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

Evolutionary game of coalition building under external pressure

We study the fragmentation-coagulation (or merging and splitting) evolutionary control model as introduced recently by one of the authors, where $N$ small players can form coalitions to resist to the pressure exerted by the principal. It is a Markov chain in continuous time and the players have a common reward to optimize. We study the behavior as $N$ grows and show that the problem converges to a (one player) deterministic optimization problem in continuous time, in the infinite dimensional state space

An investigation of South Pole HOx chemistry: Comparison of model results with ISCAT observations

Unexpected high levels of OH and NO were recorded at the South Pole (SP) Atmospheric Research Observatory during the 1998-99 ISCAT field study. Model simulations suggest a major photochemical linkage between observed OH and NO. A detailed comparison of the observations with model predictions revealed good agreement for OH at NO levels between 120 and 380 pptv. However, the model tended to overestimate OH for NO levels < 120 pptv, while it underestimated OH at levels > 380 pptv. The reasons for these deviations appear not to involve NO directly but rather HOx radical scavenging for the low NO conditions and additional HOx sources for the high NO conditions. Because of the elevated levels of NO and highly activated HOx photochemistry, the SP was found to be a strong net source of surface ozone. It is quite likely that the strong oxidizing environment found at the South Pole extends over the entire polar plateau

Anomaly and a QCD-like phase diagram with massive bosonic baryons

We study a strongly coupled $Z_2$ lattice gauge theory with two flavors of quarks, invariant under an exact $\mathrm{SU}(2)\times \mathrm{SU}(2) \times \mathrm{U}_A(1) \times \mathrm{U}_B(1)$ symmetry which is the same as QCD with two flavors of quarks without an anomaly. The model also contains a coupling that can be used to break the $\mathrm{U}_A(1)$ symmetry and thus mimic the QCD anomaly. At low temperatures $T$ and small baryon chemical potential $\mu_B$ the model contains massless pions and massive bosonic baryons similar to QCD with an even number of colors. In this work we study the $T-\mu_B$ phase diagram of the model and show that it contains three phases : (1) A chirally broken phase at low $T$ and $\mu_B$, (2) a chirally symmetric baryon superfluid phase at low $T$ and high $\mu_B$, and (3) a symmetric phase at high $T$. We find that the nature of the finite temperature chiral phase transition and in particular the location of the tricritical point that seperates the first order line from the second order line is affected significantly by the anomaly.Comment: 22 pages, 16 figures, 5 tables, references adde

Unusual Formation of Point-Defect Complexes in the Ultrawide-Band-Gap Semiconductor β-Ga2 O3

Understanding the unique properties of ultra-wide band gap semiconductors requires detailed information about the exact nature of point defects and their role in determining the properties. Here, we report the first direct microscopic observation of an unusual formation of point defect complexes within the atomic-scale structure of β-Ga2O3 using high resolution scanning transmission electron microscopy (STEM). Each complex involves one cation interstitial atom paired with two cation vacancies. These divacancy-interstitial complexes correlate directly with structures obtained by density functional theory, which predicts them to be compensating acceptors in β-Ga2O3. This prediction is confirmed by a comparison between STEM data and deep level optical spectroscopy results, which reveals that these complexes correspond to a deep trap within the band gap, and that the development of the complexes is facilitated by Sn doping through increased vacancy concentration. These findings provide new insight on this emerging material's unique response to the incorporation of impurities that can critically influence their properties

Removal of NOx and NOy in Asian outflow plumes: Aircraft measurements over the western Pacific in Januray 2002

The Pacific Exploration of Asian Continental Emission Phase A (PEACE-A) aircraft measurement campaign was conducted over the western Pacific in January 2002. Correlations of carbon monoxide (CO) with carbon dioxide (CO2) and back trajectories are used to identify plumes strongly affected by Asian continental emissions. ΔCO/ΔCO2 ratios (i.e., linear regression slopes of CO-CO2) in the plumes generally fall within the variability range of the CO/CO2 emission ratios estimated from an emission inventory for east Asia, demonstrating the consistency between the aircraft measurements and the emission characterization. Removal rates of reactive nitrogen (NOx and NOy) for the study region (altitude <4 km, 124°-140°E, 25°-45°N) are estimated using the correlation with CO2, the photochemical age of the plumes, and the NOx/ CO2 emission ratio derived from the emission inventory. The plume age is estimated from the rates of hydrocarbon decay and hydroxyl radical (OH) concentration calculated using a constrained photochemical box model. The average lifetime of NOx is estimated to be 1.2 ± 0.4 days. Possible processes controlling the NOx lifetime are discussed in conjunction with results from earlier studies. The average lifetime of NOy is estimated to be 1.7 ± 0.5 days, which is comparable to the NOy lifetime of 1.7-1.8 days that has been previously reported for outflow from the United States. This similarity suggests the importance of chemical processing near the source regions in determining the NOy abundance. Copyright 2004 by the American Geophysical Union

