Progressive Deterioration Research Articles

Combining transfer learning and numerical modelling to deal with the lack of training data in data-based SHM

Structural health monitoring (SHM) involves continuously surveilling the performance of structures to identify progressive damage or deterioration that might evolve over time. Recently, machine learning (ML) algorithms have been successfully employed in various SHM applications, including damage detection. However, supervised ML algorithms often require labelled data for multiple possible damage states of the structure for successful damage identification. Although it may be feasible to gather such data for low-value structures, obtaining damage data for expensive structures such as aircraft could be highly challenging. Herein, this data insufficiency is addressed by combining Finite Element (FE) models with domain adaptation, specifically transfer component analysis (TCA) and joint domain adaptation (JDA). The proposed methodology is showcased in two case studies, a Brake–Reuß beam, where damage scenarios correspond to different torque settings on a lap joint and a wingbox laboratory structure where damage is introduced as saw-cuts. Supervised learning algorithms in the form of Artificial Neural Networks (ANNs) and K-Nearest Neighbours (KNNs) are trained based on FE data after domain adaptation is applied and are then tested with the experimental data. It is shown that even though the performance of classifiers in distinct scenarios of dual, three, four and five-class cases is sensitive to choices in the training stage, the use of TCA or JDA allows for the use of FE data for training and significantly reduces the need for expensive experimental damage data to be used for training. These results can pave the way for a broader use of ML algorithms in SHM of critical and/or expensive structures.

The impact of bronchiectasis and its severity on long-term renal outcomes.

<sec><title>INTRODUCTION</title>While bronchiectasis is associated with adverse cardiovascular outcomes, data regarding its impact on long-term renal outcomes is lacking.</sec><sec><title>METHODS</title>We reviewed bronchiectasis patients followed up at Queen Mary Hospital in 2017 and examined their clinical/renal outcomes in the subsequent five years. The relationships between the severity of bronchiectasis as defined by FACED (FEV1, Age, Chronic colonisation, Extension, Dyspnoea) scores and adverse renal outcomes were evaluated.</sec><sec><title>RESULTS</title>A total of 315 bronchiectasis patients were included. Seventy-five patients (23.8%) showed renal progression. Baseline FACED score showed a positive correlation with renal progression over 5 years of follow-up (adjusted odds ratio [aOR] 1.30 (95% CI 1.083-1.559, P = 0.005). Patients with moderate-to-severe bronchiectasis (FACED score ≥3) showed an increased risk of renal progression (aOR 1.833, 95% CI 1.082-3.106; P = 0.024) and more rapid decline in estimated glomerular filtration rate than those with mild disease (-4.77 ± 4.19 mL/min/1.73 m²/year vs. -3.49 ± 3.94 mL/min/1.73 m²/year; P = 0.006). Patients who developed renal progression had a higher risk of death (adjusted hazard ratio [aHR] 3.056, 95% CI 1.505-6.206; P = 0.002) and subsequent rates of hospitalisation (1.56 ± 2.81 episodes/year vs. 0.60 ± 1.18 episodes/year; P < 0.001) compared to those without renal progression.</sec><sec><title>CONCLUSIONS</title>Progressive renal function deterioration is prevalent among bronchiectasis patients, and the severity of bronchiectasis is a robust predictor of renal progression.</sec>.

Cerebellar cognitive affective syndrome and vertebrobasilar ischemia. From cerebello-cerebral diaschisis to "dysmetria of thought"

