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"D. Stewart"
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Total leadership : be a better leader, have a richer life
\"Now in paperback, this national bestseller proves more than ever, your success as a leader isn't just about being great at business. You must be a great person, performing well in all domains of your life-including work, home, community, and your private self. The good news is that, contrary to conventional wisdom about \"balance,\" you don't have to assume that these domains compete in a zero-sum game. Total Leadership is a game-changing blueprint for how to perform well as a leader not by trading off one domain for another, but by finding mutual value among all four. Stew Friedman shows you how to achieve these \"four-way wins\" as a leader who can be real, be whole, and be innovative. With engaging examples and clear instruction, Friedman provides more than thirty hands-on tools for using these proven principles to produce stronger business results, find clearer purpose in what you do, feel more connected to the people who matter most, and generate sustainable change. Total Leadership is a unique resource that shows how to win in all domains of life. \"-- Provided by publisher.
Book
LOCAL CLIMATE ZONES FOR URBAN TEMPERATURE STUDIES
The effect of urban development on local thermal climate is widely documented in scientific literature. Observations of urban–rural air temperature differences—or urban heat islands (UHIs)—have been reported for cities and regions worldwide, often with local field sites that are extremely diverse in their physical and climatological characteristics. These sites are usually described only as “urban” or “rural,” leaving much uncertainty about the actual exposure and land cover of the sites. To address the inadequacies of urban–rural description, the “local climate zone” (LCZ) classification system has been developed. The LCZ system comprises 17 zone types at the local scale (10² to 10⁴ m). Each type is unique in its combination of surface structure, cover, and human activity. Classification of sites into appropriate LCZs requires basic metadata and surface characterization. The zone definitions provide a standard framework for reporting and comparing field sites and their temperature observations. The LCZ system is designed primarily for urban heat island researchers, but it has derivative uses for city planners, landscape ecologists, and global climate change investigators.
Journal Article
Leading the life you want : skills for integrating work and life /
\"Must professional accomplishments come at the expense of having a full life? Not according to Wharton professor and leadership and work-life expert Stewart D. Friedman. In his new book, Friedman identifies critical skills for leading an authentic and balanced life, and illustrates them through the compelling stories of six remarkable high-profile people. He also shows how to develop and apply each skill through a series of exercises anyone can use. Each leader showcased in the book-Bruce Springsteen, Michelle Obama, Sheryl Sandberg, Tom Tierney, Eric Greitens, and Julie Foudy-exemplifies a specific set of skills for achieving greater harmony between work and life. Friedman identifies these discrete skills-for being real, being whole, and being innovative-that reduce conflict. Then, based on in depth interviews and research, he paints a dramatic picture of the creative ways these six very different leaders pursue authenticity and harmony every day. Friedman also includes exercises for practicing each skill, along with actionable ideas curated from research in organizational psychology and related fields, for applying them. This book will inspire and reinforce the changes people want to make to lead more balanced lives and to become better leaders\"-- Provided by publisher.
Book
Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases
Metabolic processes can influence disease risk and provide therapeutic targets. By conducting genome-wide association studies of 1,091 blood metabolites and 309 metabolite ratios, we identified associations with 690 metabolites at 248 loci and associations with 143 metabolite ratios at 69 loci. Integrating metabolite-gene and gene expression information identified 94 effector genes for 109 metabolites and 48 metabolite ratios. Using Mendelian randomization (MR), we identified 22 metabolites and 20 metabolite ratios having estimated causal effect on 12 traits and diseases, including orotate for estimated bone mineral density, α-hydroxyisovalerate for body mass index and ergothioneine for inflammatory bowel disease and asthma. We further measured the orotate level in a separate cohort and demonstrated that, consistent with MR, orotate levels were positively associated with incident hip fractures. This study provides a valuable resource describing the genetic architecture of metabolites and delivers insights into their roles in common diseases, thereby offering opportunities for therapeutic targets.
Genome-wide association studies comprising 1,091 metabolites and 309 metabolite ratios in 8,299 individuals from the Canadian Longitudinal Study on Aging provide insights into the genetic architecture of metabolites and their role in human diseases.
