Exploring the impact of vibrational cavity coupling strength on ultrafast CN + cc-C6_6H12_{12} reaction dynamics

Molecular polaritons, hybrid light-matter states resulting from strong cavity coupling of optical transitions, may provide a new route to guide chemical reactions. However, demonstrations of cavity-modified reactivity in clean benchmark systems are still needed to clarify the mechanisms and scope of polariton chemistry. Here, we use transient absorption to observe the ultrafast dynamics of CN radicals interacting with a cyclohexane ($c$-C$_6$H$_{12}$) and chloroform (CHCl$_3$) solvent mixture under vibrational strong coupling of the brightest C$-$H stretching mode of $c$-C$_6$H$_{12}$. By modulating the $c$-C$_6$H$_{12}$:CHCl$_3$ ratio, we explore how solvent complexation and hydrogen (H)-abstraction processes proceed under collective cavity coupling strengths ranging from 55$-$85 cm$^{-1}$. Reaction rates remain unchanged for all extracavity, on resonance, and off-resonance cavity coupling conditions, regardless of coupling strength. These results suggest that insufficient vibrational cavity coupling strength may not be the determining factor for the negligible cavity effects observed previously in H-abstraction reactions of CN with CHCl$_3$

A Screen for Genetic Modifiers of Protein Phosphatase 1 Function in Drosophila Collective Cell Cohesion and Migration

Cells can migrate collectively in tightly or loosely-associated groups during tissue and organ formation, during embryonic development, in tumor metastases, and in wound healing. Drosophilaborder cellsserve as an excellent genetic model of collective cell migration inside a developing tissue. During ovarian development, 6-8 cells form the border cell cluster and migrate together as a cohesive group to reach the large oocyte. Previous experiments have shown that Nuclear inhibitor of Protein Serine Threonine Phosphatase 1 (NiPP1) causes border cells to separate into single cells, rather than stay in a group, and limits their ability to migrate. NiPP1 inhibits the activity of the Protein Phosphatase 1 (PP1) enzyme. Therefore, overexpressing NiPP1, though a modifier screen, will allows us identify genes that work with PP1 to promote the adhesion and collective migration of border cells. To carry out this genetic screen, females expressing NiPP1 in border cells are crossed to a collection of mutant strains, called deficiencies, that remove a number of genes. Ovaries from the resulting progeny are assayed for cohesion and migration of the border cell cluster by fluorescent microscopy. In this project, larger deficiencies have been shown to suppress (“revert to wild type”), or enhance (“make worse”) the mutant phenotype. The goal is to identify the exact gene required for this suppression or enhancement, using smaller deficiency mutant strains that delete only a few genes. Such mutant deficiencies represent candidate NiPP1 modifying genes. The candidate genes will be knocked out by RNAi one by one to definitively determine the genes required for PP1 function in cell-to-cell adhesion and collective migration. Because many Drosophilagenes have human homologs, these studies of PP1 have implications for collective cell migration in humans

Ultrafast dynamics of CN radical reactions with chloroform solvent under vibrational strong coupling

Polariton chemistry may provide a new means to control molecular reactivity, permitting remote, reversible modification of reaction energetics, kinetics, and product yields. A considerable body of experimental and theoretical work has already demonstrated that strong coupling between a molecular vibrational mode and the confined electromagnetic field of an optical cavity can alter chemical reactivity without external illumination. However, the mechanisms underlying cavity-altered chemistry remain unclear in large part because the experimental systems examined previously are too complex for detailed analysis of their reaction dynamics. Here, we experimentally investigate photolysis-induced reactions of cyanide (CN) radicals with strongly-coupled chloroform (CHCl$_3$) solvent molecules and examine the intracavity rates of photofragment recombination, solvent complexation, and hydrogen abstraction. We use a microfluidic optical cavity fitted with dichroic mirrors to facilitate vibrational strong coupling (VSC) of the C-H stretching mode of CHCl$_3$ while simultaneously permitting optical access at visible wavelengths. Ultrafast transient absorption experiments performed with cavities tuned on- and off-resonance reveal that VSC of the CHCl$_3$ C-H stretching transition does not significantly modify any measured rate constants, including those associated with the hydrogen abstraction reaction. This work represents, to the best of our knowledge, the first experimental study of an elementary bimolecular reaction under VSC. We discuss how the conspicuous absence of cavity-altered effects in this system may provide insights into the mechanisms of modified ground state reactivity under VSC and help bridge the divide between experimental results and theoretical predictions in vibrational polariton chemistry

Nanoscale integration of single cell biologics discovery processes using optofluidic manipulation and monitoring.

