Measurement of SiPM gain and photon detection efficiency at different temperatures and bias voltages

Gain and photon detection efficiency (PDE) of silicon photomultipliers (SiPMs) are important characteristics to understand SiPM-based detector systems in low light level applications. In this work, experimental setups are developed to quantify SiPM gain and PDE at different temperatures and bias voltages with a light source of fixed wavelength 405 nm, where a novel light-tight connected device of two integrating spheres is implemented to produce weak light onto SiPM. We present methods and results of the breakdown voltage, gain and PDE measurements for a Hamamatsu S13360-2050VE MPPC. At 25 Celsius, consistent results are obtained with the datasheet from the manufacturer. The temperature and bias voltage dependence of SiPM performances can guide its usage, such as in gain compensation at readout circuits, optical modeling of SiPMs and optimization of operating conditions of SiPM-based detectors.Comment: 9 pages, 14 figure

Adjusting the dose of traditional drugs combined with immunotherapy: reshaping the immune microenvironment in lung cancer

Immunotherapy is currently the most promising clinical treatment for lung cancer, not only revolutionizing second-line therapy but now also approved for first-line treatment. However, its clinical efficiency is not high and not all patients benefit from it. Thus, finding the best combination strategy to expand anti-PD-1/PD-L1-based immunotherapy is now a hot research topic. The conventional use of chemotherapeutic drugs and targeted drugs inevitably leads to resistance, toxic side effects and other problems. Recent research, however, suggests that by adjusting the dosage of drugs and blocking the activation of mutational mechanisms that depend on acquired resistance, it is possible to reduce toxic side effects, activate immune cells, and reshape the immune microenvironment of lung cancer. Here, we discuss the effects of different chemotherapeutic drugs and targeted drugs on the immune microenvironment. We explore the effects of adjusting the dosing sequence and timing, and the mechanisms of such responses, and show how the effectiveness and reliability of combined immunotherapy provide improved treatment outcomes

Delivery of Quantum Dot-siRNA Nanoplexes in SK-N-SH Cells for BACE1 Gene Silencing and Intracellular Imaging

The fluorescent quantum dots (QDs) delivered small interfering RNAs (siRNAs) targeting β-secretase (BACE1) to achieve high transfection efficiency of siRNAs and reduction of β-amyloid (Aβ) in nerve cells. The CdSe/ZnS QDs with the conjugation of amino-polyethylene glycol (PEG) were synthesized. Negatively charged siRNAs were electrostatically adsorbed to the surface of QDs to develop QD-PEG/siRNA nanoplexes. The QD-PEG/siRNAs nanoplexes significantly promote the transfection efficiency of siRNA, and the siRNAs from non-packaged nanoplexes were widely distributed in cell bodies and processes and efficiently silenced BACE1 gene, leading to the reduction of Aβ. The biodegradable PEG polymer coating could protect QDs from being exposed to the intracellular environment and restrained the release of toxic Cd2+. Therefore, the QD-PEG/siRNA nanoplexes reported here might serve as ideal carriers for siRNAs. We developed a novel method of siRNA delivery into nerve cells. We first reported that the QD-PEG/siRNA nanoplexes were generated by the electrostatic interaction and inhibited the Alzheimer's disease (AD)-associated BACE1 gene. We also first revealed the dynamics of QD-PEG/siRNAs within nerve cells via confocal microscopy and the ultrastructural evidences under transmission electron microscopy (TEM). This technology might hold promise for the treatment of neurodegenerative diseases such as AD

