Operations capability, productivity and business performance: the moderating effect of environmental dynamism

Purpose – The purpose of this study is to investigate the relationships between operations capability, productivity and business performance in the context of environmental dynamism. Design/methodology/approach – A proposed conceptual framework grounded in the resourcebased view (RBV) and dynamic capability view (DCV) is analysed using archival data from 193 automakers in the UK. Findings – The results show that operations capability, as an important dynamic capability, has a significant positive effect on productivity, which in turn leads to improved business performance. The results also suggest that productivity fully mediates the relationship between operations capability and business performance, and that environmental dynamism significantly moderates the relationship between operations capability and productivity. Practical implications – The research findings provide practical insights that will help managers develop operations capability to gain greater productivity and business performance in a dynamic environment

CCND1 as a Predictive Biomarker of Neoadjuvant Chemotherapy in Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma

BACKGROUND: Cyclin D1 (CCND1) has been associated with chemotherapy resistance and poor prognosis. In this study, we tested the hypothesis that CCND1 expression determines response and clinical outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. METHODOLOGY AND FINDINGS: 224 patients with HNSCC were treated with either cisplatin-based chemotherapy followed by surgery and radiotherapy (neoadjuvant group, n = 100) or surgery and radiotherapy (non-neoadjuvant group, n = 124). CCND1 expression was assessed by immunohistochemistry. CCND1 levels were analyzed with chemotherapy response, disease-free survival (DFS) and overall survival (OS). There was no significant difference between the neoadjuvant group and non-neoadjuvant group in DFS and OS (p = 0.929 and p = 0.760) when patients treated with the indiscriminate administration of cisplatin-based chemotherapy. However, in the neoadjuvant group, patients whose tumors showed a low CCND1 expression more likely respond to chemotherapy (p<0.001) and had a significantly better OS and DFS than those whose tumors showed a high CCND1 expression (73% vs 8%, p<0.001; 63% vs 6%, p<0.001). Importantly, patients with a low CCND1 expression in neoadjuvant group received more survival benefits than those in non-neoadjuvant group (p = 0.016), however patients with a high CCND1 expression and treated with neoadjuvant chemotherapy had a significantly poor OS compared to those treated with surgery and radiotherapy (p = 0.032). A multivariate survival analysis also showed CCND1 expression was an independent predictive factor (p<0.001). CONCLUSIONS: This study suggests that some but not all patients with HNSCC may benefit from neoadjuvant chemotherapy with cisplatin-based regimen and CCND1 expression may serve as a predictive biomarker in selecting patients undergo less than two cycles of neoadjuvant chemotherapy

The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Gambogic acid (GA) is a major active ingredient of gamboge, a widely used traditional Chinese medicine that has been reported to be a potent cytotoxic agent against some malignant tumors. Many studies have shown that the NF-kappa B signaling pathway plays an important role in anti-apoptosis and the drug resistance of tumor cells during chemotherapy. In this study, the effects and mechanisms of GA and the NF-kappa B inhibitor celastrol on oral cancer cells were investigated.</p> <p>Methods</p> <p>Three human oral squamous cell carcinoma cell lines, Tca8113, TSCC and NT, were treated with GA alone, celastrol alone or GA plus celastrol. Cytotoxicity was assessed by MTT assay. The rate of apoptosis was examined with annexin V/PI staining as well as transmission electronic microscopy in Tca8113 cells. The level of constitutive NF-kappa B activity in oral squamous cell carcinoma cell lines was determined by immunofluorescence assays and nuclear extracts and electrophoretic mobility shift assays (EMSAs) <it>in vitro</it>. To further investigate the role of NF-kappa B activity in GA and celastrol treatment in oral squamous cell carcinoma, we used the dominant negative mutant SR-IκBα to inhibit NF-kappa B activity and to observe its influence on the effect of GA.</p> <p>Results</p> <p>The results showed that GA could inhibit the proliferation and induce the apoptosis of the oral squamous cell carcinoma cell lines and that the NF-kappa B pathway was simultaneously activated by GA treatment. The minimal cytotoxic dose of celastrol was able to effectively suppress the GA-induced NF-kappa B pathway activation. Following the combined treatment with GA and the minimal cytotoxic dose of celastrol or the dominant negative mutant SR-IκBα, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased.</p> <p>Conclusion</p> <p>The combination of GA and celastrol has a synergistic antitumor effect. The effect can be primarily attributed to apoptosis induced by a decrease in NF-kappa B pathway activation. The NF-kappa B signaling pathway plays an important role in this process. Therefore, combining GA and celastrol may be a promising modality for treating oral squamous cell carcinoma.</p

Regular Patterns for Proteome-Wide Distribution of Protein Abundance across Species

