ALBERT

Description: High performance improvement (+88% in peak G m and 〉30% in linear and saturation region drain currents) was observed for N-MOSFETs with Oxygen-Inserted (OI) Si channel. From TCAD analysis of the C-V measurement data, the improvement was confirmed to be due to electron mobility enhancement of the OI Si channel (+75% at N inv  = 4.0 × 10 12  cm −2 and +25% at N inv  = 8.0 × 10 12  cm −2 ). Raman and high-resolution Rutherford backscattering measurements confirmed that negligible strain is induced in the OI Si layer, and hence, it cannot be used to explain the origin of mobility improvement. Poisson-Schrödinger based quantum mechanical simulation was performed, taking into account phonon, surface roughness and Coulomb scatterings. The OI layer was modeled as a “quasi barrier” region with reference to the Si conduction band edge to confine inversion electrons. Simulation explains the measured electron mobility enhancement as the confinement effect of inversion electrons while the formation of an super-steep retrograde well doping profile in the channel (as a result of dopant diffusion blocking effect accompanied by introduction of the OI layer) also contributes 50%–60% of the mobility improvement.

Description: Though climate models exhibit broadly similar agreement on key long-term trends, they have significant temporal and spatial differences due to inter-model variability. Such variability should be considered when using climate models to project the future marine Arctic. Here we present multiple scenarios of 21 st -century Arctic marine access as driven by sea ice output from 10 CMIP5 models known to represent well the historical trend and climatology of Arctic sea ice. Optimal vessel transits from North America and Europe to the Bering Strait are estimated for two periods representing early-century (2011–2035) and mid-century (2036–2060) conditions under two forcing scenarios (RCP 4.5/8.5), assuming Polar Class 6 and open-water vessels with medium and no ice-breaking capability, respectively. Results illustrate that projected shipping viability of the Northern Sea Route (NSR) and Northwest Passage (NWP) depends critically on model choice. The eastern Arctic will remain the most reliably accessible marine space for trans-Arctic shipping by mid-century, while outcomes for the NWP are particularly model-dependent. Omitting three models (GFDL-CM3, MIROC-ESM-CHEM, MPI-ESM-MR), our results would indicate minimal NWP potential even for routes from North America. Furthermore, the relative importance of the NSR will diminish over time as the number of viable central Arctic routes increases gradually toward mid-century. Compared to vessel class, climate forcing plays a minor role. These findings reveal the importance of model choice in devising projections for strategic planning by governments, environmental agencies, and the global maritime industry.

Description: Although disturbances such as fire and native insects can contribute to natural dynamics of forest health, exceptional droughts, directly and in combination with other disturbance factors, are pushing some temperate forests beyond thresholds of sustainability. Interactions from increasing temperatures, drought, native insects and pathogens, and uncharacteristically severe wildfire are resulting in forest mortality beyond the levels of 20th-century experience. Additional anthropogenic stressors, such as atmospheric pollution and invasive species, further weaken trees in some regions. Although continuing climate change will likely drive many areas of temperate forest toward large-scale transformations, management actions can help ease transitions and minimize losses of socially valued ecosystem services.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Millar, Constance I -- Stephenson, Nathan L -- New York, N.Y. -- Science. 2015 Aug 21;349(6250):823-6. doi: 10.1126/science.aaa9933.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉U.S. Department of Agriculture Forest Service, Pacific Southwest Research Station, Albany, CA 94710, USA. cmillar@fs.fed.us. ; U.S. Geological Survey, Western Ecological Research Center, Three Rivers, CA 93271, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26293954" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karkas, Markus D -- Matsuura, Bryan S -- Stephenson, Corey R J -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1285-6. doi: 10.1126/science.aad0193.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. ; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. crjsteph@umich.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383937" target="_blank"〉PubMed〈/a〉

Description: Murray's law states that the volumetric flow rate is proportional to the cube of the radius in a cylindrical channel optimized to require the minimum work to drive and maintain the fluid. However, application of this principle to the biomimetic design of micro/nano fabricated networks requires optimization of channels with arbitrary cross-sectional shape (not just circular) and smaller than is valid for Murray's original assumptions. We present a generalized law for symmetric branching that (a) is valid for any cross-sectional shape, providing that the shape is constant through the network; (b) is valid for slip flow and plug flow occurring at very small scales; and (c) is valid for networks with a constant depth, which is often a requirement for lab-on-a-chip fabrication procedures. By considering limits of the generalized law, we show that the optimum daughter-parent area ratio Γ, for symmetric branching into N daughter channels of any constant cross-sectional shape, is Γ = N − 2 / 3 for large-scale channels, and Γ = N − 4 / 5 for channels with a characteristic length scale much smaller than the slip length. Our analytical results are verified by comparison with a numerical optimization of a two-level network model based on flow rate data obtained from a variety of sources, including Navier-Stokes slip calculations, kinetic theory data, and stochastic particle simulations.

