Real Time Optimal Tuning of Quadcopter Attitude Controller Using Particle Swarm Optimization

A real-time novel algorithm for proportional, integral and derivative (PID) controller tuning for quadcopters is introduced. The particle swarm optimization (PSO) method is utilized to search the quadcopter solution space to find the best PID controller parameters. A fuzzy logic (FL) controller is used to provide proper velocity reference signals to serve as tracking set points to be achieved by the PID controller. This nested loop design is proposed for stabilizing the quadcopter, where the fuzzy logic controller (FL) is used in the stable loop (i.e. outer loop) to control the desired angle, while the PID controller is used for the rate loop (i.e. inner loop). Finally, the optimum generated PID parameters were achieved in real time using the PSO search algorithm. The generated parameters were tested successfully using an experimental quadcopter setup at the University of Jordan

Mesenchymal Stem Cells Loaded with p5, Derived from CDK5 Activator p35, Inhibit Calcium-Induced CDK5 Activation in Endothelial Cells.

The potential use of stem cells as therapeutics in disease has gained momentum over the last few years and recently phase-I clinical trials have shown favourable results in treatment of a small cohort of acute stroke patients. Similarly, they have been used in preclinical models drug-loaded for the effective treatment of solid tumours. Here we have characterized uptake and release of a novel p5-cyclin-dependent kinase 5 (CDK5) inhibitory peptide by mesenchymal stem cells and showed release levels capable of blocking aberrant cyclin-dependent kinase 5 (CDK5) signaling pathways, through phosphorylation of cyclin-dependent kinase 5 (CDK5) and p53. These pathways represent the major acute mechanism stimulating apoptosis after stroke and hence its modulation could benefit patient recovery. This work indicates a potential use for drug-loaded stem cells as delivery vehicles for stroke therapeutics and in addition as anticancer receptacles particularly, if a targeting and/or holding mechanism can be defined

Expression of monomeric C-reactive protein in infarcted brain tissue from patients with Alzheimer’s disease

Objective: We have previously shown that monomeric-C-reactive protein is deposited in significant quantities within the brain parenchyma after stroke. Since we have recently identified a possible role of this protein in supporting neurodegeneration and aberrant vascular development, we identified a small group of post-mortem brain samples from individuals who had Alzheimer’s disease and evidence of tissue infarction/ micro-infarction on histological examination. Material and Method: We used immunohistochemistry staining to identify the monomeric-C-reactive protein expressed in the infarcted brain tissues. Results: We showed that monomeric-C-reactive protein deposition was highest in those regions affected by stroke or vascular disruption, and that within those same areas, there was more interaction and co-localization between major classical proteins of neurodegeneration (β-amyloid and tau). Conclusion: We hypothesise that vascular disruption and concomitant release of monomeric-C-reactive protein within the brain tissue could exacerbate ongoing neurological damage via stimulation of neuro-inflammation and from direct consequences of its action on both neuronal and vascular cells

Monomeric C-Reactive Protein Localized in the Cerebral Tissue of Damaged Vascular Brain Regions Is Associated With Neuro-Inflammation and Neurodegeneration-An Immunohistochemical Study

Monomeric C-reactive protein (mCRP) is now accepted as having a key role in modulating inflammation and in particular, has been strongly associated with atherosclerotic arterial plaque progression and instability and neuroinflammation after stroke where a build-up of the mCRP protein within the brain parenchyma appears to be connected to vascular damage, neurodegenerative pathophysiology and possibly Alzheimer's Disease (AD) and dementia. Here, using immunohistochemical analysis, we wanted to confirm mCRP localization and overall distribution within a cohort of AD patients showing evidence of previous infarction and then focus on its co-localization with inflammatory active regions in order to provide further evidence of its functional and direct impact. We showed that mCRP was particularly seen in large amounts within brain vessels of all sizes and that the immediate micro-environment surrounding these had become laden with mCRP positive cells and extra cellular matrix. This suggested possible leakage and transport into the local tissue. The mCRP-positive regions were almost always associated with neurodegenerative, damaged tissue as hallmarked by co-positivity with pTau and β-amyloid staining. Where this occurred, cells with the morphology of neurons, macrophages and glia, as well as smaller microvessels became mCRP-positive in regions staining for the inflammatory markers CD68 (macrophage), interleukin-1 beta (IL-1β) and nuclear factor kappa B (NFκB), showing evidence of a perpetuation of inflammation. Positive staining for mCRP was seen even in distant hypothalamic regions. In conclusion, brain injury or inflammatory neurodegenerative processes are strongly associated with mCRP localization within the tissue and given our knowledge of its biological properties, it is likely that this protein plays a direct role in promoting tissue damage and supporting progression of AD after injury.The authors extend their appreciations to the deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for funding this research work through the project number (lFP-2020-36). The authors would also like to thank Deanship of Scientific Research at Majmaah University, Al Majmaah-11952, Saudi Arabia for supporting this work. This work was supported from a grant from the Competitiveness Operational programme 2014–2020: C-reactive protein therapy for stroke-associated dementia: ID_P_37_674, My SMIS code:103432 contract 51/05.09.2016

Citicoline induces angiogenesis improving survival of vascular/human brain microvessel endothelial cells through pathways involving ERK1/2 and insulin receptor substrate-1.

BACKGROUND: Citicoline is one of the neuroprotective agents that have been used as a therapy in stroke patients. There is limited published data describing the mechanisms through which it acts. METHODS: We used in vitro angiogenesis assays: migration, proliferation, differentiation into tube-like structures in Matrigel™ and spheroid development assays in human brain microvessel endothelial cells (hCMEC/D3). Western blotting was performed on protein extraction from hCMEC/D3 stimulated with citicoline. An analysis of citicoline signalling pathways was previously studied using a Kinexus phospho-protein screening array. A staurosporin/calcium ionophore-induced apoptosis assay was performed by seeding hCMEC/D3 on to glass coverslips in serum poor medium. In a pilot in vivo study, transient MCAO in rats was carried out with and without citicoline treatment (1000 mg/Kg) applied at the time of occlusion and subsequently every 3 days until euthanasia (21 days). Vascularity of the stroke-affected regions was examined by immunohistochemistry. RESULTS: Citicoline presented no mitogenic and chemotactic effects on hCMEC/D3; however, it significantly increased wound recovery, the formation of tube-like structures in Matrigel™ and enhanced spheroid development and sprouting. Citicoline induced the expression of phospho-extracellular-signal regulated kinase (ERK)-1/2. Kinexus assays showed an over-expression of insulin receptor substrate-1 (IRS-1). Knock-down of IRS-1 with targeted siRNA in our hCMEC/D3 inhibited the pro-angiogenic effects of citicoline. The percentage of surviving cells was higher in the presence of citicoline. Citicoline treatment significantly increased the numbers of new, active CD105-positive microvessels following MCAO. CONCLUSIONS: The findings demonstrate both a pro-angiogenic and protective effect of citicoline on hCMEC/D3 in vitro and following middle cerebral artery occlusion (MCAO) in vivo

Transcriptomics-based characterization of the toxicity of ZnO nanoparticles against chronic myeloid leukemia cells

Introduction: Zinc oxide nanoparticles (ZnO NPs) have recently attracted attention as potential anti-cancer agents. To the best of our knowledge, the toxicity of ZnO NPs against human chronic myeloid leukemia cells (K562 cell line) has not been studied using transcriptomics approach. Objective: The goals of this study were to evaluate the capability of ZnO NPs to induce apoptosis in human chronic myeloid leukemia cells (K562 cells) and to investigate the putative mechanisms of action. Methods: We used viability assay and flowcytometry coupled with Annexin V-FITC and propidium iodide to investigate the toxicity of ZnO NPs on K562 cells and normal peripheral blood mononuclear cells. Next we utilized a DNA microarray-based transcriptomics approach to characterize the ZnO NPs-induced changes in the transcriptome of K562 cells. Results: ZnO NPs exerted a selective toxicity (mainly by apoptosis) on the leukemic cells (p≤ 0.005) and altered their transcriptome; 429 differentially expressed genes (DEGs) with fold change (FC)≥ 4 and p≤ 0.008 with corrected p≤ 0.05 were identified in K562 cells post treatment with ZnO NPs. The over-expressed genes were implicated in “response to zinc”, “response to toxic substance” and “negative regulation of growth” (corrected p≤ 0.05). In contrast, the repressed genes positively regulated “cell proliferation”, “cell migration”, “cell adhesion”, “receptor signaling pathway via JAK-STAT” and “phosphatidylinositol 3-kinase signaling” (corrected p≤ 0.05). Lowering the FC to ≥ 1.5 with p≤ 0.05 and corrected p≤ 0.1 showed that ZnO NPs over-expressed the anti-oxidant defense system, drove K562 cells to undergo mitochondrial-dependent apoptosis, and targeted NF-κB pathway. Conclusion: Taken together, our findings support the earlier studies that reported anti-cancer activity of ZnO NPs and revealed possible molecular mechanisms employed by ZnO NPs to induce apoptosis in K562 cells

(123)I-FP-CIT SPECT imaging in early diagnosis of dementia in patients with and without a vascular component.