Cerebellum, along with it' s role in coordinating motor functions, exercises a significant regulatory influence in fields of cognitive and affective functions. Therefore, studying the effect of cerebrovascular atherosclerotic pathology on mood and cognition should not be limited to stenotic dysfunctions of carotid arteries, but also extend its methodological framework to the consideration of the integrity of vertebrobasilar system (VBS), cerebellar perfusion and posterior cerebral circulation in general, as it has not been yet sufficiently addressed whether VBS insufficiency is associated with deterioration of patients' mental and emotional status and quality of life (QoL). Vertebrobasilar circulatory dysfunction has been pointed out, since decades, as a cause of progressive memory impairment and dementia, due to multiple infarcts in cerebral areas which are topographically critical for mental and emotional functions. Indicative of the pathophysiological and anatomic-functional association of VBS with these neuro-psychiatric domains are cerebellar cognitive-affective syndrome (CCAS) and crossed cerebello-cerebral diaschisis (CCCD). Mental and psychiatric components of CCAS, along with ataxic motor disability, constitute the conceptual hypothesis of "dysmetry of thought", while diagnostic significance of mental dysfunctions and psychopathological manifestations, in terms of symptoms preceding motor impairments that ascribe cerebellar malfunction in the epicenter of their pathophysiology, such as cerebellar ataxias, in which, early recognition of CCAS may facilitate therapeutic interventions aimed at improving QoL, reveal that cerebellar pathology, either of degenerative etiology or vascular substrate on the ground of vertebrobasilar insufficiency (VBI) or other surgical conditions of the posterior fossa, is associated with deterioration of patients' QoL which is related to significant impairments in their cognitive functions with (co)manifested emotional disorders. Studies in animal models also support these conclusions. Since VBI is responsible for a wide range of psychiatric and neurological symptoms, new findings concurred with current indications advocating that, without consideration of VBS disorders, it is impossible to clarify the connection of cerebral perfusion dysfunctions to neurocognitive deficits. The inclusion of cerebellar perfusion disorders in scientific research and clinical approaches to cognitive and affective disorders that may occur in patients with cerebrovascular lesions constitutes a paradigm of best clinical practices implementation and interdisciplinary convergence of neurosciences and vascular medicine.

Introduction of an RS1 mutation causative variant consistent with identified XLRS patient using CRISPR/Cas9 technology in normal iPSC

X-linked retinoschisis (XLRS) is a common retinal genetic disease that occurs in juvenile males and causes progressive visual impairment. this presents a schisis in the macula or peripheral retina of bilateral eyes and currently has no effective treatment. Here, we introduced the RS1 (c.C304T, p.R102W) mutation into a normal induced pluripotent stem (iPS) cell line using CRISPR/Cas9 technology. This missense mutation was consistent with that observed in the XLRS patient-derived iPS cell line (CSUASOi001-A). Conclusively, establishing a directed gene mutation cell line (CSUi007-A) provides a useful cell resource to investigate XLRS pathogenesis.

Exploring the molecular mechanisms of PPARγ agonists in modulating memory impairment in neurodegenerative disorders.

Neurodegenerative diseases are characterized by progressive memory impairment and cognitive decline. This review aims to unravel the molecular mechanisms involved in the enhancement of memory function and mitigation of memory impairment through the activation of PPARγ agonists in neurodegenerative diseases. The findings suggest that PPARγ agonists modulate various molecular pathways involved in memory formation and maintenance. Activation of PPARγ enhances synaptic plasticity, promotes neuroprotection, suppresses neuroinflammation, attenuates oxidative stress, and regulates amyloid-beta metabolism. The comprehensive understanding of these molecular mechanisms would facilitate the development of novel therapeutic approaches targeting PPARγ to improve memory function and ultimately to alleviate the burden of neurodegenerative diseases. Further research, including clinical trials, is warranted to explore the efficacy, safety, and optimal use of specific PPARγ agonists as potential therapeutic agents in the treatment of memory impairments associated with neurodegenerative diseases.

Epidemiological Changes in Transthyretin Cardiac Amyloidosis: Evidence from In Vivo Data and Autoptic Series.

Cardiac amyloidosis is an infiltrative disease that causes progressive myocardial impairment secondary to amyloid fibril deposition in the extracellular space of the myocardium. Many amyloid precursors, including transthyretin protein, are known to determine cardiac damage by aggregating and precipitating in cardiac tissue. Transthyretin cardiac amyloidosis may be either caused by rare genetic mutations of the transthyretin gene in the hereditary variant, or may arise as a consequence of age-related mechanisms in the acquired form. Although it has been labeled as a rare disease, in recent years, transthyretin cardiac amyloidosis has stood out as an emerging cause of aortic stenosis, unexplained left ventricular hypertrophy and heart failure with preserved ejection fraction, particularly in the elderly. Indeed, the integration of data deriving from both in vivo imaging techniques (whose advancement in the last years has allowed to achieve an easier and more accessible non-invasive diagnosis) and forensic studies (showing a prevalence of amyloid deposition in cardiac tissue of elderly patients up to 29%) suggests that cardiac amyloidosis is a more common disease than traditionally considered. Thanks to all the improvements in non-invasive diagnostic techniques, along with the development of efficacious therapies offering improvements in survival rates, transthyretin cardiac amyloidosis has been transformed from an incurable and infrequent condition to a relatively more diffuse and treatable disease, which physicians should take into consideration in the differential diagnostic processes in daily clinical practice.

Construction of landscape ecological network based on MCR risk assessment Model: A case study of Liaoning Province, China

Numerous disorderly expansions of impervious surfaces have resulted from the ongoing urbanization process, eroding the ecological security pattern and exacerbating ecological risks, subsequently leading to a progressive deterioration in its integrity. The tension between the expansion of ecological space and urban spatial expansion is becoming increasingly acute. Exploring the connection between ecological risks in urban landscapes is important for effectively managing regional ecological risks and optimizing patterns of regional ecological security. However, previous studies focus on selecting ecological sources in an ecological network and ignore how ecological resilience is impacted by factors such as species diversity, ecological structure complexity, etc. Based on remote sensing images of Liaoning Province in 2000, 2010, and 2020, the study used the landscape core index as the main indicator of ecological risk assessment, constructed a landscape ecological risk assessment model, and analyzed the spatiotemporal evolution of landscape ecological risk over the past 20 years. The impact of landscape ecological risk on ecological resistance was further explored, and the landscape ecological risk results in 2020 were used as one of the resistance factors to construct a multi-indicator comprehensive resistance surface. After identifying important ecological sources, an ecological network based on the minimum cumulative resistance model (MCR) was constructed, the optimal path connecting important ecological source areas was determined, and the distribution pattern characteristics of the internal ecological network in Liaoning Province were revealed. The findings indicate a general shift in ecological risks from high to low, following a distribution pattern of “high in the east and low in the west”. Additionally, the study identified 8 ecological sources and established 28 ecological corridors, spanning a total length of roughly 8160 km. This study aims to furnish a scientific foundation for developing an ecological security pattern network and optimizing the landscape pattern within Liaoning Province.

Overview of Neuro-Ophthalmic Findings in Leukodystrophies.

Background: Leukodystrophies are a group of rare genetic diseases that primarily affect the white matter of the central nervous system. The broad spectrum of metabolic and pathological causes leads to manifestations at any age, most often in childhood and adolescence, and a variety of symptoms. Leukodystrophies are usually progressive, resulting in severe disabilities and premature death. Progressive visual impairment is a common symptom. Currently, no overview of the manifold neuro-ophthalmologic manifestations and visual impact of leukodystrophies exists. Methods: Data from 217 patients in the Hamburg leukodystrophy cohort were analyzed retrospectively for neuro-ophthalmologic manifestations, age of disease onset, and magnetic resonance imaging, visual evoked potential, and optical coherence tomography findings and were compared with data from the literature. Results: In total, 68% of the patients suffered from neuro-ophthalmologic symptoms, such as optic atrophy, visual neglect, strabismus, and nystagmus. Depending on the type of leukodystrophy, neuro-ophthalmologic symptoms occurred early or late during the course of the disease. Magnetic resonance imaging scans revealed pathologic alterations in the visual tract that were temporally correlated with symptoms. Conclusions: The first optical coherence tomography findings in Krabbe disease and metachromatic leukodystrophy allow retinal assessments. Comprehensive literature research supports the results of this first overview of neuro-ophthalmologic findings in leukodystrophies.

Degradation of andrographolide in Andrographis paniculata over 1 year storage.

Andrographolide is a bioactive component found in the medicinal herb Andrographis paniculata (Burm. f.) Wall. ex Nees (Family-Acanthaceae) is well-known for its ability to cure liver disorders and as a bitter tonic. In this study, the rate of degradation of andrographolide was examined over the course of a year of storage. New and old (1-year storage) A.paniculata powder samples were used in the study. High-performance liquid chromatography (HPLC) was used to assess the concentration of andrographolide after its extraction using ethanol as the solvent. The findings demonstrated a 69.26% progressive deterioration of andrographolide over the storage period. Temperature and crystallinity are two factors that affect how quickly andrographolide degrades. The results emphasize how crucial it is to retain the effectiveness of A.paniculata extract by avoiding prolonged storage or by providing ideal storage conditions.

Computational Analysis of Marker Genes in Alzheimer’s Disease across Multiple Brain Regions

Alzheimer’s disease (AD) is the most common cause of neurodegenerative dementia in the elderly, which is characterized by progressive cognitive impairment. Herein, we undertake a sophisticated computational analysis by integrating single-cell RNA sequencing (scRNA-seq) data from multiple brain regions significantly affected by the disease, including the entorhinal cortex, prefrontal cortex, superior frontal gyrus, and superior parietal lobe. Our pipeline combines datasets derived from the aforementioned tissues into a unified analysis framework, facilitating cross-regional comparisons to provide a holistic view of the impact of the disease on the cellular and molecular landscape of the brain. We employed advanced computational techniques such as batch effect correction, normalization, dimensionality reduction, clustering, and visualization to explore cellular heterogeneity and gene expression patterns across these regions. Our findings suggest that enabling the integration of data from multiple batches can significantly enhance our understanding of AD complexity, thereby identifying key molecular targets for potential therapeutic intervention. This study established a precedent for future research by demonstrating how existing data can be reanalysed in a coherent manner to elucidate the systemic nature of the disease and inform the development of more effective diagnostic tools and targeted therapies.

Additive effect of metabolic dysfunction-associated fatty liver disease on left ventricular function and global strain in type 2 diabetes mellitus patients: a 3.0 T cardiac magnetic resonance feature tracking study

BackgroundType 2 diabetes mellitus (T2DM) and metabolic-associated fatty liver disease (MAFLD) are both metabolic disorders that negatively impact the cardiovascular system. This study comprehensively analyzed the additive effect of MAFLD on left ventricular function and global strain in T2DM patients by cardiac magnetic resonance (CMR).MethodsData of 261 T2DM patients, including 109 with and 152 without MAFLD, as well as 73 matched normal controls from our medical center between June 2015 and March 2022 were retrospectively analyzed. CMR-derived parameters, including LV function and global strain parameters, were compared among different groups. Univariate and multivariate linear regression analyses were conducted to investigate the impact of various factors on LV function and global strain.ResultsOur investigation revealed a progressive deterioration in LV functional parameters across three groups: control subjects, T2DM patients without MAFLD, and T2DM patients with MAFLD. Statistically significant increases in left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular mass index (LVMI) were observed, along with decreases in left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI). Among these three groups, significant reductions were also noted in the absolute values of LV global radial, circumferential, and longitudinal peak strains (GRPS, GCPS, and GLPS), as well as in peak systolic (PSSR) and peak diastolic strain rates (PDSR). MAFLD was identified as an independent predictor of LVEF, LVMI, LVGFI, GRPS, GCPS, and GLPS in multivariate linear analysis. Besides, the incidence of late gadolinium enhancement was higher in MAFLD patients than in non-MAFLD patients (50/109 [45.9%] vs. 42/152 [27.6%], p = 0.003). Furthermore, escalating MAFLD severity was associated with a numerical deterioration in both LV function parameters and global strain values.ConclusionsThis study thoroughly compared CMR parameters in T2DM patients with and without MAFLD, uncovering MAFLD’s adverse impact on LV function and deformation in T2DM patients. These findings highlight the critical need for early detection and comprehensive management of cardiac function in T2DM patients with MAFLD.

