Transformative Geomorphic Research Using Laboratory Experimentation

Laboratory experiments in geomorphology is the theme of the 46th annual Binghamton Geomorphology Symposium (BGS). While geomorphic research historically has been dominated by field-based endeavors, laboratory experimentation has emerged as an important methodological approach to study these phenomena, employed primarily to address issues related to scale and the analytical treatment of the geomorphic processes. It is contended here that geomorphic laboratory experiments have resulted in transformative research. Several examples drawn from the fluvial and aeolian research communities are offered as testament to this belief, and these select transformative endeavors often share very similar attributes. The 46th BGS will focus on eight broad themes within laboratory experimentation, and a strong and diverse group of scientists have been assembled to speak authoritatively on these topics, featuring several high-profile projects worldwide. This special issue of the journal Geomorphology represents a collection of the papers written in support of this symposium

Correlations between the Electronic Properties of \u3cem\u3eShewanella oneidensis\u3c/em\u3e Cytochrome \u3cem\u3ec\u3c/em\u3e Nitrite Reductase (ccNiR) and Its Structure: Effects of Heme Oxidation State and Active Site Ligation

The electrochemical properties of Shewanella oneidensis cytochrome c nitrite reductase (ccNiR), a homodimer that contains five hemes per protomer, were investigated by UV–visible and electron paramagnetic resonance (EPR) spectropotentiometries. Global analysis of the UV–vis spectropotentiometric results yielded highly reproducible values for the heme midpoint potentials. These midpoint potential values were then assigned to specific hemes in each protomer (as defined in previous X-ray diffraction studies) by comparing the EPR and UV–vis spectropotentiometric results, taking advantage of the high sensitivity of EPR spectra to the structural microenvironment of paramagnetic centers. Addition of the strong-field ligand cyanide led to a 70 mV positive shift of the active site’s midpoint potential, as the cyanide bound to the initially five-coordinate high-spin heme and triggered a high-spin to low-spin transition. With cyanide present, three of the remaining hemes gave rise to distinctive and readily assignable EPR spectral changes upon reduction, while a fourth was EPR-silent. At high applied potentials, interpretation of the EPR spectra in the absence of cyanide was complicated by a magnetic interaction that appears to involve three of five hemes in each protomer. At lower applied potentials, the spectra recorded in the presence and absence of cyanide were similar, which aided global assignment of the signals. The midpoint potential of the EPR-silent heme could be assigned by default, but the assignment was also confirmed by UV–vis spectropotentiometric analysis of the H268M mutant of ccNiR, in which one of the EPR-silent heme’s histidine axial ligands was replaced with a methionine

Exploring differences in adverse symptom event grading thresholds between clinicians and patients in the clinical trial setting

Symptomatic adverse event (AE) monitoring is essential in cancer clinical trials to assess patient safety, as well as inform decisions related to treatment and continued trial participation. As prior research has demonstrated that conventional concordance metrics (e.g., intraclass correlation) may not capture nuanced aspects of the association between clinician and patient-graded AEs, we aimed to characterize differences in AE grading thresholds between doctors (MDs), registered nurses (RNs), and patients using the Bayesian Graded Item Response Model (GRM)

Lessons learned in extended-extended Spitzer Space Telescope operations

The Spitzer Space Telescope is executing the ninth year of extended operations beyond its 5.5-year prime mission. The project anticipated a maximum extended mission of about four years when the first mission extension was proposed. The robustness of the observatory hardware and the creativity of the project engineers and scientists in overcoming hurdles to operations has enabled a substantially longer mission lifetime. This has led to more challenges with an aging groundsystem due to resource reductions and decisions made early in the extended mission based on a shorter planned lifetime. We provide an overview of the extended mission phases, challenges met in maintaining and enhancing the science productivity, and what we would have done differently if the extended mission was planned from the start to be nearly twice as long as the prime mission

A Texture Bestiary

Textures are topologically nontrivial field configurations which can exist in a field theory in which a global symmetry group $G$ is broken to a subgroup $H$, if the third homotopy group \p3 of $G/H$ is nontrivial. We compute this group for a variety of choices of $G$ and $H$, revealing what symmetry breaking patterns can lead to texture. We also comment on the construction of texture configurations in the different models.Comment: 34 pages, plain Tex. (Minor corrections to an old paper.

The association between clinician-based common terminology criteria for adverse events (CTCAE) and patient-reported outcomes (PRO): a systematic review

Symptomatic adverse events (AEs) are monitored by clinicians as part of all US-based clinical trials in cancer via the U.S. National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) for the purposes of ensuring patient safety. Recently there has been a charge toward capturing the patient perspective for those AEs amenable to patient self-reporting via patient-reported outcomes (PRO). The aim of this review was to summarize the empirically reported association between analogous CTCAE and PRO ratings

Wisdom of Crowds, Wisdom of the Few: Expertise versus Diversity across Epistemic Landscapes

In a series of formal studies and less formal applications, Hong and Page offer a ‘diversity trumps ability’ result on the basis of a computational experiment accompanied by a mathematical theorem as explanatory background (Hong & Page 2004, 2009; Page 2007, 2011). “[W]e find that a random collection of agents drawn from a large set of limited-ability agents typically outperforms a collection of the very best agents from that same set” (2004, p. 16386). The result has been extremely influential as an epistemic justification for diversity policy initiatives. Here we show that the ‘diversity trumps ability’ result is tied to the particular random landscape used in Hong and Page’s simulation. We argue against interpreting results on that random landscape in terms of ‘ability’ or ‘expertise.’ These concepts are better modeled on smother and more realistic landscapes, but keeping other parameters the same those are landscapes on which it is groups of the best performing that do better. Smoother landscapes seem to vindicate both the concept and the value of expertise. Change in other parameters, however, also vindicates diversity. With an increase in the pool of available heuristics, diverse groups again do better. Group dynamics makes a difference as well; simultaneous ‘tournament’ deliberation in a group in place of the ‘relay’ deliberation in Hong and Page’s original model further emphasizes an advantage for diversity. ‘Tournament’ 2 dynamics particularly shows the advantage of mixed groups that include both experts and non-experts. As a whole, our modeling results suggest that relative to problem characteristics and conceptual resources, the wisdom of crowds and the wisdom of the few each have a place. We regard ours as a step toward attempting to calibrate their relative virtues in different modelled contexts of intellectual exploration

Imidazo[1,2-b]pyridazines as inhibitors of DYRK kinases

Selective inhibitors of DYRK1A are of interest for the treatment of cancer, Type 2 diabetes and neurological disorders. Optimization of imidazo [1,2-b]pyridazine fragment 1 through structure−activity relationship exploration and in silico drug design efforts led to the discovery of compound 17 as a potent cellular inhibitor of DYRK1A with selectivity over much of the kinome. The binding mode of compound 17 was elucidated with X-ray crystallography, facilitating the rational design of compound 29, an imidazo [1,2-b]pyridazine with improved kinase selectivity with respect to closely related CLK kinases.</p

Imidazo[1,2-b]pyridazines as inhibitors of DYRK kinases

Selective inhibitors of DYRK1A are of interest for the treatment of cancer, Type 2 diabetes and neurological disorders. Optimization of imidazo [1,2-b]pyridazine fragment 1 through structure−activity relationship exploration and in silico drug design efforts led to the discovery of compound 17 as a potent cellular inhibitor of DYRK1A with selectivity over much of the kinome. The binding mode of compound 17 was elucidated with X-ray crystallography, facilitating the rational design of compound 29, an imidazo [1,2-b]pyridazine with improved kinase selectivity with respect to closely related CLK kinases.</p