cssi/SciSciGPT-SciSciNet huggingface dataset:
The ATP-Binding Cassette Transporter ABCB6 Is Induced by Arsenic and Protects against Arsenic Cytotoxicity

Arsenic, an environmental carcinogen, remains a major public health problem. Arsenic damages biological systems through multiple mechanisms, including the generation of reactive oxygen species. ABCB6 is an ATP-binding cassette transporter that is highly expressed in cells resistant to arsenic. We have recently demonstrated that ABCB6 expression protects against cellular stressors. In the present study, we evaluated the significance of ABCB6 expression to arsenic toxicity both in mice and in cell culture. We show that sodium arsenite induces ABCB6 expression in a dose-dependent manner both in mice fed sodium arsenite in drinking water and in cells exposed to sodium arsenite in vitro. Arsenite-induced ABCB6 expression was transcriptionally regulated, but this induction was not mediated by the redox-sensitive transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2). We demonstrate that, in HepG2 and Hep3B cells, knockdown of ABCB6 expression using ABCB6-specific small interfering RNA sensitized the cells to arsenite toxicity. In contrast, stable overexpression of ABCB6 conferred a strong survival advantage toward arsenite-induced oxidative stress. Collectively, these results, obtained by both loss of function and gain of function analysis, suggest that ABCB6 expression in response to sodium arsenite might be an endogenous protective mechanism activated to protect cells against arsenite-induced oxidative stress.
Quadrivalent Human Papillomavirus Vaccine Initiation in Boys Before and Since Routine Use: Southern California, 2009-2013.

Objectives. We examined the trends and correlates of quadrivalent human papillomavirus vaccine (HPV4) initiation in insured boys during the periods before and after routine use recommendation.Methods. We grouped data from electronic medical records of boys aged 9 to 17 years from the Kaiser Permanente Southern California prepaid health plan into 3 open cohorts: permissive use: 2009 to 2010; anal cancer indication added: 2010 to 2011; and routine use: 2011 to 2013. We estimated adjusted risk ratios (ARRs) between demographics and vaccination initiation using Poisson regression.Results. HPV4 initiation increased across cohorts—1.6%, 3.4%, and 18.5%—with the greatest increase among boys aged 11 to 12 years in cohort 3. Initiation was associated with receiving influenza vaccination in the previous year in all cohorts (cohort 3: ARR = 1.48; 95% confidence interval [CI] = 1.46, 1.51) and with non-White race/ethnicity following routine recommendation (cohort 3, non-Hispanic Black: ARR = 1.18; 95% CI = 1.08, 1.30...
A power efficient pulsed MAC protocol for Body Area Networks

The need for a reduction in healthcare cost has escalated over the past decade. Therefore, preventive medicine through remote health monitoring and Body Area Networks has gained more attention. In this paper a novel Medium Access Control (MAC) protocol, called Pulsed-MAC or simply PMAC, is introduced to efficiently manage wireless communications in Body Area Networks. PMAC notably extends the network life time by augmenting sensor nodes with charge pumping circuitry which harvest energy from a pulsed signal used to wake up the nodes. By measuring the average radio power consumption in a sensor node over a 24 hour simulation period, results show that PMAC outperforms conventional SMAC by up to three times and will easily allow for a Body Area Network to last beyond 200 days.
“Native” striated collagen produced by chick notochordal epithelial cells in vitro

We report here the observation of striated collagen produced by notochordal cells in vitro. Fibrils with collagen-like striations were seen in large intercellular spaces following three days of incubation in vitro. Surprisingly, similar fibrils and large sheets (1,500 A wide) of collagen showing a 510 A periodicity were seen in notochordal tissues cultured in the presence of β-aminopropionitrile (BAPN), a known inhibitor of cross-linking in tropocollagen. These observations support the view that the notochord should be considered one of several embryonic epithelial tissues known to secrete collagen.
Age differences in constraints encountered by seniors in their use of computers and the internet

The purpose of this cross-sectional study was to explore older computer users' constraints at various age stages. We investigated perceived barriers experienced by older adults in the use of computer-mediated information technology in different age segments (the pre-senior, the young-old, and the older-old). Two hundred forty-three senior computer users participated in the study. Respondents' ages ranged from 50 to 93. Results from exploratory factor analysis and one-way analysis of variance suggested that there were four dimensions of constraints encountered by seniors while dealing with computer-based technologies: Intrapersonal, interpersonal, structural, and functional constraints. These results indicated that senior users might face diverse barriers at different age stages. Implications for developing an effective programming for older adults and research limitations were discussed at the end.
New Components for Building Fuzzy Logic Circuits

