From antiangiogenesis to hypoxia: current research and future directions

Angiogenesis has long been recognized as an essential element in tumor growth. Since the conception of antiangiogenesis for cancer therapeutics, great strides have been made in understanding the molecular biology underlying angiogenesis, both in cancer and in physiology. By capitalizing on these advancements through bench-to-bedside research, potent antiangiogenic agents have been developed and tested. To date, the clinical results of most of these antiangiogenic agents have not met expectations. Even with the most successful agents, such as bevacizumab, used either as single agents or in combination with chemotherapy, gains in overall survival of cancer patients have been modest in most cases. In this article, the authors present the evolving views of antiangiogenic therapy, review recent experimental and clinical studies on antiangiogenesis, and address the fundamental role of hypoxia in tumor progression, which may be key to improving the efficacy of antiangiogenic therapy

Multiple Scattering Theory for Two-dimensional Electron Gases in the Presence of Spin-Orbit Coupling

In order to model the phase-coherent scattering of electrons in two-dimensional electron gases in the presence of Rashba spin-orbit coupling, a general partial-wave expansion is developed for scattering from a cylindrically symmetric potential. The theory is applied to possible electron flow imaging experiments using a moveable scanning probe microscope tip. In such experiments, it is demonstrated theoretically that the Rashba spin-orbit coupling can give rise to spin interference effects, even for unpolarized electrons at nonzero temperature and no magnetic field.Comment: 34 pages, 7 figure

Physiological and immunoblot analyses of a nitric oxide synthase (NOS)-like protein of pea (Pisum sativum L.)

Nitric oxide (NO) functions as a signal molecule in different biological processes in plants, including disease resistance. Its production is related to nitric oxide synthase (NOS). The application of chemicals that induce systemic resistance in plants did not induce NOS activity in pea, suggesting that NO functions upstream of salicylic acid (SA) in the signaling pathway of defense responses in plants. NOS activity was induced in both the incompatible and compatible interactions of pea with Ralstonia solanacearum and Pseudomonas syringae pv pisi, respectively, between 3 h to 6 h post-infiltration, indicating that NOS was involved in both resistance and disease development responses in pea. Antibodies raised against mammalian NOS did not have specificity in detecting a NOS-like protein in pea, suggesting that the pea NOS-like protein could be structurally different from mammalian NOS, and immunodetection of a plant NOS-like protein must be conducted with caution and verified with functional assays

High-sensitivity photoacoustic leak testing

The photoacoustic effect may be exploited for the detection and localization of gas leaks from otherwise sealed components. The technique involves filling the test component with a tracer gas, and radiating the component to produce photoacoustic sound from any leak site where tracer gas is present. This paper describes demonstration experiments utilizing 10.6-µ radiation from a carbon-dioxide laser and sulfur hexafluoride as a tracer gas for photoacoustic leak testing at leak rates between 6×10–5 cm3/s (1 cm3 in 4.6 h) and 5×10–9 cm3/s (1 cm3 in 6.3 years). The technique may reach or exceed the capabilities of the most sensitive commercial leak test systems using helium mass-spectrometers. In addition, comparison of the measured results to a simple scaling law suggests that tracer gas cloud geometry influences the photoacoustic signal amplitude

Generalized Pseudopotentials for Higher Partial Wave Scattering

We derive a generalized zero-range pseudopotential applicable to all partial wave solutions to the Schroedinger equation based on a delta-shell potential in the limit that the shell radius approaches zero. This properly models all higher order multipole moments not accounted for with a monopolar delta function at the origin, as used in the familiar Fermi pseudopotential for s-wave scattering. By making the strength of the potential energy dependent, we derive self-consistent solutions for the entire energy spectrum of the realistic potential. We apply this to study two particles in an isotropic harmonic trap, interacting through a central potential, and derive analytic expressions for the energy eigenstates and eigenvalues.Comment: RevTeX 4 pages, 1 figure, final published versio

The Drosophila caspase Ice is important for many apoptotic cell deaths and for spermatid individualization, a nonapoptotic process

