This study proposes a broadband complementary metal-oxide semiconductor (CMOS) low-noise amplifier (LNA) with intrinsic band-selective out-of-band (OB) blocker rejection capabilities. The proposed ...LNA design utilizes a differential four-phase N-path filter as the amplifier load to offer a substantial total load impedance difference between the in-band (IB) and OB frequency bands. This ensures that the LNA design securely accomplishes a high-quality-factor frequency selectivity response with lower radio frequency signal losses and its OB rejection performance is maintained against process, voltage, and temperature variations, compared with the case of using the N-path filter as a signal path. To validate its blocker-tolerable performance, the designed LNA was fabricated using a 65-nm CMOS technology and was primarily characterized in the frequency division duplexing bands of the long-term evolution and fifth-generation new radio standards, spanning from 1.7 to 2.7 GHz. The implemented design consistently achieved a transmitter leakage rejection greater than 17 dB across all target frequency bands from several samples. Furthermore, the design attained IB voltage gains greater than 36.4 dB and 40.4 dB, noise figures (NFs) of 1.78 dB and 1.5 dB, OB input 1-dB compression point greater than -27.0 dBm and -26.7 dBm, and full-/half-duplexing OB input-referred third-order intercept points greater than 4.1/3.8 dBm and 4.8/5.0 dBm at the mid- and high-bands, respectively. The OB-induced NF degradation was maintained at less than 0.7 dB. A total bias current of 37.7 mA was required with a nominal supply voltage of 1.2 V. The occupied active area of the implemented design was approximately 0.77 mm2, excluding the bonding pads and input/output cells.
Since the completion of the HapMap project, huge numbers of individual genotypes have been generated from many kinds of laboratories. The efforts of finding or interpreting genetic association ...between disease and SNPs/haplotypes have been on-going widely. So, the necessity of the capability to analyze huge data and diverse interpretation of the results are growing rapidly.
We have developed an advanced tool to perform linkage disequilibrium analysis, and genetic association analysis between disease and SNPs/haplotypes in an integrated web interface. It comprises of four main analysis modules: (i) data import and preprocessing, (ii) haplotype estimation, (iii) LD blocking and (iv) association analysis. Hardy-Weinberg Equilibrium test is implemented for each SNPs in the data preprocessing. Haplotypes are reconstructed from unphased diploid genotype data, and linkage disequilibrium between pairwise SNPs is computed and represented by D', r2 and LOD score. Tagging SNPs are determined by using the square of Pearson's correlation coefficient (r2). If genotypes from two different sample groups are available, diverse genetic association analyses are implemented using additive, codominant, dominant and recessive models. Multiple verified algorithms and statistics are implemented in parallel for the reliability of the analysis.
SNPAnalyzer 2.0 performs linkage disequilibrium analysis and genetic association analysis in an integrated web interface using multiple verified algorithms and statistics. Diverse analysis methods, capability of handling huge data and visual comparison of analysis results are very comprehensive and easy-to-use.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Epigallocatechin gallate (EGCG) exhibits antioxidant, anti-cancer, and anti-inflammatory properties; however, low cellular permeability and stability limit its bioavailability. Liposomes have the ...potential for enhancing bioactive compounds’ bioavailability. Yet, low entrapment efficiency (EE) and burst release of hydrophilic substances make them impractical for food industry use. Here, we incorporated gelatin into liposomes to overcome these limitations. EGCG-loaded conventional liposomes (EGCG/CLs) and gelatinized-core liposomes (EGCG/GLs) had small particle sizes and high absolute zeta potentials. Encapsulation in EGCG/GLs significantly improved the EE of EGCG compared to that in EGCG/CLs (p < 0.05). EGCG/GLs retained EGCG in the hydrophilic region, whereas EGCG/CLs exhibited significantly higher release of EGCG during storage (p < 0.05). Additionally, in comparison to EGCG/CLs, gelatin incorporation significantly enhanced the sustained release, cellular permeability, and cellular antioxidant activity of EGCG (p < 0.05). This study emphasizes the capability of gelatinized-core liposomes as a potent delivery system for enhancing the stability and bioavailability of EGCG/CLs, broadening the prospects for utilizing them in the food industry.
•Gelatin was incorporated within the hydrophilic region of liposomes.•Gelatin-core liposomes improved the entrapment efficiency of EGCG.•Gelatin-core liposomes improved the storage and heat stability of EGCG.•Gelatin-core liposomes enhanced the cellular properties of EGCG.•Gelatin incorporation could broaden the applications of EGCG-loaded liposomes.
