Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects

The anti-tumour effects of thalidomide have been associated with its anti-angiogenic properties. Second generation thalidomide analogues are distinct compounds with enhanced therapeutic potential. Although these compounds are beginning to enter trials for the treatment of cancer there is very little information regarding the anti-angiogenic activity of these clinically relevant compounds. Furthermore, it is not known how the various immunomodulatory activities of these compounds relate to anti-angiogenic activity. In this study we assessed the anti-angiogenic activity of compounds from both IMiD™ and SelCID™ classes of analogues using a novel in vitro multicellular human assay system and the established rat aorta assay. Our results show that both the IMiDs and SelCIDs tested are significantly more potent than thalidomide. The anti-angiogenic potency of the analogues was not related to inhibition of endothelial cell proliferation, nor their TNF-α/PDE type 4 inhibitory properties. However, anti-migratory effects in vitro and inhibition of tumour growth in vivo was observed with the analogue IMiD-1 (clinically known as REVIMID™). Our results show that anti-angiogenic activity spans both currently defined classes of thalidomide analogue and is not related to their previously described immunomodulatory properties. Identification of the differential effects of these compounds will enable targeting of such compounds into the appropriate clinical setting. British Journal of Cancer (2002) 87, 1166–1172. doi:10.1038/sj.bjc.6600607 www.bjcancer.com © 2002 Cancer Research U

Arithmetical Congruence Preservation: from Finite to Infinite

Various problems on integers lead to the class of congruence preserving functions on rings, i.e. functions verifying $a-b$ divides $f(a)-f(b)$ for all $a,b$. We characterized these classes of functions in terms of sums of rational polynomials (taking only integral values) and the function giving the least common multiple of $1,2,\ldots,k$. The tool used to obtain these characterizations is "lifting": if $\pi\colon X\to Y$ is a surjective morphism, and $f$ a function on $Y$ a lifting of $f$ is a function $F$ on $X$ such that $\pi\circ F=f\circ\pi$. In this paper we relate the finite and infinite notions by proving that the finite case can be lifted to the infinite one. For $p$-adic and profinite integers we get similar characterizations via lifting. We also prove that lattices of recognizable subsets of $Z$ are stable under inverse image by congruence preserving functions

Intensified Arctic warming under greenhouse warming by vegetation–atmosphere–sea ice interaction

Observations and modeling studies indicate that enhanced vegetation activities over high latitudes under an elevated CO2 concentration accelerate surface warming by reducing the surface albedo. In this study, we suggest that vegetation-atmosphere-sea ice interactions over high latitudes can induce an additional amplification of Arctic warming. Our hypothesis is tested by a series of coupled vegetation-climate model simulations under 2xCO(2) environments. The increased vegetation activities over high latitudes under a 2xCO(2) condition induce additional surface warming and turbulent heat fluxes to the atmosphere, which are transported to the Arctic through the atmosphere. This causes additional sea-ice melting and upper-ocean warming during the warm season. As a consequence, the Arctic and high-latitude warming is greatly amplified in the following winter and spring, which further promotes vegetation activities the following year. We conclude that the vegetation-atmosphere-sea ice interaction gives rise to additional positive feedback of the Arctic amplification.open1188sciescopu

Robust simulation methodology for surface-roughness loss in interconnect and package modelings

In multigigahertz integrated-circuit design, the extra energy loss caused by conductor surface roughness in metallic interconnects and packagings is more evident than ever before and demands explicit consideration for accurate prediction of signal integrity and energy consumption. Existing techniques based on analytical approximation, despite simple formulations, suffer from restrictive valid ranges, namely, either small or large roughness/frequencies. In this paper, we propose a robust and efficient numerical-simulation methodology applicable to evaluating general surface roughness, described by parameterized stochastic processes, across a wide frequency band. Traditional computation-intensive electromagnetic simulation is avoided via a tailored scalar-wave modeling to capture the power loss due to surface roughness. The spectral stochastic collocation method is applied to construct the complete statistical model. Comparisons with full wave simulation as well as existing methods in their respective valid ranges then verify the effectiveness of the proposed approach. © 2009 IEEE.published_or_final_versio

IFN-gamma is associated with risk of Schistosoma japonicum infection in China.

Before the start of the schistosomiasis transmission season, 129 villagers resident on a Schistosoma japonicum-endemic island in Poyang Lake, Jiangxi Province, 64 of whom were stool-positive for S. japonicum eggs by the Kato method and 65 negative, were treated with praziquantel. Forty-five days later the 93 subjects who presented for follow-up were all stool-negative. Blood samples were collected from all 93 individuals. S. japonicum soluble worm antigen (SWAP) and soluble egg antigen (SEA) stimulated IL-4, IL-5 and IFN-gamma production in whole-blood cultures were measured by ELISA. All the subjects were interviewed nine times during the subsequent transmission season to estimate the intensity of their contact with potentially infective snail habitats, and the subjects were all re-screened for S. japonicum by the Kato method at the end of the transmission season. Fourteen subjects were found to be infected at that time. There was some indication that the risk of infection might be associated with gender (with females being at higher risk) and with the intensity of water contact, and there was evidence that levels of SEA-induced IFN-gamma production were associated with reduced risk of infection

