Giardiavirus internal ribosome entry site has an apparently unique mechanism of initiating translation.

Giardiavirus (GLV) utilizes an internal ribosome entry site (IRES) for translation initiation in the early branching eukaryote Giardia lamblia. Unlike most of the viral IRESs among higher eukaryotes, which localize primarily within the 5'-untranslated region (UTR), the GLV IRES comprises 253 nts of 5'UTR and the initial 264 nts in the open-reading-frame (ORF). To test if GLV IRES also functions in higher eukaryotic systems, we examined it in rabbit reticulocyte lysate (RRL) and found that it functions much less efficiently than the IRES from the Encephalomyocarditis virus (EMCV) or Cricket paralysis virus (CrPV). In contrast, both EMCV-IRES and CrPV-IRESs were inactive in transfected Giardia cells. Structure-function analysis indicated that only the stem-loop U5 from the 5'UTR and the stem-loop I plus the downstream box (Dbox) from the ORF of GLV IRES are required for limited IRES function in RRL. Edeine, a translation initiation inhibitor, did not significantly affect the function of GLV IRES in either RRL or Giardia, indicating that a pre-initiation complex is not required for GLV IRES-mediated translation initiation. However, the small ribosomal subunit purified from Giardia did not bind to GLV IRES, indicating that additional protein factors may be necessary. A member of the helicase family IBP1 and two known viral IRES binding proteins La autoantigen and SRp20 have been identified in Giardia that bind to GLV IRES in vitro. These three proteins could be involved in facilitating small ribosome recruitment for initiating translation

Diseño, síntesis y estudio de acoplamiento molecular de híbridos de quinazolinona- tiazolidin-4-onas como agentes anticancerígenos

A series of 4-(2-(4-substituted phenyl)-4-oxoquinazolin-3(4H)-yl)-N-(2-(4-fluorophenyl)-4-oxo-5- (arylidene)thiazolidin-3-yl) benzamides (VIa-n) have been synthesized by condensation of N-(2-(4- fluorophenyl)-4-oxothiazolidin-3-yl)-4-(4-oxo-2-(4-substituted phenyl)quinazolin-3(4H)-yl)benzamides (Va-b) with various aryl/heteroaryl aldehydes using conventional methodology. All compounds were screened for their in vitro anticancer activity against the human breast cancer cell lines (MCF-7), human lung cancer cell lines (A549) using MTT assay method and doxorubicin is used as standard drug. Compound VId, VIk and VIn showed high potency against A549 cell lines with IC50 values 0.035±0.002 μM, 0.031±0.002 μM and 0.030±0.002 μM respectively compared to 0.023±0.002 μM showed by the standard. However, highest activity against MCF-7 cell lines was exhibited by Va, Vb, VIk and VIn with IC50 values between 0.040 - 0.050 μM. All the remaining compounds showed moderate anticancer activity against both the MCF-7 and A549 cell lines. To understand the interactions with active binding site of receptor, molecular docking study was also performed.Una serie de 2- (4-sustituido fenil) -4-oxoquinazolin-3 (4H) -il) -N- (2- (4-fluorofenil) -4-oxo-5- (arilideno) tiazolidin-3-ilo) benzamidas (VIa-n) han sido sintetizadas por condensación de N- (2- (4-fluorofenil) -4-oxotiazolidin-3-il) -4- (4-oxo-2- (4-fenil sustituido) quinazolin-3 (4H) -il) benzamidas (Va-b) con diversos aldehídos de arilo / heteroarilo usando metodología convencional. Todos los compuestos se cribaron para su actividad anticancerosa in vitro contra las líneas celulares de cáncer de mama humano (MCF-7), líneas celulares de cáncer de pulmón humano (A549) usando el método de ensayo MTT y se usa doxorrubicina como fármaco estándar. El compuesto VId, VIk y VIn mostraron alta potencia contra las líneas celulares A549 con valores IC50 de 0.035 ± 0.002 μM, 0.031 ± 0.002 μM y 0.030 ± 0.002 μM, respectivamente, en comparación con 0.023 ± 0.002 μM mostrada por el estándar. Sin embargo, la actividad más alta contra líneas celulares MCF-7 fue exhibida por Va, Vb, VIk y VIn con valores de CI50 entre 0.040 - 0.050 μM. Todos los compuestos restantes mostraron una actividad anticancerígena moderada contra las líneas celulares MCF-7 y A549. Para comprender las interacciones con el sitio de unión activa del receptor, también se realizó el estudio de acoplamiento molecular

