•Optimal UHPCC for protective structures against projectile penetration was prepared.•Triaxial compressive behavior of UHPCC with confining pressure up to 100MPa was tested.•Normalized peak axial ...strain increases linearly with the rising of confinement ratio.•UHPCC under triaxial compression obey Willam-Warnke and Power-law failure criteria.•Strength parameters of HJC constitutive model for HSC were confirmed and validated.
For the constructions of protective structures against potential projectile high-speed impact, the optimal ultra-high performance cement based composite (UHPCC) (straight steel fiber with the volumetric ratio of 2%, high-strength basalt aggregates with the size range of 5-10mm, the designed uniaxial compressive strength of∼100MPa) was prepared. By casting two batches of 50mm×100mm cylindrical UHPCC specimens with the uniaxial compressive strengths of 95MPa and 129MPa, the triaxial compressive behavior of UHPCC under high confining pressure (up to 100MPa) was experimentally studied. Based on the deviatoric stress-strain curves under various confining pressure, the failure criteria and toughness of UHPCC under triaxial compression were discussed. At last, the dominant strength parameters of Holmquist-Johnson-Cook constitutive model were confirmed based on the present and existing triaxial compression tests on high-strength concrete. The validity of which was verified based on eleven sets of projectile penetration or perforation tests on concrete-like targets with the uniaxial compressive strength ranged from 60MPa to 157MPa.
Large-scale genome-wide genetic profiling using markers of single nucleotide polymorphisms (SNPs) has offered the opportunities to investigate the possibility of using those biomarkers for predicting ...genetic risks. Because of the special data structure characterized with a high dimension, signal-to-noise ratio and correlations between genes, but with a relative small sample size, the data analysis needs special strategies. We propose a robust data reduction technique based on a hybrid between genetic algorithm and support vector machine. The major goal of this hybridization is to fully exploit their respective merits (e.g., robustness to the size of solution space and capability of handling a very large dimension of features) for identification of key SNP features for risk prediction. We have applied the approach to the Genetic Analysis Workshop 14 COGA data to predict affection status of a sib pair based on genome-wide SNP identical-by-decent (IBD) informatics. This application has demonstrated its potential to extract useful information from the massive SNP data.
NGC 4945 is one of the nearest (D ≈ 3.8 Mpc; 1″ ≈ 19 pc) starburst galaxies. To investigate the structure, dynamics, and composition of the dense nuclear gas of this galaxy, ALMA band 3 (λ ≈ 3−4 mm) ...observations were carried out with ≈2″ resolution. Three HCN and two HCO+ isotopologues, CS, C3H2, SiO, HCO, and CH3C2H were measured. Spectral line imaging demonstrates the presence of a rotating nuclear disk of projected size 10″ × 2″ reaching out to a galactocentric radius of r ≈ 100 pc with position angle PA = 45° ± 2°, inclination i = 75° ± 2° and an unresolved bright central core of size ≲2″. The continuum source, representing mostly free-free radiation from star forming regions, is more compact than the nuclear disk by a linear factor of two but shows the same position angle and is centered 0.′′39 ± 0.′′14 northeast of the nuclear accretion disk defined by H2O maser emission. Near the systemic velocity but outside the nuclear disk, both HCN J = 1 → 0 and CS J = 2 → 1 delineate molecular arms of length ≳15″ (≳285 pc) on opposite sides of the dynamical center. These are connected by a (deprojected) ≈ 0.6 kpc sized molecular bridge, likely a dense gaseous bar seen almost ends-on, shifting gas from the front and back side into the nuclear disk. Modeling this nuclear disk located farther inside (r ≲100 pc) with tilted rings provides a good fit by inferring a coplanar outflow reaching a characteristic deprojected velocity of ≈50 km s−1. All our molecular lines, with the notable exception of CH3 C2H, show significant absorption near the systemic velocity (≈571 km s−1), within the range ≈500–660 km s−1. Apparently, only molecular transitions with low critical H2 density (ncrit ≲ 104 cm−3) do not show absorption. The velocity field of the nuclear disk, derived from CH3 C2H, provides evidence for rigid rotation in the inner few arcseconds and a dynamical mass of Mtot = (2.1 ± 0.2) × 108 M⊙ inside a galactocentric radius of 2.′′45 (≈45 pc), with a significantly flattened rotation curve farther out. Velocity integrated line intensity maps with most pronounced absorption show molecular peak positions up to ≈1.′′5 (≈30 pc) southwest of the continuum peak, presumably due to absorption, which appears to be most severe slightly northeast of the nuclear maser disk. A nitrogen isotope ratio of 14N/15N ≈ 200–450 is estimated. This range of values is much higher then previously reported on a tentative basis. Therefore, because 15N is less abundant than expected, the question for strong 15N enrichment by massive star ejecta in starbursts still remains to be settled.
