ANALYSIS AND CHARACTERIZATION OF A PROGRAMMABLE LOW-DROPOUT REGULATOR

As portable electronic devices become a part of daily life, it creates a huge market for electronic components for those battery driven devices. Low-dropout (LDO) voltage regulator is an important part that provides steady DC supplies for other components. Low power, low noise and high stability are the desired features of a regulator. Detailed analyses on CMOS LDO design and the designs of two different compensation schemes for LDO are presented in this thesis. Experimental results of the designed compensation programmable low-power low-dropout (LDO) Voltage Regulator, in comparison with an existing compensated LDO, are also presented. The designed compensation implementation demonstrates a fast transient response and high stability in all programmable output levels. Testing chip fabricated in a standard 0.35 CMOS technology provided the important parameters of the regulator, e.g. transient response, load regulation, line regulation, power supply rejection ratio (PSRR)

Research on the Protective Effect of Twin-groyne Arrangement on Riverbank

A curved channel with intersecting streams can be easily scoured by incoming flow, and the concave bank is badly damaged. This research showed that the twin-groyne could effectively adjust and optimize the flow velocity distribution, change the shape of the free water surface of the bend, prevent erosion, and promote silting on the concave bank, and it could provide a scouring and silting effect on the convex bank. When the spacing of twin-groyne was increased to more than four times the body length of the single-groyne (spur dike), the protective effect on the concave bank was weakened, and the scouring and silting effect of the convex bank was reduced. Excessive spacing of the twin-groyne could cause local erosion damage to the concave bank. When the distance exceeded the theoretical optimum, it was equivalent to the effect of single-groyne. With the increase in the submergence degree, the velocity of the concave bank decreased first and then increased, while the velocity of convex bank decreased continuously. The protective effect of a non-submerged twin-groyne with a dam spacing of four times the body length of the single-groyne was better than that of other conditions, and it is recommended to be used in practice

Anti-PD-L1/TGF-βR fusion protein (SHR-1701) overcomes disrupted lymphocyte recovery-induced resistance to PD-1/PD-L1 inhibitors in lung cancer

Background Second-generation programmed cell death-protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors, such as bintrafusp alfa (M7824), SHR-1701, and YM101, have been developed to simultaneously block PD-1/PD-L1 and transforming growth factor-beta/transforming growth factor-beta receptor (TGF-β/TGF-βR). Consequently, it is necessary to identify predictive factors of lung cancer patients who are not only resistant to PD-1/PD-L1 inhibitors but also sensitive to bifunctional drugs. The purpose of this study was to search for such predictors. Methods Multivariable Cox regression was used to study the association between the clinical outcome of treatment with PD-1/PD-L1 inhibitors and lymphocyte recovery after lymphopenia in lung cancer patients. Murine CMT167 lung cancer cells were engineered to express the firefly luciferase gene and implanted orthotopically in the lung of syngeneic mice. Bioluminescence imaging, flow cytometry, and immunohistochemistry were employed to determine response to immunotherapy and function of tumor-infiltrating immune cells. Results For lung cancer patients treated with anti-PD-1/PD-L1 antibodies, poor lymphocyte recovery was associated with a shorter progression-free survival (PFS; P < 0.001), an accumulation of regulatory T cells (Tregs), and an elimination of CD8+ T cells in the peripheral blood. Levels of CD8+ T cells and Treg cells were also imbalanced in the tumors and peripheral immune organs of mice with poor lymphocyte recovery after chemotherapy. Moreover, these mice failed to respond to anti-PD-1 antibodies but remained sensitive to the anti-PD-L1/TGF-βR fusion protein (SHR-1701). Consistently, SHR-1701 but not anti-PD-1 antibodies, markedly enhanced IFN-γ production and Ki-67 expression in peripheral CD8+ T cells from patients with impaired lymphocyte recovery. Conclusions Lung cancer patients with poor lymphocyte recovery and suffering from persistent lymphopenia after previous chemotherapy are resistant to anti-PD-1/PD-L1 antibodies but might be sensitive to second-generation agents such as SHR-1701.publishedVersio

A modified clinically relevant post-operative pancreatic fistula risk evaluation model based on ultrasound shear wave elastography: a prospective study

