Chain‐Growth Polymerization of Aryl Grignards Initiated by a Stabilized NHC‐Pd Precatalyst

An N‐heterocyclic carbene‐ligated palladium catalyst was discovered to mediate living, chain‐growth polymerizations of both phenylene‐ and thiophene‐based monomers. Polymerization of a fluorene‐based monomer, on the other hand, did not proceed through a living, chain‐growth pathway. Excitingly, block copolymerizations of phenylene and thiophene proceeded via a chain‐growth pathway, regardless of the order of monomer addition. Although some chain termination was observed during these copolymerizations, this pathway could be minimized when the second monomer was added shortly after consumption of the first monomer. These results suggest that the catalyst resting‐state at the end of polymerization is unstable. As a result, modifications to the NHC‐scaffold or the 3‐chloropyridine ligand will be necessary to generate an improved catalyst. A Pd catalyst that can mediate a living, chain‐growth polymerization of π‐conjugated monomers is reported. Using (IPr)Pd(3‐chloropyridine)Cl 2 as a precatalyst, both homopolymers and block copolymers of phenylene‐ and thiophene‐based monomers were prepared. Although a living, chain‐growth mechanism is observed during polymerization, the catalyst resting state is somewhat unstable after the monomer is consumed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92031/1/marc_201200096_sm_suppl.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/92031/2/842_ftp.pd

Blaming the Ref: Understanding the Effect of Unexpected Emotional Cues on Family Violence

Domestic violence generates long-term effects on offenders, victims, and other household members. Insight into triggers of family violence can inform policy and improve services aimed at reducing abusive behavior. We investigate potential domestic violence triggers by analyzing unexpected losses in National Basketball Association games. The literature identifies increasing in-home violence after unexpected losses in the National Football League. Combining information on referee accuracy and fatigue, we develop a unique identification strategy to explore the impact of human error on family violence following unexpected losses. Results indicate that as referees are more accurate (more rested) in unexpected losses, family violence decreases, suggesting that the ability to place blame for a loss on referees increases the likelihood of violent outbursts. Further investigation shows that these results concentrate in games where referees are less rested and betting markets were less certain of the game outcome

An Artificial Habitat Increases the Reproductive Fitness of a Range-shifting Species within a Newly Colonized Ecosystem

When a range-shifting species colonizes an ecosystem it has not previously inhabited, it may experience suboptimal conditions that challenge its continued persistence and expansion. Some impacts may be partially mitigated by artificial habitat analogues: artificial habitats that more closely resemble a species\u27 historic ecosystem than the surrounding habitat. If conditions provided by such habitats increase reproductive success, they could be vital to the expansion and persistence of range-shifting species. We investigated the reproduction of the mangrove tree crab Aratus pisonii in its historic mangrove habitat, the suboptimal colonized salt marsh ecosystem, and on docks within the marsh, an artificial mangrove analogue. Crabs were assessed for offspring production and quality, as well as measures of maternal investment and egg quality. Aratus pisonii found on docks produced more eggs, more eggs per unit energy investment, and higher quality larvae than conspecifics in the surrounding salt marsh. Yet, crabs in the mangrove produced the highest quality larvae. Egg lipids suggest these different reproductive outcomes result from disparities in the quality of diet-driven maternal investments, particularly key fatty acids. This study suggests habitat analogues may increase the reproductive fitness of range-shifting species allowing more rapid expansion into, and better persistence in, colonized ecosystems

TGF-β Suppresses β-Catenin-Dependent Tolerogenic Activation Program in Dendritic Cells

