835 research outputs found
Real Estate Development Feasibility and Hurdle Rate Selection
The main findings are that most developers use specific âgo/no-goâ hurdle rate mechanisms irrespective of primary real estate type, with the majority using margin on development cost (MDC) or internal rate of return (IRR); the boundaries between traditional speculative development and real estate investment through the use of securitisation methods have become blurred; many developers use both quantitative metrics, with qualitative methods and specific structural checks to manage the risks involved; and the two most frequent methods of determining site value prior to acquisition are the residual land value and DCF methods. Most place a heavy reliance on industryâaccepted heuristics and do not have a predetermined process and method for altering or adapting the chosen hurdle rates and benchmarks
Allele quantification using molecular inversion probes (MIP)
Detection of genomic copy number changes has been an important research area, especially in cancer. Several high-throughput technologies have been developed to detect these changes. Features that are important for the utility of technologies assessing copy number changes include the ability to interrogate regions of interest at the desired density as well as the ability to differentiate the two homologs. In addition, assessing formaldehyde fixed and paraffin embedded (FFPE) samples allows the utilization of the vast majority of cancer samples. To address these points we demonstrate the use of molecular inversion probe (MIP) technology to the study of copy number. MIP is a high-throughput genotyping technology capable of interrogating >20â000 single nucleotide polymorphisms in the same tube. We have shown the ability of MIP at this multiplex level to provide copy number measurements while obtaining the allele information. In addition we have demonstrated a proof of principle for copy number analysis in FFPE samples
Caenorhabditis elegans Maintains Highly Compartmentalized Cellular Distribution of Metals and Steep Concentration Gradients of Manganese
Bioinorganic chemistry is critical to cellular function. Homeostasis of manganese (Mn), for example, is essential for life. A lack of methods for direct in situ visualization of Mn and other biological metals within intact multicellular eukaryotes limits our understanding of management of these metals. We provide the first quantitative subcellular visualization of endogenous Mn concentrations (spanning two orders of magnitude) associated with individual cells of the nematode, Caenorhabditis elegans
Immunoglobulin and T Cell Receptor Gene High-Throughput Sequencing Quantifies Minimal Residual Disease in Acute Lymphoblastic Leukemia and Predicts Post-Transplantation Relapse and Survival
AbstractMinimal residual disease (MRD) quantification is an important predictor of outcome after treatment for acute lymphoblastic leukemia (ALL). Bone marrow ALL burden â„ 10â4 after induction predicts subsequent relapse. Likewise, MRD â„ 10â4 in bone marrow before initiation of conditioning for allogeneic (allo) hematopoietic cell transplantation (HCT) predicts transplantation failure. Current methods for MRD quantification in ALL are not sufficiently sensitive for use with peripheral blood specimens and have not been broadly implemented in the management of adults with ALL. Consensus-primed immunoglobulin (Ig), TÂ cell receptor (TCR) amplification and high-throughput sequencing (HTS) permit use of a standardized algorithm for all patients and can detect leukemia at 10â6 or lower. We applied the LymphoSIGHT HTS platform (Sequenta Inc., South San Francisco, CA) to quantification of MRD in 237 samples from 29 adult BÂ cell ALL patients before and after allo-HCT. Using primers for the IGH-VDJ, IGH-DJ, IGK, TCRB, TCRD, and TCRG loci, MRD could be quantified in 93% of patients. Leukemia-associated clonotypes at these loci were identified in 52%, 28%, 10%, 35%, 28%, and 41% of patients, respectively. MRD â„ 10â4 before HCT conditioning predicted post-HCT relapse (hazard ratio [HR], 7.7; 95% confidence interval [CI], 2.0 to 30; PÂ =Â .003). In post-HCT blood samples, MRD â„10â6 had 100% positive predictive value for relapse with median lead time of 89Â days (HR, 14; 95% CI, 4.7 to 44, PÂ <Â .0001). The use of HTS-based MRD quantification in adults with ALL offers a standardized approach with sufficient sensitivity to quantify leukemia MRD in peripheral blood. Use of this approach may identify a window for clinical intervention before overt relapse
Reducing the Probability of Capture into Resonance
A migrating planet can capture planetesimals into mean motion resonances.
However, resonant trapping can be prevented when the drift or migration rate is
sufficiently high. Using a simple Hamiltonian system for first and second order
resonances, we explore how the capture probability depends on the order of the
resonance, drift rate and initial particle eccentricity. We present scaling
factors as a function of the planet mass and resonance strength to estimate the
planetary migration rate above which the capture probability drops to less than
1/2. Applying our framework to multiple extra solar planetary systems that have
two planets locked in resonance, we estimate lower limits for the outer
planet's migration rate allowing resonance capture of the inner planet. Mean
motion resonances are comprised of multiple resonant subterms. We find that the
corotation subterm can reduce the probability of capture when the planet
eccentricity is above a critical value. We present factors that can be used to
estimate this critical planet eccentricity. Applying our framework to the
migration of Neptune, we find that Neptune's eccentricity is near the critical
value that would make its 2:1 resonance fail to capture twotinos. The capture
probability is affected by the separation between resonant subterms and so is
also a function of the precession rates of the longitudes of periapse of both
planet and particle near resonance.Comment: Accepted for publication in MNRA
Transit Timing Observations from Kepler: III. Confirmation of 4 Multiple Planet Systems by a Fourier-Domain Study of Anti-correlated Transit Timing Variations
We present a method to confirm the planetary nature of objects in systems
with multiple transiting exoplanet candidates. This method involves a
Fourier-Domain analysis of the deviations in the transit times from a constant
period that result from dynamical interactions within the system. The
combination of observed anti-correlations in the transit times and mass
constraints from dynamical stability allow us to claim the discovery of four
planetary systems Kepler-25, Kepler-26, Kepler-27, and Kepler-28, containing
eight planets and one additional planet candidate.Comment: Accepted to MNRA
Planet Occurrence within 0.25 AU of Solar-type Stars from Kepler
We report the distribution of planets as a function of planet radius (R_p),
orbital period (P), and stellar effective temperature (Teff) for P < 50 day
orbits around GK stars. These results are based on the 1,235 planets (formally
"planet candidates") from the Kepler mission that include a nearly complete set
of detected planets as small as 2 Earth radii (Re). For each of the 156,000
target stars we assess the detectability of planets as a function of R_p and P.
We also correct for the geometric probability of transit, R*/a. We consider
first stars within the "solar subset" having Teff = 4100-6100 K, logg =
4.0-4.9, and Kepler magnitude Kp < 15 mag. We include only those stars having
noise low enough to permit detection of planets down to 2 Re. We count planets
in small domains of R_p and P and divide by the included target stars to
calculate planet occurrence in each domain. Occurrence of planets varies by
more than three orders of magnitude and increases substantially down to the
smallest radius (2 Re) and out to the longest orbital period (50 days, ~0.25
AU) in our study. For P < 50 days, the radius distribution is given by a power
law, df/dlogR= k R^\alpha. This rapid increase in planet occurrence with
decreasing planet size agrees with core-accretion, but disagrees with
population synthesis models. We fit occurrence as a function of P to a power
law model with an exponential cutoff below a critical period P_0. For smaller
planets, P_0 has larger values, suggesting that the "parking distance" for
migrating planets moves outward with decreasing planet size. We also measured
planet occurrence over Teff = 3600-7100 K, spanning M0 to F2 dwarfs. The
occurrence of 2-4 Re planets in the Kepler field increases with decreasing
Teff, making these small planets seven times more abundant around cool stars
than the hottest stars in our sample. [abridged]Comment: Submitted to ApJ, 22 pages, 10 figure
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