Phenotypic and Functional Characterization of Human Mammary Stem/Progenitor Cells in Long Term Culture

Background: Cancer stem cells exhibit close resemblance to normal stem cells in phenotype as well as function. Hence, studying normal stem cell behavior is important in understanding cancer pathogenesis. It has recently been shown that human breast stem cells can be enriched in suspension cultures as mammospheres. However, little is known about the behavior of these cells in long-term cultures. Since extensive self-renewal potential is the hallmark of stem cells, we undertook a detailed phenotypic and functional characterization of human mammospheres over long-term passages. Methodology: Single cell suspensions derived from human breast `organoids' were seeded in ultra low attachment plates in serum free media. Resulting primary mammospheres after a week (termed T1 mammospheres) were subjected to passaging every 7th day leading to the generation of T2, T3, and T4 mammospheres. Principal Findings: We show that primary mammospheres contain a distinct side-population (SP) that displays a CD24(low)/CD44(low) phenotype, but fails to generate mammospheres. Instead, the mammosphere-initiating potential rests within the CD44(high)/CD24(low) cells, in keeping with the phenotype of breast cancer-initiating cells. In serial sphere formation assays we find that even though primary (T1) mammospheres show telomerase activity and fourth passage T4 spheres contain label-retaining cells, they fail to initiate new mammospheres beyond T5. With increasing passages, mammospheres showed an increase in smaller sized spheres, reduction in proliferation potential and sphere forming efficiency, and increased differentiation towards the myoepithelial lineage. Significantly, staining for senescence-associated beta-galactosidase activity revealed a dramatic increase in the number of senescent cells with passage, which might in part explain the inability to continuously generate mammospheres in culture. Conclusions: Thus, the self-renewal potential of human breast stem cells is exhausted within five in vitro passages of mammospheres, suggesting the need for further improvisation in culture conditions for their long-term maintenance.

A note on the Hadwiger number of circular arc graphs

The intention of this note is to motivate the researchers to study Hadwiger's conjecture for circular arc graphs. Let η(G) denote the largest clique minor of a graph G, and let χ(G) denote its chromatic number. Hadwiger's conjecture states that η(G)greater-or-equal, slantedχ(G) and is one of the most important and difficult open problems in graph theory. From the point of view of researchers who are sceptical of the validity of the conjecture, it is interesting to study the conjecture for graph classes where η(G) is guaranteed not to grow too fast with respect to χ(G), since such classes of graphs are indeed a reasonable place to look for possible counterexamples. We show that in any circular arc graph G, η(G)less-than-or-equals, slant2χ(G)−1, and there is a family with equality. So, it makes sense to study Hadwiger's conjecture for this family.

Measurement of shock stand-off distance on a 120 degrees blunt cone model at hypersonic Mach number in Argon

The flow around a 120 degrees blunt cone model with a base radius of 60mm has been visualised at Mach 14.8 and 9.1 using argon as the test gas, at the newly established high speed schlieren facility in the IISc hypersonic shock tunnel HST2. The experimental shock stand off distance around the blunt cone is compared with that obtained using a commercial CFD package. The computed values of shock stand off distance of the blunt cone is found to agree reasonably well with the experimental data.

Long-lived giant number fluctuations in a swarming granular nematic

Coherently moving flocks of birds, beasts, or bacteria are examples of living matter with spontaneous orientational order. How do these systems differ from thermal equilibrium systems with such liquid crystalline order? Working with a fluidized monolayer of macroscopic rods in the nematic liquid crystalline phase, we find giant number fluctuations consistent with a standard deviation growing linearly with the mean, in contrast to any situation where the central limit theorem applies. These fluctuations are long-lived, decaying only as a logarithmic function of time. This shows that flocking, coherent motion, and large-scale inhomogeneity can appear in a system in which particles do not communicate except by contact.

Hadwiger Number and the Cartesian Product of Graphs

The Hadwiger number eta(G) of a graph G is the largest integer n for which the complete graph K-n on n vertices is a minor of G. Hadwiger conjectured that for every graph G, eta(G) >= chi(G), where chi(G) is the chromatic number of G. In this paper, we study the Hadwiger number of the Cartesian product G square H of graphs. As the main result of this paper, we prove that eta(G(1) square G(2)) >= h root 1 (1 - o(1)) for any two graphs G(1) and G(2) with eta(G(1)) = h and eta(G(2)) = l. We show that the above lower bound is asymptotically best possible when h >= l. This asymptotically settles a question of Z. Miller (1978). As consequences of our main result, we show the following: 1. Let G be a connected graph. Let G = G(1) square G(2) square ... square G(k) be the ( unique) prime factorization of G. Then G satisfies Hadwiger's conjecture if k >= 2 log log chi(G) + c', where c' is a constant. This improves the 2 log chi(G) + 3 bound in [2] 2. Let G(1) and G(2) be two graphs such that chi(G1) >= chi(G2) >= clog(1.5)(chi(G(1))), where c is a constant. Then G1 square G2 satisfies Hadwiger's conjecture. 3. Hadwiger's conjecture is true for G(d) (Cartesian product of G taken d times) for every graph G and every d >= 2. This settles a question by Chandran and Sivadasan [2]. ( They had shown that the Hadiwger's conjecture is true for G(d) if d >= 3).

