Significance of KRAS/PAK1/Crk pathway in non-small cell lung cancer oncogenesis.

BackgroundKey effector(s) of mutated KRAS in lung cancer progression and metastasis are unknown. Here we investigated the role of PAK1/Crk axis in transduction of the oncogenic KRAS signal in non-small cell lung cancer (NSCLC).MethodsWe used NSCLC clinical specimens to examine the correlation among KRAS mutations (codon 12, 13 and 61); PAK1/Crk axis activation [p-PAK1(Thr423), p-Crk(Ser41)]; and adhesion molecules expression by immunohistochemistry. For assessing the role of proto-oncogene c-Crk as a KRAS effector, we inhibited KRAS in NSCLC cells by a combination of farnesyltransferase inhibitor (FTI) and geranylgeranyltransferase inhibitor (GGTI) and measured p-Crk-II(Ser41) by western blotting. Finally, we disrupted the signaling network downstream of KRAS by blocking KRAS/PAK1/Crk axis with PAK1 inhibitors (i.e., IPA-3, FRAX597 or FRAX1036) along with partial inhibition of all other KRAS effectors by prenylation inhibitors (FTI + GGTI) and examined the motility, morphology and proliferation of the NSCLC cells.ResultsImmunohistochemical analysis demonstrated an inverse correlation between PAK1/Crk phosphorylation and E-cadherin/p120-catenin expression. Furthermore, KRAS mutant tumors expressed higher p-PAK1(Thr423) compared to KRAS wild type. KRAS prenylation inhibition by (FTI + GGTI) completely dephosphorylated proto-oncogene c-Crk on Serine 41 while Crk phosphorylation did not change by individual prenylation inhibitors or diluent. Combination of PAK1 inhibition and partial inhibition of all other KRAS effectors by (FTI + GGTI) dramatically altered morphology, motility and proliferation of H157 and A549 cells.ConclusionsOur data provide evidence that proto-oncogene c-Crk is operative downstream of KRAS in NSCLC. Previously we demonstrated that Crk receives oncogenic signals from PAK1. These data in conjunction with the work of others that have specified the role of PAK1 in transduction of KRAS signal bring forward the importance of KRAS/PAK1/Crk axis as a prominent pathway in the oncogenesis of KRAS mutant lung cancer

Competency Ddevelopment Strategies of Gglobal Transformational Lleadership in Iran’s Ministry of Energy

Abstract Global Transformational Leadership (GTL) is an approach that focuses on understanding, adopting and directing change by creating a global network and teamwork and learning environment in order to compete in the global arena. The GTL has attracted the attention of organizations that operate globally, but there are uncertainties regarding its various dimensions, especially the strategies for developing its competencies in organizational leaders. Iran's Ministry of Energy (IME), as a vital government agency, has a global orientation, but is facing challenges to develop its leaders in an increasingly competitive global marketplace. Thus, this research aims to explore strategies for developing GTL competencies in the context of IME. The research method is qualitative with an exploratory approach. The study population is managers with experience and expertise in the international projects of IME. To collect data, 15 of these managers were selected using the purposeful sampling method and participated in semi-structured interviews. The thematic method was used to analyze the collected data. The findings led to identifying strategies to develop transformative leadership competencies in IME. Two overarching strategies identified, namely empowerment strategies and individual development strategies are discussed and their implications for IME are highlighted.Introduction Today, the stated goals and missions of many organizations oriented toward global markets with emphasis on continuous interactions with foreign suppliers, partners, employees, shareholders and customers. The global environment, along with the transformation that has created in the competitive landscape of businesses, has changed the approach of directing organizations and developing the competencies leaders need to be successful globally. Thus, it is expected that the global leaders are equipped with the new knowledge, skills and attitudes which enable them to effectively guide organizations in a complex, changing and often ambiguous global environment. Given the reality of today’s global markets, it is argued that organizations should revisit and reassess their leadership development strategy and focus on developing their leaders' competencies that meet their existing requirements in the face of global competitive forces. To meet this challenge, a key decision for all organizations is choosing the right strategies for developing leaders’ competencies. The main purpose of this article is to present strategies for the development of global transformative leadership competencies in IME based on the views of its experts and managers with international experience.Case studiesThis research is carried out in Iran’s Ministry of Energy and its affiliated companies that operate offshores.Materials and methodsThis research uses qualitative method and collect its data through semi-structured interviews. The theme analysis method was used to identify strategies for developing GTL competencies.The data collected in semi-structured interviews from 15 experts and senior managers of IME, who hold senior positions, such as deputies and advisors to the minister and CEOs of international companies affiliated with the Ministry of Energy, with relevant work experience in international projects.Results and discussions The analysis of the themes in interviews led to the identification of 123 concepts were identified. After allocation of these concepts to themes and refining them several times, 56 basic themes, six organizing themes and two overarching themes were obtained. The findings revealed that although IME bears responsibility for developmental strategies that aim to equip leaders with necessary competencies, but the onus of the competence development strategies primarily rests on individual leaders themselves. In other words, it is argued that individual strategies are complementary to organizational strategies in leadership competency development.ConclusionsThe findings of the research highlight the critical role of empowerment and individual development strategies for developing GTL competencies. The empowerment strategies include professional development, knowledge enhancement, provision of opportunities for cross boarder presence and experience, and granting authority. The individual development strategies, on the other hand, are consist of reflective learning approaches, self-learning and independent study, and revision and reshaping of leader’s mentality