Description: Invasive surgery brings with it a unique set of post-surgical risks that are directly dependent on various factors including the specific surgical approach used, pre-existing comorbidities and features such as gender and age. Pulmonary thromboembolism is one of the most feared complications following surgery, and diagnosis and treatment of this entity is a challenging task for the clinician. Here we describe a case of massive pulmonary thromboembolism and associated coronary artery thromboemboli status post spinal fusion surgery in a 68 year-old man with an undetected patent foramen ovale (PFO). Although the decedent was managed clinically with proper deep venous thrombosis prophylaxis protocols and physical rehabilitation, he went into cardiorespiratory arrest after experiencing acute oxygen desaturation and newly detected right bundle branch block. PFO can be incidentally found in 25% of the adult population. Several clinical syndromes including stroke, migraine headaches and obstructive sleep apnea have been associated in patients with PFO, the last two from which the decedent suffered. The pathology of this unique case of massive pulmonary thromboembolism resulting in coronary artery thromboemboli in the setting of an undetected PFO is discussed. The discovery of PFO in patients prior to surgery, if detected early, may improve post-surgical outcomes. Figure 1. Massive pulmonary artery thromboembolism in situ, gross examination. Figure 1. Massive pulmonary artery thromboembolism in situ, gross examination. Figure 2. Histology, hematoxylin and eosin. A. Pulmonary thromboembolus at the bifurcation of the pulmonary arteries and pulmonary trunk. B. Hemorrhagic infarct and thromboemboli in varying stages of organization, right lower lobe, lung. C. Cross section of the proximal left anterior descending coronary artery with thromboembolus. D. Cross section of the posterior descending coronary artery with thromboembolus. Figure 2. Histology, hematoxylin and eosin. A. Pulmonary thromboembolus at the bifurcation of the pulmonary arteries and pulmonary trunk. B. Hemorrhagic infarct and thromboemboli in varying stages of organization, right lower lobe, lung. C. Cross section of the proximal left anterior descending coronary artery with thromboembolus. D. Cross section of the posterior descending coronary artery with thromboembolus. Figure 3. Patent foramen ovale, gross examination. Figure 3. Patent foramen ovale, gross examination. Disclosures No relevant conflicts of interest to declare.

Description: The Multiple Myeloma Research Foundation (MMRF) CoMMpass trial (NCT145429) is a longitudinal study of 1000 patients with newly-diagnosed multiple myeloma from clinical sites in the United States, Canada, Spain, and Italy. Each patient receives a treatment regimen containing a proteasome inhibitor, immunumodulatory agent, or both. Clinical parameters are collected at study enrollment and every three months through the five-year observation period. To identify molecular determinants of clinical outcome each baseline and progression tumor specimen is characterized using Whole Genome Sequencing, Exome Sequencing, and RNA sequencing. This will be the first public presentation of the interim analysis seven cohort with 760 enrolled patients of whom 565 are molecularly characterized. This cohort of patients includes 14 patients with baseline and secondary samples along with 7 patients with characterized tumor samples from the bone marrow and peripheral blood. Although the median follow-up time for the cohort is only 260 days the patients on proteasome and IMiD based combinations are currently showing a PFS and OS benefit compared to those receiving combinations with each agent alone. From the raw mutational analysis we identified 24 significant genes that are recurrently mutated and the mutated allele is detectably expressed in all but one, DNAH5. Suggesting these mutations are likely contributing to myelomagenesis through an unconventional mechanism. Interestingly, DIS3 mutations are independent of KRAS, NRAS, and BRAF indicating a potential mechanistic link while PRKD2 mutations are associated with t(4;14). To identify events driving the initiation of myeloma we performed a detailed clonality analysis using a bayesian clustering method that corrects for copy number abnormalities and tumor purity to assign mutations into distinct clonal branches versus the initiating trunk mutations. On average 63.8% of mutations are trunk mutations and in 86.7% of patients at least one trunk mutation is associated with somatic hypermutation of an immunoglobulin gene as expected in a late stage B-cell malignancy. This identified many expressed trunk mutations that did not come out in the classic significance analysis like ATM, EGR1, and CCND1. To identify molecular subtypes we performed unsupervised clustering using a consensus clustering approach on independent discovery and validation cohorts, which identified 12 distinct subtypes, using a combination of silhouette score and cumulative distribution of consensus scores. This analysis identified two distinct groups associated with t(4;14) with mutations in FGFR3 and DIS3 being exclusive to one subgroup. In addition, this analysis separates patients with cyclin D translocations into three different groups, with one group having the second lowest PFS proportion. Three patients without CCND1 or CCND3 translocations were found to have IgH translocations targeting CCND2. The MAF subgroup was associated with the lowest OS and PFS proportion, and the three MAF/MAFB translocation negative patients in the subgroup all had MAFA translocations. The remaining 6 subgroups are associated with hyperdiploid copy number profiles and harbor the majority of the IgH-MYC translocation events. Two of the hyperdiploid groups are associated with a low level of NFKB activation compared to the remaining four, one of these is defined by the highest proliferation index but paradoxically the other has the second worst OS proportion. Another group is enriched with FAM46C and NRAS mutations. The genomic profiles of the paired tumors isolated from the peripheral blood and bone marrow are highly similar indicating these are not genetically distinct tumor compartments, at least in this subset of seven patients. Applying our bayesian clustering method to the serial samples resolved additional clonal clusters as mutations with similar cancer cell fractions at diagnosis clearly diverged at later timepoints. These analyses have identified tumor initiating mutations and new subtypes of myeloma, which are associated with distinct molecular events and clinical outcomes. Disclosures Jagannath: Novartis: Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Merck: Honoraria; Janssen: Honoraria. Siegel:Celgene Corporation: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Novartis: Speakers Bureau; Merck: Speakers Bureau. Vij:Takeda, Onyx: Research Funding; Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy. Zimmerman:Amgen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Millennium: Honoraria, Speakers Bureau; Onyx: Honoraria. Niesvizky:Celgene: Consultancy, Speakers Bureau. Rifkin:Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy, Membership on an entity's Board of Directors or advisory committees. Lonial:Millennium: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.