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In this paper, a CMOS wideband low-pass filter is proposed. In the wide band active filter design, the unit gain frequency (GBW) of OPAMP should be larger than GHz. The GBW of the proposed OPAMP is around 2.3 GHz. Additionally, the OPAMP with a complementary structure in signal and common mode feedback is proposed and has a wide operating voltage range at the input and output. The 1-dB gain compression point (P1dB) at the output is 4.9 dBm. A source follower is employed for driving 50 Ω output impedance without degrading the bandwidth and linearity of the filter. The power consumption is 27 mW from a 1-V supply voltage. The 3 dB bandwidth of the filter ranges from 330 MHz to 660 MHz with 3-bit cap tuning. This work is implemented in a 65-nm CMOS process, with a chip area of 0.18 mm2.

In this paper, an energy-efficient switching scheme with additional quarter-reference voltage sources in a successive approximation register (SAR) analog-to-digital converter (ADC) is proposed for a low power and small area device for frequency modulated continuous wave (FMCW) radar transceivers. Recently, state-of-the-art ADCs have adopted a configuration that also uses Vref/2 as the reference voltage of the ADCs to improve the switching energy of capacitive digital-to-analog converter (CDAC). The proposed switching configuration additionally uses Vref/4 and 3Vref/4 reference voltages as the reference voltage of CDAC. Compared to state-of-the-art configurations that use the additional reference voltage of Vref/2, the average switching energy, and the total capacitance of CDAC in the proposed configuration are reduced by about 87.5% and 50%, respectively. In this switching scheme, the CDAC output voltage gradually converges to Vref/2, like with conventional SAR ADCs, which minimizes the dynamic offset that deteriorates the linearity of the SAR ADC.

The Korean Society of Laryngology, Phoniatrics and Logopedics appointed a task force to establish clinical practice guidelines for the management of unilateral vocal fold paralysis (UVFP). These guidelines cover a comprehensive range of management-related factors, including the diagnosis and treatment of UVFP, and provide in-depth information based on current, up-to-date knowledge. Detailed evidence profiles are provided for each recommendation. The CORE databases, including OVID Medline, Embase, the Cochrane Library, and KoreaMed, were searched to identify all relevant papers, using a predefined search strategy. When insufficient evidence existed, expert opinions and Delphi questionnaires were used to fill the evidence gap. The committee developed 16 evidence-based recommendations in six categories: initial evaluation (R1–4), spontaneous recovery (R5), medical treatment (R6), surgical treatment (R7–14), voice therapy (R15), and aspiration prevention (R16). The goal of these guidelines is to assist general otolaryngologists and speech-language pathologists who are primarily responsible for treating patients with UVFP. These guidelines are also intended to facilitate understanding of the condition among other health-care providers, including primary care physicians, nurses, and policy-makers.

This paper examines the relationship of the leading financial assets, Bitcoin, Gold, and S&P 500 with GARCH-Dynamic Conditional Correlation (DCC), Nonlinear Asymmetric GARCH DCC (NA-DCC), Gaussian copula-based GARCH-DCC (GC-DCC), and Gaussian copula-based Nonlinear Asymmetric-DCC (GCNA-DCC). Under the high volatility financial situation such as the COVID-19 pandemic occurrence, there exist a computation difficulty to use the traditional DCC method to the selected cryptocurrencies. To solve this limitation, GC-DCC and GCNA-DCC are applied to investigate the time-varying relationship among Bitcoin, Gold, and S&P 500. In terms of log-likelihood, we show that GC-DCC and GCNA-DCC are better models than DCC and NA-DCC to show relationship of Bitcoin with Gold and S&P 500. We also consider the relationships among time-varying conditional correlation with Bitcoin volatility, and S&P 500 volatility by a Gaussian Copula Marginal Regression (GCMR) model. The empirical findings show that S&P 500 and Gold price are statistically significant to Bitcoin in terms of log-return and volatility.

