Photocages are light-sensitive chemical protecting groups that provide external control over when, where, and how much of a biological substrate is activated in cells using targeted light ...irradiation. Regrettably, most popular photocages (e.g., o-nitrobenzyl groups) absorb cell-damaging ultraviolet wavelengths. A challenge with achieving longer wavelength bond-breaking photochemistry is that long-wavelength-absorbing chromophores have shorter excited-state lifetimes and diminished excited-state energies. However, here we report the synthesis of a family of BODIPY-derived photocages with tunable absorptions across the visible/near-infrared that release chemical cargo under irradiation. Derivatives with appended styryl groups feature absorptions above 700 nm, yielding photocages cleaved with the highest known wavelengths of light via a direct single-photon-release mechanism. Photorelease with red light is demonstrated in living HeLa cells, Drosophila S2 cells, and bovine GM07373 cells upon ∼5 min irradiation. No cytotoxicity is observed at 20 μM photocage concentration using the trypan blue exclusion assay. Improved B-alkylated derivatives feature improved quantum efficiencies of photorelease ∼20-fold larger, on par with the popular o-nitrobenzyl photocages (εΦ = 50–100 M–1 cm–1), but absorbing red/near-IR light in the biological window instead of UV light.
Abstract
Objectives
To assess the effect of rituximab (RTX) on the lung function parameters in SSc interstitial lung disease (SSc-ILD) patients.
Methods
PubMed and Embase were searched to identify ...studies on SSc-ILD treated with RTX, confined to a predefined inclusion and exclusion criteria. A systematic review and meta-analysis were performed on the included studies on changes in forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) from baseline to 6 and 12 months of follow-up.
Results
A total of 20 studies (2 randomized controlled trials, 6 prospective studies, 5 retrospective studies and 7 conference abstracts) were included (n = 575). RTX improved FVC from baseline by 4.49% (95% CI 0.25, 8.73) at 6 months and by 7.03% (95% CI 4.37, 9.7) at 12 months. Similarly, RTX improved DLCO by 3.47% (95% CI 0.99, 5.96) at 6 months and 4.08% (95% CI 1.51, 6.65) at 12 months. In the two studies comparing RTX with other immunosuppressants, improvement of FVC by 6 months in the RTX group was 1.03% (95% CI 0.11, 1.94) greater than controls. At the 12 month follow-up, RTX treatment was similar to controls in terms of both FVC and DLCO. Patients treated with RTX had a lower chance of developing infections compared with controls odds ratio 0.256 (95% CI 0.104, 0.626), I2 = 0%, P = 0.47).
Conclusions
Treatment with RTX in SSc-ILD was associated with a significant improvement of both FVC and DLCO during the first year of treatment. RTX use was associated with lower infectious adverse events.
Leptospirosis has a mortality rate of 5-20%. Poor prognostic factors are older age; oliguria; elevated potassium, creatinine and/or bilirubin levels; and altered mental status. We conducted this ...retrospective study to analyse the predictors of mortality among Indian patients with leptospirosis.
Clinical, biochemical, demographic and treatment related data (time between onset of symptoms and commencement of leptospira specific antibiotics) of 101 leptospirosis patients were reviewed. Predictors identified by univariate analysis were analysed by multivariable Cox regression for survival analysis.
Prominent clinical features were: fever (101/101, 100%), jaundice (62, 62.4%), vomiting (42, 41.6%), oliguria (35, 34.7%), cough (18, 17.8%) and dyspnoea (10, 10.0%). Common complications were acute kidney injury (22, 21.8%), cardiovascular collapse (13, 12.9%), haemorrhages (10, 10.0%), meningitis (7, 6.9%), acute respiratory distress syndrome and pancreatitis (5, 5.0% each). Seventeen patients died (16.8%). Univariate predictors of mortality were older age, delayed antibiotic therapy, higher bilirubin, aspartate aminotransferase, alkaline phosphatase, leucocyte count and aspartate/alanine aminotransferase ratio (AAR). Only AAR (HR 1.208, 95% CI 1.051-1.388) and number of days the patient was symptomatic before access to specific antibiotic therapy (HR 1.304, 95% CI 1.081-1.574) remained significant predictors after Cox regression.
