THE PHENOLOGY AND DISTRIBUTION OF APHIDS IN CALIFORNIA ALFALFA AS MODIFIED BY LADYBIRD BEETLE PREDATION (COLEOPTERA: COCCINELLIDAE)

The phenologies and distributions of pea aphid (Acyrthosiphon pisum (Harris)), blue alfalfa aphid (A. kondoi (Shinji)), and spotted alfalfa aphid (Therioaphis maculata (Buckton)) were intensively studied in California alfalfa. The results showed, as expected, that aphid populations across all densities were aggregated; but that ladybird beetle (Hippodamia convergens (G.-M.)) predation increased the degree of aggregation. The distribution parameters of the aphids were estimated using methods developed by Iwao and Kuno (1971

MULTITROPHIC MODELS OF PREDATOR-PREY ENERGETICS: I. AGE-SPECIFIC ENERGETICS MODELS—PEA APHID ACYRTHOSIPHON PISUM (HOMOPTERA: APHIDIDAE) AS AN EXAMPLE

A simple age-specific energetics (calories or biomass) model for the growth and development, reproduction, respiration, ageing, and intrinsic survivorship as a function of temperature and per capita energy availability for pea aphid (Acyrthosiphon pisum (Harris)) is reported. The ratio of energy supply-demand is used to scale all of the rates in the model. The maximum demand for energy based upon current state values is used to drive the Frazer-Gilbert functional response model (i.e. food acquisition), which is a component of the metabolic pool model used to assimilate energy to growth, reproduction, respiration, and egestion. The extensive data sets on pea aphid energetics published by Randolph et al. (1975) were used to develop the model. As the model estimates reproduction (Mx ) and survivorship (Lx ) values, extensive published age-specific life-data sets on pea aphids are used to test it. The results suggest: (1) the lower thermal threshold for development is raised and the upper threshold is lowered as food resources are decreased (2) the temperature-dependent rate of development is slowed with decreasing energy resources (3) the size of individuals and reproduction become smaller as temperature approaches the upper and lower thermal thresholds.A simple model for multitrophic level interactions incorporating the acquisition and assimilation functions is presente

Will climate change increase ozone depletion from low-energy-electron precipitation?

We investigate the effects of a strengthened stratospheric/mesospheric residual circulation on the transport of nitric oxide (NO) produced by energetic particle precipitation. During periods of high geomagnetic activity, energetic electron precipitation (EEP) is responsible for winter time ozone loss in the polar middle atmosphere between 1 and 6 hPa. However, as climate change is expected to increase the strength of the Brewer-Dobson circulation including extratropical downwelling, the enhancements of EEP NO<sub>x</sub> concentrations are expected to be transported to lower altitudes in extratropical regions, becoming more significant in the ozone budget. Changes in the mesospheric residual circulation are also considered. We use simulations with the chemistry climate model system EMAC to compare present day effects of EEP NO<sub>x</sub> with expected effects in a climate change scenario for the year 2100. In years of strong geomagnetic activity, similar to that observed in 2003, an additional polar ozone loss of up to 0.4 μmol/mol at 5 hPa is found in the Southern Hemisphere. However, this would be approximately compensated by an ozone enhancement originating from a stronger poleward transport of ozone from lower latitudes caused by a strengthened Brewer-Dobson circulation, as well as by slower photochemical ozone loss reactions in a stratosphere cooled by risen greenhouse gas concentrations. In the Northern Hemisphere the EEP NO<sub>x</sub> effect appears to lose importance due to the different nature of the climate-change induced circulation changes

Corrigendum to "Geomagnetic activity related NOx enhancements and polar surface air temperature variability in a chemistry climate model: modulation of the NAM index" published in Atmos. Chem. Phys., 11, 4521–4531, 2011

No abstract available

Highly dynamic robotic leg for non-biomimetic walking robots

Due to a predisposition of DNA to generate symmetric anatomy, there are no tripedal animals in nature. Yet, threelegged walking might be the sweet spot between the energy efficiency of bipeds and the stability of quadrupeds. This paper presents the non-biomimetic leg for the TriPed, a novel three-legged mobile walking robot that aims to study the advantages and disadvantages of three-legged walking. We showcase its new non-biomimetic leg design that allows for fast repositioning by keeping the leg mass close to the body. This is done using physical experiments as well as a simscape simulation. The experiments show that the legs are capable of moving about 3 m/s

SHP-1 phosphatase activity counteracts increased T cell receptor affinity.

Anti-self/tumor T cell function can be improved by increasing TCR-peptide MHC (pMHC) affinity within physiological limits, but paradoxically further increases (K(d) < 1 μM) lead to drastic functional declines. Using human CD8(+) T cells engineered with TCRs of incremental affinity for the tumor antigen HLA-A2/NY-ESO-1, we investigated the molecular mechanisms underlying this high-affinity-associated loss of function. As compared with cells expressing TCR affinities generating optimal function (K(d) = 5 to 1 μM), those with supraphysiological affinity (K(d) = 1 μM to 15 nM) showed impaired gene expression, signaling, and surface expression of activatory/costimulatory receptors. Preferential expression of the inhibitory receptor programmed cell death-1 (PD-1) was limited to T cells with the highest TCR affinity, correlating with full functional recovery upon PD-1 ligand 1 (PD-L1) blockade. In contrast, upregulation of the Src homology 2 domain-containing phosphatase 1 (SHP-1/PTPN6) was broad, with gradually enhanced expression in CD8(+) T cells with increasing TCR affinities. Consequently, pharmacological inhibition of SHP-1 with sodium stibogluconate augmented the function of all engineered T cells, and this correlated with the TCR affinity-dependent levels of SHP-1. These data highlight an unexpected and global role of SHP-1 in regulating CD8(+) T cell activation and responsiveness and support the development of therapies inhibiting protein tyrosine phosphatases to enhance T cell-mediated immunity

CD8 T cell function and cross-reactivity explored by stepwise increased peptide-HLA versus TCR affinity.

