Enhancing the accuracy of engine calibration through a computer aided calibration algorithm

Abstract This paper addresses a novel Computer Aided Calibration software developed by the authors to overcome a critical issue of the traditional calibration process: improve the calibration accuracy. The algorithm includes some innovative features aimed at error minimization through a complete parametric analysis of a target ECU functions. Therefore, it is possible to assess if further quantities that are not considered as calibration parameters within the current ECU function model actually affect the quantity estimated by the function itself. If so, a more accurate physical model can be implemented within the ECU function to increase the accuracy of the calibration process

Two Conserved Cysteine Triads in Human Ero1α Cooperate for Efficient Disulfide Bond Formation in the Endoplasmic Reticulum

Human Ero1alpha is an endoplasmic reticulum (ER)-resident protein responsible for protein disulfide isomerase (PDI) oxidation. To clarify the molecular mechanisms underlying its function, we generated a panel of cysteine replacement mutants and analyzed their capability of: 1) complementing a temperature-sensitive yeast Ero1 mutant, 2) favoring oxidative folding in mammalian cells, 3) forming mixed disulfides with PDI and ERp44, and 4) adopting characteristic redox-dependent conformations. Our results reveal that two essential cysteine triads (Cys85-Cys94-Cys99 and Cys391-Cys394-Cys397) cooperate in electron transfer, with Cys94 likely forming mixed disulfides with PDI. Dominant negative phenotypes arise when critical residues within the triads are mutated (Cys394, Cys397, and to a lesser extent Cys99). Replacing the first cysteine in either triad (Cys85 or Cys391) generates mutants with weaker activity. In addition, mutating either Cys85 or Cys391, but not Cys397, reverts the dominant negative phenotype of the C394A mutant. These findings suggest that interactions between the two triads, dependent on Cys85 and Cys391, are important for Ero1alpha function, possibly stabilizing a platform for efficient PDI oxidation

Motion artefacts in cone beam CT: an in vitro study about the effects on the images

OBJECTIVE: In cone beam CT (CBCT), imperfect patient immobility, caused by involuntary movements, is one of the most important causes of artefacts and image quality degradation. Various works in literature address this topic, but seldom is the nature of the movement correlated with the type of artefact and the image degradation in a systematic manner, and the correlation analyzed and explained. METHODS: All three types of movements that can occur during a scan—nodding, tilting and rolling—were applied to a dry skull, in various manners from abrupt to gradual through the entire scan, at different times and angles, over a wide range of displacements. 84 scans were performed, with different skull movements, and the resulting images examined by two skilled radiologists, rated in a four-point scale and statistically analyzed. A commercial CBCT machine was used, featuring supine patient positioning. RESULTS: Different types of movements induce different artefacts, in different parts of the anatomy. In general, movement of short duration may lead to double contours (bilateral or monolateral depending upon the angle of the scan at which they occur), whereas gradual movements result into blurring. CONCLUSION: Not all movements cause motion artefacts that equally jeopardize the image. Rolling is the type of movement that most severely affects the image diagnostic value. ADVANCES IN KNOWLEDGE: These findings may help practitioners to identify the causes of motion artefacts and the resulting image degradation, and remediate them, and manufacturers to improve the patient-positioning devices

COMT Val158Met polymorphism and socioeconomic status interact to predict attention deficit/hyperactivity problems in children aged 10–14

The functional Val158Met COMT polymorphism appears to affect a host of behaviours mediated by the pre-frontal cortex, and has been found associated to the risk for disruptive behaviours including ADHD. Parental socioeconomic status (SES) has also been reported as a predictor for the same childhood disorders. In a general population sample of 575 Italian pre-adolescents aged 10–14, we examined the association of the functional Val158Met COMT polymorphism and SES—both as linear and interactive effects—with oppositional defiant problems, conduct problems, and attention deficit/hyperactivity problems, as defined by the newly established Child Behaviour Check-List/6-18 DSM oriented scales. Multivariate- and subsequent univariate-analysis of covariance showed a significant association of COMT × SES interaction with CBCL 6/18 DOS attention deficit/hyperactivity problems (p = 0.004), and revealed higher scores among those children with Val/Val COMT genotype who belonged to low-SES families. We also found a significant association of SES with attention deficit/hyperactivity problems and conduct problems DOS (p = 0.04 and 0.01, respectively). Our data are consistent with a bulk of recent literature suggesting a role of environmental factors in moderating the contribution of specific genetic polymorphisms to human variability in ADHD. While future investigations will refine and better clarify which specific environmental and genetic mechanisms are at work in influencing the individual risk to ADHD in pre-adolescence, these data may contribute to identify/prevent the risk for ADHD problems in childhood

Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health Hazard

Infection with Mycobacterium tuberculosis (TB) induces pulmonary immunopathology mediated by classical Th1 type of acquired immunity with hepatic involvement in up to 80% of disseminated cases. Since PPAR agonists cause immune responses characterized by a decrease in the secretion of Th1 cytokines, we investigated the impact of activating these receptors on hepatic pathology associated with a well-characterized model of Th1-type pulmonary response. Male Fischer 344 rats were either maintained on a drug-free diet (groups I and II), or a diet containing diethylhexylphthalate (DEHP), a compound transformed in vivo to metabolites known to activate PPARs, for 21 days (groups III and IV). Subsequently, animals were primed with Mycobacterium bovis purified protein derivative (PPD) in a Complete Freund's Adjuvant. Fifteen days later, animals in groups II and IV were challenged with Sepharose 4B beads covalently coupled with PPD, while animals in groups I and III received blank Sepharose beads. Animals with Th1 response (group II) showed a marked structural disruption in the hepatic lobule. Remarkably, these alterations were conspicuously absent in animals which received DEHP (group IV), despite noticeable accumulation of T cells in the periportal triads. Immunostaining and confocal microscopy revealed hepatic accumulation of IFNγ+ Th1 and IL-4+ Th2 cells in animals from groups II and IV, respectively. Our data suggest a PPARα-mediated suppression of the development of a Th1 immune response in the liver, resulting in hepatoprotective effect. However, potentially negative consequences of PPAR activation, such as decreased ability of the immune system to fight infection and interference with the efficacy of vaccines designed to evoke Th1 immune responses, remain to be investigated

