The consequences of (not) seeing eye-to-eye about the past:The role of supervisor–team fit in past temporal focus for supervisors' leadership behavior

This study seeks to advance our understanding of the leadership consequences that may ensue when supervisors and their teams have similar versus differing orientations toward the past. Integrating a leader–team fit perspective with functional leadership theory, we cast incongruence between supervisor and team past temporal focus as a key antecedent of supervisors' active (i.e., task-oriented and relationship-oriented) and passive (i.e., laissez-faire) leadership behaviors toward the team. We tested our hypotheses in a team-level study that included a field sample of 84 super-visors and their teams using polynomial regression and response surface analyses.Results illustrated that supervisors demonstrated more task-oriented and relationship-oriented leadership when supervisors' and their team's past temporal focus were incongruent rather than aligned. Furthermore, in situations of supervisor–team congruence, supervisors engaged in less task-oriented and relationship-oriented leadership and more laissez-faire leadership with higher (rather than lower)levels of supervisor and team past temporal focus. In sum, these findings support a complex (mis)fit model such that supervisors' attention to the past may hinder their productive leadership behaviors in some team contexts but not in others. Hence, this research advances a novel, multiple-stakeholder perspective on the role of both supervisors' and their team's past temporal focus for important leadership behavio

Development Toward a Ground-Based Interferometric Phased Array for Radio Detection of High Energy Neutrinos

The in-ice radio interferometric phased array technique for detection of high energy neutrinos looks for Askaryan emission from neutrinos interacting in large volumes of glacial ice, and is being developed as a way to achieve a low energy threshold and a large effective volume at high energies. The technique is based on coherently summing the impulsive Askaryan signal from multiple antennas, which increases the signal-to-noise ratio for weak signals. We report here on measurements and a simulation of thermal noise correlations between nearby antennas, beamforming of impulsive signals, and a measurement of the expected improvement in trigger efficiency through the phased array technique. We also discuss the noise environment observed with an analog phased array at Summit Station, Greenland, a possible site for an interferometric phased array for radio detection of high energy neutrinos.Comment: 13 Pages, 14 Figure

Associations between neuropsychiatric symptoms and ADRD serum biomarkers in Mexican American and non-Hispanic white adults with mild cognitive impairment

Background: Mild cognitive impairment (MCI) is a heterogenous diagnostic category with trajectories ranging from reversion to unimpaired cognition to progression to dementia. Neuropsychiatric symptoms such as depression and irritability are common and influence quality of life of patients and caregivers. The role of neuropsychiatric symptoms on disease biology, presentation, and course remains poorly understood. The goal of this study was to evaluate the associations between neuropsychiatric symptoms and serum ADRD biomarkers in Mexican American and non-Hispanic white participants diagnosed with MCI. Method: Participants from the Texas Alzheimer’s Research and Care Consortium underwent a blood draw and clinical evaluation, including psychopathological and cognitive assessments. Diagnoses of MCI were adjudicated in consensus reviews. The presence and severity of neuropsychiatric symptoms were assessed by informant report using the Neuropsychiatric Inventory (NPI). Serum levels of total tau, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were assessed using Simoa HD-X Analyzer. Associations between NPI total score and individual items with serum biomarker levels were assessed using linear regression adjusted for age and sex. Result: A total of 425 participants (mean age: 71 ± 9 years, 62% female, 74% Mexican American) had a diagnosis of MCI and serum ADRD biomarkers (Table 1). Total NPI score was not associated with total tau (ß=0.002, p=0.609), NfL (ß=0.001, p=0.658), or GFAP (ß=0.001, p=0.777). However, endorsement of appetite changes was associated with higher NfL (ß=0.077, p=0.006) and GFAP (ß=0.088, p=0.002) levels. Stratified analyses indicated associations of appetite changes with serum NfL (ß=0.108, p=0.002) and GFAP (ß=0.095, p=0.003) in Mexican Americans, but not in non-Hispanic whites (NfL: ß=0.022, p=0.633, GFAP: ß=0.102, p=0.066).There were no other significant associations between individual items on the NPI with serum biomarkers (p\u3e0.05, Bonferroni adjustment p±0.003). Conclusion: Within Mexican American adults with MCI, changes in appetite were associated with higher serum NFL and GFAP levels. As elevations in circulating NfL and GFAP levels are associated with ADRD pathology and accelerated disease progression, appetite changes, a non-invasive and easily discernible behavioral phenotype, may predict higher likelihood of worsening cognitive course. Future longitudinal studies will be necessary to confirm predictive utility of appetite changes for disease progression