Recruitment and activation of CD8 T cells occur through specific triggering of T cell receptor (TCR) by peptide-bound human leucocyte antigen (HLA) ligands. Within the generated trimeric TCR-peptide:HLA complex, the molecular binding affinities between peptide and HLA, and between TCR and peptide:HLA both impact T cell functional outcomes. However, how their individual and combined effects modulate immunogenicity and overall T cell responsiveness has not been investigated systematically. Here, we established two panels of human tumor peptide variants differing in their affinity to HLA. For precise characterization, we developed the "blue peptide assay", an upgraded cell-based approach to measure the peptide:HLA affinity. These peptide variants were then used to investigate the cross-reactivity of tumor antigen-specific CD8 T cell clonotypes derived from blood of cancer patients after vaccination with either the native or an affinity-optimized Melan-A/MART-1 epitope, or isolated from tumor infiltrated lymph nodes (TILNs). Vaccines containing the native tumor epitope generated T cells with better functionality, and superior cross-reactivity against potential low affinity escape epitopes, as compared to T cells induced by vaccines containing an HLA affinity-optimized epitope. Comparatively, Melan-A/MART-1-specific TILN cells displayed functional and cross-reactive profiles that were heterogeneous and clonotype-dependent. Finally, we took advantage of a collection of T cells expressing affinity-optimized NY-ESO-1-specific TCRs to interrogate the individual and combined impact of peptide:HLA and TCR-pHLA affinities on overall CD8 T cell responses. We found profound and distinct effects of both biophysical parameters, with additive contributions and absence of hierarchical dominance. Altogether, the biological impact of peptide:HLA and TCR-pHLA affinities on T cell responses was carefully dissected in two antigenic systems, frequently targeted in human cancer immunotherapy. Our technology and stepwise comparison open new insights into the rational design and selection of vaccine-associated tumor-specific epitopes and highlight the functional and cross-reactivity profiles that endow T cells with best tumor control capacity

Low Avidity T Cells Do Not Hinder High Avidity T Cell Responses Against Melanoma

The efficacy of T cells depends on their functional avidity, i. e., the strength of T cell interaction with cells presenting cognate antigen. The overall T cell response is composed of multiple T cell clonotypes, involving different T cell receptors and variable levels of functional avidity. Recently, it has been proposed that the presence of low avidity tumor antigen-specific CD8 T cells hinder their high avidity counterparts to protect from tumor growth. Here we analyzed human cytotoxic CD8 T cells specific for the melanoma antigen Melan-A/MART-1. We found that the presence of low avidity T cells did not result in reduced cytotoxicity of tumor cells, nor reduced cytokine production, by high avidity T cells. In vivo in NSG-HLA-A2 mice, the anti-tumor effect of high avidity T cells was similar in presence or absence of low avidity T cells. These data indicate that low avidity T cells are not hindering anti-tumor T cell responses, a finding that is reassuring because low avidity T cells are an integrated part of natural T cell responses

Rapid and Continued T-Cell Differentiation into Long-term Effector and Memory Stem Cells in Vaccinated Melanoma Patients.

<b>Purpose:</b> Patients with cancer benefit increasingly from T-cell-based therapies, such as adoptive T-cell transfer, checkpoint blockade, or vaccination. We have previously shown that serial vaccinations with Melan-A <sup>MART-1</sup> <sub>26-35</sub> peptide, CpG-B, and incomplete Freund adjuvant (IFA) generated robust tumor-specific CD8 T-cell responses in patients with melanoma. Here, we describe the detailed kinetics of early- and long-term establishment of T-cell frequency, differentiation (into memory and effector cells), polyfunctionality, and clonotype repertoire induced by vaccination. <b>Experimental Design:</b> Twenty-nine patients with melanoma were treated with multiple monthly subcutaneous vaccinations consisting of CpG-B, and either the native/EAA ( <i>n</i> = 13) or the analogue/ELA ( <i>n</i> = 16) Melan-A <sup>MART-1</sup> <sub>26-35</sub> peptide emulsified in IFA. Phenotypes and functionality of circulating Melan-A-specific CD8 T cells were assessed directly <i>ex vivo</i> by multiparameter flow cytometry, and TCR clonotypes were determined <i>ex vivo</i> by mRNA transcript analyses of individually sorted cells. <b>Results:</b> Our results highlight the determining impact of the initial vaccine injections on the rapid and strong induction of differentiated effector T cells in both patient cohorts. Moreover, long-term polyfunctional effector T-cell responses were associated with expansion of stem cell-like memory T cells over time along vaccination. Dominant TCR clonotypes emerged early and persisted throughout the entire period of observation. Interestingly, one highly dominant clonotype was found shared between memory and effector subsets. <b>Conclusions:</b> Peptide/CpG-B/IFA vaccination induced powerful long-term T-cell responses with robust effector cells and stem cell-like memory cells. These results support the further development of CpG-B-based cancer vaccines, either alone or as specific component of combination therapies. <i>Clin Cancer Res; 23(13); 3285-96. ©2016 AACR</i>