A proteome of the bio-entity, including cell, tissue, organ, and organism, consists of proteins of diverse abundance. The principle that determines the abundance of different proteins in a proteome is of fundamental significance for an understanding of the building blocks of the bio-entity. Here, we report three regular patterns in the proteome-wide distribution of protein abundance across species such as human, mouse, fly, worm, yeast, and bacteria: in most cases, protein abundance is positively correlated with the protein's origination time or sequence conservation during evolution; it is negatively correlated with the protein's domain number and positively correlated with domain coverage in protein structure, and the correlations became stronger during the course of evolution; protein abundance can be further stratified by the function of the protein, whereby proteins that act on material conversion and transportation (mass category) are more abundant than those that act on information modulation (information category). Thus, protein abundance is intrinsically related to the protein's inherent characters of evolution, structure, and function

Geology, Mineralogy, Fluid Inclusion, and H–O–S–Pb Isotope Constraints on Ore Genesis of the Keyue Sb–Pb–Zn–Ag Deposit in Southern Tibet

The Keyue deposit is a medium-sized deposit similar to the Zhaxikang deposit within the North Himalayan Metallogenic Belt (NHMB). The ore formation can be divided into Pb–Zn mineralization (stages 1 and 2), Sb–Ag mineralization (stages 3 and 4), and Sb–Hg mineralization (stages 5 and 6). The fluid inclusion data show that the first two pulses of mineralization have different characteristics, but both belong to the epithermal category (stage 2: 172.9~277.2°C, 7.4~17.0 wt% NaCl eq.; stages 3 and 4: 142.1~321.0°C, 2.7~17.96 wt% NaCl eq.). The H–O isotopic compositions of stages 3 and 4 quartz (δDV-SMOW: –174‰~−120‰, δ18OH2O: 1.59‰~11.34‰) are similar to those of stages 3 and 4 minerals (δDV-SMOW: –165‰~−150‰, δ18OH2O: 6.14‰~13.03‰), whereas they are different from stage 1 and 2 (δDV-SMOW: –108.3‰~−103.6‰, δ18OH2O: 1.92‰~3.82‰) and stage 5 and 6 (δDV-SMOW: –165‰~−138‰, δ18OH2O: −12.91‰~0.82‰) minerals from the Zhaxikang deposit. Additionally, stage 2 sulfides have δ34S values of 5.4‰~11.2‰ that are similar to stage 2 sulfides in the Zhaxikang deposit (7.8‰~12.2‰), and these δ34S values overlap those of many SEDEX-type deposits. The δ34S values also show a decreasing trend from stage 2 through stages 3 and 4 to stage 5 in Keyue and Zhaxikang deposits, which may relate to the overprint by later mineralization events. The Pb isotopic data (206Pb/204Pb: 18.530~19.780, 207Pb/204Pb: 15.674~15.939, and 208Pb/204Pb: 38.618~40.559) show a significant crustal contribution. However, the minerals from different pulses of mineralization also exhibit slightly different Pb isotopic characteristics. These inferences from fluid inclusions and isotope are also demonstrated by geological and mineralogical evidence. Overall, the Keyue deposit is an epithermal deposit and has mainly experienced three pulses of mineralization

Prognostic significance of PTK7 in human malignancies

Background. Protein tyrosine kinase 7 (PTK7) is a member of receptor protein tyrosine kinase-like molecules, which is involved in tumorigenesis. However, the association between PTK7 expression and its pathological significance in survival prognosis remains under investigation. The purpose of this meta-analysis is to clarify the prognostic value of PTK7 expression in human malignancies. Methods. A comprehensive literature search was performed in databases of PubMed, Embase and Cochrane Library. The statistical procedures were conducted by Stata 14.0 and the effect size was displayed by model of relative risk. Subgroup analyses were additionally implemented to disclose the potential confounding elements. Sensitivity analysis was used for evaluating the outcome stability, both Begg’s test and Egger’s test were utilized to detect the publication bias across the included studies. Results. We identified 11 studies published with a total sample-size of 2431 participants. Patients with higher PTK7 expression were significantly associated with cancer risk (RR=2.995, 95% CI: 1.048-8.56, p=0.041, random model), and histological grade (RR=0.696, 95% CI: 0.499-0.972, p=0.033, random model). PTK7 was also found to be an unfavorable prognostic marker for overall survival (HR=2.621 95% CI: 1.980-3.468, p=0.000, fixed model) and shorter disease free survival (HR=2.242, 95% CI: 1.112-4.521, p=0.024, random model). Conclusions. Higher expression of PTK7 significantly indicates worse prognosis in human malignancies

Femtosecond-Level Frequency Transfer at 10 GHz over Long Fiber Link with Optical&ndash;Electronic Joint Compensation

We report a fiber-optic 10 GHz frequency transfer technique based on an optical&ndash;electronic joint phase compensator. A highly stable frequency signal at 10 GHz was transferred in a 50-km long fiber link by using this technique. Two key parameters of the frequency dissemination, the timing fluctuation and frequency stability were both measured. The experimental results show the root-mean-square timing fluctuation of the transferred microwave is about 103 fs within 10,000 s, and the frequency stability for the transmission link is 2.2 &times; 10&minus;14 at 1 s and 8.5 &times; 10&minus;17 at 2000 s. The technique proposed in this paper provides a powerful tool which can be used to transfer atomic clocks (e.g., commercial H-master and Cs clocks) in a long fiber link