Morphology and reactivity of size-selected titanium oxide nanoclusters on Au(111).

The morphology and reactivity of mass-selected titania clusters, Ti3O6 and Ti3O5, deposited onto Au(111) were studied by scanning tunneling microscopy and temperature programmed desorption. Despite differing by only one oxygen atom, the stoichiometric Ti3O6 and the sub-stoichiometric ("reduced") Ti3O5 clusters exhibit very different structures and preferred binding sites. The Ti3O6 clusters bind at step edges and form small assemblies (2-4 clusters) on Au terraces, while the "reduced" Ti3O5 clusters form much larger fractal-like assemblies that can extend across step boundaries. Annealing the Ti3O5,6/Au(111) systems to higher temperatures causes changes in the size-distributions of cluster assemblies, but does not lead to the formation of TiOx nanoislands for temperatures ≤700 K. Reactivity studies show that the reduced Ti3O5 cluster has higher activity than Ti3O6 for 2-propanol dehydration, although both clusters exhibit substantial activity for dehydrogenation to acetone. Calculations using DFT+U suggest that the differences in aggregate morphology and reactivity are associated with the number of undercoordinated Ti3c sites in the supported clusters

Unaccustomed eccentric contractions impair plasma K+ regulation in the absence of changes in muscle Na+,K+-ATPase content

The Na+,K+-ATPase (NKA) plays a fundamental role in the regulation of skeletal muscle membrane Na+ and K+ gradients, excitability and fatigue during repeated intense contractions. Many studies have investigated the effects of acute concentric exercise on K+ regulation and skeletal muscle NKA, but almost nothing is known about the effects of repeated eccentric contractions. We therefore investigated the effects of unaccustomed maximal eccentric knee extensor contractions on K+ regulation during exercise, peak knee extensor muscle torque, and vastus lateralis muscle NKA content and 3-O-MFPase activity. Torque measurements, muscle biopsies, and venous blood samples were taken before, during and up to 7 days following the contractions in six healthy adults. Eccentric contractions reduced peak isometric muscle torque immediately post-exercise by 26±11% and serum creatine kinase concentration peaked 24 h post-exercise at 339±90 IU/L. During eccentric contractions, plasma [K+] rose during Set 1 and remained elevated at ∼4.9 mM during sets 4-10; this was despite a decline in work output by Set 4, which fell by 18.9% at set 10. The rise in plasma [K+] x work(-1) ratio was elevated over Set 2 from Set 4- Set 10. Eccentric contractions had no effect on muscle NKA content or maximal in-vitro 3-O-MFPase activity immediately post- or up to 7 d post-exercise. The sustained elevation in plasma [K+] despite a decrease in work performed by the knee extensor muscles suggests an impairment in K+ regulation during maximal eccentric contractions, possibly due to increased plasma membrane permeability or to excitation-contraction uncoupling

Interannual middle-latitude atmosphere-ocean interactions

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Earth, Atmospheric, and Planetary Sciences, 2001.Includes bibliographical references (p. 144-151).This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.This thesis discusses the interaction of atmosphere and ocean in midlatitudes on interannual and decadal timescales. We investigate the extent to which mutuallycoupled atmosphere-ocean feedback can explain the observed coupled variability on these timescales, and look for preferred modes of atmospheric response to forcing by sea-surface temperature anomalies. First, we formulate and study a very simple analytical model of the mutual interaction of the middle-latitude atmosphere and ocean. The model is found to support coupled modes in which oceanic baroclinic Rossby waves of decadal period grow through positive coupled feedback between the thermal forcing of the atmosphere induced by associated SST anomalies and the resulting windstress forcing of the ocean. Growth only occurs if the atmospheric response to thermal forcing is equivalent barotropic, with a particular phase relationship with the underlying SST anomalies. The dependence of the growth rate and structure of the modes on the nature of the assumed physics of air-sea interaction is explored, and their possible relation to observed phenomena discussed. We then construct a numerical model with the same physics; this enables us to consider the effects of nontrivial boundary conditions and background flows within the model. We find that the finite fetch of a closed ocean basin reduces growth rate and can lead to decay. However, the coupled mode described above remains the least-damped, and is thus the pattern most easily energized by stochastic forcing. Using a non-uniform atmospheric background flow focuses perturbation energy into particular areas, so that the coupled mode's expression in the atmosphere becomes fixed in space, rather than propagating. This improves the mode's resemblance to observed patterns of variability, such as the North Atlantic Oscillation, which are generally stationary patterns which fluctuate in intensity. The atmospheric component of the coupled mode exists in a balance between Rossby-wave propagation and vorticity advection. This is the same balance as the "neutral vectors" described by Marshall and Molteni (1993). Neutral vectors are the right singular vectors of the linearized atmospheric model's tendency matrix that have the smallest eigenvalues; they are also the patterns that exhibit the largest response to forcing perturbations in the linear model. We explain how the coupled mode arises as the ocean excites atmospheric neutral vectors. Neutral vectors act as pattern-specific amplifiers of ocean SST anomalies. We then proceed to study the neutral vectors of a quasigeostrophic model with realistic mean flow. We find a striking similarity between these patterns and the dominant patterns of variability observed in both the full nonlinear model and in the real world. We provide a mathematical explanation for this connection. Investigation of the "optimal forcing patterns" - the left singular vectors - proves to be less fruitful. The neutral modes have equivalent barotropic vertical structure, but their optimal forcing patterns are baroclinic and seem to be associated with low level heating. But the horizontal patterns of the forcing patterns are not robust, and are sensitive to the form of the inner product used in the SVD analysis. Additionally, applying "optimal" forcing patterns as perturbations to the full nonlinear model does not generate the response suggested by the linear model.by Jason Goodman.Ph.D

