A fully integrated concurrent triple-band low noise amplifier (LNA) is designed and presented in this paper. It has been fabricated using TSMC 0.25-/spl mu/m mixed-signal CMOS process. A two stage ...topology with bias-current reuse technique has been used to simultaneously achieve high gain and good matching without large amount of power consumption at all three desired band -1.8GHz, 2.45GHz and 5.25GHz. It also achieves similar good performance at these three different frequencies. We will show its post simulation results to demonstrate this good performance. The LNA exhibits input matching to 50ohm with S/sub 11/ of -10.6dB at 1.8GHz, -10.4dB at 2.45GHz and -19.9dB at 5.25GHz as well as output matching to 50ohm with S/sub 22/of -15.5dB, -12.5dB and -12.0dB, respectively. And it provides forward gain (S/sub 21/) of 10.1dB, 10.8dB and 11.8dB with noise figure of 3.72dB, 4.76dB and 6.38dB respectively while drawing 39mW from a 2.5V supply voltage.
Background
The clinicopathological features and prognosis of breast cancer in Asia are different from those in the Western countries. Tumor‐infiltrating immune cells can influence the outcome of ...patients with breast cancer, but they have not been systemically evaluated in Asian patients with breast cancer.
Methods
We compared the immune score, composition, and prognostic impact of infiltrating immune cells between Asian and Western patients with breast cancer by analyzing gene expression profiles from eight Gene Expression Omnibus data sets and The Cancer Genome Atlas data set. The Estimation of Stromal and Immune Cells in Malignant Tumours Using Expression Data (ESTIMATE) and Cell Type Identification by Estimating Relative Subsets of Known RNA Transcripts (CIBERSORT) algorithms were used to determine the immune score and composition of tumor‐infiltrating immune cells, respectively.
Findings
This study included 462 Asian patients and 2,186 Western patients. Tumors of Asian patients had significantly higher immune score, particularly in the luminal B and HER2‐enriched subtypes. High immune score was associated with favorable prognosis in both Asian and Western patients, and Asian race with a high ESTIMATE immune score provided additional power to predict longer disease‐free survival. Activated CD4 T cells and M2 macrophages were the most strongly associated with survival in both Asian and Western patients.
Interpretation
Our study highlights the difference in tumor immune microenvironments between Asian and Western patients. The higher ESTIMATE immune score, which represents more abundant tumor‐infiltrating immune cells, in tumors of Asian patients partly explains their favorable prognosis.
Implications for Practice
The tumor microenvironment serves as an interface that affects the human body's reaction to cancer cells. Evidence has revealed that tumor‐infiltrating immune cells were associated with patient prognosis. This study demonstrated the disparity of tumor microenvironments and their prognostic impact between Asian and Western patients with breast cancer. The differences in immune score partially explained the racial survival differences noted in recent studies. Integrated analysis of tumor cells, tumor microenvironment, and racial effect may significantly improve recurrence risk prediction for patients with stage I–III breast cancer. Because the effect of tumor microenvironment varies across different populations, a model of interaction between immune score and race/ethnicity is recommended in accessing the risk of patients with cancer.
Statistics indicate that the incidence of breast cancer in Asia has increased in the past three decades. This article evaluates tumor‐infiltrating immune cells of breast cancer, comparing a representative amount and the composition of infiltrating immune cells in breast cancer between Asian and Western patients.
Purpose
This paper aims to examine the operating frontier, trajectory and absorptive capacity influencing proactive and reactive dimension of supply chain resilience and implementation in ...inter-organizational relationships.
Design/methodology/approach
This paper presents a research model comprises six research hypotheses with five constructs, including trajectory, absorptive capacity, operating frontier, proactive and reactive dimension of supply chain resilience. The hypotheses are tested on data collected from 297 senior managers of Taiwanese manufacturing firms, using structural equation modeling.
Findings
The study provides insights into how supply chain members can reinforce their operating frontier, trajectory and absorptive capacity activities to improve proactive and reactive dimension of supply chain resilience.
Research limitations/implications
The resultant findings cannot be generalized for all forms of supply chains, as they exclusively reflect those in Taiwan. With the research model developed, cross-industrial studies on various forms of supply chains would be worth conducting to investigate whether their inter-relationship effects differ in relation to inter-organizational supply chain resilience.
Practical implications
This study provides multiple insights for managers and practices seeking to improve inter-organizational supply chain resilience, which have become increasingly popular because their factors enhance coping strategies to achieve corporate goals. The proactive and reactive dimension of supply chain resilience can be effectively improved by enhancing trajectory, absorptive capacity and operating frontier.
Originality/value
This empirical research attempted to fill the gaps created by trajectory and resource-based perspectives in inter-organizational supply chain resilience. This study reveals how supply chain members can reinforce the factors of their coping strategies (i.e. operating frontier, trajectory and absorptive capacity) to make significant improvements, which is not dealt with in previous studies.
