Experiments and Simulations of short-pulse laser-pumped extreme ultraviolet lasers

Recent experimental work on the development of extreme ultraviolet lasers undertaken using as the pumping source the VULCAN laser at the Rutherford Appleton Laboratory is compared to detailed simulations. It is shown that short duration (similar topicosecond) pumping can produce X-ray laser pulses of a few picosecond duration and that measurement of the emission from the plasma can give an estimate of the duration of the gain coefficient. The Ehybrid fluid and atomic physics code developed at the University of York is used to simulate X-ray laser gain and plasma emission. Two postprocessors to the Ehybrid code are utilized: 1) to raytrace the X-ray laser beam amplification and refraction and 2) to calculate the radiation emission in the kiloelectronvolt photon energy range. The raytracing and spectral simulations are compared, respectively, to measured X-ray laser output and the output of two diagnostics recording transverse X-ray emission. The pumping laser energy absorbed in the plasma is examined by comparing the simulations to experimental results. It is shown that at high pumping irradiance (>10(15) Wcm(-2)), fast electrons are produced by parametric processes in the preformed long scale-length plasmas. These fast electrons do not pump the population inversion and so pumping efficiency is reduced at high irradiance

Existence and uniqueness of near-coupled coincidence points in partial cone-interval metric spaces

This paper introduces a new type of space called partial cone-interval metric space, and explores some of its topological properties. Using a novel fixed-point technique, we investigate the existence and uniqueness of near-coupled coincidence points in this setting. We provide numerical examples to demonstrate the effectiveness of our approach

Design, synthesis, antitumor activity and molecular docking study of novel 5-deazaalloxazine analogs

open access articleProtein tyrosine kinases (PTKs) are the most potential therapeutic targets for cancer. Herein, we present a sound rationale for synthesis of a series of novel 2-(methylthio), 2-(substituted alkylamino), 2-(heterocyclic substituted), 2-amino, 2,4-dioxo and 2-deoxo-5-deazaalloxazine derivatives by applying structure-based drug design (SBDD) using AutoDock 4.2. Their antitumor activities against human CCRF-HSB-2, KB, MCF-7 and HeLa have been investigated in vitro. Many 5-deazaalloxazine analogs revealed high selective activities against MCF-7 tumor cell lines (IC50: 0.17–2.17 µM) over HeLa tumor cell lines (IC50 > 100 µM). Protein kinase profiling revealed that compound 3h induced multi- targets kinase inhibition including −43% against (FAK), −40% against (CDKI) and −36% against (SCR). Moreover, the Annexin-V/PI apoptotic assay elucidate that compound 3h showed 33% and potentially 140% increase in early and late apoptosis to MCF-7 cells respectively, compared to the control. The structure-activity relationship (SAR) and molecular docking study using PTK as a target enzyme for the synthesized 7-deazaalloaxazine derivatives were investigated as potential antitumor agents. The AutoDock binding affinities of the 5deazaalloxazine analogs into c-kit PTK (PDB code: 1t46) revealed reasonable correlations between their AutoDock binding free energy and IC50

Evaluation of biofertilization on antimicrobial activity and phytochemical profile of Moringa olifera plant

Pot experiment was carried out during May 2019 at private farm in el Manyial, Cairo, Egypt. The investigation target was to find out the difference between using plant growth promoting rhizobacteria (B. cereus, Streptomyces chibaensis, B. megaterium, B. polymyxa) either individual or in combination with each other and mineral fertilization on antimicrobial activity and some phytochemical constitutes of Moringa olifera leaves. The highest values of antimicrobial activity recorded for mineral fertilization on treatment followed by mixed biofertilization treatment (GP4) (B. megaterium, B. polymyxa) against seven foodborne pathogens Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, Pseudomonas aeruginosa, Aspergillus niger, Rhizopus stolonifer and Botrytis cinera, as compared with the control treatment. Biofertilization treatment (B. megaterium, B. polymyxa) recorded increasing over control in (GP10) by 160.8% and decreasing of chemical fertilization by 5.41% for polyphenol content, also, the antioxidant content shown increasing over the control (GP10) by 81.1% and decreasing of chemical fertilization (GP9) by 5.6% as well as vitamin C and A were increased with mineral and biofertilizer (GP4) treatments after 55 days. Biofertilization in (GP4) recorded increasing over control group (GP10) by 48.89%, 27.08% and 58% for vitamin A, C and chlorophyll respectively. Ethyl acetate extract was found to be most potent extract than ethanol and water against all tested microorganism

