Simultaneous cyclization and derivatization of peptides using cyclopentenediones

Unprotected linear peptides containing N-terminal cysteines and another cysteine residue can be simultaneously cyclized and derivatized using 2,2-disubstituted cyclopentenediones. High yields of cyclic peptide conjugates may be obtained in short reaction times using only a slight excess of the cyclopentenedione moiety under TEMPO catalysis and in the presence of LiCl

BENIN (Nigeria) (Río). Mapas hidrográficos (1785)

Escala [ca. 1:309000], 3 leguas [= 5,4 cm] para el mapa del curso del río Gato. Coordenadas referidas al meridiano de Cádiz (N 5°40'30''/E 11°20'43'') ; escala [ca. 1:77000], 2 millas [= 4,8 cm] para el mapa de la rada de Bissau. Coordenadas referidas al meridiano de Cádiz (N 11°40'30''/O 9°09'30'') y escala [ca. 1:278000], 6 millas [= 4 cm] para el de la ensenada de Bassa. Coordenadas referidas al meridiano de París (N 5°54'00''/O 12°28'00'')Indica sondas batimétricas y fondeaderosEn el márgen superior : "Africa" ularmenteTítulo del verso del mapa: Plano del Curso del Río Gato, con la entrada del Río Benin, y Rada de Bissao, por Dalzel en 178

Rapides établissement et examen effectués en collaboration des compétences requises dans les programmes de résidence en médecine familiale durant la pandémie de la COVID-19

Background: In March 2020, the COVID-19 pandemic disrupted competency-based medical education in Family Medicine programs across Canada. Faculty and residents identified a need for clear, relevant, and specific competencies to frame teaching, learning, supervision and feedback during the pandemic. Methods: A rapid, iterative, educational quality improvement process was launched. Phase 1 involved experienced educators defining gaps in our program’s existing competency-database, reviewing emerging public health and regulatory guidelines, and drafting competencies. Phase 2 involved translation, member-checking, and anonymous feedback and editing of draft competencies by residents and other educational leaders. Phase 3 involved wider dissemination, collaborative editing and feedback from residents and faculty throughout the department. Results: A total of 44 physicians including residents and faculty from multiple contexts provided detailed feedback, review, and editing of an ultimate list of 33 competencies organized by CanMEDS-FM roles. Broad agreement was obtained that the competencies form reasonable learning outcomes during the COVID-19 pandemic. Conclusions: These competencies represent learning objectives reflecting the initial educational mindsets of a wide range of teachers and learners experiencing a global pandemic. The project illustrates a novel collaboration across educational portfolios as a rapid educational response to a public health crisis

Synthesis of HDAC substrate peptidomimetic inhibitors (SPIs) using Fmoc amino acids incorporating zinc-binding groups

Syntheses of Fmoc amino acids having zinc-binding groups were prepared and incorporated into substrate inhibitor H3K27 peptides using Fmoc/tBu solid-phase peptide synthesis (SPPS). Peptide 11, prepared using Fmoc-Asu(NHOtBu)-OH, is a potent inhibitor (IC50 = 390 nM) of the core NuRD corepressor complex (HDAC1–MTA1–RBBP4). The Fmoc amino acids have the potential to facilitate the rapid preparation of substrate peptidomimetic inhibitor (SPI) libraries in the search for selective HDAC inhibitors

Improving Revenue Capture and Patient Safety in an ICU Setting

IMPROVING REVENUE CAPTURE AND PATIENT SAEFTY IN AN INTENSIVE CARE SETTING Materials management department is responsible for restocking chargeable supplies in an intensive care unit (ICU) at an academic tertiary medical center. Staff confusion as to what items were considered chargeable often led to low supply par levels resulting in delays of critical patient care. Using baseline metrics, a team of caregivers created several performance improvement goals to increase nursing compliance with appropriate supply charging. The results of a root cause analysis spearheaded the development of a KPI that encompassed staff education, lost charge tracking and charge supply labeling. Post KPI inception, a significant increase in compliance was realized. The next step is to complete a two year retrospective cost benefit analysis to determine lost revenue and compare that to the cost of three automate

Six-Month Mortality among HIV-Infected Adults Presenting for Antiretroviral Therapy with Unexplained Weight Loss, Chronic Fever or Chronic Diarrhea in Malawi.

