Federated Data Modeling for Built Environment Digital Twins

The digital twin (DT) approach is an enabler for data-driven decision making in architecture, engineering, construction, and operations. Various open data models that can potentially support the DT developments, at different scales and application domains, can be found in the literature. However, many implementations are based on organization-specific information management processes and proprietary data models, hindering interoperability. This article presents the process and information management approaches developed to generate a federated open data model supporting DT applications. The business process modeling notation and transaction and interaction modeling techniques are applied to formalize the federated DT data modeling framework, organized in three main phases: requirements definition, federation, validation and improvement. The proposed framework is developed adopting the cross-disciplinary and multiscale principles. A validation on the development of the federated building-level DT data model for the West Cambridge Campus DT research facility is conducted. The federated data model is used to enable DT-based asset management applications at the building and built environment levels

Communication

The geometry of reaction compartments can affect the local outcome of interface-restricted reactions. Giant unilamellar vesicles (GUVs) are commonly used to generate cell-sized, membrane-bound reaction compartments, which are, however, always spherical. Herein, we report the development of a microfluidic chip to trap and reversibly deform GUVs into cigar-like shapes. When trapping and elongating GUVs that contain the primary protein of the bacterial Z ring, FtsZ, we find that membrane-bound FtsZ filaments align preferentially with the short GUV axis. When GUVs are released from this confinement and membrane tension is relaxed, FtsZ reorganizes reversibly from filaments into dynamic rings that stabilize membrane protrusions; a process that allows reversible GUV deformation. We conclude that microfluidic traps are useful for manipulating both geometry and tension of GUVs, and for investigating how both affect the outcome of spatially-sensitive reactions inside them, such as that of protein self-organization.We acknowledge the MPIB Biochemistry Core Facility for assistance in protein purification

Charm Production in DPMJET

In this work, charm production in the {\sc dpmjet} hadronic jet simulation is compared to experimental data. Since the major application of {\sc dpmjet} is the simulation of cosmic ray-induced air showers, the version of the code integrated in the CORSIKA simulation package has been used for the comparison. Wherever necessary, adjustments have been made to improve agreement between simulation and data. With the availability of new muon/neutrino detectors that combine a large fiducial volume with large amounts of shielding, investigation of prompt muons and neutrinos from cosmic ray interactions will be feasible for the first time. Furthermore, above $\gtrsim 100$ TeV charmed particle decay becomes the dominant background for diffuse extraterrestrial neutrino flux searches. A reliable method to simulate charm production in high-energy proton-nucleon interactions is therefore required.Comment: 10 pages, to be published in JCA

Molecular mechanism of Gαi activation by non-GPCR proteins with a Gα-Binding and Activating motif

Heterotrimeric G proteins are quintessential signalling switches activated by nucleotide exchange on Gα. Although activation is predominantly carried out by G-protein-coupled receptors (GPCRs), non-receptor guanine-nucleotide exchange factors (GEFs) have emerged as critical signalling molecules and therapeutic targets. Here we characterize the molecular mechanism of G-protein activation by a family of non-receptor GEFs containing a Gα-binding and -activating (GBA) motif. We combine NMR spectroscopy, computational modelling and biochemistry to map changes in Gα caused by binding of GBA proteins with residue-level resolution. We find that the GBA motif binds to the SwitchII/α3 cleft of Gα and induces changes in the G-1/P-loop and G-2 boxes (involved in phosphate binding), but not in the G-4/G-5 boxes (guanine binding). Our findings reveal that G-protein-binding and activation mechanisms are fundamentally different between GBA proteins and GPCRs, and that GEF-mediated perturbation of nucleotide phosphate binding is sufficient for Gα activation

Cost-Utility Analysis of a Medication Adherence Management Service Alongside a Cluster Randomized Control Trial in Community Pharmacy.

