Fast, Verified Computation for Candle

This paper describes how we have added an efficient function for computation to the kernel of the Candle interactive theorem prover. Candle is a CakeML port of HOL Light which we have, in prior work, proved sound w.r.t. the inference rules of the higher-order logic. This paper extends the original implementation and soundness proof with a new kernel function for fast computation. Experiments show that the new computation function is able to speed up certain evaluation proofs by several orders of magnitude

The relationship between biophysical variables and halocarbon distributions in the waters of the Amundsen and Ross Seas, Antarctica

Little is known regarding the distribution of volatile halogenated organic compounds (halocarbons) in Antarctic waters and their relation to biophysical variables. During the austral summer (December to January) in 2007-08 halocarbon and pigment concentrations were measured in the Amundsen (100-130 degrees W) and Ross Sea (158 degrees W-160 degrees E). In addition, halocarbons were determined in air, snow and sea ice. The distribution of halocarbons was influenced to a large extent by sea ice, and to a much lesser extent by pelagic biota. Concentrations of naturally produced halocarbons were elevated in the surface mixed layer in ice covered areas compared to open waters in polynyas and in the bottom waters of the Ross Sea. Higher concentrations of halocarbons were also found in sea ice brine compared to the surface waters. Incubations of snow revealed an additional source of halocarbons. The distribution of halocarbons also varied considerably between the Amundsen and Ross Seas, mainly due to the different oceanographic settings. For iodinated compounds, weak correlations were found with the presence of pigments indicative of Phaeocystis, mainly in the Ross Sea. Surface waters of the Amundsen and Ross Seas are a sink for bromoform (saturation anomalies, SA, -83 to 11%), whereas sea ice was found to be both a source and sink (SA -61-97%). In contrast, both surface waters and sea ice were found to be a source of chloroiodomethane (SA -6-1 200% and 91-22 000 resp.). Consequently, polar waters can have a substantial impact on global halocarbon budgets and need to be included in large-scale assessments. (C) 2012 Elsevier B.V. All rights reserved

Contribution of sea ice in the Southern Ocean to the cycling of volatile halogenated organic compounds

The contribution of sea ice to the flux of biogenic volatile halogenated organic compounds to the atmosphere in the Southern Ocean is currently not known. To approach this question, we measured halocarbons in sea ice, sea ice brine, and surface water of the Amundsen and Ross Seas. Concentrations in sea ice of these compounds, normalized to seawater salinity, ranged from 0.2 to 810 pmol L-1. Salinity-normalized chlorophyll a concentrations in the ice ranged from 3.5 to 190 mu gL(-1). Our results suggest biological production of halocarbons in sea ice, with maxima of halogenated organics and chlorophyll a commonly found in the interior of the ice cores. Iodinated VHOCs were found to be more enriched in sea ice than brominated ones. Furthermore, depth distributions indicated a transport of halocarbons from sea ice to air and underlying water

Proof-Producing Synthesis of CakeML from Monadic HOL Functions

We introduce an automatic method for producing stateful ML programs together with proofs of correctness from monadic functions in HOL. Our mechanism supports references, exceptions, and I/O operations, and can generate functions manipulating local state, which can then be encapsulated for use in a pure context. We apply this approach to several non-trivial examples, including the instruction encoder and register allocator of the otherwise pure CakeML compiler, which now benefits from better runtime performance. This development has been carried out in the HOL4 theorem prover

Cold SO_2 molecules by Stark deceleration

We produce SO_2 molecules with a centre of mass velocity near zero using a Stark decelerator. Since the initial kinetic energy of the supersonic SO_2 molecular beam is high, and the removed kinetic energy per stage is small, 326 deceleration stages are necessary to bring SO_2 to a complete standstill, significantly more than in other experiments. We show that in such a decelerator possible loss due to coupling between the motional degrees of freedom must be considered. Experimental results are compared with 3D Monte-Carlo simulations and the quantum state selectivity of the Stark decelerator is demonstrated.Comment: 7 pages, 5 figure

The First Galaxies: Chemical Enrichment, Mixing, and Star Formation

Using three-dimensional cosmological simulations, we study the assembly process of one of the first galaxies, with a total mass of 10^8 M_sun, collapsing at z = 10. Our main goal is to trace the transport of the heavy chemical elements produced and dispersed by a pair-instability supernova exploding in one of the minihalo progenitors. To this extent, we incorporate an efficient algorithm into our smoothed particle hydrodynamics code which approximately models turbulent mixing as a diffusion process. We study this mixing with and without the radiative feedback from Population III stars that subsequently form in neighboring minihalos. Our simulations allow us to constrain the initial conditions for second-generation star formation, within the first galaxy itself, and inside of minihalos that virialize after the supernova explosion. We find that most minihalos remain unscathed by ionizing radiation or the supernova remnant, while some are substantially photoheated and enriched to supercritical levels, likely resulting in the formation of low-mass Population III or even Population II stars. At the center of the newly formed galaxy, 10^5 M_sun of cold, dense gas uniformly enriched to 10^-3 Z_sun are in a state of collapse, suggesting that a cluster of Population II stars will form. The first galaxies, as may be detected by the James Webb Space Telescope, would therefore already contain stellar populations familiar from lower redshifts.Comment: 13 pages, 9 figures, published in Ap

