Multimodal therapy for complete regression of malignant melanoma using constrained nonlinear optimal dynamic inversion

Using a realistic nonlinear mathematical model for melanoma dynamics and the technique of optimal dynamic inversion (exact feedback linearization with static optimization), a multimodal automatic drug dosage strategy is proposed in this paper for complete regression of melanoma cancer in humans. The proposed strategy computes different drug dosages and gives a nonlinear state feedback solution for driving the number of cancer cells to zero. However, it is observed that when tumor is regressed to certain value, then there is no need of external drug dosages as immune system and other therapeutic states are able to regress tumor at a sufficiently fast rate which is more than exponential rate. As model has three different drug dosages, after applying dynamic inversion philosophy, drug dosages can be selected in optimized manner without crossing their toxicity limits. The combination of drug dosages is decided by appropriately selecting the control design parameter values based on physical constraints. The process is automated for all possible combinations of the chemotherapy and immunotherapy drug dosages with preferential emphasis of having maximum possible variety of drug inputs at any given point of time. Simulation study with a standard patient model shows that tumor cells are regressed from 2 x 107 to order of 105 cells because of external drug dosages in 36.93 days. After this no external drug dosages are required as immune system and other therapeutic states are able to regress tumor at greater than exponential rate and hence, tumor goes to zero (less than 0.01) in 48.77 days and healthy immune system of the patient is restored. Study with different chemotherapy drug resistance value is also carried out. (C) 2014 Elsevier Ltd. All rights reserved.

Genomic mapping of cAMP receptor protein (CRPMt) in Mycobacterium tuberculosis: relation to transcriptional start sites and the role of CRPMt as a transcription factor

Chromatin immunoprecipitation identified 191 binding sites of Mycobacterium tuberculosis cAMP receptor protein (CRPMt) at endogenous expression levels using a specific alpha-CRPMt antibody. Under these native conditions an equal distribution between intragenic and intergenic locations was observed. CRPMt binding overlapped a palindromic consensus sequence. Analysis by RNA sequencing revealed widespread changes in transcriptional profile in a mutant strain lacking CRPMt during exponential growth, and in response to nutrient starvation. Differential expression of genes with a CRPMt-binding site represented only a minor portion of this transcriptional reprogramming with similar to 19% of those representing transcriptional regulators potentially controlled by CRPMt. The subset of genes that are differentially expressed in the deletion mutant under both culture conditions conformed to a pattern resembling canonical CRP regulation in Escherichia coli, with binding close to the transcriptional start site associated with repression and upstream binding with activation. CRPMt can function as a classical transcription factor in M. tuberculosis, though this occurs at only a subset of CRPMt-binding sites.

UNO Gets Easier for a Single Player

This work is a follow up to 2, FUN 2010], which initiated a detailed analysis of the popular game of UNO (R). We consider the solitaire version of the game, which was shown to be NP-complete. In 2], the authors also demonstrate a (O)(n)(c(2)) algorithm, where c is the number of colors across all the cards, which implies, in particular that the problem is polynomial time when the number of colors is a constant. In this work, we propose a kernelization algorithm, a consequence of which is that the problem is fixed-parameter tractable when the number of colors is treated as a parameter. This removes the exponential dependence on c and answers the question stated in 2] in the affirmative. We also introduce a natural and possibly more challenging version of UNO that we call ``All Or None UNO''. For this variant, we prove that even the single-player version is NP-complete, and we show a single-exponential FPT algorithm, along with a cubic kernel.

Subexponential Algorithm for d-Cluster Edge Deletion: Exception or Rule?

The correlation clustering problem is a fundamental problem in both theory and practice, and it involves identifying clusters of objects in a data set based on their similarity. A traditional modeling of this question as a graph theoretic problem involves associating vertices with data points and indicating similarity by adjacency. Clusters then correspond to cliques in the graph. The resulting optimization problem, Cluster Editing (and several variants) are very well-studied algorithmically. In many situations, however, translating clusters to cliques can be somewhat restrictive. A more flexible notion would be that of a structure where the vertices are mutually ``not too far apart'', without necessarily being adjacent. One such generalization is realized by structures called s-clubs, which are graphs of diameter at most s. In this work, we study the question of finding a set of at most k edges whose removal leaves us with a graph whose components are s-clubs. Recently, it has been shown that unless Exponential Time Hypothesis fail (ETH) fails Cluster Editing (whose components are 1-clubs) does not admit sub-exponential time algorithm STACS, 2013]. That is, there is no algorithm solving the problem in time 2 degrees((k))n(O(1)). However, surprisingly they show that when the number of cliques in the output graph is restricted to d, then the problem can be solved in time O(2(O(root dk)) + m + n). We show that this sub-exponential time algorithm for the fixed number of cliques is rather an exception than a rule. Our first result shows that assuming the ETH, there is no algorithm solving the s-Club Cluster Edge Deletion problem in time 2 degrees((k))n(O(1)). We show, further, that even the problem of deleting edges to obtain a graph with d s-clubs cannot be solved in time 2 degrees((k))n(O)(1) for any fixed s, d >= 2. This is a radical contrast from the situation established for cliques, where sub-exponential algorithms are known.

