Direct numerical simulations are performed to explore the effects of the rotating direction of the vertically asymmetric rough wall on the transport properties of Taylor–Couette (TC) flow, up to a Taylor number of ${Ta} = 2.39\times 10^{7}$. It is shown that, compared with the smooth wall, the rough wall with vertical asymmetric strips can enhance the dimensionless torque ${Nu}_{\omega }$. More importantly, at high Ta, clockwise rotation of the inner rough wall (where the fluid is sheared by the steeper slope side of the strips) results in a significantly greater torque enhancement compared to counter-clockwise rotation (where the fluid is sheared by the smaller slope side of the strips), due to the larger convective contribution to the angular velocity flux. However, the rotating direction has a negligible effect on the torque at low Ta. The larger torque enhancement caused by the clockwise rotation of the vertically asymmetric rough wall at high Ta is then explained by the stronger coupling between the rough wall and the bulk, attributed to the larger biased azimuthal velocity towards the rough wall at the mid-gap of the TC system, the increased turbulence intensity manifested by larger Reynolds stress and a thinner boundary layer, and the more significant contribution of the pressure force on the surface of the rough wall to the torque.

A wideband tunable balanced phase shifter is achieved by utilizing varactor-loaded coupled lines (VLCLs)-embedded multistage branch-line structure. The tunable phase shift with low in-band phase deviation is attributed to the regulation in phase shift of the VLCLs and the horizontal microstrip lines in series. The wideband differential-mode (DM) impedance matching and common-mode (CM) suppression are due to multiple DM transmission poles and CM transmission zeros, which are brought about by the cascade of VLCLs and a microstrip line with short-circuited stubs in the DM-equivalent circuit and open-circuited stubs in the CM-equivalent circuit, respectively. Compared with the state-of-the-art tunable balanced phase shifters, the proposed design not only has the advantages of wide operating bandwidth (BW) with low in-band phase deviation but also has low insertion loss and easily fabricated structure. Theoretical analysis and design procedure were conducted, resulting in a prototype covering the frequency of 1.8 GHz. This prototype offers a tunable phase shift capability ranging from 0° to 90°. The prototype exhibits an operating BW of 45%, with a maximum phase deviation of ±6°. It also achieves a 10 dB DM return loss and CM suppression, while maintaining a maximum insertion loss of 2.5 dB.

The relationship between magmatism and gold mineralization has been a topic of interest in understanding the formation of ore deposits. The Baizhangzi gold deposit, located in the northern margin of the North China Craton, is hosted by the Baizhangzi granite (BZG) and provides a case to evaluate the relation between granite and gold mineralization in Late Triassic. In this study, we present petrography, bulk geochemistry, zircon U-Pb isotope and trace elements data, as well as major elements of biotite and plagioclase for the BZG to evaluate the petrogenesis and link with gold mineralization. The BZG comprises biotite monzogranite, biotite-bearing monzogranite and monzogranite (BZGs). Zircon U-Pb geochronology shows that all the granitoids of BZGs were coeval with a formation age of 232 Ma. The granitoids, with high SiO2, Al2O3 and Sr, while low Y and Yb, show adakitic affinity. They are enriched in LILFs (e.g., Rb, Ba, Th, U and Sr) and LREEs, while depletion in HFSEs (e.g., Nb, Ta, P and Ti). The geochemical and mineral chemical data suggest that the granitoids have experienced the fractional crystallization of biotite + plagioclase + K- feldspar + apatite. Crystallization temperature is estimated as ca. 700°C, and pressure is between 0.71 kbar and 1.60 kbar. The monzogranite shows higher values of logfO2, △FMQ and △NNO than the biotite-bearing monzogranite, ranging from −19.76 to −11.71, −4.93 to +3.67 and −5.48 to +3.11, respectively. The fractional crystallization, together with high fO2, K-metasomatism and low evolution degree, provided favourable conditions for gold mineralization.