PureCake: A verified compiler for a lazy functional language

We present PureCake, a mechanically-verified compiler for PureLang, a lazy, purely functional programming language with monadic effects. PureLang syntax is Haskell-like and indentation-sensitive, and its constraint-based Hindley-Milner type system guarantees safe execution. We derive sound equational reasoning principles over its operational semantics, dramatically simplifying some proofs. We prove end-to-end correctness for the compilation of PureLang down to machine code---the first such result for any lazy language---by targeting CakeML and composing with its verified compiler. Multiple optimisation passes are necessary to handle realistic lazy idioms effectively. We develop PureCake entirely within the HOL4 interactive theorem prover

Characteristics of white blood cell count in acute lymphoblastic leukemia : A COST LEGEND phenotype-genotype study

Background White blood cell count (WBC) as a measure of extramedullary leukemic cell survival is a well-known prognostic factor in acute lymphoblastic leukemia (ALL), but its biology, including impact of host genome variants, is poorly understood. Methods We included patients treated with the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-2008 protocol (N = 2347, 72% were genotyped by Illumina Omni2.5exome-8-Bead chip) aged 1-45 years, diagnosed with B-cell precursor (BCP-) or T-cell ALL (T-ALL) to investigate the variation in WBC. Spline functions of WBC were fitted correcting for association with age across ALL subgroups of immunophenotypes and karyotypes. The residuals between spline WBC and actual WBC were used to identify WBC-associated germline genetic variants in a genome-wide association study (GWAS) while adjusting for age and ALL subtype associations. Results We observed an overall inverse correlation between age and WBC, which was stronger for the selected patient subgroups of immunophenotype and karyotypes (rho(BCP-ALL )= -.17, rho(T-ALL )= -.19; p < 3 x 10(-4)). Spline functions fitted to age, immunophenotype, and karyotype explained WBC variation better than age alone (rho = .43, p << 2 x 10(-6)). However, when the spline-adjusted WBC residuals were used as phenotype, no GWAS significant associations were found. Based on available annotation, the top 50 genetic variants suggested effects on signal transduction, translation initiation, cell development, and proliferation. Conclusion These results indicate that host genome variants do not strongly influence WBC across ALL subsets, and future studies of why some patients are more prone to hyperleukocytosis should be performed within specific ALL subsets that apply more complex analyses to capture potential germline variant interactions and impact on WBC.Peer reviewe

Causes of mortality in laying hens in different housing systems in 2001 to 2004

<p>Abstract</p> <p>Background</p> <p>The husbandry systems for laying hens were changed in Sweden during the years 2001 – 2004, and an increase in the number of submissions for necropsy from laying hen farms was noted. Hence, this study was initiated to compare causes of mortality in different housing systems for commercial laying hens during this change.</p> <p>Methods</p> <p>Based on results from routine necropsies of 914 laying hens performed at the National Veterinary Institute (SVA) in Uppsala, Sweden between 2001 and 2004, a retrospective study on the occurrence of diseases and cannibalism, i.e., pecking leading to mortality, in different housing systems was carried out. Using the number of disease outbreaks in caged flocks as the baseline, the expected number of flocks with a certain category of disease in the other housing systems was estimated having regard to the total number of birds in the population. Whether the actual number of flocks significantly exceeded the expected number was determined using a Poisson distribution for the variance of the baseline number, a continuity correction and the exact value for the Poisson distribution function in Excel 2000.</p> <p>Results</p> <p>Common causes of mortality in necropsied laying hens included colibacillosis, erysipelas, coccidiosis, red mite infestation, lymphoid leukosis and cannibalism. Less common diagnoses were Newcastle Disease, pasteurellosis and botulism. Considering the size of the populations in the different housing systems, a larger proportion of laying hens than expected was submitted for necropsy from litter-based systems and free range production compared to hens in cages (<it>P </it>< 0.001). The study showed a significantly higher occurrence of bacterial and parasitic diseases and cannibalism in laying hens kept in litter-based housing systems and free-range systems than in hens kept in cages (<it>P </it>< 0.001). The occurrence of viral diseases was significantly higher in indoor litter-based housing systems than in cages (<it>P </it>< 0.001).</p> <p>Conclusion</p> <p>The results of the present study indicated that during 2001–2004 laying hens housed in litter-based housing systems, with or without access to outdoor areas, were at higher risk of infectious diseases and cannibalistic behaviour compared to laying hens in cages. Future research should focus on finding suitable prophylactic measures, including efficient biosecurity routines, to reduce the risk of infectious diseases and cannibalism in litter-based housing systems for laying hens.</p

Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting

PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p 10(-4) associated with a CIR5y = 22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.Peer reviewe