In sub-Saharan Africa, early mortality is high following initiation of antiretroviral therapy (ART). We investigated 6-month outcomes and factors associated with mortality in HIV-infected adults being assessed for ART initiation and presenting with weight loss, chronic fever or diarrhea, and with negative TB sputum microscopy

Age- and puberty-dependent association between IQ score in early childhood and depressive symptoms in adolescence

BACKGROUND: Lower cognitive functioning in early childhood has been proposed as a risk factor for depression in later life but its association with depressive symptoms during adolescence has rarely been investigated. Our study examines the relationship between total intelligence quotient (IQ) score at age 8 years, and depressive symptoms at 11, 13, 14 and 17 years. METHOD: Study participants were 5250 children and adolescents from the Avon Longitudinal Study of Parents and their Children (ALSPAC), UK, for whom longitudinal data on depressive symptoms were available. IQ was assessed with the Wechsler Intelligence Scale for Children III, and self-reported depressive symptoms were measured with the Short Mood and Feelings Questionnaire (SMFQ). RESULTS: Multi-level analysis on continuous SMFQ scores showed that IQ at age 8 years was inversely associated with depressive symptoms at age 11 years, but the association changed direction by age 13 and 14 years (age-IQ interaction, p<0.0001; age squared-IQ interaction, p<0.0001) when a higher IQ score was associated with a higher risk of depressive symptoms. This change in IQ effect was also found in relation to pubertal stage (pubertal stage-IQ interaction, 0.00049<p=0.038). At age 17 years, however, sex-specific differences emerged (sex-age squared-IQ interaction, p=0.0075). Whilst the risk effect of higher childhood IQ scores for depressive symptoms declined in females, and some analyses even supported an inverse association by age 17 years, it persisted in males. CONCLUSIONS: Our results suggest that the association between cognitive ability in childhood and depressive symptoms in adolescence varies according to age and/or pubertal stage

Stabilization of the RAS:PDE6D complex is a novel strategy to inhibit RAS signaling

This work was supported by Cancer Research UK core funding number A17196.RAS is a major anticancer drug target which requires membrane localization to activate downstream signal transduction. The direct inhibition of RAS has proven to be challenging. Here, we present a novel strategy for targeting RAS by stabilizing its interaction with the prenyl-binding protein PDE6D and disrupting its localization. Using rationally designed RAS point mutations, we were able to stabilize the RAS:PDE6D complex by increasing the affinity of RAS for PDE6D, which resulted in the redirection of RAS to the cytoplasm and the primary cilium and inhibition of oncogenic RAS/ERK signaling. We developed an SPR fragment screening and identified fragments that bind at the KRAS:PDE6D interface, as shown through cocrystal structures. Finally, we show that the stoichiometric ratios of KRAS:PDE6D vary in different cell lines, suggesting that the impact of this strategy might be cell-type-dependent. This study forms the foundation from which a potential anticancer small-molecule RAS:PDE6D complex stabilizer could be developed.Publisher PDFPeer reviewe

The Lantern Vol. 27, No. 2, Spring 1959

• The Case for a Stratified Society • Education Courses • Some Thoughts for God\u27s Thinking Creatures • Sawdust to the Oats? • To Change the Things I Can... • Vignette • I Meet Goliath • Reverie and Reminiscence • On Flight • In Defense of Jazz • A Description • Line of Retreat • Alan Lomax and the American Folk Song • Dawn Stillness • Seasons • Two Poems • Despair • Too Late • Education • For All Practical Purposes He Was Bald • Contrast • I Belong to the Sea • Waves • Love • The Glory and the Dreamhttps://digitalcommons.ursinus.edu/lantern/1077/thumbnail.jp