Notch ligand Delta-like 1 promotes the metastasis of melanoma by enhancing tumor adhesion

Notch signaling plays a vital role in tumorigenicity and tumor progression by regulating proliferation, invasion, and the tumor microenvironment. Previous research by our group indicated that Notch ligand Delta-like 1 (Dll1) is involved in angiogenesis in melanoma, and we noticed that it took a longer time to trypsinize Dll1-expressing B16 melanoma cells than the control cells. In this article, we extended our study to investigate the effects of Dll1 on tumor cell adhesion and metastasis. Dll1 overexpression activated Notch signaling in B16 tumor cells and significantly enhanced the adhering capacity of B16 tumor cells both in vitro and in vivo. B16-Dll1 cells also had a higher metastatic potential than their counterpart in the mouse model of lung metastasis. Along with increased Dll1 expression, N-cadherin, but not E-cadherin, was upregulated in B16-Dll1 cells. These data suggested that Notch ligand Dll1 may enhance the adhesion and metastasis of melanoma cells by upregulation of N-cadherin.

Attentional bias modulation by reappraisal in patients with generalized anxiety disorder: an event-related potential study

Affective states influence subsequent attention allocation. We evaluated emotional negativity bias modulation by reappraisal in patients with generalized anxiety disorder (GAD) relative to normal controls. Event-related potential (ERP) recordings were obtained, and changes in P200 and P300 amplitudes in response to negative or neutral words were noted after decreasing negative emotion or establishing a neutral condition. We found that in GAD patients only, the mean P200 amplitude after negative word presentation was much higher than after the presentation of neutral words. In normal controls, after downregulation of negative emotion, the mean P300 amplitude in response to negative words was much lower than after neutral words, and this was significant in both the left and right regions. In GAD patients, the negative bias remained prominent and was not affected by reappraisal at the early stage. Reappraisal was observed to have a lateralized effect at the late stage.

Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome

The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg2), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg2). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement.

Involvement of the TRPV1 channel in the modulation of spontaneous locomotor activity, physical performance and physical exercise-induced physiological responses

Physical exercise triggers coordinated physiological responses to meet the augmented metabolic demand of contracting muscles. To provide adequate responses, the brain must receive sensory information about the physiological status of peripheral tissues and organs, such as changes in osmolality, temperature and pH. Most of the receptors involved in these afferent pathways express ion channels, including transient receptor potential (TRP) channels, which are usually activated by more than one type of stimulus and are therefore considered polymodal receptors. Among these TRP channels, the TRPV1 channel (transient receptor potential vanilloid type 1 or capsaicin receptor) has well-documented functions in the modulation of pain sensation and thermoregulatory responses. However, the TRPV1 channel is also expressed in non-neural tissues, suggesting that this channel may perform a broad range of functions. In this review, we first present a brief overview of the available tools for studying the physiological roles of the TRPV1 channel. Then, we present the relationship between the TRPV1 channel and spontaneous locomotor activity, physical performance, and modulation of several physiological responses, including water and electrolyte balance, muscle hypertrophy, and metabolic, cardiovascular, gastrointestinal, and inflammatory responses. Altogether, the data presented herein indicate that the TPRV1 channel modulates many physiological functions other than nociception and thermoregulation. In addition, these data open new possibilities for investigating the role of this channel in the acute effects induced by a single bout of physical exercise and in the chronic effects induced by physical training.

How Lean Six Sigma and Agile principles optimize ITIL-based processes

Imagine the potential implications of an organization whose business and IT processes are well aligned and are capable of reactively and proactively responding to the external and internal changes. The Philips IT Infrastructure and Operations department (I&O) is undergoing a series of transformation activities to help Philips business keeping up with the changes. I&O would serve a critical function in any business sectors; given that the I&O’s strategy switched from “design, build and run” to “specify, acquire and performance manage”, that function is amplified. In 2013, I&O’s biggest transforming programme I&O Futures engaged multiple interdisciplinary departments and programs on decommissioning legacy processes and restructuring new processes with respect to the Information Technology Internet Library (ITIL), helping I&O to achieve a common infrastructure and operating platform (CI&OP). The author joined I&O Futures in the early 2014 and contributed to the CI&OP release 1, during which a designed model Bing Box and its evaluations were conducted through the lens of six sigma’s structured define-measure-analyze-improve-control (DMAIC) improvement approach. This Bing Box model was intended to firstly combine business and IT principles, namely Lean IT, Agile, ITIL best practices, and Aspect-oriented programming (AOP) into a framework. Secondly, the author implemented the modularized optimization cycles according to the defined framework into Philips’ ITIL-based processes and, subsequently, to enhance business process performance as well as to increase efficiency of the optimization cycles. The unique of this thesis is that the Bing Box model not only provided comprehensive optimization approaches and principles for business process performance, but also integrated and standardized optimization modules for the optimization process itself. The research followed a design research guideline that seek to extend the boundaries of human and organizational capabilities by creating new and innovative artifacts. The Chapter 2 firstly reviewed the current research on Lean Six Sigma, Agile, AOP and ITIL, aiming at identifying the broad conceptual bases for this study. In Chapter 3, we included the process of constructing the Bing Box model. The Chapter 4 described the adoption of Bing Box model: two-implementation case validated by stakeholders through observations and interviews. Chapter 5 contained the concluding remarks, the limitation of this research work and the future research areas. Chapter 6 provided the references used in this thesis.

