The intermediate evolution phase in case of truncated selection

Using methods of statistical physics, we present rigorous theoretical calculations of Eigen's quasispecies theory with the truncated fitness landscape which dramatically limits the available sequence space of a reproducing quasispecies. Depending on the mutation rates, we observe three phases, a selective one, an intermediate one with some residual order and a completely randomized phase. Our results are applicable for the general case of fitness landscape.Comment: 8 page

Eigen model as a quantum spin chain: exact dynamics

We map Eigen model of biological evolution [Naturwissenschaften {\bf 58}, 465 (1971)] into a one-dimensional quantum spin model with non-Hermitean Hamiltonian. Based on such a connection, we derive exact relaxation periods for the Eigen model to approach static energy landscape from various initial conditions. We also study a simple case of dynamic fitness function.Comment: 10 pages. Physical Revew E vol. 69, in press (2004

Tolerability and safety of the intake of bovine milk oligosaccharides extracted from cheese whey in healthy human adults.

Mechanistic research suggests a unique evolutionary relationship between complex milk oligosaccharides and cognate bifidobacteria enriched in breast-fed infants. Bovine milk oligosaccharides (BMO) were recently identified as structurally and functionally similar to human milk oligosaccharides. The present single-blind three-way crossover study is the first to determine the safety and tolerability of BMO consumption by healthy human participants (n 12) and its effects on faecal microbiota and microbial metabolism. Participants consumed each supplement (placebo-control; low- and high-BMO doses) for eleven consecutive days, followed by a 2-week washout period prior to initiating the next supplement arm. Low and high BMO doses were consumed as 25 and 35 % of each individual's daily fibre intake, respectively. Safety and tolerability were measured using standardised questionnaires on gut and stomach discomfort and stool consistency. Faecal extracts were profiled for bacterial populations by next-generation sequencing (NGS) and bifidobacteria presence was confirmed using quantitative PCR. Urine was analysed for changes in microbial metabolism using nuclear magnetic resonance spectroscopy (1H-NMR). Consumption of both the low and high BMO doses was well tolerated and did not change stool consistency from baseline. Multivariate analysis of the NGS results demonstrated no change in faecal microbiota phyla among the placebo-control and BMO supplement groups. In conclusion, BMO supplementation was well tolerated in healthy adults and has the potential to shift faecal microbiota toward beneficial strains as part of a synbiotic treatment with probiotic cultures that selectively metabolise oligosaccharides

The ACS Fornax Cluster Survey. II. The Central Brightness Profiles of Early-Type Galaxies: A Characteristic Radius on Nuclear Scales and the Transition from Central Luminosity Deficit to Excess

We analyse HST surface brightness profiles for 143 early-type galaxies in the Virgo and Fornax Clusters. Sersic models provide accurate descriptions of the global profiles with a notable exception: the observed profiles deviate systematically inside a characteristic "break" radius of R_b ~ 0.02R_e where R_e is the effective radius of the galaxy. The sense of the deviation is such that bright galaxies (M_B < -20) typically show central light deficits with respect to the inward extrapolation of the Sersic model, while the great majority of low- and intermediate-luminosity galaxies (-19.5 < M_B < -15) show central light excesses; galaxies occupying a narrow range of intermediate luminosities (-20 < M_B < -19.5) are usually well fitted by Sersic models over all radii. The slopes of the central surface brightness profiles, when measured at fixed fractions of R_e, vary smoothly as a function of galaxy luminosity in a manner that depends sensitively on the choice of measurement radius. We show that a recent claim of strong bimodality in slope is likely an artifact of the galaxy selection function used in that study. To provide a more robust characterization of the inner regions of galaxies, we introduce a parameter that describes the central luminosity deficit or excess relative to the inward extrapolation of the outer Sersic model. We find that this parameter varies smoothly over the range of ~ 720 in blue luminosity spanned by the Virgo and Fornax sample galaxies, with no evidence for a dichotomy. We argue that the central light excesses (nuclei) in M_B > -19 galaxies may be the analogs of the dense central cores that are predicted by some numerical simulations to form via gas inflows. (ABRIDGED)Comment: To appear in the Astrophysical Journal, December 2007. Full resolution paper available at http://www.cfa.harvard.edu/~ajordan/ACSFCS/Home.htm

PROSAC: A Submillimeter Array Survey of Low-Mass Protostars. I. Overview of Program: Envelopes, Disks, Outflows and Hot Cores