A cost effective pipelined divider for double precision floating point number

he growth of high-performance application in computer graphics, signal processing and scientific computing is a key driver for high performance, fixed latency; pipelined floating point dividers. Solutions available in the literature use large lookup table for double precision floating point operations.In this paper, we propose a cost effective, fixed latency pipelined divider using modified Taylor-series expansion for double precision floating point operations. We reduce chip area by using a smaller lookup table. We show that the latency of the proposed divider is 49.4 times the latency of a full-adder. The proposed divider reduces chip area by about 81% than the pipelined divider in [9] which is based on modified Taylor-series.

An Estimator Algorithm For Learning Automata With Changing Number Of Actions

In many problems of decision making under uncertainty the system has to acquire knowledge of its environment and learn the optimal decision through its experience. Such problems may also involve the system having to arrive at the globally optimal decision, when at each instant only a subset of the entire set of possible alternatives is available. These problems can be successfully modelled and analysed by learning automata. In this paper an estimator learning algorithm, which maintains estimates of the reward characteristics of the random environment, is presented for an automaton with changing number of actions. A learning automaton using the new scheme is shown to be e-optimal. The simulation results demonstrate the fast convergence properties of the new algorithm. The results of this study can be extended to the design of other types of estimator algorithms with good convergence properties.

Design of crosspoint-irredundant PLAs using minimal number of control inputs

The problem of determining a minimal number of control inputs for converting a programmable logic array (PLA) with undetectable faults to crosspoint-irredundant PLA for testing has been formulated as a nonstandard set covering problem. By representing subsets of sets as cubes, this problem has been reformulated as familiar problems. It is noted that this result has significance because a crosspoint-irredundant PLA can be converted to a completely testable PLA in a straightforward fashion, thus achieving very good fault coverage and easy testability.

Evolution of polyandry by reduction in progeny number variance in structured populations

When there is a variation in the quality of males in a population, multiple mating can lead to an increase in the genetic fitness of a female by reducing the variance of the progeny number. The extent of selective advantage obtainable by this process is investigated for a population subdivided into structured demes. It is seen that for a wide range of model parameters (deme size, distribution of male quality, local resource level), multiple mating leads to a considerable increase in the fitness. Frequency-dependent selection or a stable coexistence between polyandry and monandry can also result when the possible costs involved in multiple mating are taken into account.

On Finding the Natural Number of Topics with Latent Dirichlet Allocation: Some Observations

It is important to identify the ``correct'' number of topics in mechanisms like Latent Dirichlet Allocation(LDA) as they determine the quality of features that are presented as features for classifiers like SVM. In this work we propose a measure to identify the correct number of topics and offer empirical evidence in its favor in terms of classification accuracy and the number of topics that are naturally present in the corpus. We show the merit of the measure by applying it on real-world as well as synthetic data sets(both text and images). In proposing this measure, we view LDA as a matrix factorization mechanism, wherein a given corpus C is split into two matrix factors M-1 and M-2 as given by C-d*w = M1(d*t) x Q(t*w).Where d is the number of documents present in the corpus anti w is the size of the vocabulary. The quality of the split depends on ``t'', the right number of topics chosen. The measure is computed in terms of symmetric KL-Divergence of salient distributions that are derived from these matrix factors. We observe that the divergence values are higher for non-optimal number of topics - this is shown by a `dip' at the right value for `t'.

Design of speaker identification schemes for large number of speakers (A)

Design of speaker identification schemes for a small number of speakers (around 10) with a high degree of accuracy in controlled environment is a practical proposition today. When the number of speakers is large (say 50–100), many of these schemes cannot be directly extended, as both recognition error and computation time increase monotonically with population size. The feature selection problem is also complex for such schemes. Though there were earlier attempts to rank order features based on statistical distance measures, it has been observed only recently that the best two independent measurements are not the same as the combination in two's for pattern classification. We propose here a systematic approach to the problem using the decision tree or hierarchical classifier with the following objectives: (1) Design of optimal policy at each node of the tree given the tree structure i.e., the tree skeleton and the features to be used at each node. (2) Determination of the optimal feature measurement and decision policy given only the tree skeleton. Applicability of optimization procedures such as dynamic programming in the design of such trees is studied. The experimental results deal with the design of a 50 speaker identification scheme based on this approach.