Nonlinear signaling on biological networks: the role of stochasticity and spectral clustering

Signal transduction within biological cells is governed by networks of interacting proteins. Communication between these proteins is mediated by signaling molecules which bind to receptors and induce stochastic transitions between different conformational states. Signaling is typically a cooperative process which requires the occurrence of multiple binding events so that reaction rates have a nonlinear dependence on the amount of signaling molecule. It is this nonlinearity that endows biological signaling networks with robust switch-like properties which are critical to their biological function. In this study, we investigate how the properties of these signaling systems depend on the network architecture. Our main result is that these nonlinear networks exhibit bistability where the network activity can switch between states that correspond to a low and high activity level. We show that this bistable regime emerges at a critical coupling strength that is determined by the spectral structure of the network. In particular, the set of nodes that correspond to large components of the leading eigenvector of the adjacency matrix determines the onset of bistability. Above this transition, the eigenvectors of the adjacency matrix determine a hierarchy of clusters, defined by its spectral properties, which are activated sequentially with increasing network activity. We argue further that the onset of bistability occurs either continuously or discontinuously depending upon whether the leading eigenvector is localized or delocalized. Finally, we show that at low network coupling stochastic transitions to the active branch are also driven by the set of nodes that contribute more strongly to the leading eigenvector.Comment: 30 pages, 12 figure

SYSTEMS ANALYSIS OF ARMY MATERIEL REPORTING FOR THE MIDDLE TIER OF ACQUISITION PATHWAY

The Acquisition Modernization Integration (AMI) team within the ASA(ALT) office is critical in the Army decision-making process. The AMI creates reports that include actionable knowledge rendered to Army strategic leaders. These reports include vital data on critical Army programs integrated into the modernization efforts. Part of this necessary data are the First Unit Issued (FUI) and the First Unit Equipped (FUE) dates. These reported dates directly affect Army units’ training, deployment, and logistics support timelines as they become part of the data-driven analytics on reports provided to decision-makers. Because of the initiatives to improve efficiency in the acquisition process, realignment, and creation of new organizations, the AMI needs a system that facilitates accurate and consistent FUI and FUE dates reporting. This research used several systems engineering (SE) concepts and methods such as stakeholders’ analysis, functional analysis, mapping of functions to systems’ parameters, modeling-based systems engineering, and analysis of alternatives. The application of these SE tools resulted in identifying a system/process that will accurately and consistently facilitate FUI and FUE date reporting to meet the AMI’s needs. This system/process provides a reporting capability for current and future acquisition programs and could be implemented across the DOD and all other government agencies and departments.Major, United States ArmyCaptain, United States ArmyCaptain, United States ArmyCaptain, United States ArmyCaptain, United States ArmyApproved for public release. Distribution is unlimited

Minds of monsters : scary imbalances between cognition and emotion

Four studies investigate a fear of imbalanced minds hypothesis: that threatening agents perceived to be relatively mismatched in capacities for cognition (e.g., self-control and reasoning) and emotion (e.g., sensations and emotions) will be rated as scarier and more dangerous by observers. In ratings of fictional monsters (e.g., zombies, vampires) targets seen as more imbalanced between capacities for cognition and emotion (high cognition-low emotion or low cognition-high emotion) were rated as scarier compared to those with equally matched levels of cognition and emotion (Studies 1 & 2). Similar effects were observed using ratings of scary animals (e.g., tigers, sharks; Studies 2 & 3), and infected humans (Study 4). Moreover, these effects are explained through diminished perceived control/predictability over the target agent. These findings highlight the role of balance between cognition and emotion in appraisal of threatening agents, in part because those agents are seen as more chaotic and uncontrollable

Copper-Water and Hybrid Aluminum-Ammonia Heat Pipes for Spacecraft Thermal Control Applications

Copper-water heat pipes are commonly used for thermal management of electronics systems on earth and aircraft, but have not been used in spacecraft thermal control applications to date, due to the satellite industry's requirement that any device or system be successfully tested in a microgravity environment prior to adoption. Recently, Advanced Cooling Technologies Inc., (ACT), NASA Marshall Space Flight Center, and the International Space Station office at NASA's Johnson Space Center demonstrated flight heritage in Low-Earth Orbit. The testing was conducted aboard the International Space Station (ISS) under the Advanced Passive Thermal eXperiment (APTx) project. The heat pipes were embedded in a high conductivity (HiK"TM") aluminum base plate and subject to a variety of thermal tests over a temperature range of -10 to 38 C for a ten-day period. Results showed excellent agreement with both predictions and ground tests. In addition, novel hybrid wick aluminum-ammonia heat pipes are developed to handle heat flux requirements for spacecraft thermal control applications. The 5-10 W/cm2 heat density limitation of aluminum-ammonia grooved heat pipes has been a fundamental limitation in the current design for space applications. The recently demonstrated 50 W/cm2 capability of the hybrid high heat flux heat pipes provides a realistic means of managing the high heat density anticipated for the next generation space designs

2014-2015 Children\u27s Concert

https://spiral.lynn.edu/conservatory_otherseasonalconcerts/1005/thumbnail.jp

Quality Indicators for the Diagnosis and Management of Primary Hyperparathyroidism

