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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jbusres.2008.12.007 Byline: Kuo-Feng Huang Abstract: Cheng and Chang [Cheng SL, Chang HC. Performance Implications of Cognitive Complexity: An Empirical Study of Cognitive Strategic Groups in Semiconductor Industry. Journal Business Research 2009athis issue] empirically investigate how a strategic group's cognitive complexity affects firm performance in the context of Taiwan's semiconductor industry. This commentary essay explores the authors' contribution to the multidisciplinary strategic group literature. The commentary also considers how Cheng and Chang's results can be integrated with important work in the competitive dynamic studies. Author Affiliation: Department of Business Administration, National Chengchi University, No. 64, Sec. 2, Zhi-Nan Road, Taipei, 116, Taiwan Article History: Received 1 December 2008; Revised 1 December 2008; Accepted 1 December 2008

Ultraviolet (UV) irradiation causes cellular oxidative stress. Under redox imbalance, Keap1-dependent Nrf2 degradation is minimal. In this study, we examined the role of Ca2+ in Nrf2 homeostasis after UVB irradiation using human dermal fibroblasts. UVB irradiation stimulates 12-lipoxygenase and the product 12-hydroxyeicosatetraenoic acid then activates TRPV1 increasing the cell's cytosolic Ca2+ concentration. UVB irradiation induced reactive oxygen species generation and apoptosis are inhibited in the absence of Ca2+ or in the presence of either a 12-lipoxygenase inhibitor or a TRPV1 inhibitor during and after UVB irradiation. Thus, the Ca2+ increase via TRPV1 is a critical factor in UVB irradiation induced oxidative stress. UVB irradiation induces a Ca2+ dependent Nrf2 degradation and thus activation of TRPV1 with 12-hydroxyeicosatetraenoic acid also decreasing Nrf2 levels. UVB irradiation induced Nrf2 degradation is inhibited by co-treatment of cells with W-7, cyclosporin A, SB-216763 or MG-132, which are inhibitors of calmodulin, calcineurin, GSK3β and the proteasome, respectively. Furthermore, UVB irradiation in parallel induces GSK3β dephosphorylation in a Ca2+ dependent manner. Co-immunoprecipitation showed that UVB irradiation induces an increase in Nrf2 phosphorylation, an increase in the binding of β-TrCP and Nrf2, and an increase in Nrf2 ubiquitination; these effects are all Ca2+ dependent. These findings suggest that UVB irradiation induced GSK3β activation in a Ca2+ dependent manner, which then stimulates the phosphorylation and ubiquitination of Nrf2 via β-TrCP. Indeed, silencing of β-TrCP was found to inhibit UVB irradiation-induced oxidative stress, Nrf2 degradation and apoptosis, while it had no effect on the Ca2+ increase. Taken together, our results suggest that a Ca2+ influx via TRPV1 is responsible for UVB irradiation-induced Nrf2 degradation and that modulation of the Ca2+-calmodulin-calcineurin-GSK3β-Nrf2-β-TrCP-Cullin-1 pathway may explain Ca2+ dependent Nrf2 degradation. Image 1 • UVB irradiation causes Ca2+ increase via TRPV1 after 12-lipoxygenase activation. • UVB irradiation induced Nrf2 degradation, ROS generation and apoptosis requires Ca2+. • Calcineurin dephosphorylates and activates GSK3β, which then phosphorylates Nrf2. • The P-Nrf2-β-TrCP complex ubiquitinates Nrf2 and targets it for proteasomal degradation. [ABSTRACT FROM AUTHOR]

Abstract: A series of symmetrical disubstituded 1,8-diamidoanthraquinones were synthesized and evaluated for anti-proliferation, telomerase inhibitory by TRAP assay, and hTERT expression by SEAP assay. All of the compounds tested, except for compounds 3a and 3s were selected by the NCI screening system. In addition, compounds 4e and 4k exhibited inhibitory effects on telomerase activity. Taken together, our findings indicated that the analysis of cytotoxicity and telomerase inhibition might provide information applicable for further developing potential telomerase targeting strategy. [Copyright &y& Elsevier]