Methamphetamine is a highly addictive drug that has a neurotoxic effect on the brain. A growing body of evidence suggests that brain-derived neurotrophic factor (BDNF) is associated with addictive ...behavior. The present study investigated the changes in plasma BDNF concentration that were induced by chronic methamphetamine use. Using an enzyme-linked immunosorbent assay (ELISA), we measured peripheral BDNF levels in methamphetamine users and in a control group. The plasma BDNF concentrations of methamphetamine users were significantly higher compared with those of controls (2536.3
pg/ml versus 1352.6
pg/ml). This finding suggests that BDNF plays some role in the neurotoxicity of methamphetamine.
Abstract Background and Aims Urine creatinine excretion is a surrogate marker of muscle mass and low urine creatinine excretion is a predictor of poor clinical outcome. There are several methods to ...estimate urine creatinine excretion. However, little is known about the clinical implication of discrepancy between actual and estimated urine creatinine excretion in chronic kidney disease (CKD). The aim of this study is to investigate the association between actual and estimated urine creatinine excretion discrepancy and mortality in CKD. Method This study analysed 1805 participants from the KNOW-CKD cohort. They underwent 24-hr urine collection and measured urine creatinine excretion at baseline. Their estimated urine creatinine excretion was calculated by Joachim's method. Discrepancy between actual and estimated urine creatinine excretion (dUCr) was defined as actual urine creatinine excretion minus estimated urine creatinine excretion. Patients were divided into 3 groups according to their tertile of dUCr. The study endpoint was all-cause death. Results During a follow-up of 13 062 person-years (median 8.0 years), 151 patients (8.4%) died, with a corresponding death rate of 11.6 (95% CI 9.9-13.6) per 1000 patients-years. 86 (14.4%), 41 (6.8%) and 24 (3.4%) patients from each 1st to 3rd tertile of dUCr died (P < 0.001). In multivariate Cox proportional hazard analysis, there was a graded association of dUCr with all-cause mortality. The adjusted hazard ratios (95% CI) of 2nd and 3rd tertile were 0.58 (0.39-0.86) and 0.36 (0.22-0.58) compared with the 1st tertile. Conclusion Higher discrepancy between actual and estimated urine creatinine excretion is associated with lower risk of mortality in predialysis CKD patients. This association was independent of various conventional and CKD-related risk factors.
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Background: We evaluated the survival benefit of levetiracetam as a chemosensitizer of temozolomide for patients with newly diagnosed glioblastoma. Methods: This was an open-label, ...multicenter, phase II study (NCT02815410). Eligible patients were aged 18 years or older and had newly diagnosed glioblastoma with an ECOG performance status of 0-2. All patients received radiotherapy with concurrent temozolomide (75 mg/m
2
/day) followed by adjuvant temozolomide (150-200 mg/m
2
/day for 5 days during six 28-day cycles). The first dose of levetiracetam was given just after the surgery at 250mg orally twice a day and increased up to 500mg twice a day prior to radiation. This prospective study was designed to test whether levetiracetam in conjunction with temozolomide improved survival. The historical control group was based on data from a study by Gwak et al. for Korean patients with newly diagnosed glioblastoma with a median overall survival(OS) of 17.5 months and a median progression-free survival (PFS) of 10.1 months. Results: Forty-six patients were enrolled between August 2016 and January 2019. The median follow-up duration was 24.9 months (range, 7.9-35.5). All patients completed standard radiation therapy with temozolomide, and 39 (84.8%) patients completed six cycles of adjuvant temozolomide. Median overall survival (OS) was 30.0 months, and median PFS was 15.0 months. OS at 6, 12, and 24 months was 100%, 91.3%, and 60.7%, respectively. PFS at 6, 12, and 24 months was 93.2%, 65.3%, and 22.6%, respectively. Conclusions: Addition of levetiracetam during concurrent and adjuvant temozolomide along with radiotherapy in patients with newly diagnosed glioblastoma may result in improved outcomes compared to historical data and merits further study. Clinical trial information: NCT02815410 .