Reduced binding activity of vaccine serum to omicron receptor-binding domain

Coronavirus disease 2019 (COVID-19) vaccination regimens contribute to limiting the spread of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). However, the emergence and rapid transmission of the SARS-CoV-2 variant Omicron raise a concern about the efficacy of the current vaccination strategy. Here, we expressed monomeric and dimeric receptor-binding domains (RBDs) of the spike protein of prototype SARS-CoV-2 and Omicron variant in E. coli and investigated the reactivity of anti-sera from Chinese subjects immunized with SARS-CoV-2 vaccines to these recombinant RBDs. In 106 human blood samples collected from 91 participants from Jiangxi, China, 26 sera were identified to be positive for SARS-CoV-2 spike protein antibodies by lateral flow dipstick (LFD) assays, which were enriched in the ones collected from day 7 to 1 month post-boost (87.0%) compared to those harvested within 1 week post-boost (23.8%) (P < 0.0001). A higher positive ratio was observed in the child group (40.8%) than adults (13.6%) (P = 0.0073). ELISA results showed that the binding activity of anti-SARS-CoV-2 antibody-positive sera to Omicron RBDs dropped by 1.48- to 2.07-fold compared to its homogeneous recombinant RBDs. Thus, our data indicate that current SARS-CoV-2 vaccines provide restricted humoral protection against the Omicron variant

Efficient control of atmospheric sulfate production based on three formation regimes

The formation of sulfate (SO₄²⁻) in the atmosphere is linked chemically to its direct precursor, sulfur dioxide (SO₂), through several key oxidation paths for which nitrogen oxides or NO_x (NO and NO₂) play essential roles. Here we present a coherent description of the dependence of SO₄²⁻ formation on SO₂ and NO_x under haze-fog conditions, in which fog events are accompanied by high aerosol loadings and fog-water pH in the range of 4.7–6.9. Three SO₄²⁻ formation regimes emerge as defined by the role played by NO_x. In the low-NO_x regime, NO_x act as catalyst for HO_x, which is a major oxidant for SO₂, whereas in the high-NO_x regime, NO₂ is a sink for HO_x. Moreover, at highly elevated NO_x levels, a so-called NO₂-oxidant regime exists in which aqueous NO₂ serves as the dominant oxidant of SO₂. This regime also exists under clean fog conditions but is less prominent. Sensitivity calculations using an emission-driven box model show that the reduction of SO₄²⁻ is comparably sensitive to the reduction of SO₂ and NO_x emissions in the NO₂-oxidant regime, suggesting a co-reduction strategy. Formation of SO₄²⁻ is relatively insensitive to NO_x reduction in the low-NO_x regime, whereas reduction of NO_x actually leads to increased SO₄²⁻ production in the intermediate high-NO_x regime

Reconciling discrepancies in the source characterization of VOCs between emission inventories and receptor modeling

Emission inventory (EI) and receptor model (RM) are two of the three source apportionment (SA) methods recommended by Ministry of Environment of China and used widely to provide independent views on emission source identifications. How to interpret the mixed results they provide, however, were less studied. In this study, a cross-validation study was conducted in one of China's fast-developing and highly populated city cluster- the Pearl River Delta (PRD) region. By utilizing a highly resolved speciated regional EI and a region-wide gridded volatile organic compounds (VOCs) speciation measurement campaign, we elucidated underlying factors for discrepancies between EI and RM and proposed ways for their interpretations with the aim to achieve a scientifically plausible source identification. Results showed that numbers of species, temporal and spatial resolutions used for comparison, photochemical loss of reactive species, potential missing sources in EI and tracers used in RM were important factors contributed to the discrepancies. Ensuring the consensus of species used in EIs and RMs, utilizing a larger spatial coverage and longer time span, addressing the impacts of photochemical losses, and supplementing emissions from missing sources could help reconcile the discrepancies in VOC source characterizations acquired using both approaches. By leveraging the advantages and circumventing the disadvantages in both methods, the EI and RM could play synergistic roles to obtain robust SAs to improve air quality management practices