KHSRP ameliorates acute liver failure by regulating pre-mRNA splicing through its interaction with SF3B1

Acute liver failure (ALF) is characterized by the rapidly progressive deterioration of hepatic function, which, without effective medical intervention, results in high mortality and morbidity. Here, using proteomic and transcriptomic analyses in murine ALF models, we found that the expression of multiple splicing factors was downregulated in ALF. Notably, we found that KH-type splicing regulatory protein (KHSRP) has a protective effect in ALF. Knockdown of KHSRP resulted in dramatic splicing defects, such as intron retention, and led to the exacerbation of liver injury in ALF. Moreover, we demonstrated that KHSRP directly interacts with splicing factor 3b subunit 1 (SF3B1) and enhances the binding of SF3B1 to the intronic branch sites, thereby promoting pre-mRNA splicing. Using splicing inhibitors, we found that Khsrp protects against ALF by regulating pre-mRNA splicing in vivo. Overall, our findings demonstrate that KHSRP is an important splicing activator and promotes the expression of genes associated with ALF progression by interacting with SF3B1; thus, KHSRP could be a possible target for therapeutic intervention in ALF.

Analyzing the Effects of Monochromatic Lights on the Fungal Growth to Control the Progression of Microbial Deterioration on Animal Collections Preserved in the Zoological Museum of Naples, Italy

ABSTRACT Exposing artworks and artifacts in museums is fundamental to disseminate culture and knowledge but is also risky since the exposure to environmental conditions can deteriorate exhibited objects. Light is crucial, being able to trigger photochemical effects, and jointly responsible (with temperature and humidity) for biological risk generation. In this context, fungal growth in museum artifacts is a damaging factor that should not be underestimated. Consequently, the study of lighting effects on fungi development is essential. In this work, five different fungal strains (Aspergillus fumigatus, Bjerkandera adusta, Fusarium oxysporum, Penicillium chrysogenum, and Penicillium granulatum) isolated from samplings on animal exhibits hosted in the Zoological Museum of Naples, Italy, are cultivated inside four experimental boxes, equipped with monochromatic LEDs with different peak wavelengths (460 nm, 518 nm, 594 nm, and 638 nm). The growth rate, the protein and carbohydrate contents are analyzed and compared to results obtained in darkness (typical growth conditions for studies about fungi). Results demonstrate that, even if fungi are heterotrophic organisms and do not need light to grow and develop, their growth rate, and their protein and carbohydrate contents are affected by the exposure to monochromatic radiation, but the spectral sensitivity strictly depends on the analyzed species. For this reason, it is not possible to infer general practical guidelines for lighting applications, and it becomes urgent to establish accurate and shared analysis protocols to be applied case by case, to study the effects of the environmental conditions on microorganisms and drive-specific design choices.

Болезнь Помпе с поздним началом

Pompe disease is a rare neuromuscular disorder associated with acid maltase deficiency. The severity of clinical manifestations and age of onset correlate with the type of mutation in the GAA gene and residual activity of lysosomal α-1,4-glucosidase. The infantile form of Pompe disease is characterized by hypertrophic cardiomyopathy, generalized muscle weakness, hypotonia, hepatomegaly and death from respiratory failure within the first year of life. Late-onset Pompe disease may develop at any age and affects skeletal muscle, causing slowly progressive muscle weakness and respiratory impairment. We report a case of late-onset Pompe disease in a 30-year-old female who was diagnosed only at 8 years after the onset of disease. The initial complaints were limited to difficulty in getting up from chairs and the need to help herself by hands. Diagnosis of Pompe disease was established by low α-1,4-glucosidase activity in dried blood spot and genetic testing that showed compound heterozygous mutations in the GAA gene (c.-32-13T&gt;G and c.2104C&gt;T).

Risk of depression in amyotrophic lateral sclerosis: A nationwide cohort study in South Korea