Objective·To modify previous clinically relevant post-operative pancreatic fistula (CR-POPF) risk evaluation models with quantitative evaluation of pancreatic tissue stiffness by ultrasound shear wave elastography (SWE).Methods·In this prospective study, the patients who were diagnosed as having pancreatic tumors and scheduled to undergo pancreatectomy at Zhongshan Hospital, Fudan University were initially enrolled, whose clinical information was collected. Virtual touch tissue imaging and quantification technology (VTIQ) assessment was applied to the patients within one week before the surgery to measure the shear wave velocity (SWV) of pancreatic lesions and the normal parenchyma of pancreatic body in the superficial layer of the portal vein. During the surgery, the surgeons qualitatively evaluated the stiffness of pancreases via direct palpation and divided them into soft pancreases and medium-hard pancreases. During the 3-week follow-up period after pancreatectomy, CR-POPF was diagnosed according to 2016 International Study Group of Pancreatic Fistula (ISGPF) standard. Peri-operative risk factors of CR-POPF were analyzed by univariate and multivariate Logistic regression to build the prediction model. Evaluation and comparison of diagnostic efficacy and clinical benefits among different models were then performed via receiver operating characteristic (ROC) curve and decision curve analysis (DCA).Results·From September 2021 to March 2022, 100 patients were enrolled in this study, including 33 patients (33.0%) who received pancreaticoduodenectomy (PD) and 67 patients (67.0%) who received distal pancreatectomy. CR-POPF was diagnosed in 35 patients (35.0%) during the 3-week post-pancreatectomy follow-up. Multivariate Logistic regression analysis revealed that the SWV value of the body part of pancreatic parenchyma in the superficial layer of the portal vein [lgOR=-2.934 (95%CI -4.387‒-1.479), P=0.000] and the presence of a non-dilated main pancreatic duct (≤3 mm) [lgOR=0.805 (95%CI 0.274‒1.335), P=0.003] were independent risk factors that significantly correlated with the occurrence of CR-POPF after pancreatectomy. The modified model based on the SWE parameter achieved the area under the ROC curve of 0.842, with the sensitivity, the specificity, the positive predictive value, the negative predictive value and the likelihood ratio of 85.7%, 64.6%, 70.5%, 81.8% and 2.422 in predicting CR-POPF. DCA revealed a better clinical benefit of the modified model compared to the previous prediction models [fistula risk score (FRS) and alternative fistula risk score (a-FRS)].Conclusion·The modified model based on the SWE parameter and identified clinical risk factors can make non-invasive, quantitative and objective evaluation of CR-POPF risk before pancreatectomy, and provide sufficient diagnostic efficacy and clinical benefits

This is what we know: Assessing the stock status of the data-poor skipjack tuna (Katsuwonus pelamis) fishery in the South China Sea

Skipjack tuna (Katsuwonus pelamis) is a highly migratory species of significant value in global marine fisheries. The South China Sea (SCS) is the largest marginal sea in the northwestern Pacific Ocean, and many tuna and tuna-like species occur within it. Although a recent Western and Central Pacific Fisheries Commission report identified skipjack tuna in the western and central Pacific to be sustainably fished, the exploitation status of skipjack tuna in the SCS is still unclear, due to limited data. We apply two data-poor methods, length-based Bayesian biomass estimation (LBB) and length-based spawning potential ratio (LBSPR), to assess the status of skipjack tuna stock in the SCS. We use electronic length frequency analysis to estimate von Bertalanffy growth parameters (asymptotic length Linf and growth coefficient K) to serve as priors for LBB and LBSPR estimation. Estimates are calculated for SCS skipjack tuna Linf (68.3 cm), K (0.325 year−1), natural mortality (0.49 year−1) and mean fork length at 50% sexual maturity (36.7 cm). LBB analysis reveals the estimated relative stock size (0.29) indicates that the SCS skipjack tuna stock maybe heavily overfished. LBSPR analysis reveals the estimated spawning potential ratio for this fishery to be 3%, which is significantly below the limit reference point of 20%. Accordingly, for the SCS skipjack tuna stock we identify a need to reduce fishing mortality by controlling fishing effort and increasing catchable size

Boosting with an aerosolized Ad5-nCoV elicited robust immune responses in inactivated COVID-19 vaccines recipients

IntroductionThe SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required.MethodsWe have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. ResultsThe aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. DiscussionOur findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=152729, identifier ChiCTR2200057278

A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer.

peer reviewedCurrent therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II-III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)-0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3-41.3). RCB-0/I is 55.7% (95% CI, 44.7-66.1). ORR is 87.4%, (95% CI, 78.1-93.2) and bpCR is 35.4% (95% CI, 25.8-46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Alterations of cortical morphology in age-related hearing loss

We provided data (demographic, audimeotry, and cognitive variables in Sub_info.xlsx, preprocessed MRS data in metabolites.mat, and preprocessed MRI data in preprocessed_images.zip) and the codes for the paper below. Qiu, Xiaofan and Yang, Jing and Hu, Xin and Li, Junle and Zhao, Min and Ren, Fuxin and Weng, Xuchu and Edden, Richard and Gao, Fei and Wang, Jinhui, Plastic Alterations in Cortical Morphology Due to Age-Related Hearing Loss: Multiparametric Mapping, Multiscale Neurobiological Underpinnings and Roles in Cognitive Impairment. Available at SSRN: https://ssrn.com/abstract=4605793 or http://dx.doi.org/10.2139/ssrn.460579