Introduction

Introduction to: The University against itself: The NYU Strike and the Future of the Academic Workplac

Structure/Function Relationships in Nickel-Peptide Complexes: Impact of the Primary Coordination Sphere on Square-Planar Nickel Chemistry

The novel metal-binding tripeptide asparagine-cysteine-cysteine (NCC) is capable of coordinating a metal ion, and we are exploring its use in several biological applications. Different metals may be incorporated into this tag, and when it is placed in line with a peptide or protein that has the potential to be used as a targeting agent, it has the potential to facilitate the diagnosis, treatment, and evaluation of cancers and other diseases. For example, platinum may be used as an anti-cancer therapeutic, whereas nickel generates a catalytic antioxidant. The advantage of this tag is that it is extremely small, is composed of naturally occurring amino acids, and binds metal with unique geometry. Metal binds irreversibly at physiological pH but is released upon modest acidification, as occurs with endocytosis. In order to utilize the tripeptide as a metal-binding tag, it is important to understand the structure, reactivity, and stability of this novel system. Initial studies with nickel established that NCC binds metal with 2N:2S geometry. Electronic absorption, circular dichroism (CD), and magnetic CD (MCD) data collected for Ni-NCC are consistent with a diamagnetic NiII center bound in square planar geometry. This complex acts as a mimic of the enzyme nickel superoxide dismutase (Ni-SOD), which catalyzes the disproportionation of superoxide to hydrogen peroxide and molecular oxygen. Changes in the CD signal of Ni-NCC indicate the optical activity of the complex changes over time, but mass spectrometry data show that the mass of the complex is unchanged, which suggests chiral rearrangement of the complex occurs. Performing the reaction in D2O allows incorporation of deuterium into non-exchangeable positions, indicating chiral inversion occurs at two of the alpha carbon atoms in the peptide. Control peptides were also used to verify the chirality of the final nickel-peptide complex is DLD-NCC. Characterization of the NCC sequence within a longer peptide shows that the geometry of metal coordination is maintained, though the electronic properties of the complex are varied to a small extent due to bis-amide coordination. Chiral inversion does not happen in the same two positions, though initial studies suggest inversion at a different location in the peptide may occur

Faithful unto Death: The Dog Burials of the Gaston Site in Halifax County, North Carolina

Excavated by prominent archaeologists Dr. Stanley South and Dr. Lewis Binford in 1955, the Gaston site in Halifax County continues to play an important role in the understanding of Native American lifeways 1,000 years ago in the North Carolina Piedmont. Excavations uncovered an unusually large number of domestic dogs (Canis lupus familiaris) that had been intentionally buried upon death by the human occupants of the site, but these dog burials have remained largely unstudied for over 60 years. This thesis seeks to analyze these canine remains by determining each dog’s age, sex, and skeletal health in order to evaluate their life histories. It places the 16 Gaston site dog burials within the larger context of dog burials found at sites across North Carolina, including two sites in particular with similarly large numbers of dog burials: Broad Reach and Contentnea Creek (also known as Wilson). This research desire to address two main questions: (1) Can any general patterns (temporal, geographic, cultural, etc.) be proposed from an in-depth study of dog burial distributions throughout the state? and (2) How do the dog burials at the Gaston site fit into these larger patterns?Bachelor of Art

Listen Up: A case study examination of focused listening

Today, most everyday music listening is an accompaniment to other activities; it is far less common that listening is someone’s primary activity, receiving most of their attention. In this article, we present a case study, Listen Up, run by Indigo Project, a mental health organization in Sydney, Australia, in which we explored relationships between participants’ responses to the experience and their demographics and styles of music engagement. A sample of 187 Australian residents (aged 20–64 years) who attended Listen Up completed a survey measuring music engagement; emotional responses to the experience; perceived outcomes of the session; pre- and post-measures of stress, mood, and anxiety; and free-text responses to questions concerning their experiences of listening mindfully and any thoughts or feelings that arose during the session. Participants experienced an increased mood and decreased levels of stress and arousal after taking part in Listen Up. Their focused-listening experiences were not simply characterized by enjoying the music; rather, the emotions evoked were varied and complex. We characterized their emotional responses as negative, positive, evocative and expressive, and sad; in addition, participants characterized their own experiences as a cathartic journey resolving into a positive, peaceful, and calm state. Reported outcomes of participating in Listen Up included experiences described as being emotionally challenging, therapeutic, and physically uncomfortable. An affective music engagement style was positively associated with evocative and expressive and sad emotional experiences, and therapeutic outcomes. As a focused-listening experience, Listen Up provides participants with the opportunity not only to attend to music but also to reflect on and process their personal thoughts and feelings. This research provides evidence for the emotional and mental health benefits of focused music listening, such that, focused listening reflects opportunities for strong experiences with music in today’s listening landscape

Incidence of HIV-related anal cancer remains increased despite long-term combined antiretroviral treatment: results from the french hospital database on HIV.

