are connected, reflecting a middle-range theory that bridges theory and practice. The methodological contribution lies in presenting models that address gaps associated with the inconsistent use of terminologies in philosophical assumptions, and lack of rigor in deploying case study research methods. In terms of its practical contribution, this research offers insights that practitioners could adopt to enhance their performance. They can do so without necessarily having to forgo certain desired outcomes using targeted integrative strategies and drawing on their dynamic capabilities
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