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Milnor-Witt cycle modules over an excellent DVR
No full textThe definition of Milnor-Witt cycle modules in [5] can easily be adapted over general regular base schemes. However, there are simple examples (see (2.9)) to show that Gersten complex fails to be exact for cycle modules in general if the base is not a field. The goal of this article is to show that, for a restricted class of Milnor-Witt cycle modules over an excellent DVR satisfying an extra axiom, called here as R5, the expected properties of exactness of Gersten complex and A 1-invariance hold. Moreover R5 is vacuously satisfied when the base is a field and it is also satisfied by KMWover any base. As a corollary, we obtain the strict A 1-invariance and the exactness of Gersten complex KMWfor over an excellent DVR
Trends of humoral immune responses to heterologous antigenic exposure due to vaccination & omicron SARS-CoV-2 infection: Implications for boosting
No full textBackground & objectives:
Vaccination and natural infection can both augment the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how omicron infection has affected the vaccine-induced and hybrid immunity is not well studied in Indian population. The present study was aimed to assess the durability and change in responses of humoral immunity with age, prior natural infection, vaccine type and duration with a minimum gap of six months post-two doses with either ChAdOx1 nCov-19 or BBV152 prior- and post-emergence of the omicron variant.
Methods:
A total of 1300 participants were included in this observational study between November 2021 and May 2022. Participants had completed at least six months after vaccination (2 doses) with either ChAdOx1 nCoV-19 or an inactivated whole virus vaccine BBV152. They were grouped according to their age (≤ or ≥60 yr) and prior exposure of SARS-CoV-2 infection. Five hundred and sixteen of these participants were followed up after emergence of the Omicron variant. The main outcome was durability and augmentation of the humoral immune response as determined by anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations, anti-nucleocapsid antibodies and anti-omicron RBD antibodies. Live virus neutralization assay was conducted for neutralizing antibodies against four variants – ancestral, delta and omicron and omicron sublineage BA.5.
Results:
Before the omicron surge, serum anti-RBD IgG antibodies were detected in 87 per cent participants after a median gap of eight months from the second vaccine dose, with a median titre of 114 [interquartile range (IQR) 32, 302] BAU/ml. The levels increased to 594 (252, 1230) BAU/ml post-omicron surge (P<0.001) with 97 per cent participants having detectable antibodies, although only 40 had symptomatic infection during the omicron surge irrespective of vaccine type and previous history of infection. Those with prior natural infection and vaccination had higher anti-RBD IgG titre at baseline, which increased further [352 (IQR 131, 869) to 816 (IQR 383, 2001) BAU/ml] (P<0.001). The antibody levels remained elevated after a mean time gap of 10 months, although there was a decline of 41 per cent. The geometric mean titre was 452.54, 172.80, 83.1 and 76.99 against the ancestral, delta, omicron and omicron BA.5 variants in the live virus neutralization assay.
Interpretation & conclusions:
Anti-RBD IgG antibodies were detected in 85 per cent of participants after a median gap of eight months following the second vaccine dose. Omicron infection probably resulted in a substantial proportion of asymptomatic infection in the first four months in our study population and boosted the vaccine-induced humoral immune response, which declined but still remained durable over 10 months
All-Optical study of Gilbert damping and spin orbit torque in Ta/CoFeB/SiO2 heterostructures
No full textPure spin-current induced spin–orbit torque in a magnetic layer can externally control its magnetization dynamics including Gilbert damping. Here, we demonstrate control over Gilbert damping (Δα) in Substrate/β-Ta(t)/CoFeB(3 nm)/SiO2(2 nm) heterostructures with widely varying Ta thickness (3 ≤ t ≤ 20 nm) having stable β-phase using all-optical time-resolved magneto-optical Kerr effect. The pure spin-current due to the spin Hall effect in β-Ta exerts both damping-like and field-like spin–orbit torque to the CoFeB layer. We estimate the damping-like-torque efficiency over a wide range of t with and without Joule heating. In both cases, we obtained a remarkably high-value of damping-like-torque efficiency (ξDL) ∼ 0.40, suggesting that Joule heating has a negligible effect on the Δα. However, the modulation of precession frequency mainly originates from the Joule heating where contributions from field-like-torque and Oersted field are negligible. The high-value of ξDL and its stability over a wide-range of t will be key ingredients for future energy-efficient spintronic and magnonic devices
“Smart” drug delivery: A window to future of translational medicine
No full textChemotherapy is the mainstay of cancer treatment today. Chemotherapeutic drugs are non-selective and can harm both cancer and healthy cells, causing a variety of adverse effects such as lack of specificity, cytotoxicity, short half-life, poor solubility, multidrug resistance, and acquiring cancer stem-like characteristics. There is a paradigm shift in drug delivery systems (DDS) with the advent of smarter ways of targeted cancer treatment. Smart Drug Delivery Systems (SDDSs) are stimuli responsive and can be modified in chemical structure in response to light, pH, redox, magnetic fields, and enzyme degradation can be future of translational medicine. Therefore, SDDSs have the potential to be used as a viable cancer treatment alternative to traditional chemotherapy. This review focuses mostly on stimuli responsive drug delivery, inorganic nanocarriers (Carbon nanotubes, gold nanoparticles, Meso-porous silica nanoparticles, quantum dots etc.), organic nanocarriers (Dendrimers, liposomes, micelles), antibody-drug conjugates (ADC) and small molecule drug conjugates (SMDC) based SDDSs for targeted cancer therapy and strategies of targeted drug delivery systems in cancer cells
Photoelectron spectra of benzene: Can path dependent diabatic surfaces provide unique observables?