OBJECTIVES/GOALS: Determine if the Conserved Transcriptional Response to Adversity transcriptomic profile established in primary blood mononuclear cells (PBMC) of chronically stress caregivers, is present in individuals with early Alzheimer’s disease. Chronic stress is a risk factor for Alzheimer’s, and may be an untapped biomarker for disease risk and pathology. METHODS/STUDY POPULATION: To collect preliminary data on the Conserved Transcriptional Response to Adversity profile in individuals with Alzheimer’s disease, we were able to utilize primary blood mononuclear cell samples from a small open label pilot study called Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease, designed to clear stressed senescent cells. We hypothesized senolytics may beneficially reverse this stress profile. We developed a NanoString assay (measuring 19 inflammatory, 31 type-1 interferon, and 3 antibody synthesis genes) to compare these transcriptomic changes within 4 individuals measured at baseline, post-treatment with an intermittent 12-week senolytic therapy, and at an optional extended post-treatment follow-up time point > 3 months after their post treatment visit. RESULTS/ANTICIPATED RESULTS: There was relative downregulation of expression in transcription in 7 of 19 measured inflammatory genes (FOS, PTGS2, IL8, FOS, Il1b, JUNB, and JUN) in Alzheimer’s disease participants after receiving senolytic treatment (baseline vs. post-treatment). This is consistent with a decrease in the inflammatory arm of the Conserved Transcriptional Response to Adversity profile. These differences were not significant between baseline and the extended follow-up, indicative of a transient effect of senolytic. There were no changes in type 1 interferon or antibody synthesis genes. This data provides preliminary evidence for larger controlled studies to further establish this profile in Alzheimer’s disease, providing exciting evidence for transcript changes that may be reproducible with senolytic therapy. DISCUSSION/SIGNIFICANCE: Literature relevant to Alzheimer’s disease indicates global increases in inflammation paired with deficits in immune response, capturing some genes associated with the Conserved Transcriptional Response to Adversity. This profile may be a useful biomarker for prediction of disease severity or risk of dementia due to chronic stress.

Exploiting two quasi-natural experiments, we find that firms increase emissions of toxic pollution following decreases in analyst coverage. The effects are stronger for firms with low initial analyst coverage, poor corporate governance, and firms subject to less stringent monitoring by environmental regulators. Decreases in environmental-related questions raised in conference calls, an increased cost of monitoring to institutional shareholders, reductions in pollution abatement investment, and the weakening of internal governance related to environmental performance are channels through which reduced analyst coverage contributes to increases in firm pollution. Our study highlights the monitoring role analysts play in shaping corporate environmental policies.

Although immune checkpoint inhibitors (ICIs) have produced remarkable responses in non-small cell lung cancer (NSCLC) patients, receivers still have a relatively low response rate. Initial response assessment by conventional imaging and evaluation criteria is often unable to identify whether patients can achieve durable clinical benefit from ICIs. Overall, there are sparse effective biomarkers identified to screen NSCLC patients responding to this therapy. A lot of studies have reported that patients with specific gene mutations may benefit from or resist to immunotherapy. However, the single gene mutation may be not effective enough to predict the benefit from immunotherapy for patients. With the advancement in sequencing technology, further studies indicate that many mutations often co-occur and suggest a drastic transformation of tumour microenvironment phenotype. Moreover, co-mutation events have been reported to synergise to activate or suppress signalling pathways of anti-tumour immune response, which also indicates a potential target for combining intervention. Thus, the different mutation profile (especially co-mutation) of patients may be an important concern for predicting or promoting the efficacy of ICIs. However, there is a lack of comprehensive knowledge of this field until now. Therefore, in this study, we reviewed and elaborated the value of cancer mutation profile in predicting the efficacy of immunotherapy and analysed the underlying mechanisms, to provide an alternative way for screening dominant groups, and thereby, optimising individualised therapy for NSCLC patients.

Prolonged parturition duration has been widely demonstrated to be a risk factor for incidence of stillbirth. This study evaluated the supply of dietary fibre on the parturition duration, gut microbiota and metabolome using sows as a model. A total of 40 Yorkshire sows were randomly given diet containing normal level of dietary fibre (NDF, 17·5 % dietary fibre) or high level of dietary fibre (HDF, 33·5 % dietary fibre). Faecal microbiota profiled with 16S rRNA amplicon sequencing, SCFA and metabolome in the faeces and plasma around parturition were compared between the dietary groups. Correlation analysis was conducted to further explore the potential associations between specific bacterial taxa and metabolites. Results showed that HDF diet significantly improved the parturition process as presented by the shorter parturition duration. HDF diet increased the abundance of the phyla Bacteroidetes and Synergistetes and multiple genera. Except for butyrate, SCFA levels in the faeces and plasma of sows at parturition were elevated in HDF group. The abundances of fifteen and twelve metabolites in the faeces and plasma, respectively, markedly differ between HDF and NDF sows. These metabolites are involved in energy metabolism and bacterial metabolism. Correlation analysis also showed associations between specific bacteria taxa and metabolites. Collectively, our study indicates that the improvement of parturition duration by high fibre intake in late gestation is associated with gut microbiota, production of SCFA and other metabolites, potentially serving for energy metabolism.

