Effects of The BCR-ABLl Oncogene on DNA Damage and Repair

Chronic myeloid leukemia (CML) is a two-stage disease caused by the p210 BCR-ABL protein. BCR-ABL is a constitutively activated tyrosine kinase that activates signaling pathways to enhance proliferation and inhibit apoptosis. BCR-ABL kinase activity directly causes CML chronic phase, the first stage of CML, but the role of BCR-ABL in transitioning to blast crisis (BC), the second stage of disease, remains under investigation. Given that CML BC is marked by additional chromosomal abnormalities, the role of BCR-ABL in contributing to genomic instability through effects on DNA damage and DNA repair processes has been studied. We investigated what impact BCR-ABL has on the development of DNA double strand breaks (DSBs) and mis-repair in a cell system that is unable to undergo apoptosis. We determined that the failure of cells to undergo apoptosis after DNA damage leads to genomic instability, which is not further increased by BCR-ABL expression. We expressed BCR-ABL in a mouse hematopoietic cell line null for the pro-apoptotic proteins Bax and Bak (DKO). Both DKO cells and the BCR-ABL-expressing cell line (DBA) fail to undergo apoptosis after γ-irradiation (IR). DKO cells are dependent on interleukin-3 (IL-3) for growth and proliferation, but expression of BCR-ABL renders them IL-3 independent. We compared the induction of DSBs after IR and determined that unlike apoptosis-competent cell lines, which demonstrate increased DSB formation in the presence of BCR-ABL, there was no difference in DSB formation comparing DKO to DBA cells. This suggests that the Bax/Bak-mediated induction of apoptosis may be important in the DNA damage response. We also evaluated the level of misrepair in DKO and DBA cells after IR using spectral karyotype (SKY) analysis. We determined that DKO and DBA cells showed a similar accumulation of new chromosomal abnormalities, including gains and losses of chromosomes as well as translocations, after IR and repair. These results suggest that the BCR-ABL-mediated effects on DNA damage and repair pathways may occur through inhibition of apoptosis rather than or in addition to direct effects on DNA repair pathways. We postulate that BCR-ABL shifts the apoptotic threshold, allowing a group of cells with an increased amount of damage to survive

Developing a Mobile Application to Reduce Risks for Runaway Youth in Bangkok, Thailand

There are 100 million runaway youths worldwide. These youth face an increased risk of physical and emotional harm. Our team worked with the Sati Foundation, a non-profit organization in Bangkok, Thailand, to develop a mobile application to reduce risks for runaway youth. We designed our project using the Software Development Life Cycle methodology. To learn about the runaway youth and their needs, we conducted interviews and followed user-centered design to create our application. We created features that connect runaways to emergency help, show the locations of free resources, and teach runaways about health and wellness. These features help to ensure that runaways do not have to resort to dangerous or illegal activities to fulfill their basic needs

A PDA-based dietary self-monitoring intervention to reduce sodium intake in an in-center hemodialysis patient

Objective: The purpose of the BalanceWise-hemodialysis study is to determine the efficacy of a dietary intervention to reduce dietary sodium intake in patients receiving maintenance, in-center hemodialysis (HD). Personal digital assistant (PDA)-based dietary self-monitoring is paired with behavioral counseling. The purpose of this report is to present a case study of one participant's progression through the intervention. Methods: The PDA was individually programmed with the nutritional requirements of the participant. With 25 minutes of personalized instruction, the participant was able to enter his meals into the PDA using BalanceLog® software. Nutritional counseling was provided based on dietary sodium intake reports generated by BalanceLog®. Results: At initiation of the study the participant required 4 HD treatments per week. The participant entered 342 meals over 16 weeks (≥3 meals per day). BalanceLog® revealed that the participant consumed restaurant/fast food on a regular basis, and consumed significant amounts of corned beef as well as canned foods high in sodium. The study dietitian worked with the participant and his wife to identify food alternatives lower in sodium. Baseline sodium consumption was 4,692 mg, and decreased at a rate of 192 mg/week on average. After 11 weeks of intervention, interdialytic weight gains were reduced sufficiently to permit the participant to reduce HD treatments from 4 to 3 per week. Because of a low serum albumin at baseline (2.9 g/dL) the study dietitian encouraged the participant to increase his intake of high quality protein. Serum albumin level at 16 weeks was unchanged (2.9 g/dL). Because of intense pruritis and a high baseline serum phosphorus (6.5 mg/dL) BalanceLog® electronic logs were reviewed to identify sources of dietary phosphorus and counsel the participant regarding food alternatives. At 16 weeks the participant's serum phosphorus fell to 5.5 mg/dL. Conclusions: Self-monitoring rates were excellent. In a HD patient who was willing to self-monitor his dietary intake, BalanceLog® allowed the dietitian to target problematic foods and provide counseling that appeared to be effective in reducing sodium intake, reducing interdialytic weight gain, and alleviating hyperphosphatemia and hyperkalemia. Additional research is needed to evaluate the efficacy of the intervention. © 2008 Sevick et al, publisher and licensee Dove Medical Press Ltd

“What if There's Something Wrong with Her?”‐How Biomedical Technologies Contribute to Epistemic Injustice in Healthcare

While there is a steadily growing literature on epistemic injustice in healthcare, there are few discussions of the role that biomedical technologies play in harming patients in their capacity as knowers. Through an analysis of newborn and pediatric genetic and genomic sequencing technologies (GSTs), I argue that biomedical technologies can lead to epistemic injustice through two primary pathways: epistemic capture and value partitioning. I close by discussing the larger ethical and political context of critical analyses of GSTs and their broader implications for just and equitable healthcare delivery

