Densovirus induces winged morphs in asexual clones of the rosy apple aphid, Dysaphis plantaginea

Winged morphs of aphids are essential for their dispersal and survival. We discovered that the production of the winged morph in asexual clones of the rosy apple aphid, Dysaphis plantaginea, is dependent on their infection with a DNA virus, Dysaphis plantaginea densovirus (DplDNV). Virus-free clones of the rosy apple aphid, or clones infected singly with an RNA virus, rosy apple aphid virus (RAAV), did not produce the winged morph in response to crowding and poor plant quality. DplDNV infection results in a significant reduction in aphid reproduction rate, but such aphids can produce the winged morph, even at low insect density, which can fly and colonize neighboring plants. Aphids infected with DplDNV produce a proportion of virus-free aphids, which enables production of virus-free clonal lines after colonization of a new plant. Our data suggest that a mutualistic relationship exists between the rosy apple aphid and its viruses. Despite the negative impact of DplDNV on rosy apple aphid reproduction, this virus contributes to their survival by inducing wing development and promoting dispersal

HDAC inhibition potentiates immunotherapy in triple negative breast cancer.

Triple-negative breast cancer (TNBC) represents a more aggressive and difficult subtype of breast cancer where responses to chemotherapy occur, but toxicity is significant and resistance often follows. Immunotherapy has shown promising results in various types of cancer, including breast cancer. Here, we investigated a new combination strategy where histone deacetylase inhibitors (HDACi) are applied with immune checkpoint inhibitors to improve immunotherapy responses in TNBC. Testing different epigenetic modifiers, we focused on the mechanisms underlying HDACi as priming modulators of immunotherapy. Tumor cells were co-cultured with human peripheral blood mononuclear cells (PBMCs) and flow cytometric immunophenotyping was performed to define the role of epigenetic priming in promoting tumor antigen presentation and immune cell activation. We found that HDACi up-regulate PD-L1 mRNA and protein expression in a time-dependent manner in TNBC cells, but not in hormone responsive cells. Focusing on TNBC, HDACi up-regulated PD-L1 and HLA-DR on tumor cells when co-cultured with PBMCs and down-regulated CD4+ Foxp3+ Treg in vitro. HDACi significantly enhanced the in vivo response to PD-1/CTLA-4 blockade in the triple-negative 4T1 breast cancer mouse model, the only currently available experimental system with functional resemblance to human TNBC. This resulted in a significant decrease in tumor growth and increased survival, associated with increased T cell tumor infiltration and a reduction in CD4+ Foxp3+ T cells in the tumor microenvironment. Overall, our results suggest a novel role for HDAC inhibition in combination with immune checkpoint inhibitors and identify a promising therapeutic strategy, supporting its further clinical evaluation for TNBC treatment

Implementation of Model-Based Design of Experiments: Application of Computational Modeling to Support HRP Studies

This study illustrates the potential gains obtained by leveraging computational modeling to improve experimental efficiency in NASA research and counter measures studies through implementation of Model-Based Design of Experiments (MBDOE). MBDOE is a method to utilize analogous computational models to improve understanding of complex, multifactor, experimental responses and to determine experimental conditions and optimize information in the fewest number of experimental tests

Universality of Mixed Action Extrapolation Formulae

Mixed action theories with chirally symmetric valence fermions exhibit very desirable features both at the level of the lattice calculations as well as in the construction and implementation of the low energy mixed action effective field theory. In this work we show that when such a mixed action effective field theory is projected onto the valence sector, both the Lagrangian and the extrapolation formulae become universal in form through next to leading order, for all variants of discretization methods used for the sea fermions. Our conclusion relies on the chiral nature of the valence quarks. The result implies that for all sea quark methods which are in the same universality class as QCD, the numerical values of the physical coefficients in the various mixed action chiral Lagrangians will be the same up to lattice spacing dependent corrections. This allows us to construct a prescription to determine the mixed action extrapolation formulae for a large class of hadronic correlation functions computed in partially quenched chiral perturbation theory at the one-loop level. For specific examples, we apply this prescription to the nucleon twist--2 matrix elements and the nucleon--nucleon system. In addition, we determine the mixed action extrapolation formula for the neutron EDM as this provides a nice example of a theta-dependent observable; these observables are exceptions to our prescription.Comment: 36 pages, appendix on twisted mass sea fermions added, expanded discussion of NLO operators, version published in JHEP; typographical errors corrected in Eqs. (68) and (69

Drought reduces transmission of Turnip yellows virus , an insect-vectored circulative virus