PURPOSE: To study recent trends in the incidence of anal cancer in HIV-infected patients receiving long-term combined antiretroviral treatment (cART) compared with the general population. PATIENTS AND METHODS: From the French Hospital Database on HIV, we identified 263 cases of invasive anal squamous cell carcinoma confirmed histologically between 1992 and 2008. We compared incidence rates of anal cancer across four calendar periods: 1992-1996 (pre-cART period), 1997-2000 (early cART period), and 2001-2004 and 2005-2008 (recent cART periods). Standardized incidence ratios (SIRs) were calculated by using general population incidence data from the French Network of Cancer Registries. RESULTS: In HIV-infected patients, the hazard ratio (HR) in the cART periods versus the pre-cART period was 2.5 (95% CI, 1.28 to 4.98). No difference was observed across the cART calendar periods (HR, 0.9; 95% CI, 0.6 to 1.3). In 2005-2008, HIV-infected patients compared with the general population had an excess risk of anal cancer, with SIRs of 109.8 (95% CI, 84.6 to 140.3), 49.2 (95% CI, 33.2 to 70.3), and 13.1 (95% CI, 6.8 to 22.8) for men who have sex with men (MSM), other men, and women, respectively. Among patients with CD4 cell counts above 500/μL for at least 2 years, SIRs were 67.5 (95% CI, 41.2 to 104.3) when the CD4 nadir was less than 200/μL for more than 2 years and 24.5 (95% CI, 17.1 to 34.1) when the CD4 nadir was more than 200/μL. CONCLUSION: Relative to that in the general population, the risk of anal cancer in HIV-infected patients is still extremely high, even in patients with high current CD4 cell counts. cART appears to have no preventive effect on anal cancer, particularly in MSM

Persistent transient myocardial ischemia despite beta-adrenergic blockade predicts a higher risk of adverse cardiac events in patients with coronary artery disease

AbstractObjectives. We evaluated the prevalence and prognostic significance of transient myocardial ischemia despite beta-adrenergic blockade in patients with coronary artery disease.Background. Persistence of transient ischemia despite therapy may correspond to a subset of high risk patients with coronary disease. The impact of beta-blocker withdrawal in these patients remains unknown.Methods. Patients (n = 313) with documented coronary artery disease and beta-blocker therapy, with (group I, n = 84) or without (group II, n = 229) transient ischemia on ambulatory electrocardiographic monitoring, were followed up during 21 ± 9 months for cardiac events (death, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass surgery and worsening angina). Occurrence of events was compared by log-rank test.Results. The number of coronary stenoses did not differ significantly between groups I and II. Beta-blocker therapy was discontinued more frequently during follow-up in group II (25% vs. 14% in group I, p = 0.04). Cumulative percentage of death or myocardial infarction, or both, tended to be higher in group I at 30 months (17% vs. 5% in group II, p = 0.09). Coronary angioplasty and bypass surgery were significantly more frequent in group I (p = 0.01 and 0.0008, respectively). Transient ischemia was associated with a higher cumulative probability of adverse events (p = 0.004). The number of coronary stenoses, presence of transient ischemia and beta-blocker withdrawal were the only significant prognostic factors of cardiac events in the Cox model. In group I patients, the relative hazard of cardiac events was increased threefold when beta-blocker therapy was interrupted.Conclusions. These data suggest that 1) the occurrence of transient ischemia despite beta-blocker therapy identifies a subset of high risk patients with coronary artery disease, and 2) the interruption of beta-blocker therapy increases the risk of adverse cardiac events

MAPping the Chiral Inversion and Structural Transformation of a Metal-Tripeptide Complex having Ni-SOD Activity

This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Inorganic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ic102295s.The metal abstraction peptide (MAP) tag is a tripeptide sequence capable of abstracting a metal ion from a chelator and binding it with extremely high affinity at neutral pH. Initial studies on the nickel-bound form of the complex demonstrate that the tripeptide asparagine-cysteine-cysteine (NCC) binds metal with 2N:2S, square planar geometry and behaves as both a structural and functional mimic of Ni superoxide dismutase (Ni-SOD). Electronic absorption, circular dichroism (CD), and magnetic CD (MCD) data collected for Ni-NCC are consistent with a diamagnetic NiII center. It is apparent from the CD signal of Ni-NCC that the optical activity of the complex changes over time. Mass spectrometry data show that the mass of the complex is unchanged. Combined with the CD data, this suggests that chiral rearrangement of the complex occurs. Following incubation of the nickel-containing peptide in D2O and back-exchange into H2O, incorporation of deuterium into non-exchangeable positions is observed, indicating chiral inversion occurs at two of the alpha carbon atoms in the peptide. Control peptides were used to further characterize the chirality of the final nickel-peptide complex, and DFT calculations were performed to validate the hypothesized position of the chiral inversions. In total, these data indicate Ni-SOD activity is increased proportionally to the degree of structural change in the complex over time, as cross-correlation between the change in CD signal and change in SOD activity reveals a linear relationship

