Development, Production and Evaluation of Aerosol Climate Data Records from European Satellite Observations (Aerosol_cci)

Producing a global and comprehensive description of atmospheric aerosols requires integration of ground-based, airborne, satellite and model datasets. Due to its complexity, aerosol monitoring requires the use of several data records with complementary information content. This paper describes the lessons learned while developing and qualifying algorithms to generate aerosol Climate Data Records (CDR) within the European Space Agency (ESA) Aerosol_cci project. An iterative algorithm development and evaluation cycle involving core users is applied. It begins with the application-specific refinement of user requirements, leading to algorithm development, dataset processing and independent validation followed by user evaluation. This cycle is demonstrated for a CDR of total Aerosol Optical Depth (AOD) from two subsequent dual-view radiometers. Specific aspects of its applicability to other aerosol algorithms are illustrated with four complementary aerosol datasets. An important element in the development of aerosol CDRs is the inclusion of several algorithms evaluating the same data to benefit from various solutions to the ill-determined retrieval problem. The iterative approach has produced a 17-year AOD CDR, a 10-year stratospheric extinction profile CDR and a 35-year Absorbing Aerosol Index record. Further evolution cycles have been initiated for complementary datasets to provide insight into aerosol properties (i.e., dust aerosol, aerosol absorption).Peer reviewe

Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library

The COVID−19 pandemic not only resulted in a global crisis, but also accelerated vaccine development and antibody discovery. Herein we report a synthetic humanized VHH library development pipeline for nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) isolation. Trinucleotide-based randomization of CDRs by Kunkel mutagenesis with the subsequent rolling-cycle amplification resulted in more than 1011 diverse phage display library in a manageable for a single person number of electroporation reactions. We identified a number of nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) by screening a novel synthetic humanized antibody library. In order to explore the most robust and fast method for affinity improvement, we performed affinity maturation by CDR1 and CDR2 shuffling and avidity engineering by multivalent trimeric VHH fusion protein construction. As a result, H7-Fc and G12x3-Fc binders were developed with the affinities in nM and pM range respectively. Importantly, these affinities are weakly influenced by most of SARS-CoV-2 VoC mutations and they retain moderate binding to BA.4\5. The plaque reduction neutralization test (PRNT) resulted in IC50 = 100 ng\ml and 9.6 ng\ml for H7-Fc and G12x3-Fc antibodies, respectively, for the emerging Omicron BA.1 variant. Therefore, these VHH could expand the present landscape of SARS-CoV-2 neutralization binders with the therapeutic potential for present and future SARS-CoV-2 variants

Design and Immunogenicity of SARS-CoV-2 DNA Vaccine Encoding RBD-PVXCP Fusion Protein

The potential of immune-evasive mutation accumulation in the SARS-CoV-2 virus has led to its rapid spread, causing over 600 million confirmed cases and more than 6.5 million confirmed deaths. The huge demand for the rapid development and deployment of low-cost and effective vaccines against emerging variants has renewed interest in DNA vaccine technology. Here, we report the rapid generation and immunological evaluation of novel DNA vaccine candidates against the Wuhan-Hu-1 and Omicron variants based on the RBD protein fused with the Potato virus X coat protein (PVXCP). The delivery of DNA vaccines using electroporation in a two-dose regimen induced high-antibody titers and profound cellular responses in mice. The antibody titers induced against the Omicron variant of the vaccine were sufficient for effective protection against both Omicron and Wuhan-Hu-1 virus infections. The PVXCP protein in the vaccine construct shifted the immune response to the favorable Th1-like type and provided the oligomerization of RBD-PVXCP protein. Naked DNA delivery by needle-free injection allowed us to achieve antibody titers comparable with mRNA-LNP delivery in rabbits. These data identify the RBD-PVXCP DNA vaccine platform as a promising solution for robust and effective SARS-CoV-2 protection, supporting further translational study

DataSheet_1_Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library.pdf

The COVID−19 pandemic not only resulted in a global crisis, but also accelerated vaccine development and antibody discovery. Herein we report a synthetic humanized VHH library development pipeline for nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) isolation. Trinucleotide-based randomization of CDRs by Kunkel mutagenesis with the subsequent rolling-cycle amplification resulted in more than 1011 diverse phage display library in a manageable for a single person number of electroporation reactions. We identified a number of nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) by screening a novel synthetic humanized antibody library. In order to explore the most robust and fast method for affinity improvement, we performed affinity maturation by CDR1 and CDR2 shuffling and avidity engineering by multivalent trimeric VHH fusion protein construction. As a result, H7-Fc and G12x3-Fc binders were developed with the affinities in nM and pM range respectively. Importantly, these affinities are weakly influenced by most of SARS-CoV-2 VoC mutations and they retain moderate binding to BA.4\5. The plaque reduction neutralization test (PRNT) resulted in IC50 = 100 ng\ml and 9.6 ng\ml for H7-Fc and G12x3-Fc antibodies, respectively, for the emerging Omicron BA.1 variant. Therefore, these VHH could expand the present landscape of SARS-CoV-2 neutralization binders with the therapeutic potential for present and future SARS-CoV-2 variants.</p