This paper presents a large spectral line and continuum survey of 8 deeply embedded, low-mass protostellar cores using the Submillimeter Array. Each source was observed in high excitation lines of some of the most common molecular species, CO, HCO+, CS, SO, H2CO, CH3OH and SiO. Line emission from 11 species originating from warm and dense gas have been imaged at high angular resolution (1-3"; typically 200-600 AU) together with continuum emission at 230 GHz (1.3 mm) and 345 GHz (0.8 mm). Compact continuum emission is observed for all sources which likely originates in marginally optically thick circumstellar disks, with typical lower limits to their masses of 0.1 M_sun (1-10% of the masses of their envelopes) and having a dust opacity law with beta approximately 1. Prominent outflows are present in CO 2-1 observations in all sources: the most diffuse outflows are found in the sources with the lowest ratios of disk-to-envelope mass, and it is suggested that these sources are in a phase where accretion of matter from the envelope has almost finished and the remainder of the envelope material is being dispersed by the outflows. Other characteristic dynamical signatures are found with inverse P Cygni profiles indicative of infalling motions seen in the 13CO 2-1 lines toward NGC1333-IRAS4A and -IRAS4B. Outflow-induced shocks are present on all scales in the protostellar environments and are most clearly traced by the emission of CH3OH in NGC1333-IRAS4A and -IRAS4B. These observations suggest that the emission of CH3OH and H2CO from these proposed "hot corinos" are related to the shocks caused by the protostellar outflows. Only one source, NGC1333-IRAS2A, has evidence for hot, compact CH3OH emission coincident with the embedded protostar.Comment: Accepted for publication in ApJ (52 pages; 9 figures). Abstract abridge

ULBPs, Novel MHC Class I–Related Molecules, Bind to CMV Glycoprotein UL16 and Stimulate NK Cytotoxicity through the NKG2D Receptor

AbstractThe human cytomegalovirus glycoprotein, UL16, binds to two members of a novel family of molecules, the ULBPs, and to the MHC class I homolog, MICB. The ULBPs are GPI-linked glycoproteins belonging to the extended MHC class I family but are only distantly related to MICB. The ULBP and MICB molecules are ligands for the activating receptor, NKG2D/DAP10, and this interaction is blocked by a soluble form of UL16. The ULBPs stimulate cytokine and chemokine production from NK cells, and expression of ULBPs in NK cell–resistant target cells confers susceptibility to NK cell cytotoxicity. Masking of NK cell recognition of ULBP or MIC antigens by UL16 provides a potential mechanism by which human cytomegalovirus–infected cells might evade attack by the immune system

Long-term culture captures injury-repair cycles of colonic stem cells

The colonic epithelium can undergo multiple rounds of damage and repair, often in response to excessive inflammation. The responsive stem cell that mediates this process is unclear, in part because of a lack of in vitro models that recapitulate key epithelial changes that occur in vivo during damage and repair. Here, we identify a Hop

Correlation Between Trough Plasma Dabigatran Concentrations and Estimates of Glomerular Filtration Rate Based on Creatinine and Cystatin C

AIMS: Dabigatran is largely cleared by renal excretion. Renal function is thus a major determinant of trough dabigatran concentrations, which correlate with the risk of thromboembolic and haemorrhagic outcomes. Current dabigatran dosing guidelines use the Cockcroft–Gault (CG) equation to gauge renal function, instead of contemporary equations including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations employing creatinine (CKD-EPI_Cr), cystatin C (CKD-EPI_Cys) and both renal biomarkers (CKD-EPI_CrCys). METHODS: A linear regression model including the dabigatran etexilate maintenance dose rate, relevant interacting drugs and genetic polymorphisms (including CES1), was used to analyse the relationship between the values from each renal function equation and trough steady-state plasma dabigatran concentrations. RESULTS: The median dose-corrected trough steady-state plasma dabigatran concentration in 52 patients (38–94 years) taking dabigatran etexilate was 60 µg/L (range 9–279). The dose-corrected trough concentration in a patient on phenytoin and phenobarbitone was >3 standard deviations below the cohort mean. The CG, CKD-EPI_Cr, CKD-EPI_Cys and CKD-EPI_CrCys equations explained (R(2), 95 % CI) 32 % (9–55), 37 % (12–60), 41 % (16–64) and 47 % (20–69) of the variability in dabigatran concentrations between patients, respectively. One-way analysis of variance (ANOVA) comparing the R(2) values for each equation was not statistically significant (p = 0.74). DISCUSSION: Estimates of renal function using the four equations accounted for 32–47 % of the variability in dabigatran concentrations between patients. We are the first to provide evidence that co-administration of phenytoin/phenobarbitone with dabigatran etexilate is associated with significantly reduced dabigatran exposure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40268-014-0045-9) contains supplementary material, which is available to authorized users