Journal Article
Marine heatwaves disrupt ecosystem structure and function via altered food webs and energy flux
The prevalence and intensity of marine heatwaves is increasing globally, disrupting local environmental conditions. The individual and population-level impacts of prolonged heatwaves on marine species have recently been demonstrated, yet whole-ecosystem consequences remain unexplored. We leveraged time series abundance data of 361 taxa, grouped into 86 functional groups, from six long-term surveys, diet information from a new diet database, and previous modeling efforts, to build two food web networks using an extension of the popular Ecopath ecosystem modeling framework, Ecotran. We compare ecosystem models parameterized before and after the onset of recent marine heatwaves to evaluate the cascading effects on ecosystem structure and function in the Northeast Pacific Ocean. While the ecosystem-level contribution (prey) and demand (predators) of most functional groups changed following the heatwaves, gelatinous taxa experienced the largest transformations, underscored by the arrival of northward-expanding pyrosomes. We show altered trophic relationships and energy flux have potentially profound consequences for ecosystem structure and function, and raise concerns for populations of threatened and harvested species.
This work leverages a new diet database and six long term monitoring efforts of 361 taxa to build comparable pre- and post-heatwave ecosystem models. The study provides empirical demonstration of changes in ecosystem-wide patterns of energy flux and biomass in response to marine heatwaves.
Journal Article
Molecular basis of USP7 inhibition by selective small-molecule inhibitors
Ubiquitination controls the stability of most cellular proteins, and its deregulation contributes to human diseases including cancer. Deubiquitinases remove ubiquitin from proteins, and their inhibition can induce the degradation of selected proteins, potentially including otherwise ‘undruggable’ targets. For example, the inhibition of ubiquitin-specific protease 7 (USP7) results in the degradation of the oncogenic E3 ligase MDM2, and leads to re-activation of the tumour suppressor p53 in various cancers. Here we report that two compounds, FT671 and FT827, inhibit USP7 with high affinity and specificity
in vitro
and within human cells. Co-crystal structures reveal that both compounds target a dynamic pocket near the catalytic centre of the auto-inhibited apo form of USP7, which differs from other USP deubiquitinases. Consistent with USP7 target engagement in cells, FT671 destabilizes USP7 substrates including MDM2, increases levels of p53, and results in the transcription of p53 target genes, induction of the tumour suppressor p21, and inhibition of tumour growth in mice.
Small molecules are identified that inhibit the ubiquitin-specific protease USP7 with high affinity and specificity as explained by co-crystal structures, and are shown to reduce tumour growth in mice.
Interfering inhibitors show toxicity to tumours
Deubiquitinating enzymes remove the small modifier protein ubiquitin from target substrates regulating their stability. One such enzyme, USP7, is a potential target for anti-cancer therapy, as its inhibition would result in the degradation of the ubiquitinated oncoprotein MDM2, leading to reactivation of the tumour suppressor protein p53. However, selective inhibitors of USP7 have remained elusive. Here, David Komander and colleagues identify two small molecules that inhibit USP7 with high affinity and specificity both
in vitro
and within cells. The authors provide structural insights into the mechanism of action of these inhibitors and demonstrate their ability to inhibit tumour growth. Elsewhere in this issue, Ingrid Wertz and colleagues independently develop two such USP7 inhibitors and also demonstrate their toxicity towards tumour cells.
Journal Article
E2 enzymes： more than just middle men
Ubiquitin-conjugating enzymes （E2s） are the central players in the trio of enzymes responsible for the attachment of ubiquitin （Ub） to cellular proteins. Humans have -40 E2s that are involved in the transfer of Ub or Ub-like （Ubl） proteins （e.g., SUMO and NEDDS）. Although the majority of E2s are only twice the size of Ub, this remarkable family of enzymes performs a variety of functional roles. In this review, we summarize common functional and structural features that define unifying themes among E2s and highlight emerging concepts in the mechanism and regulation of E2s.
Journal Article