No full textWhile carrying out Beyond Born-Oppenheimer theory based diabatization, the solutions of adiabatic-to-diabatic transformation equations depend on the paths of integration over two-dimensional cross-sections of multi-dimensional space of nuclear degrees of freedom. It is shown that such path-dependent solutions leading to diabatic potential energy surface matrices computed along any two different paths are related through an orthogonal matrix, and thereby, those surface matrices should provide unique observables. While exploring the numerical validity of the theoretical framework, we construct diabatic Hamiltonians for the five low-lying electronic states (X̂2E1g, B̂2E2g, and Ĉ2AE2u) of benzene radical cation (C6H6+) along three different approaches of contour integration over two dimensional nuclear planes constituted by seven non-adiabatically active normal modes. Three different diabatic surface matrices are further employed to generate the photoelectron spectra of the benzene molecule (C6H6). It is interesting to note that the spectral peak positions and intensity patterns for all three cases are almost close to each other and also exhibit very good agreement with the experimental results
Waltzing binaries: probing the line-of-sight acceleration of merging compact objects with gravitational waves
No full textThe line-of-sight acceleration of a compact binary coalescence (CBC) event would modulate the shape of the gravitational waves (GWs) it produces with respect to the corresponding nonaccelerated CBC. Such modulations could be indicative of its astrophysical environment. We investigate the prospects of detecting this acceleration in future observing runs of the LIGO-Virgo-KAGRA network, as well as in next-generation (XG) detectors and the proposed DECIGO. We place the first observational constraints on this acceleration for putative binary neutron star mergers GW170817 and GW190425. We find no evidence of line-of-sight acceleration in these events at 90% confidence. Prospective constraints for the fifth observing run of the LIGO at A+ sensitivity suggest that accelerations for typical binary neutron stars (BNSs) could be constrained with a precision of a/c ∼ 10−7 [s−1], assuming a signal-to-noise ratio of 10. These improve to a/c ∼ 10−9 [s−1] in XG detectors, and a/c ∼ 10−16 [s−1] in DECIGO. We also interpret these constraints in the context of mergers around supermassive black holes
Constraints on the cosmic expansion history from GWTC–3
No full textWe use 47 gravitational wave sources from the Third LIGO–Virgo–Kamioka Gravitational Wave Detector Gravitational Wave Transient Catalog (GWTC–3) to estimate the Hubble parameter H(z), including its current value, the Hubble constant H0. Each gravitational wave (GW) signal provides the luminosity distance to the source, and we estimate the corresponding redshift using two methods: the redshifted masses and a galaxy catalog. Using the binary black hole (BBH) redshifted masses, we simultaneously infer the source mass distribution and H(z). The source mass distribution displays a peak around 34 M⊙, followed by a drop-off. Assuming this mass scale does not evolve with the redshift results in a H(z) measurement, yielding H0 = 68-8+12km s-1 Mpc-1(68% credible interval) when combined with the H0 measurement from GW170817 and its electromagnetic counterpart. This represents an improvement of 17% with respect to the H0 estimate from GWTC–1. The second method associates each GW event with its probable host galaxy in the catalog GLADE+, statistically marginalizing over the redshifts of each event's potential hosts. Assuming a fixed BBH population, we estimate a value of H0 = 68-68km s-1 Mpc-1 with the galaxy catalog method, an improvement of 42% with respect to our GWTC–1 result and 20% with respect to recent H0 studies using GWTC–2 events. However, we show that this result is strongly impacted by assumptions about the BBH source mass distribution; the only event which is not strongly impacted by such assumptions (and is thus informative about H0) is the well-localized event GW190814
Photoradical‐mediated catalyst‐independent protein cross‐link with unusual fluorescence properties
No full textPhoto-actively modified natural amino acids have served as lucrative probes for precise mapping of the dynamics, interaction networks, and turnover of cytosolic proteins both in vivo and ex vivo. In our attempts to extend the utility of photoreactive reporters to map the molecular characteristics of vital membrane proteins, we carried out site-selective incorporation of 7-fluoro-indole in the human mitochondrial outer membrane protein VDAC2 (voltage-dependent anion channel isoform 2), with the aim of generating Trp−Phe/Tyr cross-links. Prolonged irradiation at 282 nm provided us with a surprisingly unusual fluorophore that displayed sizably red-shifted excitation (λex-max=280 nm→360 nm) and emission (λem-max=330 nm→430 nm) spectra that was reversible with