Queueing Theory Software Packages

At the beginning of the thesis, I talked about the Theoretical part of the queuing theory and its principles. Introducing the types of programs used for testing and examining the software packages by giving some examples and explanations, later then at the last chapter I talked about Queueing Network both open and closed classes.BSc/BAcomputer science engineerin

Evaluation of acute flaccid paralysis surveillance system in the River Nile State - Northern Sudan, 2021

Abstract Background One of the four main elements of the worldwide polio eradication strategy is acute flaccid paralysis surveillance (AFP). This system is based on (acute flaccid paralysis (AFP) cases reported and tested at World Health Organization (WHO) accredited laboratories. To measure and monitor performance, indicators were created. The current study aims to evaluate the system components, performance, and efficiency in River Nile State, Northern Sudan, and their compliance with World Health Organization (WHO) requirements for it to be adopted as a good system; its results can be used to certify whether a country is polio-free or not. Material and methods A facility-based retrospective descriptive study was conducted in the River Nile State, Northern Sudan, from Jan 2017 to Dec 2020. This study included all reporting sites/units, workers who reported acute flaccid paralysis (AFP) cases, and officers at the locality level. A total of 50 health institutions were visited for surveillance, and interviews with 59 health workers who were part of the AFP surveillance system were undertaken. The data were collected from participants using a pre-tested questionnaire designed and constructed by the World Health Organization (WHO) framework, and the data were analyzed using the SPSS version (22). Results The River Nile State’s AFP surveillance system was of high quality in terms of the infrastructure that had been put in place and the effectiveness of the system’s operations, as evidenced by the following statistics: from 2017 to 2020, the reported non-polio acute flaccid paralysis (AFP) cases were at a mean rate of 4.02 per 100,000 children under the age of 15; the majority of AFP reported cases were under 10 years; and males made up 73.3% of reported cases; The completeness of reports and surveillance documents exceeded 80%, and active surveillance was applied in 80% of reporting sites. Conclusion Despite the fact that the surveillance system is capable of detecting cases, Sudan continues to report cases of imported polio from other countries, highlighting the need to strengthen surveillance systems and eradication efforts in these countries

Vascular hypertrophy-associated hypertension of profilin1 transgenic mouse model leads to functional remodeling of peripheral arteries

Increased mechanical stress/hypertension in the vessel wall triggers the hypertrophic signaling pathway, resulting in structural remodeling of vasculature. Vascular hypertrophy of resistance vessels leads to reduced compliance and elevation of blood pressure. We showed before that increased expression of profilin1 protein in the medial layer of the aorta induces stress fiber formation, triggering the hypertrophic signaling resulting in vascular hypertrophy and, ultimately, hypertension in older mice. Our hypothesis is that profilin1 induced vascular hypertrophy in resistance vessels, which led to elevation of blood pressure, both of which contributed to the modulation of vascular function. Our results showed significant increases in the expression of α1- and β1-integrins (280 ± 6.3 and 325 ± 7.4%, respectively) and the activation of the Rho/Rho-associated kinase (ROCK) II pathway (260 and 350%, respectively, P < 0.05) in profilin1 mesenteric arteries. The activation of Rho/ROCK led to the inhibition of endothelial nitric oxide synthase expression (39 ± 5.4%; P < 0.05) and phosphorylation (35 ± 4.5%; P < 0.05) but also an increase in myosin light chain 20 phosphorylation (372%, P < 0.05). There were also increases in hypertrophic signaling pathways in the mesenteric arteries of profilin1 mice such as phospho-extracellular signal-regulated kinase 1/2 and phospho-c-Jun NH2-terminal kinase (312.15 and 232.5%, respectively, P < 0.05). Functional analyses of mesenteric arteries toward the vasoactive drugs were assessed using wire-myograph and showed significant increases in the vascular responses of profilin1 mesenteric arteries toward phenylephrine, but significant decreases in response toward ROCK inhibitor Y-27632, ACh, sodium nitrite, and cytochalasin D. The changes in vascular responses in the mesenteric arteries of profilin1 mice are due to vascular hypertrophy and the elevation of blood pressure in the profilin1 transgenic mice

UTP – Gated Signaling Pathways of 5-HT Release from BON Cells as a Model of Human Enterochromaffin Cells

