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Peter Paul Rubens was the most inventive and prolific northern European artist of his age. This book discusses his life and work in relation to three interrelated themes: spirit, ingenuity, and genius. It argues that Rubens and his reception were pivotal in the transformation of early modern ingenuity into Romantic genius. Ranging across the artist's entire career, it explores Rubens's engagement with these themes in his art and life. Alexander Marr looks at Rubens's forays into altarpiece painting in Italy as well as his collaborations with fellow artists in his hometown of Antwerp, and his complex relationship with the spirit of pleasure. It concludes with his late landscapes in connection to genius loci, the spirit of the place.

\"Before Romantic genius, there was ingenuity. Early modern ingenuity defined every person--not just exceptional individuals--as having their own attributes and talents, stemming from an \"inborn nature\" that included many qualities, not just intelligence. Through ingenuity and its family of related terms, early moderns sought to understand and appreciate differences between peoples, places, and things in an attempt to classify their ingenuities and assign professions that were best suited to one's abilities. Logodaedalus, a prehistory of genius, explores the various ways this language of ingenuity was defined, used, and manipulated between 1470 and 1750. By analyzing printed dictionaries and other lexical works across a range of languages--Latin, Italian, Spanish, French, English, German, and Dutch--the authors reveal the ways in which significant words produced meaning in history and found expression in natural philosophy, medicine, natural history, mathematics, mechanics, poetics, and artistic theory\"-- Provided by publisher.

Vineyards in wine regions around the world are reservoirs of yeast with oenological potential. Saccharomyces cerevisiae ferments grape sugars to ethanol and generates flavor and aroma compounds in wine. Wineries place a high-value on identifying yeast native to their region to develop a region-specific wine program. Commercial wine strains are genetically very similar due to a population bottleneck and in-breeding compared to the diversity of S. cerevisiae from the wild and other industrial processes. We have isolated and microsatellite-typed hundreds of S. cerevisiae strains from spontaneous fermentations of grapes from the Okanagan Valley wine region in British Columbia, Canada. We chose 75 S. cerevisiae strains, based on our microsatellite clustering data, for whole genome sequencing using Illumina paired-end reads. Phylogenetic analysis shows that British Columbian S. cerevisiae strains cluster into 4 clades: Wine/European, Transpacific Oak, Beer 1/Mixed Origin, and a new clade that we have designated as Pacific West Coast Wine. The Pacific West Coast Wine clade has high nucleotide diversity and shares genomic characteristics with wild North American oak strains but also has gene flow from Wine/European and Ecuadorian clades. We analyzed gene copy number variations to find evidence of domestication and found that strains in the Wine/European and Pacific West Coast Wine clades have gene copy number variation reflective of adaptations to the wine-making environment. The “wine circle/Region B”, a cluster of 5 genes acquired by horizontal gene transfer into the genome of commercial wine strains is also present in the majority of the British Columbian strains in the Wine/European clade but in a minority of the Pacific West Coast Wine clade strains. Previous studies have shown that S. cerevisiae strains isolated from Mediterranean Oak trees may be the living ancestors of European wine yeast strains. This study is the first to isolate S. cerevisiae strains with genetic similarity to nonvineyard North American Oak strains from spontaneous wine fermentations.