Caspase family proteases play important roles in the regulation of apoptotic cell death. Initiator caspases are activated in response to death stimuli, and they transduce and amplify these signals by cleaving and thereby activating effector caspases. In Drosophila, the initiator caspase Nc (previously Dronc) cleaves and activates two short-prodomain caspases, Dcp-1 and Ice (previously Drice), suggesting these as candidate effectors of Nc killing activity. dcp-1-null mutants are healthy and possess few defects in normally occurring cell death. To explore roles for Ice in cell death, we generated and characterized an Ice null mutant. Animals lacking Ice show a number of defects in cell death, including those that occur during embryonic development, as well as during formation of adult eyes, arista and wings. Ice mutants exhibit subtle defects in the destruction of larval tissues, and do not prevent destruction of salivary glands during metamorphosis. Cells from Ice animals are also markedly resistant to several stresses, including X-irradiation and inhibition of protein synthesis. Mutations in Ice also suppress cell death that is induced by expression of Rpr, Wrinkled (previously Hid) and Grim. These observations demonstrate that Ice plays an important non-redundant role as a cell death effector. Finally, we demonstrate that Ice participates in, but is not absolutely required for, the non-apoptotic process of spermatid differentiation

Widespread initiation, reactivation, and acceleration of landslides in the northern California Coast Ranges due to extreme rainfall

Episodically to continuously active slow‐moving landslides are driven by precipitation. Climate change, which is altering both the frequency and magnitude of precipitation worldwide, is therefore predicted to have a major impact on landslides. Here we examine the behavior of hundreds of slow‐moving landslides in northern California in response to large changes in annual precipitation that occurred between 2016 and 2018. We quantify the landslide displacement using repeat‐pass radar interferometry and pixel offset tracking techniques on a novel dataset from the airborne NASA/JPL Uninhabited Aerial Vehicle Synthetic Aperture Radar. We found that 312 landslides were moving due to extreme rainfall during 2017, compared to 119 during 2016, which was the final year of a historic multi‐year drought. However, with a return to below‐average rainfall in 2018, only 146 landslides remained in motion. The increased number of landslides during 2017 was primarily accommodated by landslides that were smaller than the landslides that remained active between 2016 and 2018. Furthermore, by examining a subset of 51 landslides, we found that 49 had increased velocities during 2017 when compared to 2016. Our results show that slow‐moving landslides are sensitive to large changes in annual precipitation, particularly the smaller and thinner landslides that likely experience larger basal pore‐water pressure changes. Based on climate model predictions for the next century in California, which include increases in average annual precipitation and increases in the frequency of dry‐to‐wet extremes, we hypothesize that there will be an overall increase in landslide activity

Mixed Effects Modeling of Proliferation Rates in Cell-Based Models: Consequence for Pharmacogenomics and Cancer

The International HapMap project has made publicly available extensive genotypic data on a number of lymphoblastoid cell lines (LCLs). Building on this resource, many research groups have generated a large amount of phenotypic data on these cell lines to facilitate genetic studies of disease risk or drug response. However, one problem that may reduce the usefulness of these resources is the biological noise inherent to cellular phenotypes. We developed a novel method, termed Mixed Effects Model Averaging (MEM), which pools data from multiple sources and generates an intrinsic cellular growth rate phenotype. This intrinsic growth rate was estimated for each of over 500 HapMap cell lines. We then examined the association of this intrinsic growth rate with gene expression levels and found that almost 30% (2,967 out of 10,748) of the genes tested were significant with FDR less than 10%. We probed further to demonstrate evidence of a genetic effect on intrinsic growth rate by determining a significant enrichment in growth-associated genes among genes targeted by top growth-associated SNPs (as eQTLs). The estimated intrinsic growth rate as well as the strength of the association with genetic variants and gene expression traits are made publicly available through a cell-based pharmacogenomics database, PACdb. This resource should enable researchers to explore the mediating effects of proliferation rate on other phenotypes.</p