Integrated Science Investigation of the Sun (ISIS): Design of the Energetic Particle Investigation

The Integrated Science Investigation of the Sun (ISIS) is a complete science investigation on the Solar Probe Plus (SPP) mission, which flies to within nine solar radii of the Sun's surface. ISIS comprises a two-instrument suite to measure energetic particles over a very broad energy range, as well as coordinated management, science operations, data processing, and scientific analysis. Together, ISIS observations allow us to explore the mechanisms of energetic particles dynamics, including their: (1) Origins-defining the seed populations and physical conditions necessary for energetic particle acceleration; (2) Acceleration-determining the roles of shocks, reconnection, waves, and turbulence in accelerating energetic particles; and (3) Transport-revealing how energetic particles propagate from the corona out into the heliosphere. The two ISIS Energetic Particle Instruments measure lower (EPI-Lo) and higher (EPI-Hi) energy particles. EPI-Lo measures ions and ion composition from approx. 20 keV/nucleon-15 MeV total energy and electrons from approx.25-1000 keV. EPI-Hi measures ions from approx. 1-200 MeV/nucleon and electrons from approx. 0.5-6 MeV. EPI-Lo comprises 80 tiny apertures with fields-of-view (FOVs) that sample over nearly a complete hemisphere, while EPI-Hi combines three telescopes that together provide five large-FOV apertures. ISIS observes continuously inside of 0.25 AU with a high data collection rate and burst data (EPI-Lo) coordinated with the rest of the SPP payload; outside of 0.25 AU, ISIS runs in low-rate science mode whenever feasible to capture as complete a record as possible of the solar energetic particle environment and provide calibration and continuity for measurements closer in to the Sun. The ISIS Science Operations Center plans and executes commanding, receives and analyzes all ISIS data, and coordinates science observations and analyses with the rest of the SPP science investigations. Together, ISIS' unique observations on SPP will enable the discovery, untangling, and understanding of the important physical processes that govern energetic particles in the innermost regions of our heliosphere, for the first time. This paper summarizes the ISIS investigation at the time of the SPP mission Preliminary Design Review in January 2014

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Overdiagnosis and overtreatment of breast cancer: Is overdiagnosis an issue for radiologists?

Overdiagnosis is diagnosis of cancers that would not present within the life of the patient and is one of the downsides of screening. This applies to low-grade ductal carcinoma in situ and some small grade 1 invasive cancers. Radiologists are responsible for cancer diagnosis, but at the time of diagnosis they cannot determine whether a particular low-grade diagnosis is one to which the definition of overdiagnosis applies. Overdiagnosis is likely to be driven by technological developments, including digital mammography, computer-aided detection and improved biopsy techniques. It is also driven by the patient's fear that cancer will be missed and the doctor's fear of litigation. It is therefore an issue of importance for radiologists, presenting them with difficult fine-tuned decisions in every assessment clinic that are ultimately counted later by those who evaluate their screening

Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1

Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse. Utilizing single-cell RNA-Seq, ChiP-Seq, ATAC-Seq, RNA-Seq, RPPA, and mass cytometry (CyTOF) analyses, present pre-clinical studies elucidate gene-expression correlates of MI efficacy in AML cells harboring MLL1-r or mtNPM1. Notably, MI-mediated genome-wide, concordant, log2 fold-perturbations in ATAC-Seq and RNA-Seq peaks were observed at the loci of MLL-FP target genes, with upregulation of mRNAs associated with AML differentiation. MI treatment also reduced the number of AML cells expressing the stem/progenitor cell signature. A protein domain-focused CRISPR-Cas9 screen in MLL1-r AML cells identified targetable co-dependencies with MI treatment, including BRD4, EP300, MOZ and KDM1A. Consistent with this, in vitro co-treatment with MI and BET, MOZ, LSD1 or CBP/p300 inhibitor induced synergistic loss of viability of AML cells with MLL1-r or mtNPM1. Co-treatment with MI and BET or CBP/p300 inhibitor also exerted significantly superior in vivo efficacy in xenograft models of AML with MLL1-r. These findings highlight novel, MI-based combinations that could prevent escape of AML stem/progenitor cells following MI monotherapy, which is responsible for therapy-refractory AML relapse

Diamond field-effect transistors with V2O5-induced transfer doping: scaling to 50-nm gate length

We report on the fabrication and measurement of hydrogen-terminated diamond field-effect transistors (FETs) incorporating V2O5 as a surface acceptor material to induce transfer doping. Comparing a range of gate lengths down to 50 nm, we observe inversely scaling peak output current and transconductance. Devices exhibited a peak drain current of ~700 mA/mm and a peak transconductance of ~150 mS/mm, some of the highest reported thus far for a diamond metal semiconductor FET (MESFET). Reduced sheet resistance of the diamond surface after V2O5 deposition was verified by four probe measurement. These results show great potential for improvement of diamond FET devices through scaling of critical dimensions and adoption of robust transition metal oxides such as V2O5

