Digital Triplet Approach for Real-Time Monitoring and Control of an Elevator Security System

As Digital Twins gain more traction and their adoption in industry increases, there is a need to integrate such technology with machine learning features to enhance functionality and enable decision making tasks. This has lead to the emergence of a concept known as Digital Triplet; an enhancement of Digital Twin technology through the addition of an ’intelligent activity layer’. This is a relatively new technology in Industrie 4.0 and research efforts are geared towards exploring its applicability, development and testing of means for implementation and quick adoption. This paper presents the design and implementation of a Digital Triplet for a three-floor elevator system. It demonstrates the integration of a machine learning (ML) object detection model and the system Digital Twin. This was done to introduce an additional security feature that enabled the system to make a decision, based on objects detected and take preliminary security measures. The virtual model was designed in Siemens NX and programmed via Total Integrated Automation (TIA) portal software. The corresponding physical model was fabricated and controlled using a Programmable Logic Controller (PLC) S7 1200. A control program was developed to mimic the general operations of a typical elevator system used in a commercial building setting. Communication, between the physical and virtual models, was enabled using the OPC-Unified Architecture (OPC-UA) protocol. Object recognition using “You only look once” (YOLOV3) based machine learning algorithm was incorporated. The Digital Triplet’s functionality was tested, ensuring the virtual system duplicated actual operations of the physical counterpart through the use of sensor data. Performance testing was done to determine the impact of the ML module on the real-time functionality aspect of the system. Experiment results showed the object recognition contributed an average of 1.083s to an overall signal travel time of 1.338 s

Cost-effectiveness of implementing a digital psychosocial intervention for patients with psychotic spectrum disorders in low- and middle-income countries in Southeast Europe: Economic evaluation alongside a cluster randomised trial

BACKGROUND: DIALOG+ is a digital psychosocial intervention aimed at making routine meetings between patients and clinicians therapeutically effective. This study aimed to evaluate the cost-effectiveness of implementing DIALOG+ treatment for patients with psychotic disorders in five low- and middle-income countries in Southeast Europe alongside a cluster randomised trial. METHODS: Resource use and quality of life data were collected alongside the multi-country cluster randomised trial of 468 participants with psychotic disorders. Due to COVID-19 interruptions of the trial’s original 12-month intervention period, adjusted costs and quality-adjusted life years (QALYs) were estimated at the participant level using a mixed-effects model over the first 6 months only. We estimated the incremental cost-effectiveness ratio (ICER) with uncertainty presented using a cost-effectiveness plane and a cost-effectiveness acceptability curve. Seven sensitivity analyses were conducted to check the robustness of the findings. RESULTS: The average cost of delivering DIALOG+ was €91.11 per participant. DIALOG+ was associated with an incremental health gain of 0.0032 QALYs (95% CI –0.0015, 0.0079), incremental costs of €84.17 (95% CI –8.18, 176.52), and an estimated ICER of €26,347.61. The probability of DIALOG+ being cost-effective against three times the weighted gross domestic product (GDP) per capita for the five participating countries was 18.9%. CONCLUSION: Evidence from the cost-effectiveness analyses in this study suggested that DIALOG+ involved relatively low costs. However, it is not likely to be cost-effective in the five participating countries compared with standard care against a willingness-to-pay threshold of three times the weighted GDP per capita per QALY gained

Beating the confusion limit: The necessity of high angular resolution for probing the physics of Sagittarius A* and its environment: Opportunities for LINC-NIRVANA (LBT), GRAVITY (VLTI) and and METIS (E-ELT)

The super-massive 4 million solar mass black hole (SMBH) SgrA* shows variable emission from the millimeter to the X-ray domain. A detailed analysis of the infrared light curves allows us to address the accretion phenomenon in a statistical way. The analysis shows that the near-infrared flux density excursions are dominated by a single state power law, with the low states of SgrA* limited by confusion through the unresolved stellar background. We show that for 8-10m class telescopes blending effects along the line of sight will result in artificial compact star-like objects of 0.5-1 mJy that last for about 3-4 years. We discuss how the imaging capabilities of GRAVITY at the VLTI, LINC-NIRVANA at the LBT and METIS at the E-ELT will contribute to the investigation of the low variability states of SgrA*.Comment: 19 pages, 5 figure, Conf. Proc. SPIE Astronomical Telescopes + Instrumentation 1 - 6 July 2012. Amsterdam No. 8445-

Single-cell sequencing of the human midbrain reveals glial activation and a neuronal state specific to Parkinson's disease

Parkinson's disease (PD) etiology is associated with genetic and environmental factors that lead to a loss of dopaminergic neurons. However, the functional interpretation of PD-associated risk variants and how other midbrain cells contribute to this neurodegenerative process are poorly understood. Here, we profiled >41,000 single-nuclei transcriptomes of postmortem midbrain tissue from 6 idiopathic PD (IPD) patients and 5 matched controls. We show that PD-risk variants are associated with glia- and neuron-specific gene expression patterns. Furthermore, Microglia and astrocytes presented IPD-specific cell proliferation and dysregulation of genes related to unfolded protein response and cytokine signalling. IPD-microglia revealed a specific pro-inflammatory trajectory. Finally, we discovered a neuronal cell cluster exclusively present in IPD midbrains characterized by CADPS2 overexpression and a high proportion of cycling cells. We conclude that elevated CADPS2 expression is specific to dysfunctional dopaminergic neurons, which have lost their dopaminergic identity and unsuccessful attempt to re-enter the cell cycle

Monitoring the Dusty S-Cluster Object (DSO/G2) on its Orbit towards the Galactic Center Black Hole

