In July 2018 entered into force new provisions of European law about package travel and other travel services and their sale by organizers and retailers to consumers. The new legislative framework is ...a direct consequence of the changes that came on the travel market in the last decades and it expresses the European legislator's pursuit of the changes concerned to be adequately reflected in the legal order. The subjects of this study are the main principles of Directive (EU) 2015/2302 on package travel and linked travel arrangements and their role in improving the protection of travel services consumers. In particular, the article analyzes issues relating to the scope of protection of the new Directive about consumers, the meaning of the term “package travel”, the trader's obligation to provide certain information to the consumer before concluding the contract, the rights arising out of the contract, the liability for the proper performance of a package, the means of protection in case of organizer’s insolvency.
A fundamental question in developmental biology is how the early embryo establishes the spatial coordinate system that is later important for the organization of the embryonic body plan. Although we ...know a lot about the signaling and gene-regulatory networks required for this process, much less is understood about how these can operate to pattern tissues in the context of the extensive cell movements that drive gastrulation. In zebrafish, germ layer specification depends on the inheritance of maternal mRNAs 1–3, cortical rotation to generate a dorsal pole of β-catenin activity 4–8, and the release of Nodal signals from the yolk syncytial layer (YSL) 9–12. To determine whether germ layer specification is robust to altered cell-to-cell positioning, we separated embryonic cells from the yolk and allowed them to develop as spherical aggregates. These aggregates break symmetry autonomously to form elongated structures with an anterior-posterior pattern. Both forced reaggregation and endogenous cell mixing reveals how robust early axis specification is to spatial disruption of maternal pre-patterning. During these movements, a pole of Nodal signaling emerges that is required for explant elongation via the planar cell polarity (PCP) pathway. Blocking of PCP-dependent elongation disrupts the shaping of opposing poles of BMP and Wnt/TCF activity and the anterior-posterior patterning of neural tissue. These results lead us to suggest that embryo elongation plays a causal role in timing the exposure of cells to changes in BMP and Wnt signal activity during zebrafish gastrulation.
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•Whole-zebrafish 256-cell stage embryo explants elongate•Patterned germ layers are established•Mesoderm formation is robust to extensive cell mixing•Inhibition of morphogenesis blocks formation of signaling gradients
Fulton et al. demonstrate that, through explanting zebrafish blastomeres, termed pescoids, at the 256-cell stage, embryonic cells have the potential to form mesoderm, even in the absence of yolk-derived pre-pattern information caused by extensive cell mixing. Blocking explant morphogenesis results in failure to correctly pattern the neural tissue.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Tissue cell polarity plays a major role in plant and animal development. We propose that a fundamental building block for tissue cell polarity is the process of intracellular partitioning, which can ...establish individual cell polarity in the absence of asymmetric cues. Coordination of polarities may then arise through cell-cell coupling, which can operate directly, through membrane-spanning complexes, or indirectly, through diffusible molecules. Polarity is anchored to tissues through organisers located at boundaries. We show how this intracellular partitioning-based framework can be applied to both plant and animal systems, allowing different processes to be placed in a common evolutionary and mechanistic context.
The COVID-19 pandemic caused the education system to suddenly move from offline to online learning, so it takes a variety of effective learning design trials. This research aims to find out the ...effectiveness of the advance organiser learning model assisted by the Zoom Meeting application. This research was conducted at State Junior High School 3 Binamu, Jeneponto Regency. The research sample was 20 people. The research was conducted with an embedded design model of mixed methods. The findings show that the online advance organiser learning model uses an effective Zoom Meeting application for use, where 1) the application of advance organiser learning has a positive relationship with student learning outcomes; 2) the implementation of learning takes place in the category of ‘good’; 3) students’ positive activities increase in each meeting and 4) students respond well to the implementation of the advance organiser learning model/ using the Zoom Meeting application. The implementation of advance organiser online learning using the Zoom Meeting application, however, is no more effective when compared to the implementation of learning conducted offline or under normal conditions.