The vacuolar H+-adenosine triphosphatase (ATPase) subunit V0C (ATP6V0C), a proton-conducting, pore-forming subunit of vacuolar ATPase, maintains pH homeostasis and induces organelle acidification. The intracellular and extracellular pH of cancer cells affects their growth; however, the role of ATP6V0C in highly invasive esophageal cancer cells (ECCs) remains unclear. In this study, we examined the role of ATP6V0C in glucose metabolism in ECCs. The ATP6V0C depletion attenuated ECC proliferation, invasion, and suppressed glucose metabolism, as indicated by reduced glucose uptake and decreased lactate and adenosine triphosphate (ATP) production in cells. Consistent with this, expression of glycolytic enzyme and the extracellular acidification rate (ECAR) were also decreased by ATP6V0C knockdown. Mechanistically, ATP6V0C interacted with pyruvate kinase isoform M2 (PKM2), a key regulator of glycolysis in ECCs. The ATP6V0C depletion reduced PKM2 phosphorylation at tyrosine residue 105 (Tyr105), leading to inhibition of nuclear translocation of PKM2. In addition, ATP6V0C was recruited at hypoxia response element (HRE) sites in the lactate dehydrogenase A (LDHA) gene for glycolysis. Thus, our data suggest that ATP6V0C enhances aerobic glycolysis and motility in ECCs.

In current business management, knowledge is considered to be a strategic resource that can strengthen an organization’s competitiveness. Today, under the process of continuous globalization, almost all companies are rapidly exposed to global competition regardless of their scale or type of business. However, multinational management is very complicated and uncertain and it is hard for multinationals to effectively coordinate and manage their global value chains. In light of this, the utility of multinational management based on knowledge is increased. The present study examines multinational firms’ knowledge management systems, knowledge creation processes and global supply chain performance and attempts to reveal any significant linkages between these latent variables. For this research interest, we proposed 18 items to measure four types of knowledge creation processes (SECI) designed by Nonaka (1994) and revised by authors considering the global business environment, in particular involving the global supply chain management concept. Utilizing the confirmed SECI model, 128 sample companies were classified into four groups according to the levels of their knowledge creation processes. The empirical results of this study reveal important linkages between a multinational firm’s knowledge management system and knowledge creation process, as well as between its knowledge creation process and global supply chain management performance. In particular, the current work suggests that the creation and conversion of tacit knowledge as well as explicit knowledge can be effectively supported by information and communication technology.

Prostate cancer gene 3 (PCA3) is a non-coding gene specifically overexpressed in prostate cancer (PCa) that has great potential as a clinical biomarker for predicting prostate biopsy outcome. However, genetic determinants of PCA3 expression level remain unknown. To investigate the association between genetic variants and PCA3 mRNA level, a genome-wide association study was conducted in 1371 men of European descent in the REduction by DUtasteride of prostate Cancer Events trial. First-voided urine specimens containing prostate cells were obtained after digital rectal examination. The PROGENSA PCA3 assay was used to determine PCA3 score in the urinary samples. A linear regression model was used to detect the associations between (single nucleotide polymorphisms) SNPs and PCA3 score under an additive genetic model, adjusting for age and population stratification. Two SNPs, rs10993994 in β-microseminoprotein at 10q11.23 and rs10424878 in kallikrein-related peptidase 2 at 19q13.33, were associated with PCA3 score at genome-wide significance level (P = 1.22 x 10-9 and 1.06 x 10-8, respectively). Men carrying the rs10993994 “T” allele or rs10424878 “A” allele had higher PCA3 score compared with men carrying rs10993994 “C” allele or rs10424878 “G” allele (β = 1.25 and 1.24, respectively). This is the first comprehensive search for genetic determinants of PCA3 score. The novel loci identified may provide insight into the molecular mechanisms of PCA3 expression as a potential marker of PCa.

BACKGROUND: Percentage of free-to-total prostate-specific antigen (%fPSA) is an independent predictor of risk for prostate cancer among men with modestly elevated level of total PSA (tPSA) in blood. Physiological and pathological factors have been shown to influence the %fPSA value and diagnostic accuracy. MATERIALS/METHODS: To evaluate genetic determinants of %fPSA, we conducted a genome-wide association study of serum %fPSA by genotyping 642,584 single nucleotide polymorphisms (SNPs) in 3192 men of European ancestry, each with a tPSA level of 2.5 to 10 ng/ml, that were recruited in the REduction by DUtasteride of Prostate Cancer Events study. Single nucleotide polymorphisms (SNPs) with P

