Two-dimensional fluid queues with temporary assistance

We consider a two-dimensional stochastic fluid model with $N$ ON-OFF inputs and temporary assistance, which is an extension of the same model with $N = 1$ in Mahabhashyam et al. (2008). The rates of change of both buffers are piecewise constant and dependent on the underlying Markovian phase of the model, and the rates of change for Buffer 2 are also dependent on the specific level of Buffer 1. This is because both buffers share a fixed output capacity, the precise proportion of which depends on Buffer 1. The generalization of the number of ON-OFF inputs necessitates modifications in the original rules of output-capacity sharing from Mahabhashyam et al. (2008) and considerably complicates both the theoretical analysis and the numerical computation of various performance measures

Baltic Cooperation in Marine Spatial Planning

Marine spatial planning is a relatively new area of cooperation in the Baltic Sea region — a site of long-term joint efforts towards environmental protection and sustainable development. At the beginning of the 21st century, the integrated management of coastal zones and marine spatial planning emerged as a new area of international cooperation. Despite intensive theoretical work on the mentioned concepts, the development of a harmonised spatial planning in the Baltic Sea region is complicated by the complex nature of the problem, a relatively intensive exploitation of marine resources, diverse interests of the stakeholders, and differences in national institutional systems. We describe the key stages of the process, which is regulated by the EU standards on the one hand and affected by the activity of such organisations as VASAB and HELCOM, on the other. In this article, we examine basic documents defining the principles and scope of marine planning and analyse recent research works into spatial development. We conclude that marine spatial planning is a principal tool of the EU’s integrated policy. Many European countries of the Baltic region are seeking cooperation with Russia to preserve the natural and economic environment of the Baltic Sea. Most joint spatial planning projects have been initiated by Finland, Sweden, Germany, and Poland

Modelling direct and indirect water requirements of construction

Water consumed directly by the construction industry is known to be of little importance. However, water consumed in the manufacture of goods and services required by construction may be significant in the context of a building\u27s life cycle water requirements and the national water budget. This paper evaluates the significance of water embodied in the construction of individual buildings. To do this, an input-output-based hybrid embodied water analysis was undertaken on 17 Australian non-residential case studies. It was found that there is a considerable amount of water embodied in construction. The highest value was 20.1 kilolitres (kL)/m2 gross floor area (GFA), representing many times the enclosed volume of the building, and many years worth of operational water. The water required by the main construction process is minimal. However, the water embodied in building materials is considerable. These findings suggest that the selection of elements and materials has a great impact on a building\u27s embodied water. This research allows the construction industry to evaluate design and construction in broad environmental terms to select options that might be cost neutral or possibly cost positive while retaining their environmental integrity. The research suggests policies focused on operational water consumption alone are inadequate. <br /

Baltic Cooperation in Marine Spatial Planning

Marine spatial planning is a relatively new area of cooperation in the Baltic Sea region — a site of long-term joint efforts towards environmental protection and sustainable development. At the beginning of the 21st century, the integrated management of coastal zones and marine spatial planning emerged as a new area of international cooperation. Despite intensive theoretical work on the mentioned concepts, the development of a harmonised spatial planning in the Baltic Sea region is complicated by the complex nature of the problem, a relatively intensive exploitation of marine resources, diverse interests of the stakeholders, and differences in national institutional systems. We describe the key stages of the process, which is regulated by the EU standards on the one hand and affected by the activity of such organisations as VASAB and HELCOM, on the other. In this article, we examine basic documents defining the principles and scope of marine planning and analyse recent research works into spatial development. We conclude that marine spatial planning is a principal tool of the EU’s integrated policy. Many European countries of the Baltic region are seeking cooperation with Russia to preserve the natural and economic environment of the Baltic Sea. Most joint spatial planning projects have been initiated by Finland, Sweden, Germany, and Poland

Two refreshing views of Fluctuation Theorems through Kinematics Elements and Exponential Martingale

In the context of Markov evolution, we present two original approaches to obtain Generalized Fluctuation-Dissipation Theorems (GFDT), by using the language of stochastic derivatives and by using a family of exponential martingales functionals. We show that GFDT are perturbative versions of relations verified by these exponential martingales. Along the way, we prove GFDT and Fluctuation Relations (FR) for general Markov processes, beyond the usual proof for diffusion and pure jump processes. Finally, we relate the FR to a family of backward and forward exponential martingales.Comment: 41 pages, 7 figures; version2: 45 pages, 7 figures, minor revisions, new results in Section

Partial versus total resetting for Lévy flights in d dimensions: similarities and discrepancies

While stochastic resetting (or total resetting) is a less young and more established concept in stochastic processes, partial stochastic resetting (PSR) is a relatively new field. PSR means that, at random moments in time, a stochastic process gets multiplied by a factor between and ⁠, thus approaching but not reaching the resetting position. In this paper, we present new results on PSR highlighting the main similarities and discrepancies with total resetting. Specifically, we consider both symmetric -stable Lévy processes (Lévy flights) and Brownian motion with PSR in arbitrary dimensions. We derive explicit expressions for the propagator and its stationary measure and discuss in detail their asymptotic behavior. Interestingly, while approaching to stationarity, a dynamical phase transition occurs for the Brownian motion, but not for Lévy flights. We also analyze the behavior of the process around the resetting position and find significant differences between PSR and total resetting

A reciprocal relationship between markers of genomic DNA damage and alpha-synuclein pathology in dementia with Lewy bodies

