Posterior inference of Hi-C contact frequency through sampling

Hi-C is one of the most widely used approaches to study three-dimensional genome conformations. Contacts captured by a Hi-C experiment are represented in a contact frequency matrix. Due to the limited sequencing depth and other factors, Hi-C contact frequency matrices are only approximations of the true interaction frequencies and are further reported without any quantification of uncertainty. Hence, downstream analyses based on Hi-C contact maps (e.g., TAD and loop annotation) are themselves point estimations. Here, we present the Hi-C interaction frequency sampler (HiCSampler) that reliably infers the posterior distribution of the interaction frequency for a given Hi-C contact map by exploiting dependencies between neighboring loci. Posterior predictive checks demonstrate that HiCSampler can infer highly predictive chromosomal interaction frequency. Summary statistics calculated by HiCSampler provide a measurement of the uncertainty for Hi-C experiments, and samples inferred by HiCSampler are ready for use by most downstream analysis tools off the shelf and permit uncertainty measurements in these analyses without modifications

A new upper limit on the reflected starlight from Tau Bootis b

Using improved doppler tomographic signal-analysis techniques we have carried out a deep search for starlight reflected from the giant planet orbiting the star Tau Bootis. We combined echelle spectra secured at the 4.2 m William Herschel telescope in 1998 and 1999 (which yielded a tentative detection of a reflected starlight component from the orbiting companion) with new data obtained in 2000 (which failed to confirm the detection). The combined dataset comprises 893 high resolution spectra with a total integration time of 75 hr 32 min spanning 17 nights. We establish an upper limit on the planet's geometric albedo p<0.39 (at the 99.9 % significance level) at the most probable orbital inclination i=36 degrees, assuming a grey albedo, a Venus-like phase function and a planetary radius R_p=1.2 R_Jup. We are able to rule out some combinations of the predicted planetary radius and atmospheric albedo models with high, reflective cloud decks. Although a weak candidate signal appears near to the most probable radial velocity amplitude, its statistical significance is insufficient for us to claim a detection with any confidence.Comment: 13 pages, 18 figures, MNRAS accepted 12 June 200

Calibrating Water Depths of Ordovician Communities: Lithological and Ecological Controls on Depositional Gradients in Upper Ordovician Strata of Southern Ohio and North-Central Kentucky, USA

Limestone and shale facies of the Upper Ordovician Grant Lake Formation (Katian: Cincinnatian, Maysvillian) are well exposed in the Cincinnati Arch region of southern Ohio and north-central Kentucky, USA. These rocks record a gradual change in lithofacies and biofacies along a gently northward-sloping ramp. This gradient spans very shallow, olive-gray, platy, laminated dolostones with sparse ostracodes in the south to offshore, nodular, phosphatic, brachiopod-rich limestones and marls in the north. This study uses facies analysis in outcrop to determine paleoenvironmental parameters, particularly those related to water depth (e.g., position of the photic zone and shoreline, relative degree of environmental energy). Within a tightly correlated stratigraphic interval (the Mount Auburn and Straight Creek members of the Grant Lake Formation and the Terrill Member of the Ashlock Formation), we document the occurrence of paleoenvironmental indicators, including desiccation cracks and light-depth indicators, such as red and green algal fossils and oncolites. This permitted recognition of a ramp with an average gradient of 10.20 cm water depth per horizontal kilometer. Thus, shallow subtidal (.lagoonal.) deposits in the upramp portion fall within the 1.5.6 m depth range, cross-bedded grainstones representing shoal-type environments fall within the 6.18 m depth range and subtidal, shell-rich deposits in the downramp portion fall within the 20.30 m depth range. These estimates match interpretations of depth independently derived from faunal and sedimentologic evidence that previously suggested a gentle ramp gradient and contribute to ongoing and future high-resolution paleontologic and stratigraphic studies of the Cincinnati Arch region