Multivariate analysis showed high AAR and delayed antibiotic therapy might be associated with fatality.
In recent years, the intracellular oxidation-reduction (redox) state has gained increasing attention as a critical mediator of cell signaling, gene expression changes and proliferation. This review ...discusses the evidence for a redox cycle (i.e., fluctuation in the cellular redox state) regulating the cell cycle. The presence of redox-sensitive motifs (cysteine residues, metal co-factors in kinases and phosphatases) in several cell cycle regulatory proteins indicate periodic oscillations in intracellular redox state could play a central role in regulating progression from G0/G1 to S to G2 and M cell cycle phases. Fluctuations in the intracellular redox state during cell cycle progression could represent a fundamental mechanism linking oxidative metabolic processes to cell cycle regulatory processes. Proliferative disorders are central to a variety of human pathophysiological conditions thought to involve oxidative stress. Therefore, a more complete understanding of redox control of the cell cycle could provide a biochemical rationale for manipulating aberrant cell proliferation.
Weyl fermions have been observed as three-dimensional, gapless topological excitations in weakly correlated, inversion-symmetry-breaking semimetals. However, their realization in spontaneously ...time-reversal-symmetry-breaking phases of strongly correlated materials has so far remained hypothetical. Here, we report experimental evidence for magnetic Weyl fermions in Mn
Sn, a non-collinear antiferromagnet that exhibits a large anomalous Hall effect, even at room temperature. Detailed comparison between angle-resolved photoemission spectroscopy (ARPES) measurements and density functional theory (DFT) calculations reveals significant bandwidth renormalization and damping effects due to the strong correlation among Mn 3d electrons. Magnetotransport measurements provide strong evidence for the chiral anomaly of Weyl fermions-namely, the emergence of positive magnetoconductance only in the presence of parallel electric and magnetic fields. Since weak magnetic fields (approximately 10 mT) are adequate to control the distribution of Weyl points and the large fictitious fields (equivalent to approximately a few hundred T) produced by them in momentum space, our discovery lays the foundation for a new field of science and technology involving the magnetic Weyl excitations of strongly correlated electron systems such as Mn
Sn.
The modification of fluid turbulence due to suspended particles is analysed using direct numerical simulations for the fluid turbulence and discrete particle simulations where the point-particle ...approximation is used for the particle force on the fluid. Two values of the Reynolds number based on the channel width
$h$
and the average gas velocity
$\bar{u}$
,
$(\unicodeSTIX{x1D70C}_{f}\bar{u}h/\unicodeSTIX{x1D702}_{f})=3300$
and 5600 are considered, where
$\unicodeSTIX{x1D70C}_{f}$
and
$\unicodeSTIX{x1D702}_{f}$
are the gas density and viscosity. The particle Reynolds number based on the root mean square of the difference in the particle and fluid velocities is in the range 4–15. The particle volume fraction is small, in the range
$0{-}3.5\times 10^{-3}$
, the mass loading is varied in the range 0–13.5 and the particle Stokes number (ratio of particle relaxation time and fluid integral time) is varied in the range 1–420. Multiple models for the force on the particles are examined, the Stokes drag law, the Schiller–Naumann correlation, a correction to determine the ‘undisturbed’ fluid velocity at the particle centre, the lift force and wall corrections. In all cases, as the particle volume fraction is systematically increased, there is a discontinuous decrease in the turbulence intensities at a critical volume fraction. The mean square velocities and the rate of production of turbulent energy decrease by 1–2 orders of magnitude when the volume fraction is increased by
$10^{-4}$
at the critical volume fraction. There is no compensatory increase in the particle fluctuating velocities or the energy dissipation rate due to the drag force on the particles, and there is a significant decrease in the total fluid energy dissipation rate at the critical volume fraction. This shows that the turbulence collapse is due to a catastrophic reduction in the turbulent energy production rate. This is contrary to the current understanding that turbulence attenuation is caused by the enhanced dissipation due to particle drag.
