28 research outputs found
Role of Stearoyl-CoA desaturase-1 (SCD1) in the activation of epidermal growth factor receptor (EGFR) in lung cancer cells
No full textCancer cells activate lipogenic enzymes, including StearoylCoA Desaturase-1 (SCD1), the key enzyme that converts saturated fatty acids (SFA) into monounsaturated fatty acids (MUFA). Previously, we established that SCD1 regulates lipogenesis, cell proliferation and invasiveness in lung cancer cells, as well as tumor formation in mice. We recently reported that SCD1 modulates the PI3K/Akt pathway, a central signaling cascade, along with ERK, which are involved in the regulation of lipid biosynthesis, growth and survival of mammalian cells. Growth factor-activated tyrosine kinase receptors, such as epidermal growth factor (EGF) receptors (EGFR), are main activators of Akt and ERK signals, two cascades that are most often deranged in cancer. A hallmark of cancer is the metabolic shift towards macromolecular synthesis to support cell replication. SCD1 expression increases in cancer cells. The molecular mechanisms by which SCD1 regulates the biological phenotype of cancer cells is still unknown. The poor prognosis and ineffective treatments of some cancers, such as lung cancer, calls for better understanding of their mechanisms and for finding novel targets that, like SCD1, modulate the Akt and ERK pathways. Here we provide evidence that SCD1 activity controls the activation of EGFR and its downstream signaling targets, Akt and ERK. Using H460 human lung cancer cells, we observed that the activating phosphorylation of Tyr1068 and Tyr1086 residues in EGFR upon EGF stimulation was markedly impaired when SCD1 activity was blocked with CVT-11127, a novel small molecule SCD inhibitor. In addition, supplementation with oleic acid, the product of SCD1, restored EGF-induced phosphorylation of EGFR but not the full phosphorylation of Akt. Finally, abrogation of SCD1 dramatically altered distribution of rafts and non-raft domains, suggesting that the regulation of EGFR function by SCD1 may involve the alteration of membrane lipid domains. All results are representative of 3 separate experiments. In conclusion, our data indicate that SCD1 may coordinate the regulation of lipid biosynthesis and the transduction signals that control cancer cell metabolism, proliferation, survival and tumorigenesis by modulating EGFR activation, which subsequently modifies the Akt and ERK signaling platforms. Our findings also suggest SCD1 is a potential target for novel pharmacological interventions in lung cancer.M.S.Includes bibliographical referencesby Mary Nashe
Maxwell-f(Q) Theory
No full textExploring the four-dimensional AdS black hole is crucial within the framework of the AdS/CFT correspondence. In this research, four-dimensional stationary and rotating AdS solutions in the framework of the (Formula presented.) gravitational theory are investigated, considering the charged scenario. Author\u27s emphasis is on the power-law ansatz, which consistent with observations and is deemed the most viable. Because this solution does not have an uncharged version or relate to general relativity, it falls into a new category, which derives its features from changes in non-metricity and incorporates the Maxwell domain. The singularities of such a solution are analyzed, computing all the quantities of different curvature and non-metricity invariants. Author\u27s results indicate the presence of a central singularity, albeit with a softer nature compared to standard non-metricity or Einstein general relativity, attributed to the influence of the effect of (Formula presented.). Several physical characteristics of black hole from thermodynamics perspective and demonstrate the existence of an outer event horizon in addition to the inner Cauchy horizons are examined. However, under the conditions of sufficiently large electric charge, a naked singularity emerges. Finally, a class of rotating black hole in four-dimensional (Formula presented.) gravity that are asymptotically anti-de Sitter charged is derived
New Black Hole Solution in f(R) Theory and Its Related Physics
No full textRecent observations suggest that General Relativity (GR) faces challenges in fully explaining phenomena in regimes of strong gravitational fields. A promising alternative is the f(R) theory of gravity, where R denotes the Ricci scalar. This modified theory aims to address the limitations observed in standard GR. In this study, we derive a black hole (BH) solution without introducing nonlinear electromagnetic fields or imposing specific constraints on R or the functional form of f(R) gravity. The BH solution obtained here is different from the classical Schwarzschild solution in GR and, under certain conditions, reduces to the Schwarzschild (A)dS solution. This BH is characterized by the gravitational mass of the system and an additional parameter, which distinguishes it from GR BHs, particularly in the asymptotic regime. We show that the curvature invariants of this solution remain well defined at both small and large values of r. Furthermore, we analyze their thermodynamic properties, demonstrating consistency with established principles such as Hawking radiation, entropy, and quasi-local energy. This analysis supports their viability as alternative models to classical GR BHs
Liqui-Mass Technology as a Novel Tool to Produce Sustained Release Liqui-Tablet Made from Liqui-Pellets