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53
Background: Acute Palliative Care Units (ACPUs) are novel inpatient programs in tertiary care centers that provide aggressive symptom management and assist transition to hospice. ...However, patients often die in the APCU before successfully transferring to hospice. The aim of this study was to evaluate the symptom burden and characteristics of advanced cancer patients who die in the APCU. Methods: We retrospectively reviewed the medical records of all advanced cancer patients admitted to the APCU between April, 2015 and March, 2016 at a tertiary cancer center in Korea. Basic characteristics and symptom burden assessed by the Edmonton Symptom Assessment System (ESAS) were obtained from consultation upon APCU admission. Statistical analyses were conducted to compare patients who died in the APCU with those who were discharged alive. Results: Of the 267 patients analyzed, 87 patients (33%) died in the APCU. The median age of patients was 66 (range, 23-97). Patients who died in the APCU had higher ESAS scores of drowsiness (6 vs 5, P = 0.002), dyspnea (4 vs 2, P = 0.001), anorexia (8 vs 6, P = 0.014) and insomnia (6 vs 4, P = 0.001) compared to patients who discharged alive. Total symptom distress scores (SDS) were also significantly higher (47 vs 40, P = 0.001). Patients who died in the APCU were more likely to be male (odds ratio OR for female patients 0.38, 95% confidence interval CI 0.22-0.67, P < 0.001) and have higher ESAS scores of drowsiness (OR 2.08, 95% CI, 1.08-3.99, P = 0.029) and dyspnea (OR 2.19, 95% CI 1.26-3.80, P = 0.005). These patients showed significantly shorter survival after APCU admission (7 days vs 31 days, P < 0.001). Conclusions: Advanced cancer patients who die in the APCU are more likely to be male and have significantly higher symptom burden that include drowsiness and dyspnea. These patients show rapid clinical deterioration after APCU admission. More proactive and timely end-of-life care is needed for these patients.
The dehydration responsive element binding protein 2C (DREB2C) is a dehydration responsive element/C-repeat (DRE/CRT)-motif binding transcription factor that induced by mild heat stress. Previous ...experiments established that overexpression of DREB2C cDNA driven by the cauliflower mosaic virus 35S promoter (35S:DREB2C) resulted in increased heat tolerance in Arabidopsis. We first analyzed the proteomic profiles in wild-type and 35S:DREB2C plants at a normal temperature (22℃), but could not detect any differences between the proteomes of wild-type and 35S:DREB2C plants. The transcript level of DREB2C in 35S:DREB2C plants after treatment with mild heat stress was increased more than two times compared with expression in 35S:DREB2C plants under unstressed condition. A proteomic approach was used to decipher the molecular mechanisms underlying thermotolerance in 35S:DREB2C Arabidopsis plants. Eleven protein spots were identified as being differentially regulated in 35S:DREB2C plants. Moreover, in silico motif analysis showed that peptidyl-prolyl isomerase ROC4, glutathione transferase 8, pyridoxal biosynthesis protein PDX1, and elongation factor Tu contained one or more DRE/CRT motifs. To our knowledge, this study is the first to identify possible targets of DREB2C transcription factors at the protein level. The proteomic results were in agreement with transcriptional data.
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TPS9636
Background: In patients with activating EGFR mutations and ALK fusion, target specific tyrosine kinase inhibitor (TKI) showed significant survival improvement compared to the ...cytotoxic chemotherapy. However, the questions remain which combination strategy will be the best option for the patients who have failed from TKI. Especially, the role of an immune checkpoint inhibitor (ICI) in this population is still unclear. This study is designed and conducted based on the recent subgroup analyses from the IMpower 150 study which showed the positive clinical outcomes of atezolizumab combined with VEGF inhibitor and conventional cytotoxic chemotherapy in EGFR mutation and ALK translocation. Methods: This study is the phase III, open-label, multicenter study of atezolizumab in combination with bevacizumab + carboplatin + paclitaxel (ABCP, Arm A) compared with pemetrexed + cisplatin or carboplatin (Arm B). The study population will be randomized to either Arm A (n = 152) or Arm B (n = 72) based on two stratification factors, EGFR vs. ALK and presence of brain metastases. In Arm A, patients will be treated with 4 or 6 cycles of ABCP followed by maintenance atezolizumab and bevacizumab every three weeks. In Arm B, pemetrexed maintenance therapy will be applied every three weeks after 4 or 6 cycles of pemetrexed + cisplatin or carboplatin. As key inclusion criteria, the patients must be diagnosed with stage IV non-squamous non-small cell lung cancer with either activating EGFR mutation or ALK translocation. All the patients need to be cytotoxic chemotherapy naïve and must have experienced disease progression to treatment with at least one EGFR or ALK TKI. If the patients have T790M mutation after 1
st
or 2
nd
generation EGFR TKI, second line 3
rd
generation EGFR TKI treatment is mandatory. The number of T790M positive patients is restricted to under 30% of the entire study population. The primary endpoint is progression-free survival and the major secondary endpoints are overall survival, objective response rate and duration of response. A total of 228 subjects will be enrolled to detect a hazard ratio of 0.67. The first subject received treatment in Aug. 2019 and 19 patients receive the treatment. This study is opened in 3 sites and expected to be opened at 18 sites in South Korea. The time point for the primary analyses is Q3. 2022. Clinical trial information: NCT03991403 .
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