The mechanisms that underlie the critical dendritic cell (DC) function in maintainance of peripheral immune tolerance are incompletely understood, although the β-catenin signaling pathway is critical for this role. The molecular details by which β-catenin signaling is regulated in DCs are unknown. Mechanical disruption of murine bone marrow-derived DC (BMDC) clusters activates DCs while maintaining their tolerogenic potential and this activation is associated with β-catenin signaling, providing a useful model with which to explore tolerance-associated β-catenin signaling in DCs. In this report, we demonstrate novel molecular features of the signaling events that control DC activation in response to mechanical stimulation. Non-canonical β-catenin signaling is an essential component of this tolerogenic activation and is modulated by adhesion molecules, including integrins. This unique β-catenin-dependent signaling pathway is constitutively active at low levels, suggesting that mechanical stimulation is not necessarily required for induction of this unique activation program. We additionally find that the immunomodulatory cytokine TGF-β antagonizes β-catenin in DCs, thereby selectively suppressing signaling associated with tolerogenic DC activation while having no impact on LPS-induced, β-catenin-independent immunogenic activation. These findings provide new molecular insight into the regulation of a critical signaling pathway for DC function in peripheral immune tolerance

How Bulk Sensitive is Hard X-ray Photoelectron Spectroscopy: Accounting for the Cathode-Electrolyte Interface when Addressing Oxygen Redox.

Sensitivity to the "bulk" oxygen core orbital makes hard X-ray photoelectron spectroscopy (HAXPES) an appealing technique for studying oxygen redox candidates. Various studies have reported an additional O 1s peak (530-531 eV) at high voltages, which has been considered a direct signature of the bulk oxygen redox process. Here, we find the emergence of a 530.4 eV O 1s HAXPES peak for three model cathodes-Li2MnO3, Li-rich NMC, and NMC 442-that shows no clear link to oxygen redox. Instead, the 530.4 eV peak for these three systems is attributed to transition metal reduction and electrolyte decomposition in the near-surface region. Claims of oxygen redox relying on photoelectron spectroscopy must explicitly account for the surface sensitivity of this technique and the extent of the cathode degradation layer

Spatial variation of Anopheles-transmitted Wuchereria bancrofti and Plasmodium falciparum infection densities in Papua New Guinea.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.The spatial variation of Wuchereria bancrofti and Plasmodium falciparum infection densities was measured in a rural area of Papua New Guinea where they share anopheline vectors. The spatial correlation of W. bancrofti was found to reduce by half over an estimated distance of 1.7 km, much smaller than the 50 km grid used by the World Health Organization rapid mapping method. For P. falciparum, negligible spatial correlation was found. After mass treatment with anti-filarial drugs, there was negligible correlation between the changes in the densities of the two parasites

Development of a health care systems curriculum.

Background: There is currently no gold standard for delivery of systems-based practice in medical education, and it is challenging to incorporate into medical education. Health systems competence requires physicians to understand patient care within the broader health care system and is vital to improving the quality of care clinicians provide. We describe a health systems curriculum that utilizes problem-based learning across 4 years of systems-based practice medical education at a single institution. Methods: This case study describes the application of a problem-based learning approach to system-based practice medical education. A series of behavioral statements, called entrustable professional activities, was created to assess student health system competence. Student evaluation of course curriculum design, delivery, and assessment was provided through web-based surveys. Results: To meet competency standards for system-based practice, a health systems curriculum was developed and delivered across 4 years of medical school training. Each of the health system lectures and problem-based learning activities are described herein. The majority of first and second year medical students stated they gained working knowledge of health systems by engaging in these sessions. The majority of the 2016 graduating students (88.24%) felt that the course content, overall, prepared them for their career. Conclusion: A health systems curriculum in undergraduate medical education using a problem-based learning approach is feasible. The majority of students learning health systems curriculum through this format reported being prepared to improve individual patient care and optimize the health system\u27s value (better care and health for lower cost)

Personalized ctDNA micro-panels can monitor and predict clinical outcomes for patients with triple-negative breast cancer