Background: It is necessary to determine the cost utility of adherence interventions in chronic diseases due to humanistic and economic burden of non-adherence. Purpose: To evaluate, alongside a cluster-randomized controlled trial, the cost-utility of a pharmacist-led medication adherence management service (MAMS) compared with usual care in community pharmacies. Materials and Methods: The trial was conducted over six months. Patients with treatments for hypertension, asthma or chronic obstructive pulmonary disease (COPD) were included. Patients in the intervention group (IG) received a MAMS based on a brief complex intervention, whilst patients in the control group (CG) received usual care. The cost–utility analysis adopted a health system perspective. Costs related to medications, healthcare resources and adherence intervention were included. The effectiveness was estimated as quality-adjusted life years (QALYs), using a multiple imputation missing data model. The incremental cost–utility ratio (ICUR) was calculated on the total sample of patients. Results: A total of 1186 patients were enrolled (IG: 633; CG: 553). The total intervention cost was estimated to be € 27.33 ± 0.43 per patient for six months. There was no statistically significant difference in total cost of medications and healthcare resources per patient between IG and CG. The values of EQ-5D-5L at 6 months were significantly higher in the IG [IG: 0.881 ± 0.005 vs CG: 0.833 ± 0.006; p = 0.000]. In the base case, the service was more expensive and more effective than usual care, resulting in an ICUR of € 1,494.82/QALY. In the complete case, the service resulted in an ICUR of € 2,086.30/QALY, positioned between the north-east and south-east quadrants of the cost–utility plane. Using a threshold value of € 20,000/QALY gained, there is a 99% probability that the intervention is cost-effective. Conclusion: The medication adherence management service resulted in an improvement in the quality of life of the population with chronic disease, with similar costs compared to usual care. The service is cost-effective

Characterization of Oral Enterobacteriaceae Prevalence and Resistance Profile in Chronic Kidney Disease Patients Undergoing Peritoneal Dialysis

Chronic Kidney Disease (CKD) is a growing public-health concern worldwide. Patients exhibit compromised immunity and are more prone to infection than other populations. Therefore, oral colonization by clinically relevant members of the Enterobacteriaceae family, major agents of both nosocomial and dialysis-associated infections with frequent prevalence of antibiotic resistances, may constitute a serious risk. Thus, this study aimed to assess the occurrence of clinically relevant enterobacteria and their antibiotic resistance profiles in the oral cavity of CKD patients undergoing peritoneal dialysis (CKD-PD) and compare it to healthy controls. Saliva samples from all the participants were cultured on MacConkey Agar and evaluated regarding the levels of urea, ammonia, and pH. Bacterial isolates were identified and characterized for antibiotic resistance phenotype and genotype. The results showed that CKD-PD patients exhibited significantly higher salivary pH, urea, and ammonia levels than controls, that was accompanied by higher prevalence and diversity of oral enterobacteria. Out of all the species isolated, only the prevalence of Raoultella ornithinolytica varied significantly between groups, colonizing the oral cavity of approximately 30% of CKD-PD patients while absent from controls. Antibiotic resistance phenotyping revealed mostly putative intrinsic resistance phenotypes (to amoxicillin, ticarcillin, and cephalothin), and resistance to sulfamethoxazole (~43% of isolates) and streptomycin (~17%). However, all isolates were resistant to at least one of the antibiotics tested and multidrug resistance isolates were only found in CKD-PD group (31,6%). Mobile genetic elements and resistance genes were detected in isolates of the species Raoultella ornithinolytica, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, and Enterobacter asburiae, mostly originated from CKD-PD patients. PD-related infection history revealed that Enterobacteriaceae were responsible for ~8% of peritonitis and ~ 16% of exit-site infections episodes in CKD-PD patients, although no association was found to oral enterobacteria colonization at the time of sampling. The results suggest that the CKD-induced alterations of the oral milieu might promote a dysbiosis of the commensal oral microbiome, namely the proliferation of clinically relevant Enterobacteriaceae potentially harboring acquired antibiotic resistance genes. This study highlights the importance of the oral cavity as a reservoir for pathobionts and antibiotic resistances in CKD patients undergoing peritoneal dialysis.This work is a result of the project POCI-01-0145-FEDER-029777, co-financed by Competitiveness and Internationalisation Operational Programme (POCI), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and through national funds by the FCT – Fundação para a Ciência e a Tecnologia. CC fellowship was supported by FCT/MCTES scholarship with the reference 2020.08540.BD. This work and CF were financially supported by FEDER through project “Assessing the risks associated with environmental antibiotic resistant bacteria: propagation and transmission to humans” (PTDC/CTA-AMB/28196/2017) – Programa Operacional Competitividade e Internacionalização, and by National Funds from FCT – Fundação para a Ciência e a Tecnologia and was hosted by CBQF through FCT project UIDB/50016/2020

