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

Two Approximation Results for Divergence Free Measures

In this paper we prove two approximation results for divergence free measures. The first is a form of an assertion of J. Bourgain and H. Brezis concerning the approximation of solenoidal charges in the strict topology: Given $F \in M_b(\mathbb{R}^d;\mathbb{R}^d)$ such that $\operatorname*{div} F=0$ in the sense of distributions, there exist oriented $C^1$ loops $\Gamma_{i,l}$ with associated measures $\mu_{\Gamma_{i,l}}$ such that $$F= \lim_{l \to \infty} \frac{\|F\|_{M_b(\mathbb{R}^d;\mathbb{R}^d)}}{n_l \cdot l} \sum_{i=1}^{n_l} \mu_{\Gamma_{i,l}}$$ weakly-star in the sense of measures and $$\lim_{l \to \infty} \frac{1}{n_l \cdot l} \sum_{i=1}^{n_l} \|\mu_{\Gamma_{i,l}}\|_{M_b(\mathbb{R}^d;\mathbb{R}^d)} = 1.$$ The second, which is an almost immediate consequence of the first, is that smooth compactly supported functions are dense in $$\left\{ F \in M_b(\mathbb{R}^d;\mathbb{R}^d): \operatorname*{div}F=0 \right\}$$ with respect to the strict topology.Comment: 13 page

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

Secondary Bacterial Pneumonias and Bloodstream Infections in Patients Hospitalized with COVID-19

Group Name: The Emory COVID-19 Quality and Clinical Research Collaborative Background: Patients hospitalized with COVID-19 are at risk of secondary infections—10%–33% develop bacterial pneumonia and 2%–6% develop bloodstream infection (BSI). We conducted a retrospective cohort study to identify the prevalence, microbiology, and outcomes of secondary pneumonias and BSIs in patients hospitalized with COVID-19. Methods: Patients aged ≥18 years with a positive SARS-CoV-2 real-time polymerase chain reaction assay admitted to 4 academic hospitals in Atlanta, Georgia, between February 15 and May 16, 2020, were included. We extracted electronic medical record data through June 16, 2020. Microbiology tests were performed according to standard protocols. Possible ventilator-associated pneumonia (PVAP) was defined according to Centers for Disease Control and Prevention (CDC) criteria. We assessed in-hospital mortality, comparing patients with and without infections using the χ(2) test. SAS University Edition software was used for data analyses. Results: In total, 774 patients were included (median age, 62 years; 49.7% female; 66.6% black). In total, 335 patients (43.3%) required intensive care unit (ICU) admission, 238 (30.7%) required mechanical ventilation, and 120 (15.5%) died. Among 238 intubated patients, 65 (27.3%) had a positive respiratory culture, including 15 with multiple potential pathogens, for a total of 84 potential pathogens. The most common organisms were Staphylococcus aureus (29 of 84; 34.5%), Pseudomonas aeruginosa (16 of 84; 19.0%), and Klebsiella spp (14 of 84; 16.7%). Mortality did not differ between intubated patients with and without a positive respiratory culture (41.5% vs 35.3%; P = .37). Also, 5 patients (2.1%) had a CDC-defined PVAP (1.7 PVAPs per 1,000 ventilator days); none of them died. Among 536 (69.3%) nonintubated patients, 2 (0.4%) had a positive Legionella urine antigen and 1 had a positive respiratory culture (for S. aureus). Of 774 patients, 36 (4.7%) had BSI, including 5 with polymicrobial BSI (42 isolates total). Most BSIs (24 of 36; 66.7%) had ICU onset. The most common organisms were S. aureus (7 of 42; 16.7%), Candida spp (7 of 42; 16.7%), and coagulase-negative staphylococci (5 of 42; 11.9%); 12 (28.6%) were gram-negative. The most common source was central-line–associated BSI (17 of 36; 47.2%), followed by skin (6 of 36; 16.7%), lungs (5 of 36; 13.9%), and urine (4 of 36; 11.1%). Mortality was 50% in patients with BSI versus 13.8% without (p < 0.0001). Conclusions: In a large cohort of patients hospitalized with COVID-19, secondary infections were rare: 2% bacterial pneumonia and 5% BSI. The risk factors for these infections (intubation and central lines, respectively) and causative pathogens reflect healthcare delivery and not a COVID-19–specific effect. Clinicians should adhere to standard best practices for preventing and empirically treating secondary infections in patients hospitalized with COVID-19. Funding: No Disclosures: Non

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

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