Background: African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host, but it is unknown whether either process is essential to the parasite. Methodology/Principal Findings: Pyrimidine requirements for growth were investigated using strictly pyrimidine-free media, with or without single added pyrimidine sources. Growth rates of wild-type bloodstream form Trypanosoma brucei brucei were unchanged in pyrimidine-free medium. The essentiality of the de novo pyrimidine biosynthesis pathway was studied by knocking out the PYR6-5 locus that produces a fusion product of orotate phosphoribosyltransferase (OPRT) and Orotidine Monophosphate Decarboxylase (OMPDCase). The pyrimidine auxotroph was dependent on a suitable extracellular pyrimidine source. Pyrimidine starvation was rapidly lethal and non-reversible, causing incomplete DNA content in new cells. The phenotype could be rescued by addition of uracil; supplementation with uridine, 29deoxyuridine, and cytidine allowed a diminished growth rate and density. PYR6-52/ 2 trypanosomes were more sensitive to pyrimidine antimetabolites and displayed increased uracil transport rates and uridine phosphorylase activity. Pyrimidine auxotrophs were able to infect mice although the infection developed much more slowly than infection with the parental, prototrophic trypanosome line. Conclusions/Significance: Pyrimidine salvage was not an essential function for bloodstream T. b. brucei. However, trypanosomes lacking de novo pyrimidine biosynthesis are completely dependent on an extracellular pyrimidine source, strongly preferring uracil, and display reduced infectivity. As T. brucei are able to salvage sufficient pyrimidines from the host environment, the py

African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host. However, uptake of pyrimidines in bloodstream form trypanosomes has not been investigated, making it difficult to judge the relative importance of salvage and synthesis or to design a pyrimidine-based chemotherapy. Detailed characterization of pyrimidine transport activities in bloodstream form Trypanosoma brucei brucei found that these cells express a high-affinity uracil transporter (designated TbU3) that is clearly distinct from the procyclic pyrimidine transporters. This transporter had low affinity for uridine and 2′deoxyuridine and was the sole pyrimidine transporter expressed in these cells. In addition, thymidine was taken up inefficiently through a P1-type nucleoside transporter. Of importance, the anticancer drug 5-fluorouracil was an excellent substrate for TbU3, and several 5-fluoropyrimidine analogs were investigated for uptake and trypanocidal activity; 5F-orotic acid, 5F-2′deoxyuridine displayed activity in the low micromolar range. The metabolism and mode of action of these analogs was determined using metabolomic assessments of T. brucei clonal lines adapted to high levels of these pyrimidine analogs, and of the sensitive parental strains. The analysis showed that 5-fluorouracil is incorporated into a large number of metabolites but likely exerts toxicity through incorporation into RNA. 5F-2′dUrd and 5F-2′dCtd are not incorporated into nucleic acids but act as prodrugs by inhibiting thymidylate synthase as 5F-dUMP. We present the most complete model of pyrimidine salvage in T. brucei to date, supported by genome-wide profiling of the predicted pyrimidine biosynthesis and conversion enzymes.

The aim was to build an educational website to teach preschoolers aged 2-5 years old some skills; related to reading, writing and pronouncing alphabet, numbers, animal names, shapes and other common words. Also, assist parents and teachers by providing digital game-based learning environment to “edutainment” the children. The study illustrated the usability and usefulness of this educational game-based website and provided future insights for researchers and developers to take into account in future work.

one of the challenges recently occurred in the concept of hiding data is the

robustness of hiding data in the way that is difficult to access or detect. Most of the steganography

schemes are based commonly on embed data within images or video frames on their original form

(uncompressed domain).

This paper presents a new methodology for data hiding in MPEG-2 video standard. Data will be

embedding during the compression stage of the AVI-MPEG2 encoding. The BPCS algorithm has

been modified and used in all our experiments for embed data, and the DES (Data Encryption

Standard) algorithm has been used to encrypt data before hiding. It only embeds encrypted data

bits in the quantized AC coefficients (low-frequency AC coefficients) of Y components (Luminance)

for the I-Frame. The obtained results demonstrate that the proposed method has the considerable

advantage over previous steganography schemes with a good PSNR values for the embedded

ABSTRACT

The objective of the study was to evaluate the effect of Diabetes in elderly females.

Oxidative stress is regarded as a main causal factor for natural ageing. This study tested

the hypothesis that healthy elderly people show higher oxidative DNA damage levels and

lower antioxidative enzymatic defense capacities. In type II diabetic patients, persistence

of hyperglycemia is one of the causes of increased in oxygen free radicals. This increase

oxidative stress and makes the life threatening cardiovascular complications. Blood

samples were drawn from selective 100 elderly females (with and without diabetes). In

elderly females having menopause, there occur hypercholesterolemia,

hypertriglyceridemia, and hyperlipoproteinemia, these on the body, escort an increase in

free radicals, with mounting oxidative stress. In diabetes the body suffers with a poor or

negligible glycemic control. All diabetic post menopausal females with CVD have been

reported a significant high levels of Fasting Blood Sugar, Total Cholesterol, Triglycerides,

LDL-C, VLDL-C, CAT, NT-proBNP and MDA and significantly lower levels of HDL-C, GPx,

SOD as compared to control subjects. In type-II diabetes mellitus elderly female patients

during the postmenopause, the probability of secondary complications of cardiovascular

diseases increases.

With the development of the internet and multimedia technology digital video encryption has attracted a great deal of

research interest in the recent few years in applications. In this paper, we propose a method to encrypt video data. The proposed

algorithm is based on the MPEG video coding standard. It selectively encrypts some DCT coefficients in the I frame, B frame and P

frame in MPEG video compression by using chaotic systems. The key in this paper is chaotic sequence based on logistic mapping. It

can produce the pseudo-random sequences with good randomness. The experimental results based on chaotic maps prove the

effectiveness of the proposed method, showing advantages of large key space and high-level security. The proposed algorithm was

measured through a series of tests and achieved good results. The results indicate that the algorithm can be implemented for video

encryption efficiently and it provides considerable levels of security

The classic problem for a logistically evolving single species population being harvested involves three parameters: rate constant, carrying capacity and harvesting rate, which are taken to be positive constants. However, in real world situations, these parameters may vary with time. This paper considers the situation where these vary on a time scale much longer than that intrinsic to the population evolution itself. Application of a multiple time scale approach gives approximate explicit closed form expressions for the changing population, that compare favorably with those generated from numerical solutions.

This paper proposes an estimation method based on the reflection of the (manifest) explanatory variable to estimate the parameters of a simple linear regression model when both response and explanatory variables are subject to measurement error (ME). The reflection method (RM) uses all observed data points, and does not exclude or ignore part of the data or replace them by their ranks. The RM is straightforward, and easy to implement. We show that the RM is equivalent or asymptotically equivalent to the orthogonal regression (OR) method. Simulation studies show that the RM produces estimators that are nearly asymptotically unbiased and efficient under the assumption that the ratio of the error variances equals one. Moreover, it allows to define the sum of squares of errors uniquely, the same way as in the case of no measurement error. Simulation based numerical comparisons of the RM with the ordinary least square (OLS) and OR methods are also included.

0

0