Implementing Information-Theoretically Secure Oblivious Transfer from Packet Reordering

If we assume that adversaries have unlimited computational capabilities, secure computation between mutually distrusting players can not be achieved using an error-free communication medium. However, secure multi-party computation becomes possible when a noisy channel is available to the parties. For instance, the Binary Symmetric Channel (BSC) has been used to implement Oblivious Transfer (OT), a fundamental primitive in secure multi-party computation. Current research is aimed at designing protocols based on real-world noise sources, in order to make the actual use of information-theoretically secure computation a more realistic prospect for the future. In this paper, we introduce a modified version of the recently proposed Binary Discrete-time Delaying Channel (BDDC), a noisy channel based on communication delays. We call our variant Reordering Channel (RC), and we show that it successfully models packet reordering, the common behavior of packet switching networks that results in the reordering of the packets in a stream during their transit over the network. We also show that the protocol implementing oblivious transfer on the BDDC can be adapted to the new channel by using a different sending strategy, and we provide a functioning implementation of this modified protocol. Finally, we present strong experimental evidence that reordering occurrences between two remote Internet hosts are enough for our construction to achieve statistical security against honest-but-curious adversaries

Radiation hardness qualification of PbWO4 scintillation crystals for the CMS Electromagnetic Calorimeter

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2010 IOPEnsuring the radiation hardness of PbWO4 crystals was one of the main priorities during the construction of the electromagnetic calorimeter of the CMS experiment at CERN. The production on an industrial scale of radiation hard crystals and their certification over a period of several years represented a difficult challenge both for CMS and for the crystal suppliers. The present article reviews the related scientific and technological problems encountered

BLASTing small molecules—statistics and extreme statistics of chemical similarity scores

Motivation: Small organic molecules, from nucleotides and amino acids to metabolites and drugs, play a fundamental role in chemistry, biology and medicine. As databases of small molecules continue to grow and become more open, it is important to develop the tools to search them efficiently. In order to develop a BLAST-like tool for small molecules, one must first understand the statistical behavior of molecular similarity scores

A complete pupillometry toolbox for real-time monitoring of locus coeruleus activity in rodents

The locus coeruleus (LC) is a region in the brainstem that produces noradrenaline and is involved in both normal and pathological brain function. Pupillometry, the measurement of pupil diameter, provides a powerful readout of LC activity in rodents, primates and humans. The protocol detailed here describes a miniaturized setup that can screen LC activity in rodents in real-time and can be established within 1–2 d. Using low-cost Raspberry Pi computers and cameras, the complete custom-built system costs only ~300 euros, is compatible with stereotaxic surgery frames and seamlessly integrates into complex experimental setups. Tools for pupil tracking and a user-friendly Pupillometry App allow quantification, analysis and visualization of pupil size. Pupillometry can discriminate between different, physiologically relevant firing patterns of the LC and can accurately report LC activation as measured by noradrenaline turnover. Pupillometry provides a rapid, non-invasive readout that can be used to verify accurate placement of electrodes/fibers in vivo, thus allowing decisions about the inclusion/exclusion of individual animals before experiments begin

Education and Optimal Dynamic Taxation

We study optimal tax and educational policies in a dynamic private information economy, in which ex-ante heterogeneous individuals make an educational investment early in their life and face a stochastic wage distribution. We characterize labor and education wedges in this setting analytically and numerically, using a calibrated example. We present ways to implement the optimum. In one implementation there is a common labor income tax schedule, and a repayment schedule for government loans given out to agents during education. These repayment plans are contingent on loan size and income and capture the history dependence of the labor wedges. Applying the model to US-data and a binary education decision (graduating from college or not) we characterize optimal labor wedges for individuals without college degree and with college degree. The labor wedge of college graduates as a function of income lies first strictly above their counterparts from high-school, but this reverses at higher incomes. The loan repayment schedule is hump-shaped in income for college graduates

A physicochemical descriptor-based scoring scheme for effective and rapid filtering of kinase-like chemical space