The Magnetic Fields of Classical T Tauri Stars

We report new magnetic field measurements for 14 classical T Tauri stars (CTTSs). We combine these data with one previous field determination in order to compare our observed field strengths with the field strengths predicted by magnetospheric accretion models. We use literature data on the stellar mass, radius, rotation period, and disk accretion rate to predict the field strength that should be present on each of our stars according to these magnetospheric accretion models. We show that our measured field values do not correlate with the field strengths predicted by simple magnetospheric accretion theory. We also use our field strength measurements and literature X-ray luminosity data to test a recent relationship expressing X-ray luminosity as a function of surface magnetic flux derived from various solar feature and main sequence star measurements. We find that the T Tauri stars we have observed have weaker than expected X-ray emission by over an order of magnitude on average using this relationship. We suggest the cause for this is actually a result of the very strong fields on these stars which decreases the efficiency with which gas motions in the photosphere can tangle magnetic flux tubes in the corona.Comment: 25 pages, 5 figure

Is TIMP-1 immunoreactivity alone or in combination with other markers a predictor of benefit from anthracyclines in the BR9601 adjuvant breast cancer chemotherapy trial?

INTRODUCTION: Predictive cancer biomarkers to guide the right treatment to the right patient at the right time are strongly needed. The purpose of the present study was to validate prior results that tissue inhibitor of metalloproteinase 1 (TIMP-1) alone or in combination with either HER2 or TOP2A copy number can be used to predict benefit from epirubicin (E) containing chemotherapy compared with cyclophosphamide, methotrexate and fluorouracil (CMF) treatment. METHODS: For the purpose of this study, formalin fixed paraffin embedded tumor tissue from women recruited into the BR9601 clinical trial, which randomized patients to E-CMF versus CMF, were analyzed for TIMP-1 immunoreactivity. Using previously collected data for HER2 amplification and TOP2A gene aberrations, we defined patients as "anthracycline non-responsive", that is, 2T (TIMP-1 immunoreactive and TOP2A normal) and HT (TIMP-1 immunoreactive and HER2 negative) and anthracycline responsive (all other cases). RESULTS: In total, 288 tumors were available for TIMP-1 analysis with (183/274) 66.8%, and (181/274) 66.0% being classed as 2T and HT responsive, respectively. TIMP-1 was neither associated with patient prognosis (relapse free survival or overall survival) nor with a differential effect of E-CMF and CMF. Also, TIMP-1 did not add to the predictive value of HER2, TOP2A gene aberrations, or to Ki67 immunoreactivity. CONCLUSION: This study could not confirm the predictive value of TIMP-1 immunoreactivity in patients randomized to receive E-CMF versus CMF as adjuvant treatment for primary breast cancer

Descriptive Analysis of a Baseline Concussion Battery Among U.S. Service Academy Members: Results from the Concussion Assessment, Research, and Education (CARE) Consortium

Introduction The prevalence and possible long-term consequences of concussion remain an increasing concern to the U.S. military, particularly as it pertains to maintaining a medically ready force. Baseline testing is being used both in the civilian and military domains to assess concussion injury and recovery. Accurate interpretation of these baseline assessments requires one to consider other influencing factors not related to concussion. To date, there is limited understanding, especially within the military, of what factors influence normative test performance. Given the significant physical and mental demands placed on service academy members (SAM), and their relatively high risk for concussion, it is important to describe demographics and normative profile of SAMs. Furthermore, the absence of available baseline normative data on female and non-varsity SAMs makes interpretation of post-injury assessments challenging. Understanding how individuals perform at baseline, given their unique individual characteristics (e.g., concussion history, sex, competition level), will inform post-concussion assessment and management. Thus, the primary aim of this manuscript is to characterize the SAM population and determine normative values on a concussion baseline testing battery. Materials and Methods All data were collected as part of the Concussion Assessment, Research and Education (CARE) Consortium. The baseline test battery included a post-concussion symptom checklist (Sport Concussion Assessment Tool (SCAT), psychological health screening inventory (Brief Symptom Inventory (BSI-18) and neurocognitive evaluation (ImPACT), Balance Error Scoring System (BESS), and Standardized Assessment of Concussion (SAC). Linear regression models were used to examine differences across sexes, competition levels, and varsity contact levels while controlling for academy, freshman status, race, and previous concussion. Zero inflated negative binomial models estimated symptom scores due to the high frequency of zero scores. Results Significant, but small, sex effects were observed on the ImPACT visual memory task. While, females performed worse than males (p < 0.0001, pη2 = 0.01), these differences were small and not larger than the effects of the covariates. A similar pattern was observed for competition level on the SAC. There was a small, but significant difference across competition level. SAMs participating in varsity athletics did significantly worse on the SAC compared to SAMs participating in club or intramural athletics (all p’s < 0.001, η2 = 0.01). When examining symptom reporting, males were more than two times as likely to report zero symptoms on the SCAT or BSI-18. Intramural SAMs had the highest number of symptoms and severity compared to varsity SAMs (p < 0.0001, Cohen’s d < 0.2). Contact level was not associated with SCAT or BSI-18 symptoms among varsity SAMs. Notably, the significant differences across competition level on SCAT and BSI-18 were sub-clinical and had small effect sizes. Conclusion The current analyses provide the first baseline concussion battery normative data among SAMs. While statistically significant differences may be observed on baseline tests, the effect sizes for competition and contact levels are very small, indicating that differences are likely not clinically meaningful at baseline. Identifying baseline differences and significant covariates is important for future concussion-related analyses to inform concussion evaluations for all athlete levels