organic solvents. By measuring the kinetics of the photo-activated cross-linking with a library of hVDAC2 variants, we demonstrate that formation of this unusual fluorophore is kinetically retarded, independent of tryptophan, and is site-specific. Using other membrane (Tom40 and Sam50) and cytosolic (MscR and DNA Pol I) proteins, we additionally show that formation of this fluorophore is protein-independent. Our findings reveal the photoradical-mediated accumulation of reversible tyrosine cross-links, with unusual fluorescent properties. Our findings have immediate applications in protein biochemistry and UV-mediated protein aggregation and cellular damage, opening avenues for formulating therapeutics that prolong cell viability in humans
A Zn‐dependent structural transition of SOD1 modulates its ability to undergo phase separation
No full textThe misfolding and mutation of Cu/Zn superoxide dismutase (SOD1) is commonly associated with amyotrophic lateral sclerosis (ALS). SOD1 can accumulate within stress granules (SGs), a type of membraneless organelle, which is believed to form via liquid–liquid phase separation (LLPS). Using wild‐type, metal‐deficient, and different ALS disease mutants of SOD1 and computer simulations, we report here that the absence of Zn leads to structural disorder within two loop regions of SOD1, triggering SOD1 LLPS and amyloid formation. The addition of exogenous Zn to either metal‐free SOD1 or to the severe ALS mutation I113T leads to the stabilization of the loops and impairs SOD1 LLPS and aggregation. Moreover, partial Zn‐mediated inhibition of LLPS was observed for another severe ALS mutant, G85R, which shows perturbed Zn‐binding. By contrast, the ALS mutant G37R, which shows reduced Cu‐binding, does not undergo LLPS. In addition, SOD1 condensates induced by Zn‐depletion exhibit greater cellular toxicity than aggregates formed by prolonged incubation under aggregating conditions. Overall, our work establishes a role for Zn‐dependent modulation of SOD1 conformation and LLPS properties that may contribute to amyloid formation
Synthetic copolymers with natural product side‐chain pendents.
No full textDehydroabietic acid is a natural product in the class of rosins. Here we report the design, synthesis and characterization of copolymers containing dehydroabietate side-chain pendents, derived from homologated dehydroabietic ethyl methacrylate and tert-butoxy carbonyl (Boc) l-alanine methacryloyloxyethyl ester with varying comonomer proportions by reversible addition fragmentation chain transfer polymerization. The cleavage of Boc groups from the copolymers resulted in water-soluble copolymers with cationic surface charge. Since proper hydrophobic−hydrophilic balance in a single polymer chain is maintained, the copolymers self-assembled in aqueous media with a critical aggregation concentration of 2.8–3.0 mg L−1, confirmed by fluorescence spectroscopy. 1H NMR spectroscopy, dynamic light scattering, SEM and AFM were used to further investigate the aqueous solution self-assembly of random copolymers. The collective findings from 1H NMR, dynamic light scattering, SEM and AFM clearly revealed the existence of micellar particles in water with alanine units on the surface of the nanoDehydroabietic acid is a natural product in the class of rosins. Here we report the design, synthesis and characterization of copolymers containing dehydroabietate side-chain pendents, derived from homologated dehydroabietic ethyl methacrylate and tert-butoxy carbonyl (Boc) l-alanine methacryloyloxyethyl ester with varying comonomer proportions by reversible addition fragmentation chain transfer polymerization. The cleavage of Boc groups from the copolymers resulted in water-soluble copolymers with cationic surface charge. Since proper hydrophobic−hydrophilic balance in a single polymer chain is maintained, the copolymers self-assembled in aqueous media with a critical aggregation concentration of 2.8–3.0 mg L−1, confirmed by fluorescence spectroscopy. 1H NMR spectroscopy, dynamic light scattering, SEM and AFM were used to further investigate the aqueous solution self-assembly of random copolymers. The collective findings from 1H NMR, dynamic light scattering, SEM and AFM clearly revealed the existence of micellar particles in water with alanine units on the surface of the nanoaggregates and homologated dehydroabietate pendents along with the hydrophobic main-chain backbone in the core. In addition, to get a clear insight into the nanoaggregates' potential for drug encapsulation in aqueous medium, Nile Red was incorporated as a model hydrophobic dye. © 2023 Society of Industrial Chemistry.aggregates and homologated dehydroabietate pendents along with the hydrophobic main-chain backbone in the core. In addition, to get a clear insight into the nanoaggregates' potential for drug encapsulation in aqueous medium, Nile Red was incorporated as a model hydrophobic dye. © 2023 Society of Industrial Chemistry