Inferring clonal evolution of tumors from single nucleotide somatic mutations

High-throughput sequencing allows the detection and quantification of frequencies of somatic single nucleotide variants (SNV) in heterogeneous tumor cell populations. In some cases, the evolutionary history and population frequency of the subclonal lineages of tumor cells present in the sample can be reconstructed from these SNV frequency measurements. However, automated methods to do this reconstruction are not available and the conditions under which reconstruction is possible have not been described. We describe the conditions under which the evolutionary history can be uniquely reconstructed from SNV frequencies from single or multiple samples from the tumor population and we introduce a new statistical model, PhyloSub, that infers the phylogeny and genotype of the major subclonal lineages represented in the population of cancer cells. It uses a Bayesian nonparametric prior over trees that groups SNVs into major subclonal lineages and automatically estimates the number of lineages and their ancestry. We sample from the joint posterior distribution over trees to identify evolutionary histories and cell population frequencies that have the highest probability of generating the observed SNV frequency data. When multiple phylogenies are consistent with a given set of SNV frequencies, PhyloSub represents the uncertainty in the tumor phylogeny using a partial order plot. Experiments on a simulated dataset and two real datasets comprising tumor samples from acute myeloid leukemia and chronic lymphocytic leukemia patients demonstrate that PhyloSub can infer both linear (or chain) and branching lineages and its inferences are in good agreement with ground truth, where it is available

The Infra‐Red Spectrum of C2H6

The infra‐red spectrum of C2H6 gas has been studied in the region between 1.6 and 13μ with a spectrometer of high resolving power. From measurements on four resolved ∥ bands the value IB0 = (42.234±0.011)×10−40 g cm2 has been obtained for the large moment of inertia in the ground state. From measurements on the three fundamental ⊥ bands the best value at present available for the small moment of inertia is IA = 10.81×10−40 g cm2. Because of uncertainties concerning the perturbations of degenerate state ν8, of which a semi‐quantitative explanation which is apparently basically correct has been obtained, this value is provisional but appears to be fairly reliable. With these values of IB0 and IA, if one assumes C☒C = 1.55A, one obtains C☒H = 1.098A and ≰HCC = 109° 3′. From the considerations of the perturbations of state ν8 and of the frequencies and line spacings of the combination ⊥ bands, spectroscopic evidence indicating that the configuration of C2H6 is staggered (point group D3d) has for the first time been obtained. Also from these considerations the reliable value ν8 = 1472.2 cm−1 and the values ν4 = 290 cm−1 for the torsion frequency and ν12 = 1190 cm−1 for the ``uncertain'' frequency have been obtained. The latter two values are perhaps somewhat more reliable and not inconsistent with values obtained previously by other methods. These and other results are summarized in Figs. 1 and 14 and in Tables XII—XV.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70901/2/JCPSA6-17-2-139-1.pd

Synthesis of 1-Aryl-3-Pyrazolidinones through 3-(2\u27-Arylaminoethyl)-1,4,2-Dioxide-5-one intermediates

A new preparation of 1-arylpyrazolidinones, not involving the prior preparation of arylhydrazines , is reported. The reaction of 3-arylaminopropiono hydroxamic acids with chloroformates gives the title compounds. This transformation is discussed in terms of the intermediacy of the corresponding l,4,2-dioxazol-5-one ring system. These intermediates undergo mild nitrogen-atom induced decomposition with simultaneous N-N bond formation. The effects of chloroformates and aryl substitution is discussed

Carers\u27 preferences for the delivery of therapy services for people with disability in rural Australia: Evidence from a discrete choice experiment

Background: The implementation of the Australian National Disability Insurance Scheme (NDIS) is expected to generate a responsive, person-centred system that will empower people with disability to choose the services and support they receive. However little attention has been paid to examine how users of the NDIS will choose and spend their individual budgets. This study aimed to determine quantitatively the relative importance that carers of people with a disability living in rural Australia place on different therapy service delivery characteristics. Methods: A stated preference discrete choice experiment (DCE) was incorporated into a survey of carers of people with disability living in rural Australia. Carers chose between therapy delivery services differing in attributes such as travel time to receive therapy, sector providing the service (i.e. Government, not-for-profit, private), out-of-pocket costs, person who delivers the therapy (therapist or other staff) and waiting time. Results: A total of 133 carers completed the DCE. The majority of respondents cared for a child with a disability (84%), the average age of the person they cared for was 17 years (SD 14.25). Participants expressed strong preferences for a short waiting time (0-3 months) to receive therapy services; services delivered by a therapist, no out of pocket cost and travelling up to 4 hours to receive a therapy session (p Conclusion: Carers of people with a disability in rural Australia exhibited strongest preferences for short waiting times (0-3 months). Therapy services that are delivered by therapy assistants or support workers will require careful introduction to achieve uptake and acceptability

Embedded Ribbons of Graphene Allotropes: An Extended Defect Perspective

Four fundamental dimer manipulations can be used to produce a variety of localized and extended defect structures in graphene. Two-dimensional templates result in graphene allotropes, here viewed as extended defects, which can exhibit either metallic or semiconducting electrical character. \emph{Embedded allotropic ribbons}--i.e. thin swaths of the new allotropes--can also be created within graphene. We examine these ribbons and find that they maintain the electrical character of their parent allotrope even when only a few atoms in width. Such extended defects may facilitate the construction of monolithic electronic circuitry.Comment: 24 pages, 21 figure

Should I stay or should I go? Exploring the job preferences of allied health professionals working with people with disability in rural Australia

Introduction: The uneven distribution of allied health professionals (AHPs) in rural and remote Australia and other countries is well documented. In Australia, like elsewhere, service delivery to rural and remote communities is complicated because relatively small numbers of clients are dispersed over large geographic areas. This uneven distribution of AHPs impacts significantly on the provision of services particularly in areas of special need such as mental health, aged care and disability services. Objective: This study aimed to determine the relative importance that AHPs (physiotherapists, occupational therapists, speech pathologists and psychologists – “therapists”) living in a rural area of Australia and working with people with disability, place on different job characteristics and how these may affect their retention. Methods: A cross-sectional survey was conducted using an online questionnaire distributed to AHPs working with people with disability in a rural area of Australia over a 3-month period. Information was sought about various aspects of the AHPs’ current job, and their workforce preferences were explored using a best–worst scaling discrete choice experiment (BWSDCE). Conditional logistic and latent class regression models were used to determine AHPs’ relative preferences for six different job attributes. Results: One hundred ninety-nine AHPs completed the survey; response rate was 51 %. Of those, 165 completed the BWSDCE task. For this group of AHPs, “high autonomy of practice” is the most valued attribute level, followed by “travel BWSDCE arrangements: one or less nights away per month”, “travel arrangements: two or three nights away per month” and “adequate access to professional development”. On the other hand, the least valued attribute levels were “travel arrangements: four or more nights per month”, “limited autonomy of practice” and “minimal access to professional development”. Except for “some job flexibility”, all other attributes had a statistical influence on AHPs’ job preference. Preferences differed according to age, marital status and having dependent children. Conclusions: This study allowed the identification of factors that contribute to AHPs’ employment decisions about staying and working in a rural area. This information can improve job designs in rural areas to increase retention

High-Resolution Nanoscale Solid-State Nuclear Magnetic Resonance Spectroscopy

We present a new method for high-resolution nanoscale magnetic resonance imaging (nano-MRI) that combines the high spin sensitivity of nanowire-based magnetic resonance detection with high spectral resolution nuclear magnetic resonance (NMR) spectroscopy. By applying NMR pulses designed using optimal control theory, we demonstrate a factor of $500$ reduction of the proton spin resonance linewidth in a $(50\text{-nm})^{\text{3}}$ volume of polystyrene and image proton spins in one dimension with a spatial resolution below $2~\text{nm}$.Comment: Main text: 8 pages, 6 figures; supplementary information: 10 pages, 10 figure

Observables in the Decays of B to Two Vector Mesons

In general there are nine observables in the decay of a B meson to two vector mesons defined in terms of polarization correlations of these mesons. Only six of these can be detected via the subsequent decay angular distributions because of parity conservation in those decays. The remaining three require the measurement of the spin polarization of one of the decay products.Comment: 12 pages, no figur