1,547 research outputs found
Special Issue “Advances in Molecular Research on Autoimmune Diseases”
No full textAutoimmune diseases represent a diverse array of disorders in which the immune system mistakenly attacks the body’s own cells and tissues [...
The Role of Immune Dysfunction in Parkinson’s Disease Development
No full textRecent research has unveiled intriguing insights suggesting that the body’s immune system may be implicated in Parkinson’s disease (PD) development. Studies have observed disparities in pro-inflammatory and anti-inflammatory markers between PD patients and healthy individuals. This finding underscores the potential influence of immune system dysfunction in the genesis of this condition. A dysfunctional immune system can serve as a primary catalyst for systemic inflammation in the body, which may contribute to the emergence of various brain disorders. The identification of several genes associated with PD, as well as their connection to neuroinflammation, raises the likelihood of disease susceptibility. Moreover, advancing age and mitochondrial dysfunction can weaken the immune system, potentially implicating them in the onset of the disease, particularly among older individuals. Compromised integrity of the blood–brain barrier could facilitate the immune system’s access to brain tissue. This exposure may lead to encounters with native antigens or infections, potentially triggering an autoimmune response. Furthermore, there is mounting evidence supporting the notion that gut dysbiosis might represent an initial trigger for brain inflammation, ultimately promoting neurodegeneration. In this comprehensive review, we will delve into the numerous hypotheses surrounding the role of both innate and adaptive immunity in PD
Intrinsic timing properties of ideal 3D-trench silicon sensor with fast front-end electronics
No full textThis paper describes the fundamental timing properties of a single-pixel
sensor for charged particle detection based on the 3D-trench silicon structure.
We derive the results both analytically and numerically by considering a simple
ideal sensor and the corresponding fast front-end electronics in two different
case scenarios: ideal integrator and real fast electronics (trans-impedance
amplifier). The particular shape of the Time of Arrival (TOA) distribution is
examined and the relation between the time resolution and the spread of
intrinsic charge collection time is discussed, by varying electronics
parameters and discrimination thresholds. The results are obtained with and
without simulated electronics noise. We show that the 3D-trench sensors are
characterized by a , i.e. a portion of the active volume
which leads to the same TOA values when charged particles cross it. The
synchronous region size is dependent on the front-end electronics and
discrimination threshold, and the phenomenon represents an intrinsic physical
effect that leads to the excellent time resolution of these sensors. Moreover,
we show that the TOA distribution is characterized by an intrinsic asymmetry,
due to the 3D geometry only, that becomes negligible in case of significant
electronics jitter
Correlation between antibodies against the pathogenic pHERV-W envelope protein and the inflammatory phase of multiple sclerosis
No full text: The role of retroviral envelope proteins belonging to the Human Endogenous Retroviral family 'W' (HERV-W), specifically syncytin-1 and pathogenic HERV-W (pHERV-W), as potential risk factors in multiple sclerosis (MS) has been established. This study aimed to investigate the humoral response to syncytin-1 and pHERV-W-derived peptides in a group of relapsing remitting MS patients categorized as having acute or stable disease. Furthermore, an inhibition assay was conducted to assess the extent of cross-reactivity between the two epitopes. The findings revealed that MS patients in the acute phase exhibited a higher specific antibody response to the pHERV-W env epitope compared to syncytin-1. This suggests a potential pathogenic role for pHERV-W env during the inflammatory stages of central nervous system involvement, and these antibody responses could serve as useful biomarkers for monitoring the progression of the disease
MAP3738c and MptD are specific tags of Mycobacterium avium subsp. paratuberculosis infection in type I diabetes mellitus.