Oxidative stress‐induced brain cell damage is a crucial factor in the pathogenesis of reactive oxygen species (ROS)‐associated neurological diseases. Further, studies show that astrocytes are an ...important immunocompetent cell in the brain and play a potentially significant role in various neurological diseases. Therefore, elimination of ROS overproduction might be a potential strategy for preventing and treating neurological diseases. Accumulating evidence indicates that calycosin, a main active ingredient in the Chinese herbal medicine Huangqi (Radix Astragali Mongolici), is a potential therapeutic candidate with anti‐inflammation and/or anticancer effects. Here, we investigated the protective effect of calycosin in brain astrocytes by mimicking in vitro oxidative stress using H2O2. The results revealed that H2O2 significantly induced ROS and inflammatory factor (tumor necrosis factor TNF‐α and interleukin IL‐1β) production, whereas post‐treatment with calycosin dramatically and concentration‐dependently suppressed H2O2‐induced damage by enhancing cell viability, repressing ROS and inflammatory factor production, and increasing superoxide dismutase (SOD) expression. Additionally, we found that calycosin facilitated nuclear factor erythroid 2‐related factor 2 (Nrf2) expression and promoted its nuclear translocation, thereby inducing the expression of antioxidant molecules (heme oxygenase HO‐1 and SOD) following H2O2 treatment. Moreover, calycosin did not attenuated H2O2‐induced astrocyte damage and ROS production in the presence of the ML385 (a Nrf2‐specific inhibitor) and following Nrf2 silencing. Furthermore, calycosin failed to increase Akt phosphorylation and mitigate H2O2‐induced astrocyte damage in the presence of the LY294002 (a selective phosphatidylinositol 3‐kinase inhibitor), indicating that calycosin‐mediated regulation of oxidative‐stress homeostasis involved Akt/Nrf2/HO‐1 signaling. These findings demonstrated that calycosin protects against oxidative injury in brain astrocytes by regulating oxidative stress through the AKT/Nrf2/HO‐1 signaling pathway.
Lateral ankle instability (LAI) compromises the normal kinematics of the ankle, affecting activities of daily living. In vitro kinematics of ankles with LAI during single‐plane motions are available, ...but the active control stability of these motions remains unclear. The current study measured the 3D ankle kinematics during unresisted single‐plane motion tests using a bi‐plane fluoroscope with a CT model‐based 2D/3D registration method in 12 patients with LAI and 14 healthy peers. The coupling of the kinematic components at the talocrural and subtalar joints was quantified by the path difference between the forward and return paths of the coupled motion. Significantly increased path differences were found in the subtalar dorsiflexion/plantarflexion and inversion/eversion components during internal/external rotation tests (p < 0.05). During inversion/eversion, significantly reduced tibiocalcaneal ranges of motion and the path differences in the talocrural and subtalar dorsiflexion/plantarflexion components were noted (p < 0.05). The current results suggest that chronic LAI had compromised control stability at the subtalar joint during internal/external rotation tests and a conservative motion control strategy with significantly reduced ranges of motion to maintain good control of out‐of‐plane motion components in response to direct challenges of the anterior talofibular ligament during inversion/eversion tests. The current results also suggest that, compared to kinematic patterns of individual components, the path difference of the coupled motion may serve as a better measure of the motion control stability of the ankle in differentiating LAI from healthy controls.
The removal of large bile duct stones (> 15 mm) by conventional endoscopic sphincterotomy (EST) and endoscopic papillary balloon dilation (EPBD) can be challenging, requiring mechanical lithotripsy ...(ML) in addition to EST or EPBD. The primary complication of ML is basket and stone impaction, which can lead to complications such as pancreatitis and cholangitis. The present study aims to investigate the efficacy of limited EST plus endoscopic papillary large balloon dilation (EST-EPLBD) for large bile duct stone extraction with an extent of cutting < 1/2 the length of the papillary mound.
We enrolled 185 patients with ≥15 mm bile duct stones who received EST, EPLBD and limited EST-EPLBD treatment from January 1, 2010 to February 28, 2018, at Kaohsiung Chang Gung Memorial Hospital (Kaohsiung, Taiwan). All patients were categorized into three groups: EST group (n = 31), EPLBD group (n = 96), and limited EST-EPLBD group (n = 58). The primary outcome variables were the success rate of complete stone removal and complications.
The limited EST-EPLBD group exhibited a higher success rate of the first-session treatment compared with the EST and EPLBD groups (98.3% vs. 83.9% vs. 86.5%; P = 0.032) but required a longer procedure time (32 (12-61) min vs. 23.5 (17-68) min vs. 25.0 (14-60) min; P = 0.001). The need for ML during the procedure was 4 (12.9%) in the EST group, 10 (10.4%) in the EPLBD group and 2 (3.4%) in the limited EST-EPLBD group. Post-procedure bleeding in the EST group was more common than that in the limited EST-EPLBD group (9.7% vs. 0%; P = 0.038). Furthermore, dilated bile duct was the only risk factor for bile duct stone recurrence in the limited EST-EPLBD group.