Abstract: Surgical or traumatic brain injury often leads to loss of cerebral parenchyma but there is as yet no clinically effective strategy for neural regeneration. Collagen glycosaminoglycan (collagen-GAG, CG) scaffolds have previously been used in many tissues in vivo but have never been utilized in the brain. Using an animal model, we investigated the effects of the implantation of CG scaffold matrix following surgical brain trauma. Results indicated that implantation of CG scaffold could significantly promote functional recovery following surgical brain trauma. The CG scaffold was found to facilitate proliferation, differentiation and migration of endogenous neural precursor cells (NPCs) both in the intra-matrix zone (IMZ) and lesion boundary zone (LBZ). The tissue concentration of brain-derived neurotrophic factor (BDNF) and glia-derived neurotrophic factor (GDNF) in the cortex demonstrated a sustained increase after implantation of CG scaffold following surgical brain trauma. These results suggest that the utilization of CG scaffolds can be considered as a potential clinical strategy for tissue regeneration and functional recovery after brain injury. [Copyright &y& Elsevier]

Abstract: A series of diversely asymmetrical mono- or disubstituted 1,2-diamidoanthraquinone derivatives were synthesized and evaluated for drug-induced cytotoxicity by SRB assay, telomerase inhibitory activity by TRAP assay, and hTERT expression by SEAP assay. Interestingly, compounds 4, 11, 21, 32 and 36 exhibited selective potent antiproliferative activities by NCI with IC50 values in the micromolar range. Of these, only compound 8 showed an IC50 value of 0.95 μM against PC-3 cell lines (human prostate cancer) by SRB assay. All the synthesized compounds exhibited a poor or modest telomerase inhibitory activity by TRAP assay suggesting another mode of action for these compounds. Compound 11 showed broad inhibition against different types of cancer cell lines in the micromolar and submicromolar range. [Copyright &y& Elsevier]

Abstract: Telomerase is important in tumor initiation and cellular immortalization. Given the striking correlations between telomerase activity and proliferation capacity in tumor cells, telomerase had been considered as a potentially important molecular target in cancer therapeutics. A series of 2,7-diamidoanthraquinone were designed and synthesized. They were evaluated for their effects on telomerase activity, hTERT expression, cell proliferations, and cytotoxicity. In the series, compounds (6, 10, 13, 16, 18, 19, 20–22, and 24) showed potent telomerase inhibitory activity, while compounds 19, 21, and 22 activated hTERT expression in normal human fibroblasts. The results indicated that 2,7-diamidoanthraquinones represent an important class of compounds for telomerase-related drug developments. Compounds 8, 16, 18, 26, and 32 were also selected by the NCI for Screening Program and demonstrated high anti-proliferative activity against 60 human cancer cell lines. Structure–activity relationships (SAR) study revealed that the test compounds with side chains two carbon spacer between amido and amine are important structural moiety for telomerase inhibition. Although the exact mechanism of how this amine group contributes to its activity is still unclear, however, the amine group in the extended arm of the bis-substituted anthraquinone might contribute to proper binding to the residues within the grove of G-quadruplex structure. Our results indicated that the 2,7-disubstituted amido-anthraquinones are potent telomerase inhibitors that have the potential to be further developed into novel anticancer chemotherapeutic agents. [Copyright &y& Elsevier]

Background/purpose: Cervical cancer remains a health problem among women worldwide. Delineation of genetic changes is critical to understanding the molecular basis of tumor progression, as well as for identifying genetic markers for early identification of patients at high risk for a poor outcome.Methods: To provide comparative genomic hybridization data for cervical squamous cell carcinoma in Taiwan, and to gain further insight into genetic markers associated with lymph node metastasis of this disease, we performed comparative genomic hybridization analysis of 30 consecutive cases of cervical squamous cell carcinoma (24 stage IB and 6 stage IIB).Results: The results disclosed that higher staged tumors or those with lymph node metastasis had more chromosomal imbalances. The commonly recurrent chromosomal imbalances were gains of 3q (46.7%), 1q (36.7%) and 8q (20.0%) and losses of 11q (36.7%), 3p (33.3%), 6q (23.3%), and 2q (20.0%). The frequencies of these chromosomal imbalances in stage IB and IIB tumors did not differ significantly. However, when compared with tumors without lymph node metastasis, the loss of 11q14-q22 (5/9 vs. 3/21, p = 0.019) and gains of 3q11-q22 and 3q26-qter (6/9 vs. 5/21, p = 0.026) were significantly more prevalent in tumors with lymph node metastasis.Conclusion: The results suggest that certain tumor-associated genes residing on 3q and 11q warrant further investigation to elucidate their role in the progression of this disease. [ABSTRACT FROM AUTHOR]