No full textThe Liqui-Mass technology (also known as Liqui-Pellet technology) has shown promising results in terms of enhancing the drug release rate of water insoluble drugs in a simplistic approach. However, there is no current study on sustained-release formulation using the Liqui-Mass technology. In this study, an attempt was made to produce a sustained-release Liqui-Tablet for the first time using a matrix-based approach. The non-volatile co-solvent used in the investigation included Tween 80, Tween 20 and Kolliphor EL. The production of sustained-release propranolol hydrochloride Liqui-Tablet was successful, and data from the saturation solubility test and dissolution test did not show much difference among the mentioned non-volatile co-solvent. The best Liqui-Tablet formulation took 24 h for drug release to reach at around 100%. There seemed to be a synergistic retarding drug release effect when a non-volatile co-solvent and Eudragit RS PO were used together. The increase of Eudragit RS PO concentration increased the retardant effect. Kinetic drug release analysis suggests that the best formulation followed the Higuchi model. The flowability of pre-compressed Liqui-Tablet pellets had no issues and its size distribution was narrow. Liqui-Tablet was generally robust and most formulations passed the friability test. The study revealed that Liqui-Mass technology can be employed to sustain drug release
An investigation and study from the chapter of divorce of the patient to the chapter of seizure from the book "Tuhfat al-Akhayyar Ala al-Dur al-Mukhtar" which was written by Abu al-Safa Burhan al-Din Ibrahim bin Mustafa al-Halabi
No full textBu çalışma İstanbul Sebahattin Zaim üniversitesinde İslami ilimler programı yüksek lisans derecesi kazanmak için takdim edilmiş ilmi bir çalışmadır. Tez konumuzun başlığı Ebü'l-Sefâ Burhânüddîn İbrâhîm b. Mustafa el-Halebî'nin Tuhfetü'l-Ahyâr alâ Dürrü'l-mu'târ eserinden "talâkul merîz babından istîlâ babına kadar olan bölümün tahkik ve incelemesini teşkil etmektedir. Tuhfetü'l-Ahyâr, Muhammed b. Abdullah et-Timurtaşî'nin Tenvîrü'l-eb'âr adlı eserine Haskefî'nin ed-Dürrü'l-mu'târ adıyla yazdığı şerh üzerine yazılmış bir hâşiyedir. El-Halebî haşiyesinde kapalı ibareleri açıklamış, problemli yerlere notlar düşmüş, bazen tashih bazen beyan bazense tasvipte bulunmuştur. Halebî'nin bu haşiyesi bu kitap üzerine yazılmış haşiyelerin en önemlilerindendir. Arzu edilen amaca yönelik en faydalı, kabul gören bir düzene sahip, mümkün olduğunca doğru görüşler belirtilmiştir. Yazar, eserindeki itiraz tashih ve düzeltmelerde ulemaya karşı saygısını korumuştur. Tahkik edilen bölüme talâk kitabından bir miktar, ricat, îlâ, Hulu, zihar, li'ân, anin ve iddet bablarından ayrıca itk kitabından da bir bölüm ilave etmiştir. Çalışmamı iki ana bölüme ayırdım; Bir: inceleme İki: seçili bölümün tahkiki Tüm bunları inşallah yeri geldikçe açıklayacağım. Yüce Rabbimden takdim ettiğim çalışmamın bana fayda sağlamasını niyaz ediyorum. İmam el-Halebî'ye ilim ve ilim ehline sağladığı katkılardan ötürü mükafatların en hayırlısını bahşetmesini diliyorum. Rabbimden bu çalışmamı yazarın Murad ettiği incelikleri tespit ederek itmam etme konusunda yardım talep ediyorum. Rabbul âlemin her şeye gücü yeten ve her şeyin sahibidir.This Scientific Thesis Was Prepared In An Effort To Obtain A Master's Degree In The Islamic Studies Program At The Istanbul Sabahattin Zaim University. It Is Titled "An Investigation And Study From The Chapter Of Divorce Of The Patient To The Chapter Of Seizure" From The Book "Tuhfat Al-Akhayyar Ala Al-Dur Al-Mukhtar" Which Was Written By Abu Al-Safa Burhan Al-Din Ibrahim Bin Mustafa Al-Halabi. Tuhfat Al-Akhayyar Is An Annotation Placed On "Al-Durr Al-Mukhtar" By Ala Al-Din Al-Hasakfi In His Commentary On Tanwir Al-Absar By Muhammad Al-Tamrtashi. Al-Halabi Has Explained In His Annotation The Ambiguous Phrases And Commented On The Touchy Issues As Well As Added Some Corrections. That Is Why Al-Habibi's Explanation Was One Of The Most Important Annotations To This Book. It Served A Great Purpose And Coordinated An Acceptable Method Of Making Corrections. He Was As Polite And Humble With The Scholars In His Objection, Criticism And Correction. This Investigative Thesis Has Included Some Of The Divorce Chapter, The Chapters Of Rajah, Lla, Khule, Zihar, Li'an. Eanan, Iddah And Some Of The Manumission Chapter. I Divided The Thesis Into Two Parts. First, Being The Study Of The Content And The Second Being The Investigation Of The Assigned Section. This Will Be Explained In Detail Within The Thesis, Allah Willing. Finally, I Ask Allah Almighty To Benefit Me From What I Have Endeavored Upon, And To Reward Imam Al-Halabi For His Knowledge The Best Reward, And To Help Me To Produce This Thesis Accurately As It Was Desired By It's Author
Physical-chemical Properties of Aqueous TBAOH Solution for Gas Hydrates Promotion