This paper presents two new designs of fuzzy logic circuit components. Currently due to the lack of fuzzy components, many fuzzy systems cannot be fully implemented in hardware. We propose the designs of a new fuzzy memory cell and a new fuzzy logic gate. Unlike a digital memory cell that can only store either a zero or a one, our fuzzy memory cell can store any value ranging from zero to one. The fuzzy memory cell can also be used as a D-type fuzzy flip-flop, which is the first design of a D-type fuzzy flip-flop. We also designed a new fuzzy NOT gate based only on digital NOT gates that can easily be implemented in CMOS microchips. Our D-type fuzzy flip-flop and fuzzy NOT gate together with fuzzy AND gate and fuzzy OR gate allow us to design and implement fuzzy logic circuits to fully exploit fuzzy paradigms in hardware.
Belowground bud banks of tallgrass prairie are insensitive to multi-year, growing-season drought

In tallgrass prairie plant communities, new shoots are recruited from belowground bud banks, often in response to disturbance. We explored the contribution of belowground bud banks to grassland stability when perturbed by severe drought. We sought to quantify changes in bud bank density and demography, assess the contribution of the bud bank to aboveground net primary productivity, and compare shifts in above- and belowground plant community structure in response to drought. We experimentally reduced precipitation 76% from ambient levels for two years, and compared responses of drought plots to ambient and irrigated controls during the two years of drought and two years of recovery. We measured belowground bud bank density and aboveground shoot density, canopy cover, and aboveground net primary productivity. While aboveground net primary productivity and C4 grass flowering shoot density declined during drought, bud bank density was insensitive to drought. Rapid resilience of the aboveground plant community following cessation of drought appears to be mediated by the resistance of bud banks to drought. Shoot density, but not bud bank density, was positively correlated with total aboveground net primary productivity. Furthermore, proportional reductions in aboveground net primary productivity increased as shoot density increased. Plant community structure shifted both above- and belowground in response to precipitation treatments. Our results suggest that the response of perennial grasslands to drought may be mediated by the stable belowground bud bank, with shifts in abundance of individual species maintaining overall bud bank density and ecosystem function.
Longitudinal Predictors of Stopping Smoking in Young Adulthood

This study aims to describe the longitudinal individual and environmental predictors of stopping smoking among a group of young adult smokers.
Randomized, Prospective Trial of Antioxidant Supplementation in Critically Ill Surgical Patients

OBJECTIVE: To determine the effectiveness of early, routine antioxidant supplementation using α-tocopherol and ascorbic acid in reducing the rate of pulmonary morbidity and organ dysfunction in critically ill surgical patients. SUMMARY BACKGROUND DATA: Oxidative stress has been associated with the development of the acute respiratory distress syndrome (ARDS) and organ failure through direct tissue injury and activation of genes integral to the inflammatory response. In addition, depletion of endogenous antioxidants has been associated with an increased risk of nosocomial infections. The authors postulated that antioxidant supplementation in critically ill surgical patients may reduce the incidence of ARDS, pneumonia, and organ dysfunction. METHODS: This randomized, prospective study was conducted to compare outcomes in patients receiving antioxidant supplementation (α-tocopherol and ascorbate) vs those receiving standard care. The primary endpoint for analysis was pulmonary morbidity (a composite measure ...
Barriers to follow-up eye care after preschool vision screening in the primary care setting: findings from a pilot study.

Timely follow-up after an abnormal preschool vision screening test is necessary for the prevention of amblyopia. A previous large community-based preschool vision screening program found that only approximately half of those children who were referred were documented to have received follow-up care.1 No similar data are available regarding follow-up from the primary care setting. We present findings from a pilot study designed to identify barriers to follow-up care faced by families screened by pediatricians and family physicians. These data will be used in larger studies to measure rates of follow-up and to develop interventions to improve the detection of amblyopia and conditions associated with the development of amblyopia.
Hemodynamic and metabolic responses to graded microvascular occlusion.