Primitive lamprophyres in orogenic belts can provide crucial insights into the nature of the subcontinental lithosphere and the relevant deep crust–mantle interactions. This paper reports a suite of relatively primitive lamprophyre dykes from the North Qiangtang, central Tibetan Plateau. Zircon U–Pb ages of the lamprophyre dykes range from 214 Ma to 218 Ma, with a weighted mean age of 216 ± 1 Ma. Most of the lamprophyre samples are similar in geochemical compositions to typical primitive magmas (e.g. high MgO contents, Mg no. values and Cr, with low FeOt/MgO ratios), although they might have experienced a slightly low degree of olivine crystallization, and they show arc-like trace-element patterns and enriched Sr–Nd isotopic composition ((87Sr/86Sr)i = 0.70538–0.70540, ϵNd(t) = −2.96 to −1.65). Those geochemical and isotopic variations indicate that the lamprophyre dykes originated from partial melting of a phlogopite- and spinel-bearing peridotite mantle modified by subduction-related aqueous fluids. Combining with the other regional studies, we propose that slab subduction might have occurred during Late Triassic time, and the rollback of the oceanic lithosphere induced the lamprophyre magmatism in the central Tibetan Plateau.

The article aims to estimate and forecast the transmissibility of shigellosis and explore the association of meteorological factors with shigellosis. The mathematical model named Susceptible–Exposed–Symptomatic/Asymptomatic–Recovered–Water/Food (SEIARW) was used to explore the feature of shigellosis transmission based on the data of Wuhan City, China, from 2005 to 2017. The study applied effective reproduction number (Reff) to estimate the transmissibility. Daily meteorological data from 2008 to 2017 were used to determine Spearman's correlation with reported new cases and Reff. The SEIARW model fit the data well (χ2 = 0.00046, p > 0.999). The simulation results showed that the reservoir-to-person transmission of the shigellosis route has been interrupted. The Reff would be reduced to a transmission threshold of 1.00 (95% confidence interval (CI) 0.82–1.19) in 2035. Reducing the infectious period to 11.25 days would also decrease the value of Reff to 0.99. There was a significant correlation between new cases of shigellosis and atmospheric pressure, temperature, wind speed and sun hours per day. The correlation coefficients, although statistically significant, were very low (<0.3). In Wuhan, China, the main transmission pattern of shigellosis is person-to-person. Meteorological factors, especially daily atmospheric pressure and temperature, may influence the epidemic of shigellosis.

As the corona virus disease 2019 (COVID-19) pandemic continues around the world, understanding the transmission characteristics of COVID-19 is vital for prevention and control. We conducted the first study aiming to estimate and compare the relative risk of secondary attack rates (SARs) of COVID-19 in different contact environments. Until 26 July 2021, epidemiological studies and cluster epidemic reports of COVID-19 were retrieved from SCI, Embase, PubMed, CNKI, Wanfang and CBM in English and Chinese, respectively. Relative risks (RRs) were estimated in pairwise comparisons of SARs between different contact environments using the frequentist NMA framework, and the ranking of risks in these environments was calculated using the surface under the cumulative ranking curve (SUCRA). Subgroup analysis was performed by regions. Thirty-two studies with 68 260 participants were identified. Compared with meal or gathering, transportation (RR 10.55, 95% confidence interval (CI) 1.43–77.85), medical care (RR 11.68, 95% CI 1.58–86.61) and work or study places (RR 10.15, 95% CI 1.40–73.38) had lower risk ratios for SARs. Overall, the SUCRA rankings from the highest to the lowest were household (95.3%), meal or gathering (81.4%), public places (58.9%), daily conversation (50.1%), transportation (30.8%), medical care (18.2%) and work or study places (15.3%). Household SARs were significantly higher than other environments in the subgroup of mainland China and sensitive analysis without small sample studies (<100). In light of the risks, stratified personal protection and public health measures need to be in place accordingly, so as close contacts categorising and management.

The effects of early thiamine use on clinical outcomes in critically ill patients with acute kidney injury (AKI) are unclear. The purpose of this study was to investigate the associations between early thiamine administration and clinical outcomes in critically ill patients with AKI. The data of critically ill patients with AKI within 48 h after ICU admission were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. PSM was used to match patients early receiving thiamine treatment to those not early receiving thiamine treatment. The association between early thiamine use and in-hospital mortality due to AKI was determined using a logistic regression model. A total of 15 066 AKI patients were eligible for study inclusion. After propensity score matching (PSM), 734 pairs of patients who did and did not receive thiamine treatment in the early stage were established. Early thiamine use was associated with lower in-hospital mortality (OR 0·65; 95 % CI 0·49, 0·87; P < 0·001) and 90-d mortality (OR 0·58; 95 % CI 0·45, 0·74; P < 0·001), and it was also associated with the recovery of renal function (OR 1·26; 95 % CI 1·17, 1·36; P < 0·001). In the subgroup analysis, early thiamine administration was associated with lower in-hospital mortality in patients with stages 1 to 2 AKI. Early thiamine use was associated with improved short-term survival in critically ill patients with AKI. It was possible beneficial role in patients with stages 1 to 2 AKI according to the Kidney Disease: Improving Global Outcomes criteria.