Organizational Cynicism of the Nurses: A Phenomenological Study

Introduction: Organizational cynicism, as newly conceived concept of staff-manager relations, and as one of the most important attitudes of employees, has recently received considerable attention from many researchers and managers. Provided that pessimistic feelings grow among nurses with respect to the hospital they serve, their workplace suffers severe damages and hardships which lead to a substantial decline in its performances. Given the key role of nurses as valuable human resources in providing services to people, the main purpose of this study was to explore the experiences of nurses about organizational cynicism. Method: This was a qualitative research, with phenomenological approach. The participatns were selected from nurses employed in public hospitals of North Khorasan Province, Iran. Purposive sampling was used to select 19 participants. In-depth semi-structured interviews were the date collection method. In addition, data were analyzed using Colaizzi’s method. Results: The results of this study revealed 3 main themes including cognitive factors (disrespecting the nurses, injustice, hypocrisy, unexceptionable environment, nepotism, violation of the psychological contract, and incompetent authorities of the hospital), feeling factors (hospital politicization, lack of social means, and feeling an imposed forced labor on nurses), and behavior factors (not recommending the nursing profession to the others, no tendency to an early retirement, no desire to see the progress of others, criticizing and not accompanying the management decisions, and allowing to personally utilize the hospital’s facilities). Conclusion: The findings indicate that preventing the nepotisme, organizational justice, respecting nurses, and reducing political games of the hospital have a significant impact on the reduction of organizational cynicism among the nurses. As a result, the emphasis on aspects of procedural, interactional, and interactive justice could reduce organizational cynicism of nurses. On the other hand, reverence and respect for nurses will have a significant effect on reduction of organizational cynicism. Therefore, having nurses incentivized in different events, it is possible to mitigate their organizational cynicism feelings. Keywords: Nurses, Organizational culture, Qualitative researc

Analyzing Contents of Emotional Labor Dimensions among Exemplar Iranian Nurses

Introduction: Since nursing profession is deeply rooted in the concept of emotions, and emotions management in order to express the expected emotion demonstration has got high importance, conducting descriptive researches in different fields of exploring latent aspects of the relevant field are deemed essential. Therefore, the main objective of the current research was to explore contents of emotional labor dimensions among exemplary nurses in public hospitals of Mashhad City, Iran. Method: This was a descriptive research drawing upon the strategy of phenomenology. Semi-structured deep interviews were used to collect the data. In order to analyze collected data, Colaizzi approach was employed. The research population included all national exemplar nurses at public hospitals of Mashhad City. They were interviewed considering purposeful sampling and its adequacy. Results: For surface acting dimension, 5 sub-categories in 2 main themes of the emotional mask, and emotional deal, and for deep acting dimension, 15 sub-categories in 5 main themes of emotional withdrawal, emotional empathy, emotional arousal, emotional sharing, and emotional reflection were achieved. Conclusion: Findings of the current research provide valuable insight regarding emotional labor performed by national exemplar nurses in the population. Thus, a correct understanding of this concept as a valid source in constructing professional knowledge of nurses can be placed as the main part of nursing competency; through which the quality of patients’ care can be promoted and life quality can be improved as a result. Keywords: Emotions, Emotional labor, Surface acting, Deep actin

c-Crk proto-oncogene contributes to transcriptional repression of p120-catenin in non-small cell lung cancer cells