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Photometry of Particles Ejected From Active Asteroid (101955) Bennu

AbstractNear‐Earth asteroid (101955) Bennu is an active asteroid experiencing mass loss in the form of ejection events emitting up to hundreds of millimeter‐ to centimeter‐scale particles. The close proximity of the Origins, Spectral Interpretations, Resource Identification, and Security–Regolith Explorer spacecraft enabled monitoring of particles for a 10‐month period encompassing Bennu's perihelion and aphelion. We found 18 multiparticle ejection events, with masses ranging from near zero to hundreds of grams (or thousands with uncertainties) and translational kinetic energies ranging from near zero to tens of millijoules (or hundreds with uncertainties). We estimate that Bennu ejects ~104 g per orbit. The largest event took place on 6 January 2019 and consisted of ~200 particles. The observed mass and translational kinetic energy of the event were between 459 and 528 g and 62 and 77 mJ, respectively. Hundreds of particles not associated with the multiparticle ejections were also observed. Photometry of the best‐observed particles, measured at phase angles between ~70° and 120°, was used to derive a linear phase coefficient of 0.013 ± 0.005 magnitudes per degree of phase angle. Ground‐based data back to 1999 show no evidence of past activity for Bennu; however, the currently observed activity is orders of magnitude lower than observed at other active asteroids and too low be observed remotely. There appears to be a gentle decrease in activity with distance from the Sun, suggestive of ejection processes such as meteoroid impacts and thermal fracturing, although observational bias may be a factor

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

OSIRIS-REx Encounters Bennu: Initial Assessment from the Approach Phase

The OSIRIS-REx spacecraft launched on September 8, 2016, on a seven-year journey to return samples from asteroid (101955) Bennu. This presentation summarizes the scientific results from the Approach and Preliminary Survey phases. Bennu observations are set to begin on August 17, 2018,when the asteroid is bright enough for detection by the PolyCam. PolyCam and MapCam collect data to survey the asteroid environment for any hazards and characterize the asteroid point-source photometric properties. Resolved images acquired during final approach, starting in late October 2018, allow the creation of a shape model using stereophotoclinometry (SPC), needed by both the navigation team and science planners. The OVIRS and OTES spectrometers characterize the point- source spectral properties over a full rotation period, providing a first look at any features and thermophysical properties. TAGSAM is released from the launch container and deployed into the sampling configuration then returned to the stow position.Preliminary Survey follows the Approach Phase in early December 2018. This phase consists of a series of hyperbolic trajectories that cross over the North and South poles and the equator of Bennu at a close-approach distance of 7 km. Images from these Preliminary Survey passes provide data to complete the 75-cm resolution SPC global shape model and solve for the rotation state. Once the shape model is complete, the asteroid coordinate system is defined for co-registration of all data products. These higher-resolution images also constrain the photometric properties and allow for an initial assessment of the geology. In Preliminary Survey the team also obtains the first OLA data, providing a measure of the surface topography. OVIRS and OTES collect data as "ride-along" instruments, with the spacecraft pointing driven by imaging constraints. These data provide a first look at the spectral variation across the surface of Bennu. Radio science measurements, combined with altimetry and imagery, determine Bennu's mass, a prerequisite to placing the spacecraft into orbit in late December 2018. Together, data from the Approach and Preliminary Survey phases set the stage for the extensive mapping planned for 2019. These dates are the baseline plan. Any contingency or unexpected discovery may change this mission profile

Working Inside for Smoking Elimination (Project W.I.S.E.) study design and rationale to prevent return to smoking after release from a smoke free prison

<p>Abstract</p> <p>Background</p> <p>Incarcerated individuals suffer disproportionately from the health effects of tobacco smoking due to the high smoking prevalence in this population. In addition there is an over-representation of ethnic and racial minorities, impoverished individuals, and those with mental health and drug addictions in prisons. Increasingly, prisons across the U.S. are becoming smoke free. However, relapse to smoking is common upon release from prison, approaching 90% within a few weeks. No evidence based treatments currently exist to assist individuals to remain abstinent after a period of prolonged, forced abstinence.</p> <p>Methods/Design</p> <p>This paper describes the design and rationale of a randomized clinical trial to enhance smoking abstinence rates among individuals following release from a tobacco free prison. The intervention is six weekly sessions of motivational interviewing and cognitive behavioral therapy initiated approximately six weeks prior to release from prison. The control group views six time matched videos weekly starting about six weeks prior to release. Assessments take place in-person 3 weeks after release and then for non-smokers every 3 months up to 12 months. Smoking status is confirmed by urine cotinine.</p> <p>Discussion</p> <p>Effective interventions are greatly needed to assist these individuals to remain smoke free and reduce health disparities among this socially and economically challenged group.</p> <p>Trial Registration</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=01122589">NCT01122589</a></p

Inner/Outer Nuclear Membrane Fusion in Nuclear Pore Assembly: Biochemical Demonstration and Molecular Analysis

The nuclear pore complex (NPC) is characterized by a long-lived membrane-lined channel connecting the inner and outer nuclear membranes. This stabilized membrane channel, within which the nuclear pore is built, has little evolutionary precedent. In this report we demonstrate and map the inner/outer nuclear membrane fusion in NPC assembly