Quality of 'Delta Valencia' orange grown in semiarid climate and stored under refrigeration after coating with wax

The effects of carnauba-based wax on the quality of 'Delta Valencia' orange produced in Ceará state, Brazil, were studied. The fruits were coated with carnauba-based wax and refrigerated (7 ± 2 ºC and 85 ± 2% R.H.) for 28 days. The quality attribute parameters assessed were weight loss, peel color (brightness, hue angle, and chromaticity), peel moisture, pH, soluble solids (SS), titratable acidity (TA), SS/TA ratio, ascorbic acid, total soluble sugars, reducing sugars, yellow flavonoids, and polyphenols. The results showed that 'Delta Valencia' oranges grown in the dry climate of Ceará state has excellent quality. The coated fruits lost mass at a lower rate than the the control fruits. No significant loss of soluble solids, titratable acidity, pH, and SS/TA ratio was observed, while ascorbic acid, soluble sugars, reducing sugars, yellow flavonoids, and polyphenols increased during storage in both the coated and control fruits. Carnauba-based wax coated fruits showed no signal of dehydration keeping their shiny green peel up to the end of the storage. The use of coating was crucial for the maintenance of visual quality by reducing mass loss, as well as keeping peel moisture.

Depressed cardiac autonomic modulation in patients with chronic kidney disease

Introduction: A dysfunctional autonomic nervous system (ANS) has also been recognized as an important mechanism contributing to the poor outcome in CKD patients, with several studies reporting a reduction in heart rate variability (HRV). Objective: Evaluate the sympathovagal balance in patients with chronic kidney disease on conservative treatment. Methods: In a cross-sectional study, patients with CKD stages 3, 4 and 5 not yet on dialysis (CKD group) and age-matched healthy subjects (CON group) underwent continuous heart rate recording during two twenty-minute periods in the supine position (pre-inclined), followed by passive postural inclination at 70° (inclined period). Power spectral analysis of the heart rate variability was used to assess the normalized low frequency (LFnu), indicative of sympathetic activity, and the normalized high frequency (HFnu), indicative of parasympathetic activity. The LFnu/HFnu ratio represented sympathovagal balance. Results: After tilting, CKD patients had lower sympathetic activity, higher parasympathetic activity, and lower sympathovagal balance than patients in the CON group. Compared to patients in stage 3, patients in stage 5 had a lower LFnu/HFnu ratio, suggesting a more pronounced impairment of sympathovagal balance as the disease progresses. Conclusion: CKD patients not yet on dialysis have reduced HRV, indicating cardiac autonomic dysfunction early in the course of CKD.

Modulation of TGF-β signaling by Hypoxia

A tumor is a fast-growing malignant tissue. This creates areas inside the tumor that are distant from local blood vessels to be able to get enough oxygen. This hypoxic condition activates a transcription factor called hypoxia inducible factor (HIF). HIF responses help a cell to adapt to decreased oxygen by activating glycolytic and angiogenesis pathways and by regulating apoptotic responses. Hypoxia drives the upregulation of a growth factor called transforming growth factor beta (TGF-beta). Similar to a hypoxia response, TGF is an important regulator of cell fate. TGF-β and HIF pathways regulate partially overlapping target genes. This regulation can also be cooperative. The TGF-beta signal is initiated by activation of plasma membrane receptors that then activate effector proteins called small mothers against decapentaplegic (Smad) homologs. In healthy tissue, TGF-β keeps cell proliferation and growth under control. During cancer progression, TGF-beta has shown a dual role, whereby it inhibits initial tumor formation but, conversely, in an existent tumor, TGF-beta drives malignant progression. Along with HIF and TGF-beta also protein dephosphorylation is an important regulatory mechanism of cell fate. Protein dephosphorylation is catalyzed by protein phosphatases such as Protein phosphatase 2A (PP2A). PP2A is a ubiquitous phosphatase that can exist in various active forms. PP2A can specifically regulate TGF-beta signaling either by enhancing or inhibiting the receptor activity. This work demonstrates that during hypoxia, PP2A is able to fine-tune TGF-beta signal by specifically targeting Smad3 effector in a Smad7-dependent manner. Inactivation of Smad3 in hypoxia leads to malignant conversion of TGF-beta signaling.

