Exploiting diverse chemical collections to uncover novel antifungals

The rise in drug resistance amongst pathogenic fungi, paired with the limited arsenal of antifungals available is an imminent threat to our medical system. To address this, we screened two distinct compound libraries to identify novel strategies to expand the antifungal armamentarium. The first collection wasthe RIKEN Natural Product Depository (NPDepo), which was screened for antifungal activity against four major human fungal pathogens: Candida albicans, Candida glabrata, Candida auris, and Cryptococcus neoformans. Through a prioritization pipeline, one compound, NPD6433, emerged as having broad-spectrum antifungal activity and minimal mammalian cytotoxicity. Chemical-genetic and biochemical assays demonstrated that NPD6433 inhibits the essential fungal enzyme fatty acid synthase 1 (Fas1). Treatment with NPD6433 inhibited various virulence traits in C. neoformans and C. auris, and rescued mammalian cell growth in a co-culture model with C. auris. The second compound library screened was adiversity-oriented collectionfrom Boston University. This chemical screen was focused on identifying novel molecules that enhance the activity of the widely deployed antifungal, fluconazole, against C. auris. Through this endeavour, we discovered a potent compound that enhanced fluconazole efficacy against C. auris through increasing azole intracellular accumulation. This activity was dependent on expression of the multidrug transporter geneCDR1, suggesting that this compound targets efflux mechanisms. Furthermore, this molecule significantly reduced fungal burden alone and in combination with fluconazole in a murine model of C. auris disseminated infection. Overall, this work identifies novel compounds with bioactivity against fungal pathogens, revealing important biology, and paving the way for the critical development of therapeutic strategies.

On the Notion of Person in Confucianism

The article presents the notion of person in Confucianism in the context of biographical background of Confucius (551-479 B.C.). As an itinerant sage Confucius taught the practical significance of moral values in the social and political life. His disciples collected his teachings in Analects, in which Confucius noticed that at his age of 50 he knew the will of Heaven (A 11:4). He began to teach Humanism with respect to Transcendence (T’ien).According to the great specialists, Prof. Tu Wei-Ming (Harvard University) and Prof. John Berthrong (Boston University), “the social dimension” of the human person in Confucianism is important and the person is conceived as “a center of relationships” and as a self of personal development (selfhood as creative transformation). There are five universal ways in human relations which are governed by five moral principles. The five ways are those governing the relationships between ruler and minister, between father and son, between husband and wife, between elder and younger brothers, and those in the intercourse between friends. The core of the human person is humanity (jen or ren).Just as “compassion” is the greatest Buddhist virtue, and “love” the Christian, jen is the ultimate goal of conduct and self-transformation for the Confucian. According to Confucius, education reforms a personal life as well as a social and political life in order to realize a universal love and a personal development of man (juncy).

Pose Estimation of Driver’s Head Panning Based on Interpolation and Motion Vectors under a Boosting Framework

Over the last decade, a driver’s distraction has gained popularity due to its increased significance and high impact on road accidents. Various factors, such as mood disorder, anxiety, nervousness, illness, loud music, and driver’s head rotation, contribute significantly to causing a distraction. Many solutions have been proposed to address this problem; however, various aspects of it are still unresolved. The study proposes novel geometric and spatial scale-invariant features under a boosting framework for detecting a driver’s distraction due to the driver’s head panning. These features are calculated using facial landmark detection algorithms, including the Active Shape Model (ASM) and Boosted Regression with Markov Networks (BoRMaN). The proposed approach is compared with six existing state-of-the-art approaches using four benchmark datasets, including DrivFace dataset, Boston University (BU) dataset, FT-UMT dataset, and Pointing’04 dataset. The proposed approach outperforms the existing approaches achieving an accuracy of 94.43%, 92.08%, 96.63%, and 83.25% on standard datasets.

Survival of endodontically treated permanent teeth among children: a retrospective cohort study

Background Outcome studies of nonsurgical root canal treatment (NSRCT) in permanent teeth of children are scarce. This study investigated survival and assessed the variables associated with failure of endodontically treated teeth (ETT) in 6- to 18-year-olds. Methods Records of subjects who received NSRCT at age 6–18 years at Boston University between 2007 and 2015 were assessed for the occurrence of untoward events. Kaplan–Meier survival curves were used to investigate the survival of ETT in the total sample. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated. Results The analysis included 341 patients (424 ETT). Kaplan–Meier survival curves differed according to age at treatment (log-rank P = 0.026), with survival being the lowest among the youngest age group. The estimated 5-year survival probability was 80% for 15- to 18-year-olds, 64.8% for 12- to 14-year-olds and 46.4% for 6- to 11-year-olds. Compared to age at treatment of 15–18 years, age at treatment of 6–11 years (aHR: 2.19, 95% CI 1.02–4.67) and 12–14 years (aHR: 2.02, 95% CI 1.15–3.55) was associated with an increased risk of ETT failure. In the total study sample, the estimated cumulative survival probability was 93.3% at 12 months, 88.0% at 24 months, 76.2% at 36 months, 71.0% at 48 months, and 69.1% at 60 months. Conclusions In children, ETT are more likely to survive when NSRCTs are performed at an older age.

