122 research outputs found

    Manpower information

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    A description of the NAL nominal roll database (listing basic information about NAL employees) created using the Ingres relational database software. Using this database it is possible to provide a wide variety of reports about NAL staff, respond to a wide assortment of queries and undertake elementary statistical analysis to tabulate (and pictorially depict) the average age of NAL scientists, the future retirement pattern of NAL employees etc

    Probabilistic Analysis of the Median Rule: Asymptotics and Applications

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    The solution of integer optimization problems by relaxation methods consists of three parts. First, the discrete problem is converted into a continuous optimization problem, which is generally more tractable. Second, the relaxed problem is solved efficiently, yielding a optimal solution in the continuous space. Finally, an assignment procedure is used to map this solution to a suitable discrete solution. One heuristic - we call it the relaxation heuristic - that often guides the choice and design of assignment algorithms is: given a continuous optimal solution, the corresponding integer optimal solution is likely to be nearby (with respect to some well defined metric). Intuitively, this heuristic is reasonable for objective functions that are, say, Lipschitz functions. For such functions, an assignment algorithm might map the continuous optimal solution to the nearest feasible solution in the discrete space, in the hope that the discrete solution will be optimal as well. In this paper, we consider properties of a particular assignment algorithm known as the median rule. Define a binary vector to be balanced when the numbers of its 1 \u27s and 0\u27s differ at most by one. The median rule used to assign n-dimensional real vectors to n-dimensional balanced binary vectors, may be loosely described as follows: map the ith component of a real vector to a 0 or 1, depending on whether that component is smaller or greater than the median value of the vector components. We address two aspects of the median rule. The first result is that given a real vector, the median rule produces the closest balanced binary vector, with respect to any Schur-convex distance criteria. This includes several Minkowski norms, entropy measures, gauge functions etc. In this sense, the median rule optimally implements the relaxation heuristic. The second result addresses the issue of relaxation error. Though the median rule produces the nearest balanced integer solution to a given real vector, it is possible that this solution is sub-optimal, and the actual optimal solution is located elsewhere. The difference between the actual optimal cost and the cost of the solution obtained by the median rule is called the relaxation error. We consider the optimization of real valued, parametrized, multivariable Lipschitz functions where domains are the set of balanced binary vectors. Varying the parameters over the range of their values, we obtain an ensemble of such problems. Each problem instance in the ensemble has an optimal real cost, an integer cost, and an associated relaxation error. We establish upper bounds on the probability that the relaxation error is greater than a given threshold t. In general, these bounds depend on the random model being considered. These results have an immediate bearing on the important graph bisection width problem, which involves the minimization of a certain semidefinite quadratic cost function over balanced binary domains. This important problem arises in a variety of areas including load balancing, [11,16], storage management [22], distributed directories [15], and VLSI design [10]. The results obtained indicate that the median rule in a certain precise sense, is an optimal assignment procedure for this problem. The rest of the paper is organized as follows: In section 3, we prove the shortest distance properties of the median rule. In section 4, we introduce the concept of relaxation error and the Lipschitz bisection problem. Upper bounds on the relaxation error are obtained in Section 5. A discussion on these results is given in Section 6

    Characterization of a Class of Sigmoid Functions with Applications to Neural Networks

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    Sigmoid functions, whose graphs are S-shaped curves, appear in a great variety of contexts, such as the transfer functions in many neural networks. Their ubiquity is no accident; these curves are the among the simplest non-linear curves, striking a graceful balance between linear and non-linear behavior

    Putting Humpty-Dumpty together again: Reconstructing functions from their projections.

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    We present a problem decomposition approach to reduce neural net training times. The basic idea is to train neural nets in parallel on marginal distributions obtained from the original distribution (via projection), and then reconstruct the original table from the marginals (via a procedure similar to the join operator in database theory). A function is said to be reconstructible, if it may be recovered without error from its projections. Most distributions are non-reconstructible. The main result of this paper is the Reconstruction theorem, which enables non-reconstructible functions to be expressed in terms of reconstructible ones, and thus facilitates the application of decomposition methods

    Molecular-receptor-specific, non-toxic, near-infrared-emitting Au cluster-protein nanoconjugates for targeted cancer imaging

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    Molecular-receptor-targeted imaging of folate receptor positive oral carcinoma cells using folic-acid-conjugated fluorescent Au25 nanoclusters (Au NCs) is reported. Highly fluorescent Au25 clusters were synthesized by controlled reduction of Au+ ions, stabilized in bovine serum albumin (BSA), using a green-chemical reducing agent, ascorbic acid (vitamin-C). For targeted-imaging-based detection of cancer cells, the clusters were conjugated with folic acid (FA) through amide linkage with the BSA shell. The bioconjugated clusters show excellent stability over a wide range of pH from 4 to 14 and fluorescence efficiency of ~5.7% at pH 7.4 in phosphate buffer saline (PBS), indicating effective protection of nanoclusters by serum albumin during the bioconjugation reaction and cell-cluster interaction. The nanoclusters were characterized for their physico-chemical properties, toxicity and cancer targeting efficacy in vitro. X-ray photoelectron spectroscopy (XPS) suggests binding energies correlating to metal Au 4f7/2˜83.97 eV and Au 4f5/2~87.768 eV. Transmission electron microscopy and atomic force microscopy revealed the formation of individual nanoclusters of size ~1 nm and protein cluster aggregates of size ~8 nm. Photoluminescence studies show bright fluorescence with peak maximum at ~674 nm with the spectral profile covering the near-infrared (NIR) region, making it possible to image clusters at the 700-800 nm emission window where the tissue absorption of light is minimum. The cell viability and reactive oxygen toxicity studies indicate the non-toxic nature of the Au clusters up to relatively higher concentrations of 500 µg ml-1. Receptor-targeted cancer detection using Au clusters is demonstrated on FR+ve oral squamous cell carcinoma (KB) and breast adenocarcinoma cell MCF-7, where the FA-conjugated Au25 clusters were found internalized in significantly higher concentrations compared to the negative control cell lines. This study demonstrates the potential of using non-toxic fluorescent Au nanoclusters for the targeted imaging of cancer

