Fe65 Is Phosphorylated on Ser289 after UV-Induced DNA Damage

Fe65 undergoes a phosphatase-sensitive gel mobility shift after DNA damage, consistent with protein phosphorylation. A recent study identified Ser228 as a specific site of phosphorylation, targeted by the ATM and ATR protein kinases, with phosphorylation inhibiting the Fe65-dependent transcriptional activity of the amyloid precursor protein (APP). The direct binding of Fe65 to APP not only regulates target gene expression, but also contributes to secretase-mediated processing of APP, producing cytoactive proteolytic fragments including the APP intracellular domain (AICD) and cytotoxic amyloid β (Aβ) peptides. Given that the accumulation of Aβ peptides in neural plaques is a pathological feature of Alzheimer’s disease (AD), it is essential to understand the mechanisms controlling Aβ production. This will aid in the development of potential therapeutic agents that act to limit the deleterious production of Aβ peptides. The Fe65-APP complex has transcriptional activity and the complex is regulated by multiple post-translational modifications and other protein binding partners. In the present study, we have identified Ser289 as a novel site of UV-induced phosphorylation. Interestingly, this phosphorylation was mediated by ATM, rather than ATR, and occurred independently of APP. Neither phosphorylation nor mutation of Ser289 affected the Fe65-APP interaction, though this was markedly decreased after UV treatment, with a concomitant decrease in the protein levels of APP in cells. Using mutagenesis, we demonstrated that Fe65 Ser289 phosphorylation did not affect the transcriptional activity of the Fe65-APP complex, in contrast to the previously described Ser228 site

Effect of Root Opening on Distortion of Butt-Joints in Submerged Arc Welding

The dimensional differences in steel bridge manufacturing caused by weld deformation often occur for butt joints of thin plates. The problems of distortion, residual stresses and reduced strength of structure in and around a welded joint are of major concern in the shipbuilding industry and other similar manufacturing industries. The various distortions induced by welding process and restriction of these distortions may lead to higher residual stresses. The prediction of distortions in ship panels are of great importance from the point of view of dimensional control. In view of this, it has been investigated the effect of root opening on the transverse shrinkage, longitudinal shrinkage and angular distortions of butt joints. The experimental investigations are carried out using Submerged Arc Welding with zero mm, 1 mm and 2 mm root opening for constant heat input. The transverse and longitudinal shrinkage increase but the angular distortion decreases with increase in the root opening

A RAPID RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR THE QUANTITATIVE ESTIMATION RIBAVIRIN IN TABLETS

Objective: To develop an accurate, precise and linear Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method and validate as per ICH guidelines for the quantitative estimation of Ribavirin (200mg) in tablets.Methods: The optimized method uses a reverse phase column, Enable Make KromasilC18 (250 X 4.6 mm; 5μ), a mobile phase of phosphate buffer (pH 4.2): acetonitrile in the proportion of 85:15 v/v, flow rate of 1.0 ml/min and a detection wavelength of 215 nm using a PDA detector.Results: The developed method resulted in Ribavirin eluting at 2.606 min. Ribavirin exhibited linear in the range 25-150μg/ml. The precision is exemplified by the relative standard deviation of 0.4%. Percentage Mean recovery was found to be in the range of 98â€102, during accuracy studies. The limit of detection (LOD) and limit of quantitiation (LOQ) was found to be 0.24ng/ml and 0.73ng/ml respectively.Conclusion: An accurate, precise and linear RP-HPLC method was developed and validated for the quantitative estimation of Ribavirin in VIRAZIDE (200mg) tablets as per ICH guidelines and hence it can be used for the routine analysis in various pharmaceutical industries.Â

A Low-Complexity Semi-Analytical Approximation to the Block Error Rate in Nakagami-m Block Fading Channels

<p>There are few analytical formulas that can be used for calculating the block error rate (BLER) in block fading channels. Thus, an estimate of the BLER is often obtained using numerical methods. One such method is the threshold method which assigns 0 or 1 to the instantaneous BLER given the signal to noise ratio (SNR) level. It has been shown that utilizing such a method results in an accurate approximation of the BLER in Nakagami-m block fading channels for a wide range of m.</p> <p>In this work, we consider a recently proposed simple method of obtaining the threshold and study the effect of adopting different physical layer and channel parameters on that threshold. We show that, while the value of this threshold depends on the modulation, coding, and block size, it is almost unaffected by the m parameter of Nakagami-m channels for a wide range of practical values. In addition, for a given modulation and coding method, the threshold is shown to be a simple function of block size. As a result, the computational complexity required to obtain the threshold can be significantly reduced.</p

Internal migration and political change in India : a case study of a new industrial town

