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"Johnson, W"
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Constructive controversy : theory, research, practice
\"Why do people make decisions based on their own perspective without considering alternative points of view? Do differences of opinion enhance or obstruct critical thinking? Is it wise to seek out people who disagree with you and listen to their objections to your conclusions? Focusing on the theory, research, and application of constructive controversy, this book analyses the nature of disagreement among members of decision-making groups, project teams, academic study groups, and other groups that are involved in solving problems. Johnson demonstrates that this theory is one of the most effective methods of enhancing creativity and innovation, decision making, teaching, and political discourse. The book includes entertaining and intriguing examples of how constructive controversy has been used in a variety of historical periods to advance creativity, achieve innovations, and guide democracies. It will be welcomed by students in the fields of social psychology, management/business studies, education, and communication studies\"-- Provided by publisher.
Book
NASA concept vehicles and the engineering of advanced air mobility aircraft
NASA is conducting investigations in Advanced Air Mobility (AAM) aircraft and operations. AAM missions are characterised by ranges below 300 nm, including rural and urban operations, passenger carrying as well as cargo delivery. Urban Air Mobility (UAM) is a subset of AAM and is the segment that is projected to have the most economic benefit and be the most difficult to develop. The NASA Revolutionary Vertical Lift Technology project is developing UAM VTOL aircraft designs that can be used to focus and guide research activities in support of aircraft development for emerging aviation markets. These NASA concept vehicles encompass relevant UAM features and technologies, including propulsion architectures, highly efficient yet quiet rotors, and aircraft aerodynamic performance and interactions. The configurations adopted are generic, intentionally different in appearance and design detail from prominent industry arrangements. Already these UAM concept aircraft have been used in numerous engineering investigations, including work on meeting safety requirements, achieving good handling qualities, and reducing noise below helicopter certification levels. Focusing on the concept vehicles, observations are made regarding the engineering of Advanced Air Mobility aircraft.
Journal Article
ComBat-seq: batch effect adjustment for RNA-seq count data
The benefit of integrating batches of genomic data to increase statistical power is often hindered by batch effects, or unwanted variation in data caused by differences in technical factors across batches. It is therefore critical to effectively address batch effects in genomic data to overcome these challenges. Many existing methods for batch effects adjustment assume the data follow a continuous, bell-shaped Gaussian distribution. However in RNA-seq studies the data are typically skewed, over-dispersed counts, so this assumption is not appropriate and may lead to erroneous results. Negative binomial regression models have been used previously to better capture the properties of counts. We developed a batch correction method, ComBat-seq, using a negative binomial regression model that retains the integer nature of count data in RNA-seq studies, making the batch adjusted data compatible with common differential expression software packages that require integer counts. We show in realistic simulations that the ComBat-seq adjusted data results in better statistical power and control of false positives in differential expression compared to data adjusted by the other available methods. We further demonstrated in a real data example that ComBat-seq successfully removes batch effects and recovers the biological signal in the data.
Journal Article
Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow
Breast cancer cells frequently home to the bone marrow, where they may enter a dormant state before forming a bone metastasis. Several members of the interleukin-6 (IL-6) cytokine family are implicated in breast cancer bone colonization, but the role for the IL-6 cytokine leukaemia inhibitory factor (LIF) in this process is unknown. We tested the hypothesis that LIF provides a pro-dormancy signal to breast cancer cells in the bone. In breast cancer patients, LIF receptor (LIFR) levels are lower with bone metastases and are significantly and inversely correlated with patient outcome and hypoxia gene activity. Hypoxia also reduces the LIFR:STAT3:SOCS3 signalling pathway in breast cancer cells. Loss of the LIFR or STAT3 enables otherwise dormant breast cancer cells to downregulate dormancy-, quiescence- and cancer stem cell-associated genes, and to proliferate in and specifically colonize the bone, suggesting that LIFR:STAT3 signalling confers a dormancy phenotype in breast cancer cells disseminated to bone.
Johnson
et al.
report that loss of leukaemia inhibitory factor receptor (LIFR) signalling reduces the expression of genes associated with dormancy in metastatic breast cancer cells, and promotes bone marrow colonization and osteoclastogenesis.