Tailoring block copolymer nanoporous thin films with acetic acid as a small guest molecule

Block copolymers offer the fabrication of mesoporous thin films with distinct nanoscale structural features. In this contribution, we present the use of acetic acid (CH3COOH) as a low‐molecular‐weight guest molecule to tune the supramolecular assembly of poly[styrene‐block‐(4‐vinylpyridine)] (PS‐b‐P4VP), offering a versatile and straightforward method to obtain tailored nanostructured films with controlled topography and pore size. Spin‐coating toluene solutions of PS‐b‐P4VP, with a variable amount of CH3COOH, leads to micellar thin films, where the micelles contain the carboxylic acid as a guest molecule. The size can be conveniently modified in these films (from 48 to 75 nm) by varying the amount of organic acid in the starting solutions. Subsequent surface reconstruction of micellar films using ethanol leads to ring‐shaped copolymer nanoporous films with modulated diameter. Controlling the micelle reconstruction process, cylindrical porous films are also obtained. Interestingly, changing the type of aliphatic carboxylic acid leads to a modification of the observed film morphology from micelles to out‐of‐plane P4VP cylinders (or lamellae) in a PS matrix

Guiding the humoral response against HIV-1 toward a MPER adjacent region by immunization with a VLP-formulated antibody-selected envelope variant

Preventive HIV-1 vaccine strategies rely on the elicitation of broadly neutralizing antibody (bNAb) responses, but their induction in vivo by vaccination remains challenging. Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region). Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop. Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env. Furthermore, the amino acids specific for the selected variant are associated with an increased sensitivity for 4E10 and 2F5 antibodies. In vivo studies showed that sera from mice immunized with LR1-C1 viruses possessed an improved neutralizing activity compared to the wild-type AC10_29 env. While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region. Our data establish a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions

Effectiveness of a medication adherence management intervention in a community pharmacy setting: a cluster randomised controlled trial

BackgroundNon-adherence to medications continues to be a burden worldwide, with significant negative consequences. Community pharmacist interventions seem to be effective at improving medication adherence. However, more evidence is needed regarding their impact on disease-specific outcomes. The aim was to evaluate the impact of a community pharmacist-led adherence management intervention on adherence and clinical outcomes in patients with hypertension, asthma and chronic obstructive pulmonary disease (COPD).MethodsA 6-month cluster randomised controlled trial was conducted in Spanish community pharmacies. Patients suffering from hypertension, asthma and COPD were recruited. Patients in the intervention group received a medication adherence management intervention and the control group received usual care. The intervention was based on theoretical frameworks for changing patient behaviour. Medication adherence, disease-specific outcomes (Asthma Control Questionnaire (ACQ) scores, Clinical COPD Questionnaire (CCQ) scores and blood pressure levels) and disease control were evaluated. A multilevel regression model was used to analyse the data.ResultsNinety-eight pharmacies and 1186 patients were recruited, with 1038 patients completing the study. Patients receiving the intervention had an OR of 5.12 (95% CI 3.20 to 8.20, pConclusionsA community pharmacist-led medication adherence intervention was effective at improving medication adherence and clinical outcomes in patients suffering from hypertension, asthma and COPD. Future research should explore the implementation of these interventions in routine practice.Trial registration numberACTRN12618000410257