In India the western-educated urban professional elites (such as the lawyers, landed gentry, journalists, businessmen, and academics) who had implicit faith in British parliamentary democracy played an important role in forming, organizing, and supporting the nationalist movement mainly under the banner of the Indian National Congress (Ghosh 1960:11,12; Krishna 1966b).^ It was a small elite, homogeneous in social background and mainly upper caste, and it constituted almost a one-class ensemble. Sections of this class joined the British administrative structure and in a sense shared power with the British (Weiner 1968:38). According to Kothari, the new middle class created by English education and drawn by the concepts of liberty, democracy, and socialism, was indeed the greatest legacy of the British Raj. This class eventually inherited power from the British and declared itself a modern nation and a sovereign democratic republic (Kothari 1970d:40)

Effect of Included Angle in V-Groove Butt Joints on Shrinkages in Submerged Arc Welding Process

Abstract: The problems of distortion, residual stresses and reduced strength of structure in and around a welded joint are of major concern in the shipbuilding industry and in other similar manufacturing industries. The predictions of the degree of shrinkages in ship panels due to welding are of great importance from the point of view of dimensional control and it is important to analyze transverse and longitudinal shrinkage. This paper deals with the experimental analysis of transverse and longitudinal shrinkage in single and double V-groove butt joints in submerged arc welding by varying included angle and keeping process parameters constant. It is found that, the maximum shrinkage was at the centre of the plate and minimum at the ends. It is also found that, the transverse and longitudinal shrinkage increase with increase in the included angle. There is a significant increase in the transverse shrinkage and small variation in longitudinal shrinkage

Characterization and evaluation of morphological and yield traits of tamarind genotypes

The evaluation of morphological and yield traits of tamarind genotypes was carried out during 2017-18 at Forest Research Station, Govinkovi, Honnali taluk, Davangere district. The experiment was laid out in randomized complete block design with 16 genotypes and three replications. Trees were 14-years-old and of grafted origin. All the morphological and yield traits showed significant difference among the selected genotypes indicating the presence of adequate variations. The genotypes recorded morphological variation in terms of tree shape (semi-circle to irregular shape), foliage arrangement (dense to sparse), flowering time (early, mid and late), stem colour (dark brown, brown and light brown), bud colour (greenish white, pink, dark pink), petal colour (yellow and pale yellow), pod colour (greyish brown, brown, light brown and dark brown), pulp colour (light brown, brown and reddish brown), pod shape (straight, slightly curved, curved and deeply curved) and pod size (very big, big, medium and small). The analysis of variance revealed significant difference with respect to tree height, stem girth, pod traits, pod yield per tree (K-9 : 12.80 kg), number of pods per tree (NTI-52 : 989.07) and pulp per cent (K-9 : 48.87). Among the 16 genotypes, the genotype K-9 was found superior with respect to pod size, pod weight, pulp weight and pod yield per tree. Genotype K-9 was found promising and due to perennial in nature further evaluation is required for stability

Formulation and evaluation of oral sustained release of Diltiazem Hydrochloride using rosin as matrix forming material

Rosin, a natural resin, was used as a hydrophobic matrix material for the controlled release, using diltiazem HCl as model drug. Matrix tablets were prepared by direct compression method using rosin as matrix forming material in different proportions and with different diluent combinations. The tablets prepared were flat faced, retained their shape throughout. The method of preparation of matrix system and its concentration were found to have pronounced effect on the release of diltiazem HCl. The release was found to follow both the first order kinetics and fickian diffusion. The drug delivery was analyzed using the paddle method according to USP XXIII. All the studies were done in phosphate buffer pH 7.4. The matrix tablets were evaluated for its thickness, hardness, friability, weight variation, drug content and invitro release studies. The results suggest that the rosin is useful in developing sustained release matrix tablets, prolong release of water soluble drug for up to 24h. Rosin thus promises considerable utility in the development of oral sustained release drug delivery systems

Novel Mannich bases bearing pyrazolone moiety. Synthesis, characterization and electrochemical studies

The present investigation describes a series of new {4-[3-Methyl-5-oxo-4-(4|-substituted phenyl hydrazono)-4,5-dihydro-pyrazol-1-yl]-phenoxy}-acetic acid (2-oxo-1-piperidine-1-ylmethyl-1,2-dihydro–indol-3-ylidene)-hydrazides synthesized by the Mannich reaction of {4-[3-Methyl-5-oxo-4-(4|-substituted phenyl hydrazono)-4,5-dihydro-pyrazol-1-yl]-phenoxy}-acetic acid (2-oxo-1,2-dihydro-indol-3-ylidene)-hydrazide with aqueous formaldehyde and a solution of piperidine in dimethylformamide. These novel Mannich bases were characterized by elemental analysis, IR, 1H NMR and mass spectral data. Electrochemical behavior of these compounds were studied by two techniques namely polarography and cyclic voltammetry. The results from both the techniques were compared and the reduction mechanism in acidic as well as basic medium was proposed