An EPTAS for Scheduling on Unrelated Machines of Few Different Types

In the classical problem of scheduling on unrelated parallel machines, a set of jobs has to be assigned to a set of machines. The jobs have a processing time depending on the machine and the goal is to minimize the makespan, that is the maximum machine load. It is well known that this problem is NP-hard and does not allow polynomial time approximation algorithms with approximation guarantees smaller than $1.5$ unless P$=$NP. We consider the case that there are only a constant number $K$ of machine types. Two machines have the same type if all jobs have the same processing time for them. This variant of the problem is strongly NP-hard already for $K=1$. We present an efficient polynomial time approximation scheme (EPTAS) for the problem, that is, for any $\varepsilon > 0$ an assignment with makespan of length at most $(1+\varepsilon)$ times the optimum can be found in polynomial time in the input length and the exponent is independent of $1/\varepsilon$. In particular we achieve a running time of $2^{\mathcal{O}(K\log(K) \frac{1}{\varepsilon}\log^4 \frac{1}{\varepsilon})}+\mathrm{poly}(|I|)$, where $|I|$ denotes the input length. Furthermore, we study three other problem variants and present an EPTAS for each of them: The Santa Claus problem, where the minimum machine load has to be maximized; the case of scheduling on unrelated parallel machines with a constant number of uniform types, where machines of the same type behave like uniformly related machines; and the multidimensional vector scheduling variant of the problem where both the dimension and the number of machine types are constant. For the Santa Claus problem we achieve the same running time. The results are achieved, using mixed integer linear programming and rounding techniques

POCS-based reconstruction of multiplexed sensitivity encoded MRI (POCSMUSE): A general algorithm for reducing motion-related artifacts.

PURPOSE: A projection onto convex sets reconstruction of multiplexed sensitivity encoded MRI (POCSMUSE) is developed to reduce motion-related artifacts, including respiration artifacts in abdominal imaging and aliasing artifacts in interleaved diffusion-weighted imaging. THEORY: Images with reduced artifacts are reconstructed with an iterative projection onto convex sets (POCS) procedure that uses the coil sensitivity profile as a constraint. This method can be applied to data obtained with different pulse sequences and k-space trajectories. In addition, various constraints can be incorporated to stabilize the reconstruction of ill-conditioned matrices. METHODS: The POCSMUSE technique was applied to abdominal fast spin-echo imaging data, and its effectiveness in respiratory-triggered scans was evaluated. The POCSMUSE method was also applied to reduce aliasing artifacts due to shot-to-shot phase variations in interleaved diffusion-weighted imaging data corresponding to different k-space trajectories and matrix condition numbers. RESULTS: Experimental results show that the POCSMUSE technique can effectively reduce motion-related artifacts in data obtained with different pulse sequences, k-space trajectories and contrasts. CONCLUSION: POCSMUSE is a general post-processing algorithm for reduction of motion-related artifacts. It is compatible with different pulse sequences, and can also be used to further reduce residual artifacts in data produced by existing motion artifact reduction methods

Psychometric precision in phenotype definition is a useful step in molecular genetic investigation of psychiatric disorders

Affective disorders are highly heritable, but few genetic risk variants have been consistently replicated in molecular genetic association studies. The common method of defining psychiatric phenotypes in molecular genetic research is either a summation of symptom scores or binary threshold score representing the risk of diagnosis. Psychometric latent variable methods can improve the precision of psychiatric phenotypes, especially when the data structure is not straightforward. Using data from the British 1946 birth cohort, we compared summary scores with psychometric modeling based on the General Health Questionnaire (GHQ-28) scale for affective symptoms in an association analysis of 27 candidate genes (249 single-nucleotide polymorphisms (SNPs)). The psychometric method utilized a bi-factor model that partitioned the phenotype variances into five orthogonal latent variable factors, in accordance with the multidimensional data structure of the GHQ-28 involving somatic, social, anxiety and depression domains. Results showed that, compared with the summation approach, the affective symptoms defined by the bi-factor psychometric model had a higher number of associated SNPs of larger effect sizes. These results suggest that psychometrically defined mental health phenotypes can reflect the dimensions of complex phenotypes better than summation scores, and therefore offer a useful approach in genetic association investigations

Optically pumped ultraviolet lasing from nitride nanopillars at room temperature

A vertical cavity structure composing of an in situ grown bottom Al x Ga 1-x N/Al y Ga 1-y N distributed Bragg reflector and a top SiO 2 / HfO 2 dielectric mirror for ultraviolet (UV) emission has been demonstrated. Close-packed nanopillars with diameters of around 500 nm have been achieved by the route of nanosphere lithography combined with inductively-coupled plasma etching. Optically-pumped UV lasing at a wavelength of 343.7 nm (3.608 eV) was observed at room temperature, with a threshold excitation density of 0.52 MW/ cm 2. The mechanism of the lasing action is discussed in detail. Our investigation indicates promising possibilities in nitride-based resonant cavity devices, particularly toward realizing the UV nitride-based vertical-cavity surface-emitting laser. © 2010 American Institute of Physics.published_or_final_versio