Paramyxovirus Infection Regulates T Cell Responses by BDCA-1 + and BDCA-3 + Myeloid Dendritic Cells

Abstract Respiratory syncytial virus (RSV) and human Metapneumovirus (hMPV), viruses belonging to the family Paramyxoviridae, are the most important causes of lower respiratory tract infection in young children. Infections with RSV and hMPV are clinically indistinguishable, and both RSV and hMPV infection have been associated with aberrant adaptive immune responses. Myeloid Dendritic cells (mDCs) play a pivotal role in shaping adaptive immune responses during infection; however, few studies have examined how interactions of RSV and hMPV with individual mDC subsets (BDCA-1 + and BDCA-3 + mDCs) affect the outcome of anti-viral responses. To determine whether RSV and hMPV induce virus-specific responses from each subset, we examined co-stimulatory molecules and cytokines expressed by BDCA-1 + and BDCA-3 + mDCs isolated from peripheral blood after infection with hMPV and RSV, and examined their ability to stimulate T cell proliferation and differentiation. Our data show that RSV and hMPV induce virus-specific and subset-specific patterns of co-stimulatory molecule and cytokine expression. RSV, but not hMPV, impaired the capacity of infected mDCs to stimulate T cell proliferation. Whereas hMPVinfected BDCA-1 + and BDCA-3 + mDCs induced expansion of Th17 cells, in response to RSV, BDCA-1 + mDCs induced expansion of Th1 cells and BDCA-3 + mDCs induced expansion of Th2 cells and Tregs. These results demonstrate a virusspecific and subset-specific effect of RSV and hMPV infection on mDC function, suggesting that these viruses may induce different adaptive immune responses

A Systematic Review Establishing the Current State-of-the-Art, the Limitations, and the DESIRED Checklist in Studies of Direct Neural Interfacing With Robotic Gait Devices in Stroke Rehabilitation

Background: Stroke is a disease with a high associated disability burden. Robotic-assisted gait training offers an opportunity for the practice intensity levels associated with good functional walking outcomes in this population. Neural interfacing technology, electroencephalography (EEG), or electromyography (EMG) can offer new strategies for robotic gait re-education after a stroke by promoting more active engagement in movement intent and/or neurophysiological feedback. Objectives: This study identifies the current state-of-the-art and the limitations in direct neural interfacing with robotic gait devices in stroke rehabilitation. Methods: A pre-registered systematic review was conducted using standardized search operators that included the presence of stroke and robotic gait training and neural biosignals (EMG and/or EEG) and was not limited by study type. Results: From a total of 8,899 papers identified, 13 articles were considered for the final selection. Only five of the 13 studies received a strong or moderate quality rating as a clinical study. Three studies recorded EEG activity during robotic gait, two of which used EEG for BCI purposes. While demonstrating utility for decoding kinematic and EMG-related gait data, no EEG study has been identified to close the loop between robot and human. Twelve of the studies recorded EMG activity during or after robotic walking, primarily as an outcome measure. One study used multisource information fusion from EMG, joint angle, and force to modify robotic commands in real time, with higher error rates observed during active movement. A novel study identified used EMG data during robotic gait to derive the optimal, individualized robot-driven step trajectory. Conclusions: Wide heterogeneity in the reporting and the purpose of neurobiosignal use during robotic gait training after a stroke exists. Neural interfacing with robotic gait after a stroke demonstrates promise as a future field of study. However, as a nascent area, direct neural interfacing with robotic gait after a stroke would benefit from a more standardized protocol for biosignal collection and processing and for robotic deployment. Appropriate reporting for clinical studies of this nature is also required with respect to the study type and the participants' characteristics

PROGNOSTIC IMPACT OF IMMUNOHISTOCHEMICAL P53 EXPRESSION IN BONE MARROW BIOPSY IN HIGHER RISK MDS: A PILOT STUDY

Background and objectives: Mutations of the TP53 gene have an unfavorable prognosis in Myelodysplastic Syndromes (MDS). The product of the TP53gene is the p53 protein. Most of TP53mutations entail the accumulation of the protein in the nucleus of tumor cells. The immunohistochemical (IHC) staining for p53 can be a surrogate suggesting a mutational status and, if overexpressed, seems to be of prognostic value by itself. The best prognostic cut-off value of overexpression is controversial. The aim of this pilot study is to investigate about the correct value from a homogenous group of patients with higher IPSS-R risk MDS. Methods: In sixty consecutive patients diagnosed with MDS and categorized as IPSS-R risk “intermediate”, “high” and “very high”, the bone marrow biopsies performed at the diagnosis were retrospectively re-examined for IHC p53 expression. The result of p53 expression was subsequently related to survival.  Results: A worst overall survival was observed both in patients whose IHC p53 expression was ≥5% and ≥ 10% compared to the patients with a p53 expression respectively below 5% (p= 0.0063) or 10% (p=0.0038).  Conclusions: The ICH p53 expression in bone marrow biopsy in higher risk MDS was confirmed to have prognostic value.  These results indicate more than 10% expression as the best cut off value