Introduction

This volume presents contributions from scholars spread across three continents and domiciled in twelve different countries, whose common interest is evidence theory as related to law. Evidence theory as related to law stayed mostly dormant until the advent of the “New Evidence Scholarship” in the mid-eighties of the twentieth century. The publication of William Twining’s book, Theories of Evidence: Bentham & Wigmore in 1985 and the 1986 Boston University Law Review Evidence Symposium volume have changed things around. These publications have irreversibly changed the direction of the study of evidence by shifting evidence scholars’ focus from rules to reasons. The shift from rules to reasons was transformative along two dimensions: interdisciplinarity and internationalization. The realization that reasons moving the factfinding process forward are antecedent to, and consequently more important than, evidentiary rules has opened up new paths of inquiry that connected adjudicative factfinding to epistemology, mathematics, economics, psychology, sociology, political morality, and linguistics, and led to further and richer explorations of how theories of probability and induction affect the understanding and reform of the law of evidence. The primacy of reasons has also created a sizable common ground for theorizing for evidence scholars from different countries. With a focus on reasons rather than rules, the differences between factfinding in the more regulated Anglo-American systems vis-à-vis the freer European systems—once understood as dramatic—became less important. The Introduction to the volume presents its chapters and highlights the major philosophical and interdisciplinary insights discussed in it.

Detailed Overview of the Buildout and Integration of an Automated High-Throughput CLIA Laboratory for SARS-CoV-2 Testing on a Large Urban Campus

In 2019, the first cases of SARS-CoV-2 were detected in Wuhan, China, and by early 2020 the cases were identified in the United States. SARS-CoV-2 infections increased in the US causing many states to implement stay-at-home orders and additional safety precautions to mitigate potential outbreaks. As policies changed throughout the pandemic and restrictions lifted, there was an increase in demand for Covid-19 testing which was costly, difficult to obtain, or had long turn-around times. Some academic institutions, including Boston University, created an on-campus Covid-19 screening protocol as part of planning for the safe return of students, faculty, and staff to campus with the option for in-person classes. At BU, we stood up an automated high-throughput clinical testing lab with the capacity to run 45,000 individual tests weekly by fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed RT-PCR test, robotic instrumentation, and trained CLIA certified staff. There were challenges to overcome, including the supply chain issues for PPE testing materials, and equipment that were in high demand. The Boston University Clinical Testing Laboratory was operational at the start of the fall 2020 academic year. The lab performed over 1 million SARS-CoV-2 RT-PCR tests during the 2020-2021 academic year.

El diptongo/hiato como rasgo contrastivo: un estudio perceptual con hablantes de herencia de español

This study examines the perception of diphthongs and hiatuses in 11 heritage Spanish speakers and 6 Spanish-dominant bilingual speakers with an AXB discrimination task (Lukyanchenko, Anna & Kira Gor. 2011. Perceptual correlates of phonological representations in heritage speakers and L2 learners. In Nick Danis, Kate Mesh & Hyunsuk Sung (eds.), Proceedings of the 35th annual Boston University conference on language development, 414–426. Sommerville, MA: Cascadilla Press). In Spanish, diphthongs and hiatuses represent distinct vocalic sequences (Schwegler, Armin, Juergen Kempff & Ana Ameal-Guerra. 2010. Fonética y fonología españolas, 4th edn. Hoboken, NJ: Wiley). However, there are words in which the pronunciation of the vocalic sequence as either a diphthong or hiatus serves as a contrastive feature, as in the example of ley / leí (Face, Timothy L. & Scott M. Alvord. 2004. Lexical and acoustic factors in the perception of the Spanish diphthong vs. Hiatus contrast. Hispania 87(3). 553–564; Hualde, José I. & Mónica Prieto. 2002. On the diphthong/hiatus contrast in Spanish: Some experimental results. Linguistics 40(2). 217–234). Given that these features also exist in English, albeit in different forms, does L2 influence of English impact heritage Spanish listeners' perception of diphthongs and hiatuses in Spanish? Specifically, this study examines discrimination between the diphthong / hiatus as a contrasting feature with /a e o/ as the nucleic vowel in the diphthongs. Results indicate that there is not a significant difference in discrimination between heritage speakers and Spanish-dominant bilinguals. Additionally, the nucleic vowel in the diphthong tokens is a significant factor for the ability to discriminate diphthongs vs. hiatuses in heritage Spanish speakers. The findings of this study contribute to the corpus of phonetic studies focusing on heritage Spanish speakers and perception in their heritage language.

Evolution of Esophageal Motility Testing: From Kronecker to Clouse

Esophageal motility, the science of quantifying the mechanical function of the esophagus, was initiated by Hugo Kronecker in Germany in 1882. Little progress was made until after World War II, when motility studies began in the Mayo Clinic and Boston University. After 1960, several key figures promoted the science, including Lauran Harris, Don Castell, Jerry Dodds, Tom DeMeester, Peter Kahrilas, and Ray Clouse. All were inspirational teachers and mentors as well as scientists. The technical developments from balloons and perfused catheters to the current solid-state catheters and sophisticated software has provided insights which have helped physicians to treat patients with dysfunction of the esophagus with increasing success.

Conclusion

The book concludes with a discussion of the trajectory of Thurman’s career and the Fellowship Church since Thurman’s departure in 1953. It examines his work as dean of the Marsh Chapel and professor of theology at Boston University and explores his successes and failures in replicating the ideas promoted at the Fellowship Church in the new, high-stakes environment. The Conclusion then turns to the life of the Fellowship Church until the present day—evaluating its overall struggles and successes and its ability to remain in operation and support a lively congregation. It ultimately ends with an evaluation of its broad influence and contemporary relevance.