<p>Abstract</p> <p>Background</p> <p>The current chemical space of known small molecules is estimated to exceed 10⁶⁰structures. Though the largest physical compound repositories contain only a few tens of millions of unique compounds, virtual screening of databases of this size is still difficult. In recent years, the application of physicochemical descriptor-based profiling, such as Lipinski's rule-of-five for drug-likeness and Oprea's criteria of lead-likeness, as early stage filters in drug discovery has gained widespread acceptance. In the current study, we outline a kinase-likeness scoring function based on known kinase inhibitors.</p> <p>Results</p> <p>The method employs a collection of 22,615 known kinase inhibitors from the ChEMBL database. A kinase-likeness score is computed using statistical analysis of nine key physicochemical descriptors for these inhibitors. Based on this score, the kinase-likeness of four publicly and commercially available databases, i.e., National Cancer Institute database (NCI), the Natural Products database (NPD), the National Institute of Health's Molecular Libraries Small Molecule Repository (MLSMR), and the World Drug Index (WDI) database, is analyzed. Three of these databases, i.e., NCI, NPD, and MLSMR are frequently used in the virtual screening of kinase inhibitors, while the fourth WDI database is for comparison since it covers a wide range of known chemical space. Based on the kinase-likeness score, a kinase-focused library is also developed and tested against three different kinase targets selected from three different branches of the human kinome tree.</p> <p>Conclusions</p> <p>Our proposed methodology is one of the first that explores how the narrow chemical space of kinase inhibitors and its relevant physicochemical information can be utilized to build kinase-focused libraries and prioritize pre-existing compound databases for screening. We have shown that focused libraries generated by filtering compounds using the kinase-likeness score have, on average, better docking scores than an equivalent number of randomly selected compounds. Beyond library design, our findings also impact the broader efforts to identify kinase inhibitors by screening pre-existing compound libraries. Currently, the NCI library is the most commonly used database for screening kinase inhibitors. Our research suggests that other libraries, such as MLSMR, are more kinase-like and should be given priority in kinase screenings.</p

Natural products in modern life science

With a realistic threat against biodiversity in rain forests and in the sea, a sustainable use of natural products is becoming more and more important. Basic research directed against different organisms in Nature could reveal unexpected insights into fundamental biological mechanisms but also new pharmaceutical or biotechnological possibilities of more immediate use. Many different strategies have been used prospecting the biodiversity of Earth in the search for novel structure–activity relationships, which has resulted in important discoveries in drug development. However, we believe that the development of multidisciplinary incentives will be necessary for a future successful exploration of Nature. With this aim, one way would be a modernization and renewal of a venerable proven interdisciplinary science, Pharmacognosy, which represents an integrated way of studying biological systems. This has been demonstrated based on an explanatory model where the different parts of the model are explained by our ongoing research. Anti-inflammatory natural products have been discovered based on ethnopharmacological observations, marine sponges in cold water have resulted in substances with ecological impact, combinatory strategy of ecology and chemistry has revealed new insights into the biodiversity of fungi, in depth studies of cyclic peptides (cyclotides) has created new possibilities for engineering of bioactive peptides, development of new strategies using phylogeny and chemography has resulted in new possibilities for navigating chemical and biological space, and using bioinformatic tools for understanding of lateral gene transfer could provide potential drug targets. A multidisciplinary subject like Pharmacognosy, one of several scientific disciplines bridging biology and chemistry with medicine, has a strategic position for studies of complex scientific questions based on observations in Nature. Furthermore, natural product research based on intriguing scientific questions in Nature can be of value to increase the attraction for young students in modern life science

Mutation D816V Alters the Internal Structure and Dynamics of c-KIT Receptor Cytoplasmic Region: Implications for Dimerization and Activation Mechanisms

The type III receptor tyrosine kinase (RTK) KIT plays a crucial role in the transmission of cellular signals through phosphorylation events that are associated with a switching of the protein conformation between inactive and active states. D816V KIT mutation is associated with various pathologies including mastocytosis and cancers. D816V-mutated KIT is constitutively active, and resistant to treatment with the anti-cancer drug Imatinib. To elucidate the activating molecular mechanism of this mutation, we applied a multi-approach procedure combining molecular dynamics (MD) simulations, normal modes analysis (NMA) and binding site prediction. Multiple 50-ns MD simulations of wild-type KIT and its mutant D816V were recorded using the inactive auto-inhibited structure of the protein, characteristic of type III RTKs. Computed free energy differences enabled us to quantify the impact of D816V on protein stability in the inactive state. We evidenced a local structural alteration of the activation loop (A-loop) upon mutation, and a long-range structural re-organization of the juxta-membrane region (JMR) followed by a weakening of the interaction network with the kinase domain. A thorough normal mode analysis of several MD conformations led to a plausible molecular rationale to propose that JMR is able to depart its auto-inhibitory position more easily in the mutant than in wild-type KIT and is thus able to promote kinase mutant dimerization without the need for extra-cellular ligand binding. Pocket detection at the surface of NMA-displaced conformations finally revealed that detachment of JMR from the kinase domain in the mutant was sufficient to open an access to the catalytic and substrate binding sites