Multi-level Contextual Type Theory

Contextual type theory distinguishes between bound variables and meta-variables to write potentially incomplete terms in the presence of binders. It has found good use as a framework for concise explanations of higher-order unification, characterize holes in proofs, and in developing a foundation for programming with higher-order abstract syntax, as embodied by the programming and reasoning environment Beluga. However, to reason about these applications, we need to introduce meta^2-variables to characterize the dependency on meta-variables and bound variables. In other words, we must go beyond a two-level system granting only bound variables and meta-variables. In this paper we generalize contextual type theory to n levels for arbitrary n, so as to obtain a formal system offering bound variables, meta-variables and so on all the way to meta^n-variables. We obtain a uniform account by collapsing all these different kinds of variables into a single notion of variabe indexed by some level k. We give a decidable bi-directional type system which characterizes beta-eta-normal forms together with a generalized substitution operation.Comment: In Proceedings LFMTP 2011, arXiv:1110.668

A Lambda Term Representation Inspired by Linear Ordered Logic

We introduce a new nameless representation of lambda terms inspired by ordered logic. At a lambda abstraction, number and relative position of all occurrences of the bound variable are stored, and application carries the additional information where to cut the variable context into function and argument part. This way, complete information about free variable occurrence is available at each subterm without requiring a traversal, and environments can be kept exact such that they only assign values to variables that actually occur in the associated term. Our approach avoids space leaks in interpreters that build function closures. In this article, we prove correctness of the new representation and present an experimental evaluation of its performance in a proof checker for the Edinburgh Logical Framework. Keywords: representation of binders, explicit substitutions, ordered contexts, space leaks, Logical Framework.Comment: In Proceedings LFMTP 2011, arXiv:1110.668

A mechanistic study of AIE processes of TPE luminogens: Intramolecular rotation vs. configurational isomerization

Chromophores containing olefinic double bonds are the core components of many important luminogen systems that show the novel photophysical effect of aggregation-induced emission (AIE). The role and extent of E–Z isomerization (EZI) of the double bond in affecting the solution emissions of the AIE luminogens (AIEgens), however, have not been fully understood. In this work, we verified the occurrence of EZI in the dilute solutions of TPE-cored AIEgens by NMR spectroscopy using elaborate experimental procedures. We further designed a TPE-fluorescein adduct to quantify that EZI plays a minor role whereas intramolecular rotation plays a major role in the emission quenching processes of the AIEgen solutions. This study fills the gap in the research on the restriction of the intramolecular rotation (RIR) mechanism for the AIE effect and provides a useful tool for the mechanistic investigation of photoluminescence processes

De Colorando Auro: Medieval colouring techniques researched using modern analytical techniques

The visual appearance of gold and gilding can be influenced in many ways, such as by changing the composition of the gold alloy or the nature of the gilded substrate. A less known medieval technique, reported in historical treatises, is the chemical treatment of the gilded surface itself, after application and burnishing of the gilding. We reporte here results regarding the study of the Holy Lady Shrine of Huy (13th c AD Mosan, Belgium) on which a possible artificial colouration of the gildings was detected. This led to many questions regarding applicable conservation-restoration treatments. Here is an overview of the results obtained, along with a discussion of the methodology that was developed to study this colouration process, also highlighting the necessary complementarity between laboratory and synchrotron-based analytical approaches. The 3-steps methodology proposed in this paper is generic for most cultural heritage problems where the application of ancient surface modification recipes is suspected but where the scarcity of the historical samples does not allow a direct study of such samples.L’aspect visuel de l’or et des dorures peut être modifié de diverses manières, notamment en changeant la composition de l’alliage ou la nature du support doré. Une technique médiévale moins connue, évoquée dans les traités anciens, consiste à provoquer une réaction chimique après application et brunissage de la dorure. Les recherches sur la châsse de Notre-Dame de Huy (art mosan du xiiie siècle) ont révélé une possible coloration artificielle des dorures. Cette découverte soulève de nombreuses questions quant aux traitements de conservation-restauration utilisables. Nous présentons ici un exposé sommaire des résultats obtenus ainsi qu’un compte rendu de la méthode mise au point pour étudier ce procédé de coloration, en soulignant la complémentarité indispensable entre les examens de laboratoire et l’analyse par rayonnement synchrotron. Dans les sciences du patrimoine culturel, cette méthode en trois temps concerne la plupart des situations où une recette ancienne semble avoir été employée pour modifier la surface, mais où la rareté des échantillons historiques ne permet pas l’étude directe de sous-échantillons

Excess Synaptojanin 1 Contributes to Place Cell Dysfunction and Memory Deficits in the Aging Hippocampus in Three Types of Alzheimer’s Disease

The phosphoinositide phosphatase synaptojanin 1 (SYNJ1) is a key regulator of synaptic function. We first tested whether SYNJ1 contributes to phenotypic variations in familial Alzheimer’s disease (FAD) and show that SYNJ1 polymorphisms are associated with age of onset in both early- and late-onset human FAD cohorts. We then interrogated whether SYNJ1 levels could directly affect memory. We show that increased SYNJ1 levels in autopsy brains from adults with Down syndrome (DS/AD) are inversely correlated with synaptophysin levels, a direct readout of synaptic integrity. We further report age-dependent cognitive decline in a mouse model overexpressing murine Synj1 to the levels observed in human sporadic AD, triggered through hippocampal hyperexcitability and defects in the spatial reproducibility of place fields. Taken together, our findings suggest that SYNJ1 contributes to memory deficits in the aging hippocampus in all forms of AD

Non-invasive, Focused Ultrasound-Facilitated Gene Delivery for Optogenetics

Optogenetics, a widely used technique in neuroscience research, is often limited by its invasive nature of application. Here, we present a noninvasive, ultrasound-based technique to introduce optogenetic channels into the brain by temporarily opening the blood-brain barrier (BBB). We demonstrate the efficiency of the method developed and evaluate the bioactivity of the non-invasively introduced channelrhodopsin channels by performing stimulation in freely behaving mice

European and Developing Countries Clinical Trials Partnership (EDCTP): the path towards a true partnership

European and Developing Countries Clinical Trials Partnership (EDCTP) was founded in 2003 by the European Parliament and Council. It is a partnership of 14 European Union (EU) member states, Norway, Switzerland, and Developing Countries, formed to fund acceleration of new clinical trial interventions to fight the human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), malaria and tuberculosis (TB) in the sub-Saharan African region. EDCTP seeks to be synergistic with other funding bodies supporting research on these diseases. EDCTP promotes collaborative research supported by multiple funding agencies and harnesses networking expertise across different African and European countries. EDCTP is different from other similar initiatives. The organisation of EDCTP blends important aspects of partnership that includes ownership, sustainability and responds to demand-driven research. The Developing Countries Coordinating Committee (DCCC); a team of independent scientists and representatives of regional health bodies from sub-Saharan Africa provides advice to the partnership. Thus EDCTP reflects a true partnership and the active involvement and contribution of these African scientists ensures joint ownership of the EDCTP programme with European counterparts. The following have been the major achievements of the EDCTP initiative since its formation in 2003; i) increase in the number of participating African countries from two to 26 in 2008 ii) the cumulative amount of funds spent on EDCTP projects has reached 150 m euros, iii) the cumulative number of clinical trials approved has reached 40 and iv) there has been a significant increase number and diversity in capacity building activities. While we recognise that EDCTP faced enormous challenges in its first few years of existence, the strong involvement of African scientists and its new initiatives such as unconditional funding to regional networks of excellence in sub-Saharan Africa is envisaged to lead to a sustainable programme. Current data shows that the number of projects supported by EDCTP is increasing. DCCC proposes that this success story of true partnership should be used as model by partners involved in the fight against other infectious diseases of public health importance in the region

Simulation of modern and middle Cretaceous marine δ 18 O with an ocean‐atmosphere general circulation model

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95522/1/palo1494.pd

Recombination Resulting in Virulence Shift in Avian Influenza Outbreak, Chile

Influenza A viruses occur worldwide in wild birds and are occasionally associated with outbreaks in commercial chickens and turkeys. However, avian influenza viruses have not been isolated from wild birds or poultry in South America. A recent outbreak in chickens of H7N3 low pathogenic avian influenza (LPAI) occurred in Chile. One month later, after a sudden increase in deaths, H7N3 highly pathogenic avian influenza (HPAI) virus was isolated. Sequence analysis of all eight genes of the LPAI virus and the HPAI viruses showed minor differences between the viruses except at the hemagglutinin (HA) cleavage site. The LPAI virus had a cleavage site similar to other low pathogenic H7 viruses, but the HPAI isolates had a 30 nucleotide insert. The insertion likely occurred by recombination between the HA and nucleoprotein genes of the LPAI virus, resulting in a virulence shift. Sequence comparison of all eight gene segments showed the Chilean viruses were also distinct from all other avian influenza viruses and represent a distinct South American clade