Abstract The hemodynamic and metabolic consequences of microvascular occlusion, often present in the runoff bed of distal arterial reconstructions, have been difficult to quantitate clinically. To investigate these pathophysiologic relationships, a porcine hindlimb model was developed in which arteriolar patency, which we term outflow capacity, may be quantitatively defined and reduced by serial distal microembolization with 70 μm flow-directed glass bubbles. In 10 anesthetized adult pigs, hindlimb perfusion was limited to femoral artery flow (FAF) by collateral ligation. Serial measurements of outflow resistance (OR), femoral artery flow, and resting muscle pH (mpH), a metabolic index of tissue perfusion, were made as relative outflow capacity (ROC) underwent graded reduction from 1.0 (baseline) to 0 (complete occlusion). Femoral artery flow decreased linearly (FAF = 87 ROC − 3), and outflow resistance increased in hyperbolic fashion (OR = 1.66/ROC) in response to graded peripheral microembolization, whereas resting muscle pH followed a more complex relationship (In mpH = 0.055 ROC + 1.95). An integrated analysis of these results suggests that a 50% to 60% reduction in arteriolar patency represents a critical point beyond which outflow resistance rises rapidly and hindlimb flow decreases to levels that are inadequate to support the metabolic demands of resting tissues. (J V ASC S URG 1991;13:867-75.)
The Theory of Democratic Peace and Threat Perception

President Franklin D. Roosevelt's assessment of Hitler as a potential threat to American security in the aftermath of the Munich crisis highlights the role of liberal-democratic norms in shaping the threat perceptions of democratic leaders. A critical factor in Roosevelt's post-Munich expectation of future trouble for the United States was his judgment that Hitler's contempt for democratic processes of accommodation forecasted unlimited aims. Since Roosevelt did not link his perception of threat to regime type, however, this episode also calls into question a central tenet of the theory of democratic peace: the notion that democracies invariably harbor a “presumption of enmity” toward nondemocracies. Nevertheless, the Munich case allows us to see which democratic norms do matter in threat perception and establishes that they are not simply the epiphenomena of state interests. Moreover, Roosevelt's response to the Munich crisis shows that threat can be assessed primarily on the basis of intentions and suggests how democratic predispositions can provide indicators of intent. Finally, in analyzing why some democratic leaders derive diagnostic information about aggressive intentions from such indicators, while others do not, this article explores the connection between different leaders' perceptions and the foreign policy processes of democratic states.
A survey of the use of non-euclidean geometry in electrical engineering

Abstract An attempt is made to give a brief resume of some of the non-Euclidean geometry models and some of their applications in electrical engineering. The survey starts with a discussion of diff rent two-dimensional and three-dimensional non-Euclidean geometry models, both of the hyperbolic and elliptic types. The interconnections of the two-dimensional models are studied geometrically and analytically by means of a simple impedance transformation example. The treatment is then formally extended to three-dimensional models. Finally, some applications of non-Euclidean geometry models in electrical engineering are discussed. An appendix gives a historical note on the evolution of non-Euclidean geometry.
DIGITALIZATION IN NEW MEDIA: DATING IN DOHA

This project reviews how digitalization has changed the social lives of young adults in the Arab Gulf, specifically in Doha, Qatar. Technologies including Bluetooth, television channels allowing for flirting via text message, and Blackberry messenger services have allowed unprecedented contact between the sexes in a mostly traditional society. By placing this phenomenon in the larger category of “Western,” some traditionalists have signalled that Qatari culture is fundamentally challenged by the encroachment of these “Western” behaviors. Simultaneously, Turkish soap operas such as “Noor” are also held up as examples of “Western” infiltration of Qatari society. However, this project seeks to identify the unique ways in which young adults in the Gulf adapt seemingly “Western” technologies, digitalizations, and media formats and use them in ways that are distinctly Gulfi.
Effects of Hyperfine Particles on Reflectance Spectra from 0.3 to 25 μm

Fine grained particles ,50 mm in size dominate particle size changes in the volume scattering region, the Christiansen feadistributions of many planetary surfaces. Despite the predomi- ture, restrahlen bands, and transparency features. The quartz nance of fine particles in planetary regoliths, there have been particle size series were less well modeled, with the greatest few investigations of the systematic effects of the finest particles discrepancies in the restrahlen bands and the overall spectral on reflectance spectra, and on the ability of quantitative models contrast. © 1997 Academic Press to extract compositional and/or textural information from remote observations. The effects of fine particles that are approximately the same size as the wavelength of light on reflectance
Ultrasensitive serum prostate specific antigen nadir accurately predicts the risk of early relapse after radical prostatectomy