KCNQ channels are critical determinants of neuronal excitability, thus emerging as a novel target of anti-epileptic drugs. To date, the mechanisms of KCNQ channel modulation have been mostly characterized to be inhibitory via Gq-coupled receptors, Ca2+/CaM, and protein kinase C. Here we demonstrate that methylation of KCNQ by protein arginine methyltransferase 1 (Prmt1) positively regulates KCNQ channel activity, thereby preventing neuronal hyperexcitability. Prmt1+/- mice exhibit epileptic seizures. Methylation of KCNQ2 channels at 4 arginine residues by Prmt1 enhances PIP2 binding, and Prmt1 depletion lowers PIP2 affinity of KCNQ2 channels and thereby the channel activities. Consistently, exogenous PIP2 addition to Prmt1+/- neurons restores KCNQ currents and neuronal excitability to the WT level. Collectively, we propose that Prmt1-dependent facilitation of KCNQ-PIP2 interaction underlies the positive regulation of KCNQ activity by arginine methylation, which may serve as a key target for prevention of neuronal hyperexcitability and seizures.

Tuberculous trochanteric bursitis is rare. We report on a 48-year-old man with a huge gravitational abscess in the thigh secondary to tuberculosis of the trochanteric bursa.

In utero injection of a retroviral vector into the embryonic telencephalon aided by ultrasound backscatter microscopy permits introduction of a gene of interest at an early stage of development. In this study, we compared the tissue distribution of gene expression in adult mice injected with retroviral vectors at different embryonic ages in utero. Following ultrasound image-guided gene delivery (UIGD) into the embryonic telencephalon, adult mice were subjected to whole-body luciferase imaging and immunohistochemical analysis at 6 weeks and 1 year postinjection. Luciferase activity was observed in a wide range of tissues in animals injected at embryonic age 9.5 (E9.5), whereas animals injected at E10.5 showed brain-localized reporter gene expression. These results suggest that mouse embryonic brain creates a closed and impermeable structure around E10. Therefore, by injecting a transgene before or after E10, transgene expression can be manipulated to be local or systemic. Our results also provide information that widens the applicability of UIGD beyond neuroscience studies.

Complement C3 and C4 play key roles in the main physiological activities of complement system, and their deficiencies or over-expression are associated with many clinical infectious or immunity diseases. A two-stage genome-wide association study (GWAS) was performed for serum levels of C3 and C4. The first stage was conducted in 1,999 healthy Chinese men, and the second stage was performed in an additional 1,496 subjects. We identified two SNPs, rs3753394 in CFH gene and rs3745567 in C3 gene, that are significantly associated with serum C3 levels at a genome-wide significance level (P = 7.33 × 10(-11) and P = 1.83 × 10(-9), respectively). For C4, one large genomic region on chromosome 6p21.3 is significantly associated with serum C4 levels. Two SNPs (rs1052693 and rs11575839) were located in the MHC class I area that include HLA-A, HLA-C, and HLA-B genes. Two SNPs (rs2075799 and rs2857009) were located 5' and 3' of C4 gene. The other four SNPs, rs2071278, rs3763317, rs9276606, and rs241428, were located in the MHC class II region that includes HLA-DRA, HLA-DRB, and HLA-DQB genes. The combined P-values for those eight SNPs ranged from 3.19 × 10(-22) to 5.62 × 10(-97). HBsAg-positive subjects have significantly lower C3 and C4 protein concentrations compared with HBsAg-negative subjects (P

The p53 tumor suppressor function can be compromised in many tumors by the cellular antagonist HDM2 and human papillomavirus oncogene E6 that induce p53 degradation. Restoration of p53 activity has strong therapeutic potential. Here, we identified TSC-22 as a novel p53-interacting protein and show its novel function as a positive regulator of p53. We found that TSC-22 level was significantly down-regulated in cervical cancer tissues. Moreover, over-expression of TSC-22 was sufficient to inhibit cell proliferation, promote cellular apoptosis in cervical cancer cells and suppress growth of xenograft tumors in mice. Expression of also TSC-22 enhanced the protein level of p53 by protecting it from poly-ubiquitination. When bound to the motif between amino acids 100 and 200 of p53, TSC-22 inhibited the HDM2- and E6-mediated p53 poly-ubiquitination and degradation. Consequently, ectopic over-expression of TSC-22 activated the function of p53, followed by increased expression of p21(Waf1/Cip1) and PUMA in human cervical cancer cell lines. Interestingly, TSC-22 did not affect the interaction between p53 and HDM2. Knock-down of TSC-22 by small interfering RNA clearly enhanced the poly-ubiquitination of p53, leading to the degradation of p53. These results suggest that TSC-22 acts as a tumor suppressor by safeguarding p53 from poly-ubiquitination mediated-degradation.