Circulating tumor DNA (ctDNA) in peripheral blood has been used to predict prognosis and therapeutic response for triple-negative breast cancer (TNBC) patients. However, previous approaches typically use large comprehensive panels of genes commonly mutated across all breast cancers. Given the reduction in sequencing costs and decreased turnaround times associated with panel generation, the objective of this study was to assess the use of custom micro-panels for tracking disease and predicting clinical outcomes for patients with TNBC. Paired tumor-normal samples from patients with TNBC were obtained at diagnosis (T0) and whole exome sequencing (WES) was performed to identify somatic variants associated with individual tumors. Custom micro-panels of 4-6 variants were created for each individual enrolled in the study. Peripheral blood was obtained at baseline, during Cycle 1 Day 3, at time of surgery, and in 3-6 month intervals after surgery to assess variant allele fraction (VAF) at different timepoints during disease course. The VAF was compared to clinical outcomes to evaluate the ability of custom micro-panels to predict pathological response, disease-free intervals, and patient relapse. A cohort of 50 individuals were evaluated for up to 48 months post-diagnosis of TNBC. In total, there were 33 patients who did not achieve pathological complete response (pCR) and seven patients developed clinical relapse. For all patients who developed clinical relapse and had peripheral blood obtained ≤ 6 months prior to relapse (n = 4), the custom ctDNA micro-panels identified molecular relapse at an average of 4.3 months prior to clinical relapse. The custom ctDNA panel results were moderately associated with pCR such that during disease monitoring, only 11% of patients with pCR had a molecular relapse, whereas 47% of patients without pCR had a molecular relapse (Chi-Square; p-value = 0.10). In this study, we show that a custom micro-panel of 4-6 markers can be effectively used to predict outcomes and monitor remission for patients with TNBC. These custom micro-panels show high sensitivity for detecting molecular relapse in advance of clinical relapse. The use of these panels could improve patient outcomes through early detection of relapse with preemptive intervention prior to symptom onset

Case report: response to the ERK1/2 inhibitor ulixertinib in BRAF D594G cutaneous melanoma.

Melanoma is characterized by oncogenic mutations in pathways regulating cell growth, proliferation, and metabolism. Greater than 80% of primary melanoma cases harbor aberrant activation of the mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) pathway, with oncogenic mutations in BRAF, most notably BRAF V600E, being the most common. Significant progress has been made in BRAF-mutant melanoma using BRAF and MEK inhibitors; however, non-V600 BRAF mutations remain a challenge with limited treatment options. We report the case of an individual diagnosed with stage III BRAF D594G-mutant melanoma who experienced an extraordinary response to the ERK1/2 inhibitor ulixertinib as fourth-line therapy. Ulixertinib was obtained via an intermediate expanded access protocol with unique flexibility to permit both single-agent and combination treatments, dose adjustments, breaks in treatment to undergo surgery, and long-term preventive treatment following surgical resection offering this patient the potential for curative treatment

ManyDogs Project: A Big Team Science Approach to Investigating Canine Behavior and Cognition

Dogs have a special place in human history as the first domesticated species and play important roles in many cultures around the world. However, their role in scientific studies has been relatively recent. With a few notable exceptions (e.g., Darwin, Pavlov, Scott, and Fuller), domestic dogs were not commonly the subject of rigorous scientific investigation of behavior until the late 1990s. Although the number of canine science studies has increased dramatically over the last 20 years, most research groups are limited in the inferences they can draw because of the relatively small sample sizes used, along with the exceptional diversity observed in dogs (e.g., breed, geographic location, experience). To this end, we introduce the ManyDogs Project, an international consortium of researchers interested in taking a big team science approach to understanding canine behavioral science. We begin by discussing why studying dogs provides valuable insights into behavior and cognition, evolutionary processes, human health, and applications for animal welfare. We then highlight other big team science projects that have previously been conducted in canine science and emphasize the benefits of our approach. Finally, we introduce the ManyDogs Project and our mission: (a) replicating important findings, (b) investigating moderators that need a large sample size such as breed differences, (c) reaching methodological consensus, (d) investigating cross-cultural differences, and (e) setting a standard for replication studies in general. In doing so, we hope to address previous limitations in individual lab studies and previous big team science frameworks to deepen our understanding of canine behavior and cognition