BRIEF REPORT Testing for a Historical Population Bottleneck in Wild Verreaux's Sifaka (Propithecus verreauxi verreauxi ) Using Microsatellite Data

The degree to which historical human activities negatively impacted past and present lemur species is a long-standing question in primatology. At present, most evidence addressing this issue comes from archaeology, paleontology, and behavioral studies. Genetic data provide another source of evidence. In this study, six microsatellite loci, genotyped on more than 360 wild Verreaux's sifaka, are used in order to test the hypothesis that this population experienced a population bottleneck in the last 2000 years. Excess heterozygosity is compared with the heterozygosity expected under mutation-drift equilibrium in order to test for the genetic signature of a rapid population contraction in the past. The results indicate that the sifaka population did not experience a population bottleneck. Various methodological and conceptual implications of this result are discussed. Am

Staircase polygons: moments of diagonal lengths and column heights

We consider staircase polygons, counted by perimeter and sums of k-th powers of their diagonal lengths, k being a positive integer. We derive limit distributions for these parameters in the limit of large perimeter and compare the results to Monte-Carlo simulations of self-avoiding polygons. We also analyse staircase polygons, counted by width and sums of powers of their column heights, and we apply our methods to related models of directed walks.Comment: 24 pages, 7 figures; to appear in proceedings of Counting Complexity: An International Workshop On Statistical Mechanics And Combinatorics, 10-15 July 2005, Queensland, Australi

Symmetry breaking orbital anisotropy on detwinned Ba(Fe1-xCox)2As2 above the spin density wave transition

Nematicity, defined as broken rotational symmetry, has recently been observed in competing phases proximate to the superconducting phase in the cuprate high temperature superconductors. Similarly, the new iron-based high temperature superconductors exhibit a tetragonal to orthorhombic structural transition (i.e. a broken C4 symmetry) that either precedes or is coincident with a collinear spin density wave (SDW) transition in undoped parent compounds, and superconductivity arises when both transitions are suppressed via doping. Evidence for strong in-plane anisotropy in the SDW state in this family of compounds has been reported by neutron scattering, scanning tunneling microscopy, and transport measurements. Here we present an angle resolved photoemission spectroscopy study of detwinned single crystals of a representative family of electron-doped iron-arsenide superconductors, Ba(Fe1-xCox)2As2 in the underdoped region. The crystals were detwinned via application of in-plane uniaxial stress, enabling measurements of single domain electronic structure in the orthorhombic state. At low temperatures, our results clearly demonstrate an in-plane electronic anisotropy characterized by a large energy splitting of two orthogonal bands with dominant dxz and dyz character, which is consistent with anisotropy observed by other probes. For compositions x>0, for which the structural transition (TS) precedes the magnetic transition (TSDW), an anisotropic splitting is observed to develop above TSDW, indicating that it is specifically associated with TS. For unstressed crystals, the band splitting is observed close to TS, whereas for stressed crystals the splitting is observed to considerably higher temperatures, revealing the presence of a surprisingly large in-plane nematic susceptibility in the electronic structure.Comment: final version published in PNAS, including supplementary informatio

Scaling prediction for self-avoiding polygons revisited

We analyse new exact enumeration data for self-avoiding polygons, counted by perimeter and area on the square, triangular and hexagonal lattices. In extending earlier analyses, we focus on the perimeter moments in the vicinity of the bicritical point. We also consider the shape of the critical curve near the bicritical point, which describes the crossover to the branched polymer phase. Our recently conjectured expression for the scaling function of rooted self-avoiding polygons is further supported. For (unrooted) self-avoiding polygons, the analysis reveals the presence of an additional additive term with a new universal amplitude. We conjecture the exact value of this amplitude.Comment: 17 pages, 3 figure

HER2-HER3 heterodimer quantification by FRET-FILM and patient subclass analysis of the COIN colorectal trial

BACKGROUND: The phase 3 MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based chemotherapy in first-line treatment of advanced colorectal cancer. This study exploits additional information on HER2-HER3 dimerization to achieve patient stratification and reveal previously hidden subgroups of patients who had differing disease progression and treatment response. METHODS: HER2-HER3 dimerization was quantified by 'FLIM Histology' in primary tumor samples from 550 COIN trial patients receiving oxaliplatin and fluoropyrimidine chemotherapy +/-cetuximab. Bayesian latent class analysis (LCA) and covariate reduction was performed to analyze the effects of HER2-HER3 dimer, RAS mutation and cetuximab on progression-free survival (PFS) and overall survival (OS). All statistical tests were two-sided. RESULTS: LCA on a cohort of 398 patients revealed two patient subclasses with differing prognoses (median OS: 1624 days [95%CI=1466-1816] vs 461 [95%CI=431-504]): Class 1 (15.6%) showed a benefit from cetuximab in OS (HR = 0.43 [95%CI=0.25-0.76]; p = 0.004). Class 2 showed an association of increased HER2-HER3 with better OS (HR = 0.64 [95%CI=0.44-0.94]; p = 0.02). A class prediction signature was formed and tested on an independent validation cohort (N = 152) validating the prognostic utility of the dimer assay. Similar subclasses were also discovered in full trial dataset (N = 1,630) based on 10 baseline clinicopathological and genetic covariates. CONCLUSIONS: Our work suggests that the combined use of HER dimer imaging and conventional mutation analyses will be able to identify a small subclass of patients (>10%) who will have better prognosis following chemotherapy. A larger prospective cohort will be required to confirm its utility in predicting the outcome of anti-EGFR treatment

