Aryl Phosphoramidates of 5-Phospho Erythronohydroxamic Acid, A New Class of Potent Trypanocidal Compounds

RNAi and enzymatic studies have shown the importance of 6-phosphogluconate dehydrogenase (6-PGDH) in Trypanosoma brucei for the parasite survival and make it an attractive drug target for the development of new treatments against human African trypanosomiasis. 2,3-O-Isopropylidene-4-erythrono hydroxamate is a potent inhibitor of parasite Trypanosoma brucei 6-phosphogluconate dehydrogenase (6-PGDH), the third enzyme of the pentose phosphate pathway. However, this compound does not have trypanocidal activity due to its poor membrane permeability. Consequently, we have previously reported a prodrug approach to improve the antiparasitic activity of this inhibitor by converting the phosphate group into a less charged phosphate prodrug. The activity of prodrugs appeared to be dependent on their stability in phosphate buffer. Here we have successfully further extended the development of the aryl phosphoramidate prodrugs of 2,3-O-isopropylidene-4-erythrono hydroxamate by synthesizing a small library of phosphoramidates and evaluating their biological activity and stability in a variety of assays. Some of the compounds showed high trypanocidal activity and good correlation of activity with their stability in fresh mouse blood

Holistic Representations of Internal and External Face Features are Used to Support Recognition

Face recognition is impaired when changes are made to external face features (e.g., hairstyle), even when all internal features (i.e., eyes, nose, mouth) remain the same. Eye movement monitoring was used to determine the extent to which altered hairstyles affect processing of face features, thereby shedding light on how internal and external features are stored in memory. Participants studied a series of faces, followed by a recognition test in which novel, repeated, and manipulated (altered hairstyle) faces were presented. Recognition was higher for repeated than manipulated faces. Although eye movement patterns distinguished repeated from novel faces, viewing of manipulated faces was similar to that of novel faces. Internal and external features may be stored together as one unit in memory; consequently, changing even a single feature alters processing of the other features and disrupts recognition

Human cancers over express genes that are specific to a variety of normal human tissues

We have analyzed gene expression data from 3 different kinds of samples: normal human tissues, human cancer cell lines and leukemic cells from lymphoid and myeloid leukemia pediatric patients. We have searched for genes that are over expressed in human cancer and also show specific patterns of tissue-dependent expression in normal tissues. Using the expression data of the normal tissues we identified 4346 genes with a high variability of expression, and clustered these genes according to their relative expression level. Of 91 stable clusters obtained, 24 clusters included genes preferentially expressed either only in hematopoietic tissues or in hematopoietic and 1-2 other tissues; 28 clusters included genes preferentially expressed in various non-hematopoietic tissues such as neuronal, testis, liver, kidney, muscle, lung, pancreas and placenta. Analysis of the expression levels of these 2 groups of genes in the human cancer cell lines and leukemias, identified genes that were highly expressed in cancer cells but not in their normal counterparts, and were thus over expressed in the cancers. The different cancer cell lines and leukemias varied in the number and identity of these over expressed genes. The results indicate that many genes that are over expressed in human cancer cells are specific to a variety of normal tissues, including normal tissues other than those from which the cancer originated. It is suggested that this general property of cancer cells plays a major role in determining the behavior of the cancers, including their metastatic potential.Comment: To appear in PNA

Monte Carlo simulation method for Laughlin-like states in a disk geometry

We discuss an alternative accurate Monte Carlo method to calculate the ground-state energy and related quantities for Laughlin states of the fractional quantum Hall effect in a disk geometry. This alternative approach allows us to obtain accurate bulk regime (thermodynamic limit) values for various quantities from Monte Carlo simulations with a small number of particles (much smaller than that needed with standard Monte Carlo approaches).Comment: 13 pages, 6 figures, 2 table

CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the CNS

No abstract available

Explicit expressions for the minimum efficiency and most penetrating particle size of Nuclepore filters