The Mpumalanga Men's Study (MPMS) is the assessment of the Project Boithato HIV prevention intervention for South African MSM. Boithato aims to increase consistent condom use, regular testing for HIV-negative MSM, and linkage to care for HIV-positive MSM. The MPMS baseline examined HIV prevalence and associated risk behaviors, and testing, care, and treatment behaviors among MSM in Gert Sibande and Ehlanzeni districts in Mpumalanga province, South Africa in order to effectively target intervention activities. We recruited 307 MSM in Gert Sibande and 298 in Ehlanzeni through respondent-driven sampling (RDS) between September 2012-March 2013. RDS-adjusted HIV prevalence estimates are 28.3% (95% CI 21.1%-35.3%) in Gert Sibande, and 13.7% (95% CI 9.1%-19.6%) in Ehlanzeni. Prevalence is significantly higher among MSM over age 25 [57.8% (95% CI 43.1%-72.9%) vs. 17.9% (95% CI 10.6%-23.9%), P<0.001 in Gert Sibande; 34.5% (95%CI 20.5%-56.0%) vs. 9.1% (95% CI 4.6%-13.9%), P<0.001 in Ehlanzeni]. In Gert Sibande, prevalence is higher among self-identified gay and transgender MSM vs. other MSM [39.3% (95%CI, 28.3%-47.9%), P<0.01], inconsistent condom users [38.1% (18.1%-64.2%), P<0.05], those with a current regular male partner [35.0% (27.1%-46.4%), P<0.05], and those with lifetime experience of intimate partner violence with men [40.4%, (95%CI 28.9%-50.9%), P<0.05]. Prevalence of previous HIV testing was 65.8% (95%CI 58.8%-74.0%) in Gert Sibande, and 69.3% (95%CI 61.9%-76.8%) in Ehlanzeni. Regular HIV testing was uncommon [(34.6%, (95%CI 27.9%-41.4%) in Gert Sibande; 31.0% (95%CI 24.9%-37.8%) in Ehlanzeni]. Among HIV-positive participants, few knew their status (28.1% in Gert Sibande and 14.5% in Ehlanzeni), or were appropriately linked to care (18.2% and 11.3%, respectively), or taking antiretroviral therapy (13.6% and 9.6% respectively). MPMS results demonstrate the importance of implementing interventions for MSM to increase consistent condom use, regular HIV testing, and linkage and engagement in care for HIV-infected MSM.

Acute myeloid leukemia (AML) is a highly aggressive hematologic cancer with poor survival across a broad range of molecular subtypes. Development of efficacious and well-tolerable therapies encompassing the range of mutations that can arise in AML remains an unmet need. The bromo- and extra-terminal domain (BET) family of proteins represents an attractive therapeutic target in AML due to their crucial roles in many cellular functions, regardless of any specific mutation. Many BET inhibitors (BETi) are currently in pre-clinical and early clinical development, but acquisition of resistance continues to remain an obstacle for the drug class. Novel methods to circumvent this development of resistance could be instrumental for the future use of BET inhibitors in AML, both as monotherapy and in combination. To date, many investigations into possible drug combinations of BETi with CDK inhibitors have focused on CDK9, which has a known physical and functional interaction with the BET protein BRD4. Therefore, we wished to investigate possible synergy and additive effects between inhibitors of these targets in AML. Here, we describe combination therapy with the multi-CDK inhibitor dinaciclib and the BETi PLX51107 in pre-clinical models of AML. Dinaciclib and PLX51107 demonstrate additive effects in AML cell lines, primary AML samples, and in vivo. Further, we demonstrate novel activity of dinaciclib through inhibition of the canonical/β-catenin dependent Wnt signaling pathway, a known resistance mechanism to BETi in AML. We show dinaciclib inhibits Wnt signaling at multiple levels, including downregulation of β-catenin, the Wnt co-receptor LRP6, as well as many Wnt pathway components and targets. Moreover, dinaciclib sensitivity remains unaffected in a setting of BET resistance, demonstrating similar inhibitory effects on Wnt signaling when compared to BET-sensitive cells. Ultimately, our results demonstrate rationale for combination CDKi and BETi in AML. In addition, our novel finding of Wnt signaling inhibition could have potential implications in other cancers where Wnt signaling is dysregulated and demonstrates one possible approach to circumvent development of BET resistance in AML.