No full textAbstractGas hydrates attract the attention of many industries for various potential applications such as gas separation and storage. To industrialize the gas hydrate technology, rapid hydrate formation at mild conditions is crucial. Chemical additives such as ionic liquids were investigated for hydrate promotion. The knowledge of physical-chemical properties of ionic liquids is crucial in development of gas hydrate technology in industry as these fundamental properties determined the hydrate formation rate. This work measures the density, pH, electrical conductivity, and surface tension of aqueous tetrabutylammonium hydroxide solutions. The concentrations were chosen to cover the common hydrate promotion range of 0.001-10 wt%. The results showed high dependence of the studied properties on the concentration. pH and electrical conductivity were increased with increase of TBAOH concentration conversely to density and surface tension. The amount of CO2 consumed to form the hydrate was measured at a pressure of 35bar and a temperature 274.15. Significant increase of CO2 consumption in the presence of TBAOH solutions was observed. However, as the concentration increased, more CO2 was consumed
Biorthogonality and reproducing property
No full textIntegral operators involving the Szego, the Bergman and the Cauchy kernels are known to have the reproducing property, i.e. all of them reproduce holomorphic functions. Both the Szego and the Bergman kernels have series representations in terms of orthonormal basis. In this paper we derive the Cauchy kernel by means of biorthogonality. The ideas involved are then applied to construct a non-Hermitian kernel admitting reproducing property for a space associated with the Bergman kernel
Effect of pH, Ionic Strength and Agitation Rate on Dissolution Behaviour of 3D-Printed Tablets, Tablets Prepared from Ground Hot-Melt Extruded Filaments and Physical Mixtures
No full textWith the current focus on 3D-printing technologies, it is essential to understand the processes involved in such printing methods and approaches to minimize the variability in dissolution behaviour to achieve better quality control outcomes. For this purpose, two formulations of theophylline tablets were prepared using hydroxypropyl cellulose (HPC) and ethyl cellulose (EC). Among the two types of tablets, three different methods (physical mixture (PM), hot-melt extrusion (HME) and 3D-printing fused deposition modelling (FDM)) were applied and their dissolution behaviours were studied under various conditions using a biodissolution tester. This was carried out at pH values of 1.2, 2.2, 5.8, 6.8, 7.2 and 7.5, mimicking the medium in the gastrointestinal tract. Dissolution tests under two dipping rates (10 dpm and 20 dpm) and two ionic strengths (0.2 M and 0.4 M) were conducted to mimic fed and fasting conditions. The dissolution efficiency (DE%), release rate, similarity factor (f2) and difference factor (f1) were calculated. When comparing the DE%, the formulation containing EC showed less sensitivity to changes in the dipping rate and ionic strength compared to the HPC formulation. As for the manufacturing method, 3D-printing FDM could improve the robustness of the dissolution behaviour of both formulations to dipping rate changes. However, for ionic strength changes, the effect of the manufacturing method was dependent on the formulation composition. For example, the 3D-printed tablets of the HPC formulation were more sensitive to changes in ionic strength compared to the EC-containing formulation. The release mechanism also changed after the thermal process, where n values in the Korsmeyer–Peppas model were much higher in the printing and HME methods compared to the PM. Based on the formulation composition, the 3D-printing method could be a good candidate method for tablets with a robust dissolution behaviour in the GI tract. Compared to HPC polymers, using hydrophobic EC polymers in printable formulations can result in a more robust dissolution behaviour in fed and fasting states
Liqui-mass technology as a novel tool to produce sustained release liqui-tablet made from liqui-pellets
No full textThe Liqui-Mass technology (also known as Liqui-Pellet technology) has shown promising results in terms of enhancing the drug release rate of water insoluble drugs in a simplistic approach. However, there is no current study on sustained-release formulation using the Liqui-Mass technology. In this study, an attempt was made to produce a sustained-release Liqui-Tablet for the first time using a matrix-based approach. The non-volatile co-solvent used in the investigation included Tween 80, Tween 20 and Kolliphor EL. The production of sustained-release propranolol hydrochloride Liqui-Tablet was successful, and data from the saturation solubility test and dissolution test did not show much difference among the mentioned non-volatile co-solvent. The best Liqui-Tablet formulation took 24 h for drug release to reach at around 100%. There seemed to be a synergistic retarding drug release effect when a non-volatile co-solvent and Eudragit RS PO were used together. The increase of Eudragit RS PO concentration increased the retardant effect. Kinetic drug release analysis suggests that the best formulation followed the Higuchi model. The flowability of pre-compressed Liqui-Tablet pellets had no issues and its size distribution was narrow. Liqui-Tablet was generally robust and most formulations passed the friability test. The study revealed that Liqui-Mass technology can be employed to sustain drug release
Numerical conformal mapping for symmetric regions via the Bergman kernel
No full textThe Bergman kernel functions is known to satisfy a certain boundary integral equation of the second kind. For boundaries that possess some symmetry, it is shown how to transform the integral equation into another integral equation that uses only a small part of the original boundary. This provides an efficient computation of the Riemann mapping function for symmetric regions via the Bergman kernel