The mean physical and optical properties of regional haze dominated by biomass burning aerosol measured from the C-130 aircraft during SAFARI 2000

Original article can be found at: http://www.agu.org/journals/jd/ Copyright American Geophysical Union DOI: 10.1029/2002JD002226 [Full text of this article is not available in the UHRA]Instrumentation on the Met Office C-130 aircraft measured aerosol physical and optical properties during the Southern African Regional Science Initiative (SAFARI 2000) in September 2002 while flying from Windhoek, Namibia. Filter measurements of aged regional haze suggest a ratio of apparent elemental carbon (ECa) to organic carbon (OC) of 0.12 ± 0.02 and mass fractions of 5% ECa, 25% inorganic compounds, and 70% organic matter (OC plus associated elements). The submicron size distribution of aged regional haze may be fitted with three lognormal distributions with geometric mean radii (rn) of 0.12 ± 0.01, 0.26 ± 0.01, and 0.80 ± 0.01 μm and geometric standard deviations (σ) of 1.3 ± 0.1, 1.5 ± 0.1, and 1.9 ± 0.4. Measurements over 2500 km from the emission region show similar rn and σ for the smallest two modes, while the third mode is absent presumably as a result of sedimentation. At a wavelength (λ) of 0.55 μm, effective medium approximations suggest a refractive index of 1.54 − 0.018i for aged regional haze aerosol. The single scattering albedo (ωoλ) derived using this refractive index and measured size distributions are consistent with those from the nephelometer and Particle Soot Absorption Photometer (PSAP). The optical parameters for aged regional haze a few days old are specific extinction coefficient (keλ=0.55) of 5.0 ± 0.8 m2 g−1, asymmetry factor (gλ=0.55) of 0.59 ± 0.02, and ωoλ=0.55 of 0.91 ± 0.04. Measurements of fresh biomass burning aerosol a few minutes old show smaller more absorbing particles. Vertical profiles of carbon monoxide, aerosol concentration, and aerosol scattering show a good correlation. Over land, aerosols become well mixed in the vertical from the surface to approximately 500 hPa. Over ocean, the aerosols can be separated from underlying stratocumulus cloud by a clear gap and a strong inversion, which may limit the indirect effect.Peer reviewe

Inverse modeling of biomass burning emissions using Total Ozone Mapping Spectrometer aerosol index for 1997

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95187/1/jgrd12041.pd

The impact of cortical lesions on thalamo-cortical network dynamics after acute ischaemic stroke: a combined experimental and theoretical study

The neocortex and thalamus provide a core substrate for perception, cognition, and action, and are interconnected through different direct and indirect pathways that maintain specific dynamics associated with functional states including wakefulness and sleep. It has been shown that a lack of excitation, or enhanced subcortical inhibition, can disrupt this system and drive thalamic nuclei into an attractor state of low-frequency bursting and further entrainment of thalamo-cortical circuits, also called thalamo-cortical dysrhythmia (TCD). The question remains however whether similar TCD-like phenomena can arise with a cortical origin. For instance, in stroke, a cortical lesion could disrupt thalamo-cortical interactions through an attenuation of the excitatory drive onto the thalamus, creating an imbalance between excitation and inhibition that can lead to a state of TCD. Here we tested this hypothesis by comparing the resting-state EEG recordings of acute ischaemic stroke patients (N = 21) with those of healthy, age-matched control-subjects (N = 17). We observed that these patients displayed the hallmarks of TCD: a characteristic downward shift of dominant α-peaks in the EEG power spectra, together with increased power over the lower frequencies (δ and θ-range). Contrary to general observations in TCD, the patients also displayed a broad reduction in β-band activity. In order to explain the genesis of this stroke-induced TCD, we developed a biologically constrained model of a general thalamocortical module, allowing us to identify the specific cellular and network mechanisms involved. Our model showed that a lesion in the cortical component leads to sustained cell membrane hyperpolarization in the corresponding thalamic relay neurons, that in turn leads to the de-inactivation of voltage-gated T-type Ca2+-channels, switching neurons from tonic spiking to a pathological bursting regime. This thalamic bursting synchronises activity on a population level through divergent intrathalamic circuits, and entrains thalamo-cortical pathways by means of propagating low-frequency oscillations beyond the restricted region of the lesion. Hence, pathological stroke-induced thalamo-cortical dynamics can be the source of diaschisis, and account for the dissociation between lesion location and non-specific symptoms of stroke such as neuropathic pain and hemispatial neglect.This work was supported by the European Research Council under the European Union's Seventh Framework Programme FP7/2007-2013/ERC grant agreement n. 341196 [CDAC], and the Research and Technological Development Programme FP7-ICT-612139 in the WYSIWYD project to PFMJV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript