Identifying genetic determinants of progression in Parkinson's disease

Parkinson’s disease (PD) is a progressive neurodegenerative condition for which there are currently no treatments to stop or slow disease progression. A number of genome-wide association studies (GWASs) of PD patients compared to controls have identified genetic variants associated with disease risk, however these cannot inform us about the genetic factors and biology underpinning progression. The aim of this PhD is to identify genetic variants associated with disease progression. I first examined the frequency and baseline clinical features of patients carrying rare pathogenic Mendelian mutations (including variants in LRRK2, SNCA, Parkin, and PINK1) in the Tracking Parkinson’s cohort. I showed that Parkin and PINK1 carriers had better cognition than other early-onset patients at baseline despite having longer disease duration, suggesting slower progression. In analysis of longitudinal data, I also showed that GBA carriers appeared to have more rapid motor and cognitive progression than non-carriers. Prior to conducting GWASs, I sought to understand the clinical predictors of progression and showed that age at onset and gender were associated with progression to clinical milestones. Following a new method from the Huntington’s disease progression GWAS, I used principal components analysis (PCA) to combine multiple motor and cognitive scales in PD to create composite progression scores. I showed that APOE ε4 was strongly associated with cognitive progression, and identified a novel signal in ATP8B2 which was nominally associated with motor progression. Finally, I conducted large-scale GWASs of survival to clinical milestones: mortality, Hoehn and Yahr stage 3, and dementia, using data from Tracking Parkinson’s, Oxford Discovery, Parkinson’s Progression Markers Initiative, Queen Square Brain Bank, UK Biobank, and Calypso studies. I identified loci in or near APOE, ADRA2A, and SH3GL2 which were nominally associated with progression to mortality. I also showed that the APOE ε4 variant, rs429358, was strongly associated with progression to dementia

Modeling and characterization of InAs∕GaAs quantum dot lasers grown using metal organic chemical vapor deposition

We report on the lasing characteristics of three- and five-stack InAs∕GaAsquantum dot(QD) lasers grown by metal organic chemical vapor deposition. By increasing the number of stacked dot layers to 5, lasing was achieved from the ground state at 1135nm for device lengths as short as 1.5mm (no reflectivity coatings). The unamplified spontaneous emission and Z ratio as a function of injection current were also investigated. While the five-stack QD lasers behaved as expected with Z ratios of ≈2 prior to lasing, the three-stack QD lasers, which lased from the excited state, exhibited Z-ratio values as high as 4. A simple model was developed and indicated that high Z ratios can be generated by three nonradiative recombination pathways: (i) high monomolecular recombination within the wetting layer, (ii) Auger recombination involving carriers within the QDs (“unmixed” Auger), and (iii) Auger recombination involving both the QD and wetting layer states (“mixed” Auger), which dominate once the excited and wetting layer states become populated.We also acknowledge the financial support of the Australian Research Council

Suppression of thermal atomic interdiffusion in C-doped InGaAs∕AlGaAs quantum well laser structures using TiO₂ dielectric layers

The effects of thermal annealing on C-doped InGaAs∕AlGaAs quantum well laser structures capped with titanium dioxide (TiO₂) layers were investigated. The atomic interdiffusion was greatly suppressed by the presence of a TiO₂ capping layer during annealing, inhibiting even the thermal intermixing observed in the uncapped sample. An increase in the amount of lattice contraction associated with the presence of substitutional carbonCAs after annealing without a capping layer was observed, but not after annealing with a TiO₂ capping layer. Capacitance–voltage measurements confirmed the electrical activation of carbon after annealing without a dielectric layer and show a negligible change after annealing using a TiO₂ capping layer. The possible mechanisms involving both the atomic intermixing on the group III sublattice and carbon activation on the group V sublattice and the implications for optoelectronic device integration using impurity-free intermixing are discussed.P.L.G. acknowledges the scholarship funded by the Australian Agency for International Development (AusAID). Australian Research Council is gratefully acknowledged for the financial support

Dissecting the limited genetic overlap of Parkinson's and Alzheimer's disease

Parkinson's disease and Alzheimer's disease show overlapping features both clinically and neuropathologically and elucidating shared mechanisms could have important implications for therapeutic strategies. Evidence for genetic overlap is limited, although enrichment of heritability in genomic regions relevant to microglia has been demonstrated in both disorders. Using summary statistics from genome-wide association studies, we assessed genetic covariance stratified by cell types and local genetic correlation between Parkinson's and Alzheimer's disease. Significant covariance was observed for neurons only (p = 0.00046), and local genetic correlation was significant only in the human leukocyte antigen region (p = 1.0e-05). Our findings support a minor genetic overlap between these two disorders

Strategies and actions for achieving carbon neutrality in Portuguese residential buildings by 2050