Novel opsin gene variation in large-bodied, diurnal lemurs

Some primate populations include both trichromatic and dichromatic (red-green colour blind) individuals due to allelic variation at the X-linked opsin locus. This polymorphic trichromacy is well described in day-active New World monkeys. Less is known about colour vision in Malagasy lemurs, but, unlike New World monkeys, only some day-active lemurs are polymorphic, while others are dichromatic. The evolutionary pressures underlying these differences in lemurs are unknown, but aspects of species ecology, including variation in activity pattern, are hypothesized to play a role. Limited data on X-linked opsin variation in lemurs make such hypotheses difficult to evaluate. We provide the first detailed examination of X-linked opsin variation across a lemur clade (Indriidae). We sequenced the X-linked opsin in the most strictly diurnal and largest extant lemur, Indri indri, and nine species of smaller, generally diurnal indriids (Propithecus). Although nocturnal Avahi (sister taxon to Propithecus) lacks a polymorphism, at least eight species of diurnal indriids have two or more X-linked opsin alleles. Four rainforest-living taxa-I. indri and the three largest Propithecus species-have alleles not previously documented in lemurs. Moreover, we identified at least three opsin alleles in Indri with peak spectral sensitivities similar to some New World monkeys

Perspectives on Astrophysics Based on Atomic, Molecular, and Optical (AMO) Techniques

About two generations ago, a large part of AMO science was dominated by experimental high energy collision studies and perturbative theoretical methods. Since then, AMO science has undergone a transition and is now dominated by quantum, ultracold, and ultrafast studies. But in the process, the field has passed over the complexity that lies between these two extremes. Most of the Universe resides in this intermediate region. We put forward that the next frontier for AMO science is to explore the AMO complexity that describes most of the Cosmos.Comment: White paper submission to the Decadal Assessment and Outlook Report on Atomic, Molecular, and Optical (AMO) Science (AMO 2020

A Two Micron All-Sky Survey View of the Sagittarius Dwarf Galaxy: VI. s-Process and Titanium Abundance Variations Along the Sagittarius Stream

We present high-resolution spectroscopic measurements of the abundances of titanium (Ti), yttrium (Y) and lanthanum (La) for M giant candidates of the Sagittarius (Sgr) dwarf spheroidal (dSph) + tidal tail system pre-selected on the basis of position and radial velocity. The majority of these stars show peculiar abundance patterns compared to those of nominal Milky Way (MW) stars. The overall [Ti/Fe], [Y/Fe], [La/Fe] and [La/Y] patterns with [Fe/H] of the Sgr stream plus Sgr core do resemble those seen in the Large Magellanic Cloud (LMC) and other dSphs, only shifted [Fe/H] by ~+0.4 from the LMC and by ~+1 dex from the other dSphs; these relative shifts reflect the faster and/or more efficient chemical evolution of Sgr compared to the other satellites, and show that Sgr has had an enrichment history more like the LMC than the other dSphs. By tracking the evolution of the abundance patterns along the Sgr stream we can follow the time variation of the chemical make-up of dSph stars donated to the MW halo by Sgr. This evolution demonstrates that while the bulk of the stars currently in the Sgr dSph are quite unlike those of the MW halo, an increasing number of stars farther along the Sgr stream have abundances like MW halo stars, a trend that shows clearly how the MW halo could have been contributed by present day satellite galaxies even if the present chemistry of those satellites is now different from typical halo field stars. Finally, we analyze the chemical abundances of a moving group of M giants among the Sgr leading arm stars at the North Galactic Cap, but having radial velocities unlike the infalling Sgr leading arm debris there. Through use of "chemical fingerprinting", we conclude that these northern hemisphere M giants also are Sgr stars, likely trailing arm debris overlapping the leading arm in the north.Comment: Accepted for publication in Ap

Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer

OBJECTIVE: Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes.DESIGN: RG analysis was conducted by a multidisciplinary panel of patients, clinicians and researchers (n=71). Eight working groups (WG) were constituted: discovery science; risk; prevention; early diagnosis and screening; pathology; curative treatment; stage IV disease; and living with and beyond CRC. A series of discussions led to development of draft papers by each WG, which were evaluated by a 20-strong patient panel. A final list of RGs and research recommendations (RR) was endorsed by all participants.RESULTS: Fifteen critical RGs are summarised below: RG1: Lack of realistic models that recapitulate tumour/tumour micro/macroenvironment; RG2: Insufficient evidence on precise contributions of genetic/environmental/lifestyle factors to CRC risk; RG3: Pressing need for prevention trials; RG4: Lack of integration of different prevention approaches; RG5: Lack of optimal strategies for CRC screening; RG6: Lack of effective triage systems for invasive investigations; RG7: Imprecise pathological assessment of CRC; RG8: Lack of qualified personnel in genomics, data sciences and digital pathology; RG9: Inadequate assessment/communication of risk, benefit and uncertainty of treatment choices; RG10: Need for novel technologies/interventions to improve curative outcomes; RG11: Lack of approaches that recognise molecular interplay between metastasising tumours and their microenvironment; RG12: Lack of reliable biomarkers to guide stage IV treatment; RG13: Need to increase understanding of health related quality of life (HRQOL) and promote residual symptom resolution; RG14: Lack of coordination of CRC research/funding; RG15: Lack of effective communication between relevant stakeholders.CONCLUSION: Prioritising research activity and funding could have a significant impact on reducing CRC disease burden over the next 5 years.</p