The characterization of a cell line (designated SR-91) from a patient with clinical and morphological diagnosis of acute lymphoblastic leukemia (CD3-, CD2+, CD7+, germline TCR genes) who relapsed ...early after allogeneic bone marrow transplantation, is reported. The line was established from blood cells obtained at diagnosis and placed in suspension culture with medium conditioned by 5637 cells. SR-91 cells are negative for lymphoid surface markers (CD3-, CD2-, CD7-) but positive for markers indicative of myeloid progenitor cells, such as CD33 and CD34. It is likely that the conditioned medium has induced myeloid differentiation from a lymphohematopoietic progenitor cell. After establishment, cells proliferated in response to GM-CSF stimulation but they are not factor-dependent and do not produce GM-CSF. No proliferative response to IL-1, IL-2, IL-3, IL-4, IL-6 or M-CSF was observed. Cells were completely resistant to anti-proliferative effects of tumor necrosis factor-alpha and interferon-alpha or -gamma, and showed no lysis after incubation with freshly isolated natural killer cells or IL-2-activated natural killer cells.
Cancer chemotherapeutic agents such as cisplatin exert their cytotoxic effect by inducing DNA damage and activating programmed cell death (apoptosis). The tumour-suppressor protein p53 is an ...important activator of apoptosis. Although p53-deficient cancer cells are less responsive to chemotherapy, their resistance is not complete, which suggests that other apoptotic pathways may exist. A p53-related gene, p73, which encodes several proteins as a result of alternative splicing, can also induce apoptosis. Here we show that the amount of p73 protein in the cell is increased by cisplatin. This induction of p73 is not seen in cells unable to carry out mismatch repair and in which the nuclear enzyme c-Abl tyrosine kinase is not activated by cisplatin. The half-life of p73 is prolonged by cisplatin and by co-expression with c-Abl tyrosine kinase; the apoptosis-inducing function of p73 is also enhanced by the c-Abl kinase. Mouse embryo fibroblasts deficient in mismatch repair or in c-Abl do not upregulate p73 and are more resistant to killing by cisplatin. Our results indicate that c-Abl and p73 are components of a mismatch-repair-dependent apoptosis pathway which contributes to cisplatin-induced cytotoxicity.
We demonstrate a novel form of thermally-assisted hysteresis in the transfer curves of monolayer MoS2 FETs, characterized by the appearance of a large gate-voltage window and distinct current levels ...that differ by a factor of ∼102. The hysteresis emerges for temperatures in excess of 400 K and, from studies in which the gate-voltage sweep parameters are varied, appears to be related to charge injection into the SiO2 gate dielectric. The thermally-assisted memory is strongly suppressed in equivalent measurements performed on bilayer transistors, suggesting that weak screening in the monolayer system plays a vital role in generating its strongly sensitive response to the charge-injection process. By exploiting the full features of the hysteretic transfer curves, programmable memory operation is demonstrated. The essential principles demonstrated here point the way to a new class of thermally assisted memories based on atomically thin two-dimensional semiconductors.
Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, ...genetic origin, and clinical management remain controversial.
Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes.
The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0–11.2).
The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.
•The adenocarcinoma component and squamous cell carcinoma component of adenosquamous carcinoma share a common clonal origin.•High incidence of trunk EGFR and TP53 mutation were noted in adenosqumous cell carcinoma, while the overall genomic profile of adenosqumous cell carcinoma is more similar to adenocarcinoma than squmous cell carcinoma.•EGFR-TKIs should be the standard first-line therapy for advanced stage adenosquamous carcinoma with EGFR mutation.
Abstract
Background
Test-negative design studies for evaluating influenza vaccine effectiveness (VE) enroll patients with acute respiratory infection. Enrollment typically occurs before influenza ...status is determined, resulting in over-enrollment of influenza-negative patients. With availability of rapid and accurate molecular clinical testing, influenza status could be ascertained before enrollment, thus improving study efficiency. We estimate potential biases in VE when using clinical testing.
Methods
We simulate data assuming 60% vaccinated, 25% of those vaccinated are influenza positive, and VE of 50%. We show the effect on VE in 5 scenarios.
Results
Vaccine effectiveness is affected only when clinical testing preferentially targets patients based on both vaccination and influenza status. Vaccine effectiveness is overestimated by 10% if nontesting occurs in 39% of vaccinated influenza-positive patients and 24% of others. VE is also overestimated by 10% if nontesting occurs in 8% of unvaccinated influenza-positive patients and 27% of others. Vaccine effectiveness is underestimated by 10% if nontesting occurs in 32% of unvaccinated influenza-negative patients and 18% of others.
Conclusions
Although differential clinical testing by vaccine receipt and influenza positivity may produce errors in estimated VE, bias in testing would have to be substantial and overall proportion of patients tested would have to be small to result in a meaningful difference in VE.
To improve study efficiency, clinical influenza testing may be used to estimate vaccine effectiveness, as long as the majority of acute respiratory infection patients are tested, and testing does not preferentially target patients based on both vaccination and influenza status.
Rocks are heterogeneous multiscale porous media: two rock samples with identical bulk properties can vary widely in microstructure. The advent of digital rock technology and modern 3‐D printing ...provides new opportunities to replicate rocks. However, the inherent trade‐off between imaging resolution and sample size limits the scales over which microstructure and macrostructure can be identified and related to each other. Here, we develop a multiscale digital rock construction strategy by combining X‐ray computed microtomography and focused‐ion beam (FIB)‐scanning electron microscope (SEM) images, and we apply the technique to a tight sandstone. The computed tomography (CT) scanning images characterize macroscale pore structures, while the FIB‐SEM images capture microscale pore textures. The FIB‐SEM images are then coupled to CT images via a template‐matching algorithm and superposition. Bulk properties, including porosity and pore and throat size distribution, can be recovered with this approach. Permeability prediction with a pore network model for the largest connected pore network are 3 orders and 1 order of magnitude greater than the bulk rock measured value using the CT‐only and the SEM‐CT coupled images, respectively.
Key Points
High‐resolution images are used to define templates of microscopic rock textures
Templates are used to locally refine the details of macroscopic structures in lower‐resolution images
Multiscale reconstruction recovers the bulk density and pore and throat size distribution of natural tight sandstone samples
We recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 ...cell cycle arrest.
We now validate a clinical test for urinary TIMP-2·IGFBP7 at a high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse population of critically ill patients.
We conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary TIMP-2·IGFBP7 to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were masked to the results of the test.
Urinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. The primary endpoint was reached in 17% of patients. For a single urinary TIMP-2·IGFBP7 test, sensitivity at the prespecified high-sensitivity cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval CI, 85-98%) with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill patients with urinary TIMP-2·IGFBP7 greater than 0.3 had seven times the risk for AKI (95% CI, 4-22) compared with critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary TIMP-2·IGFBP7 remained statistically significant and a strong predictor of AKI (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs. area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus TIMP-2·IGFBP7).
Urinary TIMP-2·IGFBP7 greater than 0.3 (ng/ml)(2)/1,000 identifies patients at risk for imminent AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 01573962).
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