IMPORTANCE Primary hyperparathyroidism (pHPT) is a common endocrine disorder with many diagnostic and treatment challenges. Despite high-quality guidelines, care is variable, and there is low adherence to evidence-based treatment pathways. OBJECTIVE To develop quality indicators (QIs) to evaluate the diagnosis and treatment of pHPT that could measure, improve, and optimize quality of care and outcomes for patients with this disease. DESIGN, SETTING, AND PARTICIPANTS This quality improvement study used a guideline-based approach to develop QIs that were ranked by a Canadian 9-member expert panel of 3 endocrinologists, 3 otolaryngologists, and 3 endocrine surgeons. Data were analyzed between September 2020 and May 2021. MAIN OUTCOMES AND MEASURES Candidate indicators (CIs) were extracted from published primary hyperparathyroidism guidelines and summarized with supporting evidence. The 9-member expert panel rated each CI on the validity, reliability, and feasibility of measurement. Final QIs were selected from CIs using the modified RAND-University of California, Los Angeles appropriateness methodology. All panelists were then asked to rank the top 5 QIs for primary, endocrine, and surgical care. RESULTS Forty QIs were identified and evaluated by the expert panel. After 2 rounds of evaluations and discussion, a total of 18 QIs were selected as appropriate measures of high-quality care. The top 5 QIs for primary, endocrine, and surgical care were selected following panelist rankings. CONCLUSIONS AND RELEVANCE This quality improvement study proposes 18 QIs for the diagnosis and management of pHPT. Furthermore, the top 5 QIs applicable to physicians commonly treating pHPT, including general physicians, internists, endocrinologists, otolaryngologists, and surgeons, are included. These QIs not only assess the quality of care to guide the process of improvement, but also can assess the implementation of evidence-based guideline recommendations. Using these indicators in clinical practice and health system registries can improve quality and cost-effectiveness of care for patients with pHPT

A comprehensive assessment of benign genetic variability for neurodegenerative disorders

Over the last few years, as more and more sequencing studies have been performed, it has become apparent that the identification of pathogenic mutations is, more often than not, a complex issue. Here, with a focus on neurodegenerative diseases, we have performed a survey of coding genetic variability that is unlikely to be pathogenic. We have performed whole-exome sequencing in 478 samples derived from several brain banks in the United Kingdom and the United States of America. Samples were included when subjects were, at death, over 60 years of age, had no signs of neurological disease and were subjected to a neuropathological examination, which revealed no evidence of neurodegeneration. This information will be valuable to studies of genetic variability as a causal factor for neurodegenerative syndromes. We envisage it will be particularly relevant for diagnostic laboratories as a filter step to the results being produced by either genome-wide or gene-panel sequencing. We have made this data publicly available at www.alzforum.org/exomes/hex

Comorbid depression and anxiety effects on pregnancy and neonatal outcome

The effects of comorbid depression and anxiety were compared to the effects of depression alone and anxiety alone on pregnancy mood states and biochemistry and on neonatal outcomes in a large multi-ethnic sample. At the prenatal period the comorbid and depressed groups had higher scores than the other groups on the depression measure. But, the comorbid group had higher anxiety, anger and daily hassles scores than the other groups, and they had lower dopamine levels. As compared to the non-depressed group, they also reported more sleep disturbances and relationship problems. The comorbid group also experienced a greater incidence of prematurity than the depressed, the high anxiety and the non-depressed groups. Although the comorbid and anxiety groups were lower birthweight than the non-depressed and depressed groups, the comorbid group did not differ from the depressed and anxiety groups on birth length. The neonates of the comorbid and depressed groups had higher cortisol and norepinephrine and lower dopamine and serotonin levels than the neonates of the anxiety and non-depressed groups as well as greater relative right frontal EEG. These data suggest that for some measures comorbidity of depression and anxiety is the worst condition (e.g., incidence of prematurity), while for others, comorbidity is no more impactful than depression alone.This research was supported by a Merit Award (MH #46586), an NIH grant (AT #00370) and Senior Research Scientist Awards (MH #0033 1 and AT #001585) and a March of Dimes Grant (#12-FYO3-48) to Tiffany Field and funding from Johnson and Johnson Pediatric Institute to the Touch Research Institute

MHC class I-related chain A and B ligands are differentially expressed in human cervical cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Natural killer (NK) cells are an important resource of the innate immune system directly involved in the spontaneous recognition and lysis of virus-infected and tumor cells. An exquisite balance of inhibitory and activating receptors tightly controls the NK cell activity. At present, one of the best-characterized activating receptors is NKG2D, which promotes the NK-mediated lysis of target cells by binding to a family of cell surface ligands encoded by the MHC class I chain-related (MIC) genes, among others. The goal of this study was to describe the expression pattern of MICA and MICB at the molecular and cellular levels in human cervical cancer cell lines infected or not with human papillomavirus, as well as in a non-tumorigenic keratinocyte cell line.</p> <p>Results</p> <p>Here we show that MICA and MICB exhibit differential expression patterns among HPV-infected (SiHa and HeLa) and non-infected cell lines (C33-A, a tumor cell line, and HaCaT, an immortalized keratinocyte cell line). Cell surface expression of MICA was higher than cell surface expression of MICB in the HPV-positive cell lines; in contrast, HPV-negative cells expressed lower levels of MICA. Interestingly, the MICA levels observed in C33-A cells were overcome by significantly higher MICB expression. Also, all cell lines released higher amounts of soluble MICB than of soluble MICA into the cell culture supernatant, although this was most pronounced in C33-A cells. Additionally, Real-Time PCR analysis demonstrated that MICA was strongly upregulated after genotoxic stress.</p> <p>Conclusions</p> <p>This study provides evidence that even when MICA and MICB share a high degree of homology at both genomic and protein levels, differential regulation of their expression and cell surface appearance might be occurring in cervical cancer-derived cells.</p