Nucleolar organiser regions (NORs) are loops of DNA which are responsible for ribosomal RNA (rRNA) transcription in the nucleus of cells. NORs can be selectively stained by silver methods. The NORs ...agyrophilia is due to a group of nucleolar proteins, which have affinity for silver (Agyrophilic Nucleolar Organizer Regions, AgNOR proteins). The aim of the present study is to assess proliferative index in different grades of invasive ductal carcinoma (IDC) by using AgNOR as a marker. A total of 18 formalin fixed paraffin-embedded breast tissue blocks were retrieved from the archives of the histopathology department of the Komfo Anokye Teaching Hospital, Ghana. The tissue blocks included 17 IDC, (with 8 as grade 2 IDC, 9 as grade 3 IDC) and 1 normal breast tissues. Tissue sections were diagnosed and graded following haematoxylin and eosin (H&E) staining. Silver staining was used to demonstrate the presence of AgNOR. The AgNOR dots were manually counted in 50 and 100 cells. The mean AgNOR count (mAgNOR) and proliferative index, (pAgNOR, percentage of cells with ≥5 AgNOR dots per nucleus), significantly increased with increasing grade of IDC. The mAgNOR and pAgNOR were low in normal breast, (at p-value less than 0.05). There was no significant difference in the mAgNOR and pAgNOR score for counting 50 and 100 cells (at a p-value of 0.01). mAgNOR and pAgOR increases with increase in grade of IDC and hence can be used to assess proliferative index of IDC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In order to generate the tissues and organs of a multicellular organism, different cell types have to be generated during embryonic development. The first step in this process of cellular ...diversification is the formation of the three germ layers: ectoderm, endoderm and mesoderm. The ectoderm gives rise to the nervous system, epidermis and various neural crest-derived tissues, the endoderm goes on to form the gastrointestinal, respiratory and urinary systems as well as many endocrine glands, and the mesoderm will form the notochord, axial skeleton, cartilage, connective tissue, trunk muscles, kidneys and blood. Classic experiments in amphibian embryos revealed the tissue interactions involved in germ layer formation and provided the groundwork for the identification of secreted and intracellular factors involved in this process. We will begin this review by summarising the key findings of those studies. We will then evaluate them in the light of more recent genetic studies that helped clarify which of the previously identified factors are required for germ layer formation in vivo, and to what extent the mechanisms identified in amphibians are conserved across other vertebrate species. Collectively, these studies have started to reveal the gene regulatory network (GRN) underlying vertebrate germ layer specification and we will conclude our review by providing examples how our understanding of this GRN can be employed to differentiate stem cells in a targeted fashion for therapeutic purposes.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
As part of a remarkable wave of perennial contemporary art events in Thailand, the Bangkok Biennial was organised for the first time in 2018. Without central curation or funding, the organisational ...strategy of this artist‐led, open‐access event was strikingly different from the state‐organised Thailand Biennale and the corporate Bangkok Art Biennale that were inaugurated several months later. Through the eyes of the literature on “commoning” as a third way of organising next to the state and market, we explore the “common spaces” that the Bangkok Biennial has produced. Reflecting on arguments articulated in the introduction to this thematic issue, as well as on Chantal Mouffe’s analysis of the detrimental nature of an “exodus strategy” for counter‐hegemonic action, we focus on the connections—if any—of the Bangkok Biennial with the state and corporations. Specifically, we address the following research questions: What are the characteristics of the Bangkok Biennial as a common art event? Which connections with the state and market have its organisers developed? And what are the consequences of this strategy for its sustainability and counter‐hegemonic potential? We conclude that the organisers have consciously resisted developing relationships with the state and market, and argue that this “exodus strategy” is a necessity in Thailand’s socio‐political setting. And while this strategy might endanger the sustainability of this biennial as an art event, we argue that at the same time it supports an infrastructure for counter‐hegemonic action inside and—possibly more importantly—outside art.