Depression is frequently reported in amyotrophic lateral sclerosis (ALS) due to the disastrous prognosis of progressive motor impairment, but the risk of depression in ALS is still unclear. Therefore, we investigated the risk of depression in ALS and analyzed the effect of ALS-related physical disability on the risk of developing depression using the Korean National Health Insurance Service (KNHIS) database. A total of 2241 ALS patients, as defined by the International Classification Diseases (ICD, G12.21) and Rare Intractable Disease codes (V123), and 1:10 sex- and age-matched controls were selected from the KNHIS. After applying exclusion criteria (non-participation in national health screening, history of depression, or having missing data), 595 ALS patients and 9896 non-ALS individuals were finally selected. Primary outcome is newly diagnosed depression during follow-up duration defined by ICD code (F32 or F33). A Cox regression model was used to examine the hazard ratios (HRs) after adjustment for potential confounders. During the follow-up period, 283 cases of depression in the ALS group and 1547 in the controls were recorded. The adjusted HR for depression in ALS was 9.1 (95% confidence interval [CI] 7.87−10.60). The risk of depression was slightly higher in the disabled ALS group (aHR 10.1, 95% CI 7.98−12.67) than in the non-disabled ALS group (aHR 8.78, 95% CI 7.42−10.39). The relative risk of depression was higher in younger patients than in older patients, and in obese patients than in non-obese patients. Our study showed that ALS patients have an increased risk of depression compared to non-ALS individuals.

Causal relationship between imaging-derived phenotypes and neurodegenerative diseases: a Mendelian randomization study.

Neurodegenerative diseases are incurable conditions that lead to gradual and progressive deterioration of brain function in patients. With the aging population, the prevalence of these diseases is expected to increase, posing a significant economic burden on society. Imaging techniques play a crucial role in the diagnosis and monitoring of neurodegenerative diseases. This study utilized a two-sample Mendelian randomization (MR) analysis to assess the causal relationship between different imaging-derived phenotypes (IDP) in the brain and neurodegenerative diseases. Multiple MR methods were employed to minimize bias and obtain reliable estimates of the potential causal relationship between the variable exposures of interest and the outcomes. The study found potential causal relationships between different IDPs and Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and frontotemporal dementia (FTD). Specifically, the study identified potential causal relationships between 2 different types of IDPs and AD, 8 different types of IDPs and PD, 11 different types of imaging-derived phenotypes and ALS, 1 type of IDP and MS, and 1 type of IDP and FTD. This study provides new insights for the prevention, diagnosis, and treatment of neurodegenerative diseases, offering important clues for understanding the pathogenesis of these diseases and developing relevant intervention strategies.

Targeting Neurological Aspects of Mucopolysaccharidosis Type II: Enzyme Replacement Therapy and Beyond.

Mucopolysaccharidosis type II (MPS II) is a rare, pediatric, neurometabolic disorder due to the lack of activity of the lysosomal hydrolase iduronate 2-sulfatase (IDS), normally degrading heparansulfate and dermatansulfate within cell lysosomes. The deficit of activity is caused by mutations affecting the IDS gene, leading to the pathological accumulation of both glycosaminoglycans in the lysosomal compartment and in the extracellular matrix of most body districts. Although a continuum of clinical phenotypes is described, two main forms are commonly recognized-attenuated and severe-the latter being characterized by an earlier and faster clinical progression and by a progressive impairment of central nervous system (CNS) functions. However, attenuated forms havealso been recently described as presenting some neurological involvement, although less deep, such as deficits of attention and hearing loss. The main treatment for the disease is represented by enzyme replacement therapy (ERT), applied in several countries since 2006, which, albeit showing partial efficacy on some peripheral organs, exhibited a very poor efficacy on bones and heart, and a total inefficacy on CNS impairment, due to the inability of the recombinant enzyme to cross the blood-brain barrier (BBB). Together with ERT, whose design enhancements, performed in the last few years, allowed a possible brain penetration of the drug through the BBB, other therapeutic approaches aimed at targeting CNS involvement in MPS II were proposed and evaluated in the last decades, such as intrathecal ERT, intracerebroventricular ERT, ex vivo gene therapy, or adeno-associated viral vector (AAV) gene therapy. The aim of this review is to summarize the main clinical aspects of MPS II in addition to current therapeutic options, with particular emphasis on the neurological ones and on the main CNS-targeted therapeutic approaches explored through the years.

