Exploring 4d and 5d analysis in bim environment for infrastructures: A case study

Building Information Modelling (BIM) has emerged as a focal point in the construction industry, garnering substantial attention due to its capacity to elevate product quality, facilitate accurate quantity determination, and enhance scheduling efficiency. The inherent complexity of construction projects necessitates the integration of BIM models endowed with automation functionalities for schedules and cost estimation. This integration ensures that updates seamlessly occur throughout the construction process, thereby mitigating project uncertainties and reducing overall costs. While the potential benefits of BIM are recognized, a substantial challenge persists in the Architecture, Engineering, and Construction (AEC) field defining workflows for the automated generation of optimized 4D/5D BIM simulation and analysis. The effective utilization of BIM as a transformative tool requires addressing this challenge to unlock its full potential in project management. BIM serves as a pivotal conduit for project data, providing a structured approach to elevate overall product quality, streamline processes, and minimize contingencies and costs associated with construction projects. Consequently, the successful implementation of BIM with automated 4D/5D simulation and analysis stands as a critical milestone in advancing the capabilities of the AEC industry, ensuring greater efficiency, accuracy, and cost-effectiveness in construction projects. According to these aspects, the time-cost analysis (4D/5D) of a project for the North-South railway station in Riyadh, designed by Architect Engineer Dia Hilal, was investigated

A model independent and rephase invariant parametrization of CP violation

The phenomenological description of the neutral B meson system is proposed in terms of the fundamental CP-violating observables and within a rephasing invariant formalism. This generic formalism can select the time-dependent and time-integrated asymmetries which provide the basic tools to discriminate the different kinds of possible CP-violating effects in dedicated experimental B-meson facilities.Comment: 19 pages, Plain Te

Functional characterization of the sea urchin sns chromatin insulator in erythroid cells

Chromatin insulators are regulatory elements that determine domains of genetic functions. We have previously described the characterization of a 265 bp insulator element, termed sns, localized at the 3' end of the early historic H2A gene of the sea urchin Paracentrotus lividus. This sequence contains three cis-acting elements (Box A, Box B, and Box C+T) all needed for the enhancer-blocking activity in both sea urchin and human cells. The goal of this Study was to further characterize the sea urchin sns insulator in the erythroid environment. We employed colony assays in human (K562) and mouse (MEL) erythroid cell lines. We tested the capability of sns to interfere with the communication between the 5HS2 enhancer of the human beta-globin LCR and the gamma-globin promoter. We found that the sns sequence displays directional enhancer-blocking activity. By the use of antibodies against known DNA binding proteins, in electrophoretic mobility shift assays, we demonstrated the binding of the erythroid-specific GATA-1 and the ubiquitous Oct-1 and Sp1 transcription factors. These factors bind to Box A, Box B, and Box C+T, respectively, in both K562 and MEL nuclear extracts. These results may have significant implications for the conservation of insulator function ill evolutionary distant organisms and may prove to be of practical benefit in gene transfer applications for erythroid disorders such as hemoglobinopathies and thalassemias

Wharton’s Jelly Mesenchymal Stromal Cells Support the Expansion of Cord Blood–derived CD34 + Cells Mimicking a Hematopoietic Niche in a Direct Cell–cell Contact Culture System

Wharton’s jelly mesenchymal stromal cells (WJ-MSCs) have been recently exploited as a feeder layer in coculture systems to expand umbilical cord blood–hematopoietic stem/progenitor cells (UCB-HSPCs). Here, we investigated the role of WJ-MSCs in supporting ex vivo UCB-HSPC expansion either when cultured in direct contact (DC) with WJ-MSCs or separated by a transwell system or in the presence of WJ-MSC–conditioned medium. We found, in short-term culture, a greater degree of expansion of UCB-CD34 + cells in a DC system (15.7 ± 4.1-fold increase) with respect to the other conditions. Moreover, in DC, we evidenced two different CD34 + cell populations (one floating and one adherent to WJ-MSCs) with different phenotypic and functional characteristics. Both multipotent CD34 + /CD38 − and lineage-committed CD34 + /CD38 + hematopoietic progenitors were expanded in a DC system. The former were significantly more represented in the adherent cell fraction than in the floating one (18.7 ± 11.2% vs. 9.7 ± 7.9% over the total CD34 + cells). Short-term colony forming unit (CFU) assays showed that HSPCs adherent to the stromal layer were able to generate a higher frequency of immature colonies (CFU-granulocyte/macrophage and burst-forming unit erythroid/large colonies) with respect to the floating cells. In the attempt to identify molecules that may play a role in supporting the observed ex vivo HSPC growth, we performed secretome analyses. We found a number of proteins involved in the HSPC homing, self-renewal, and differentiation in all tested conditions. It is important to note that a set of sixteen proteins, which are only in part reported to be expressed in any hematopoietic niche, were exclusively found in the DC system secretome. In conclusion, WJ-MSCs allowed a significant ex vivo expansion of multipotent as well as committed HSPCs. This may be relevant for future clinical applications

The sea urchin sns5 chromatin insulator settles a gene therapy vector into an independent domain of expression in the vertebrate genome