The new and rapid advancement in the complexity of biologics drug discovery has been driven by a deeper understanding of biological systems combined with innovative new therapeutic modalities, paving the way to breakthrough therapies for previously intractable diseases. These exciting times in biomedical innovation require the development of novel technologies to facilitate the sophisticated, multifaceted, high-paced workflows necessary to support modern large molecule drug discovery. A high-level aspiration is a true integration of "lab-on-a-chip" methods that vastly miniaturize cellulmical experiments could transform the speed, cost, and success of multiple workstreams in biologics development. Several microscale bioprocess technologies have been established that incrementally address these needs, yet each is inflexibly designed for a very specific process thus limiting an integrated holistic application. A more fully integrated nanoscale approach that incorporates manipulation, culture, analytics, and traceable digital record keeping of thousands of single cells in a relevant nanoenvironment would be a transformative technology capable of keeping pace with today's rapid and complex drug discovery demands. The recent advent of optical manipulation of cells using light-induced electrokinetics with micro- and nanoscale cell culture is poised to revolutionize both fundamental and applied biological research. In this review, we summarize the current state of the art for optical manipulation techniques and discuss emerging biological applications of this technology. In particular, we focus on promising prospects for drug discovery workflows, including antibody discovery, bioassay development, antibody engineering, and cell line development, which are enabled by the automation and industrialization of an integrated optoelectronic single-cell manipulation and culture platform. Continued development of such platforms will be well positioned to overcome many of the challenges currently associated with fragmented, low-throughput bioprocess workflows in biopharma and life science research

Lessons Learned from Historical Analysis of Seven Decades of Educational Scholarship at McMaster University School of Nursing

The McMaster School of Nursing (SON) was approaching its 70th anniversary prompting a time of reflection on its contributions to nursing education. Were there lessons learned from the past that could provide a compass to navigate current day challenges and orient future strategies in the continued pursuit of excellence in nursing education? While the history of nursing education in Canada has been previously documented, there has been limited research into the evolution of different educational approaches. We decided to conduct in-depth historical analysis of the conditions that fostered educational scholarship and practice at our SON from 1946 to 2016. Using Danto’s (2009) descriptive historiography approach, we first compiled a chronological catalogue of evidences of educational scholarship and of major events that occurred within the SON through literature and archival document searches and 23 key informant interviews. We included a cultural historiography lens that uses a cultural framework to help explain influences on and of the SON activities. Several key areas of educational innovation and scholarship that have influenced nursing education nationally and internationally were identified. However, this article focuses on the historical development of three highly interrelated educational approaches in which the McMaster SON was an early leader: problem-based learning, evidence based nursing, and academic/community partnerships. The article further traces the influences on and of these approaches, set within the context of major events of the SON. Several lessons were uncovered by this historical analysis including building on existing strengths while being open to opportunities, being cognizant of the impact of organizational culture over time, using a proactive planning approach, and exploiting the exponential effect of innovations. A cautionary lesson on nursing’s voice in promoting our own knowledge was also uncovered. Applying the historical methodology taught us lessons on the preservation of nursing-specific information. This historical analysis of one school of nursing’s educational scholarship has provided insights in terms of understanding the forces that have shaped its educational approaches and how this history orients the thinking on educational changes proposed in response to ongoing challenges. Résumé À l’approche de son 70e anniversaire, l’école de sciences infirmières McMaster a pris un temps de réflexion par rapport à ses contributions à la formation en sciences infirmières. Des leçons apprises dans le passé pourraient-elles servir de guide pour gérer les défis d’aujourd’hui et orienter les futures stratégies dans la poursuite continue de l’excellence de la formation en sciences infirmières? Bien que l’histoire de la formation en sciences infirmières au Canada ait été documentée par le passé, il y a eu peu de recherche sur l’évolution des différentes approches pédagogiques. Nous avons décidé de réaliser une analyse historique en profondeur des conditions qui ont favorisé l’avancement des connaissances et la pratique à notre école de sciences infirmières de 1946 à 2016. En nous basant sur l’approche d’historiographie descriptive de Danto (2009), nous avons d’abord compilé un catalogue chronologique de faits sur les programmes pédagogiques et des évènements marquants qui ont eu lieu au sein de l’école de sciences infirmières par le biais de recherches dans la littérature et les archives et d’entrevues avec 23 informateurs clés. Nous avons inclus le point de vue de l’historiographie culturelle, qui utilise un cadre culturel pour aider à expliquer les influences sur et de l’école de sciences infirmières. Plusieurs domaines clés de l’innovation et des programmes pédagogiques qui ont influencé la formation en sciences infirmières au pays et ailleurs dans le monde ont été identifiés. Toutefois, cet article se concentre sur le développement historique de trois approches pédagogiques fortement reliées pour lesquelles l’école de sciences infirmières de McMaster était un chef de file précoce : l’apprentissage basé sur les problèmes, les sciences infirmières fondées sur des données probantes et les partenariats entre les universités et les communautés. L’article retrace également les influences de ces approches dans le contexte des évènements marquants de l’école. Plusieurs leçons ont été apprises grâce à cette analyse historique, notamment de compter sur des forces existantes tout en étant ouverts aux opportunités, reconnaître l’impact de la culture organisationnelle au fil du temps, utiliser une approche de planification proactive et exploiter les effets exponentiels de l’innovation. Une mise en garde a également été établie sur la voix des sciences infirmières pour promouvoir nos propres connaissances. L’application de la méthodologie historique nous a appris des leçons sur la conservation d’informations spécifiques aux sciences infirmières et l’analyse historique de la formation et l’avancement des connaissances d’une école de sciences infirmières a donné un aperçu des forces qui ont forgé ses approches pédagogiques et la façon dont l’histoire guide la réflexion sur les changements pédagogiques proposés en réponse aux défis perpétuels

