Founded in 1872, the Glee Club is Rutgers University's oldest
continuously active student organization, as well as one of the
first glee clubs in the United States. For the past 150 years, it
has ...represented the university and presented an image of the
Rutgers man on a national and international stage. This volume
offers a comprehensive history of the Rutgers Glee Club, from its
origins adopting traditions from the German Männerchor and
British singing clubs to its current manifestation as a
world-recognized ensemble. Along the way, we meet the colorful and
charismatic men who have directed the group over the years, from
the popular composer and minstrel performer Loren Bragdon to the
classically-trained conductor Patrick Gardner. And of course, we
learn what the club has meant to the generations of talented and
dedicated young men who have sung in it. A History of the
Rutgers University Glee Club recounts the origins of the
group's most beloved traditions, including the composition of the
alma mater's anthem "On the Banks of the Old Raritan" and the
development of the annual Christmas in Carol and Song concerts.
Meticulously researched, including a complete discography of the
club's recordings, this book is a must-have for all the Rutgers
Glee Club's many fans and alumni.
Founded in 1872, the Glee Club is Rutgers University's oldest
continuously active student organization, as well as one of the
first glee clubs in the United States. For the past 150 years, it
has ...represented the university and presented an image of the
Rutgers man on a national and international stage. This volume
offers a comprehensive history of the Rutgers Glee Club, from its
origins adopting traditions from the German Männerchor and
British singing clubs to its current manifestation as a
world-recognized ensemble. Along the way, we meet the colorful and
charismatic men who have directed the group over the years, from
the popular composer and minstrel performer Loren Bragdon to the
classically-trained conductor Patrick Gardner. And of course, we
learn what the club has meant to the generations of talented and
dedicated young men who have sung in it. A History of the
Rutgers University Glee Club recounts the origins of the
group's most beloved traditions, including the composition of the
alma mater's anthem "On the Banks of the Old Raritan" and the
development of the annual Christmas in Carol and Song concerts.
Meticulously researched, including a complete discography of the
club's recordings, this book is a must-have for all the Rutgers
Glee Club's many fans and alumni.
The bromodomain and extraterminal (BET) protein BRD2-4 inhibitors hold therapeutic promise in preclinical models of hematologic malignancies. However, translation of these data to molecules suitable ...for clinical development has yet to be accomplished. Herein we expand the mechanistic understanding of BET inhibitors in multiple myeloma by using the chemical probe molecule I-BET151. I-BET151 induces apoptosis and exerts strong antiproliferative effect in vitro and in vivo. This is associated with contrasting effects on oncogenic MYC and HEXIM1, an inhibitor of the transcriptional activator P-TEFb. I-BET151 causes transcriptional repression of MYC and MYC-dependent programs by abrogating recruitment to the chromatin of the P-TEFb component CDK9 in a BRD2-4–dependent manner. In contrast, transcriptional upregulation of HEXIM1 is BRD2-4 independent. Finally, preclinical studies show that I-BET762 has a favorable pharmacologic profile as an oral agent and that it inhibits myeloma cell proliferation, resulting in survival advantage in a systemic myeloma xenograft model. These data provide a strong rationale for extending the clinical testing of the novel antimyeloma agent I-BET762 and reveal insights into biologic pathways required for myeloma cell proliferation.