Angular momentum transport and evolution of lopsided galaxies

The surface brightness distribution in the majority of stellar galactic discs falls off exponentially. Often what lies beyond such a stellar disc is the neutral hydrogen gas whose distribution also follows a nearly exponential profile at least for a number of nearby disc galaxies. Both the stars and gas are commonly known to host lopsided asymmetry especially in the outer parts of a galaxy. The role of such asymmetry in the dynamical evolution of a galaxy has not been explored so far. Following Lindblad's original idea of kinematic density waves, we show that the outer part of an exponential disc is ideally suitable for hosting lopsided asymmetry. Further, we compute the transport of angular momentum in the combined stars and gas disc embedded in a dark matter halo. We show that in a pure star and gas disc, there is a transition point where the free precession frequency of a lopsided mode, Omega - kappa, changes from retrograde to prograde and this in turn reverses the direction of angular momentum flow in the disc leading to an unphysical behaviour. We show that this problem is overcome in the presence of a dark matter halo, which sets the angular momentum flow outwards as required for disc evolution, provided the lopsidedness is leading in nature. This, plus the well-known angular momentum transport in the inner parts due to spiral arms, can facilitate an inflow of gas from outside perhaps through the cosmic filaments.

STM verification of the reduction of the Young's modulus of CdS nanoparticles at smaller sizes

We demonstrate the first STM evaluation of the Young's modulus (E) of nanoparticles (NPs) of different sizes. The sample deformation induced by tip-sample interaction has been determined using current-distance (I-Z) spectroscopy. As a result of tip-sample interaction, and the induced surface deformations, the I-z curves deviates from pure exponential dependence. Normally, in order to analyze the deformation quantitatively, the tip radius must be known. We show, that this necessity is eliminated by measuring the deformation on a substrate with a known Young's modulus (Au(111)) and estimating the tip radius, and afterwards, using the same tip (with a known radius) to measure the (unknown) Young's modulus of another sample (nanoparticles of CdS). The Young's modulus values found for 3 NP's samples of average diameters of 3.7, 6 and 7.5 nm, were E similar to 73%, 78% and 88% of the bulk value, respectively. These results are in a good agreement with the theoretically predicted reduction of the Young's modulus due to the changes in hydrostatic stresses which resulted from surface tension in nanoparticles with different sizes. Our calculation using third order elastic constants gives a reduction of E which scales linearly with 1/r (r is the NP's radius). This demonstrates the applicability of scanning tunneling spectroscopy for local mechanical characterization of nanoobjects. The method does not include a direct measurement of the tip-sample force but is rather based on the study of the relative elastic response. (C) 2014 Elsevier B.V. All rights reserved.

Influence of Spatial Variability on Pavement Responses Using Latin Hypercube Sampling on Two-Dimensional Random Fields

Although uncertainties in material properties have been addressed in the design of flexible pavements, most current modeling techniques assume that pavement layers are homogeneous. The paper addresses the influence of the spatial variability of the resilient moduli of pavement layers by evaluating the effect of the variance and correlation length on the pavement responses to loading. The integration of the spatially varying log-normal random field with the finite-difference method has been achieved through an exponential autocorrelation function. The variation in the correlation length was found to have a marginal effect on the mean values of the critical strains and a noticeable effect on the standard deviation which decreases with decreases in correlation length. This reduction in the variance arises because of the spatial averaging phenomenon over the softer and stiffer zones generated because of spatial variability. The increase in the mean value of critical strains with decreasing correlation length, although minor, illustrates that pavement performance is adversely affected by the presence of spatially varying layers. The study also confirmed that the higher the variability in the pavement layer moduli, introduced through a higher value of coefficient of variation (COV), the higher the variability in the pavement response. The study concludes that ignoring spatial variability by modeling the pavement layers as homogeneous that have very short correlation lengths can result in the underestimation of the critical strains and thus an inaccurate assessment of the pavement performance. (C) 2014 American Society of Civil Engineers.

