777 research outputs found
Failure Time of Loaded Wooden Beams During Fire
A model is presented for predicting the failure time of loaded wooden beams of rectangular cross-section exposed to elevated temperatures or to fire. Failure times calculated by the model were compared to failure times measured in this study using 19.05 mm x 19.05 mm simply supported southern pine beams, and to failure times measured by the National Bureau of Standards during the fire of a full scale room. Reasonable agreements were found between the calculated failure times and the data.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69007/2/10.1177_073490418300100407.pd
A functional role for the cancer disparity-linked genes, CRYβB2 and CRYβB2P1, in the promotion of breast cancer
Background: In the USA, the breast cancer mortality rate is 41% higher for African-American women than non-Hispanic White women. While numerous gene expression studies have classified biological features that vary by race and may contribute to poorer outcomes, few studies have experimentally tested these associations. CRYβB2 gene expression has drawn particular interest because of its association with overall survival and African-American ethnicity in multiple cancers. Several reports indicate that overexpression of the CRYβB2 pseudogene, CRYβB2P1, and not CRYβB2 is linked with race and poor outcome. It remains unclear whether either or both genes are linked to breast cancer outcomes. This study investigates CRYβB2 and CRYβB2P1 expression in human breast cancers and breast cancer cell line models, with the goal of elucidating the mechanistic contribution of CRYβB2 and CRYβB2P1 to racial disparities. Methods: Custom scripts for CRYβB2 or CRYβB2P1 were generated and used to identify reads that uniquely aligned to either gene. Gene expression according to race and tumor subtype were assessed using all available TCGA breast cancer RNA sequencing alignment samples (n = 1221). In addition, triple-negative breast cancer models engineered to have each gene overexpressed or knocked out were developed and evaluated by in vitro, biochemical, and in vivo assays to identify biological functions. Results: We provide evidence that CRYβB2P1 is expressed at higher levels in breast tumors compared to CRYβB2, but only CRYβB2P1 is significantly increased in African-American tumors relative to White American tumors. We show that independent of CRYβB2, CRYβB2P1 enhances tumorigenesis in vivo via promoting cell proliferation. Our data also reveal that CRYβB2P1 may function as a non-coding RNA to regulate CRYβB2 expression. A key observation is that the combined overexpression of both genes was found to suppress cell growth. CRYβB2 overexpression in triple-negative breast cancers increases invasive cellular behaviors, tumor growth, IL6 production, immune cell chemoattraction, and the expression of metastasis-associated genes. These data underscore that both CRYβB2 and CRYβB2P1 promote tumor growth, but their mechanisms for tumor promotion are likely distinct. Conclusions: Our findings provide novel data emphasizing the need to distinguish and study the biological effects of both CRYβB2 and CRYβB2P1 as both genes independently promote tumor progression. Our data demonstrate novel molecular mechanisms of two understudied, disparity-linked molecules
Universality classes in nonequilibrium lattice systems
This work is designed to overview our present knowledge about universality
classes occurring in nonequilibrium systems defined on regular lattices. In the
first section I summarize the most important critical exponents, relations and
the field theoretical formalism used in the text. In the second section I
briefly address the question of scaling behavior at first order phase
transitions. In section three I review dynamical extensions of basic static
classes, show the effect of mixing dynamics and the percolation behavior. The
main body of this work is given in section four where genuine, dynamical
universality classes specific to nonequilibrium systems are introduced. In
section five I continue overviewing such nonequilibrium classes but in coupled,
multi-component systems. Most of the known nonequilibrium transition classes
are explored in low dimensions between active and absorbing states of
reaction-diffusion type of systems. However by mapping they can be related to
universal behavior of interface growth models, which I overview in section six.
Finally in section seven I summarize families of absorbing state system
classes, mean-field classes and give an outlook for further directions of
research.Comment: Updated comprehensive review, 62 pages (two column), 29 figs
included. Scheduled for publication in Reviews of Modern Physics in April
200
Leveraging gene expression subgroups to classify DLBCL patients and select for clinical benefit from a novel agent
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, commonly described by cell-of-origin (COO) molecular subtypes. We sought to identify novel patient subgroups through an unsupervised analysis of a large public dataset of gene expression profiles from newly diagnosed de novo DLBCL patients, yielding 2 biologically distinct subgroups characterized by differences in the tumor microenvironment. Pathway analysis and immune deconvolution algorithms identified higher B-cell content and a strong proliferative signal in subgroup A and enriched T-cell, macrophage, and immune/inflammatory signals in subgroup B, reflecting similar biology to published DLBCL stratification research. A gene expression classifier, featuring 26 gene expression scores, was derived from the public dataset to discriminate subgroup A (classifier-negative, immune-low) and subgroup B (classifier-positive, immune-high) patients. Subsequent application to an independent series of diagnostic biopsies replicated the subgroups, with immune cell composition confirmed via immunohistochemistry. Avadomide, a CRL4CRBN E3 ubiquitin ligase modulator, demonstrated clinical activity in relapsed/refractory DLBCL patients, independent of COO subtypes. Given the immunomodulatory activity of avadomide and the need for a patient-selection strategy, we applied the gene expression classifier to pretreatment biopsies from relapsed/refractory DLBCL patients receiving avadomide (NCT01421524). Classifier-positive patients exhibited an enrichment in response rate and progression-free survival of 44% and 6.2 months vs 19% and 1.6 months for classifier-negative patients (hazard ratio, 0.49; 95% confidence interval, 0.280-0.86; P = .0096). The classifier was not prognostic for rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone or salvage immunochemotherapy. The classifier described here discriminates DLBCL tumors based on tumor and nontumor composition and has potential utility to enrich for clinical response to immunomodulatory agents, including avadomide
Cytochrome P450 168A1 from pseudomonas aeruginosa is involved in the hydroxylation of biologically relevant fatty acids
The cytochrome P450 CYP168A1 from Pseudomonas aeruginosa was cloned and expressed in Escherichia coli followed by purification and characterization of function. CYP168A1 is a fatty acid hydroxylase that hydroxylates saturated fatty acids, including myristic (0.30 min-1), palmitic (1.61 min-1) and stearic acids (1.24 min-1), at both the ω-1- and ω-2-positions. However, CYP168A1 only hydroxylates unsaturated fatty acids, including palmitoleic (0.38 min-1), oleic (1.28 min-1) and linoleic acids (0.35 min-1), at the ω-1-position. CYP168A1 exhibited a catalytic preference for palmitic, oleic and stearic acids as substrates in keeping with the phosphatidylcholine-rich environment deep in the lung that is colonized by P. aeruginosa
Solar Intranetwork Magnetic Elements: bipolar flux appearance
The current study aims to quantify characteristic features of bipolar flux
appearance of solar intranetwork (IN) magnetic elements. To attack such a
problem, we use the Narrow-band Filter Imager (NFI) magnetograms from the Solar
Optical Telescope (SOT) on board \emph{Hinode}; these data are from quiet and
an enhanced network areas. Cluster emergence of mixed polarities and IN
ephemeral regions (ERs) are the most conspicuous forms of bipolar flux
appearance within the network. Each of the clusters is characterized by a few
well-developed ERs that are partially or fully co-aligned in magnetic axis
orientation. On average, the sampled IN ERs have total maximum unsigned flux of
several 10^{17} Mx, separation of 3-4 arcsec, and a lifetime of 10-15 minutes.