•I-BET151 and I-BET-762 induce cell cycle arrest and apoptosis in myeloma cells associated with MYC downregulation and HEXIM1 upregulation.•Preclinical functional and pharmacologic profiling of I-BET762 supports its use in phase 1 clinical studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
P300/CBP-associated factor (PCAF) and general control nonderepressible 5 (GCN5) are closely related epigenetic proteins, each containing an acetyltransferase domain and a bromodomain. Consistent with ...reported roles for these proteins in immune function, we find that PCAF-deficient macrophages exhibit a markedly reduced ability to produce cytokines upon stimulation with lipopolysaccharide (LPS). Investigating the potential to target this pathway pharmacologically, we show that chemical inhibition of the PCAF/GCN5 bromodomains is insufficient to recapitulate the diminished inflammatory response of PCAF-deficient immune cells. However, by generating the first PCAF/GCN5 proteolysis targeting chimera (PROTAC), we identify small molecules able to degrade PCAF/GCN5 and to potently modulate the expression of multiple inflammatory mediators in LPS-stimulated macrophages and dendritic cells. Our data illustrate the power of the PROTAC approach in the context of multidomain proteins, revealing a novel anti-inflammatory therapeutic opportunity for targeting PCAF/GCN5.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
Correlations in gene expression are used to infer functional and regulatory relationships between genes. However, correlations are often calculated across different cell types or perturbations, ...causing genes with unrelated functions to be correlated. Here, we demonstrate that correlated modules can be better captured by measuring correlations of steady-state gene expression fluctuations in single cells. We report a high-precision single-cell RNA-seq method called MALBAC-DT to measure the correlation between any pair of genes in a homogenous cell population. Using this method, we were able to identify numerous cell-type specific and functionally enriched correlated gene modules. We confirmed through knockdown that a module enriched for p53 signaling predicted p53 regulatory targets more accurately than a consensus of ChIP-seq studies and that steady-state correlations were predictive of transcriptome-wide response patterns to perturbations. This approach provides a powerful way to advance our functional understanding of the genome.
Deep learning has emerged as the leading method in machine learning, spawning a rapidly growing field of academic research and commercial applications across medicine. Deep learning could have ...particular relevance to rheumatology if correctly utilized. The greatest benefits of deep learning methods are seen with unstructured data frequently found in rheumatology, such as images and text, where traditional machine learning methods have struggled to unlock the trove of information held within these data formats. The basis for this success comes from the ability of deep learning to learn the structure of the underlying data. It is no surprise that the first areas of medicine that have started to experience impact from deep learning heavily rely on interpreting visual data, such as triaging radiology workflows and computer‐assisted colonoscopy. Applications in rheumatology are beginning to emerge, with recent successes in areas as diverse as detecting joint erosions on plain radiography, predicting future rheumatoid arthritis disease activity, and identifying halo sign on temporal artery ultrasound. Given the important role deep learning methods are likely to play in the future of rheumatology, it is imperative that rheumatologists understand the methods and assumptions that underlie the deep learning algorithms in widespread use today, their limitations and the landscape of deep learning research that will inform algorithm development, and clinical decision support tools of the future. The best applications of deep learning in rheumatology must be informed by the clinical experience of rheumatologists, so that algorithms can be developed to tackle the most relevant clinical problems.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Animal-sourced foods are important for human nutrition and health, but they can have a negative impact on the environment. These impacts can result in land use tensions associated with population ...growth and the loss of native forests and wetlands during agricultural expansion. Increased greenhouse gas emissions, and high water use but poor water quality outcomes can also be associated. Life cycle analysis from cradle-to-distribution has shown that novel plant-based meat alternatives can have an environmental footprint lower than that of beef finished in feedlots, but higher than for beef raised on well-managed grazed pastures. However, several technologies and practices can be used to mitigate impacts. These include ensuring that grazing occurs when feed quality is high, the use of dietary additives, breeding of animals with higher growth rates and increased fecundity, rumen microbial manipulations through the use of vaccines, soil management to reduce nitrous oxide emission, management systems to improve carbon sequestration, improved nutrient use efficacy throughout the food chain, incorporating maize silage along with grasslands, use of cover crops, low-emission composting barns, covered manure storages, and direct injection of animal slurry into soil. The technologies and systems that help mitigate or actually provide solutions to the environmental impact are under constant refinement to enable ever-more efficient production systems to allow for the provision of animal-sourced foods to an ever-increasing population.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Human health and diet are closely linked. The diversity of diets consumed by humans is remarkable, and most often incorporates both animal and plant-based foods. However, there has been a recent call ...for a reduced intake of animal-based foods due to concerns associated with human health in developed countries and perceived impacts on the environment. Yet, evidence for the superior nutritional quality of animal-sourced food such as meat, milk, and eggs, compared with plant-based foods, indicates that consumption of animal-sourced food should and will continue. This being the case, the aim here is to examine issues associated with animal-sourced foods in terms of both the quantification and mitigation of unintended consequences associated with environment, animal health, and herd management. Therefore, we examined the role of animal proteins in human societies with reference to the UN-FAO issues associated with animal-sourced foods. The emphasis is on dominant grazed pastoral-based systems, as used in New Zealand and Ireland, both with temperate moist climates and a similar reliance on global markets for generating net wealth from pastoral agricultural products. In conclusion, animal-sourced foods are shown to be an important part of the human diet. Production systems can result in unintended consequences associated with environment, animal health, and herd management, and there are technologies and systems to provide solutions to these that are available or under refinement.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Aseptic loosening remains a common cause of failure in total knee arthroplasty (TKA). There is an increased interest in using uncemented TKA to reduce this complication. Radiolucencies (RLs) ...following uncemented TKA can be concerning. We report on the 9-year history of RLs in patients with uncemented TKA.