Nature of the effective interaction between dendrimers

We have performed fully atomistic classical molecular dynamics simulations to calculate the effective interaction between two polyamidoamine dendrimers. Using the umbrella sampling technique, we have obtained the potential of mean force (PMF) between the dendrimers and investigated the effects of protonation level and dendrimer size on the PMF. Our results show that the interaction between the dendrimers can be tuned from purely repulsive to partly attractive by changing the protonation level. The PMF profiles are well-fitted by the sum of an exponential and a Gaussian function with the weight of the exponential function dominating over that of the Gaussian function. This observation is in disagreement with the results obtained in previous analytic C. Likos, M. Schmidt, H. Lowen, M. Ballauff, D. Potschke, and P. Lindner, Macromolecules 34, 2914 (2001)] and coarse-grained simulation I. Gotze, H. Harreis, and C. Likos, J. Chem. Phys. 120, 7761 (2004)] studies which predicted the effective interaction to be Gaussian. (C) 2014 AIP Publishing LLC.

Surrogate Regret Bounds for Bipartite Ranking via Strongly Proper Losses

The problem of bipartite ranking, where instances are labeled positive or negative and the goal is to learn a scoring function that minimizes the probability of mis-ranking a pair of positive and negative instances (or equivalently, that maximizes the area under the ROC curve), has been widely studied in recent years. A dominant theoretical and algorithmic framework for the problem has been to reduce bipartite ranking to pairwise classification; in particular, it is well known that the bipartite ranking regret can be formulated as a pairwise classification regret, which in turn can be upper bounded using usual regret bounds for classification problems. Recently, Kotlowski et al. (2011) showed regret bounds for bipartite ranking in terms of the regret associated with balanced versions of the standard (non-pairwise) logistic and exponential losses. In this paper, we show that such (non-pairwise) surrogate regret bounds for bipartite ranking can be obtained in terms of a broad class of proper (composite) losses that we term as strongly proper. Our proof technique is much simpler than that of Kotlowski et al. (2011), and relies on properties of proper (composite) losses as elucidated recently by Reid and Williamson (2010, 2011) and others. Our result yields explicit surrogate bounds (with no hidden balancing terms) in terms of a variety of strongly proper losses, including for example logistic, exponential, squared and squared hinge losses as special cases. An important consequence is that standard algorithms minimizing a (non-pairwise) strongly proper loss, such as logistic regression and boosting algorithms (assuming a universal function class and appropriate regularization), are in fact consistent for bipartite ranking; moreover, our results allow us to quantify the bipartite ranking regret in terms of the corresponding surrogate regret. We also obtain tighter surrogate bounds under certain low-noise conditions via a recent result of Clemencon and Robbiano (2011).

Frequency and Temperature-Independent Electrical Transport Properties of 2BaO-0.5Na(2)O-2.5Nb(2)O(5)-4.5B(2)O(3) Glass-Ceramics

The temperature (300-973K) and frequency (100Hz-10MHz) response of the dielectric and impedance characteristics of 2BaO-0.5Na(2)O-2.5Nb(2)O(5)-4.5B(2)O(3) glasses and glass nanocrystal composites were studied. The dielectric constant of the glass was found to be almost independent of frequency (100Hz-10MHz) and temperature (300-600K). The temperature coefficient of dielectric constant was 8 +/- 3ppm/K in the 300-600K temperature range. The relaxation and conduction phenomena were rationalized using modulus formalism and universal AC conductivity exponential power law, respectively. The observed relaxation behavior was found to be thermally activated. The complex impedance data were fitted using the least square method. Dispersion of Barium Sodium Niobate (BNN) phase at nanoscale in a glass matrix resulted in the formation of space charge around crystal-glass interface, leading to a high value of effective dielectric constant especially for the samples heat-treated at higher temperatures. The fabricated glass nanocrystal composites exhibited P versus E hysteresis loops at room temperature and the remnant polarization (P-r) increased with the increase in crystallite size.

Photoluminescence, photocatalysis and Judd-Ofelt analysis of Eu3+-activated layered BiOCl phosphors

Eu3+-activated layered BiOCl phosphors were synthesized by the conventional solid-state method at relatively low temperature and shorter duration (400 degrees C for 1 h). All the samples were crystallized in the tetragonal structure with the space group P4/nmm (no. 129). Field emission scanning electron microscopy (FE-SEM) studies confirmed the plate-like morphology. Photoluminescence spectra exhibit characteristic luminescent D-5(0) -> F-7(J) (J = 0-4) intra-4f shell Eu3+ ion transitions. The electric dipole transition located at 620 nm (D-5(0) -> F-7(2)) was stronger than the magnetic dipole transition located at 594 nm (D-5(0) -> F-7(1)). The evaluated Commission International de l'Eclairage (CIE) color coordinates of Eu3+-activated BiOCl phosphors were close to the commercial Y2O3:Eu3+ and Y2O2S:Eu3+ red phosphors. Intensity parameters (Omega(2), Omega(4)) and various radiative properties such as transition probability (A(tot)), radiative lifetime (tau(rad)), stimulated emission cross-section (sigma(e)), gain bandwidth (sigma(e) x Delta lambda(eff)) and optical gain (sigma(e) x tau(rad)) were calculated using the Judd-Ofelt theory. The experimental decay curves of the D-5(0) level in Eu3+-activated BiOCl have a single exponential profile. In comparison with other Eu3+ doped materials, Eu3+-activated BiOCl phosphors have a long lifetime (tau(exp)), low non-radiative relaxation rate (W-NR), high quantum efficiency (eta) and better optical gain (sigma(e) x tau(rad)). The determined radiative properties revealed the usefulness of Eu3+-activated BiOCl in developing red lasers as well as optical display devices. Further, these samples showed efficient photocatalytic activity for the degradation of rhodamine B (RhB) dye under visible light irradiation. These photocatalysts are useful for the removal of toxic and non-biodegradable organic pollutants in water.