Background:DNA damage and DNA damage repair (DDR) dysfunction are insults with broad implications for cellular physiology and have been implicated in various neurodegenerative diseases. Alpha-synuclein (aSyn), a pre-synaptic and nuclear protein associated with neurodegenerative disorders known as synucleinopathies, has been associated with DNA double strand break (DSB) repair. However, although nuclear aSyn pathology has been observed in cortical tissue of dementia with Lewy body (DLB) cases, whether such nuclear pathology coincides with the occurrence of DNA damage has not previously been investigated. Moreover, the specific types of DNA damage elevated in DLB cases and the contribution of DNA damage towards Lewy body (LB) formation is unknown.Methods:DNA damage and aSyn pathology were assessed in fixed lateral temporal cortex from clinically and neuropathologically confirmed DLB cases and controls, as well as in cortical tissue from young 3-month-old presymptomatic A30P-aSyn mice. Frozen lateral temporal cortex from DLB and control cases was subject to nuclear isolation, western blotting, aSyn seed amplification and proteomic characterisation via mass spectrometry.Results:We detected seed-competent nuclear aSyn, and elevated nuclear serine-129 phosphorylation in DLB temporal cortex, alongside the accumulation of DSBs in neuronal and non-neuronal cellular populations. DNA damage was also present in cortical tissue from presymptomatic A30P mice, demonstrating it is an early insult closely associated with pathogenic aSyn. Strikingly, in postmortem DLB tissue, markers of genomic DNA damage-derived cytoplasmic DNA (CytoDNA) were evident within the majority of LBs examined. The observed cellular pathology was consistent with nuclear upregulation of associated DDR proteins, particularly those involved in base excision repair and DSB repair pathways.Conclusions:Collectively our study demonstrates the accumulation of seed-competent pathological nuclear associated aSyn, alongside nuclear DNA damage and the potential involvement of DNA damage derived cytoDNA species in cytoplasmic aSyn pathology. Ultimately, our study supports the hypothesis of a reciprocal relationship between aSyn pathology and nuclear DNA damage and highlights a potential underlying role for DNA damage in pathological mechanisms relevant to DLB, as well as other synucleinopathies, opening novel possibilities for diagnosis and treatment

A reciprocal relationship between markers of genomic DNA damage and alpha-synuclein pathology in dementia with Lewy bodies

BackgroundDNA damage and DNA damage repair (DDR) dysfunction are insults with broad implications for cellular physiology and have been implicated in various neurodegenerative diseases. Alpha-synuclein (aSyn), a pre-synaptic and nuclear protein associated with neurodegenerative disorders known as synucleinopathies, has been associated with DNA double strand break (DSB) repair. However, although nuclear aSyn pathology has been observed in cortical tissue of dementia with Lewy body (DLB) cases, whether such nuclear pathology coincides with the occurrence of DNA damage has not previously been investigated. Moreover, the specific types of DNA damage elevated in DLB cases and the contribution of DNA damage towards Lewy body (LB) formation is unknown.MethodsDNA damage and aSyn pathology were assessed in fixed lateral temporal cortex from clinically and neuropathologically confirmed DLB cases and controls, as well as in cortical tissue from young 3-month-old presymptomatic A30P-aSyn mice. Frozen lateral temporal cortex from DLB and control cases was subject to nuclear isolation, western blotting, aSyn seed amplification and proteomic characterisation via mass spectrometry.ResultsWe detected seed-competent nuclear aSyn, and elevated nuclear serine-129 phosphorylation in DLB temporal cortex, alongside the accumulation of DSBs in neuronal and non-neuronal cellular populations. DNA damage was also present in cortical tissue from presymptomatic A30P mice, demonstrating it is an early insult closely associated with pathogenic aSyn. Strikingly, in postmortem DLB tissue, markers of genomic DNA damage-derived cytoplasmic DNA (CytoDNA) were evident within the majority of LBs examined. The observed cellular pathology was consistent with nuclear upregulation of associated DDR proteins, particularly those involved in base excision repair and DSB repair pathways.ConclusionsCollectively our study demonstrates the accumulation of seed-competent pathological nuclear associated aSyn, alongside nuclear DNA damage and the potential involvement of DNA damage derived cytoDNA species in cytoplasmic aSyn pathology. Ultimately, our study supports the hypothesis of a reciprocal relationship between aSyn pathology and nuclear DNA damage and highlights a potential underlying role for DNA damage in pathological mechanisms relevant to DLB, as well as other synucleinopathies, opening novel possibilities for diagnosis and treatment

Retinal cells derived from patients with DRAM2-dependent CORD21 dystrophy exhibit key lysosomal enzyme deficiency and lysosomal content accumulation

\ua9 2024 The Author(s)Biallelic mutations in DRAM2 lead to an autosomal recessive cone-rod dystrophy known as CORD21, which typically presents between the third and sixth decades of life. Although DRAM2 localizes to the lysosomes of photoreceptor and retinal pigment epithelium (RPE) cells, its specific role in retinal degeneration has not been fully elucidated. In this study, we generated and characterized retinal organoids (ROs) and RPE cells from induced pluripotent stem cells (iPSCs) derived from two CORD21 patients. Our investigation revealed that CORD21-ROs and RPE cells exhibit abnormalities in lipid metabolism, defects in autophagic flux, accumulation of aberrant lysosomal content, and reduced lysosomal enzyme activity. We identified potential interactions of DRAM2 with vesicular trafficking proteins, suggesting its involvement in this cellular process. These findings collectively suggest that DRAM2 plays a crucial role in maintaining the integrity of photoreceptors and RPE cells by regulating lysosomal function, autophagy, and potentially vesicular trafficking