    On Inverse Sigmoid Functions

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    Networks with sigmoid node functions have been shown to be universal approximators, and can use straightforward implementations of learning algorithms. Mathematically, what is common to different sigmoid functions used by different researchers? We establish a common representation of inverse sigmoid functions in terms of the Guass Hypergeometric function, generalizing different node function formulations. We also show that the continuous Hopfield network equation can be transformed into a Legendre differential equation, without assuming the specific form of the node function; this establishes a link between Hopfield nets and the method of function approximation using Legendre polynomial

    Avian Influenza (H7N9) Virus Infection in Chinese Tourist in Malaysia, 2014

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    Of the ≈400 cases of avian influenza (H7N9) diagnosed in China since 2003, the only travel-related cases have been in Hong Kong and Taiwan. Detection of a case in a Chinese tourist in Sabah, Malaysia, highlights the ease with which emerging viral respiratory infections can travel globally

    Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis

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    Background: Vascular elasticity is crucial for maintaining hemodynamics. Molecular mechanisms involved in human elastogenesis are incompletely understood. We describe a syndrome of lethal arteriopathy associated with a novel, identical mutation in the fibulin 4 gene (FBLN4) in a unique cohort of infants from South India. Methods: Clinical characteristics, cardiovascular findings, outcomes and molecular genetics of twenty-two infants from a distinct population subgroup, presenting with characteristic arterial dilatation and tortuosity during the period August 2004 to June 2011 were studied. Results: Patients (11 males, 11 females) presented at median age of 1.5 months, belonging to unrelated families from identical ethno-geographical background; eight had a history of consanguinity. Cardiovascular features included aneurysmal dilatation, elongation, tortuosity and narrowing of the aorta, pulmonary artery and their branches. The phenotype included a variable combination of cutis laxa (52%), long philtrum-thin vermillion (90%), micrognathia (43%), hypertelorism (57%), prominent eyes (43%), sagging cheeks (43%), long slender digits (48%), and visible arterial pulsations (38%). Genetic studies revealed an identical c.608A > C (p. Asp203Ala) mutation in exon 7 of the FBLN4 gene in all 22 patients, homozygous in 21, and compound heterozygous in one patient with a p. Arg227Cys mutation in the same conserved cbEGF sequence. Homozygosity was lethal (17/21 died, median age 4 months). Isthmic hypoplasia (n = 9) correlated with early death (<= 4 months). Conclusions: A lethal, genetic disorder characterized by severe deformation of elastic arteries, was linked to novel mutations in the FBLN4 gene. While describing a hitherto unreported syndrome in this population subgroup, this study emphasizes the critical role of fibulin-4 in human elastogenesis

    CTLA4 mRNA is downregulated by miR-155 in regulatory T cells, and reduced blood CTLA4 levels are associated with poor prognosis in metastatic melanoma patients

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    Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an immune checkpoint expressed in regulatory T (Treg) cells and activated T lymphocytes. Despite its potential as a treatment strategy for melanoma, CTLA-4 inhibition has limited efficacy. Using data from The Cancer Genome Atlas (TCGA) melanoma database and another dataset, we found that decreased CTLA4 mRNA was associated with a poorer prognosis in metastatic melanoma. To investigate further, we measured blood CTLA4 mRNA in 273 whole-blood samples from an Australian cohort and found that it was lower in metastatic melanoma than in healthy controls and associated with worse patient survival. We confirmed these findings using Cox proportional hazards model analysis and another cohort from the US. Fractionated blood analysis revealed that Treg cells were responsible for the downregulated CTLA4 in metastatic melanoma patients, which was confirmed by further analysis of published data showing downregulated CTLA-4 surface protein expression in Treg cells of metastatic melanoma compared to healthy donors. Mechanistically, we found that secretomes from human metastatic melanoma cells downregulate CTLA4 mRNA at the post-transcriptional level through miR-155 while upregulating FOXP3 expression in human Treg cells. Functionally, we demonstrated that CTLA4 expression inhibits the proliferation and suppressive function of human Treg cells. Finally, miR-155 was found to be upregulated in Treg cells from metastatic melanoma patients compared to healthy donors. Our study provides new insights into the underlying mechanisms of reduced CTLA4 expression observed in melanoma patients, demonstrating that post-transcriptional silencing of CTLA4 by miRNA-155 in Treg cells may play a critical role. Since CTLA-4 expression is downregulated in non-responder melanoma patients to anti-PD-1 immunotherapy, targeting miRNA-155 or other factors involved in regulating CTLA4 expression in Treg cells without affecting T cells could be a potential strategy to improve the efficacy of immunotherapy in melanoma. Further research is needed to understand the molecular mechanisms regulating CTLA4 expression in Treg cells and identify potential therapeutic targets for enhancing immune-based therapies
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