Modeling inorganic nitrogen deposition in Guangdong province, China

Atmospheric nitrogen deposition is an essential component of acid deposition and serves as one of main sources of nitrogen of the ecosystem. Along with rapidly developed economy, it is expected that the nitrogen deposition in Guangdong province is considerably large, due to substantial anthropogenic reactive nitrogen lost to the Pearl River Delta (PRD) region, one of the most developed region in China. However, characterization of chemical compositions of inorganic nitrogen (IN) deposition and quantification of nitrogen deposition fluxes in time and space in Guangdong province were seldom conducted, especially using a numerical modeling approach. In this study, we established a WRF/SMOKE-PRD/CMAQ model system and expanded 2006-based PRD regional emission inventories to Guangdong provincial ones, including SO2, NOx, VOC, PM10, PM2.5, and NH3 emissions for modeling nitrogen deposition in Guangdong province. Observations, including meteorological observed data, rainfall data, ground-level criteria pollutant measurements, satellite-derived data, and nitrogen deposition fluxes from field measurements were employed in the evaluation of model performance. Results showed that annual nitrogen deposition fluxes in the PRD region and Guangdong province were 31.01 kg N hm(-1) a(-1) and 26.03 kg N hm(-1) a(-1), dominated by NHx (including NH3 and NH4+), with a percentage of 63% and 71% of the total deposition flux of IN, respectively. The ratio of dry deposition to wet deposition was approximately 2:1 in the PRD region and about 3:2 in the whole Guangdong province. IN deposition was mainly distributed in the PRD region, Chaozhou, and Maoming, which was similar to the spatial distributions of NOx and NH3 emissions. The spatial distributions of chemical compositions of IN deposition implied that NH3-N and NOx-N tended to deposit in places close to emission sources, while spatial distributions of aerosol NH4+ - N and NO3- - N usually exhibited broader deposition areas, along with long-range transport of fine particles. Distinct temporal trends were found in IN components, especially for wet depositions, with peak values in August. (C) 2015 Elsevier Ltd. All rights reserved

Time-Frequency Volatility Spillovers among Major International Financial Markets: Perspective from Global Extreme Events

In the context of the gradual intensification of the Russia-Ukraine conflict and the continuous spread of the COVID-19 pandemic, this paper concentrates on the impact of global extreme events such as the COVID-19 pandemic and the Russia-Ukraine conflict on the risk spillovers among major international financial markets. First, to measure the impact of the extreme events the on the volatility spillovers among major international financial markets in the time-frequency domain, we combine the TVP-VAR-based connectedness method and BK frequency connectedness approach and focus on the total, directional, and net volatility spillovers. Second, the network visualization method is applied to outline the structural change in the risk contagion, paths, and roles among international financial markets during different periods of global extreme events. The empirical results indicate that the risk spillovers (total, directional, and net spillovers) among international financial markets and the roles played by each market in the process of risk contagion have changed significantly in different periods of global extreme events. Furthermore, volatility spillovers among international financial markets are driven mainly by the high-frequency component (short-term spillovers) during the full sample time. However, the effects of the extreme events also persist in the medium and long terms. Our findings may help understand the dynamics among international financial markets under extreme shocks and provide significant implications for portfolio managers, investors, and government agencies in times of extreme events

К вопросу о связях мозжечка и оливы

IntroductionProgrammed cell death-1 (PD-1) inhibition therapy has changed the treatment paradigm of metastatic renal cell carcinoma (MRCC) and non-small cell lung cancer (NSCLC). However, attempts to use the drug as a single agent have achieved only limited clinical success. To further enhance the clinical benefits of monotherapy, combination therapies will likely be necessary. Cytokine-induced killer (CIK) cells are a heterogeneous subset of ex vivo expanded T lymphocytes that have been shown to prolong the survival of cancer patients. We are conducting a study to evaluate the efficacy of PD-1 inhibitor in combination with CIK cells in relapsed/refractory MRCC and NSCLC and to analyze potential biomarkers to predict which patients will benefit most from the combined therapy.Case presentationThe results of two patients treated in an ongoing clinical trial for MRCC and NSCLC are described here. The tumor biopsy from Patient 1 exhibited moderate CD3+ T cell infiltration, but no PD-1 or PD-L1 expression. The tumor cells from Patient 2 strongly expressed PD-L1, and there was extensive tumor infiltration by CD3+ T cells; however, no PD-1 staining was seen. Non-synonymous single nucleotide variant (nsSNVs), along with higher indel mutations, in Patient 1 and nsSNVs along with higher tumor mutation burden in Patient 2 correlate with tumor-infiltrating CD3+ lymphocyte density. Patient 1 achieved a complete response, and Patient 2 achieved a near-complete response.ConclusionA PD-1 inhibitor in combination with CIK cells led to potent antitumor activity in MRCC and NSCLC; CD3+ T cell infiltration in baseline tumor biopsies is a potential predictive biomarker. This approach is being further investigated in an ongoing phase I trial