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  • A new wave front shape-based approach for acoustic source localization in an anisotropic plate without knowing its material properties

    Sen, Novonil; Kundu, Tribikram; Department of Aerospace and Mechanical Engineering, University of Arizona, Tucson, AZ 85721, USA; Department of Civil Engineering and Engineering Mechanics, University of Arizona, Tucson, AZ 85721, USA (ELSEVIER SCIENCE BV, 2018-07)
    Estimating the location of an acoustic source in a structure is an important step towards passive structural health monitoring. Techniques for localizing an acoustic source in isotropic structures are well developed in the literature. Development of similar techniques for anisotropic structures, however, has gained attention only in the recent years and has a scope of further improvement. Most of the existing techniques for anisotropic structures either assume a straight line wave propagation path between the source and an ultrasonic sensor or require the material properties to be known. This study considers different shapes of the wave front generated during an acoustic event and develops a methodology to localize the acoustic source in an anisotropic plate from those wave front shapes. An elliptical wave front shape-based technique was developed first, followed by the development of a parametric curve-based technique for non-elliptical wave front shapes. The source coordinates are obtained by minimizing an objective function. The proposed methodology does not assume a straight line wave propagation path and can predict the source location without any knowledge of the elastic properties of the material. A numerical study presented here illustrates how the proposed methodology can accurately estimate the source coordinates. (C) 2018 Elsevier B.V. All rights reserved.
  • Action of automorphisms on irreducible characters of symplectic groups

    Taylor, Jay; Univ Arizona, Dept Math, 617 N Santa Rita Ave, Tucson, AZ 85721 USA (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2018-07-01)
    Assume G is a finite symplectic group Sp(2n)(q) over a finite field F-q of odd characteristic. We describe the action of the automorphism group Aut(G) on the set Irr(G) of ordinary irreducible characters of G. This description relies on the equivariance of Deligne-Lusztig induction with respect to automorphisms. We state a version of this equivariance which gives a precise way to compute the automorphism on the corresponding Levi subgroup; this may be of independent interest. As an application we prove that the global condition in Spath's criterion for the inductive McKay condition holds for the irreducible characters of Sp(2n)(q). (C) 2018 Elsevier Inc. All rights reserved.
  • Characterizing Therapy Induced Polyploidy (TIP) Populations as a Resistance Mechanism in DH/DE-DLBCL and Identifying Synthetic Lethal Targeted Therapies