The smallest IN ERs have a maximum unsigned flux of several 10^{16} Mx,
separations less than 1 arcsec, and lifetimes as short as 5 minutes. Most IN
ERs exhibit a rotation of their magnetic axis of more than 10 degrees during
flux emergence. Peculiar flux appearance, e.g., bipole shrinkage followed by
growth or the reverse, is not unusual. A few examples show repeated
shrinkage-growth or growth-shrinkage, like magnetic floats in the dynamic
photosphere. The observed bipolar behavior seems to carry rich information on
magneto-convection in the sub-photospheric layer.Comment: 26 pages, 14 figure
International Consortium for Health Outcomes Measurement (ICHOM): Standardized Patient-Centered Outcomes Measurement Set for Heart Failure Patients
Whereas multiple national, international, and trial registries for heart failure have been created, international standards for clinical assessment and outcome measurement do not currently exist. The working group's objective was to facilitate international comparison in heart failure care, using standardized parameters and meaningful patient-centered outcomes for research and quality of care assessments. The International Consortium for Health Outcomes Measurement recruited an international working group of clinical heart failure experts, researchers, and patient representatives to define a standard set of outcomes and risk-adjustment variables. This was designed to document, compare, and ultimately improve patient care outcomes in the heart failure population, with a focus on global feasibility and relevance. The working group employed a Delphi process, patient focus groups, online patient surveys, and multiple systematic publications searches. The process occurred over 10 months, employing 7 international teleconferences. A 17-item set has been established, addressing selected functional, psychosocial, burden of care, and survival outcome domains. These measures were designed to include all patients with heart failure, whether entered at first presentation or subsequent decompensation, excluding cardiogenic shock. Sources include clinician report, administrative data, and validated patient-reported outcome measurement tools: the Kansas City Cardiomyopathy Questionnaire; the Patient Health Questionnaire-2; and the Patient-Reported Outcomes Measurement Information System. Recommended data included those to support risk adjustment and benchmarking across providers and regions. The International Consortium for Health Outcomes Measurement developed a dataset designed to capture, compare, and improve care for heart failure, with feasibility and relevance for patients and clinicians worldwide
Fractal Reconnection in Solar and Stellar Environments
Recent space based observations of the Sun revealed that magnetic
reconnection is ubiquitous in the solar atmosphere, ranging from small scale
reconnection (observed as nanoflares) to large scale one (observed as long
duration flares or giant arcades). Often the magnetic reconnection events are
associated with mass ejections or jets, which seem to be closely related to
multiple plasmoid ejections from fractal current sheet. The bursty radio and
hard X-ray emissions from flares also suggest the fractal reconnection and
associated particle acceleration. We shall discuss recent observations and
theories related to the plasmoid-induced-reconnection and the fractal
reconnection in solar flares, and their implication to reconnection physics and
particle acceleration. Recent findings of many superflares on solar type stars
that has extended the applicability of the fractal reconnection model of solar
flares to much a wider parameter space suitable for stellar flares are also
discussed.Comment: Invited chapter to appear in "Magnetic Reconnection: Concepts and
Applications", Springer-Verlag, W. D. Gonzalez and E. N. Parker, eds. (2016),
33 pages, 18 figure
Current status of turbulent dynamo theory: From large-scale to small-scale dynamos
Several recent advances in turbulent dynamo theory are reviewed. High
resolution simulations of small-scale and large-scale dynamo action in periodic
domains are compared with each other and contrasted with similar results at low
magnetic Prandtl numbers. It is argued that all the different cases show
similarities at intermediate length scales. On the other hand, in the presence
of helicity of the turbulence, power develops on large scales, which is not
present in non-helical small-scale turbulent dynamos. At small length scales,
differences occur in connection with the dissipation cutoff scales associated
with the respective value of the magnetic Prandtl number. These differences are
found to be independent of whether or not there is large-scale dynamo action.
However, large-scale dynamos in homogeneous systems are shown to suffer from
resistive slow-down even at intermediate length scales. The results from
simulations are connected to mean field theory and its applications. Recent
work on helicity fluxes to alleviate large-scale dynamo quenching, shear
dynamos, nonlocal effects and magnetic structures from strong density
stratification are highlighted. Several insights which arise from analytic
considerations of small-scale dynamos are discussed.Comment: 36 pages, 11 figures, Spa. Sci. Rev., submitted to the special issue
"Magnetism in the Universe" (ed. A. Balogh
- …