超越想像的生活空间 印度普纳Yoo设计酒店

举世闻名的设计大师菲利普·斯塔克（Philippe Starck）和极富远见的开发商约翰·希契考克斯（John Hitchcox）最近携手共创了一个新的设计酒店品牌——Yoo。Yoo的主要理念非常简单,创造不同凡响的、多功能的、超越想像的生活空间。     

Real‐Time Investigation of Crystallization and Phase‐Segregation Dynamics in P3HT:PCBM Solar Cells During Thermal Annealing

Crystallization and phase segregation during thermal annealing lead to the increase of power‐conversion efficiency in poly(3‐hexylthiophene) (P3HT):[6,6]‐phenyl C61‐butyric acid methyl ester (PCBM) bulk‐heterojunction solar cells. An understanding of the length and time scale on which crystallization and phase segregation occur is important to improve control of the nanomorphology. Crystallization is monitored by means of grazing incidence X‐ray diffraction in real time during thermal annealing. Furthermore, the change in film density is monitored by means of ellipsometry and the evolution of carrier mobilities by means of field effect transistors, both during annealing. From the combination of such measurements with those of device performance as a function of annealing time, it is concluded that the evolution of microstructure involves two important time windows: i) A first one of about 5 minutes duration wherein crystallization of the polymer correlates with a major increase of photocurrent; ii) a second window of about 30 minutes during which the aggregation of PCBM continues, accompanied by an increase in the fill factor.     

克莱因瓶 澳大利亚某别墅

澳大利亚的建筑与室内设计公司McBride Charles Ryan（MCR）常常设计一些很别致的建筑和室内设计项目,这些项目在外形、颜色和结构上常常会有不一样的组合方式。他们特别擅长在设计中运用几何学和数学的概念,创造一些极具视觉效果的作品。他们最近在澳大利亚完成了一个小别墅的设计。别墅坐落在墨尔本附近的海滩上,这个项目为他们带来了很多荣誉,包括2008年AIA颁布的Victorian Arc Ntecture Award和Harold Desbrowne-Annear Award。     

隐逸的大师——Maison Martin Margiela米兰专卖店

Martin Margiela生于比利时,1977年就读于安特卫普皇家艺术学院。他于1984年成为Jean Paul Gaultier的设计助理,曾担任爱马仕（Hermes）的创意总监．1988年正式单飞,建立Maison Martin Margiela品牌,于是成功创立了如今人所共识的Martin Margiela。     

Biochemical and Computational Studies of the Interaction between a Glucosamine Derivative,NAPA, and the IKKα Kinase

The glucosamine derivative 2-(N-Acetyl)-L-phenylalanylamido-2-deoxy-β-D-glucose (NAPA), was shown to inhibit the kinase activity of IKKα, one of the two catalytic subunits of IKK complex, decreasing the inflammatory status in osteoarthritis chondrocytes. In the present work we have investigated the inhibition mechanism of IKKα by NAPA by combining computational simulations, in vitro assays and Mass Spectrometry (MS) technique. The kinase in vitro assay was conducted using a recombinant IKKα and IKKtide, a 20 amino acid peptide substrate derived from IkBα kinase protein and containing the serine residues Ser32 and Ser36. Phosphorylated peptide production was measured by Ultra Performance Liquid Chromatography coupled with Mass Spectrometry (UPLC-MS), and the atomic interaction between IKKα and NAPA has been studied by molecular docking and Molecular Dynamics (MD) approaches. Here we report that NAPA was able to inhibit the IKKα kinase activity with an IC₅₀ of 0.5 mM, to decrease the K_m value from 0.337 mM to 0.402 mM and the V_max from 0.0257 mM·min−1 to 0.0076 mM·min−1. The computational analyses indicate the region between the KD, ULD and SDD domains of IKKα as the optimal binding site explored by NAPA. Biochemical data indicate that there is a non-significant difference between K_m and K_i whereas there is a statistically significant difference between the two V_max values. This evidence, combined with computational results, consistently indicates that the inhibition is non-competitive, and that the NAPA binding site is different than that of ATP or IKKtide.     

"老"公寓 意大利某公寓

和世界上许多大都市一样,要想在怫罗伦萨的市区拥有一座单独的、别致的公寓,就不得不考虑一下建筑的尺寸。本案的原建筑实际上是一座中世纪的老房子,当地的法律对这类建筑有严格的规定,绝对不允许扩大建筑的尺寸。单从复杂的交通环爱和诸多的法规限制来说,这座公寓并不是理想的居住场所,但是能在城市的中心拥有这样一座独一无二的住所实在是件让人兴奋的事情。     

水上的视觉侵略

Luca Bassani先生，从事造船行业多年，并拥有一个自己的公司Wally，该公司成立于1993年，近年来他带给世人的新型游艇，成功的改变的游艇在人们心目中的一贯形象。2001年Wally凭借着三艘运用领先科技和完美设计相结合的新型游艇，成功的打入的游艇市场，两年后，便引进了这艘长时间引领整个游艇业的118＇ Wally Power。     

An Attenuated Targeted-TNF Localizes to Tumors In Vivo and Regains Activity at the Site of Disease

Antibody-cytokine fusion proteins (immunocytokines) are gaining importance for cancer therapy, but those products are often limited by systemic toxicity related to the activity of the cytokine payload in circulation and in secondary lymphoid organs. Tumor necrosis factor (TNF) is used as a pro-inflammatory payload to trigger haemorrhagic necrosis and boost anti-cancer immunity at the tumor site. Here we describe a depotentiated version of TNF (carrying the single point mutation I97A), which displayed reduced binding affinity to its cognate receptor tumor necrosis factor receptor 1 (TNFR-1) and lower biocidal activity. The fusion of the TNF(I97A) mutant to the L19 antibody promoted restoration of anti-tumor activity upon accumulation on the cognate antigen, the alternatively spliced EDB domain of fibronectin. In vivo administration of high doses (375 μg/Kg) of the fusion protein showed a potent anti-tumor effect without apparent toxicity compared with the wild type protein. L19-TNF^I97A holds promise for the targeted delivery of TNF activity to neoplastic lesions, helping spare normal tissues.     

Why do entrepreneurs refuse venture capital?

Despite the evidence on the positive effect of venture capital (VC) on portfolio firm performance, such evidence badly pulls up alongside the non-negligible number of entrepreneurial firms that choose to refuse VC. This is the first study that investigates the determinants behind the missed realizations of VC investor-investee dyads by focusing on the Italian VC market. We theorize and empirically document that entrepreneurs’ human capital background and venture-specific characteristics influence the decision to accept or refuse VC. Specifically, our findings show that technically literate founders decrease the likelihood to refuse VC while family linkages in the ownership structure increase the likelihood to refuse VC.     

Targeting Endocannabinoid Metabolism: an Arrow with Multiple Tips Against Multiple Sclerosis

Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system. At present, there is no definitive cure, and the few available disease-modifying options display either poor efficacy or life-threatening side effects. There is clear evidence that relapsing-remitting clinical attacks in MS are driven by inflammatory demyelination and that the subsequent disease steps, being irresponsive to immunotherapy, result from neurodegeneration. The endocannabinoid system (ECS) stands halfway between three key pathomechanisms underlying MS, namely inflammation, neurodegeneration and oxidative stress, thus representing a kingpin for the identification of novel therapeutic targets in MS. This review summarizes the current state of the art in the field of endocannabinoid metabolism modulators and their in vivo effects on relevant animal models. We also highlight key molecular underpinnings of their therapeutic efficacy as well as the potential to turn them into promising clinical candidates.