Faulty Operation of Coils’ and Humidifier Valves in a Typical Air-Handling Unit: Experimental Impact Assessment of Indoor Comfort and Patterns of Operating Parameters under Mediterranean Climatic Conditions

Data-driven Automated Fault Detection and Diagnosis (AFDD) are recognized as one of the most promising options to improve the efficiency of Air-Handling Units (AHUs). In this study, the field operation of a typical single-duct dual-fan constant air volume AHU is investigated through a series of experiments carried out under Mediterranean (southern Italy) climatic conditions considering both fault-free and faulty scenarios. The AHU performances are analyzed while artificially introducing the following five different typical faults: (1) post-heating coil valve stuck at 100% (always open); (2) post-heating coil valve stuck at 0% (always closed); (3) cooling coil valve stuck at 100% (always open); (4) cooling coil valve stuck at 0% (always closed); (5) humidifier valve stuck at 0% (always closed). The measured faulty data are compared against the corresponding fault-free performance measured under the same boundary conditions with the aim of assessing the faults’ impact on both thermal/hygrometric indoor conditions, as well as patterns of 16 different key operating parameters. The results of this study can help building operators and facility engineers in identifying faults’ symptoms in typical AHUs and facilitate the related development of new AFDD tools

Mitochondrial Diabetes in Children: Seek and You Will Find It

Maternally Inherited Diabetes and Deafness (MIDD) is a rare form of diabetes due to defects in mitochondrial DNA (mtDNA). 3243 A>G is the mutation most frequently associated with this condition, but other mtDNA variants have been linked with a diabetic phenotype suggestive of MIDD. From 1989 to 2009, we clinically diagnosed mitochondrial diabetes in 11 diabetic children. Diagnosis was based on the presence of one or more of the following criteria: 1) maculopathy; 2) hearing impairment; 3) maternal heritability of diabetes/impaired fasting glucose and/or hearing impairment and/or maculopathy in three consecutive generations (or in two generations if 2 or 3 members of a family were affected). We sequenced the mtDNA in the 11 probands, in their mothers and in 80 controls. We identified 33 diabetes-suspected mutations, 1/33 was 3243A>G. Most patients (91%) and their mothers had mutations in complex I and/or IV of the respiratory chain. We measured the activity of these two enzymes and found that they were less active in mutated patients and their mothers than in the healthy control pool. The prevalence of hearing loss (36% vs 75–98%) and macular dystrophy (54% vs 86%) was lower in our mitochondrial diabetic adolescents than reported in adults. Moreover, we found a hitherto unknown association between mitochondrial diabetes and celiac disease. In conclusion, mitochondrial diabetes should be considered a complex syndrome with several phenotypic variants. Moreover, deafness is not an essential component of the disease in children. The whole mtDNA should be screened because the 3243A>G variant is not as frequent in children as in adults. In fact, 91% of our patients were mutated in the complex I and/or IV genes. The enzymatic assay may be a useful tool with which to confirm the pathogenic significance of detected variants

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Z Generation tra nostalgia e meme. La rimediazione dei movimenti Vaporwave e Aesthetic = Z Generation between nostalgia and memes. The remediation of the Vaporwave and Aesthetic movements

This paper reports on the subcultural movements of Vaporwave and Aesthetic by examining digital practices and products such as the creative and sound projects specific to the culture of the web, which are immediately welcomed by member of Generation Z through social media. Generation Z gives life to its own subcultural movements that cannot be analyzed according to the canons of the past, even if they look and are inspired by the past. In the context of the remediation under discussion, fluidity is seen as a starting paradigm, the techno-expressive boundaries mix until they are unrecognizable and perfectly integrated, and digital is an increasingly concrete dynamic. As a result, creative processes become increasingly fragmented and prismatic. The aesthetic recognizability of subcultures today is radically broken down by the logic of digital: the aesthetic canons on the web are less structured, less recognizable, more fragmented. The medialogical path informing our analysis of youth subcultures focuses on two main perspectives: nostalgia and the expressive processes of memes. 1) The movements that we will examine constantly revolve around the concept of nostalgia, which is an essential element of social media. Nostalgic subcultures listen to ultra-digital music that is imbued with elements of the past, buy vintage clothes with an affective value (those that parents bought for them as children), criticize the ""priority"" models and practices of their generation, and form their own identity on the net, growing up in a world where they feel disoriented and uncomfortable. These processes are carried out through the web, despite the widespread and inconsistent idea that the internet has "flattened" and destroyed youth subcultures. 2) The feelings of irony and lightness typical of the subcultures of the past come from the members of Generation Z completely supplanted by a condition of hidden inadequacy that is substantiated in a constant process of remediation of the past: from hashtags to communities, up to the typical product of these subcultures, which is memes