In the rapidly evolving and transforming science of the current era, it is extremely useful to maintain dynamism in the research programmes of R&D organizations. This requires identification of less ...important or less relevant areas for better focus and optimum utilization of limited resource; it is equally important to identify (or better still, initiate) new areas, both for sustained relevance and for leadership. Such dynamism necessarily requires, for limited human and infrastructure resources, shedding of some research programmes, while inducting new ones. The so called SWOT (strength, weakness, opportunity and threat) analysis is a recognized methodology to identity areas/programmes for such dynamism. Yet a SWOT analysis can be hardly effective unless it provides specific and actionable inputs for policy makers. However, the conventional SWOT analyses often fail to provide such effective inputs; a particular obstacle is either intentional or unintentional ambiguous or non-specific inputs to the SWOT analysis by the participating scientists. It would be certainly desirable to carry out a SWOT analysis by an independent third party, at least at the first level (like a first assessment); however, such an independent analysis requires objective, quantitative and unambiguous data. Thus well designed SWOT analysis for an objective, quantitative and inclusive performance (OQIP) index, based on which policy may be implemented, is necessary.
Among the blazar class, extreme blazars have exceptionally hard intrinsic X-ray/TeV spectra, and extreme peak energies in their spectral energy distribution (SED). Observational evidence suggests ...that the non-thermal emission from extreme blazars is typically non-variable. All these unique features present a challenging case for blazar emission models, especially regarding those sources with hard TeV spectra. We aim to explore the X-ray and GeV observational features of a variety of extreme blazars, including extreme-TeV, extreme-synchrotron (extreme-Syn), and regular high-frequency-peaked BL Lac objects (HBLs). Furthermore, we aim to test the applicability of various blazar emission models that could explain the very hard TeV spectra. We conducted a detailed spectral analysis of X-ray data collected with and along with quasi-simultaneous data from for five sources: 1ES\,0120+340, RGB\,J0710+591, 1ES\,1101-232, 1ES\,1741+196, and 1ES\,2322-409. We took three approaches to modelling the SEDs: (1) a steady-state one-zone synchrotron-self-Compton (SSC) code, (2) another leptonic scenario of co-accelerated electrons and protons on multiple shocks applied to the sources only (e-p co-acceleration scenario), and (3) a one-zone hadro-leptonic ( code. The latter code is used twice to explain the emission process: proton synchrotron and synchrotron emission of secondary pairs. Our X-ray analysis provides well-constrained estimates of the synchrotron peak energies for both 1ES0120+340 and 1ES1741+196. These findings categorise these latter objects as extreme -synchrotron sources, as they consistently exhibit peak energies above 1\,keV in different flux states. The multi-epoch X-ray and GeV data reveal spectral and flux variabilities in RGB\,J0710+591 and 1ES\,1741+196, even on timescales of days to weeks. As anticipated, the one-zone SSC model adequately reproduces the SEDs of regular HBLs but encounters difficulties in explaining the hardest TeV emission. Hadronic models offer a reasonable fit to the hard TeV spectrum, though with the trade-off of requiring extreme jet powers. On the other hand, the lepto-hadronic scenario faces additional challenges in fitting the GeV spectra of extreme -TeV sources. Finally, the e-p co-acceleration scenario naturally accounts for the observed hard electron distributions and effectively matches the hardest TeV spectrum of RGB\,J0710+591 and 1ES\,1101-232.
Rotating packed beds have received considerable attention as a means of process intensification for gas−liquid mass transfer over the past 2 decades. In this work, we take a critical view of the ...developments in understanding the transport processes in rotating packed beds. The intensification achieved so far falls short of the goal of 2−3 orders of magnitude volume reduction compared to that obtained conventional columns. The directions toward achieving this goal are outlined.
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