Changes in Body composition and Maintenance efficiency during periods of restricted and maintenance feeding in immature and mature sheep

Improvements in production and quality can occur, without the need for increased inputs, through the use of 'Compensatory growth' or by reducing the maintenance requirements during growth and at maturity. A series of studies were used to examine the changes in body composition that occurred during weight loss and realimentation in immature and mature sheep. The effect of variations in body composition, induced through manipulation of nutrition, on estimates for equilibrium maintenance efficiency of mature sheep was examined. Statistical methods developed, tested for seasonal cycles in body composition in an attempt to determine the impact that any endogenous pattern in tissue deposition has on estimates of efficiencies for growth and maintenance. ..... Seasonality After adjusting for differences in body composition attributable to growth using an allometric function, seasonal oscillations for total body fat and carcass muscle were apparent in growing sheep. The magnitude and phase of the sine oscillations for fat and carcass muscle suggested that seasonal cues affect the priorities for tissue deposition. Seasonal oscillations where present for mature sheep that had been fed at a constant feed level. However a more precise method of describing the patterns of change in body tissues using random effects models and cubic splines did not reveal the presence of any time based deviation in total fat, carcass muscle or visceral lean. Nevertheless, the possibility of oscillations in body composition must be considered when estimating the efficiency of growth and maintenance or when evaluating the effects of nutritional manipulation on tissue development in immature and mature sheep

First-in-human, open-label dose-escalation and dose-expansion study of the safety, pharmacokinetics, and antitumor effects of an oral ALK inhibitor ASP3026 in patients with advanced solid tumors

Abstract Background ASP3026 is a second-generation anaplastic lymphoma kinase (ALK) inhibitor that has potent in vitro activity against crizotinib-resistant ALK-positive tumors. This open-label, multicenter, first-in-human phase I study ( NCT01284192 ) assessed the safety, pharmacokinetic profile, and antitumor activity of ASP3026. Methods Advanced solid tumor patients received oral ASP3026 in 3 + 3 dose-escalation cohorts at doses of 25–800 mg once daily in 28-day cycles. The endpoints were to identify the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), and the pharmacokinetic profile of ASP3026. A phase Ib expansion cohort enrolled patients with metastatic, crizotinib-resistant ALK-positive solid tumors at the RP2D, and response was evaluated by RECIST 1.1. Results The dose-escalation cohort enrolled 33 patients, including three crizotinib-resistant, ALK-positive patients, and the dose-expansion cohort enrolled another 13 crizotinib-resistant, ALK-positive non-small cell lung cancer (NSCLC) patients. ASP3026 demonstrated both linear pharmacokinetics and dose-proportional exposure for area under the plasma concentration–time curve and maximum concentration observed with a median terminal half-life of 35 h, supporting the daily dosing. Grade 3 rash and elevated transaminase concentrations were dose-limiting toxicities observed at 800 mg; hence, 525 mg daily was the MTD and RP2D. The most common treatment-related adverse events were nausea (38 %), fatigue (35 %), and vomiting (35 %). Among the 16 patients with crizotinib-resistant ALK-positive tumors (15 NSCLC, 1 neuroblastoma), eight patients achieved partial response (overall response rate 50 %; 95 % confidence interval 25–75 %) and seven patients (44 %) achieved stable disease. Conclusions ASP3026 was well tolerated and had therapeutic activity in patients with crizotinib-resistant ALK-positive advanced tumors. Trial registration ClinTrials.gov: NCT0128419

Decision Tree Classifiers for Star/Galaxy Separation

We study the star/galaxy classification efficiency of 13 different decision tree algorithms applied to photometric objects in the Sloan Digital Sky Survey Data Release Seven (SDSS DR7). Each algorithm is defined by a set of parameters which, when varied, produce different final classification trees. We extensively explore the parameter space of each algorithm, using the set of $884,126$ SDSS objects with spectroscopic data as the training set. The efficiency of star-galaxy separation is measured using the completeness function. We find that the Functional Tree algorithm (FT) yields the best results as measured by the mean completeness in two magnitude intervals: $14\le r\le21$ ($85.2$) and $r\ge19$ ($82.1$). We compare the performance of the tree generated with the optimal FT configuration to the classifications provided by the SDSS parametric classifier, 2DPHOT and Ball et al. (2006). We find that our FT classifier is comparable or better in completeness over the full magnitude range $15\le r\le21$, with much lower contamination than all but the Ball et al. classifier. At the faintest magnitudes ($r>19$), our classifier is the only one able to maintain high completeness ($>$80%) while still achieving low contamination ($\sim2.5$). Finally, we apply our FT classifier to separate stars from galaxies in the full set of $69,545,326$ SDSS photometric objects in the magnitude range $14\le r\le21$.Comment: Submitted to A