ABSTRACT Purpose: Ultrasensitive prostate specific antigen (PSA) assays allow a lower limit of detection (less than 0.01 ng/ml) than standard PSA assays. In this study we examined the ability of ultrasensitive PSA nadir to predict relapse after radical prostatectomy (RP). Materials and Methods: A total of 906 men treated with RP were followed with PSA measurements at 3, 6 and 12 months, and yearly thereafter. Of the 906 men 545 (60%) with a PSA nadir of less than 0.01 ng/ml or at least 3 followup ultrasensitive PSA measurements underwent analysis and stratification by PSA nadir. Biochemical relapse was defined as 2 consecutive increasing post-nadir PSA measurements of 0.1 ng/ml or greater. The ability of ultrasensitive PSA nadir to predict relapse was assessed by univariate and multivariate analysis. Results: At a mean followup of 3.1 years 54 of 545 men (9.9%) experienced biochemical relapse with a mean time to relapse of 25.2 months. Relapse rates in men with a PSA nadir of less than 0.01 (423), 0.01 (75), 0.02 (19) and 0.04 or greater ng/ml (28) were 4%, 12%, 16% and 89%, respectively. Men with a nadir of less than 0.01 ng/ml had a significantly lower relapse rate than men with a nadir of 0.01 (p Conclusions: Ultrasensitive PSA nadir accurately predicts the risk of early biochemical relapse following RP. Men who achieve a nadir of less than 0.01 ng/ml have a low likelihood of early relapse. Higher nadir points may identify candidates for early adjuvant or salvage therapies.
Spt3 plays opposite roles in filamentous growth in Saccharomyces cerevisiae and Candida albicans and is required for C. albicans virulence.

Spt3 of Saccharomyces cerevisiae is required for the normal transcription of many genes in vivo. Past studies have shown that Spt3 is required for both mating and sporulation, two events that initiate when cells are at G1/START. We now show that Spt3 is needed for two other events that begin at G1/START, diploid filamentous growth and haploid invasive growth. In addition, Spt3 is required for normal expression of FLO11, a gene required for filamentous growth, although this defect is not the sole cause of the spt3/ spt3 filamentous growth defect. To extend our studies of Spt3's role in filamentous growth to the pathogenic yeast Candida albicans, we have identified the C. albicans SPT3 gene and have studied its role in C. albicans filamentous growth and virulence. Surprisingly, C. albicans spt3/spt3 mutants are hyperfila- mentous, the opposite phenotype observed for S. cerevisiae spt3/spt3 mutants. Furthermore, C. albicans spt3/spt3 mutants are avirulent in mice. These experiments demonstrate that Spt3 plays important but opposite roles in filamentous growth in S. cerevisiae and C. albicans.
AIDS vaccine trials for India: getting the facts right.

In the last several months there have been discussions in the media including in this journal (1) about issues related to how AIDS vaccine trials are conducted in India. The International AIDS Vaccine Initiative (IAVI) has partnered with the ministry of health and family welfare in India through the National AIDS Control Organisation (NACO) and the Indian Council of Medical Research (ICMR) since 2002 to implement the AIDS vaccine research and development programme. With our partners we strongly support transparency and the highest ethical standards in our joint efforts to find and deliver an AIDS vaccine that the world so desperately needs. In fact IAVIs intellectual property agreements are also used as a mechanism to avoid any delay in the introduction of vaccines to developing countries (delays of more than 10 years or so in the past) by insisting that any vaccine will be made simultaneously available in developed and developing countries (2). (excerpt)
Some Definitions and Viewpoints

This chapter defines how this book uses such basic terms as “health care” and “medicine.” It discusses certain words important in this book such as “elite,” “religion,” and “ritual.” I also set out my positions on a number of contentious issues pertinent to the book, such as how to translate ancient medical terminology, how Chinese medical writings describe the body’s contents and metabolic processes, the role of objectivity in historical studies, the meaning of “culture,” the value of cultural relativism, and the coinage of technical terminology by historians. The chapter also explains some of the book’s conventions, such as the use of “biomedicine” and “formula,” and the use of Chinese personal names.
Solving instability problem in soft body dynamics

For computer simulation, a soft body has been used in many fields such as medical applications and entertainments. The soft body is composed of a list of surface points. Each surface point in the soft body has its own properties which of them are position, force, and velocity. In each time step, new position is computed by applying a new force using integration method such as explicit method or implicit method. In explicit Euler method is simple and fast in a term of computation. However, a disadvantage of this method is that the simulation creates instability problem and causes the soft body to disappear from the simulation scene when the force is too large. Thus, implicit method has been used to avoid this problem. Unfortunately, the implicit Euler method is time consuming since it requires high computation. In this paper, a classical 4th order Runge Kutta is adopted to efficiently implement the soft body models because it can solve instability problem and requires less computation compared to implicit Euler method. The results of the simulation show that the classical 4th order Runge Kutta method can avoid instability problem and can run faster than implicit Euler method.
Antiplatelet drugs and generation of thrombin in clotting blood.