Discovery and characterization of WASP-6b, an inflated sub-Jupiter mass planet transiting a solar-type star

We report the discovery of WASP-6b, an inflated sub-Jupiter mass planet transiting every 3.3610060^{\rm + 0.0000022 }_ days a mildly metal-poor solar-type star of magnitude V = 11.9. A combined analysis of the WASP photometry, high-precision followup transit photometry and radial velocities yield a planetary mass M_{\rm p} = 0.503^_ $M_{\rm J}$ and radius R_{\rm p} = 1.224^_ $R_{\rm J}$, resulting in a density $\rho_{\rm p} = 0.27 \pm 0.05$ $\rho_{\rm J}$. The mass and radius for the host star are M_\ast = 0.88^_ $M_\odot$ and R_\ast = 0.870^_ $R_\odot$. The non-zero orbital eccentricity e = 0.054^{\rm +0.018}_ that we measure suggests that the planet underwent a massive tidal heating ~1 Gyr ago that could have contributed to its inflated radius. High-precision radial velocities obtained during a transit allow us to measure a sky-projected angle between the stellar spin and orbital axis \beta = 11^_ deg. In addition to similar published measurements, this result favors a dominant migration mechanism based on tidal interactions with a protoplanetary disk

Defining a therapeutic window for kinase inhibitors in leukemia to avoid neutropenia

Neutropenia represents one of the major dose-limiting toxicities of many current cancer therapies. To circumvent the off-target effects of cytotoxic chemotherapeutics, kinase inhibitors are increasingly being used as an adjunct therapy to target leukemia. In this study, we conducted a screen of leukemic cell lines in parallel with primary neutrophils to identify kinase inhibitors with the capacity to induce apoptosis of myeloid and lymphoid cell lines whilst sparing primary mouse and human neutrophils. We have utilized a high-throughput live cell imaging platform to demonstrate that cytotoxic drugs have limited effects on neutrophil viability but are toxic to hematopoietic progenitor cells, with the exception of the topoisomerase I inhibitor SN-38. The parallel screening of kinase inhibitors revealed that mouse and human neutrophil viability is dependent on cyclin-dependent kinase (CDK) activity but surprisingly only partially dependent on PI3 kinase and JAK/STAT signaling, revealing dominant pathways contributing to neutrophil viability. Mcl-1 haploinsufficiency sensitized neutrophils to CDK inhibition, demonstrating that Mcl-1 is a direct target for CDK inhibitors. This study reveals a therapeutic window for the kinase inhibitors BEZ235, BMS-3, AZD7762, and (R)-BI-2536 to induce apoptosis of leukemia cell lines whilst maintaining immunocompetence and hemostasis

The Metabochip, a Custom Genotyping Array for Genetic Studies of Metabolic, Cardiovascular, and Anthropometric Traits

PMCID: PMC3410907This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Regularity of Edge Ideals and Their Powers

We survey recent studies on the Castelnuovo-Mumford regularity of edge ideals of graphs and their powers. Our focus is on bounds and exact values of $\text{ reg } I(G)$ and the asymptotic linear function $\text{ reg } I(G)^q$, for $q \geq 1,$ in terms of combinatorial data of the given graph $G.$Comment: 31 pages, 15 figure