Background: Enterochromaffin cells (EC) synthesize and release 5-HT and ATP to trigger or modulate gut neural reflexes and transmit information about visceral/pain sensation. Alterations in 5-HT signaling mechanisms may contribute to the pathogenesis of IBD or IBS, but the pharmacologic or molecular mechanisms modulating Ca2+-dependent 5-HT release are not understood. Previous studies indicated that purinergic signaling via ATP and ADP is an important mechanism in modulation of 5-HT release. However, EC cells also respond to UTP and UDP suggesting uridine triphosphate receptor and signaling pathways are involved as well. We tested the hypothesis that UTP is a regulator of 5-HT release in human EC cells.Methods: UTP signaling mechanisms were studied in BON cells, a human EC model, using Fluo-4/Ca2+imaging, patch-clamp, pharmacological analysis, immunohistochemistry, western blots and qPCR. 5-HT release was monitored in BON or EC isolated from human gut surgical specimens (hEC).Results: UTP, UTPγS, UDP or ATP induced Ca2+oscillations in BON. UTP evoked a biphasic concentration-dependent Ca2+response. Cells responded in the order of UTP, ATP &gt; UTPγS &gt; UDP &gt;&gt; MRS2768, BzATP, α,β-MeATP &gt; MRS2365, MRS2690, and NF546. Different proportions of cells activated by UTP and ATP also responded to UTPγS (P2Y4, 50% cells), UDP (P2Y6, 30%), UTPγS and UDP (14%) or MRS2768 (&lt;3%). UTP Ca2+responses were blocked with inhibitors of PLC, IP3R, SERCA Ca2+pump, La3+sensitive Ca2+channels or chelation of intracellular free Ca2+ by BAPTA/AM. Inhibitors of L-type, TRPC, ryanodine-Ca2+pools, PI3-Kinase, PKC or SRC-Kinase had no effect. UTP stimulated voltage-sensitive Ca2+currents (ICa), Vm-depolarization and inhibited IK (not IA) currents. An IKv7.2/7.3 K+ channel blocker XE-991 mimicked UTP-induced Vm-depolarization and blocked UTP-responses. XE-991 blocked IK and UTP caused further reduction. La3+ or PLC inhibitors blocked UTP depolarization; PKC inhibitors, thapsigargin or zero Ca2+buffer did not. UTP stimulated 5-HT release in hEC expressing TPH1, 5-HT, P2Y4/P2Y6R. Zero-Ca2+buffer augmented Ca2+responses and 5-HT release.Conclusion: UTP activates a predominant P2Y4R pathway to trigger Ca2+oscillations via internal Ca2+mobilization through a PLC/IP3/IP3R/SERCA Ca2+signaling pathway to stimulate 5-HT release; Ca2+influx is inhibitory. UTP-induced Vm-depolarization depends on PLC signaling and an unidentified K channel (which appears independent of Ca2+oscillations or Ica/VOCC). UTP-gated signaling pathways triggered by activation of P2Y4R stimulate 5-HT release

Rac-Induced Left Ventricular Dilation in Thyroxin-Treated ZmRacD Transgenic Mice: Role of Cardiomyocyte Apoptosis and Myocardial Fibrosis

<div><p>The pathways inducing the critical transition from compensated hypertrophy to cardiac dilation and failure remain poorly understood. The goal of our study is to determine the role of Rac-induced signaling in this transition process. Our previous results showed that Thyroxin (T4) treatment resulted in increased myocardial Rac expression in wild-type mice and a higher level of expression in Zea maize RacD (ZmRacD) transgenic mice. Our current results showed that T4 treatment induced physiologic cardiac hypertrophy in wild-type mice, as demonstrated by echocardiography and histopathology analyses. This was associated with significant increases in myocardial Rac-GTP, superoxide and ERK1/2 activities. Conversely, echocardiography and histopathology analyses showed that T4 treatment induced dilated cardiomyopathy along with compensatory cardiac hypertrophy in ZmRacD mice. These were linked with further increases in myocardial Rac-GTP, superoxide and ERK1/2 activities. Additionally, there were significant increases in caspase-8 expression and caspase-3 activity. However, there was a significant decrease in p38-MAPK activity. Interestingly, inhibition of myocardial Rac-GTP activity and superoxide generation with pravastatin and carvedilol, respectively, attenuated all functional, structural, and molecular changes associated with the T4-induced cardiomyopathy in ZmRacD mice except the compensatory cardiac hypertrophy. Taken together, T4-induced ZmRacD is a novel mouse model of dilated cardiomyopathy that shares many characteristics with the human disease phenotype. To our knowledge, this is the first study to show graded Rac-mediated O₂·⁻ results in cardiac phenotype shift <em>in-vivo</em>. Moreover, Rac-mediated O₂·⁻ generation, cardiomyocyte apoptosis, and myocardial fibrosis seem to play a pivotal role in the transition from cardiac hypertrophy to cardiac dilation and failure. Targeting Rac signaling could represent valuable therapeutic strategy not only in saving the failing myocardium but also to prevent this transition process.</p> </div

Ech Table 2. Echocardiography Analysis.

<p>IVS, interventricular septum; LVID, left ventricular internal diameter; LVPW, left ventricular posterior wall; s, systole; d; diastole; BW, body weight; EF, ejection fraction; FS, fractional shortening.</p>*<p>is significant change compared to untreated WT mice,</p>**<p>is significant change compared to T4-treated and untreated WT mice,</p>#<p>is significant change compared to untreated transgenic mice, and.</p>+<p>is significant change compared to T4-treated transgenic mice (n = 8/group).</p

Dilated Cardiomyopathy of T4-Treated Transgenic Mice is Associated with Increased Cardiomyocyte Apoptosis and TNF-α expression.

<p>Representative images of in situ terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) staining in FFPE mid-ventricle sections, with bar graph for the mean % of the brown colored apoptotic nuclei (<b>A & B</b>). Western blot analysis of TNF-α in transgenic mice hearts (<b>C</b>). <b>*</b> is significant change compared to untreated WT mice, <b>**</b> is significant change compared to T4-treated and untreated WT mice, <b>#</b> is significant change compared to untreated transgenic mice, and <b>+</b> is significant change compared to T4-treated transgenic mice (n = 8/group).</p