Colorectal and Prostate Cancer Risk in Diabetes: Metformin, an Actor behind the Scene

Both diabetes and cancer are prevalent diseases whose incidence rates are increasing worldwide, especially in countries that are undergoing rapid industrialization changes. Apparently, lifestyle risk factors including diet, physical inactivity and obesity play pivotal, yet preventable, roles in the etiology of both diseases. Epidemiological studies provide strong evidence that subjects with diabetes are at significantly higher risk of developing many forms of cancer and especially solid tumors. In addition to pancreatic and breast cancer, the incidence of colorectal cancer and prostate cancer is increased in type 2 diabetes. While diabetes (type 2) and cancer share many risk factors, the biological links between the two diseases are poorly characterized. In this review, we highlight the mechanistic pathways that link diabetes to colorectal and prostate cancer and the use of Metformin, a diabetes drug, to prevent and/or treat colorectal and prostate cancer. We review the role of AMPK activation in autophagy, oxidative stress, inflammation, apoptosis, and cell cycle progression.This publication was made possible by grant #NPRP 5-409-3-112 from the Qatar National Research Fund (a member of Qatar Foundation)

Inositol 1,4,5-Trisphosphate Receptors in Hypertension.

Chronic hypertension remains a major cause of global mortality and morbidity. It is a complex disease that is the clinical manifestation of multiple genetic, environmental, nutritional, hormonal, and aging-related disorders. Evidence supports a role for vascular aging in the development of hypertension involving an impairment in endothelial function together with an alteration in vascular smooth muscle cells (VSMCs) calcium homeostasis leading to increased myogenic tone. Changes in free intracellular calcium levels ([Ca] ) are mediated either by the influx of Ca from the extracellular space or release of Ca from intracellular stores, mainly the sarcoplasmic reticulum (SR). The influx of extracellular Ca occurs primarily through voltage-gated Ca channels (VGCCs), store-operated Ca channels (SOC), and Ca release-activated channels (CRAC), whereas SR-Ca release occurs through inositol trisphosphate receptor (IPR) and ryanodine receptors (RyRs). IPR-mediated SR-Ca release, in the form of Ca waves, not only contributes to VSMC contraction and regulates VGCC function but is also intimately involved in structural remodeling of resistance arteries in hypertension. This involves a phenotypic switch of VSMCs as well as an alteration of cytoplasmic Ca signaling machinery, a phenomena tightly related to the aging process. Several lines of evidence implicate changes in expression/function levels of IPR isoforms in the development of hypertension, VSMC phenotypic switch, and vascular aging. The present review discusses the current knowledge of these mechanisms in an integrative approach and further suggests potential new targets for hypertension management and treatment.This publication was made possible by an MPP fund (#320133) from the American University of Beirut to AE

Flavin Oxidase-Induced ROS Generation Modulates PKC Biphasic Effect of Resveratrol on Endothelial Cell Survival.