Journal Article
Reinvent your business model : how to seize the white space for transformative growth
Business model innovation is the key to unlocking transformational growth--but few executives know how to apply it to their businesses. In Reinvent Your Business Model, Mark Johnson reveals the playbook. Johnson lays out an eminently practical framework that identifies the four fundamental building blocks that make business models work. In a series of in-depth case studies, he goes on to vividly illustrate how companies are using innovative business models to achieve transformational growth by - fulfilling unmet customer needs in their current markets - serving entirely new customers and creating new markets - and responding to tectonic shifts in market demand, government policy, and technologies that affect entire industries. He then lays out a structured process for designing a new model and developing it into a profitable and thriving enterprise, while investigating the vexing and sometimes paradoxical managerial challenges that have commonly thwarted so many companies in their unguided forays into the unknown. Business model innovators have reshaped entire sectors--including retail, aviation, and media--and redistributed billions of dollars of value. With road-tested frameworks, analytics, and diagnostics, this book gives executives everything they need to reshape their businesses and achieve transformative growth. Thoroughly updated to, Johnson has also added a new chapter on digital transformation, that presents a framework for digital business models and four new case studies.-- Provided by publisher.
Book
Inhibition of inflammatory microglia by dietary fiber and short-chain fatty acids
Microglia play a vital role maintaining brain homeostasis but can also cause persistent neuroinflammation. Short-chain fatty acids (SCFAs) produced by the intestinal microbiota have been suggested to regulate microglia inflammation indirectly by signaling through the gut-brain axis or directly by reaching the brain. The present work evaluated the anti-inflammatory effects of SCFAs on lipopolysaccharide (LPS)-stimulated microglia from mice fed inulin, a soluble fiber that is fermented by intestinal microbiota to produce SCFAs in vivo, and SCFAs applied to primary microglia in vitro. Feeding mice inulin increased SCFAs in the cecum and in plasma collected from the hepatic portal vein. Microglia isolated from mice fed inulin and stimulated with LPS in vitro secreted less tumor necrosis factor α (TNF-α) compared to microglia from mice not given inulin. Additionally, when mice were fed inulin and injected i.p with LPS, the ex vivo secretion of TNF-α by isolated microglia was lower than that secreted by microglia from mice not fed inulin and injected with LPS. Similarly, in vitro treatment of primary microglia with acetate and butyrate either alone or in combination downregulated microglia cytokine production with the effects being additive. SCFAs reduced histone deacetylase activity and nuclear factor-κB nuclear translocation after LPS treatment in vitro. Whereas microglia expression of SCFA receptors
Ffar2
or
Ffar3
was not detected by single-cell RNA sequencing analysis, the SCFA transporters
Mct1
and
Mct4
were. Nevertheless, inhibiting monocarboxylate transporters on primary microglia did not interfere with the anti-inflammatory effects of SCFAs, suggesting that if SCFAs produced in the gut regulate microglia directly it is likely through an epigenetic mechanism following diffusion.
Journal Article
Systematic Review and Meta-Analysis of Association of Smokeless Tobacco and of Betel Quid without Tobacco with Incidence of Oral Cancer in South Asia and the Pacific
This systematic review and meta-analysis aimed to critically appraised data from comparable studies leading to quantitative assessment of any independent association between use of oral smokeless tobacco in any form, of betel quid without tobacco and of areca nut with incidence of oral cancer in South Asia and the Pacific.
Studies (case control and/or cohort) were identified by searching Pub Med, CINAHL and Cochrane databases through June 2013 using the keywords oral cancer: chewing tobacco; smokeless tobacco; betel quid; betel quid without tobacco; areca nut; Asia, the Pacific and the reference lists of retrieved articles. A random effects model was used to compute adjusted summary OR(RE) for the main effect of these habits along with their corresponding 95% confidence intervals. To quantify the impact of between-study heterogeneity on adjusted main-effect summary OR(RE), Higgins' H and I2 statistics along with their 95% uncertainty intervals were used. Funnel plots and Egger's test were used to evaluate publication bias.
Meta-analysis of fifteen case-control studies (4,553 cases; 8,632 controls) and four cohort studies (15,342) which met our inclusion criteria showed that chewing tobacco is significantly and independently associated with an increased risk of squamous-cell carcinoma of the oral cavity (adjusted main-effect summary for case- control studies OR(RE) = 7.46; 95% CI = 5.86-9.50, P<0.001), (adjusted main-effect summary for cohort studies RR = 5.48; 95% CI = 2.56-11.71, P<0.001). Furthermore, meta-analysis of fifteen case control studies (4,648 cases; 7,847 controls) has shown betel quid without tobacco to have an independent positive association with oral cancer, with OR = 2.82 (95% CI = 2.35-3.40, P<0.001). This is presumably due to the carcinogenicity of areca nut. There was no significant publication bias.
There is convincing evidence that smokeless (aka chewing) tobacco, often used as a component of betel quid, and betel quid without tobacco, are both strong and independent risk factors for oral cancer in these populations. However, studies with better separation of the types of tobacco and the ways in which it is used, and studies with sufficient power to quantify dose-response relationships are still needed.
Journal Article