Abstract: Study objectives: This follow-up study examined the major complications among 4307 operative gynecologic laparoscopies. The overall complication rate and each individual category were compared with those of our previous study period. The clinical outcome and salvage procedures were correlated with the time of recognition and the severity of initial procedures in the individual injury type. Design: Retrospective, comparative study based on medical record reviewing (Canadian Task Force classification II-3). Setting: Tertiary teaching hospital, Chi Mei Foundation Hospital in southern Taiwan. Patients: Records of women (n = 4307) aged 40.5 ± 11.7 years (mean ± SD [95% CI 40.1–40.5]) who underwent operative gynecologic laparoscopies from January 2000 through February 2006 were reviewed in this study. The complications were compared with those of our previous study based on 1507 laparoscopies performed between December 1992 and November 1999 for follow-up comparison. Interventions: Gynecologic laparoscopic surgeries. Measurements and main results: Thirty-four complications occurred in 31 patients requiring repair procedures, 3 of whom had multiple complications, with an overall complication rate of 0.72% (31/4307). There were 13 bladder injuries (0.30%), 7 bowel injuries (0.16%), 3 cases of internal bleeding (0.07%), 4 vaginal stump hematomas or abscesses (0.09%), 3 ureteral injuries (0.07%), 3 major vessel injuries (0.07%), and 1 trocar site hematoma (0.02%). In addition, there were 125 (2.88%) postoperative blood transfusions without additional operative intervention. The major complication rate decreased compared with that of the previous study (0.72% [95% CI 0.51%–1.02%] vs 1.59% [95% CI 1.07%–2.36%]; p = .005). The overall complication rates were not significantly different between laparoscopic hysterectomy (LH) group and non-LH group. However, bladder injury happened more frequently in the LH group, whereas bowel injury was more common in the non-LH group. In addition, the severity of the original injury, timing of recognition, and accompanying salvage procedures correlated with the clinical outcomes. Conclusion: The significantly decreased major complication rate, as compared with that of our previous study period, confirms the importance of experience accumulation and use of preventive maneuvers in reducing the complication rate. There were no significant differences among the individual injury category during these 2 study periods. The manifestations of bowel injury were highly variable and individualized. The accumulation of surgical experience with the aid of preventive maneuvers is helpful to reduce the complication rate significantly. [Copyright &y& Elsevier]

Abstract: A series of 2,7-diamidofluorenones were designed, synthesized, and screened by SRB assay. Some synthesized compounds exhibited antitumor activities in submicromolar range. Ten compounds (3a, 3b, 3c, 3g, 3j, 3l, 4a, 4h, 4i, and 4j) were also selected by NCI screening system and 3c (GI50 =1.66μM) appeared to be the most active agent of this series. Furthermore, 3c attenuated topoisomerase I-mediated DNA relaxation at low micromolar concentrations. These results indicated that fluorenones have potential to be further developed into anticancer drugs. [Copyright &y& Elsevier]

Abstract: By using fragment-based design strategies, a series of 2-thio-substituted anthra[1,2-d]imidazole-6,11-diones were synthesized and evaluated for hTERT repressing activities, cell proliferations, and NCI 60-cell panel assay. Compounds 2, 3, 4, 11, 15 and 35 were selected by the NCI and 3, 4, 11 and 15 represent the GI50, TGI and LC50, respectively. Among them, all were moderate selectivity toward leukemia cancer except for 4 exhibited distinctive selectivity of CNS and renal cancer with 7.403 and 6.475. The overall of test compounds exhibited different cytostatic and cytotoxic activities for further developing potential application as anticancer drugs. [Copyright &y& Elsevier]

Background Context: Intervertebral disc (IVD) degeneration is related to numerous risk factors, including obesity. Leptin, one of the commonly measured adipokines, is proven to play an important role in the pathogenesis of IVD degeneration. In the context of IVD degeneration, matrix metalloproteinase-1 (MMP-1), which is upregulated and activated by leptin, is the most abundant catabolic enzyme. It remains unclear which of the factors mentioned above is most strongly associated with IVD degeneration.Purpose: To investigate the influence of MMP-1 in IVD degeneration, we determined the strength of different predictors, including age, sex, magnetic resonance imaging (MRI), Modic changes (MCs), body mass index (BMI), leptin, and MMP-1. This was achieved by assessing the correlation among these factors and histologic degeneration score (HDS).Study Design: This study included 89 patients undergoing cervical discectomy for disc herniation, 93 who underwent lumbar discectomy, and 90 control subjects. Herniated disc tissue and plasma were used after the study was approved by the Human Ethics Review Committee at the authors' institution.Methods: Hematoxylin and eosin (H&E), Alcian blue-PAS and immunohistochemical (IHC) staining were performed to measure the expression levels of leptin and MMP-1. Circulating plasma levels of leptin and MMP-1 were measured using an enzyme-linked immunosorbent assay. To assess the correlation with HDS, measurements of age, sex, BMI, MRI scale, MCs scale, leptin/MMP-1 plasma concentration, and leptin/MMP-1 IHC expression were analyzed.Results: Patients with cervical or lumbar discectomy had significantly higher BMI than controls. Significantly more men than women were involved in the lumbar patients as compared with the cervical patients and the control subjects. After adjustment for age and sex, plasma leptin and leptin IHC score correlated significantly with BMI in patients with cervical or lumbar discectomy. Age, sex, MRI scale, MCs scale, and leptin/MMP-1 plasma concentration were not positively correlated with HDS. HDS was significantly associated with BMI, leptin IHC score, and MMP-1 IHC score. After a stepwise-multiple linear regression analysis to evaluate the strength of the correlations between HDS and various factors, only the MMP-1 IHC score demonstrated an independent association with HDS in patients with degeneration of the cervical or lumbar disc.Conclusions: MMP-1 IHC score is an independent predictor of the severity of cervical or lumbar IVD degeneration.Clinical Significance: MMP-1 IHC score may be used as an indicator of IVD degeneration. [ABSTRACT FROM AUTHOR]