Application of a severe water deficit to Arabidopsis thaliana plants infected with a mutant of Turnip yellows virus (TuYV, Family Luteoviridae) triggers a significant alteration of several plant phenology traits and strongly reduces the transmission efficiency of the virus by aphids. Although virus accumulation in water-stressed plants was similar to that in plants grown under well-watered conditions, virus accumulation was reduced in aphids fed on plant under water deficit. These results suggest alteration of the aphid feeding behavior on plants under water deficit

One-loop corrections to the metastable vacuum decay

We evaluate the one-loop prefactor in the false vacuum decay rate in a theory of a self interacting scalar field in 3+1 dimensions. We use a numerical method, established some time ago, which is based on a well-known theorem on functional determinants. The proper handling of zero modes and of renormalization is discussed. The numerical results in particular show that quantum corrections become smaller away from the thin-wall case. In the thin-wall limit the numerical results are found to join into those obtained by a gradient expansion.Comment: 31 pages, 7 figure

Static Controls Performance Tool for Lunar Landers

This document presents a static analysis tool used to evaluate the controllability of Lunar landers. This was created as part of the NASA Lunar Cargo Transportation and Landing by Soft Touchdown (Lunar CATALYST) program. This tool is capable of accepting typical design information such as location and direction of thrusters, maximum thruster forces, gravity vectors, and center of mass locations. The tool evaluates how far the center of gravity can move from its starting position while still maintaining control. This type of analysis is intended to support results produced by time domain simulations. The code created for this project was implemented in Python, and it was designed to be integrated into systems level optimization tools to yield first-cut results on optimal thruster placement

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: A phase 1 dose-escalation study

BackgroundThis phase 1 dose-escalation trial studied MM-302, a novel HER2-targeted PEGylated antibody-liposomal doxorubicin conjugate, in HER2-positive locally advanced/metastatic breast cancer.MethodsPatients were enrolled in four cohorts: MM-302 monotherapy (8, 16, 30, 40, and 50 mg/m2 every 4 weeks [q4w]); MM-302 (30 or 40 mg/m2 q4w) plus trastuzumab (4 mg/kg q2w); MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) q3w; MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) and cyclophosphamide (450 mg/m2) q3w.ResultsSixty-nine patients were treated. The most common adverse events (AEs) were fatigue and nausea. Grade 3/4 AEs of special interest included neutropenia, fatigue, mucosal inflammation, anemia, thrombocytopenia, febrile neutropenia, and palmar-plantar erythrodysesthesia. The MTD was not reached. With MM-302 ≥ 30 mg/m2, overall response rate (ORR) was 13% and median progression-free survival (mPFS) 7.4 months (95% CI: 3·5-10·9) in all arms. In 25 anthracycline-naïve patients, ORR was 28·0% and mPFS 10·9 months (95% CI: 1·8-15·3). Imaging with 64Cu-labeled MM-302 visualized tumor-drug penetrance in tumors throughout the body, including the brain.ConclusionMM-302 monotherapy, in combination with trastuzumab, or trastuzumab plus cyclophosphamide, was well tolerated and showed promising efficacy. The selected phase 2 MM-302 dose was 30 mg/m2 plus 6 mg/kg trastuzumab q3w

Electroweak Bubble Nucleation, Nonperturbatively

We present a lattice method to compute bubble nucleation rates at radiatively induced first order phase transitions, in high temperature, weakly coupled field theories, nonperturbatively. A generalization of Langer's approach, it makes no recourse to saddle point expansions and includes completely the dynamical prefactor. We test the technique by applying it to the electroweak phase transition in the minimal standard model, at an unphysically small Higgs mass which gives a reasonably strong phase transition (lambda/g^2 =0.036, which corresponds to m(Higgs)/m(W) = 0.54 at tree level but does not correspond to a positive physical Higgs mass when radiative effects of the top quark are included), and compare the results to older perturbative and other estimates. While two loop perturbation theory slightly under-estimates the strength of the transition measured by the latent heat, it over-estimates the amount of supercooling by a factor of 2.Comment: 48 pages, including 16 figures. Minor revisions and typo fixes, nothing substantial, conclusions essentially unchange

Thermodynamics of adiabatic feedback control

We study adaptive control of classical ergodic Hamiltonian systems, where the controlling parameter varies slowly in time and is influenced by system's state (feedback). An effective adiabatic description is obtained for slow variables of the system. A general limit on the feedback induced negative entropy production is uncovered. It relates the quickest negentropy production to fluctuations of the control Hamiltonian. The method deals efficiently with the entropy-information trade off.Comment: 6 pages, 1 figur