A Complete Coverage Algorithm for 3D Structural Inspection using an Autonomous Unmanned Aerial Vehicle

This thesis presents a novel algorithm for complete coverage of three-dimensional structures to address the problem of autonomous structural inspection using an Unmanned Aerial Vehicle (UAV). The proposed approach uses a technique of cellular decomposition based on Morse decomposition to decompose the 3D target structure into 2D coverable faces that are subsequently connected using a graph-based representation. We then use graph traversal techniques such as the Traveling Salesman Problem (TSP) to generate a flight coverage path through the decomposed faces for a UAV to completely cover the target structure, while reducing the coverage time and distance. To test the validity of our proposed approach, we have performed a series of experiments using a simulated AscTec Firefly UAV in different environments with 3D structures of different sizes and geometries, within the Robot Operating System (ROS) Gazebo simulator. Our results show that our approach guarantees complete coverage of the target structure. Comparison of our coverage strategy with other strategies shows that our proposed TSP-based coverage strategy performs up to 50% better in reducing the flight path with an average of 30% fewer turns and 12% less coverage duration than a largest-area-first approach

TNF-related weak inducer of apoptosis as a regulator of β-oxidation and differentiation in murine adipocytes

https://openworks.mdanderson.org/sumexp22/1145/thumbnail.jp

Direct-Acting Antivirals in Chronic Hepatitis C Infection with Liver Cirrhosis

Chronic hepatitis C infection is a common cause of liver morbidity and mortality across the world, in part due to complications including cirrhosis and hepatocellular carcinoma. The advent of Direct-acting antiviral (DAA) therapy has the potential to change the outcome of HCV infection in the vast majority of patients. Unfortunately, the chronic nature of HCV infection means that many patients requiring direct-acting antiviral (DAA) therapy have already developed compensated cirrhosis. This chapter reviews the importance of DAAs in the treatment of HCV infection, particularly in patients with existing compensated cirrhosis. Both efficacy and safety are discussed as essential endpoints of DAA therapy. Decompensated cirrhosis, treatment failures, vitamin-D deficiency, HIV co-infection, and ethnic differences in the context of treatment response are also discussed in this chapter

Formulation and Evaluation of Sustained-Release Matrix Tablets of Timolol Maleate.

The present study was to develop an controlled release formulation of Timolol maleate to maintain constant therapeutic levels of the drug for over 12 hrs. Timolol maleate controlled release matrix tablets are prepared by wet granulation method with different grades of HPMC. An efficient extended release formulation of Timolol maleate could be designed as controlled release tablets. The optimised formulation was developed by using HPMC K100M and Ethyl cellulose(1:1).The results of dissolution studies indicated that formulation the most successful of the study, exhibited drug release pattern very close to theoretical release profile. The designed matrix tablets of timolol maleate, which release 25.38% respectively of drug in the first hour and extend the release upto 12 hours, can overcome the disadvantages associated with conventional tablets formulation of Timolol Maleate tablets. Regulated drug release in zero order kinetics attained with this formulation. The release process involves anomalous diffusion mechanism or diffusion coupled with erosion, as indicated by the n value of 0.66 in Korsmeyer’s plot. There was an alteration in the surface area and diameter of the tablets with the progressive dissolution of the matrix as a function of time, as indicated in Hixson-Crowell plot. FTIR studies combined with stability studies proved the integrity of the developed matrix tablets. Hence it can be concluded that twice a daily controlled release matrix tablet of Timolol maleate having satisfactory extended release profile which may provide an increased therapeutic efficacy. The developed formulation overcome and alleviates the drawback and limitation of extended release preparations