Controlling the Chiral Inversion Reaction of the Metallopeptide Ni-Asparagine-Cysteine-Cysteine with Dioxygen

This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Inorganic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ic301717q.Synthetically generated metallopeptides have the potential to serve a variety of roles in biotechnology applications, but the use of such systems is often hampered by the inability to control secondary reactions. We have previously reported that the NiII complex of the tripeptide LLL-asparagine-cysteine-cysteine, LLL-NiII-NCC, undergoes metal-facilitated chiral inversion to DLD-NiII-NCC, which increases the observed superoxide scavenging activity. However, the mechanism for this process remained unexplored. Electronic absorption and circular dichroism studies of the chiral inversion reaction of NiII-NCC reveal a unique dependence on dioxygen. Specifically, in the absence of dioxygen, the chiral inversion is not observed, even at elevated pH, whereas the addition of O2 initiates this reactivity and concomitantly generates superoxide. Scavenging experiments using acetaldehyde are indicative of the formation of carbanion intermediates, demonstrating that inversion takes place by deprotonation of the alpha carbons of Asn1 and Cys3. Together, these data are consistent with the chiral inversion being dependent on the formation of a NiIII-NCC intermediate from NiII-NCC and O2. The data further suggest that the anionic thiolate and amide ligands in NiII-NCC inhibit Cα–H deprotonation for the NiII oxidation state, leading to a stable complex in the absence of O2. Together, these results offer insights into the factors controlling reactivity in synthetic metallopeptides

A novel tripeptide model of nickel superoxide dismutase

This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Inorganic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ic901828m.Nickel superoxide dismutase (Ni-SOD) catalyzes the disproportionation of superoxide to molecular oxygen and hydrogen peroxide, but the overall reaction mechanism has yet to be determined. Peptide-based models of the 2N:2S nickel coordination sphere of Ni-SOD have provided some insight into the mechanism of this enzyme. Here we show that the coordination sphere of Ni-SOD can be mimicked using the tripeptide asparagine-cysteine-cysteine (NCC). NCC binds nickel with extremely high affinity at physiological pH with 2N:2S geometry, as demonstrated by electronic absorption and circular dichroism (CD) data. Like Ni-SOD, Ni-NCC has mixed amine/amide ligation that favors metal-based oxidation over ligand-based oxidation. Electronic absorption, CD, and magnetic CD data (MCD) collected for Ni-NCC are consistent with a diamagnetic Ni(II) center bound in square planar geometry. Ni-NCC is quasi-reversibly oxidized with a midpoint potential of 0.72(2) V (versus Ag/AgCl) and breaks down superoxide in an enzyme-based assay, supporting its potential use as a model for Ni-SOD chemistry

Revealing Student Misconceptions and Instructor Blind Spots with Muddiest Point Formative Feedback

Of interest to all engineering disciplines, well-designed formative feedback has the potential to enhance both instructor teaching and student learning. Delivering fundamental courses year after year, can ultimately lead faculty to use stale notes or slides from past years. This approach may save time, but does not meet the shifting needs of our students who have high expectations from their instructors. One simple method to improve teaching is to employ muddiest point reflections. Muddiest point reflections involve simply asking students to anonymously reflect on what was “muddy”, i.e. confusing, during class and to rank their level of confusion which not only addresses students falling behind, but also shows students a commitment to their education especially when the instructor puts direct student quotes on the screen. Initially, developing a formative feedback process takes some effort, but once established, using a formative feedback process requires little effort. The formative feedback process includes four steps: 1) acquiring data from student reflections; 2) assessing and characterizing student responses in order to diagnose the learning issues that can impede students from achieving their learning goals; 3) designing and synthesizing the type and mode of formative feedback that best addresses the learning issues; and 4) selecting a formative feedback delivery method that quickly communicates to students the information and/or resources that they can use to enhance progress toward their learning goals. This paper presents and discusses the nuts and bolts of implementing the feedback process when using end-of-class “Muddiest Point” (MP) student reflections. These are collected following a class topic and are collected for the purpose of identifying – and quickly correcting – points of confusion that students individually report (their muddiest point). In addition, we report on several instructor perceptions of their teaching that result from using “muddiest points” for the first time. These instructors deployed MP in a systematic way in fall, 2015 in several different materials science courses across the country. Finally, we share strategic examples from each instructor, of how using muddiest points in fall, 2015, caught a misconception or point of confusion in their teaching that probably would not have been otherwise known