Involving employees in six sigma

Six sigma is a quality improvement philosophy with systematic and formal approach. In order to successfully implement and utilize six sigma the basic disciplines of it should be adopted by the entire organization. Furthermore, employee involvement is crucial in six sigma implementation. This thesis addresses the challenges of long-lasting involvement in the case company. It focuses on gaps of involving six sigma trained employees, Black Belts. Theoretical framework of the thesis illustrates different factors influencing employee involvement. Influencing factors can be divided into ten categories: organizational culture, managerial commitment, leadership style, employee empowerment, employees’ perceptions, communication, training, goals, performance measurement and incentives. Factors and categories overlap and are related to each other. The framework provides holistic view of employee involvement in six sigma context but can be used also with other quality management philosophies. This thesis was conducted as a case study and written on an assignment to a power and automation technology company. Due to the nature of research problem, the data collection was conducted by interviewing case company personnel. In order to study involvement from employees’ point of view interview questions were designed to be open-ended and to allow the interviewees to tell freely about the phenomenon. This thesis provides empirical support on previous studies in organizational support, management commitment and employee empowerment. In addition, it indicates the importance of separate function for Black Belts in the organization. The gaps in Black Belt involvement can be categorized under two categories: Management driven gaps are related to management commitment, organizational structure and culture and information systems. Black Belt driven gaps are related to practice and effort of using six sigma. This thesis finds solutions for bridging these gaps in the case company by applying findings from literature research and suggestions given by the interviewees. For each gap, actions are suggested for bridging the discrepancy between current and desired situations. The thesis states that in order to embed six sigma in the organization the most crucial gaps, lack of management commitment, six sigma vision and possibilities to use six sigma, should be diminished.

Involving employees in six sigma

Six sigma is a quality improvement philosophy with systematic and formal approach. In order to successfully implement and utilize six sigma the basic disciplines of it should be adopted by the entire organization. Furthermore, employee involvement is crucial in six sigma implementation. This thesis addresses the challenges of long-lasting involvement in the case company. It focuses on gaps of involving six sigma trained employees, Black Belts. Theoretical framework of the thesis illustrates different factors influencing employee involvement. Influencing factors can be divided into ten categories: organizational culture, managerial commitment, leadership style, employee empowerment, employees’ perceptions, communication, training, goals, performance measurement and incentives. Factors and categories overlap and are related to each other. The framework provides holistic view of employee involvement in six sigma context but can be used also with other quality management philosophies. This thesis was conducted as a case study and written on an assignment to a power and automation technology company. Due to the nature of research problem, the data collection was conducted by interviewing case company personnel. In order to study involvement from employees’ point of view interview questions were designed to be open-ended and to allow the interviewees to tell freely about the phenomenon. This thesis provides empirical support on previous studies in organizational support, management commitment and employee empowerment. In addition, it indicates the importance of separate function for Black Belts in the organization. The gaps in Black Belt involvement can be categorized under two categories: Management driven gaps are related to management commitment, organizational structure and culture and information systems. Black Belt driven gaps are related to practice and effort of using six sigma. This thesis finds solutions for bridging these gaps in the case company by applying findings from literature research and suggestions given by the interviewees. For each gap, actions are suggested for bridging the discrepancy between current and desired situations. The thesis states that in order to embed six sigma in the organization the most crucial gaps, lack of management commitment, six sigma vision and possibilities to use six sigma, should be diminished.

Production Quality Analysis of Special Elevator Cars Based on Six Sigma Approach

Project scope is to utilize Six Sigma DMAIC approach and lean principles to improve production quality of the case company. Six Sigma tools and techniques are explored through a literature review and later used in the quality control phase. The focus is set on the Pareto analysis to demonstrate the most evident development areas in the production. Materials that are not delivered to the customer or materials that damaged during transportation comprise the biggest share of all feedbacks. The goal is set to reduce these feedbacks by 50 %. Production observation pointed out that not only material shortages but also over-production is a daily situation. As a result, an initial picking list where the purchased and own production components can be seen, is created, reduction of over- and underproduction and material marking improvement are seen the most competitive options so that the goal can be reached. The picking list development should still continue to make sure that the list can be used not only in the case study but also in the industrial scale. The reduction of material missing category can be evaluated reliably not sooner than in few years because it takes time to gather the needed statistical information.