    Islam, Md Shariful (The University of Arizona., 2018)
    Lymphoma is a blood cancer that involves the lymphatic system and is the 7th most common cancer in USA. Diffuse large B-cell lymphoma (DLBCL) and Peripheral T-cell lymphoma (PTCL) are the most common types of aggressive B-cell and T-cell non-Hodgkin lymphomas (NHL) respectively. Double-Hit or Double-Expresser DH/DE-DLBCL are high grade B-cell lymphomas characterized by translocation or over expression of MYC and BCL-2 which are mostly incurable with standard chemo-immunotherapy. Therefore, there is an unmet need for novel targeted therapy. Aurora kinase inhibition (alisertib) induces ~30% cell death (in vitro), while a portion of the remaining ~70% cells at day-4 escape apoptosis through polyploid populations which we called therapy induced polyploid cells (TIP). These TIP cells exhibited a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway. TIP also showed increased levels of phospho-Hck and phospho-Akt indicating increased BCR signaling which is a rationale for combining ibrutinib (BTK inhibitor). Combined inhibition of AK + BTK reduced phosphorylation of AKT/mTOR and ERK-1/2, up-regulated phospho-H2A-X and Chk-2 (DNA damage), reduced Bcl-6 and decreased Bcl-2 and Bcl-xL results in induced apoptosis evident by PARP cleavage. In a DE-DLBCL SCID mouse xenograft model, ibrutinib alone was inactive, while alisertib + ibrutinib was additive with a tumor growth inhibition (TGI) rate of ~25%. However, TGI for ibrutinib + rituximab was ~50-60%. In contrast, triple therapy showed a TGI rate of >90%. Kaplan-Meier survival analysis showed 67% of mice were alive at day-89 with triple therapy versus only 20% with ibrutinib + rituximab. All treatments were well tolerated with no significant changes in body weights. Anti-DLBCL chemotherapy dosing schedules are intermittent, designed to avoid damage to normal tissue such as the mucous membranes, gut and the bone marrow. TIP are common in standard anti-DLBCL therapies (e.g. vincristine, doxorubicin) and thought to be responsible for disease relapse. Some of these TIP cells die but remaining of those are capable of re-entering the cell cycle during off-therapy periods. We discovered how these TIP cells can re-enter cell cycle and molecular mechanism underlying this resistance. We have purified AK inhibitor induced polyploid DH/DE-DLBCL cells by FACS. Time-lapse microscopy of single cells revealed that following drug removal, a subset of TIP cells divide and proliferate by reductive cell division(s). This includes multipolar mitosis, meiosis like nuclear fission or budding off daughter cells. RNA-Seq, Proteomics and Kinomics proling of TIP cells demonstrated that alisertib induced polyploid cells have up-regulated DNA damage response, replication and immune evasion; amplify receptor tyrosine kinase and T-cell receptor signaling; hijacks the spindle assembly checkpoint point control via MYC dysregulation of RanGAP1, TPX2 and KPNA2. We believe these up-regulated proteins are responsible for induction of aneuploid daughter cells and disease resistance and also provide potential opportunities for novel therapy combination that warrant further exploration. Lymphomas are systemic diseases that require a comprehensive knowledge of immune mechanism in cancer as well as targeted therapeutic approach for designing an optimal therapeutic strategy and desired synergy can be achieved by rational combination of small molecule inhibitors with immune modulatory agents that could enhance host immune response. In PTCL we have shown that expression of PD-L1 relative to PD-1 is high in PTCL biopsies ( 9-fold higher) and cell lines. Combination of alisertib with pan-PI3K inhibition or VCR significantly reduced PD-L1, NF-kB expression and inhibited phosphorylation of AKT, ERK1/2 and AK with enhanced apoptosis. In a syngeneic PTCL mouse xenograft model, alisertib demonstrated tumor growth inhibition (TGI) ~30%, whilst anti-PD-L1 therapy alone was ineffective. Alisertib + anti-PD-L1 resulted in TGI >90% indicative of a synthetic lethal interaction. PF-04691502 + alisertib + anti-PD-L1 + VCR resulted in TGI 100%. Overall, mice tolerated the treatments well. Co-targeting AK, PI3K and PD-L1 is a rational and novel therapeutic strategy for PTCL. In conclusion, we have identified therapeutic targets in aggressive B- and T-cell lymphoma which can be combined with immunotherapy that warrant investigation to disrupt rapid tumor evolution of TIP cells to mitigate disease relapse.
  • An ecohydrological stream type classification of intermittent and ephemeral streams in the southwestern United States

    Levick, Lainie; Hammer, Samantha; Lyon, Russell; Murray, Joel; Birtwistle, Amy; Guertin, Phillip; Goodrich, David; Bledsoe, Brian; Laituri, Melinda; Univ Arizona (ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2018-08)
    An ecohydrological stream type classification was developed to improve decision making for ephemeral and intermittent streams at four military reservations in the southwestern U.S.: Fort Irwin, Yuma Proving Ground (YPG), Fort Huachuca, and Fort Bliss. Agglomerative hierarchical cluster analysis was used to classify stream reaches by ecohydrologic properties (vegetation, hydrologic, and geomorphic attributes derived using geographic information system analyses), and Classification and Regression Trees (CART) were used to determine thresholds for each variable for a predictive model. Final stream types were determined from statistical analyses, cluster validity tests, examination of mapped clusters, and site knowledge. Climate regime and geomorphology were most important for YPG and Fort Irwin where annual precipitation is low. Vegetation variables were important at Fort Bliss and hydrologic variables were important at Fort Huachuca where higher annual precipitation and a bimodal rainfall pattern occur. The classification results and input variables are spatially linked to specific stream reaches, allowing managers to identify locations with similar attributes to support management actions. These methods enable the development of a stream type classification in gauged or ungauged watersheds and for areas where intensive field data collection is not feasible.

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