The granulocytic inducer C/EBPalpha inactivates the myeloid master regulator PU.1

Verschiedene Transkriptionsfaktoren spielen eine Rolle in der Entwicklung myeloischer Zellen. PU.1, ein Transkriptionsfaktor aus der ETS-Familie, ist sowohl für die Entwicklung lymphatischer als auch für die Entwicklung myeloischer Zellen von Bedeutung. Der Transkriptions faktor C/EBPalpha, ein an den CCAAT-Enhancer bindendes Protein, ist hingegen wesentlich verantwortlich für die Entwicklung von Granulozyten. Wir stellen hier den ersten Nachweis dafür vor, dass C/EBPalpha die Funktion von PU.1 blockiert. PU.1 und C/EBPalpha können einander binden und sind in myeloischen Zellen kolokalisiert. Wenn C/EBPalpha PU.1 bindet, kann PU.1 einen minimalen Promotor mit Bindungsstelle für PU.1 nicht mehr aktivieren. Wir zeigen, dass der Leuzin-Zipper in der DNA-bindenden Domäne von C/EBPalpha mit der beta3/beta4-Region in der DNA-bindenden Domäne von PU.1 interagieren kann. Dadurch wird der Koaktivator von PU.1, c-jun, aus seiner Bindung mit PU.1 verdrängt. C/EBPalpha hemmt PU.1 nicht, indem es Korepressoren rekrutiert. Vielmehr vermindert C/EBPalpha die Expression von PU.1 in U-937-Zellen mit induzierbarem C/EBPalpha, indem es den autoregulatorischen Effekt PU.1 auf den PU.1-Promotor hemmt. Ausserdem blockiert C/EBPalpha die durch PU.1 bedingte Entwicklung dendritischer Zellen aus CD34+ menschlichen Nabel blutzellen. Diese funktionelle Blockade von PU.1 durch C/EBPalpha könnte einer der Mechanismen sein, mit denen C/EBPalpha den durch PU.1 determinierten Weg der Zelldifferenzierung hemmt und sich Zellen unter dem Einfluss von C/EBPalpha zu Granulozyten entwickeln.Several transcription factors have been shown to play a role in myelopoiesis. PU.1, an ets-family transcription factor, is required for the development of both myeloid and lymphoid lineages while the transcription factor CCAAT/enhancer binding protein family member C/EBPalpha is essential for granulocytic development. We present here the first evidence that C/EBPalpha blocks the function of PU.1. PU.1 and C/EBPalpha interact physically and co-localize in myeloid cells. As a consequence of this interaction C/EBPalpha can inhibit the function of PU.1 to activate a minimal promoter containing only PU.1 DNA binding sites. We further demonstrate that the leucine zipper in the DNA binding domain of C/EBPalpha interacts with the beta3/beta4 region in the DNA binding domain of PU.1, and as a result displaces the PU.1 co-activator c-Jun. Finally, C/EBPalpha blocks PU.1 induced dendritic cell development from CD34+ human cord blood cells. The functional blocking of PU.1 by C/EBPalpha could be the mechanism by which C/EBPalpha inhibits the cell fates specified by PU.1, and directs cell development to the granulocytic lineage

Effect of Annealing Temperatures on Formability of SS 304 tubes during Tube Hydroforming Process: A Numerical study

Tube hydroforming is an advanced manufacturing process which utilizes a liquid medium to deform the tube with required shape. This method has an advantage of attaining uniform pressure throughout the tube at any time during the process. The main aim of the present study was to know the effect of different annealing temperatures on the tube hydroforming of SS 304 steel. Specimens were annealed with four different temperatures, viz., 100oC, 150oC, 200oC and 250oC. Annealed samples were tested to find the tensile properties in terms of yield strength, strength coefficient, strain hardening exponent, elongation and ultimate tensile strength. The evaluated mechanical properties were utilized to run the tube hydroforming simulations using finite element code. Effects of annealing temperatures on bulge height and thickness distribution of the bulged area of the tube were studied using FEM. Numerical simulations confirmed that the annealing temperatures had an effect on the bulge height and thickness distribution in the bulged zone of the tube