Nuclepore filters are capillary pore membrane filters with an array of microscopic cylindrical holes of uniform diameters. Their structure is suitable for particle collection and ensuing offline analyses, therefore they are being widely used for exposure assessment of engineered nanoparticles, ambient PM2.5, virus, bacteria, asbestos, etc., as well as in powder manufacturing industries. However, there exists a particle size range in which all the filtration capture mechanisms are not effective. This size is the most penetrating particle size (MPPS), which corresponds to the minimum efficiency (ME) of the filter. Both MPPS and ME are important parameters for a user to select an adequate Nuclepore filter and preferred operating conditions. For rapid estimation of the MPPS and ME, we derived their explicit expressions by simplifying the formulas for the impaction, diffusion and interception deposition and differentiating the combined efficiency with respect to the particle size. The comparison between the experimental data and the prediction from the explicit expressions shows the explicit expressions can provide MPPS for a wide range of filter properties (pore radius, porosity and length) and filtration conditions (particle density, face velocity and temperature). The ME can also be estimated satisfactorily when a simplified term of filter surface diffusion deposition is further considered. By the explicit expressions of MPPS and ME, a quick screening for selecting a Nuclepore filter with the proper properties and suitable filtration conditions can be easily achieved. From the theoretical point of view, the explicit expressions facilitate better understanding of the effects of filter properties and conditions on the filtration characteristic

Driven translocation of a polynucleotide chain through a nanopore--A continuous time Monte-Carlo study

Using continuous time Monte-Carlo method we simulated the translocation of a polynucleotide chain driven through a nanopore by an electric field. We have used two models of driven diffusion due to the electric field. The chain may have strong interaction with the pore, and depends on which end of the chain first enters the pore. Depending on this interaction, in both cases, the distribution of times for the chain to pass through the pore in our model is found to have three peaks, as observed in the experiment of Kasianowicz, Brandin, Branton and Deamer (KBBD).Comment: 26 pages, 6 figure

Do the Potential Benefits of Metal-on-Metal Hip Resurfacing Justify the Increased Cost and Risk of Complications?

Metal-on-metal hip resurfacing arthroplasty (MoM HRA) may offer potential advantages over total hip arthroplasty (THA) for certain patients with advanced osteoarthritis of the hip. However, the cost effectiveness of MoM HRA compared with THA is unclear. The purpose of this study was to compare the clinical effectiveness and cost-effectiveness of MoM HRA to THA. A Markov decision model was constructed to compare the quality-adjusted life-years (QALYs) and costs associated with HRA versus THA from the healthcare system perspective over a 30-year time horizon. We performed sensitivity analyses to evaluate the impact of patient characteristics, clinical outcome probabilities, quality of life and costs on the discounted incremental costs, incremental clinical effectiveness, and the incremental cost-effectiveness ratio (ICER) of HRA compared to THA. MoM HRA was associated with modest improvements in QALYs at a small incremental cost, and had an ICER less than $50,000 per QALY gained for men younger than 65 and for women younger than 55. MoM HRA and THA failure rates, device costs, and the difference in quality of life after conversion from HRA to THA compared to primary THA had the largest impact on costs and quality of life. MoM HRA could be clinically advantageous and cost-effective in younger men and women. Further research on the comparative effectiveness of MoM HRA versus THA should include assessments of the quality of life and resource use in addition to the clinical outcomes associated with both procedures. Level I, economic and decision analysis. See Guidelines for Authors for a complete description of levels of evidence

New Records of the Spider Fauna From Sarawak, Malaysia

SHORT COMMUNICATION New Records of the Spider Fauna from Sarawak, Malaysi

Interlaboratory comparison to evaluate the methodology for determination of the media filtration efficiency against nanoparticles

Current international standards dealing with efficiency test for filters and filter media focus on measurement of the minimum efficiency at the most penetrating particle size. The available knowledge and instruments provide a solid base for development of test methods to determine the effectiveness of filtration media against airborne nanoparticles down to single-digit nanometer range. An interlaboratory evaluation was performed in the framework of the European Mandate M/461 activities, within the Technical Committee 195 of European Committee for Standardization (CEN/TC195). The purpose was to develop a methodology to determine effectiveness of filtration media against air-borne particles in the 3 – 500 nm range. Five different laboratories (Camfil, ETH/Empa, Politecnico di Torino, University of Minnesota, Unifil) participate in the round robin test in order to verify the repeatability and reproducibility of the test method. The qualification of test rig and apparatus was performed prior of the filtration efficiency and air flow resistance measurement tests.Twilled dutch weave wire mesh was chosen to perform the validation filtration efficiency tests so as to ensure high uniformity of the samples being tested by each different laboratory. We present the experimental data with the discussion about their validity