Fault Tolerant Power Electronics Systems

Research work reported in this Ph.D. thesis is in the area of power electronics systems, specifically in the sector of electrical drives. A trustworthy operation of power electronics systems in critical applications like electric vehicles, aircrafts, satellites, and so on, has pushed engineers to develop fault-tolerant solutions. Indeed, in such applications it is necessary for the system to continue its operation, possibly with downgraded performance, even under faulty case. Present thesis reports the studied solutions to make fault-tolerant a class of electric drives under faulty conditions. It has initiated by addressing the need and importance of the usage of power electronic systems in the field of transportation sector, in particular in the automobile and aerospace industry. Permanent magnet (PM) brushless (BL) drives have become very popular thanks to their higher torque-per-ampere capabilities. Among the two different types of PM BL drives, namely those with sinusoidal back-emf (BLAC) and those with trapezoidal back-emf (BLDC), the latter ones are preferred for light-duty propulsion such as minicars and scooters, and in aeronautics as control-surface actuators. However, some concern have emerged on the use of electrical drives in such applications with regard to the fault tolerance and the power capability per volume unit. A way to effectively cope with these concerns is the adoption of multiphase drives. In this sense, a five-phase drive is a promising solution as it is the most simple multiphase structure of practical interest. The thesis starts with the study of the phase current and torque behavior in three-phase PM BLDC drive in healthy conditions. To validate the mathematical findings, a study case is used, represented by an electrical drive with in-wheel motor utilized for the propulsion of a city car. Afterwards, various types of faults in voltage source inverter (VSI) of a three-phase PM BLC drive are considered, such as one leg open, one switch open and one switch shorted. Remedial control strategies for the faults of the VSI are envisaged, that enable the three-phase PM BLDC drive to continue to operate even if in a degraded way. The resulting performance is calculated in terms of developed torque and torque ripple. The mathematical findings are substantiated with graphs obtained by simulation. A five-phase PM BLDC drive is successively considered. First, its operation and its torque capabilities are investigated in healthy conditions under ideal square-wave current supply. The torque capabilities are compared to the three-phase counterpart; torque comparison is carried out by keeping motor size constant and by considering two hypotheses: equal phase back-emf and equal phase rms current. Then, the torque available from a five-phase drive is determined under various supply modes, characterized by the conduction of a reduced number of phases; the torque available is determined by imposing an rms phase current equal to the nominal one. Moreover, the current behavior during the phase commutations for the five-phase PM BLDC drives is analyzed as they exhibit some differences with respect to the three-phase counterpart. The outcomes of the current analysis are used to derive the effective torque developed by the drive and the torque ripple exhibited as a function of the motor speed. The base speed of the drive is also determined. Also for the torque results, the differences from the well-known characteristics of the three-phase PM BLDC drives are pointed out. Lastly, an algebraic approach is developed to describe the operation of a five-phase PM BLDC drive in healthy conditions. The approach has led to the formulation of a model of the phase current supply of the motor in healthy conditions. Further, the model has been suitably adjusted to derive the mode (scheduling and magnitude) of current supplying the survival phases in the case of one or more motor open phase faults. The cases of one /two/three open phase faults have been examined and, in the case of two and three faulty phases, the cases of adjacent and non-adjacent faulty phases. For each case, the current magnitude has been found by imposing that the rms value of the current in the most solicited phase is equal to the nominal value, and the torque that the drive is able to develop as well as the maximum value of the torque ripple have been calculated. The obtained results indicate that the reduction in the motor torque as well as the extent of the torque ripple is depending, besides on the number of the faulty phases, on the relative location of the faults. The thesis work also address the evolution of electrical power generation and conversion methodologies in more electric aircraft, fault-tolerant solutions under faulty Hall sensors, and the concepts of dependability and safety aspects. The thesis work has been carried out at the Laboratory of “Electric systems for automation and automotive” headed by Prof. Giuseppe Buja. The laboratory belongs to the Department of Industrial Engineering, University of Padova, Italy