Chiral patterns arising from electrostatic growth models

Recently, unusual and strikingly beautiful seahorse-like growth patterns have been observed under conditions of quasi-two-dimensional growth. These `S'-shaped patterns strongly break two-dimensional inversion symmetry; however such broken symmetry occurs only at the level of overall morphology, as the clusters are formed from achiral molecules with an achiral unit cell. Here we describe a mechanism which gives rise to chiral growth morphologies without invoking microscopic chirality. This mechanism involves trapped electrostatic charge on the growing cluster, and the enhancement of growth in regions of large electric field. We illustrate the mechanism with a tree growth model, with a continuum model for the motion of the one-dimensional boundary, and with microscopic Monte Carlo simulations. Our most dramatic results are found using the continuum model, which strongly exhibits spontaneous chiral symmetry breaking, and in particular finned `S' shapes like those seen in the experiments.Comment: RevTeX, 12 pages, 9 figure

IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Renormalon Ambiguities in NRQCD Operator Matrix Elements

We analyze the renormalon ambiguities that appear in factorization formulas in QCD. Our analysis contains a simple argument that the ambiguities in the short-distance coefficients and operator matrix elements are artifacts of dimensional-regularization factorization schemes and are absent in cutoff schemes. We also present a method for computing the renormalon ambiguities in operator matrix elements and apply it to a computation of the ambiguities in the matrix elements that appear in the NRQCD factorization formulas for the annihilation decays of S-wave quarkonia. Our results, combined with those of Braaten and Chen for the short-distance coefficients, provide an explicit demonstration that the ambiguities cancel in the physical decay rates. In addition, we analyze the renormalon ambiguities in the Gremm-Kapustin relation and in various definitions of the heavy-quark mass.Comment: 29 pages, REVTEX; revised Abstract, Introduction, Summary, corrected some typo

Cation distribution and valence in synthetic Al-Mn-O and Fe-Mn-O spinels under varying fO2 conditions

The spinel-group minerals, found in a range of igneous rocks, are resistant toweathering and can incorporate several multivalent elements, meaning they have the potential to provide insight into the redox conditions of parental magmas. Naturally occurring spinel can contain varying quantities of Mn, an element which occurs terrestrially and extra-terrestrially as Mn2+, Mn3+, Mn4+ and Mn5+. However, a lack of information on the effects of oxygen fugacity (fO2 ) on: (1) Mn valence state and cation distribution; and (2) on spinel-melt partitioning means that the potential for a Mn-in-spinel oxy-barometer remains largely untested. Here, we use electron probe microanalysis, micro-focus X-ray Absorption Near Edge Structure (XANES) spectroscopy and single-crystal X-ray diffraction (SC-XRD) to investigate cation distribution and valence state in spinels in the Al-Mn-O and Fe-Mn-O systems synthesized at ambient pressure under varying fO2 conditions. In contrast to previous studies, we find that the spectral resolution of the Mn K-edge XANES spectra is insufficient to provide quantitative data onMn valence state and site occupancy, although it does verify that Mn is incorporated as both Mn2+ and Mn3+, distributed over tetrahedral and octahedral sites. Combination of data from XANES and SC-XRD refinements can, however, be used to model Mn, Al and Fe valence and site occupancy. It would be expected thatMn-Fe spinels have the potential to record fO2 conditions in parental melts due to changes to the octahedral site under conditions that were more reducing. However, decoupling the effects of temperature and oxygen fugacity on the TFe3+-TMn2+ exchange in the Mn-Fe spinels remains challenging. In contrast, little variation is noted in Mn-Al spinels as a function of fO2 , implying that crystal chemistry and cation site geometry may significantly influence cation distribution, and by inference, crystal-melt partitioning, in spinel-group minerals

Accurate Whole-Genome Sequencing and Haplotyping from 10 to 20 Human Cells

Recent advances in whole genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, Long Fragment Read (LFR) technology, similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only ~100 pg of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants (SNVs) were assembled into long haplotype contigs. Removal of false positive SNVs not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10 Mb. Cost-effective and accurate genome sequencing and haplotyping from 10-20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications