Correlation between Resilient Modulus (M\u3csub\u3eR\u3c/sub\u3e) of Soil, Light Weight Deflectometer (LWD), and Falling Weight Deflectometer (FWD)

INDOT adopted the Mechanistic-Empirical Pavement Design Guide (MEPDG) beginning January 1, 2009, which is based on the FHWA Long Term Pavement Performance (LTTP) field study. The resilient modulus of the soil, MR, is required to implement the new design guide, as well as the pavement input parameters. The soil resilient modulus test requires special, expensive, equipment, significant time investment and effort, which has led researchers to develop MR prediction models and alternative methods to estimate the resilient modulus using non-destructive tests such as Falling Weight Deflectometer, FWD, Light Weight Deflectometer, LWD, and Dynamic Cone Penetrometer, DCP. The objectives of the project are geared toward a practical approach for pavement design procedures to effectively determine the soil resilient modulus for rehabilitation projects, targeting specifically untreated subgrade soils type A-6 and A-7-6. A total of four sites in Indiana were selected to conduct FWD, LWD, and DCP tests, as well as resilient modulus tests in the laboratory. In addition to the output from the four sites, additional data were collected from the data repository of INDOT which has geotechnical and pavement information. Extensive analysis and comparisons were done in an attempt at establishing relationships between the field tests and the laboratory results. The study showed the following: (1) high quality FWD tests conducted on top of the pavement can be used to estimate the subgrade MR, as long as site conditions and pavement layers thickness are well known; (2) the results of FWD tests on top of the subgrade are not reliable, as they are affected by the low confinement of the soils; and (3) LWD and DCP tests can be used to provide and assessment of the quality and uniformity of the subgrade, but do not provide reliable estimates of the stiffness of the subgrade

Evaluation of Radiation and Design Criteria for a Lunar Habitat

Extraterrestrial habitation has long been the object of science fiction, and experts in the fields of science and engineering have proposed many designs for a lunar base. The research conducted has focused on either structural stability, radiation protection, or meteorite-impact vulnerabilities, but rarely have these been considered together. The Resilient ExtraTerrestrial Habitats (RETH) project aims to design a lunar habitat from a hazards perspective, considering general degradation, meteorite impacts, seismic activity, radiation exposure, thermal extremes, and geomagnetic storms in addition to the physiological, psychological, and sociological aspects of astronauts living in such a habitat. Several members of the RETH team will begin the project by each quantifying an individual hazard and proposing a solution which, when combined with other members’ research, will provide specific parameters used in designing a safe, self-sustaining lunar or planetary outpost. This paper focuses on the effects of cosmic and solar radiation which can be detrimental to the health of future lunar inhabitants, and as such, quantifying the amount of radiation present in the environment is vital. Different materials such as aluminum, polyethylene, water, and regolith can provide adequate shielding with varying thickness, though the possibility of using lunar lava tubes remains open

Notch1 signaling in NOTCH1-mutated mantle cell lymphoma depends on Delta-Like ligand 4 and is a potential target for specific antibody therapy.

Background NOTCH1 gene mutations in mantle cell lymphoma (MCL) have been described in about 5-10% of cases and are associated with significantly shorter survival rates. The present study aimed to investigate the biological impact of this mutation in MCL and its potential as a therapeutic target. Methods Activation of Notch1 signaling upon ligand-stimulation and inhibitory effects of the monoclonal anti-Notch1 antibody OMP-52M51 in NOTCH1-mutated and -unmutated MCL cells were assessed by Western Blot and gene expression profiling. Effects of OMP-52M51 treatment on tumor cell migration and tumor angiogenesis were evaluated with chemotaxis and HUVEC tube formation assays. The expression of Delta-like ligand 4 (DLL4) in MCL lymph nodes was analyzed by immunofluorescence staining and confocal microscopy. A MCL mouse model was used to assess the activity of OMP-52M51 in vivo. Results Notch1 expression can be effectively stimulated in NOTCH1-mutated Mino cells by DLL4, whereas in the NOTCH1-unmutated cell line JeKo-1, less effect was observed upon any ligand-stimulation. DLL4 was expressed by histiocytes in both, NOTCH1-mutated and -unmutated MCL lymph nodes. Treatment of NOTCH1-mutated MCL cells with the monoclonal anti-Notch1 antibody OMP-52M51 effectively prevented DLL4-dependent activation of Notch1 and suppressed the induction of numerous direct Notch target genes involved in lymphoid biology, lymphomagenesis and disease progression. Importantly, in lymph nodes from primary MCL cases with NOTCH1/2 mutations, we detected an upregulation of the same gene sets as observed in DLL4-stimulated Mino cells. Furthermore, DLL4 stimulation of NOTCH1-mutated Mino cells enhanced tumor cell migration and angiogenesis, which could be abolished by treatment with OMP-52M51. Importantly, the effects observed were specific for NOTCH1-mutated cells as they did not occur in the NOTCH1-wt cell line JeKo-1. Finally, we confirmed the potential activity of OMP-52M51 to inhibit DLL4-induced Notch1-Signaling in vivo in a xenograft mouse model of MCL. Conclusion DLL4 effectively stimulates Notch1 signaling in NOTCH1-mutated MCL and is expressed by the microenvironment in MCL lymph nodes. Our results indicate that specific inhibition of the Notch1-ligand-receptor interaction might provide a therapeutic alternative for a subset of MCL patients

Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.

Genome-wide association studies have provided evidence for inherited genetic predisposition to chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms underlying CLL risk we analyze chromatin accessibility, active regulatory elements marked by H3K27ac, and DNA methylation at 42 risk loci in up to 486 primary CLLs. We identify that risk loci are significantly enriched for active chromatin in CLL with evidence of being CLL-specific or differentially regulated in normal B-cell development. We then use in situ promoter capture Hi-C, in conjunction with gene expression data to reveal likely target genes of the risk loci. Candidate target genes are enriched for pathways related to B-cell development such as MYC and BCL2 signalling. At 14 loci the analysis highlights 63 variants as the probable functional basis of CLL risk. By integrating genetic and epigenetic information our analysis reveals novel insights into the relationship between inherited predisposition and the regulatory chromatin landscape of CLL

A Criterion for Brittle Failure of Rocks Using the Theory of Critical Distances

This paper presents a new analytical criterion for brittle failure of rocks and heavily overconsolidated soils. Griffith’s model of a randomly oriented defect under a biaxial stress state is used to keep the criterion simple. The Griffith’s criterion is improved because the maximum tensile strength is not evaluated at the boundary of the defect but at a certain distance from the boundary, known as the critical distance. This fracture criterion is known as the Point Method, and is part of the Theory of Critical Distances, which is utilized in fracture mechanics. The proposed failure criterion has two parameters: the inherent tensile strength, ó0, and the ratio of the half-length of the initial crack/flaw to the critical distance, a/L. These parameters are difficult to measure but they may be correlated with the uniaxial compressive and tensile strengths, óc and ót. The proposed criterion is able to reproduce the common range of strength ratios for rocks and heavily overconsolidated soils (óc/ót=3-50) and the influence of several microstructural rock properties, such as texture and porosity. Good agreement with laboratory tests reported in the literature is found for tensile and low confining stresses.The work presented was initiated during a research project on “Structural integrity assessments of notch-type defects", for the Spanish Ministry of Science and Innovation (Ref.: MAT2010-15721)

The relation between neuromechanical parameters and Ashworth score in stroke patients

Quantifying increased joint resistance into its contributing factors i.e. stiffness and viscosity ("hypertonia") and stretch reflexes ("hyperreflexia") is important in stroke rehabilitation. Existing clinical tests, such as the Ashworth Score, do not permit discrimination between underlying tissue and reflexive (neural) properties. We propose an instrumented identification paradigm for early and tailor made interventions.BioMechanical EngineeringMechanical, Maritime and Materials Engineerin