No full textContinual Learning with Echo State Networks
No full textContinual Learning (CL) refers to a learning setup where
data is non stationary and the model has to learn without forgetting ex-
isting knowledge. The study of CL for sequential patterns revolves around
trained recurrent networks. In this work, instead, we introduce CL in the
context of Echo State Networks (ESNs), where the recurrent component
is kept fixed. We provide the first evaluation of catastrophic forgetting in
ESNs and we highlight the benefits in using CL strategies which are not
applicable to trained recurrent models. Our results confirm the ESN as a
promising model for CL and open to its use in streaming scenarios
in Enhancing the Immunogenicity of Autoantigens During Experimental Autoimmune Encephalomyelitis
No full text: Experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) requires immunization by a MOG peptide emulsified in complete Freund's adjuvant (CFA) containing inactivated Mycobacterium tuberculosis. The antigenic components of the mycobacterium activate dendritic cells to stimulate T-cells to produce cytokines that promote the Th1 response via toll-like receptors. Therefore, the amount and species of mycobacteria present during the antigenic challenge are directly related to the development of EAE. This methods paper presents an alternative protocol to induce EAE in C57BL/6 mice using a modified incomplete Freund's adjuvant containing the heat-killed Mycobacterium avium subspecies paratuberculosis strain K-10. M. paratuberculosis, a member of the Mycobacterium avium complex, is the causative agent of Johne's disease in ruminants and has been identified as a risk factor for several human T-cell-mediated disorders, including multiple sclerosis. Overall, mice immunized with Mycobacterium paratuberculosis showed earlier onset and greater disease severity than mice immunized with CFA containing the strain of M. tuberculosis H37Ra at the same doses of 4 mg/mL. The antigenic determinants of Mycobacterium avium subspecies paratuberculosis (MAP) strain K-10 were able to induce a strong Th1 cellular response during the effector phase, characterized by significantly higher numbers of T-lymphocytes (CD4+ CD27+), dendritic cells (CD11c+ I-A/I-E+), and monocytes (CD11b+ CD115+) in the spleen compared to mice immunized with CFA. Furthermore, the proliferative T-cell response to the MOG peptide appeared to be highest in M. paratuberculosis-immunized mice. The use of an encephalitogen (e.g., MOG35-55) emulsified in an adjuvant containing M. paratuberculosis in the formulation may be an alternative and validated method to activate dendritic cells for priming myelin epitope-specific CD4+ T-cells during the induction phase of EAE
Epstein–Barr Virus and Human Endogenous Retrovirus in Japanese Patients with Autoimmune Demyelinating Disorders
No full textMultiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocytes glycoprotein-antibody disease (MOGAD) are distinct autoimmune demyelinating disorders characterized by varying clinical and pathological characteristics. While the precise origins of these diseases remain elusive, a combination of genetic and environmental factors, including viral elements, have been suggested as potential contributors to their development. Our goal was to assess the occurrence of antibodies against pathogenic peptides associated with Epstein–Barr virus (EBV) and the human endogenous retrovirus-W (HERV-W) in serum samples obtained from Japanese individuals diagnosed with MS, NMOSD, and MOGAD and to make comparisons with a group of healthy controls (HCs). We conducted a retrospective analysis involving 114 Japanese participants, comprising individuals with MS (34), NMOSD (20), MOGAD (20), and HCs (40). These individuals were tested using a peptide-based enzyme-linked immunosorbent assay. A marked increase in antibody response against EBV nuclear antigen 1 (EBNA1)386–405 was observed in the serum of MS and MOGAD patients, as compared to HCs. Notably, we observed a correlation between antibodies against EBNA1386–405 and HERV-W486–504 peptides in a subset of the antibody-positive MS patients. These findings emphasize the involvement of EBV in the pathogenesis of MS and potentially MOGAD, suggesting its role in the reactivation of HERV-W
Calibration of Continual Learning Models
No full textContinual Learning (CL) focuses on maximizing the predictive performance of a model across a non-stationary stream of data. Unfortunately, CL models tend to forget previous knowledge, thus often underperforming when compared with an offline model trained jointly on the entire data stream. Given that any CL model will eventually make mistakes, it is of crucial importance to build calibrated CL models: models that can reliably tell their confidence when making a prediction. Model calibration is an active research topic in machine learning, yet to be properly investigated in CL. We provide the first empirical study of the behavior of calibration approaches in CL, showing that CL strategies do not inherently learn calibrated models. To mitigate this issue, we design a continual calibration approach that improves the performance of post-processing calibration methods over a wide range of different benchmarks and CL strategies. CL does not necessarily need perfect predictive models, but rather it can benefit from reliable predictive models. We believe our study on continual calibration represents a first step towards this direction
- …
