Allying BPR with Strategy: A New Perspective for BPR

Since early 1990’s, Business Process Reengineering (BPR) has become a buzzword around the world. Of the BPR methods and models suggested, the majority has put much attention on redesigning processes at operational levels. Those who stress the importance of strategic process reengineering tend to emphasize that redesigning should be embarked and implemented at a broader scope (crossfunctional) in order to obtain greater pay offs, whereas the impact of BPR on strategies is less studied. In this paper, we propose that BPR ally with strategies and, consequently, emphasize the importance of BPR relevant to strategies and the significant role of strategic directions in light of BPR. Thus, we develop a conceptual BPR model that links a firm’s strategy, with a real world example. The main purpose of this paper is to demonstrate the inter-relationship between BPR and strategy and to help provide guidelines for better BPR implementation to enterprises

Emerging Strategies in TCR-Engineered T Cells

Immunotherapy of cancer has made tremendous progress in recent years, as demonstrated by the remarkable clinical responses obtained from adoptive cell transfer (ACT) of patient-derived tumor infiltrating lymphocytes, chimeric antigen receptor (CAR)-modified T cells (CAR-T) and T cell receptor (TCR)-engineered T cells (TCR-T). TCR-T uses specific TCRS optimized for tumor engagement and can recognize epitopes derived from both cell-surface and intracellular targets, including tumor-associated antigens, cancer germline antigens, viral oncoproteins, and tumor-specific neoantigens (neoAgs) that are largely sequestered in the cytoplasm and nucleus of tumor cells. Moreover, as TCRS are naturally developed for sensitive antigen detection, they are able to recognize epitopes at far lower concentrations than required for CAR-T activation. Therefore, TCR-T holds great promise for the treatment of human cancers. In this focused review, we summarize basic, translational, and clinical insights into the challenges and opportunities of TCR-T. We review emerging strategies used in current ACT, point out limitations, and propose possible solutions. We highlight the importance of targeting tumor-specific neoAgs and outline a strategy of combining neoAg vaccines, checkpoint blockade therapy, and adoptive transfer of neoAg-specific TCR-T to produce a truly tumor-specific therapy, which is able to penetrate into solid tumors and resist the immunosuppressive tumor microenvironment. We believe such a combination approach should lead to a significant improvement in cancer immunotherapies, especially for solid tumors, and may provide a general strategy for the eradication of multiple cancers

Quantitative measurement of cell membrane receptor internalization by the nanoluciferase reporter: Using the G protein-coupled receptor RXFP3 as a model

AbstractNanoluciferase (NanoLuc) is a newly developed small luciferase reporter with the brightest bioluminescence to date. In the present work, we developed NanoLuc as a sensitive bioluminescent reporter to measure quantitatively the internalization of cell membrane receptors, based on the pH dependence of the reporter activity. The G protein-coupled receptor RXFP3, the cognate receptor of relaxin-3/INSL7, was used as a model receptor. We first generated stable HEK293T cells that inducibly coexpressed a C-terminally NanoLuc-tagged human RXFP3 and a C-terminally enhanced green fluorescent protein (EGFP)-tagged human RXFP3. The C-terminal EGFP-tag and NanoLuc-tag had no detrimental effects on the ligand-binding potency and intracellular trafficking of RXFP3. Based on the fluorescence of the tagged EGFP reporter, the ligand-induced RXFP3 internalization was visualized directly under a fluorescence microscope. Based on the bioluminescence of the tagged NanoLuc reporter, the ligand-induced RXFP3 internalization was measured quantitatively by a convenient bioluminescent assay. Coexpression of an EGFP-tagged inactive [E141R]RXFP3 had no detrimental effect on the ligand-binding potency and ligand-induced internalization of the NanoLuc-tagged wild-type RXFP3, suggesting that the mutant RXFP3 and wild-type RXFP3 worked independently. The present bioluminescent internalization assay could be extended to other G protein-coupled receptors and other cell membrane receptors to study ligand–receptor and receptor–receptor interactions

Equation of motion for multiqubit entanglement in multiple independent noisy channels

We investigate the possibility and conditions to factorize the entanglement evolution of a multiqubit system passing through multi-sided noisy channels. By means of a lower bound of concurrence (LBC) as entanglement measure, we derive an explicit formula of LBC evolution of the N-qubit generalized Greenberger-Horne-Zeilinger (GGHZ) state under some typical noisy channels, based on which two kinds of factorizing conditions for the LBC evolution are presented. In this case, the time-dependent LBC can be determined by a product of initial LBC of the system and the LBC evolution of a maximally entangled GGHZ state under the same multi-sided noisy channels. We analyze the realistic situations where these two kinds of factorizing conditions can be satisfied. In addition, we also discuss the dependence of entanglement robustness on the number of the qubits and that of the noisy channels.Comment: 14 page