Trans women face negative health outcomes due to multiple types of anti-trans stigma. Relationship stigma, or when people experience stigma because their romantic partnerships are devalued by society, can negatively impact experiences in relationships of trans women. Relationships and their quality are important predictors of wellness across populations, but little is known about relationship quality for trans women. This study was conducted to determine whether relationship stigma is associated with relationship quality for trans women with main partners. This is a secondary analysis of data from 89 trans women with main partners enrolled in the 2020 Partners Study, an online, interviewer-administered, cross-sectional survey of trans women in the San Francisco Bay Area. Multivariate logistic was used to test for an association between relationship stigma and relationship quality among trans women with main partners. The trans women surveyed were White (29.2%), Latinx (24.7%), or multiracial (23.6%), with the majority having never been married (65.2%). Those who often felt they must hide their partnerships had significantly lower odds of reporting satisfaction with intimacy and closeness in their relationships [odds ratio (OR): 0.07; 95% confidence interval (CI): 0.01-0.68,  = 0.02] and of reporting satisfaction with their overall relationship (OR: 0.02; 95% CI: 0.02-0.34,  < 0.01). Those whose families were not supportive of their partnerships had significantly lower odds of reporting relationship satisfaction, intimacy, and closeness with their main partners (OR: 0.08; 95% CI: 0.01-0.85,  = 0.04) and of reporting satisfaction with their overall relationship (OR: 0.08; 95% CI: 0.00, 0.51,  = 0.01). Relationship stigma was negatively associated with relationship quality for trans women with main partners in this study. Stigma from family also had a significant negative impact on relationship quality, suggesting the important influence of family on trans women's relationships. Efforts to boost family support may foster intimacy and improve relationship satisfaction for trans women in main partnerships.

Introduction The ability to objectively measure chronic stress has important implications for research, prevention, and treatment. Cortisol is currently the most used biological marker in the investigation of stress and can be measured via blood, saliva, and urine; however, these methods have disadvantages. The measurement of cortisol in hair is a more recently developed method that quantifies the cumulative production of cortisol over longer periods of time. Given the potential benefits of hair as a chronic stress biometric, research with this novel method is burgeoning, yet rarely involves transgender (“trans”) populations, despite high levels of reported stress among trans people due to experiences of stigma and discrimination. Since hair is a key part of gender presentation, trans people might be less likely than cisgender people to donate hair for research. To explore the feasibility and acceptability of hair collection for use as a stress biometric with trans women, we nested a study into an ongoing clinical trial in São Paulo, Brazil, “Manas por Manas” (Sisters for Sisters). Here, we describe the hair biometric substudy protocol, as well as the feasibility and acceptability of collecting hair in the study cohort. Methods We randomly selected a subsample (n = 180) from the Manas por Manas cohort (n = 392), all of whom are trans women, age 18 or older. We messaged participants via phone, WhatsApp, or social media for at least three attempted contacts. Study visits included four components: (1) video introduction, including a demonstration of hair sampling; (2) informed consent; (3) a brief survey with the validated Short Stress Overload Scale (translated to Portuguese) and questions on hair care that could moderate stress hormone results; and (4) hair sample collection. Hair samples were collected and stored using validated protocols. Participants were reimbursed for travel costs. Results Between April and December 2022, we messaged with 143 individuals out of the 180 sampled (79%) and invited them to participate in the study. Of those invited to participate, we scheduled study visits with 102 people (71.3% of those invited to participate), of whom 100 attended their study visits and completed all activities. Two people did not attend their study visits and stopped communication. Of those who were invited to participate and declined a study visit, four individuals declined due to the hair sample collection procedures (2.8% of those invited to participate). Other reasons for declining to participate included having moved (n = 7), lack of time (n = 11), not interested in research participation (n = 8), or unknown/stopped responding to messages (n = 11). Most participants reported that they chemically treated their hair to bleach, color, or straighten it, which could impact laboratory assays. Conclusion We found hair sampling for stress measurement to be feasible and acceptable to our participants. We successfully completed all study activities for our desired sample size, and most recruited individuals volunteered to participate. Reasons provided for declining study participation reflected general barriers to research participation, with only four people declining due to hair sample collection procedures. Hair has promising benefits as a chronic stress biometric, and research with this novel method is burgeoning, yet rarely involves transgender (“trans”) people, despite high levels of reported stress from experiences of stigma and discrimination. Since hair is a key part of gender presentation, trans women might be more hesitant than cisgender women to donate hair for research. To explore the feasibility and acceptability of hair collection with trans women, we nested a study into an ongoing clinical trial in São Paulo, Brazil, “Manas por Manas” (Sisters for Sisters). We randomly selected a subsample (n = 180) from the Manas cohort (n = 392. We invited 143 trans women to participate, of whom 100 attended their study visits and completed all activities. Of those who declined participation, only four individuals said it was because of the hair sample collection. Given these results, we found hair sampling for stress measurement to be feasible and acceptable.