PROCESS OPTIMIZATION, FORMULATION AND EVALUATION OF HYDROGEL {GUARGUM-G-POLY (ACRYLAMIDE)} BASED DOXOFYLLINE MICROBEADS

Objective: The objective of the present study was to improve the physical and chemical properties of natural polymers and to reduce the cost of product by graft copolymerization techniques using a natural polymer (Guar gum) and a synthetic polymer {poly (acrylamide)}. The optimized formulation of hydrogel was formulated as microbeads and loaded with Doxofylline and characterized with different parameters.Methods: Graft copolymer of guar gum-g-poly (acrylamide) was prepared by free radical polymerization technique in a specially designed jacked reaction vessel under constant flow of nitrogen. To initiate the reaction, Ceric ammonium nitrate (CAN) was used as reaction initiator. The graft co-polymer was characterised by using FTIR, TGA, and SEM. Polymeric blend beads of the grafted copolymer with sodium alginate were prepared by cross linking with calcium chloride in ionic gelation method and used to deliver a model new generation anti asthmatic drug, Doxofylline. Preparation condition of beads was optimized by considering the percentage entrapment efficiency, particle size, swelling capacity of beads in different PH conditions and their release data.Results: The formation of grafted copolymers is confirmed by FTIR studies and TGA studies showed a comparatively higher thermal stability of grafted copolymer. The pAAm-g-GG/sodium alginate microbeads were almost spherical in shape as indicated by the SEM studies. Swelling index was found to be maximum in Phosphate buffer PH 7.4 and minimum in Phosphate buffer PH 9.2. Release of doxofylline was found to be in a controlled manner with increasing polyacrylamide content in the copolymer and sodium alginate content in microbeads and higher release was observed in PH 7.4 medium than that of PH 1.2. In vitro release kinetics of doxofylline from the polymeric beads followed Higuchi kinetics model.Conclusion: Hydrogel based Doxofylline microbeads were successfully developed by using optimized batches of Guar gum-g-poly (acrylamide) and sodium alginate by free radical ionization technique. All the characterization parameters came under acceptance criteria.  Key words: Hydrogel, Microbeads, Guar gum, Acrylamide, Sodium alginat

FORMULATION DESIGN AND IN VITRO EVALUATION OF BILAYER SUSTAINED RELEASE MATRIX TABLETS OF DOXOFYLLINE

Objective: To develop bilayer matrix tablet of Doxofylline by providing a loading dose followed by the maintenance dose that suppose to enhance the therapeutic efficacy the drug for acute and sustainable asthma.Methods: Both immediate release layer and sustained release layer were prepared by wet granulation methods. Different Pre compression and post compression characterization of the tablet were carried out. Swelling studies were carried out for all the formulation. To optimise the immediate release layer, similarity (f2) and difference factor (f1) were calculated and optimised IR formulation was used for all formulations of bilayer tablet. In-vitro release studies were carried out in USP II paddle type dissolution apparatus for different formulations and release kinetic studies were carried out different kinetic model. FTIR and DSC studies were carried out for pure drug Doxofylline, IR layer and SR layer of optimised formulation to know the physical and chemical compatibility of drug and excipients. Accelerated stability studies were carried out to confirm the stability of dosage forms.Results: Pre compression and post compression parameters satisfied with pharmacopeia specifications. The formulation that contained highest percent of HPMC had highest swelling index. Formulation DBMF6 showed an initial release of 44% of drug within one hour as the loading dose and remaining drug were sustained release up to 12 h. Release kinetic followed Hixon-Crowell kinetic model with drug release mechanism quasi-fickian diffusion. From accelerated stability studies no significant changes in physicochemical properties were noticed.Conclusion: Doxofylline bilayer matrix tablets were successfully developed and can be used as an alternative to the conventional dosage form because it can be therapeutically beneficial for management of asthma.Â

Synthesis and Characterization of PLA/Luffa Cylindrica Composite Films

In recent days, natural fibers have been replaced with synthetic fibers as an alternative material for the reinforcement in the polymer composites due to their renewability and sustainability. The aim of the present work is to study the performance of using natural fiber powder in the preparation of composite films. The fiber powder used in the present study is extracted from the Luffa cylindrica plant. Fourier Transform Infrared (FTIR) spectrum is utilized for the identification of functional groups in the fabricated composite film. Scanning Electron Microscopy (SEM) analysis is carried out to observe the bonding between matrix and reinforcement in the composite films. Thermal degradation behaviour of the composite film is also studied by the Thermo-gravimetric Analysis (TGA). From the studies, it was observed that the natural fiber reinforced composite film were able to withstand higher temperatures. The fabricated composites films can be effectively used for different applications where there is a necessity of bio polymers