As a crucial step in addressing the climate emergency and enhancing energy security, the European Union has set ambitious targets to decarbonise its economy by 2050. While the building sector plays a pivotal role in this transition, being accountable for 36% of the EU’s total carbon emissions, it shows a renovation rate below 1% per year, which is clearly insufficient. To address this challenge, this study uses the cost-optimal methodology from private and social perspectives to assess the cost-effectiveness and environmental impact of five renovation packages with passive and active solutions currently available on the Portuguese market. The results demonstrated that from both perspectives, optimal combinations of market solutions were generally cost-effective and could lead to a 90–99% reduction in energy needs and even to zero carbon levels. Nevertheless, beyond cost-effectiveness, consideration of co-benefits, e.g., social and health improvements, is also crucial, requiring government action. To drive these essential changes, effective policy measures are imperative. Recommendations encompass robust regulatory frameworks, financial support mechanisms, knowledge dissemination, and a shift towards broader-scale renovation. For carbon reduction to be economically attractive, fostering innovative business models and leveraging legal instruments to tackle complex scenarios are needed.This work was partly financed by FCT/MCTES through national funds (PIDDAC) under the R & D Unit Institute for Sustainability and Innovation in Structural Engineering (ISISE), under reference UIDB/04029/2020 and under the Associate Laboratory Advanced Production and Intelligent Systems ARISE under reference LA/P/0112/2020. The work was also partly financed by the program Portugal Norte 2020-Projetos Estruturados I & D, with the reference NORTE 01-0145-FEDER000058—ZeroSkin+ project

Analytical expression for the quantum dot contribution to the quasistatic capacitance for conduction band characterization

This paper demonstrates an analytical expression for the quasistatic capacitance of a quantum dot layer embedded in a junction, where the reverse bias is used to discharge the initially occupied energy levels. This analysis can be used to determine the position and the Gaussian homogeneous broadening of the energy levels in the conduction band, and is applied for an InGaAs/GaAs quantum dot structure grown by metal organic chemical vapor deposition. It is shown that the Gaussian broadening of the conduction band levels is significantly larger than the broadening of the interband photoluminescence (PL) transitions involving both conduction and hole states. The analysis also reveals a contribution from the wetting layer both in PL and modeled C-V profiles which is much stronger than in typical molecular beam epitaxy grown dots. The presence of a built-in local field oriented from the apex of the dot toward its base, contrary to the direction expected for a strained dot with uniform composition (negative dipole), is also derived from fitting of the C-V experimental data

Poder local como ator fundamental no processo de reabilitação energética do parque habitacional

Estamos atrasados na reabilitação energética dos edifícios residenciais, um desígnio urgente quando pensamos na descarbonização e também na resolução de várias questões sociais. Perante desafios legais, financeiros, organizacionais e de sensibilização, o poder local pode ter um papel fundamental neste processo.UIDB/04029/202

SUPPORTING ACTIVITIES DALAM SUPPLY CHAIN MANAGEMENT: SUATU LANGKAH AWAL PADA BUMDes RANCABANGO, KECAMATAN TAROGONG KALER, KABUPATEN GARUT

Pengabdian masyarakat yang dilakukan oleh Program Studi Magister Akuntansi Universitas Kristen Maranatha ini bertujuan untuk melanjutkan program pendampingan dalam rangka mengembangkan potensi Badan Usaha Milik Desa (BUMDes) di Desa Rancabango, Kecamatan Tarogong Kaler, Kabupaten Garut, Jawa Barat. Khususnya pada tahun 2021 ini, fokus pendampingan BUMDes dilakukan melalui aktivitas mendesain supply chain management untuk mendistribusikan produk unggulan desa-desa di kota Garut yang rencananya akan didistribusikan ke pihak end-user, termasuk di kota Bandung. Aktivitas desain supply chain ini akan mendorong terbentuknya value chain yang berguna untuk mengidentifikasikan kegiatan utama dalam menciptakan nilai kepada pelanggan dan kegiatan dukungan yang terkait.  Selanjutnya, penciptaan nilai ini memungkinkan struktur biaya dapat dikelola dengan baik untuk menawarkan kemampuan harga yang kompetitif. Selain itu, fungsi atau unsur dalam value chain juga dapat meningkatkan diferensiasi dalam mendukung penetapan harga jual yang lebih tinggi. Melalui program pendampingan ini diharapkan dapat memperkuat kontribusi BUMDES Rancabango bagi penduduk desa. Kata kunci: BUMDes Rancabango, program pendampingan, value chain.   ABSTRACT This community service implemented by the Master of Accountancy program of Maranatha Christian University concentrates to resume the mentoring program in order to develop the potential of Village-Owned Enterprises (BUMDes) in Rancabango Village, Tarogong Kaler District, Garut Regency, West Java. Specifically in year 2021, the plan of assisting BUMDes is to design supply chain management activities in order to distribute superior products to villages in the city of Garut which are arranged to be distributed to end-users, including in the city of Bandung. This supply chain design activity will encourage the formation of a value chain which is useful for identifying key activities in creating value to customers and related-support activities. Furthermore, this value creation allows the cost structure to be properly managed to offer competitive pricing capabilities. In addition, functions or elements in the value chain can also increase differentiation in support of higher selling prices. Through this mentoring program, it is hoped that the contribution of BUMDES Rancabango to the villagers is strenghtened. Keywords: BUMDes Rancabango, mentoring program, value chain

Inhalation therapy in the next decade : Determinants of adherence to treatment in asthma and COPD

Peer reviewedPublisher PD