Suboptimal medication adherence is a significant threat to public health and resources. Devices that organise weekly doses by time and day are commonly used to reduce unintentional non-adherence. ...However, there is limited evidence to support their use. This systematic review was conducted to evaluate current evidence for their efficacy, safety and costs.
A pre-defined search of electronic databases from inception to January 2013 augmented with hand-searching was conducted. No limits were placed on publication date. Studies that compared organisation devices used by patients administering their own medication with standard medication packaging regardless of study design were eligible for inclusion. Studies that solely explored dispensing aspects of organisation devices were included whether or not they compared this to standard care. Screening of articles for inclusion and data extraction were completed independently by two reviewers with disagreements resolved by discussion. Outcomes were categorised into impact on health, medication adherence, healthcare utilisation, dispensing errors, supply procedures and costs. Risk of bias was also assessed.
Seventeen studies met the inclusion criteria. Health outcomes were investigated in seven studies of which three reported a positive effect associated with organisation devices. Medication adherence was reported in eight studies of which three reported a positive effect. Three studies reported health care utilisation data but overall results are inconclusive. No optimal dispensing or supply procedures were identified. Economic assessment of the impact of organisation devices is lacking. All studies were subject to a high risk of bias.
Evidence regarding the effects of medication organisation devices was limited, and the available evidence was susceptible to a high risk of bias. Organisation devices may help unintentional medication non-adherence and could improve health outcomes. There is a strong need for more studies that explore the impact of such devices on patients, and an equally pressing need for studies that explore the impacts on healthcare services.
This systematic review is registered with PROSPERO (Registration number CRD42011001718 ).
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CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Automated Storage and Retrieval systems are widely used in warehouse management due to their high uptime reliability and effective management. In India most of the warehouses and supermarkets refill ...their goods manually to avoid the high cost of automation. This situation can be avoided by implementing a storage and retrieval organiser which acts according to the user. In this project an Automated Storage Organiser (ASO) with 3 degree of freedom (DOF) has been built to handle light weight goods of about 1kg. The storage organiser detects the product on arrival and stores it automatically, retrieval is done by using a graphical user interface developed using LabVIEW software. The model has been developed using CATIA software and fabricated by necessary actuators and sensors. The main processing unit is Atmel ATmega 326. Virtual control module has been developed by using LabVIEW graphical programming software in computer so that user can directly control and monitor the movement of the system. Arduino programming has been used to develop a closed loop control algorithm for accuracy in position and speed control
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Local self-activation and long ranging inhibition provide a mechanism for setting up organising regions as signalling centres for the development of structures in the surrounding tissue. The adult ...hydra hypostome functions as head organiser. After hydra head removal it is newly formed and complete heads can be regenerated. The molecular components of this organising region involve Wnt-signalling and β-catenin. However, it is not known how correct patterning of hypostome and tentacles are achieved in the hydra head and whether other signals in addition to HyWnt3 are needed for re-establishing the new organiser after head removal. Here we show that Notch-signalling is required for re-establishing the organiser during regeneration and that this is due to its role in restricting tentacle activation. Blocking Notch-signalling leads to the formation of irregular head structures characterised by excess tentacle tissue and aberrant expression of genes that mark the tentacle boundaries. This indicates a role for Notch-signalling in defining the tentacle pattern in the hydra head. Moreover, lateral inhibition by HvNotch and its target HyHes are required for head regeneration and without this the formation of the β-catenin/Wnt dependent head organiser is impaired. Work on prebilaterian model organisms has shown that the Wnt-pathway is important for setting up signalling centres for axial patterning in early multicellular animals. Our data suggest that the integration of Wnt-signalling with Notch-Delta activity was also involved in the evolution of defined body plans in animals.
•Notch-signalling in hydra is required for patterning the adult head.•Notch-signalling defines a sharp boundary for tentacle tissue in the tentacle zone.•In the absence of Notch-signalling Wnt3a is not expressed in the regenerating tip.•Notch inhibition prevents formation of a new head organiser after head removal.•During head regeneration Notch-signalling suppresses tentacle fate of precursor cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP