Protective effect of Sildenafil on contralateral epididymal sperm concentration and motility following unilateral blunt testicular trauma in pre-pubertal male mice

Background and aims: Blunt testicular trauma adversely affects fertility in later periods. The purpose of the present study was to examine the effect of sildenafil on contralateral epididymal sperm count and motility following unilateral blunt testicular trauma in mice. Methods: In this randomized controlled experimental study, 24 pre-pubertal male mice were distributed into four groups of six mice each. In two groups of mice, the abdomen was opened and the right testis was placed on a sterile firm surface and 5 g sterile weight was dropped on to the testis from a height of 10 cm. One of these groups received sildenafil (0.1 mg/kg per day) intraperitoneally for 7 days starting from the day of induction of trauma. A control group and a sildenafil control group were also included. The left epididymal sperm characteristics of all animals were evaluated after 7 weeks. Results: Trauma caused a significant decrease in the sperm concentration and motility as compared to control mice (P<0.05). Sildenafil administration markedly ameliorated all changes in the above-mentioned parameters (P<0.05). Conclusion: Sildenafil administration could attenuate blunt testicular trauma-induced contralateral epididymal sperm impairment

Cognitive Stimulation Therapy in mild to moderate Alzheimer’s Disease: an MRI study

This research endeavor aimed at understanding the mechanisms behind the effectiveness of Cognitive Stimulation Therapy (CST) in addressing cognitive challenges in Alzheimer's disease (AD) patients. The study, conducted at the Neurology Department of Cologne University Hospital, involved mild to moderate AD patients undergoing CST. Utilizing MRI, our goal was to uncover neural transformations underlying cognitive benefits observed in CST participants, thus advancing understanding of CST's therapeutic potential. Brain plasticity refers to the brain's ability to adapt and reorganize itself in response to experiences and injuries. This process allows for the formation of new neural connections, supporting the development of new skills and improving cognitive function. CST is designed to enhance brain plasticity and promote compensatory mechanisms in individuals with cognitive decline. Building on knowledge of neuroplasticity's role in CST and its manifestation as compensatory effects in brain imaging, our study established a framework to detect resting-state compensatory effects in healthy aging and Mild Cognitive Impairment (MCI). Using graph theory analysis of resting-state functional MRI data and volumetric analyses of structural MRI, we identified compensatory regions in the brain associated with cognitive performance. Our analysis revealed increased connectivity in certain brain regions despite atrophy, suggesting a compensatory mechanism to counter cognitive decline. These findings align with existing models of compensation in aging and neurodegeneration. Specifically, we identified regions such as the prefrontal cortex and parietal lobe showing successful compensation in MCI patients, with similarity to patterns observed in task-based compensational effect, suggesting that these regions may serve as targets for non-invasive stimulation techniques to enhance neuronal performance. With evidence of brain plasticity-driven compensation in healthy aging and MCI, our study then focused on CST's capacity to mitigate cognitive decline in mild to moderate AD, using an eight-week CST program on patients with mild to moderate AD compared to a control group with no intervention. We evaluated changes in cognition, quality of life (QoL), and brain connectivity immediately after the intervention period and at a three-month follow-up. CST was found to significantly improve cognitive function, QoL, and neuropsychiatric measures in the intervention group compared to the control group. Furthermore, our study examined the role of cognitive reserve in predicting response to CST, finding a significant correlation between improvement in cognition and years of education as a proxy measure for cognitive reserve. However, baseline total brain volume did not correlate with CST outcomes, suggesting that CST efficacy is not dependent on brain reserve in patients with mild to moderate AD. Analysis of brain connectivity using functional MRI revealed enhanced connectivity between the hippocampus and memory-related regions, suggesting neuroplastic changes induced by CST. Additionally, increased connectivity in the parietal lobes is observed, consistent with compensatory mechanisms in healthy aging and prodromal AD. Our results are suggestive of CST-induced neuronal activity, promoting compensatory neuroplasticity, particularly in regions associated with memory and self-representation. Autobiographical recall and narrative tasks incorporated into the CST program may contribute to memory enhancement and restoration of self-continuity. Finally, we discussed the potential of Maintenance Cognitive Stimulation Therapy (MCST) as a longer-term intervention to maintain cognitive gains and prevent further decline in individuals with dementia. Overall, our findings highlight the effectiveness of CST in improving cognition, QoL, and brain connectivity in patients with mild to moderate AD, and provide further evidence for the broad recommendation of CST as a cost-effective non-pharmacological treatment approach for AD and emphasizes the need for its widespread accessibility in various settings, while underscoring the importance of further research to refine intervention strategies and understand underlying mechanisms

DEVELOPMENT STRATEGY AND MANAGEMENT OF AI-BASED VULNERABILITY DETECTION APPLICATIONS IN ENTERPRISE SOFTWARE ENVIRONMENT

Industries are now struggling with high level of security-risk vulnerabilities in their software environment which mainly originate from open-source dependencies. Industries’ percentage of open source in codebases is about 54% whereas ones with high security risks is about 30% (Synopsys 2018). While there are existing solutions for application security analysis, these typically only detect a limited subset of possible errors based on pre-defined rules. With the availability of open-source vulnerability resources, it is now possible to use data-driven techniques to discover vulnerabilities. Although there are a few AI-based solutions available, but there are some associated challenges: 1) use of artificial intelligence for application security (AppSec) towards vulnerability detection has been very limited and definitely not industry oriented, 2) the strategy to develop, use and manage such AppSec products in enterprises have not been investigated; therefore cybersecurity firms do not use even limited existing solutions. In this study, we aim to address these challenges with some strategies to develop such AppSec, their use management and economic values in enterprise environment

Generation and phenotypic characterization of Pde1a mutant mice

Contains fulltext : 177029.pdf (publisher's version ) (Open Access)It has been proposed that a reduction in intracellular calcium causes an increase in intracellular cAMP and PKA activity through stimulation of calcium inhibitable adenylyl cyclase 6 and inhibition of phosphodiesterase 1 (PDE1), the main enzymes generating and degrading cAMP in the distal nephron and collecting duct, thus contributing to the development and progression of autosomal dominant polycystic kidney disease (ADPKD). In zebrafish pde1a depletion aggravates and overexpression ameliorates the cystic phenotype. To study the role of PDE1A in a mammalian system, we used a TALEN pair to Pde1a exon 7, targeting the histidine-aspartic acid dipeptide involved in ligating the active site Zn++ ion to generate two Pde1a null mouse lines. Pde1a mutants had a mild renal cystic disease and a urine concentrating defect (associated with upregulation of PDE4 activity and decreased protein kinase A dependent phosphorylation of aquaporin-2) on a wild-type genetic background and aggravated renal cystic disease on a Pkd2WS25/- background. Pde1a mutants additionally had lower aortic blood pressure and increased left ventricular (LV) ejection fraction, without a change in LV mass index, consistent with the high aortic and low cardiac expression of Pde1a in wild-type mice. These results support an important role of PDE1A in the renal pathogenesis of ADPKD and in the regulation of blood pressure

Importance of Social Networks for Knowledge Sharing and the Impact of Collaboration on Network Innovation in Online Communities

Innovation results from interactions between different sources of knowledge, where these sources aggregate into groups interacting within (intra) and between (inter) groups. Interaction among groups for innovation generation is defined as the process by which an innovation is communicated through certain channels over time among members of a social system. Apart from the discussion about knowledge management within organizations and the discussion about social network analysis of organizations on the topic of innovation and talks about various trade-offs between strength of ties and bridging ties between different organizational groups, within the topic of open source software (OSS) development researchers have used social network theories to investigate OSS phenomenon including communication among developers. It is already known that OSS groups are more networked than the most organizational communities; In OSS network, programmers can join, participate and leave a project at any time, and in fact developers can collaborate not only within the same project but also among different projects or teams. One distinguished feature of the open source software (OSS) development model is the cooperation and collaboration among the members, which will cause various social networks to emerge. In this chapter, the existing gap in the literature with regard to the analysis of cluster or group structure as an input and cluster or group innovation as an output will be addressed, where the focus is on “impact of network cluster structure on cluster innovation and growth” by Behfar et al., that is, how intra- and inter-cluster coupling, structural holes and tie strength impact cluster innovation and growth, and “knowledge management in OSS communities: relationship between dense and sparse network structures.” by Behfar et al., that is, knowledge transfer in dense network (inside groups) impacts on knowledge transfer in sparse network (between groups)

Design and development of cationic liposomes as DNA vaccine adjuvants

Cationic liposomes have been extensively explored for their efficacy in delivering nucleic acids, by offering the ability to protect plasmid DNA against degradation, promote gene expression and, in the case of DNA vaccines, induce both humoural and cellular immune responses. DNA vaccines may also offer advantages in terms of safety, but they are less effective and need an adjuvant to enhance their immunogenicity. Therefore, cationic liposomes can be utilised as delivery systems and/or adjuvants for DNA vaccines to stimulate stronger immune responses. To explore the role of liposomal systems within plasmid DNA delivery, parameters such as the effect of lipid composition, method of liposome preparation and presence of electrolytes in the formulation were investigated in characterisation studies, in vitro transfection studies and in vivo biodistribution and immunisation studies. Liposomes composed of 1,2-dioleoyl-sn-glycero 3-phosphoethanolamine (DOPE) in combination with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or 1,2-stearoyl-3- trimethylammonium-propane (DSTAP) were prepared by the lipid hydration method and hydrated in aqueous media with or without presence of electrolytes. Whilst the in vitro transfection efficiency of all liposomes resulted to be higher than Lipofectin, DSTAP-based liposomes showed significantly higher transfection efficiency than DOTAP-based formulations. Furthermore, upon intramuscular injection of liposomal DNA vaccines, DSTAP-based liposomes showed a significantly stronger depot effect at the injection site. This could explain the result of heterologous immunisation studies, which revealed DSTAP-based liposomal vaccines induce stronger immune responses compared to DOTAP-based formulations. Previous studies have shown that having more liposomally associated antigen at the injection site would lead to more drainage of them into the local lymph nodes. Consequently, this would lead to more antigens being presented to antigen presenting cells, which are circulating in lymph nodes, and this would initiate a stronger immune response. Finally, in a comparative study, liposomes composed of dimethyldioctadecylammonium bromide (DDA) in combination with DOPE or immunostimulatory molecule of trehalose 6,6-dibehenate (TDB) were prepared and investigated in vitro and in vivo. Results showed that although DDA:TDB is not able to transfect the cells efficiently in vitro, this formulation induces stronger immunity compared to DDA:DOPE due to the immunostimulatory effects of TDB. This study demonstrated, while the presence of electrolytes did not improve immune responses, small unilamellar vesicle (SUV) liposomes induced stronger humoural immune responses compared to dehydration rehydration vesicle (DRV) liposomes. Moreover, lipid composition was shown to play a key role in in vitro and in vivo behaviour of the formulations, as saturated cationic lipids provided stronger immune responses compared to unsaturated lipids. Finally, heterologous prime/boost immunisation promoted significantly stronger immune responses compared to homologous vaccination of DNA vaccines, however, a single immunisation of subunit vaccine provoked comparable levels of immune response to the heterologous regimen, suggesting more immune efficiency for subunit vaccines compared to DNA vaccines

Numerical Simulation of Fault Impacts for Commercial Walk-in Freezers

Refrigeration systems can undergo many faults that could negatively affect their operation and performance. This paper describes a modeling process to simulate the fault impacts on the operation of a commercial walk-in freezer using semi-empirical models. These models often require less modeling effort than full forward models and could be used in scenarios where detailed information is missing, such as in field-measured systems. An important characteristic of a typical walk-in refrigeration system is the existence of a liquid-line receiver after the condenser, which significantly changes the behavior of the cycle, in comparison to a receiver-less system. Component models described in this paper consist of: a compressor, two heat exchangers, pipelines, receiver, and thermostatic expansion valve. The semi-empirical component models are partially based on physics, and partially based on some empirical coefficients. They are able to predict several dependent variables, including mass flow rates, heat transfer rates, power consumption, and pressures. In this paper, the individual component models are presented and trained with a limited set of faulted and fault-free experimental data. The faults are: heat exchanger fouling, liquid-line restriction, and compressor valve leakage. The results show that models for major components, such as compressor and heat exchangers, give good predictions for some of the most important performance indices. Modeling challenges and future research are outlined