Impact of thermal processing on dietary flavonoids

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGFlavonoids are widely distributed in natural products and foods as a class of polyphenols. They processed diverse bioactivities, including anti-inflammation activity, antiaging activity, and antioxidant activity. The foods rich in flavonoids are usually consumed after thermal processing. However, flavonoids are commonly vulnerable under thermal processing, and it could cause various influences on their stability and bioactivities. Therefore, in this review, the effects of thermal processing on thermal stability and bioactivities of dietary flavonoids from different food sources were first summarized. The strategies to improve thermal stability of dietary flavonoids were then discussed. Noticeably, the effect of some of the promising thermal technologies on dietary flavonoids was also clarified preliminarily in the current review. The promising thermal technologies may be an alternative to conventional thermal processing technologies.Agencia Estatal de Investigación | Ref. RYC2020-030365-

First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK) inhibitor of epidermal growth factor receptor (EGFR), displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC) in Chinese population are not sufficient.</p> <p>Purpose</p> <p>To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC), a study of single agent treatment with gefitinib in Chinese patients was conducted.</p> <p>Methods</p> <p>45 patients with advanced NSCLC were treated with gefitinib (250 mg daily) until the disease progression or intolerable toxicity.</p> <p>Results</p> <p>Among the 45 patients, 15 patients achieved partial response (PR), 17 patients experienced stable disease (SD), and 13 patients developed progression disease (PD). None of the patients achieved complete response (CR). The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively). The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively). In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively).</p> <p>Conclusions</p> <p>Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.</p

Variation of the Fine-Structure Constant from the de Sitter Invariant Special Relativity

There are obvious discrepancies among various experimental constraints on the variation of the fine-structure constant, $\alpha$. We attempt to discuss the issue in the framework of de Sitter invariant Special Relativity (${\cal SR}_{c,R}$) and to present a possible solution to the disagreement. In addition, on the basis of the observational data and the discussions presented in this Letter, we derive a rough theoretical estimate of the radius of the Universe.Comment: 8 pages, no figure

Inclination-Dependent Luminosity Function of Spiral Galaxies in the Sloan Digital Sky Survey: Implication for Dust Extinction

Using a samples of 61506 spiral galaxies selected from the SDSS DR2, we examine the luminosity function (LF) of spiral galaxies with different inclination angles. We find that the characteristic luminosity of the LF, $L^*$, decreases with increasing inclination, while the faint-end slope, $\alpha$, depends only weakly on it. The inclination-dependence of the LF is consistent with that expected from a simple model where the optical depth is proportional to the cosine of the inclination angle, and we use a likelihood method to recover both the coefficient in front of the cosine, $\gamma$, and the LF for galaxies viewed face-on. The value of $\gamma$ is quite independent of galaxy luminosity in a given band, and the values of $\gamma$ obtained in this way for the 5 SDSS bands give an extinction curve which is a power law of wavelength ($\tau\propto\lambda^{-n}$), with a power index $n=0.96\pm0.04$. Using the dust extinction for galaxies obtained by Kauffmann et al. (2003), we derive an `extinction-corrected' luminosity function for spiral galaxies. Dust extinction makes $M^*$ dimmer by about 0.5 magnitudes in the $z$-band, and about 1.2 magnitudes in the $u$- band. Since our analysis is based on a sample where selection effects are well under control, the dimming of edge-on galaxies relative to face-on galaxies is best explained by assuming that galaxy disks are optically thick in dust absorptions.Comment: 11 pages, 10 figures, accepted by Ap

GGPPS1 predicts the biological character of hepatocellular carcinoma in patients with cirrhosis

Background: Hepatocellular carcinoma (HCC) has been associated with diabetes and obesity, but a possible connection with the metabolic syndrome (MetS) and its potential interaction with hepatitis and cirrhosis are open to discussion. Our previous investigations have shown that GGPPS1 plays a critical role during hyperinsulinism. In this report, the expression and distribution of GGPPS1 in liver cancer, and its clinical significance were investigated. Methods: 70 patients with hepatocellular carcinoma (HCC) were included in this study. Three different types of tissues from each HCC patient were assembled immediately after surgical resection: tumor-free tissue >5 cm far from tumor edge (TF), adjacent nonmalignant tissue within 2 cm (AT), and tissue from the tumor (TT). Normal liver tissues from 10 liver transplant donors served as healthy control (HC) while 10 patients with liver cirrhosis as cirrhosis control (CC). The expression and distribution of GGPPS1 were detected by immunohistochemistry, western blots, or real-time PCR. The relationship between the expression of GGPPS1 and clinic pathologic index were analyzed. Results: We found that GGPPS1 was intensified mainly in the cytoplasm of liver tumor cells. Both the expression of GGPPS1 mRNA and protein were upregulated in TT comparing to AT or TF. Meanwhile, HCC patients with cirrhosis had relative higher expression of GGPPS1. In addition, many pathologic characters show close correlation with GGPPS1, such as tumor stage, vessel invasion, and early recurrence. Conclusion: GGPPS1 may play a critical role during the development of HCC from cirrhosis and is of clinical significance for predicting biological character of HCC