On the meaning of feedback parameter, transient climate response, and the greenhouse effect: Basic considerations and the discussion of uncertainties

In this paper we discuss the meaning of feedback parameter, greenhouse effect and transient climate response usually related to the globally averaged energy balance model of Schneider and Mass. After scrutinizing this model and the corresponding planetary radiation balance we state that (a) the this globally averaged energy balance model is flawed by unsuitable physical considerations, (b) the planetary radiation balance for an Earth in the absence of an atmosphere is fraught by the inappropriate assumption of a uniform surface temperature, the so-called radiative equilibrium temperature of about 255 K, and (c) the effect of the radiative anthropogenic forcing, considered as a perturbation to the natural system, is much smaller than the uncertainty involved in the solution of the model of Schneider and Mass. This uncertainty is mainly related to the empirical constants suggested by various authors and used for predicting the emission of infrared radiation by the Earth's skin. Furthermore, after inserting the absorption of solar radiation by atmospheric constituents and the exchange of sensible and latent heat between the Earth and the atmosphere into the model of Schneider and Mass the surface temperatures become appreciably lesser than the radiative equilibrium temperature. Moreover, neither the model of Schneider and Mass nor the Dines-type two-layer energy balance model for the Earth-atmosphere system, both contain the planetary radiation balance for an Earth in the absence of an atmosphere as an asymptotic solution, do not provide evidence for the existence of the so-called atmospheric greenhouse effect if realistic empirical data are used.Comment: 69 pages, 3 tables and 16 figure

Largeâ eddy simulation of biogenic VOC chemistry during the DISCOVERâ AQ 2011 campaign

Biogenic volatile organic compounds (BVOCs) are oxidized quickly in the atmosphere to form oxygenated VOC (OVOC) and play crucial roles in the formation of ozone and secondary organic aerosols. We use the National Center for Atmospheric Research’s largeâ eddy simulation model and Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality 2011 flight data to understand the role of boundary layer turbulence on the atmospheric chemistry of key BVOC species and their oxidation products. We simulate three distinct convective environments during the campaign, representing fair weather conditions (case 1: 1 July), a convective event dominated by southwesterly flow (case 2: 11 July), and a polluted event with high temperature and convection (case 3: 29 July). Isoprene segregation is greatest in the lower boundary layer under warm and convective conditions, reaching up to a 10% reduction in the isopreneâ OH reaction rate. Under warm and convective conditions, the BVOC lifetimes lengthen due to increased isoprene emission, elevated initial chemical concentrations, and OH competition. Although turbulenceâ driven segregation has less influence on the OVOC species, convection mixes more OVOC into the upper atmospheric boundary layer (ABL) and increases the total OH reactivity. Production and loss rates of ozone above 2â km in all the three cases indicate in situ ozone formation in addition to vertical convective transport of ozone from the surface and aloft, consistent with the increased contribution of OH reactivity from OVOC. Together, these results show that total OH reactivity in the ABL increases under warmer and stronger convective conditions due to enhanced isoprene emission and the OVOC contribution to ozone formation.Key PointsLES and DISCOVERâ AQ flight data are compared to understand the role of turbulence on BVOC chemistryTurbulenceâ induced segregation is less important for OVOC than isoprene, but OVOC compensates for isoprene rate reductionsConvection mixes more OVOC into the upper ABL and increases total OH reactivityPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133566/1/jgrd53113_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133566/2/jgrd53113-sup-0001-SI-S01.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133566/3/jgrd53113.pd

Novel anti-CD30/CD3 bispecific antibodies activate human T cells and mediate potent anti-tumor activity

CD30 is expressed on Hodgkin lymphomas (HL), many non-Hodgkin lymphomas (NHLs), and non-lymphoid malignancies in children and adults. Tumor expression, combined with restricted expression in healthy tissues, identifies CD30 as a promising immunotherapy target. An anti-CD30 antibody-drug conjugate (ADC) has been approved by the FDA for HL. While anti-CD30 ADCs and chimeric antigen receptors (CARs) have shown promise, their shortcomings and toxicities suggest that alternative treatments are needed. We developed novel anti-CD30 x anti-CD3 bispecific antibodies (biAbs) to coat activated patient T cells (ATCs) ex vivo prior to autologous re-infusions. Our goal is to harness the dual specificity of the biAb, the power of cellular therapy, and the safety of non-genetically modified autologous T cell infusions. We present a comprehensive characterization of the CD30 binding and tumor cell killing properties of these biAbs. Five unique murine monoclonal antibodies (mAbs) were generated against the extracellular domain of human CD30. Resultant anti-CD30 mAbs were purified and screened for binding specificity, affinity, and epitope recognition. Two lead mAb candidates with unique sequences and CD30 binding clusters that differ from the ADC in clinical use were identified. These mAbs were chemically conjugated with OKT3 (an anti-CD3 mAb). ATCs were armed and evaluated in vitro for binding, cytokine production, and cytotoxicity against tumor lines and then in vivo for tumor cell killing. Our lead mAb was subcloned to make a Master Cell Bank (MCB) and screened for binding against a library of human cell surface proteins. Only huCD30 was bound. These studies support a clinical trial in development employing ex vivo-loading of autologous T cells with this novel biAb