Super-paramagnetic clustering of yeast gene expression profiles

High-density DNA arrays, used to monitor gene expression at a genomic scale, have produced vast amounts of information which require the development of efficient computational methods to analyze them. The important first step is to extract the fundamental patterns of gene expression inherent in the data. This paper describes the application of a novel clustering algorithm, Super-Paramagnetic Clustering (SPC) to analysis of gene expression profiles that were generated recently during a study of the yeast cell cycle. SPC was used to organize genes into biologically relevant clusters that are suggestive for their co-regulation. Some of the advantages of SPC are its robustness against noise and initialization, a clear signature of cluster formation and splitting, and an unsupervised self-organized determination of the number of clusters at each resolution. Our analysis revealed interesting correlated behavior of several groups of genes which has not been previously identified

PK/PD models in antibacterial development

There is an urgent need for novel antibiotics to treat life-threatening infections caused by bacterial 'superbugs'. Validated in vitro pharmacokinetic/pharmacodynamic (PK/PD) and animal infection models have been employed to identify the most predictive PK/PD indices and serve as key tools in the antibiotic development process. The results obtained can be utilized for optimizing study designs in order to minimize the cost and duration of clinical trials. This review outlines the key in vitro PK/PD and animal infection models which have been extensively used in antibiotic discovery and development. These models have shown great potential in accelerating drug development programs and will continue to make significant contributions to antibiotic development

Coupled mechanical resonators with broken Lorentz reciprocity for sensor applications

Having simultaneously a high quality factor (i.e. a narrow resonant band) and a shorter decay time between the resonating system and the external sources (i.e. a wide resonant band) is a desirable characteristic for mechanical resonators, which however has been regarded as contradictory. This has been known as the limit of Lorentz reciprocity. We explore a configuration to achieve this desired characteristic within the mechanical regime. The configuration consists of a pair of mechanical resonators coupled together through their connecting part. One of them is encapsulated in a vacuum environment, and the other is left in the normal ambient condition. Numerical model of this configuration shows clearly the advantages such as: (a), sensitivity to the change of resonant frequency is greatly improved (the product of bandwidth and the decay time has increased at least two orders of magnitude); (b), the value of can be adjusted through the coupling stiffness

Over-expression of Thioredoxin-1 mediates growth, survival, and chemoresistance and is a druggable target in diffuse large B-cell lymphoma

Diffuse Large B cell lymphomas (DLBCL) are the most prevalent of the non-Hodgkin lymphomas and are currently initially treated fairly successfully, but frequently relapse as refractory disease, resulting in poor salvage therapy options and short survival. The greatest challenge in improving survival of DLBCL patients is overcoming chemo-resistance, whose basis is poorly understood. Among the potential mediators of DLBCL chemo-resistance is the thioredxoin (Trx) family, primarily because Trx family members play critical roles in the regulation of cellular redox homeostasis, and recent studies have indicated that dysregulated redox homeostasis also plays a key role in chemoresistance. In this study, we showed that most of the DLBCL-derived cell lines and primary DLBCL cells express higher basal levels of Trx-1 than normal B cells and that Trx-1 expression level is associated with decreased patients survival. Our functional studies showed that inhibition of Trx-1 by small interfering RNA or a Trx-1 inhibitor (PX-12) inhibited DLBCL cell growth, clonogenicity, and also sensitized DLBCL cells to doxorubicin-induced cell growth inhibition in vitro. These results indicate that Trx-1 plays a key role in cell growth and survival, as well as chemoresistance, and is a potential target to overcome drug resistance in relapsed/refractory DLBCL

Mean Field Behavior of Cluster Dynamics

The dynamic behavior of cluster algorithms is analyzed in the classical mean field limit. Rigorous analytical results below $T_c$ establish that the dynamic exponent has the value $z_{sw}=1$ for the Swendsen-Wang algorithm and $z_{uw}=0$ for the Wolff algorithm. An efficient Monte Carlo implementation is introduced, adapted for using these algorithms for fully connected graphs. Extensive simulations both above and below $T_c$ demonstrate scaling and evaluate the finite-size scaling function by means of a rather impressive collapse of the data.Comment: Revtex, 9 pages with 7 figure