Synthesis and Characterization of Coir and Luffa Cylindrica filled with CaCo3 hybrid composites

Usage of natural fiber hybrid composites is increasing in the present days because of its eco-friendly and biodegradable nature. Coir fibers were extracted from the plant bark and Luffa Cylindrical were extracted from the vegetable fruit. Later both the fibers were treated with alkaline (5% NaoH) solution to remove the greasy nature over the surface.  In the present study, composites were fabricated by using Coir and Luffa Cylindrica along with CaCo3 natural fiber hybrid composites. Each composite is tested for tensile, flexural and impact tests as per the ASTM standards. The composite specimens were characterized using Fourier transform infrared spectrophotometry (FTIR), scanning electron microscopy (SEM) and thermo-gravimetric analysis (TGA/DTA). SEM illustrated a good bonding between matrix and fibers. TGA illustrated the amount of residue leftover in the composite. FTIR illustrated which compounds are present in the composite

Multi Response Optimization of Turning Process by Considering its Cutting Parameters Implementing Grey Relational Analysis

Machining process is most broadly utilized in the manufacturing industries. The purpose of the present effort is to investigate the cutting parameters in turning process on the responses: ‘Material Removal Rate’, ‘Surface Roughness’ and ‘Tool Wear Rate’ in CNC turning of EN8 steel using tool made of tungsten carbide. Three factors namely ‘Cutting Speed’, ‘feed rate’ and ‘depth of cut’ with each of the three levels have been considered as the cutting parameters. In the present study using the Taguchi's DOE methodology, multi-response optimization is carried out using Grey Relational approach to optimize the responses. Taguchi’s L9 orthogonal array is used to conduct the experiments. The obtained results are then analyzed by the Grey Taguchi. Grey Taguchi Method is implemented to find the optimal levels for the parameters. Validation test is performed to confirm the optimal levels

PREPARATION, PHYSICAL CHARACTERIZATION, AND PHARMACOKINETIC STUDY OF DOCETAXEL NANOCRYSTALS

Objective: The main objective of this study was to prepare and evaluate the nanocrystal formulation of docetaxel. Methods: Docetaxel nanocrystals were formulated to improve the water solubility. Docetaxel nanocrystals were prepared by nanoprecipitation method using Tween 80, egg lecithin, and povidone C-12 as stabilizers and poly(lactic-co-glycolic acid) (PLGA) as polymer in acceptable limits. A total of 16 formulations were prepared by changing stabilizer and polymer ratios. The prepared nanocrystals were characterized by particle size, zeta potential, crystalline structure, surface morphology, assay, saturation solubility, and in vitro drug release. Results: Based on particle size, polydispersity index, and zeta potential data, four formulations were optimized. The formulation containing Tween 80 as stabilizer has shown lowest particle size and better drug release than the formulations containing egg lecithin and povidone C-12 as stabilizers. The formulation containing Tween 80 and PLGA has shown still lower sized particles than the Tween 80 alone and exhibited prolonged sustained drug release. The release kinetics of formulations containing Tween 80 and PLGA followed zero-order release kinetics and formulations containing egg lecithin and povidone C-12 followed Higuchi diffusion (non-Fickian). Conclusion: From the study, we concluded that as the type and concentration of stabilizer changed the size and shape of the crystals were also changed and the formulations showed sustained drug release with non-Fickian diffusion

La Vida e historia del rey Apolonio [¿Zaragoza, Juan Hurus, 1488?] y su trayectoria genérica*

En el artículo se analiza la diversa trayectoria genérica de la Vida e historia del rey Apolonio [¿Zaragoza, Juan Hurus, 1488?] desde una triple perspectiva. Por su origen, remonta a la Historia Apollonii regis Tyri, narración de origen clásico próxima a las novelas griegas. Su recepción hispánica se aleja de su género de creación, pues el texto es traducción de un capítulo de las Gesta romanorum, y se presentaría, impreso junto a los Siete sabios de Roma, como una historia ejemplar. Por último, la crítica moderna ha optado por insertarlo en la serie de los «romances de materia clásica» y en el género editorial de las «historias caballerescas breves»