Integrating a Multi-Tiered System of Supports With Comprehensive School Counseling Programs

A multi-tiered system of supports, including Response to Intervention and Positive Behavioral Interventions and Supports, is a widely utilized framework implemented in K–12 schools to address the academic and behavioral needs of all students. School counselors are leaders who facilitate comprehensive school counseling programs and demonstrate their relevance to school initiatives and centrality to the school’s mission. The purpose of this article is to discuss both a multi-tiered system of supports and comprehensive school counseling programs, demonstrating the overlap between the two frameworks. Specific similarities include: leadership team and collaboration, coordinated services, school counselor roles, data collection, evidence-based practices, equity, cultural responsiveness, advocacy, prevention, positive school climate, and systemic change. A case study is included to illustrate a school counseling department integrating a multi-tiered system of supports with their comprehensive school counseling program. In the case study, school counselors are described as interveners, facilitators and supporters regarding the implementation of a multi-tiered system of supports

The influence of meridional ice transport on Europa’s ocean stratification and heat content

Jupiter’s moon Europa likely hosts a saltwater ocean beneath its icy surface. Geothermal heating and rotating convection in the ocean may drive a global overturning circulation that redistributes heat vertically and meridionally, preferentially warming the ice shell at the equator. Here we assess the previously unconstrained influence of ocean‐ice coupling on Europa’s ocean stratification and heat transport. We demonstrate that a relatively fresh layer can form at the ice‐ocean interface due to a meridional ice transport forced by the differential ice shell heating between the equator and the poles. We provide analytical and numerical solutions for the layer’s characteristics, highlighting their sensitivity to critical ocean parameters. For a weakly turbulent and highly saline ocean, a strong buoyancy gradient at the base of the freshwater layer can suppress vertical tracer exchange with the deeper ocean. As a result, the freshwater layer permits relatively warm deep ocean temperatures.Key PointsCoupling of Europa’s ocean circulation and the ice shell impacts global stratificationA low‐latitude freshwater layer may suppress vertical heat and tracer transportParameter space is explored based on properties observed by future missionsPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137725/1/grl56051.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137725/2/grl56051-sup-0001-TextS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137725/3/grl56051_am.pd

Revisiting Epidermal Growth Factor Receptor (EGFR) Amplification as a Target for Anti-EGFR Therapy: Analysis of Cell-Free Circulating Tumor DNA in Patients With Advanced Malignancies.

PurposeTo date, evidence for tissue epidermal growth factor receptor (EGFR) overexpression as a biomarker for anti-EGFR therapies has been weak. We investigated the genomic landscape of EGFR amplification in blood-derived cell-free tumor DNA (cfDNA) across diverse cancers and the role of anti-EGFR therapies in achieving response.MethodsWe assessed EGFR amplification status among 28,584 patients with malignancies evaluated by clinical-grade next-generation sequencing (NGS) of blood-derived cfDNA (54- to 73-gene panel). Furthermore, we curated the clinical characteristics of 1,434 patients at the University of California San Diego who had cfDNA testing by this NGS test.ResultsOverall, EGFR amplification was detected in cfDNA from 8.5% of patients (2,423 of 28,584), most commonly in colorectal (16.3% [458 of 2,807]), non-small-cell lung (9.0% [1,096 of 12,197]), and genitourinary cancers (8.1% [170 of 2,104]). Most patients had genomic coalterations (96.9% [95 of 98]), frequently involving genes affecting other tyrosine kinases (72.4% [71 of 98]), mitogen-activated protein kinase cascades (56.1% [55 of 98]), cell-cycle-associated signals (52.0% [51 of 98]), and the phosphoinositide 3-kinase pathway (35.7% [35 of 98]). EGFR amplification emerged in serial cfDNA after various anticancer therapies (n = 6), including checkpoint inhibitors (n = 4), suggesting a possible role for these amplifications in acquired resistance. Nine evaluable patients with EGFR amplification were treated with anti-EGFR-based regimens; five (55.6%) achieved partial responses, including three patients whose tissue NGS lacked EGFR amplification.ConclusionEGFR amplification was detected in cfDNA among 8.5% of 28,584 diverse cancers. Most patients had coexisting alterations. Responses were observed in five of nine patients who received EGFR inhibitors. Incorporating EGFR inhibitors into the treatment regimens of patients harboring EGFR amplification in cfDNA merits additional study