Multiple Ca2+ signaling pathways regulate intracellular Ca 2+ activity in human cardiac fibroblasts

Ca2+ signaling pathways are well studied in cardiac myocytes, but not in cardiac fibroblasts. The aim of the present study is to characterize Ca2+ signaling pathways in cultured human cardiac fibroblasts using confocal scanning microscope and RT-PCR techniques. It was found that spontaneous intracellular Ca2+ (Cai 2+) oscillations were present in about 29% of human cardiac fibroblasts, and the number of cells with Cai 2+ oscillations was increased to 57.3% by application of 3% fetal bovine serum. Cai 2+ oscillations were dependent on Ca2+ entry. Cai2+ oscillations were abolished by the store-operated Ca2+ (SOC) entry channel blocker La3+, the phospholipase C inhibitor U-73122, and the inositol trisphosphate receptors (IP3Rs) inhibitor 2-aminoethoxydiphenyl borate, but not by ryanodine. The IP3R agonist thimerosal enhanced Ca2+ i oscillations. Inhibition of plasma membrane Ca2+ pump (PMCA) and Na+-Ca2+ exchanger (NCX) also suppressed Ca i 2+ oscillations. In addition, the frequency of Ca i 2+ oscillations was reduced by nifedipine, and increased by Bay K8644 in cells with spontaneous Cai 2+ oscillations. RT-PCR revealed that mRNAs for IP3R1-3, SERCA1-3, CaV1.2, NCX3, PMCA1,3,4, TRPC1,3,4,6, STIM1, and Orai1-3, were readily detectable, but not RyRs. Our results demonstrate for the first time that spontaneous Cai 2+ oscillations are present in cultured human cardiac fibroblasts and are regulated by multiple Ca2+ pathways, which are not identical to those of the well-studied contractile cardiomyocytes. This study provides a base for future investigations into how Ca2+ signals regulate biological activity in human cardiac fibroblasts and cardiac remodeling under pathological conditions. © 2009 Wiley-Liss, Inc.postprin

Climate and soil moisture content during development ofthe frst palaeosol in the southern Loess Plateau

The scientific problems concerning Quaternary soil water content and the water cycle have not been researched. This study examined the soil water content and depth of distribution of gravitational water in the south Loess Plateau during development of the first palaeosol layer (S1) by methods such as field investigation, electron microscopy, energy spectrum analysis, chemical analysis, and so on. The purpose was to reveal the climate, water balance and vegetation type at the time when S1 developed. The depth of migration of CaCO3 and Sr were 4.2 m below the upper boundary of the S1 palaeosol, and the depth of weathered loess beneath the argillic horizon was 4.0 m. Ferri‐argillans developed well in the argillic horizon and their depth of migration was 1 m below the argillic horizon. These findings suggest that the climate during the last interglacial was subtropical and humid, and the soil‐water balance was positive. Gravitational water was present to a depth of least 4.2 m from the top of S1, and the water content was adequate for tree growth. The chemical weathering index showed that this palaeosol has been moderately weathered

An invisibility cloak using silver nanowires

In this paper, we use the parameter retrieval method together with an analytical effective medium approach to design a well-performed invisible cloak, which is based on an empirical revised version of the reduced cloak. The designed cloak can be implemented by silver nanowires with elliptical cross-sections embedded in a polymethyl methacrylate host. This cloak is numerically proved to be robust for both the inner hidden object as well as incoming detecting waves, and is much simpler thus easier to manufacture when compared with the earlier proposed one [Nat. Photon. 1, 224 (2007)].Comment: 7 pages, 4 figures, 2 table