Towards a Metric for the Assessment of Safety Critical Control Systems

There is a need for better integration of the fault tolerant and the control designs for safety critical systems such as aircraft. The dependability of current designs is assessed primarily with measures of the interconnection of fault tolerant components: the reliability function and the mean time to failure. These measures do not directly take into account the interaction of the fault tolerant components with the dynamics of the aircraft. In this paper, a first step to better integrate these designs is made. It is based on the observation that unstable systems are intrinsically unreliable and that a necessary condition for reliability is the existence of a stabilizing control law that depends on the interconnection of the working fault tolerant components. Since operation of a fault tolerant interconnection of digital computers in a harsh environment can result in transient errors, a methodology to analyze the mean square stability of the fault tolerant closed-loop system is presented. A definition for mean square stabilizability is then used to introduce the new dynamical system reliability concept. An example illustrates the effect on mean square stability of several fault tolerant design choices and illustrates possible dynamical system reliability plot

Computer-aided detection system for clustered microcalcifications: comparison of performance on full-field digital mammograms and digitized screen-film mammograms

We have developed a computer-aided detection (CAD) system to detect clustered microcalcifications automatically on full-field digital mammograms (FFDMs) and a CAD system for screen-film mammograms (SFMs). The two systems used the same computer vision algorithms but their false positive (FP) classifiers were trained separately with sample images of each modality. In this study, we compared the performance of the CAD systems for detection of clustered microcalcifications on pairs of FFDM and SFM obtained from the same patient. For case-based performance evaluation, the FFDM CAD system achieved detection sensitivities of 70%, 80% and 90% at an average FP cluster rate of 0.07, 0.16 and 0.63 per image, compared with an average FP cluster rate of 0.15, 0.38 and 2.02 per image for the SFM CAD system. The difference was statistically significant with the alternative free-response receiver operating characteristic (AFROC) analysis. When evaluated on data sets negative for microcalcification clusters, the average FP cluster rates of the FFDM CAD system were 0.04, 0.11 and 0.33 per image at detection sensitivity level of 70%, 80% and 90% compared with an average FP cluster rate of 0.08, 0.14 and 0.50 per image for the SFM CAD system. When evaluated for malignant cases only, the difference of the performance of the two CAD systems was not statistically significant with AFROC analysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58099/2/pmb7_4_008.pd

Phase Stability of Hexagonal/cubic Boron Nitride Nanocomposites

Boron nitride (BN) is an exceptional material and among its polymorphs, two-dimensional (2D) hexagonal and three-dimensional (3D) cubic BN (h-BN and c-BN) phases are most common. The phase stability regimes of these BN phases are still under debate and phase transformations of h-BN/c-BN remain a topic of interest. Here, we investigate the phase stability of 2D/3D h-BN/c-BN nanocomposites and show that the co-existence of two phases can lead to strong non-linear optical properties and low thermal conductivity at room temperature. Furthermore, spark-plasma sintering of the nanocomposite shows complete phase transformation to 2D h-BN with improved crystalline quality, where 3D c-BN grain sizes governs the nucleation and growth kinetics. Our demonstration might be insightful in phase engineering of BN polymorphs based nanocomposites with desirable properties for optoelectronics and thermal energy management applications.Comment: 29 pages, 5 figure

Structural and electronic properties of 2D (graphene, hBN)/H-terminated diamond (100) heterostructures

We report a first-principles study of the structural and electronic properties of two-dimensional (2D) layer/hydrogen-terminated diamond (100) heterostructures. Both the 2D layers exhibit weak van-der-Waals (vdW) interactions and develop rippled configurations with the H-diamond (100) substrate to compensate for the induced strain. The adhesion energy of the hexagonal boron nitride (hBN) layer is slightly higher, and it exhibits a higher degree of rippling compared to the graphene layer. A charge transfer analysis reveals a small amount of charge transfer from the H-diamond (100) surface to the 2D layers, and most of the transferred charge was found to be confined within the vdW gap. In the graphene/H-diamond (100) heterostructure, the semi-metallic characteristic of the graphene layer is preserved. On the other hand, the hBN/H-diamond (100) heterostructure shows semiconducting characteristics with an indirect bandgap of 3.55 eV, where the hBN layer forms a Type-II band alignment with the H-diamond (100) surface. The resultant conduction band offset and valence band offset are 0.10 eV and 1.38 eV, respectively. A thin layer of hBN offers a defect-free interface with the H-diamond (100) surface and provides a layer-dependent tunability of electronic properties and band alignment for surface-doped diamond field effect transistors