BACKGROUND: Prostate-specific antigen (PSA) screening is growing in popularity in China, but its impact on biopsy characteristics and outcomes are poorly understood. OBJECTIVE: Our objective was to characterize prostate biopsy outcomes and trends in Chinese men over a 10-year period, since the increasing use of PSA tests. METHODS: All men (n = 1,650) who underwent prostate biopsy for PCa at Huashan Hospital, Shanghai, China from 2003-2011 were evaluated. Demographic and clinical information was collected for each patient, including age, digital rectal examination (DRE), transrectal ultrasound (prostate volume and nodule), total prostate-specific antigen (tPSA) levels and free PSA ratio (fPSA/tPSA) prior to biopsy. Prostate biopsy was performed using six cores before October 2007 or ten cores thereafter. Logistic regression and multivariate analysis were used to evaluate our data. RESULTS: The overall positive rate of prostate biopsy for PCa was 47% and the rate decreased significantly over the years from 74% in 2003 to 33% in 2011 (P-trend = 0.004). Age at diagnosis was slightly increased (P-trend = 0.04) while fPSA/tPSA was significantly decreased (P-trend = 1.11×10-5). A statistically significant trend was not observed for tPSA levels, prostate volume, or proportion of positive nodule. The model including multiple demographic and clinical variables (i.e., age, DRE, tPSA, fPSA/tPSA and transrectal ultrasound results) (AUC = 0.93) statistically outperformed models that included only PSA (AUC = 0.85) or fPSA/tPSA (AUC = 0.66) to predict PCa risks (P

Many differentially methylated genes have been identified in prostate cancer (PCa), primarily using candidate gene-based assays. Recently, several global DNA methylation profiles have been reported in PCa, however, each of these has weaknesses in terms of ability to observe global DNA methylation alterations in PCa. We hypothesize that there remains unidentified aberrant DNA methylation in PCa, which may be identified using higher resolution assay methods. We used the newly developed Illumina HumanMethylation450 BeadChip in PCa (n = 19) and adjacent normal tissues (n = 4) and combined these with gene expression data for identifying new DNA methylation that may have functional consequences in PCa development and progression. We also confirmed our methylation results in an independent data set. Two aberrant DNA methylation genes were validated among an additional 56 PCa samples and 55 adjacent normal tissues. A total 28,735 CpG sites showed significant differences in DNA methylation (FDR adjusted P

Purpose. To compare treatment outcomes after closing wedge osteotomy and plate fixation for cubitus varus deformity undertaken with or without medialisation of the distal fragment. Methods. Records of 21 men and 16 women aged 20 to 34 years who underwent closing wedge osteotomy and plate fixation for cubitus varus deformity with (n=21) or without (n=16) medialisation of the distal fragment were reviewed. A daily alternate flexion-extension splinting was applied for one week for early restoration of full range of motion. The carrying angle and range of motion of the elbow were measured. Results. All patients regained the normal carrying angle and range of motion; none had loss of fixation or limitation in range of motion exceeding 10°. Outcomes were excellent in 23 patients and good in 9. A small bony prominence over the lateral condylar region (‘lazy S’ deformity) was noted in group-1 but not group-2 patients. Conclusion. Closing wedge supracondylar osteotomy with medialisation of the distal fragment was an effective treatment for cubitus varus deformity and minimised the risk of ‘lazy S’ deformity.

Semicontinuous data are characterized by a mixture of a point probability mass at zero and a continuous distribution of positive values. This type of data is often modeled using a two-part model where the first part models the probability of dichotomous outcomes -zero or positive- and the second part models the distribution of positive values. Despite the two-part model’s popularity, variable selection in this model has not been fully addressed, especially, in high dimensional data. The objective of this study is to investigate variable selection and prediction performance of penalized regression methods in two-part models. The performance of the selected techniques in the two-part model is evaluated via simulation studies. Our findings show that LASSO and ENET tend to select more predictors in the model than SCAD and MCP. Consequently, MCP and SCAD outperform LASSO and ENET for β-specificity, and LASSO and ENET perform better than MCP and SCAD with respect to the mean squared error. We find similar results when applying the penalized regression methods to the prediction of crime incidents using community-based data. [ABSTRACT FROM AUTHOR]