Algorithmic statistics: forty years later

Algorithmic statistics has two different (and almost orthogonal) motivations. From the philosophical point of view, it tries to formalize how the statistics works and why some statistical models are better than others. After this notion of a "good model" is introduced, a natural question arises: it is possible that for some piece of data there is no good model? If yes, how often these bad ("non-stochastic") data appear "in real life"? Another, more technical motivation comes from algorithmic information theory. In this theory a notion of complexity of a finite object (=amount of information in this object) is introduced; it assigns to every object some number, called its algorithmic complexity (or Kolmogorov complexity). Algorithmic statistic provides a more fine-grained classification: for each finite object some curve is defined that characterizes its behavior. It turns out that several different definitions give (approximately) the same curve. In this survey we try to provide an exposition of the main results in the field (including full proofs for the most important ones), as well as some historical comments. We assume that the reader is familiar with the main notions of algorithmic information (Kolmogorov complexity) theory.Comment: Missing proofs adde

Experimental silicification of the extremophilic Archaea Pyrococcus abyssi and Methanocaldococcus jannaschii: applications in the search for evidence of life in early Earth and extraterrestrial rocks

International audienceHydrothermal activity was common on the early Earth and associated micro-organisms would most likely have included thermophilic to hyperthermophilic species. 3.5–3.3 billion-year-old, hydrothermally influenced rocks contain silicified microbial mats and colonies that must have been bathed in warm to hot hydrothermal emanations. Could they represent thermophilic or hyperthermophilic micro-organisms and if so, how were they preserved? We present the results of an experiment to silicify anaerobic, hyperthermophilic micro-organisms from the Archaea Domain Pyrococcus abyssi and Methanocaldococcus jannaschii, that could have lived on the early Earth. The micro-organisms were placed in a silica-saturated medium for periods up to 1 year. Pyrococcus abyssi cells were fossilized but the M. jannaschii cells lysed naturally after the exponential growth phase, apart from a few cells and cell remains, and were not silicified although their extracellular polymeric substances were. In this first simulated fossilization of archaeal strains, our results suggest that differences between species have a strong influence on the potential for different micro-organisms to be preserved by fossilization and that those found in the fossil record represent probably only a part of the original diversity. Our results have important consequences for biosignatures in hydrothermal or hydrothermally influenced deposits on Earth, as well as on early Mars, as environmental conditions were similar on the young terrestrial planets and traces of early Martian life may have been similarly preserved as silicified microfossils

CDKL5 influences RNA splicing activity by its association to the nuclear speckle molecular machinery

Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been shown to cause severe neurodevelopmental disorders including infantile spasms, encephalopathy, West-syndrome and an early-onset variant of Rett syndrome. CDKL5 is a serine/threonine kinase whose involvement in Rett syndrome can be inferred by its ability to directly bind and mediate phosphorylation of MeCP2. However, it remains to be elucidated how CDKL5 exerts its function. Here, we report that CDKL5 localizes to specific nuclear foci referred to as nuclear speckles in both cell lines and tissues. These sub-nuclear structures are traditionally considered as storage/modification sites of pre-mRNA splicing factors. Interestingly, we provide evidence that CDKL5 regulates the dynamic behaviour of nuclear speckles. Indeed, CDKL5 overexpression leads to nuclear speckle disassembly, and this event is strictly dependent on its kinase activity. Conversely, its down-regulation affects nuclear speckle morphology leading to abnormally large and uneven speckles. Similar results were obtained for primary adult fibroblasts isolated from CDKL5-mutated patients. Altogether, these findings indicate that CDKL5 controls nuclear speckle morphology probably by regulating the phosphorylation state of splicing regulatory proteins. Nuclear speckles are dynamic sites that can continuously supply splicing factors to active transcription sites, where splicing occurs. Notably, we proved that CDKL5 influences alternative splicing, at least as proved in heterologous minigene assays. In conclusion, we provide evidence that CDKL5 is involved indirectly in pre-mRNA processing, by controlling splicing factor dynamics. These findings identify a biological process whose disregulation might affect neuronal maturation and activity in CDKL5-related disorders

Propositional update operators based on formula/literal dependence

International audienceWe present and study a general family of belief update operators in a propositional setting. Its operators are based on formula/literal dependence, which is more fine-grained than the notion of formula/variable dependence that was proposed in the literature: formula/variable dependence is a particular case of formula/literal dependence. Our update operators are defined according to the "forget-then-conjoin" scheme: updating a belief base by an input formula consists in first forgetting in the base every literal on which the input formula has a negative influence, and then conjoining the resulting base with the input formula. The operators of our family differ by the underlying notion of formula/literal dependence, which may be defined syntactically or semantically, and which may or may not exploit further information like known persistent literals and pre-set dependencies. We argue that this allows to handle the frame problem and the ramification problem in a more appropriate way. We evaluate the update operators of our family w.r.t. two important dimensions: the logical dimension, by checking the status of the Katsuno-Mendelzon postulates for update, and the computational dimension, by identifying the complexity of a number of decision problems (including model checking, consistency and inference), both in the general case and in some restricted cases, as well as by studying compactability issues. It follows that several operators of our family are interesting alternatives to previous belief update operators

Efficacy of Continuous Interleukin 1 Blockade in Mevalonate Kinase Deficiency: A Multicenter Retrospective Study in 13 Adult Patients and Literature Review

OBJECTIVE: To report efficacy and tolerance of interleukin 1 blockade in adult patients with mevalonate kinase deficiency (MKD). METHODS: We retrospectively collected data on 13 patients with MKD who had received anakinra (n = 10) and canakinumab (n = 7). RESULTS: Anakinra resulted in complete or partial remission in 3/10 and 5/10 patients, respectively, and no efficacy in 2/10, but a switch to canakinumab led to partial remission. Canakinumab resulted in complete or partial remission in 3/7 and 4/7 patients, respectively. CONCLUSION: These data support frequent partial responses, showing a better response with canakinumab. The genotype and therapeutic outcomes correlation should help in the personalization of treatment

The PHIN photoinjector for the CTF3 Drive beam

A new photoinjector for the CTF3 drive beam has been designed and is now being constructed by a collaboration among LAL, CCLRC and CERN within PHIN, the second Joint Research Activity of CARE. The photoinjector will provide a train of 2332 pulses at 1.5 GHz with a complex timing structure (sub-trains of 212 pulses spaced from one another by 333 ps or 999 ps) to allow the frequency multiplication scheme, which is one of the features of CLIC, to be tested in CTF3. Each pulse of 2.33 nC will be emitted by a Cs2Te photocathode deposited by a co-evaporation process to allow high quantum efficiency in operation (>3% for a minimum of 40 h). The 3 GHz, 2 1/2 cell RF gun has a 2 port coupler to minimize emittance growth due to asymmetric fields, racetrack profile of the irises and two solenoids to keep the emittance at the output below 20 p.mm.mrad. The laser has to survive very high average powers both within the pulse train (15 kW) and overall (200 W before pulse slicing). Challenging targets are also for amplitude stability (<0.25% rms) and time jitter from pulse to pulse (<1ps rms). An offline test in a dedicated line is foreseen at CERN in 2007

First Results from Commissioning of the Phin Photo Injector for CTF3

Installation of the new photo-injector for the CTF3 drive beam (PHIN) has been completed on a stand-alone test bench. The photo-injector operates with a 2.5 cell RF gun at 3 GHz, using a Cs2Te photocathode illuminated by a UV laser beam. The test bench is equipped with transverse beam diagnostic as well as a 90-degree spectrometer. A grid of 100 micrometer wide slits can be inserted for emittance measurements. The laser used to trigger the photo-emission process is a Nd:YLF system consisting of an oscillator and a preamplifier operating at 1.5 GHz and two powerful amplifier stages. The infrared radiation produced is frequency quadrupled in two stages to obtain the UV. A Pockels cell allows adjusting the length of the pulse train between 50 nanoseconds and 50 microseconds. The nominal train length for CTF3 is 1.272 microseconds (1908 bunches). The first electron beam in PHIN was produced in November 2008. In this paper, results concerning the operation of the laser system and measurements performed to characterize the electron beam are presented

Complete Ascertainment of Intragenic Copy Number Mutations (CNMs) in the CFTR Gene and its Implications for CNM Formation at Other Autosomal Loci

Over the last 20 years since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, more than 1,600 different putatively pathological CFTR mutations have been identified. Until now, however, copy number mutations (CNMs) involving the CFTR gene have not been methodically analyzed, resulting almost certainly in the under-ascertainment of CFTR gene duplications compared with deletions. Here, high-resolution array comparative genomic hybridization (averaging one interrogating probe every 95 bp) was used to analyze the entire length of the CFTR gene (189 kb) in 233 cystic fibrosis chromosomes lacking conventional mutations. We succeeded in identifying five duplication CNMs that would otherwise have been refractory to analysis. Based upon findings from this and other studies, we propose that deletion and duplication CNMs in the human autosomal genome are likely to be generated in the proportion of approximately 2-3:1. We further postulate that intragenic gene duplication CNMs in other disease loci may have been routinely underascertained. Finally, our analysis of +/-20 bp flanking each of the 40 CFTR breakpoints characterized at the DNA sequence level provide support for the emerging concept that non-B DNA conformations in combination with specific sequence motifs predispose to both recurring and nonrecurring genomic rearrangements. Hum Mutat 31:421-428, 2010. (C) 2010 Wiley-Liss, Inc