Abstract: A series of anthra[1,2-d]imidazole-6,11-dione derivatives were synthesized and evaluated for telomerase inhibition, hTERT expression and suppression of cancer cell growth in vitro. All of the compounds tested, except for compounds 4, 7, 16, 24, 27 and 28 were selected by the NCI screening system. Among them, compounds 16, 39, and 40 repressed hTERT expression without greatly affecting cell growth, suggesting for the selectivity toward hTERT expression. Taken together, our findings indicated that the analysis of cytotoxicity and telomerase inhibition might provide information applicable for further developing potential telomerase and polypharmacological targeting strategy. [Copyright &y& Elsevier]

Abstract: A series of 1,2-heteroannelated anthraquinones and anthra[1,2-d]imidazole-6,11-dione tetracyclic analogues with different side chain were prepared using an various synthetic route via acylation, cyclization, condensation, and intramolecular heterocyclization. Tetracyclic system containing alkyl and aryl, aromatic and heterocyclic, linear and cyclic, polar and apolar, and basic and acids residues were incorporated. They were evaluated for their effects on telomerase activity, hTERT expression, cell proliferations, and in vitro cytotoxicity against NCI’s 60 cell line human tumor screen. Compounds 4, 11, 12, 14, 15, 16, 17, 19, 20, 23, 25, and 26 were selected by the NCI for one dose screening program and further studies on 4, 23 and 25 where the curves cross these lines represent the interpolated values to cause 50% growth inhibition (GI50), total growth inhibition (TGI) and 50% cell killing (LC50), respectively. Further studies did not reveal any compound that showed potent and significant on telomerase inhibitory activity and hTERT repressing ability. Comparative testing of these compounds in the NCI’s screen revealed varying levels of potency and differential cytotoxicity, apparently related to the unsaturation levels in and substitution patterns on the core ring system. It appeared that addition of a fourth planar aromatic system to a tricyclic chromophore might enhances potent cytotoxic agents, at a level equivalent to a second side chain in one of the tricyclic series. Although the exact mechanism of how this pharmacophore contributes to its activity is still unclear, however, the group in the extended arm of the tetracyclic system might contribute to proper binding to the residues within the grove of G-quadruplex structure. [Copyright &y& Elsevier]

The purpose of this study was to identify the kinematic and kinetic strategies used by patients with unilateral triple arthrodesis or subtalar fusion during level walking, stair ascent, stair descent and to determine the influence of these different conditions on kinematics and kinetics. Nine subjects with unilateral triple or subtalar fusion and five normal control subjects were recruited for this experiment. Temporal distance, kinematic and kinetic data were collected using a six camera 3-D motion analysis system and a custom fabricated set of stairs with five steps; the second and third steps were each instrumented with one force platform. During level walking, affected limbs lost all of the plantarflexion at the ankle joint during push-off and showed greater knee flexion angle during the same period of stance. During stair ascent, affected limbs showed a different movement pattern at the knee, a greater knee flexion angle during the whole stance phase and a near zero degree of plantarflexion angle during the forward continuance (FCN) phase. During descent, affected limbs showed a greater knee flexion angle during the whole stance phase and less ankle dorsiflexion angle during the same period of stance phase. At the ankle, peak moment and power values were significantly different between the affected side and the limbs of the control subjects during level walking in the push-off phase, stair ascent in the FCN phase, and stair descent in the weight acceptance (WA) phase, where the affected limbs had a lower plantarflexion moment and power values. [Copyright &y& Elsevier]