Dietary intake of natural antioxidants is thought to impart protection against oxidative-associated cardiovascular diseases. Despite many in vivo studies and clinical trials, this issue has not been conclusively resolved. Resveratrol (RES) is one of the most extensively studied dietary polyphenolic antioxidants. Paradoxically, we have previously demonstrated that high RES concentrations exert a pro-oxidant effect eventually elevating ROS levels leading to cell death. Here, we further elucidate the molecular determinants underpinning RES-induced oxidative cell death. Using human umbilical vein endothelial cells (HUVECs), the effect of increasing concentrations of RES on DNA synthesis and apoptosis was studied. In addition, mRNA and protein levels of cell survival or apoptosis genes, as well as protein kinase C (PKC) activity were determined. While high concentrations of RES reduce PKC activity, inhibit DNA synthesis and induce apoptosis, low RES concentrations elicit an opposite effect. This biphasic concentration-dependent effect (BCDE) of RES on PKC activity is mirrored at the molecular level. Indeed, high RES concentrations upregulate the proapoptotic , while downregulating the antiapoptotic , at both mRNA and protein levels. Similarly, high RES concentrations downregulate the cell cycle progression genes, , ornithine decarboxylase and cyclin D1 protein levels, while low RES concentrations display an increasing trend. The BCDE of RES on PKC activity is abrogated by the ROS scavenger Tempol, indicating that this enzyme acts downstream of the RES-elicited ROS signaling. The RES-induced BCDE on HUVEC cell cycle machinery was also blunted by the flavin inhibitor diphenyleneiodonium (DPI), implicating flavin oxidase-generated ROS as the mechanistic link in the cellular response to different RES concentrations. Finally, PKC inhibition abrogates the BCDE elicited by RES on both cell cycle progression and pro-apoptotic gene expression in HUVECs, mechanistically implicating PKC in the cellular response to different RES concentrations. Our results provide new molecular insight into the impact of RES on endothelial function/dysfunction, further confirming that obtaining an optimal benefit of RES is concentration-dependent. Importantly, the BCDE of RES could explain why other studies failed to establish the cardio-protective effects mediated by natural antioxidants, thus providing a guide for future investigation looking at cardio-protection by natural antioxidants

Dramatic outcomes in epilepsy: depression, suicide, injuries, and mortality

In this narrative review, we will discuss some of the significant risks and dramatic consequences that are associated with epilepsy: depression, suicide, seizure-related injuries, and mortality, both in adults and in children. Considering the high prevalence of depression among people with epilepsy (PWE), routine and periodic screening of all PWE for early detection and appropriate management of depression is recommended. PWE should be screened for suicidal ideation regularly and when needed, patients should be referred for a psychiatric evaluation and treatment. When starting an antiepileptic drug (AED) or switching from one to another AED, patients should be advised to report to their treating physician any change in their mood and existence of suicidal ideation. The risk of injuries for the general epilepsy population is increased only moderately. The risk is higher in selected populations attending epilepsy clinics and referral centers. This being said, there are PWE that may suffer frequent, severe, and sometimes even life-threatening seizure-related injuries. The most obvious way to reduce risk is to strive for improved seizure control. Finally, PWE have a 2–3 times higher mortality rate than the general population. Deaths in PWE may relate to the underlying cause of epilepsy, to seizures (including sudden unexpected death in epilepsy [SUDEP] and seizure related injuries) and to status epilepticus, as well as to other conditions that do not appear directly related to epilepsy. Improving seizure control and patient education may be the most important measures to reduce epilepsy related mortality in general and SUDEP in particular

Far-Lateral Cervical Approach as a Minimally Invasive Technique for Excision of Upper Cervical Anterolateral and Anterior Meningiomas and Dumbbell Schwannomas: Technical Report and Case Series

Objective To demonstrate the details of the far-lateral approach (FLA) as a minimally invasive technique for the excision of the upper cervical anterolateral and anterior meningiomas and dumbbell schwannomas, and to assess the clinical and radiological outcomes. Methods In this technical report and case series we report the FLA technique and patients who underwent the FLA for C1-C4 anterolateral and anterior meningiomas and dumbbell schwannomas between June 2007 and June 2020. All patients’ relative preoperative demographic, clinical, radiographic, operative, histopathological, and perioperative complications and follow-up clinical and radiographic data were reported. Results A total of 19 patients including 12 females and 7 males with a mean age 56.7±17.6 years and mean duration of symptoms 12.8±12.3 months were reported. 9 patients with anterolateral meningiomas, 5 with anterior meningiomas, and 5 with dumbbell schwannomas underwent uneventful FLA procedures. Gross total resection of tumors was reported in 17 patients (89.5%). Preoperative JOA score was normal in ten, grade-I in five, and grade-II in 4 patients, while at the last follow-up it improved to normal in seventeen and grade-I in two patients. Reported postoperative JOA scores at 6 months and at the last follow-up showed that all patients improved at least one grade on JOA scores. There was CSF leak in three patients and superficial wound infection in one. Conclusion Our results advocate the far-lateral cervical approach as a minimally invasive technique in the resection of the upper cervical anterolateral and anterior meningiomas and dumbbell schwannomas as a safe and effective technique