A WXW Motif Is Required for the Anticancer Activity of the TAT-RasGAP317-326 Peptide.

TAT-RasGAP317-326, a cell-permeable 10-amino acid-long peptide derived from the N2 fragment of p120 Ras GTPase-activating protein (RasGAP), sensitizes tumor cells to apoptosis induced by various anticancer therapies. This RasGAP-derived peptide, by targeting the deleted in liver cancer-1 (DLC1) tumor suppressor, also hampers cell migration and invasion by promoting cell adherence and by inhibiting cell movement. Here, we systematically investigated the role of each amino acid within the RasGAP317-326 sequence for the anticancer activities of TAT-RasGAP317-326. We report here that the first three amino acids of this sequence, tryptophan, methionine, and tryptophan (WMW), are necessary and sufficient to sensitize cancer cells to cisplatin-induced apoptosis and to reduce cell migration. The WMW motif was found to be critical for the binding of fragment N2 to DLC1. These results define the interaction mode between the active anticancer sequence of RasGAP and DLC1. This knowledge will facilitate the design of small molecules bearing the tumor-sensitizing and antimetastatic activities of TAT-RasGAP317-326

A Fully Differential Digital CMOS Pulse UWB Generator

A new fully-digital CMOS pulse generator for impulse-radio Ultra-Wide-Band (UWB) systems is presented. First, the shape of the pulse which best fits the FCC regulation in the 3.1-5 GHz sub-band of the entire 3.1-10.6 GHz UWB bandwidth is derived and approximated using rectangular digital pulses. In particular, the number and width of pulses that approximate an ideal template is found through an ad-hoc optimization methodology. Then a fully differential digital CMOS circuit that synthesizes the pulse sequence is conceived and its functionality demonstrated through post-layout simulations. The results show a very good agreement with the FCC requirements and a low power consumptio

Equality, Quasi-Implicit Products, and Large Eliminations

This paper presents a type theory with a form of equality reflection: provable equalities can be used to coerce the type of a term. Coercions and other annotations, including implicit arguments, are dropped during reduction of terms. We develop the metatheory for an undecidable version of the system with unannotated terms. We then devise a decidable system with annotated terms, justified in terms of the unannotated system. Finally, we show how the approach can be extended to account for large eliminations, using what we call quasi-implicit products.Comment: In Proceedings ITRS 2010, arXiv:1101.410

Impact of extracardiac findings during cardiac MR on patient management and outcome.

Cardiac magnetic resonance (CMR) is increasingly used to assess heart diseases. Relevant non-cardiac diseases may also be incidentally found on CMR images. The aim of this study was to determine the prevalence and nature of incidental extra-cardiac findings (IEF) and their clinical impact in non-selected patients referred for CMR. MR images of 762 consecutive patients (515 men, age: 56±18 years) referred for CMR were prospectively interpreted by 2 radiologists blinded for any previous imaging study. IEFs were classified as major when requiring treatment, follow-up, or further investigation. Clinical follow-up was performed by checking hospital information records and by calling referring physicians. The 2 endpoints were: 1) non-cardiac death and new treatment related to major IEFs, and 2) hospitalization related to major IEFs during follow-up. Major IEFs were proven in 129 patients (18.6% of the study population), 14% of those being unknown before CMR. During 15±6 month follow-up, treatment of confirmed major IEFs was initiated in 1.4%, and no non-cardiac deaths occurred. Hospitalization occurred in 8 patients (1.0% of the study population) with confirmed major IEFs and none occurred in the remaining 110 patients with unconfirmed/unexplored major IEFs (p<0.001). Screening for major IEFs in a population referred for routine CMR changed management in 1.4% of patients. Major IEFs unknown before CMR but without further exploration, however, carried a favorable prognosis over a follow-up period of 15 months

Variable-Pitch Rectangular Cross-section Radiofrequency Coils for the Nitrogen-14 Nuclear Quadrupole Resonance Investigation of Sealed Medicines Packets

This work was partly funded by a technology transfer award from the Wellcome Trust (U.K.). Additional funding was provided by the European Commission as part of 7th Framework Programme under Grant No. 261670

Strategies used as spectroscopy of financial markets reveal new stylized facts

We propose a new set of stylized facts quantifying the structure of financial markets. The key idea is to study the combined structure of both investment strategies and prices in order to open a qualitatively new level of understanding of financial and economic markets. We study the detailed order flow on the Shenzhen Stock Exchange of China for the whole year of 2003. This enormous dataset allows us to compare (i) a closed national market (A-shares) with an international market (B-shares), (ii) individuals and institutions and (iii) real investors to random strategies with respect to timing that share otherwise all other characteristics. We find that more trading results in smaller net return due to trading frictions. We unveiled quantitative power laws with non-trivial exponents, that quantify the deterioration of performance with frequency and with holding period of the strategies used by investors. Random strategies are found to perform much better than real ones, both for winners and losers. Surprising large arbitrage opportunities exist, especially when using zero-intelligence strategies. This is a diagnostic of possible inefficiencies of these financial markets.Comment: 13 pages including 5 figures and 1 tabl

A consistent foundation for Isabelle/HOL

The interactive theorem prover Isabelle/HOL is based on well understood Higher-Order Logic (HOL), which is widely believed to be consistent (and provably consistent in set theory by a standard semantic argument). However, Isabelle/HOL brings its own personal touch to HOL: overloaded constant definitions, used to achieve Haskell-like type classes in the user space. These features are a delight for the users, but unfortunately are not easy to get right as an extension of HOL—they have a history of inconsistent behavior. It has been an open question under which criteria overloaded constant definitions and type definitions can be combined together while still guaranteeing consistency. This paper presents a solution to this problem: non-overlapping definitions and termination of the definition-dependency relation (tracked not only through constants but also through types) ensures relative consistency of Isabelle/HOL