Twenty-one patients (26 knees) were treated with a cruciate-retaining fully porous coated femur/tibia and cemented patella. At final follow-up, 17 patients (22 knees) were available for review. Average follow-up was 9.6 years, average age was 59.1, and average body mass index was 34.1. X-rays were taken at 6 weeks, 1 year, and at final follow-up. RLs were measured using the Knee Society scoring system and read by two separate surgeons.
At 6 weeks, we identified RL in all patients on both the tibia and femur. The majority were beneath the tibial tray and femoral chamfer. At 1 year, 4 femurs and 4 tibias showed new RLs (<2 mm) in similar zones. Eighteen femurs and 18 tibias showed fewer or no change in RLs. At final follow-up, no new tibia or femur developed a new RL. In total, 9 of the 22 tibias and 17 of the 22 femurs had remaining RLs, all less than 2 mm and none were progressive or new. Knee Society Score averaged 92.5 (6 weeks), 95.1 (1 year), and 97.3 (final).
RLs are common following uncemented TKA. Many resolve by 1 year. There does not appear to be any association between the presence of RLs and long-term follow-up function in this group of patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
CONTEXT Suicide is a leading cause of death in the United States, but identifying
persons at risk is difficult. Thus, the US surgeon general has made suicide
prevention a national priority. An ...expanding body of research suggests that
childhood trauma and adverse experiences can lead to a variety of negative
health outcomes, including attempted suicide among adolescents and adults. OBJECTIVE To examine the relationship between the risk of suicide attempts and
adverse childhood experiences and the number of such experiences (adverse
childhood experiences ACE score). DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study of 17 337 adult health maintenance
organization members (54% female; mean SD age, 57 15.3 years) who attended
a primary care clinic in San Diego, Calif, within a 3-year period (1995-1997)
and completed a survey about childhood abuse and household dysfunction, suicide
attempts (including age at first attempt), and multiple other health-related
issues. MAIN OUTCOME MEASURE Self-reported suicide attempts, compared by number of adverse childhood
experiences, including emotional, physical, and sexual abuse; household substance
abuse, mental illness, and incarceration; and parental domestic violence,
separation, or divorce. RESULTS The lifetime prevalence of having at least 1 suicide attempt was 3.8%.
Adverse childhood experiences in any category increased the risk of attempted
suicide 2- to 5-fold. The ACE score had a strong, graded relationship to attempted
suicide during childhood/adolescence and adulthood (P<.001).
Compared with persons with no such experiences (prevalence of attempted suicide,
1.1%), the adjusted odds ratio of ever attempting suicide among persons with
7 or more experiences (35.2%) was 31.1 (95% confidence interval, 20.6-47.1).
Adjustment for illicit drug use, depressed affect, and self-reported alcoholism
reduced the strength of the relationship between the ACE score and suicide
attempts, suggesting partial mediation of the adverse childhood experience–suicide
attempt relationship by these factors. The population-attributable risk fractions
for 1 or more experiences were 67%, 64%, and 80% for lifetime, adult, and
childhood/adolescent suicide attempts, respectively. CONCLUSIONS A powerful graded relationship exists between adverse childhood experiences
and risk of attempted suicide throughout the life span. Alcoholism, depressed
affect, and illicit drug use, which are strongly associated with such experiences,
appear to partially mediate this relationship. Because estimates of the attributable
risk fraction caused by these experiences were large, prevention of these
experiences and the treatment of persons affected by them may lead to progress
in suicide prevention.
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