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Noncanonical amino acid-aided synthesis of anti-PD-L1 bispecific nanobody for colon cancer immunotherapy
No full textColorectal cancer (CRC) is the second leading cause of cancer-related mortality, and the incidence of
early-onset colon cancer has been increasing globally in recent years. The development of
immunotherapies for colon cancer is critical for providing new treatment strategies to combat drug
resistance. Here, a bispecific nanobody against PD-L1 (BsNb-PD-L1) constructed using genetically
encoded noncanonical amino acids (ncAAs) is reported. A computational protocol was developed to
identify appropriate sites in the nanobody for incorporating p-acetylphenylalanine (pAcF). Variants of
nanobodies PV2 and PV3 with pAcF incorporated were conjugated with linkers containing an
aminooxy functionality to enable oxime ligation. The resulting PV2-S71 + PV3-N77 bispecific
nanobody (BsNb-ncAA) exhibited higher thermostability and binding affinity compared to the
nanobody monomers and the BsNb constructed by simply fusing two proteins. Moreover, in an in vitro
phagocytosis model, the BsNb-ncAA exhibited improved capability to inhibit immune evasion and
showed stronger biological activity compared to the fusion protein PV2-PV3. Furthermore, the BsNbncAA resulted in a marked increase in the number of CD8+ T cells within tumor tissues and
demonstrated efficient inhibitory effects against colon tumor growth in vivo. Our study provides a
general strategy for constructing BsNbs, which has potential applications in other cancer
immunotherapy
Search for UHE neutrinos from GRBs with the Pierre Auger Observatory
No full textWe report on the search for ultra-high-energy neutrinos from the prompt emission
of gamma-ray bursts (GRBs) using Surface Detector (SD) data from Phase I of the
Pierre Auger Observatory (2004–2021). A total of 570 GRBs occur within the most
neutrino-sensitive field of view of the SD, considering both Earth-skimming and
downward-going detection channels. For this purpose, GRB neutrino emission has
been modeled using the numerical software NeuCosmA, incorporating gamma-ray
measurements and inferred parameters such as the jet Lorentz factor and the
minimum variability time scale. No neutrino candidates were found, and upper limits
were obtained by stacking the individual GRB neutrino fluences. These limits are
complementary to those of IceCube and ANTARES and provide the strongest
constraints on prompt GRB neutrino fluence above 1 EeV. Additionally, limits on GRB
fluence in alternative models of neutrino production have been derived using Auger data
Sustainable Mn-doped ZnO nanoparticles as an efficient cathode catalyst for enhanced ORR and photocatalytic dye degradation in microbial fuel cells
No full textIn this study, Crocus sativus plant extract was employed in the synthesis of manganese-doped ZnO (Mn-doped ZnO) nanoparticles, which served as cathode catalysts in a Microbial Fuel Cell (MFC) for enhanced oxygen reduction reaction (ORR) and photocatalytic dye degradation. X-ray diffraction (XRD) confirmed the wurtzite hexagonal structure of ZnO, with minor peak shifts confirming successful Mn doping. UV–Vis spectroscopy revealed narrowed bandgap, enhancing visible light absorption. Fourier Transform Infrared (FTIR) spectroscopy confirmed Zn–O and Mn–O bonding. High-Resolution Transmission Electron Microscopy (HRTEM) analysis revealed well-defined nanoparticles though with slight agglomeration at higher Mn concentrations. Photocatalytic testing achieved 96.10% crystal violet degradation with 6% Mn-doped ZnO. MFC performance evaluated via polarization study, Electrochemical Impedance Spectroscopy (EIS), Linear Sweep Voltammetry (LSV), and biofouling study. MFC performance analysis showed that Mn-doped ZnO at 2 mg/cm2 achieved a maximum volumetric power density of 12.51 W/m3. Mn-doped ZnO exhibited Pt-comparable cost-effective performance, highlighting its potential as an efficient and eco-friendly cathode catalyst for MFCs and photocatalysis
Measurement of the Inelastic Proton-Proton Cross-Section at ▫▫ ▫▫ TeV using the hybrid data of the Pierre Auger Observatory
No full textMeasuring proton-proton interaction cross-sections at center-of-mass energies
above 40 TeV remains a significant challenge in particle physics. The Pierre Auger
Observatory provides a unique opportunity to study the interactions at the highest
energies through the distribution of the depth of maximum shower development
(Xmax) observed by its Fluorescence Detector. In previous studies, the determination
of the interaction cross-section at ultrahigh energies has relied on the assumption
that the tail of the Xmax distribution is proton-dominated, which restricts the analysis
to a limited energy range below the ankle and introduces related systematic uncertainties.