Elucidating glycosaminoglycan–protein–protein interactions using carbohydrate microarray and computational approaches

Glycosaminoglycan polysaccharides play critical roles in many cellular processes, ranging from viral invasion and angiogenesis to spinal cord injury. Their diverse biological activities are derived from an ability to regulate a remarkable number of proteins. However, few methods exist for the rapid identification of glycosaminoglycan–protein interactions and for studying the potential of glycosaminoglycans to assemble multimeric protein complexes. Here, we report a multidisciplinary approach that combines new carbohydrate microarray and computational modeling methodologies to elucidate glycosaminoglycan–protein interactions. The approach was validated through the study of known protein partners for heparan and chondroitin sulfate, including fibroblast growth factor 2 (FGF2) and its receptor FGFR1, the malarial protein VAR2CSA, and tumor necrosis factor-α (TNF-α). We also applied the approach to identify previously undescribed interactions between a specific sulfated epitope on chondroitin sulfate, CS-E, and the neurotrophins, a critical family of growth factors involved in the development, maintenance, and survival of the vertebrate nervous system. Our studies show for the first time that CS is capable of assembling multimeric signaling complexes and modulating neurotrophin signaling pathways. In addition, we identify a contiguous CS-E-binding site by computational modeling that suggests a potential mechanism to explain how CS may promote neurotrophin-tyrosine receptor kinase (Trk) complex formation and neurotrophin signaling. Together, our combined microarray and computational modeling methodologies provide a general, facile means to identify new glycosaminoglycan–protein–protein interactions, as well as a molecular-level understanding of those complexes

Bayesian hierarchical clustering for studying cancer gene expression data with unknown statistics

Clustering analysis is an important tool in studying gene expression data. The Bayesian hierarchical clustering (BHC) algorithm can automatically infer the number of clusters and uses Bayesian model selection to improve clustering quality. In this paper, we present an extension of the BHC algorithm. Our Gaussian BHC (GBHC) algorithm represents data as a mixture of Gaussian distributions. It uses normal-gamma distribution as a conjugate prior on the mean and precision of each of the Gaussian components. We tested GBHC over 11 cancer and 3 synthetic datasets. The results on cancer datasets show that in sample clustering, GBHC on average produces a clustering partition that is more concordant with the ground truth than those obtained from other commonly used algorithms. Furthermore, GBHC frequently infers the number of clusters that is often close to the ground truth. In gene clustering, GBHC also produces a clustering partition that is more biologically plausible than several other state-of-the-art methods. This suggests GBHC as an alternative tool for studying gene expression data. The implementation of GBHC is available at https://sites. google.com/site/gaussianbhc

Omega-3 Fatty Acids Reduce Adipose Tissue Macrophages in Human Subjects with Insulin Resistance

Fish oils (FOs) have anti-inflammatory effects and lower serum triglycerides. This study examined adipose and muscle inflammatory markers after treatment of humans with FOs and measured the effects of ω-3 fatty acids on adipocytes and macrophages in vitro. Insulin-resistant, nondiabetic subjects were treated with Omega-3-Acid Ethyl Esters (4 g/day) or placebo for 12 weeks. Plasma macrophage chemoattractant protein 1 (MCP-1) levels were reduced by FO, but the levels of other cytokines were unchanged. The adipose (but not muscle) of FO-treated subjects demonstrated a decrease in macrophages, a decrease in MCP-1, and an increase in capillaries, and subjects with the most macrophages demonstrated the greatest response to treatment. Adipose and muscle ω-3 fatty acid content increased after treatment; however, there was no change in insulin sensitivity or adiponectin. In vitro, M1-polarized macrophages expressed high levels of MCP-1. The addition of ω-3 fatty acids reduced MCP-1 expression with no effect on TNF-α. In addition, ω-3 fatty acids suppressed the upregulation of adipocyte MCP-1 that occurred when adipocytes were cocultured with macrophages. Thus, FO reduced adipose macrophages, increased capillaries, and reduced MCP-1 expression in insulin-resistant humans and in macrophages and adipocytes in vitro; however, there was no measureable effect on insulin sensitivity. Diabetes 62:1709–1717, 201

The ansamycin antibiotic, rifamycin SV, inhibits BCL6 transcriptional repression and forms a complex with the BCL6-BTB/POZ domain

BCL6 is a transcriptional repressor that is over-expressed due to chromosomal translocations, or other abnormalities, in ~40% of diffuse large B-cell lymphoma. BCL6 interacts with co-repressor, SMRT, and this is essential for its role in lymphomas. Peptide or small molecule inhibitors, which prevent the association of SMRT with BCL6, inhibit transcriptional repression and cause apoptosis of lymphoma cells in vitro and in vivo. In order to discover compounds, which have the potential to be developed into BCL6 inhibitors, we screened a natural product library. The ansamycin antibiotic, rifamycin SV, inhibited BCL6 transcriptional repression and NMR spectroscopy confirmed a direct interaction between rifamycin SV and BCL6. To further determine the characteristics of compounds binding to BCL6-POZ we analyzed four other members of this family and showed that rifabutin, bound most strongly. An X-ray crystal structure of the rifabutin-BCL6 complex revealed that rifabutin occupies a partly non-polar pocket making interactions with tyrosine58, asparagine21 and arginine24 of the BCL6-POZ domain. Importantly these residues are also important for the interaction of BLC6 with SMRT. This work demonstrates a unique approach to developing a structure activity relationship for a compound that will form the basis of a therapeutically useful BCL6 inhibitor

Fitting as a temporal sensemaking process: shifting trajectories and stable themes

This study identifies several mechanisms and the overall process by which individuals understand their evolving fit with their work environment. Prior person-environment research has emphasized one-time quantitative assessments of fit, primarily as new entrants enter their work environment. In this study, we employed a qualitative approach to investigate the following question: how do long-tenured professionals make sense of fit over time? Three key findings emerged from the fit-related histories we collected. First, we discovered four prototypical fit trajectories, which were constructed from temporal comparisons with past, present, and future fit, and employed to make momentary sense of events occurring in the work environment. Second, we identified two fit processes that played out over time: a slow accumulation journey and a sudden identity-threat journey. Third, we found that individuals’ set of fit experiences was explained by one of four enduring fit themes, explaining their pattern of fit experiences over time and their reaction to misfit. Most surprising was the significant turnover among our long-tenured participants in the year or so following our interviews. Our findings break from traditional thinking about fit as predicting outcomes in the moment, to fitting as both a journey and a retrospective and prospective process of sensemaking. Keywords: person-environment fit, misfit, temporal, time, process, sensemaking, qualitative, identit

Ruthenium-rhenium and ruthenium-palladium supramolecular photocatalysts for photoelectrocatalytic CO2 and H+ reduction.

Photoelectrocatalysis offers the opportunity to close the carbon loop and convert captured CO2 back into useful fuels and feedstocks, mitigating against anthropogenic climate change. However, since CO2 is inherently stable and sunlight is a diffuse and intermittent energy source, there are considerable scientific challenges to overcome. In this paper we present the integration of two new metal–organic photocatalysts into photocathodes for the reduction of CO2 using ambient light. The two molecular dyads contained a rhenium carbonyl or palladium-based catalytic centre bridged to a ruthenium bipyridyl photosensitizer functionalised with carboxylic acid groups to enable adsorption onto the surface of mesoporous NiO cathodes. The photocathodes were evaluated for photoelectrochemical reduction of CO2 to CO or H+ to H2 and the performances were compared directly with a control compound lacking the catalytic site. A suite of electrochemical, UV-visible steady-state/time-resolved spectroscopy, X-ray photoelectron spectroscopy and gas chromatography measurements were employed to gain kinetic and mechanistic insight to primary electron transfer processes and relate the structure to the photoelectrocatalytic performance under various conditions in aqueous media. A change in behaviour when the photocatalysts were immobilized on NiO was observed. Importantly, the transfer of electron density towards the Re–CO catalytic centre was observed, using time resolved infrared spectroscopy, only when the photocatalyst was immobilized on NiO and not in MeCN solution. We observed that photocurrent and gaseous photoproduct yields are limited by a relatively low yield of the required charge-separated state across the NiO|Photocatalyst interface. Nonetheless, the high faradaic efficiency (94%) and selectivity (99%) of the Re system towards CO evolution are very promising