We analyse and report in detail new near-infrared (1.45 - 2.45 microns) observations of the Dusty S-cluster Object (DSO/G2) during its approach to the black hole at the center of the Galaxy that were carried out with ESO VLT/SINFONI between February and September 2014. Before May 2014 we detect spatially compact Br-gamma and Pa-alpha line emission from the DSO at about 40mas east of SgrA*. The velocity of the source, measured from the red-shifted emission, is 2700+-60 km/s. No blue-shifted emission above the noise level is detected at the position of SgrA* or upstream the presumed orbit. After May we find spatially compact Br-gamma blue-shifted line emission from the DSO at about 30mas west of SgrA* at a velocity of -3320+-60 km/s and no indication for significant red-shifted emission. We do not detect any significant extension of velocity gradient across the source. We find a Br-gamma-line full width at half maximum of 50+-10 Angstroem before and 15+-10 Angstroem after the peribothron transit, i.e. no significant line broadening with respect to last year is observed. Br-gamma line maps show that the bulk of the line emission originates from a region of less than 20mas diameter. This is consistent with a very compact source on an elliptical orbit with a peribothron time passage in 2014.39+-0.14. For the moment, the flaring activity of the black hole in the near-infrared regime has not shown any statistically significant increment. Increased accretion activity of SgrA* may still be upcoming. We discuss details of a source model according to which the DSO is rather a young accreting star than a coreless gas and dust cloud.Comment: 32 pages - 3 tables - 17 figure - accepted by Ap

iPSC-Derived Microglia as a Model to Study Inflammation in Idiopathic Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease with unknown cause in the majority of patients, who are therefore considered "idiopathic" (IPD). PD predominantly affects dopaminergic neurons in the substantia nigra pars compacta (SNpc), yet the pathology is not limited to this cell type. Advancing age is considered the main risk factor for the development of IPD and greatly influences the function of microglia, the immune cells of the brain. With increasing age, microglia become dysfunctional and release pro-inflammatory factors into the extracellular space, which promote neuronal cell death. Accordingly, neuroinflammation has also been described as a feature of PD. So far, studies exploring inflammatory pathways in IPD patient samples have primarily focused on blood-derived immune cells or brain sections, but rarely investigated patient microglia in vitro. Accordingly, we decided to explore the contribution of microglia to IPD in a comparative manner using, both, iPSC-derived cultures and postmortem tissue. Our meta-analysis of published RNAseq datasets indicated an upregulation of IL10 and IL1B in nigral tissue from IPD patients. We observed increased expression levels of these cytokines in microglia compared to neurons using our single-cell midbrain atlas. Moreover, IL10 and IL1B were upregulated in IPD compared to control microglia. Next, to validate these findings in vitro, we generated IPD patient microglia from iPSCs using an established differentiation protocol. IPD microglia were more readily primed as indicated by elevated IL1B and IL10 gene expression and higher mRNA and protein levels of NLRP3 after LPS treatment. In addition, IPD microglia had higher phagocytic capacity under basal conditions-a phenotype that was further exacerbated upon stimulation with LPS, suggesting an aberrant microglial function. Our results demonstrate the significance of microglia as the key player in the neuroinflammation process in IPD. While our study highlights the importance of microglia-mediated inflammatory signaling in IPD, further investigations will be needed to explore particular disease mechanisms in these cells

Single-cell sequencing of human midbrain reveals glial activation and a Parkinson-specific neuronal state.

Idiopathic Parkinson's disease is characterized by a progressive loss of dopaminergic neurons, but the exact disease etiology remains largely unknown. To date, Parkinson's disease research has mainly focused on nigral dopaminergic neurons, although recent studies suggest disease-related changes also in non-neuronal cells and in midbrain regions beyond the substantia nigra. While there is some evidence for glial involvement in Parkinson's disease, the molecular mechanisms remain poorly understood. The aim of this study was to characterize the contribution of all cell types of the midbrain to Parkinson's disease pathology by single-nuclei RNA sequencing and to assess the cell type-specific risk for Parkinson's disease employing the latest genome-wide association study. We profiled >41 000 single-nuclei transcriptomes of postmortem midbrain from six idiopathic Parkinson's disease patients and five age-/sex-matched controls. To validate our findings in a spatial context, we utilized immunolabeling of the same tissues. Moreover, we analyzed Parkinson's disease-associated risk enrichment in genes with cell type-specific expression patterns. We discovered a neuronal cell cluster characterized by CADPS2 overexpression and low TH levels, which was exclusively present in IPD midbrains. Validation analyses in laser-microdissected neurons suggest that this cluster represents dysfunctional dopaminergic neurons. With regard to glial cells, we observed an increase in nigral microglia in Parkinson's disease patients. Moreover, nigral idiopathic Parkinson's disease microglia were more amoeboid, indicating an activated state. We also discovered a reduction in idiopathic Parkinson's disease oligodendrocyte numbers with the remaining cells being characterized by a stress-induced upregulation of S100B. Parkinson's disease risk variants were associated with glia- and neuron-specific gene expression patterns in idiopathic Parkinson's disease cases. Furthermore, astrocytes and microglia presented idiopathic Parkinson's disease-specific cell proliferation and dysregulation of genes related to unfolded protein response and cytokine signaling. While reactive patient astrocytes showed CD44 overexpression, idiopathic Parkinson's disease-microglia revealed a pro-inflammatory trajectory characterized by elevated levels of IL1B, GPNMB, and HSP90AA1. Taken together, we generated the first single-nuclei RNA sequencing dataset from the idiopathic Parkinson's disease midbrain, which highlights a disease-specific neuronal cell cluster as well as 'pan-glial' activation as a central mechanism in the pathology of the movement disorder. This finding warrants further research into inflammatory signaling and immunomodulatory treatments in Parkinson's disease