As a member of adherens junction, p120-catenin (p120ctn) plays a major role in cell adhesions through stabilization of E-cadherin. p120ctn is transcriptionally down-regulated in non-small cell lung cancer (NSCLC), although the molecular mechanisms underlying p120ctn repression are incompletely defined. Here we further investigated transcriptional regulation of p120ctn in NSCLC. We prepared a promoter reporter plasmid construct that contained p120ctn promoter region from position −1082 to +320 relative to transcription start site. Through serial deletion mutation analysis of the p120ctn promoter, we pinpointed cis-acting elements involved in regulation of p120ctn. We identified transcription factor SP1 as a transcriptional repressor of p120ctn that directly binds to segment (−9 to +36) of the p120ctn promoter. SP1 can receive multiple signals from several intracellular signaling pathways. Through examination of SP1 binding partners, we identified proto-oncogene c-Crk to be involved in transcriptional down-regulation of p120ctn. RNAi mediated silencing of CRK in A549, H157 and H358 cells increased p120ctn protein levels. On the other hand, over-expression of CRK-I and CRK-II in NSCLC cells down-regulated p120ctn, an effect that was abrogated by simultaneous silencing of SP1. In summary, our data provide evidence for the role of c-Crk proto-oncogene in transcriptional repression of p120ctn that further clarifies the mechanism by which this biochemical signal promotes metastasis in NSCLC

Evaluation of modeling and measurement techniques of ultraviolet germicidal irradiation effectiveness: towards the design of immune buildings

While concerns about occupants\u27 health, comfort, energy consumption, and environment are becoming a main design consideration for ventilation systems there are also threats to public safety and security that cannot be overlooked and need to be taken into consideration. A sudden release of chemical and biological agents can pose a safety and security threat to public buildings and can cause injuries and loss of life. Recently air-cleaner technology has been introduced for air sterilization and purification in industrial buildings and hospitals due to its long life, functionality, and sustainability. However this technology has not been applied to the nonindustrial built environment in general, and the possibility of a sudden release of chemical or biological agents in particular has not been addressed. This paper presents a detailed review of previous studies on the measurement of ultraviolet germicidal irradiation effectiveness for decontamination, particularly as related to rooms and mechanical systems (ducting) in buildings. It also discusses the methods used to model the space, as well as the measurements and methods used to measure its performance followed by a comparison of the results and discussion of the possible causes of variance in reported data

Assessment of the diagnostic accuracy of double inversion recovery sequence compared with FLAIR and T2W_TSE in detection of cerebral multiple sclerosis lesions

Background: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. MRI has an important role in early diagnosis of MS within diagnostic criteria. Aim: To determine the diagnostic value of the double inversion recovery (DIR) sequence in detection of brain MS lesions. Methods: In this cross-sectional study, 55 patients were admitted to the MRI department in Vali-E-Asr Hospital in Qaemshahr, Iran, from May 2016 to February 2016. Imaging was performed on a 1.5T Philips MR system using DIR, fluid attenuated inversion recovery (FLAIR), and T2-weighted turbo spin echo (T2W_TSE) sequences with the same parameters, including field of view (FOV), matrix, slice thickness, voxel size, and number of signal averaging (NSA). The DIR sequence has two different time inversions (TI1=3400, TI2=325ms): suppressing cerebrospinal fluid (CSF) and white matter signal. Data analysis was performed using the SPSS version 20, and p-value was gained from the patient-wise analysis by Wilcoxon analysis and paired samples t-test for matched pairs. Results: More lesions in number and size were depicted on the DIR sequence compared with FLAIR (p=0.000 with a relative ratio of 6) and T2W_TSE (p=0.000 with a relative ratio of 10). DIR demonstrated significantly more intracortical lesions compared with FLAIR (p=0.000 with a relative ratio of 2.53) and T2W_TSE (p=0.000 and relative ratio of 8.87). There was significantly higher contrast ratio between the white matter lesions and the normal appearing white matter (NAWM) in all anatomical regions especially in deep white matter (p=0.001). Conclusion: An increasing total number of MS lesions can be detected by DIR sequence; thus, we recommend adding DIR sequence in routine MR protocols for MS patients

Impact of Differentiation Strategy of Porter on Organizational Performance Via Goods Packaging in Nutrition Companies of Astan Ghods Razavi

Nowadays with high competition in area of business, companies have to use different strategies in order to face and control this competition. Without doubt not only use of these strategies influences on packaging but also this issue affect on companies’ performance. Hence, aim of this research is to study differentiation strategy of Porter as a competitive strategy on organizational performance via goods packaging. In order to achieve this aim, impact of differentiation strategy on organizational performance directly and indirectly role as a mediator variable was studied with four hypotheses. The analysis of data show that there is no a mediator role of packaging regarding relationship between differentiation strategy and organizational performance. However elements of color and design play a mediator role between differentiation strategy and organizational performance