Developing an integrated system for biological network exploration

Network analysis and visualization have been used in systems biology to extract biological insight from complex datasets. Many existing network analysis tools either focus on visualization but have limited scalability, or focus on analysis but have limited visualizations. The separation of analyzing the raw data from visualizing the analysis results causes systems biologists to jump between forming a question, building a massive network, identifying a subnetwork for visualization, and using the visualization as feedback and inspiration for the next question. This iterative process can take several days, making it difficult for researchers to maintain the mental map of the questions queried. In addition, biological data is stored in different formats and has differing annotations, thus systems biologists often run into hurdles when merging large or heterogeneous networks. The polymorphic nature of the datasets presents a challenge for researchers to integrate data to answer biological questions. A more systematic method for merging networks, resolving data conflicts, and analyzing networks may improve the efficiency and scalability of heterogeneous multi-network analysis. Towards improving and pushing forward multi-network analysis to help a researcher easily combine multiple heterogeneous biological data networks to answer biological questions, this dissertation reports several accomplishments that provide (i) a set of standard multi-network operations, (ii) standard merging rules for heterogeneous networks, (iii) standard methods to reproduce network analyses, (iv) a single integrated software environment that allows users to visualize and explore the network analysis results and (v) several examples applying these methods in biological analysis. These efforts have culminated in three academic publications

Time-Limited Trials Among Critically Ill Patients With Advanced Medical Illnesses to Reduce Nonbeneficial Intensive Care Unit Treatments: Protocol for a Multicenter Quality Improvement Study.

BackgroundInvasive intensive care unit (ICU) treatments for patients with advanced medical illnesses and poor prognoses may prolong suffering with minimal benefit. Unfortunately, the quality of care planning and communication between clinicians and critically ill patients and their families in these situations are highly variable, frequently leading to overutilization of invasive ICU treatments. Time-limited trials (TLTs) are agreements between the clinicians and the patients and decision makers to use certain medical therapies over defined periods of time and to evaluate whether patients improve or worsen according to predetermined clinical parameters. For patients with advanced medical illnesses receiving aggressive ICU treatments, TLTs can promote effective dialogue, develop consensus in decision making, and set rational boundaries to treatments based on patients' goals of care.ObjectiveThe aim of this study will be to examine whether a multicomponent quality-improvement strategy that uses protocoled TLTs as the default ICU care-planning approach for critically ill patients with advanced medical illnesses will decrease duration and intensity of nonbeneficial ICU care without changing hospital mortality.MethodsThis study will be conducted in medical ICUs of three public teaching hospitals in Los Angeles County. In Aim 1, we will conduct focus groups and semistructured interviews with key stakeholders to identify facilitators and barriers to implementing TLTs among ICU patients with advanced medical illnesses. In Aim 2, we will train clinicians to use protocol-enhanced TLTs as the default communication and care-planning approach in patients with advanced medical illnesses who receive invasive ICU treatments. Eligible patients will be those who the treating ICU physicians consider to be at high risk for nonbeneficial treatments according to guidelines from the Society of Critical Care Medicine. ICU physicians will be trained to use the TLT protocol through a curriculum of didactic lectures, case discussions, and simulations utilizing actors as family members in role-playing scenarios. Family meetings will be scheduled by trained care managers. The improvement strategy will be implemented sequentially in the three participating hospitals, and outcomes will be evaluated using a before-and-after study design. Key process outcomes will include frequency, timing, and content of family meetings. The primary clinical outcome will be ICU length of stay. Secondary outcomes will include hospital length of stay, days receiving life-sustaining treatments (eg, mechanical ventilation, vasopressors, and renal replacement therapy), number of attempts at cardiopulmonary resuscitation, frequency of invasive ICU procedures, and disposition from hospitalization.ResultsThe study began in August 2017. The implementation of interventions and data collection were completed at two of the three hospitals. As of September 2019, the study was at the postintervention stage at the third hospital. We have completed focus groups with physicians at each medical center (N=29) and interviews of family members and surrogate decision makers (N=18). The study is expected to be completed in the first quarter of 2020, and results are expected to be available in mid-2020.ConclusionsThe successful completion of the aims in this proposal may identify a systematic approach to improve communication and shared decision making and to reduce nonbeneficial invasive treatments for ICU patients with advanced medical illnesses.International registered report identifier (irrid)DERR1-10.2196/16301

Cell-Cycle Perturbations Suppress the Slow-Growth Defect of spt10Δ Mutants in Saccharomyces cerevisiae