In this contribution, we adopt a novel method for the simultaneous estimation of the
proton-proton interaction cross-section and the primary cosmic-ray mass composition
using data from the Pierre Auger Observatory, avoiding assumptions about one quantity
to infer the other and thus improving the accuracy and robustness of our analysis.
In addition, a systematic shift in the Xmax scale is fitted to account for both experimental uncertainties and theoretical constraints on the modeling of particle interactions.
The obtained results are consistent with previous analyses and provide additional
constraints on hadronic interaction models. The measured proton-proton inelastic
cross-section at ultra-high energies agrees well with extrapolations of accelerator data.
The inferred cosmic-ray composition and the Xmax-scale shift are also compatible with
previous estimates
Impact of molecular design and conjugation in diammonium A\u27-cations on the photovoltaic performance of quasi-2D perovskite solar cells
No full textBulky organic spacers are widely employed to synthetize quasi-two-dimensional (quasi-2D) metal halide perovskites (MHPs), which display enhanced stability with respect to three-dimensional (3D) MHPs. The chemical nature and size of the bulky spacers play a key role in determining the performance of the solar cells by controlling the orientation of the octahedral layers and the charge transport. This work investigates how π-conjugation versus nonconjugation in bulky spacers impacts the structure and properties of quasi-2D MHPs and their photovoltaic performance in lead halide perovskite solar cells. Thus, diammonium spacers with related chemical structures and based on diphenylacetylene units (1, 2) or biphenyl flanked with alkyne moieties (3) are synthesized and investigated in comparison with the nonconjugated 4,4′-ethylenedianiline (ET) spacer (SP). Quasi-2D Dion–Jacobson MHPs are fabricated with a nominal n = 5, i.e., blocks of five octahedral layers are separated by the organic spacers and a chemical composition of SP(FA0.9Cs0.1)4Pb5I16 (SP = ET, 1, 2, or 3). The preferential orientation of the octahedral layers was studied by X-ray diffraction measurements, revealing better alignment in the quasi-2D MHPs containing the conjugated spacers. Defect concentration was estimated from space-charge limited-current (SCLC) measurements resulting in lower values for the quasi-2D MHPs with the conjugated cations with respect to that prepared with the nonconjugated ET spacer. The lowest defect density was found for the film with the conjugated spacer 1, which is in line with the slower photoluminescence (PL) decay for this sample. The solar cells prepared with the quasi-2D MHPs incorporating the nonconjugated ET spacer display power conversion efficiencies (PCEs) of around 11%, while approx. 13% are reached in the devices prepared with the conjugated spacers 1, 2, and 3. Our study demonstrates that the incorporation of conjugation in bulky spacers decreases the defect density and ion mobility leading to higher PCEs
Water stress impacts on grapevine functioning and possible adaptation measures
No full textEurope is the continent which is heating up with the highest speed. In viticulture every year we face extreme weather events, from higher rainfalls to droguth periods. It is therefore important to know what water stress (lack of water) is and how it impacts the physiology and metabolism of grapevine plants. In addition in the lecture, main measures on how to adapt the viticulture to water stress, are presented and discussed