Verification of PCP-Related Computational Reductions in Coq

We formally verify several computational reductions concerning the Post correspondence problem (PCP) using the proof assistant Coq. Our verifications include a reduction of a string rewriting problem generalising the halting problem for Turing machines to PCP, and reductions of PCP to the intersection problem and the palindrome problem for context-free grammars. Interestingly, rigorous correctness proofs for some of the reductions are missing in the literature

Quantifying the improvement of surrogate indices of hepatic insulin resistance using complex measurement techniques

We evaluated the ability of simple and complex surrogate-indices to identify individuals from an overweight/obese cohort with hepatic insulin-resistance (HEP-IR). Five indices, one previously defined and four newly generated through step-wise linear regression, were created against a single-cohort sample of 77 extensively characterised participants with the metabolic syndrome (age 55.6±1.0 years, BMI 31.5±0.4 kg/m2; 30 males). HEP-IR was defined by measuring endogenous-glucose-production (EGP) with [6–62H2] glucose during fasting and euglycemic-hyperinsulinemic clamps and expressed as EGP*fasting plasma insulin. Complex measures were incorporated into the model, including various non-standard biomarkers and the measurement of body-fat distribution and liver-fat, to further improve the predictive capability of the index. Validation was performed against a data set of the same subjects after an isoenergetic dietary intervention (4 arms, diets varying in protein and fiber content versus control). All five indices produced comparable prediction of HEP-IR, explaining 39–56% of the variance, depending on regression variable combination. The validation of the regression equations showed little variation between the different proposed indices (r2 = 27–32%) on a matched dataset. New complex indices encompassing advanced measurement techniques offered an improved correlation (r = 0.75, P<0.001). However, when validated against the alternative dataset all indices performed comparably with the standard homeostasis model assessment for insulin resistance (HOMA-IR) (r = 0.54, P<0.001). Thus, simple estimates of HEP-IR performed comparable to more complex indices and could be an efficient and cost effective approach in large epidemiological investigations

Declining uncertainty in transient climate response as CO2 forcing dominates future climate change

Carbon dioxide has exerted the largest portion of radiative forcing and surface temperature change over the industrial era, but other anthropogenic influences have also contributed. However, large uncertainties in total forcing make it difficult to derive climate sensitivity from historical observations. Anthropogenic forcing has increased between the Fourth and Fifth Assessment Reports of the Intergovernmental Panel of Climate Change (IPCC; refs,), although its relative uncertainty has decreased. Here we show, based on data from the two reports, that this evolution towards lower uncertainty can be expected to continue into the future. Because it is easier to reduce air pollution than carbon dioxide emissions and because of the long lifetime of carbon dioxide, the less uncertain carbon dioxide forcing is expected to become increasingly dominant. Using a statistical model, we estimate that the relative uncertainty in anthropogenic forcing of more than 40% quoted in the latest IPCC report for 2011 will be almost halved by 2030, even without better scientific understanding. Absolute forcing uncertainty will also decline for the first time, provided projected decreases in aerosols occur. Other factors being equal, this stronger constraint on forcing will bring a significant reduction in the uncertainty of observation-based estimates of the transient climate response, with a 50% reduction in its uncertainty range expected by 2030

Achieving temperature-size changes in a unicellular organism.

The temperature-size rule (TSR) is an intraspecific phenomenon describing the phenotypic plastic response of an organism size to the temperature: individuals reared at cooler temperatures mature to be larger adults than those reared at warmer temperatures. The TSR is ubiquitous, affecting >80% species including uni- and multicellular groups. How the TSR is established has received attention in multicellular organisms, but not in unicells. Further, conceptual models suggest the mechanism of size change to be different in these two groups. Here, we test these theories using the protist Cyclidium glaucoma. We measure cell sizes, along with population growth during temperature acclimation, to determine how and when the temperature-size changes are achieved. We show that mother and daughter sizes become temporarily decoupled from the ratio 2:1 during acclimation, but these return to their coupled state (where daughter cells are half the size of the mother cell) once acclimated. Thermal acclimation is rapid, being completed within approximately a single generation. Further, we examine the impact of increased temperatures on carrying capacity and total biomass, to investigate potential adaptive strategies of size change. We demonstrate no temperature effect on carrying capacity, but maximum supported biomass to decrease with increasing temperature

The spatial clustering of mid-IR selected star forming galaxies at z ~ 1 in the GOODS fields

We present the first spatial clustering measurements of z~1, 24um-selected, star forming galaxies in the Great Observatories Origins Deep Survey (GOODS). The sample under investigation includes 495 objects in GOODS-South and 811 objects in GOODS-North selected down to flux densities of f_24>20 uJy and z_AB<23.5 mag, for which spectroscopic redshifts are available. The median redshift, IR luminosity and star formation rate (SFR) of the samples are z~0.8, L_IR~4.4 x 10^10 L_sun, and SFR~7.6 M_sun/yr, respectively. We measure the projected correlation function w(r_p) on scales of r_p=0.06-10 h^-1 Mpc, from which we derive a best fit comoving correlation length of r_0 = 4.0 +- 0.4 h^-1 Mpc and slope of gamma=1.5 +- 0.1 for the whole f_24>20uJy sample after combining the two fields. We find indications of a larger correlation length for objects of higher luminosity, with Luminous Infrared Galaxies (LIRGs, L_IR>10^11 L_sun) reaching r_0~5.1 h^-1 Mpc. This would imply that galaxies with larger SFRs are hosted in progressively more massive halos, reaching minimum halo masses of ~3 x 10^12 M_sun for LIRGs. We compare our measurements with the predictions from semi-analytic models based on the Millennium simulation. The variance in the models is used to estimate the errors in our GOODS clustering measurements, which are dominated by cosmic variance. The measurements from the two GOODS fields are found to be consistent within the errors. On scales of the GOODS fields, the real sources appear more strongly clustered than objects in the Millennium-simulation based catalogs, if the selection function is applied consistently. This suggests that star formation at z~0.5-1 is being hosted in more massive halos and denser environments than currently predicted by galaxy formation models.[truncated]Comment: 19 pages, 15 figures. Accepted for publication in A&A. Style and English improve

Clumpy galaxies at z~0.6: kinematics, stability, and comparison with analogs at other redshifts

Distant clumpy galaxies are thought to be Jeans-unstable disks, and an important channel for the formation of local galaxies, as suggested by recent spatially-resolved kinematic observations of z~2 galaxies. I study the kinematics of clumpy galaxies at z~0.6, and compare their properties with those of counterparts at higher and lower redshifts. I selected a sample of 11 clumpy galaxies at z~0.6 from the representative sample of emission line, intermediate-mass galaxies IMAGES. Selection was based on rest-frame UV morphology from HST/ACS images, mimicking the selection criteria commonly used at higher redshifts. Their spatially-resolved kinematics were derived in the frame of the IMAGES survey, using the VLT/FLAMES-GIRAFFE multi-integral field spectrograph. For those showing large-scale rotation, I derived the Toomre Q parameter, which characterizes the stability of their gaseous and stellar phases. I find that the fraction of UV-selected clumpy galaxies at z~0.6 is 20+/-12%. Roughly half of them (45+/-30%) have complex kinematics inconsistent with Jeans-unstable disks, while those in the remaining half (55+/-30%) show large-scale rotations. The latter reveal a stable gaseous phase, but the contribution of their stellar phase makes them globally unstable to clump formation. Clumpy galaxies appear to be less unstable at z~0.6 than at z~2, which could explain why the UV clumps tend to vanish in rest-frame optical images of z~0.6 clumpy galaxies, conversely to z~2 clumpy galaxies, in which the stellar phase can substantially fragment. This suggests that the former correspond to patchy star-formation regions superimposed on a smoother mass distribution. A possible and widespread scenario for driving clump formation relies on instabilities by cold streams penetrating the dark matter halos where clumpy galaxies inhabit. While such a gas accretion process is predicted to be significant in massive, z~2 haloes, it is also predicted to be strongly suppressed in similar, z~0.6 haloes, which could explain why lowest-z clumpy galaxies appear to be driven by a different mechanism. Instead, I found that interactions are probably the dominant driver leading to the formation of clumpy galaxies at z1 clumpy galaxies remains more uncertain. While cold flows could be an important driver at z~2, I also argue that the observed and cumulative merger fraction between z=2 and z=3 is large enough so that every z~2 galaxy might be the result of a merger that occurred within their past 1 Gyr. I conclude that it is premature to rule out mergers as a universal driver for galaxy evolution from z~2 down to z=0.Comment: Accepted for publication in MNRAS. 14 pages, 2 figures

Enriched haloes at redshift z=2z=2 with no star-formation: Implications for accretion and wind scenarios

[Abridged] In order to understand which process (e.g. galactic winds, cold accretion) is responsible for the cool (T~10^4 K) halo gas around galaxies, we embarked on a program to study the star-formation properties of galaxies selected by their MgII absorption signature in quasar spectra. Specifically, we searched for the H-alpha line emission from galaxies near very strong z=2 MgII absorbers (with rest-frame equivalent width EW>2 \AA) because these could be the sign-posts of outflows or inflows. Surprisingly, we detect H-alpha from only 4 hosts out of 20 sight-lines (and 2 out of the 19 HI-selected sight-lines), despite reaching a star-formation rate (SFR) sensitivity limit of 2.9 M/yr (5-sigma) for a Chabrier initial mass function. This low success rate is in contrast with our z=1 survey where we detected 66%\ (14/21) of the MgII hosts. Taking into account the difference in sensitivity between the two surveys, we should have been able to detect >11.4 of the 20 z=2 hosts whereas we found only 4 galaxies. Interestingly, all the z=2 detected hosts have observed SFR greater than 9 M/yr, well above our sensitivity limit, while at z=1 they all have SFR less than 9 M/yr, an evolution that is in good agreement with the evolution of the SFR main sequence. Moreover, we show that the z=2 undetected hosts are not hidden under the quasar continuum after stacking our data and that they also cannot be outside our surveyed area. Hence, strong MgII absorbers could trace star-formation driven winds in low-mass halos (Mhalo < 10^{10.6} Msun). Alternatively, our results imply that z=2 galaxies traced by strong MgII absorbers do not form stars at a rate expected (3--10 M/yr) for their (halo or stellar) masses, supporting the existence of a transition in accretion efficiency at Mhalo ~ 10^{11} Msun. This scenario can explain both the detections and the non-detections.Comment: 14 pages, 4 fig.; MNRAS in press, minor corrections to match proof

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Improving the iMM904 S. cerevisiae metabolic model using essentiality and synthetic lethality data

<p>Abstract</p> <p>Background</p> <p><it>Saccharomyces cerevisiae </it>is the first eukaryotic organism for which a multi-compartment genome-scale metabolic model was constructed. Since then a sequence of improved metabolic reconstructions for yeast has been introduced. These metabolic models have been extensively used to elucidate the organizational principles of yeast metabolism and drive yeast strain engineering strategies for targeted overproductions. They have also served as a starting point and a benchmark for the reconstruction of genome-scale metabolic models for other eukaryotic organisms. In spite of the successive improvements in the details of the described metabolic processes, even the recent yeast model (i.e., <it>i</it>MM904) remains significantly less predictive than the latest <it>E. coli </it>model (i.e., <it>i</it>AF1260). This is manifested by its significantly lower specificity in predicting the outcome of grow/no grow experiments in comparison to the <it>E. coli </it>model.</p> <p>Results</p> <p>In this paper we make use of the automated GrowMatch procedure for restoring consistency with single gene deletion experiments in yeast and extend the procedure to make use of synthetic lethality data using the genome-scale model <it>i</it>MM904 as a basis. We identified and vetted using literature sources 120 distinct model modifications including various regulatory constraints for minimal and YP media. The incorporation of the suggested modifications led to a substantial increase in the fraction of correctly predicted lethal knockouts (i.e., specificity) from 38.84% (87 out of 224) to 53.57% (120 out of 224) for the minimal medium and from 24.73% (45 out of 182) to 40.11% (73 out of 182) for the YP medium. Synthetic lethality predictions improved from 12.03% (16 out of 133) to 23.31% (31 out of 133) for the minimal medium and from 6.96% (8 out of 115) to 13.04% (15 out of 115) for the YP medium.</p> <p>Conclusions</p> <p>Overall, this study provides a roadmap for the computationally driven correction of multi-compartment genome-scale metabolic models and demonstrates the value of synthetic lethals as curation agents.</p

Hematological Changes as Prognostic Indicators of Survival: Similarities Between Gottingen Minipigs, Humans, and Other Large Animal Models

The animal efficacy rule addressing development of drugs for selected disease categories has pointed out the need to develop alternative large animal models. Based on this rule, the pathophysiology of the disease in the animal model must be well characterized and must reflect that in humans. So far, manifestations of the acute radiation syndrome (ARS) have been extensively studied only in two large animal models, the non-human primate (NHP) and the canine. We are evaluating the suitability of the minipig as an additional large animal model for development of radiation countermeasures. We have previously shown that the Gottingen minipig manifests hematopoietic ARS phases and symptoms similar to those observed in canines, NHPs, and humans.We establish here the LD50/30 dose (radiation dose at which 50% of the animals succumb within 30 days), and show that at this dose the time of nadir and the duration of cytopenia resemble those observed for NHP and canines, and mimic closely the kinetics of blood cell depletion and recovery in human patients with reversible hematopoietic damage (H3 category, METREPOL approach). No signs of GI damage in terms of diarrhea or shortening of villi were observed at doses up to 1.9 Gy. Platelet counts at days 10 and 14, number of days to reach critical platelet values, duration of thrombocytopenia, neutrophil stress response at 3 hours and count at 14 days, and CRP-to-platelet ratio were correlated with survival. The ratios between neutrophils, lymphocytes and platelets were significantly correlated with exposure to irradiation at different time intervals.As a non-rodent animal model, the minipig offers a useful alternative to NHP and canines, with attractive features including ARS resembling human ARS, cost, and regulatory acceptability. Use of the minipig may allow accelerated development of radiation countermeasures