Spt10 is a putative acetyltransferase of Saccharomyces cerevisiae that directly activates the transcription of histone genes. Deletion of SPT10 causes a severe slow growth phenotype, showing that Spt10 is critical for normal cell division. To gain insight into the function of Spt10, we identified mutations that impair or improve the growth of spt10 null (spt10Δ) mutants. Mutations that cause lethality in combination with spt10Δ include particular components of the SAGA complex as well as asf1Δ and hir1Δ. Partial suppressors of the spt10Δ growth defect include mutations that perturb cell-cycle progression through the G1/S transition, S phase, and G2/M. Consistent with these results, slowing of cell-cycle progression by treatment with hydroxyurea or growth on medium containing glycerol as the carbon source also partially suppresses the spt10Δ slow-growth defect. In addition, mutations that impair the Lsm1-7−Pat1 complex, which regulates decapping of polyadenylated mRNAs, also partially suppress the spt10Δ growth defect. Interestingly, suppression of the spt10Δ growth defect is not accompanied by a restoration of normal histone mRNA levels. These findings suggest that Spt10 has multiple roles during cell division

How does experience change firms' foreign investment decisions to non-market events?

We examine how experience with two types of non-market risks (e.g., natural disasters and armed conflicts) changes foreign direct investment (FDI) decisions. Extending research on organizational learning and FDI, we hypothesize that the greater the experience with recent, frequent and high-intensity risk, the more likely that experience can moderate the relationship between non-market risks and firm international expansion. Given a sample of 625 Fortune Global 500 firms and their investments in 117 countries between 1999 and 2008, we find that experience with recent, frequent, and high-intensity risk can change a firm?s FDI decision from risk avoidance to risk management

Traffic-related air pollution and obesity formation in children: a longitudinal, multilevel analysis.

BackgroundBiologically plausible mechanisms link traffic-related air pollution to metabolic disorders and potentially to obesity. Here we sought to determine whether traffic density and traffic-related air pollution were positively associated with growth in body mass index (BMI = kg/m2) in children aged 5-11 years.MethodsParticipants were drawn from a prospective cohort of children who lived in 13 communities across Southern California (N = 4550). Children were enrolled while attending kindergarten and first grade and followed for 4 years, with height and weight measured annually. Dispersion models were used to estimate exposure to traffic-related air pollution. Multilevel models were used to estimate and test traffic density and traffic pollution related to BMI growth. Data were collected between 2002-2010 and analyzed in 2011-12.ResultsTraffic pollution was positively associated with growth in BMI and was robust to adjustment for many confounders. The effect size in the adjusted model indicated about a 13.6% increase in annual BMI growth when comparing the lowest to the highest tenth percentile of air pollution exposure, which resulted in an increase of nearly 0.4 BMI units on attained BMI at age 10. Traffic density also had a positive association with BMI growth, but this effect was less robust in multivariate models.ConclusionsTraffic pollution was positively associated with growth in BMI in children aged 5-11 years. Traffic pollution may be controlled via emission restrictions; changes in land use that promote jobs-housing balance and use of public transit and hence reduce vehicle miles traveled; promotion of zero emissions vehicles; transit and car-sharing programs; or by limiting high pollution traffic, such as diesel trucks, from residential areas or places where children play outdoors, such as schools and parks. These measures may have beneficial effects in terms of reduced obesity formation in children

Revealing the Empty-State Electronic Structure of Single-Unit-Cell FeSe/SrTiO3_{3}

We use scanning tunneling spectroscopy to investigate the filled and empty electronic states of superconducting single-unit-cell FeSe deposited on SrTiO$_3$(001). We map the momentum-space band structure by combining quasiparticle interference imaging with decay length spectroscopy. In addition to quantifying the filled-state bands, we discover a $\Gamma$-centered electron pocket 75 meV above the Fermi energy. Our density functional theory calculations show the orbital nature of empty states at $\Gamma$ and suggest that the Se height is a key tuning parameter of their energies, with broad implications for electronic properties.Comment: 5 pages, 5 figure

An Investigation of Self-Concept, Clothing Selection, and Life Satisfaction among Disabled Consumers

Because consumer behavior research has typically focused on the population of “haves” and assumed consumers’ normalcy (Miller, 1997), the population of “have nots” has been largely ignored by researchers. As a result, we have a limited understanding of disabled individuals as consumers, particularly their behaviors related to the selection of clothing to wear. Thus, this study is designed to better understand disabled consumers and to investigate the influence of disabled individuals’ multifaceted self-concept on their motivations for clothing selection

Apolipoproteins for Cardiovascular Risk Assessment

Clinical Question: Is measurement of apolipoproteins better than traditional lipid measurements for predicting cardiovascular risk? Evidence-Based Answer: Measurement of apolipoprotein B and apolipoprotein A-I is no better than traditional lipid measurements and should not be used to predict cardiovascular risk. (Strength of Recommendation: B, based on meta-analyses with conflicting results.) Apolipoprotein B and non-high-density lipoprotein cholesterol (HDL-C) predict cardiovascular risk slightly better than low-density lipoprotein cholesterol. Elevated levels of apolipoprotein A-I predict a lower risk of cardiovascular events except stroke, but not as well as elevated HDL-C levels