Local and cluster critical dynamics of the 3d random-site Ising model

We present the results of Monte Carlo simulations for the critical dynamics of the three-dimensional site-diluted quenched Ising model. Three different dynamics are considered, these correspond to the local update Metropolis scheme as well as to the Swendsen-Wang and Wolff cluster algorithms. The lattice sizes of L=10-96 are analysed by a finite-size-scaling technique. The site dilution concentration p=0.85 was chosen to minimize the correction-to-scaling effects. We calculate numerical values of the dynamical critical exponents for the integrated and exponential autocorrelation times for energy and magnetization. As expected, cluster algorithms are characterized by lower values of dynamical critical exponent than the local one: also in the case of dilution critical slowing down is more pronounced for the Metropolis algorithm. However, the striking feature of our estimates is that they suggest that dilution leads to decrease of the dynamical critical exponent for the cluster algorithms. This phenomenon is quite opposite to the local dynamics, where dilution enhances critical slowing down.Comment: 24 pages, 16 figures, style file include

Solid state supramolecular structure of diketopyrrolopyrrole chromophores: correlating stacking geometry with visible light absorption

Mono- and di-alkylated 1,4-diketo-3,6-dithiophenylpyrrolo[3-4-c]pyrrole derivatives (TDPPs) have been synthesised and their solid state packing and absorption properties have been correlated. In this library of compounds the bulkier substituents distort the geometry of the chromophores and shift the lowest energy absorption band as a consequence of reduced π–π stacking and inter-chromophore overlap. Longitudinal displacement of the conjugated core is affected by donor–acceptor intermolecular interactions and twisting of the thiophene ring out of the plane of the DPP core, whereas lateral displacement was correlated to distortion of the NLactam–C(R) bond out of the plane of the DPP core. The di-substituted TDPP with hexyl units exhibit high molecular planarity, strong close packing of the conjugated core and significant red shift of the maximum of absorption in the solid, whereas the mono-substituted compounds with hexyl and ethyl acetate units are the least distorted of the series because of strong intermolecular hydrogen bonding that increases the molecular overlap and planarity of the chromophores. Therefore the family of mono-substituted TDPPs and more specifically the ones with ethyl acetate substituents show good potential for modulating the molecular geometry and optimizing the charge transport in materials for organic electronic applications

Carbon–GO Composites with Preferential Water versus Ethanol Uptake

The elimination of small amounts of water from alcohols is by no means a trivial issue in many practical applications like, for instance, the dehumidification of biocombustibles. The use of carbonaceous materials as sorbents has been far less explored than that of other materials because their hydrophobic character has typically limited their water uptake. Herein, we designed a synthetic process based on the use of eutectic mixtures that allowed the homogeneous dispersion of graphene oxide (GO) in the liquid containing the carbon precursor, e.g., furfuryl alcohol. Thus, after polymerization and a subsequent carbonization process, we were able to obtain porous carbon–GO composites where the combination of pore diameter and surface hydrophilicity provided a remarkable capacity for water uptake but extremely low methanol and ethanol uptake along the entire range of relative pressures evaluated in this work. Both the neat water uptake and the uptake difference between water and either methanol or ethanol of our carbon–GO composites were similar or eventually better than the uptake previously reported for other materials, also exhibiting preferential water-to-alcohol adsorption, e.g., porous coordination polymers, metal–organic frameworks, polyoxometalates, and covalent two-dimensional nanosheets embedded in a polymer matrix. Moreover, water versus alcohol uptake was particularly remarkable at low partial pressures in our carbon–GO composites.This work was supported by MINECO/FEDER (Project Numbers MAT2015-68639-R, MAT2016-80285-P, and RTI2018-097728-B-I00). L.Z.G. acknowledges the Chinese Scholarship Council for a PhD research fellowship (CSC No. 201608330266). C.C.-C. acknowledges UA for a research contract

A General Limitation on Monte Carlo Algorithms of Metropolis Type

We prove that for any Monte Carlo algorithm of Metropolis type, the autocorrelation time of a suitable ``energy''-like observable is bounded below by a multiple of the corresponding ``specific heat''. This bound does not depend on whether the proposed moves are local or non-local; it depends only on the distance between the desired probability distribution $\pi$ and the probability distribution $\pi^{(0)}$ for which the proposal matrix satisfies detailed balance. We show, with several examples, that this result is particularly powerful when applied to non-local algorithms.Comment: 8 pages, LaTeX plus subeqnarray.sty (included at end), NYU-TH-93/07/01, IFUP-TH33/9