Contribution to the analysis of the physico-chemical and rheological degradation of 15w40 lubricating oils for the optimization of drain intervals

Degradation of engine oil can lead to a reduction in its effectiveness in reducing friction, which has a negative impact on engine durability and performance. This research examined in detail the physico-chemical and rheological properties of new and used motor oils, divided into three groups (A, B and C) and subjected to different driving distances (0 km, 4000 km and 7000 km). The main findings include: Progressive degradation of kinematic viscosity at 40°C with increasing distance travelled, with greater degradation in group A. A similar degradation in kinematic viscosity at 100°C, with Group A showing the greatest degradation, suggesting a loss of efficiency at higher temperatures. A progressive decrease in viscosity index with increasing distance travelled. Significant changes in the total acid number (TAN) and total base number (TBN) of the oil with increasing distance travelled, with the greatest decrease in TBN observed in group C, suggesting acidification of the used oil. A progressive decrease in the sulfur content of used oil compared to new oil, mainly in group C. A progressive deterioration in dynamic viscosity with increasing distance travelled, particularly at higher temperatures. These results highlight the importance of regular maintenance and servicing of thermal engine lubricating oils particularly in an urban driving. future work Develop a predictive model using neural networks to analyze physical, chemical, and rheological properties, and monitor it online.

Inhibition of Calcineurin with FK506 Reduces Tau Levels and Attenuates Synaptic Impairment Driven by Tau Oligomers in the Hippocampus of Male Mouse Models.

Alzheimer's disease (AD) is the most common age-associated neurodegenerative disorder, characterized by progressive cognitive decline, memory impairment, and structural brain changes, primarily involving Aβ plaques and neurofibrillary tangles of hyperphosphorylated tau protein. Recent research highlights the significance of smaller Aβ and Tau oligomeric aggregates (AβO and TauO, respectively) in synaptic dysfunction and disease progression. Calcineurin (CaN), a key calcium/calmodulin-dependent player in regulating synaptic function in the central nervous system (CNS) is implicated in mediating detrimental effects of AβO on synapses and memory function in AD. This study aims to investigate the specific impact of CaN on both exogenous and endogenous TauO through the acute and chronic inhibition of CaN. We previously demonstrated the protective effect against AD of the immunosuppressant CaN inhibitor, FK506, but its influence on TauO remains unclear. In this study, we explored the short-term effects of acute CaN inhibition on TauO phosphorylation and TauO-induced memory deficits and synaptic dysfunction. Mice received FK506 post-TauO intracerebroventricular injection and TauO levels and phosphorylation were assessed, examining their impact on CaN and GSK-3β. The study investigated FK506 preventive/reversal effects on TauO-induced clustering of CaN and GSK-3β. Memory and synaptic function in TauO-injected mice were evaluated with/without FK506. Chronic FK506 treatment in 3xTgAD mice explored its influence on CaN, Aβ, and Tau levels. This study underscores the significant influence of CaN inhibition on TauO and associated AD pathology, suggesting therapeutic potential in targeting CaN for addressing various aspects of AD onset and progression. These findings provide valuable insights for potential interventions in AD, emphasizing the need for further exploration of CaN-targeted strategies.

Effect of wetting/drying cycles on the durability of flax fibers reinforced earth concrete

Earth concrete is composed of fine particles which make them very sensitive to humidity and affects their long-term durability. In this study, the effect of wetting/drying cycles on earth concrete according to ASTM D559 was studied by measuring the weight loss, pH, and Electrical Conductivity (EC). The effect of different percentages of flax fibers was investigated. The residual properties of reference specimens and earth concrete specimens subjected to wetting/drying cycles were evaluated by conducting compressive tests at the end of the 25 cycles. Ultrasound, Acoustic Emission (AE), and Digital Image Correlation (DIC) techniques were applied to estimate the concrete progressive deterioration during and at the end of the 25 wetting/drying cycles. The results showed that earth concrete degradation begins during the first cycle with visible cracks on the surface of the specimens. The mechanical tests showed a considerable loss of earth concrete mechanical properties after 25 cycles. The ultrasonic test showed that the degradation rate was more important for specimens without flax fibers. The cumulative acoustic activity was effectively used to assess the different damage progression phases and crack propagation. The signal parameters (energy, amplitude, etc.) evolution indicates premature damage for earth concrete specimens subjected to wetting drying cycles.