One of the critical aspects of introducing a transgene into the eukaryotic genome is the great variability of gene expression due to position effects (1). Chromatin-dependent repressive states could be overcome by incorporation in the transgene of chromatin insulators, functioning to establish and delimit domains of expression. We have previously demonstrated that the sea urchin sns5 DNA element has the typical features of an insulator: by acting as enhancer blocker, it shields promoters from neighboring regulatory elements, and by acting as barrier it buffers a transgene from the propagation of condensed chromatin (2,3). We have investigated the use of sns5 in the field of gene therapy. Our preliminary studies shown that the inclusion of sns5 in \uf0e3-retroviral vectors allows position-independent expression in erythroid cells (4). Moreover, transcription factors and histone modifications mark the sns5 chromatin at the integration site (4), suggesting that sns5 displays mechanisms of action common to other well characterized insulators. Here we show that sns5 increases the likelihood and the expression of a \uf062-globin/lentiviral vector integrated as a single copy in both murine cell clones and in a mouse model of \uf062-thalassemia. It has been proposed that two copies of insulators may direct the formation of a chromatin loop by interaction among protein complexes assembled on their sequences (5). Intriguingly, by using the 3C technology, we found that sns5-flanked vectors integrated at a single copy in the resident genome are specifically organized into an independent chromatin structure. Our findings highlight that sns5 could be a promising tool for improving the performance of vectors in the field of gene therapy. 1. Gaszner and Felsenfeld (2006). Nat Rev Genet 7:703-13 2. Palla et al (1997). PNAS USA 94:2272-7 3. Cavalieri et al (2009). Nucleic Acids Res 37:7407-15 4. D'Apolito et al (2009). Mol Ther 17:1434-41 5. Wallace and Felsenfeld (2007). Curr Op Genet Dev 17:400-

Probing SUSY-induced CP violations at B factories

In the minimal supersymmetric standard model (MSSM), the \mu-parameter and the trilinear coupling A_t may be generically complex and can affect various observables at B factories. Imposing the edm constraints, we find that there is no new large phase shift in the B^0 - \bar{B^0} mixing, CP violating dilepton asymmetry is smaller than 0.1 %, and the direct CP violation in B\to X_s \gamma can be as large as \sim \pm 16 %.Comment: 4 pages, 2 figures. Version to appear in Phys. Rev. Let

Evolution of migraine-associated symptoms in menstrually related migraine following symptomatic treatment with almotriptan

In addition to headache, migraine is characterized by a series of symptoms that negatively affects the quality of life of patients. Generally, these are represented by nausea, vomiting, photophobia, phonophobia and osmophobia, with a cumulative percentage of the onset in about 90% of the patients. From this point of view, menstrually related migraine—a particularly difficult-to-treat form of primary headache—is no different from other forms of migraine. Symptomatic treatment should therefore be evaluated not only in terms of headache relief, but also by considering its effect on these migraine-associated symptoms (MAS). Starting from the data collected in a recently completed multicentre, randomized, double-blind, placebo-controlled, cross-over study with almotriptan in menstrually related migraine, an analysis of the effect of this drug on the evolution of MAS was performed. Data suggest that almotriptan shows excellent efficacy on MAS in comparison to the placebo, with a significant reduction in the percentages of suffering patients over a 2-h period of time

Star Architecture as Socio-Material Assemblage

Taking inspiration from new materialism and assemblage, the chapter deals with star architects and iconic buildings as socio-material network effects that do not pre-exist action, but are enacted in practice, in the materiality of design crafting and city building. Star architects are here conceptualized as part of broader assemblages of actors and practices ‘making star architecture’ a reality, and the buildings they design are considered not just as unique and iconic objects, but dis-articulated as complex crafts mobilizing skills, technologies, materials, and forms of knowledge not necessarily ascribable to architecture. Overcoming narrow criticism focusing on the symbolic order of icons as unique creations and alienated repetitions of capitalist development, the chapter’s main aim is to widen the scope of critique by bridging culture and economy, symbolism and practicality, making star architecture available to a broad, fragmented arena of (potential) critics, unevenly equipped with critical tools and differentiated experiences

CD28 between tolerance and autoimmunity: The side effects of animal models [version 1; referees: 2 approved]

Regulation of immune responses is critical for ensuring pathogen clearance and for preventing reaction against self-antigens. Failure or breakdown of immunological tolerance results in autoimmunity. CD28 is an important co-stimulatory receptor expressed on T cells that, upon specific ligand binding, delivers signals essential for full T-cell activation and for the development and homeostasis of suppressive regulatory T cells. Many in vivo mouse models have been used for understanding the role of CD28 in the maintenance of immune homeostasis, thus leading to the development of CD28 signaling modulators that have been approved for the treatment of some autoimmune diseases. Despite all of this progress, a deeper understanding of the differences between the mouse and human receptor is required to allow a safe translation of pre-clinical studies in efficient therapies. In this review, we discuss the role of CD28 in tolerance and autoimmunity and the clinical efficacy of drugs that block or enhance CD28 signaling, by highlighting the success and failure of pre-clinical studies, when translated to humans

Scaling the nexus: towards integrated frameworks for analysing water, energy and food

The emergence of the water-energy-food (WEF) nexus concept following the 2011 Bonn Nexus Conference has resulted in a change to the way we perceive our natural resources. Global pressures such as climate change, and population growth have highlighted the fragility of our WEF systems, necessitating integrated solutions across multiple scales and levels. Whilst a number of frameworks and analytical tools have been developed since 2011, a comprehensive WEF nexus tool remains elusive, hindered in part by our limited data and understanding of the interdependencies and connections across the WEF systems. To achieve this, the community of academics, practitioners and policy-makers invested in WEF nexus research are addressing several critical areas that currently remain as barriers. Firstly, the plurality of scales (e.g., spatial, temporal, institutional, jurisdictional) necessitates a more comprehensive effort to assess interdependencies between water, energy and food, from household to institutional and national levels. Secondly, and closely related to scale, a lack of available data often hinders our ability to quantify physical stocks and flows of resources. In this paper, we elucidate many of the challenges that have arisen across nexus research, including the impact of multiple scales in operation across the nexus, and concomitantly, what impact these scales have on data accessibility. We review some of the critical frameworks and tools that are applied by nexus researchers and discuss some of the steps required to develop from nexus thinking to an operationalizable concept, with a consistent focus on scale and data availability