Alzheimer's disease (AD) and vascular dementia (VaD) are the most common cause of dementia. Cerebral ischemia is a major risk factor for development of dementia. (123)I-FP-CIT SPECT (DaTScan) is a complementary tool in the differential diagnoses of patients with incomplete or uncertain Parkinsonism. Additional application of DaTScan enables the categorization of Parkinsonian disease with dementia (PDD), and its differentiation from pure AD, and may further contribute to change the therapeutic decision. The aim of this study was to analyze the vascular contribution towards dementia and mild cognitive impairment (MCI). We evaluated the utility of DaTScan for the early diagnosis of dementia in patients with and without a clinical vascular component, and the association between neuropsychological function, vascular component and dopaminergic function on DaTScan. One-hundred and five patients with MCI or the initial phases of dementia were studied prospectively. We developed an initial assessment using neurologic examination, blood tests, cognitive function tests, structural neuroimaging and DaTScan. The vascular component was later quantified in two ways: clinically, according to the Framingham Risk Score (FRS) and by structural neuroimaging using Wahlund Scale Total Score (WSTS). Early diagnosis of dementia was associated with an abnormal DaTScan. A significant association was found between a high WSTS and an abnormal DaTScan (p < 0.01). Mixed AD was the group with the highest vascular component, followed by the VaD group, while MCI and pure AD showed similar WSTS. No significant associations were found between neuropsychological impairment and DaTScan independently of associated vascular component. DaTScan seems to be a good tool to discriminate, in a first clinical assessment, patients with MCI from those with established dementia. There was bigger general vascular affectation observable in MRI or CT in patients with abnormal dopaminergic uptake seen on DaTScan

Monomeric C-reactive protein localized in the cerebral tissue of damaged vascular brain regions is associated with neuro-inflammation and neurodegeneration - an immunohistochemical study

Monomeric C-reactive protein (mCRP) is now accepted as having a key role in modulating inflammation and in particular, has been strongly associated with atherosclerotic arterial plaque progression and instability and neuroinflammation after stroke where a build-up of the mCRP protein within the brain parenchyma appears to be connected to vascular damage, neurodegenerative pathophysiology and possibly Alzheimer's Disease (AD) and dementia. Here, using immunohistochemical analysis, we wanted to confirm mCRP localization and overall distribution within a cohort of AD patients showing evidence of previous infarction and then focus on its co-localization with inflammatory active regions in order to provide further evidence of its functional and direct impact. We showed that mCRP was particularly seen in large amounts within brain vessels of all sizes and that the immediate micro-environment surrounding these had become laden with mCRP positive cells and extra cellular matrix. This suggested possible leakage and transport into the local tissue. The mCRP-positive regions were almost always associated with neurodegenerative, damaged tissue as hallmarked by co-positivity with pTau and β-amyloid staining. Where this occurred, cells with the morphology of neurons, macrophages and glia, as well as smaller microvessels became mCRP-positive in regions staining for the inflammatory markers CD68 (macrophage), interleukin-1 beta (IL-1β) and nuclear factor kappa B (NFκB), showing evidence of a perpetuation of inflammation. Positive staining for mCRP was seen even in distant hypothalamic regions. In conclusion, brain injury or inflammatory neurodegenerative processes are strongly associated with mCRP localization within the tissue and given our knowledge of its biological properties, it is likely that this protein plays a direct role in promoting tissue damage and supporting progression of AD after injury

A Novel SALL4/OCT4 Transcriptional Feedback Network for Pluripotency of Embryonic Stem Cells

Background: SALL4 is a member of the SALL gene family that encodes a group of putative developmental transcription factors. Murine Sall4 plays a critical role in maintaining embryonic stem cell (ES cell) pluripotency and self-renewal. We have shown that Sall4 activates Oct4 and is a master regulator in murine ES cells. Other SALL gene members, especially Sall1 and Sall3 are expressed in both murine and human ES cells, and deletions of these two genes in mice lead to perinatal death due to developmental defects. To date, little is known about the molecular mechanisms controlling the regulation of expressions of SALL4 or other SALL gene family members. Methodology/Principal Findings: This report describes a novel SALL4/OCT4 regulator feedback loop in ES cells in balancing the proper expression dosage of SALL4 and OCT4 for the maintenance of ESC stem cell properties. While we have observed that a positive feedback relationship is present between SALL4 and OCT4, the strong self-repression of SALL4 seems to be the “break” for this loop. In addition, we have shown that SALL4 can repress the promoters of other SALL family members, such as SALL1 and SALL3, which competes with the activation of these two genes by OCT4. Conclusions/Significance: Our findings, when taken together, indicate that SALL4 is a master regulator that controls its own expression and the expression of OCT4. SALL4 and OCT4 work antagonistically to balance the expressions of other SALL gene family members. This novel SALL4/OCT4 transcription regulation feedback loop should provide more insight into the mechanism of governing the “stemness” of ES cells