EGFR Testing and Erlotinib Use in Non-Small Cell Lung Cancer Patients in Kentucky

This study determined the frequency and factors associated with EGFR testing rates and erlotinib treatment as well as associated survival outcomes in patients with non small cell lung cancer in Kentucky. Data from the Kentucky Cancer Registry (KCR) linked with health claims from Medicaid, Medicare and private insurance groups were evaluated. EGFR testing and erlotinib prescribing were identified using ICD-9 procedure codes and national drug codes in claims, respectively. Logistic regression analysis was performed to determine factors associated with EGFR testing and erlotinib prescribing. Cox-regression analysis was performed to determine factors associated with survival. EGFR mutation testing rates rose from 0.1% to 10.6% over the evaluated period while erlotinib use ranged from 3.4% to 5.4%. Factors associated with no EGFR testing were older age, male gender, enrollment in Medicaid or Medicare, smoking, and geographic region. Factors associated with not receiving erlotinib included older age, male gender, enrollment in Medicare or Medicaid, and living in moderate to high poverty. Survival analysis demonstrated EGFR testing or erlotinib use was associated with a higher likelihood of survival. EGFR testing and erlotinib prescribing were slow to be implemented in our predominantly rural state. While population-level factors likely contributed, patient factors, including geographic location (areas with high poverty rates and rural regions) and insurance type, were associated with lack of use, highlighting rural disparities in the implementation of cancer precision medicine

Are You Two Just Friends? Emotional and Sexual Infidelity Across Sexual Orientations

Lesbians are unlikely to ask if it is possible for women and women to be friends. Bisexuals have friends of each sex. It seems that it is primarily heterosexuals who have trouble with sex-of-attraction friendships. This study examined how participants perceived the emotional and sexual infidelity of their partner’s relationship with a friend differing across sexuality and biological sex. Our participants consisted of a combined sample across two studies (n = 532), participants completed measures of their perceived emotional and sexual infidelity towards 10 controlled behaviors that their partners committed with the partner’s friends. The data revealed that participants were more concerned with perceived emotional infidelity with sex(es)-of-attraction friends as a function of participants’ sexual orientation, sex, and their lover’s sexual orientation. Our evidence shows that when in relationships, people feel most threatened by the friend of the partner who possesses the same biological machinery as them. Furthermore, results suggest that people are also more likely to be threatened by their partner’s friend, who may have a mutual attraction towards their partner. The effect of the same biological machinery and the mutual attraction on perceived infidelity is additive. The pattern is seen across heterosexual, homosexual, and bisexual relationships

One-Time Compilation of Device-Level Instructions for Quantum Subroutines

A large class of problems in the current era of quantum devices involve interfacing between the quantum and classical system. These include calibration procedures, characterization routines, and variational algorithms. The control in these routines iteratively switches between the classical and the quantum computer. This results in the repeated compilation of the program that runs on the quantum system, scaling directly with the number of circuits and iterations. The repeated compilation results in a significant overhead throughout the routine. In practice, the total runtime of the program (classical compilation plus quantum execution) has an additional cost proportional to the circuit count. At practical scales, this can dominate the round-trip CPU-QPU time, between 5% and 80%, depending on the proportion of quantum execution time. To avoid repeated device-level compilation, we identify that machine code can be parametrized corresponding to pulse/gate parameters which can be dynamically adjusted during execution. Therefore, we develop a device-level partial-compilation (DLPC) technique that reduces compilation overhead to nearly constant, by using cheap remote procedure calls (RPC) from the QPU control software to the CPU. We then demonstrate the performance speedup of this on optimal pulse calibration, system characterization using randomized benchmarking (RB), and variational algorithms. We execute this modified pipeline on real trapped-ion quantum computers and observe significant reductions in compilation time, as much as 2.7x speedup for small-scale VQE problems