Embodied energy assessment of building materials in India using process and input-output analysis

Growing demand for urban built spaces has resulted in unprecedented exponential rise in production and consumption of building materials in construction. Production of materials requires significant energy and contributes to pollution and green house gas (GHG) emissions. Efforts aimed at reducing energy consumption and pollution involved with the production of materials fundamentally requires their quantification. Embodied energy (EE) of building materials comprises the total energy expenditure involved in the material production including all upstream processes such as raw material extraction and transportation. The current paper deals with EE of a few common building materials consumed in bulk in Indian construction industry. These values have been assessed based on actual industrial survey data. Current studies on EE of building materials lack agreement primarily with regard to method of assessment and energy supply assumptions (whether expressed in terms of end use energy or primary energy). The current paper examines the suitability of two basic methods; process analysis and input-output method and identifies process analysis as appropriate for EE assessment in the Indian context. A comparison of EE values of building materials in terms of the two energy supply assumptions has also been carried out to investigate the associated discrepancy. The results revealed significant difference in EE of materials whose production involves significant electrical energy expenditure relative to thermal energy use. (C) 2014 Elsevier B.V. All rights reserved.

Molecules support morphology: species status of South Indian populations of the widely distributed Hanuman langur

The taxonomy of the Hanuman langur (Semnopithecus spp.), a widely distributed Asian colobine monkey, has been in a flux for a long time due to much disagreement between various classification schemes. However, results from a recent field-based morphological study were consistent with Hill's (Ceylon J Sci 21:277-305, 1939) species level classification scheme. Here we tested the validity of S. hypoleucos and S. priam, the two South Indian species recognized by Hill. To this end, one mitochondrial and four nuclear markers were sequenced from over 72 non-invasive samples of Hanuman langurs and S. johnii collected from across India. The molecular data were subjected to various tree building methods. The nuclear data was also used in a Bayesian structure analysis and to determine the genealogical sorting index of each hypothesized species. Results from nuclear data suggest that the South Indian population of Hanuman langur consists of two units that correspond to the species recognized by Hill. However in the mitochondrial tree S. johnii and S. priam were polyphyletic probably due to retention of ancestral polymorphism and/or low levels of hybridization. Implications of these results on conservation of Hanuman langurs are also discussed.

An Algorithmic Characterization of Polynomial Functions over Z(pn)

In this paper we consider polynomial representability of functions defined over , where p is a prime and n is a positive integer. Our aim is to provide an algorithmic characterization that (i) answers the decision problem: to determine whether a given function over is polynomially representable or not, and (ii) finds the polynomial if it is polynomially representable. The previous characterizations given by Kempner (Trans. Am. Math. Soc. 22(2):240-266, 1921) and Carlitz (Acta Arith. 9(1), 67-78, 1964) are existential in nature and only lead to an exhaustive search method, i.e. algorithm with complexity exponential in size of the input. Our characterization leads to an algorithm whose running time is linear in size of input. We also extend our result to the multivariate case.

Characterizing the Impact of Feedback Delays on Wideband Rate Adaptation

In contemporary orthogonal frequency division multiplexing (OFDM) systems, such as Long Term Evolution (LTE), LTE-Advanced, and WiMAX, a codeword is transmitted over a group of subcarriers. Since different subcarriers see different channel gains in frequency-selective channels, the modulation and coding scheme (MCS) of the codeword must be selected based on the vector of signal-to-noise-ratios (SNRs) of these subcarriers. Exponential effective SNR mapping (EESM) maps the vector of SNRs into an equivalent flat-fading SNR, and is widely used to simplify this problem. We develop a new analytical framework to characterize the throughput of EESM-based rate adaptation in such wideband channels in the presence of feedback delays. We derive a novel accurate approximation for the throughput as a function of feedback delay. We also propose a novel bivariate gamma distribution to model the time evolution of EESM between the times of estimation and data transmission, which facilitates the analysis. These are then generalized to a multi-cell, multi-user scenario with various frequency-domain schedulers. Unlike prior work, most of which is simulation-based, our framework encompasses both correlated and independent subcarriers and various multiple antenna diversity modes; it is accurate over a wide range of delays.