Analysis of Information Propagation in Ethereum Network Using Combined Graph Attention Network and Reinforcement Learning to Optimize Network Efficiency and Scalability

Blockchain technology has revolutionized the way information is propagated in decentralized networks. Ethereum plays a pivotal role in facilitating smart contracts and decentralized applications. Understanding information propagation dynamics in Ethereum is crucial for ensuring network efficiency, security, and scalability. In this study, we propose an innovative approach that utilizes Graph Convolutional Networks (GCNs) to analyze the information propagation patterns in the Ethereum network. The first phase of our research involves data collection from the Ethereum blockchain, consisting of blocks, transactions, and node degrees. We construct a transaction graph representation using adjacency matrices to capture the node embeddings; while our major contribution is to develop a combined Graph Attention Network (GAT) and Reinforcement Learning (RL) model to optimize the network efficiency and scalability. It learns the best actions to take in various network states, ultimately leading to improved network efficiency, throughput, and optimize gas limits for block processing. In the experimental evaluation, we analyze the performance of our model on a large-scale Ethereum dataset. We investigate effectively aggregating information from neighboring nodes capturing graph structure and updating node embeddings using GCN with the objective of transaction pattern prediction, accounting for varying network loads and number of blocks. Not only we design a gas limit optimization model and provide the algorithm, but also to address scalability, we demonstrate the use and implementation of sparse matrices in GraphConv, GraphSAGE, and GAT. The results indicate that our designed GAT-RL model achieves superior results compared to other GCN models in terms of performance. It effectively propagates information across the network, optimizing gas limits for block processing and improving network efficiency

Filtering corso Porta Ticinese

LAUREA MAGISTRALEAfter spending two years studying Architectural Engineering at Politecnico di Milano, it was of a great interest to focus on a project with great potentials. In fact, there was not a better project than the new addition to Diocesan museum since it gives the opportunity to implement new technologies within one of the most historical and important centers of Milan. It enables us to really absorb and understand the Milanese culture. As a Thesis theme for the Master of Science in Architectural Engineering, a project which has the potential for designing and developing in Architectural and Technological as well as structural aspects was more preferred. Therefore, the project of new addition to Diocesan Museum was selected for the same reasons. Furthermore, the availability of the site to visit, well-defined brief of the competition and familiarity of the project supervisors with the competition and the site of the project were the strong points which helped the final project through its realization and removal of the constraints. The project has been approached, on the urban scale, by acquiring the necessary knowledge about the history and the urban evolution of Milan in general and Corso Porta Ticinese in particular , leading us to a fair understanding of the particularity and historical significance of the area subject to study. However, since Milan is a living city, a conscious grasp of the contemporary strategic planning had to be done. Consequently, deep studies were carried out in order to investigate the ongoing plans and strategies for the metropolitan region of Milan as well as the neighborhood area around the site in the content of the PGT of Milan. From those ongoing plans, we can mainly mention “La Passeggiata Urbana dei Bastioni”, “Raggi Verdi” that had direct impact on the vision concerning the future aspect of the historical center of Milan. The architecture concept started with the contrast between the highly dense identity of Corso Porta Ticinesse and the urban void of Parco delle Basiliche. The guidelines of the project were directly obtained from the brief of the competition of “Concorso Internazionale di Progettazione Museo Diocesano” in terms of functional requirements and areas of the spaces. Since flexibility of the spaces in the exhibition buildings are out of an extraordinary importance, therefore the structural system which is chosen should be free of structural constraints and obstacles. Steel structures are always a good solution since it provides rather large spans in a covered space. Also a system of dry construction was preferred which reinforced our choice of structural system. Furthermore, despite the previous approaches concerning the seismic design severity in Milan, the latest unfortunate events proved that more conservative attitude should be taken into account. After studying the climate situation of Milan, it was obvious that a well-insulated envelope is the sine qua non of a thermal efficient building. Moreover, the typologies of the spaces required the application of both transparent and opaque walls. Since the brief was concerned about both energy efficiency and light control, a compromising solution between indirect natural lighting and artificial lighting had to be opted. Being constrained by providing sophisticated air conditioning systems in terms of specific controlled temperature, relative humidity and air quality conditions, an all-air system was obviously chosen