Limited EST-EPLBD exhibits a higher success rate but requires marginally longer procedure time for the first-session treatment. Furthermore, dilated bile duct is the only risk factor for bile duct stone recurrence in patients undergoing limited EST-EPLBD.
BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit ...vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 μg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 μg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 μg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.
Polyethylene glycol (PEG) is a biocompatible polymer that is often attached to therapeutic molecules to improve bioavailability and therapeutic efficacy. Although antibodies with specificity for PEG ...may compromise the safety and effectiveness of PEGylated medicines, the prevalence of pre-existing anti-PEG antibodies in healthy individuals is unclear. Chimeric human anti-PEG antibody standards were created to accurately measure anti-PEG IgM and IgG antibodies by direct ELISA with confirmation by a competition assay in the plasma of 1504 healthy Han Chinese donors residing in Taiwan. Anti-PEG antibodies were detected in 44.3% of healthy donors with a high prevalence of both anti-PEG IgM (27.1%) and anti-PEG IgG (25.7%). Anti-PEG IgM and IgG antibodies were significantly more common in females as compared to males (32.0% vs 22.2% for IgM, p < 0.0001 and 28.3% vs 23.0% for IgG, p = 0.018). The prevalence of anti-PEG IgG antibodies was higher in younger (up to 60% for 20 year olds) as opposed to older (20% for >50 years) male and female donors. Anti-PEG IgG concentrations were negatively associated with donor age in both females (p = 0.0073) and males (p = 0.026). Both anti-PEG IgM and IgG strongly bound PEGylated medicines. The described assay can assist in the elucidation of the impact of anti-PEG antibodies on the safety and therapeutic efficacy of PEGylated medicines.
Objective： To compare the prognostic prediction between dichotomized and fractionated evaluations of hormone receptor expressions. Methods： Patients with stages Ⅰ-Ⅲ breast cancers, who received ...adjuvant tamoxifen, were enrolled. The expression of estrogen receptor （ER） and progesterone receptor （PR） was evaluated by immu- nohistochemistry （IHC）. A fractionated score （F score）, the percentage of positive-staining nuclei （0=none, 1=1%-10% 2= 11%-30%, 3=31%-50%, 4=51%-70%, and 5=71%-100%）, was assigned to each case. The dichotomized scoring method defines an F score 〉1 as positive. The prognostic values of both scores were compared by multiple Cox＇s proportional hazard models of disease-free survival （DFS） and overall survival （OS）. Results： Four hundred and six- teen patients with a median follow-up of 78.0 months were included. F scores for ER and PR correlated directly with DFS and OS. Although both the dichotomized and fractionated ER and PR scores were significantly associated with DFS and OS in univariate analyses, only fractionated ER and PR scores remained as independent prognostic factors of DFS and OS in the final multiple Cox＇s proportional hazard models. Conclusion： Fractionated IHC hormone receptor expression evaluation enhances the prognostic prediction compared with a dichotomized assessment.
Cadmium (Cd), one of well-known highly toxic environmental and industrial pollutants, causes a number of adverse health effects and diseases in humans. The growing epidemiological studies have ...suggested a possible link between Cd exposure and diabetes mellitus (DM). However, the toxicological effects and underlying mechanisms of Cd-induced pancreatic β-cell injury are still unknown. In this study, we found that Cd significantly decreased cell viability, and increased sub-G1 hypodiploid cells and annexin V-Cy3 binding in pancreatic β-cell-derived RIN-m5F cells. Cd also increased intracellular reactive oxygen species (ROS) generation and malondialdehyde (MDA) production and induced mitochondrial dysfunction (the loss of mitochondrial membrane potential (MMP) and the increase of cytosolic cytochrome c release), the decreased Bcl-2 expression, increased p53 expression, poly (ADP-ribose) polymerase (PARP) cleavage, and caspase cascades, which accompanied with intracellular Cd accumulation. Pretreatment with the antioxidant N-acetylcysteine (NAC) effectively reversed these Cd-induced events. Furthermore, exposure to Cd induced the phosphorylations of c-jun N-terminal kinases (JNK), extracellular signal-regulated kinases (ERK)1/2, and p38-mitogen-activated protein kinase (MAPK), which was prevented by NAC. Additionally, the specific JNK inhibitor SP600125 or JNK-specific small interference RNA (si-RNA) transfection suppressed Cd-induced β-cell apoptosis and related signals, but not ERK1/2 and p38-MAPK inhibitors (PD98059 and SB203580) did not. However, the JNK inhibitor or JNK-specific si-RNA did not suppress ROS generation in Cd-treated cells. These results indicate that Cd induces pancreatic β-cell death via an oxidative stress downstream-mediated JNK activation-triggered mitochondria-regulated apoptotic pathway.
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