Platelets participate in formation of thrombin through secretion of coagulation factors and by providing a catalytic surface on which prothrombinase complex is assembled. We studied the effects of four antiplatelet drugs on thrombin formation in healthy volunteers. Thrombin generation was monitored both in vitro--in recalcified plasma-- and ex vivo--in blood emerging from a standardized skin microvasculature injury, which also served to determine bleeding time. A mathematical model has been developed to describe the latter reaction. It is based on estimation of the rate of increase in fibrinopeptide A (FPA), a specific marker of thrombin activity, in blood emerging from skin incisions. Two hours after the ingestion of 500 mg of aspirin, thrombin formation became significantly impaired both in vitro and ex vivo. In contrast, 2 hours after the oral administration of placebo, indomethacin 50 mg, or OKY-046 (a thromboxane synthase inhibitor) 400 mg, thrombinogenesis remained unaltered. Ticlopidine, studied either 3 hours after 500 mg oral administration, or after 5 days of intake at a daily dose of 500 mg, had no effect on thrombin generation. Thus, aspirin, contrary to other antiplatelet drugs, depresses thrombin formation in clotting blood, a phenomenon that might be of clinical relevance. It is suggested that aspirin exerts this effect by acetylating prothrombin and/or macromolecules of platelet membrane.
VIBRIO PARAHAEMOLYTICUS GASTROENTERITIS OUTBREAKS ABOARD TWO CRUISE SHIPS

Outbreaks of Vibrio parahaemolyticus gastrointestinal illness occurred on two Caribbean cruise ships in late 1974 and early 1975. In all, 697 passengers and 27 crew were affected. Epidemiologic evidence incriminated seafoods served on the ships as the vehicles of transmission. The seafoods were probably contaminated by V. parahaemolyticus after cooking in seawater from the ships' internal seawater distribution systems. Use of seawater in foodhandling areas was discontinued, and no further outbreaks occurred.
Leveling the Playing Field: Cost Diffusion and the Promotion of “Responsible” Arms Export Norms

Why do states take the lead in diffusing norms they once resisted? I address this question in the context of new humanitarian arms trade norms, culminating in the 2013 Arms Trade Treaty (ATT). Although most major arms exporting states have supported the ATT and similar initiatives, only some have chosen to invest resources in becoming leaders of these initiatives to spread new norms beyond their borders. I examine British and German arms export policies and practices to argue that states that choose leadership following costly norm adoption may do so as a means to share the costs of those norms with other international actors and reduce future adaptation costs. By delving deeper into the agency of norm diffusion, the article offers insights into powerful states’ motivations for norm leadership following costly norm adoption, the dynamics of norm diffusion, and the institutional form international norms eventually take.
Remifentanil and propofol undergo separation and layering when mixed in the same syringe for total intravenous anesthesia.

Background Propofol and remifentanil can be combined to deliver total intravenous anesthesia (TIVA). Propofol and remifentanil are sometimes mixed in the same syringe. Since remifentanil is a solution and propofol is an emulsion, we hypothesized that they would separate over time when mixed in the same syringe. Methods Nine 60-ml polypropylene syringes were prepared as follows: Group A: 1.25 ml of remifentanil solution (1 mg·ml(-1) ) was added to 48.75 ml of propofol (10 mg·ml(-1) ) in three syringes. Group B: 2.5 ml of remifentanil (1 mg·ml(-1) ) was added to 47.5 ml of propofol (10 mg·ml(-1) ) in three syringes. Group C: 5 ml of remifentanil (1 mg·ml(-1) ) was added to 45 ml of propofol (10 mg·ml(-1) ) in three syringes. The remifentanil lyophilized powder was reconstituted with sterile water and added to the propofol by injection through the port on the bottom of the syringe. The syringe was then inverted five times in succession to mix the drugs. The syringes were mounted in an upright vertical position (plunger on top, port on bottom) with wire on a pegboard. Samples of the mixture were taken from the bottom port (via a 3-way stopcock) and from the top of the syringe (via a stopcock on an 18-gauge needle placed 5 mm through the plunger) at the following time intervals (min) from baseline: T0, T10, T30, T60, T120, T180, T240, T300. Remifentanil and propofol were quantified using specific and validated HPLC/MS/MS assays with automated online sample preparation. Results Concentrations of remifentanil were significantly greater at the top than the bottom of the syringes in groups A and B. Concentrations of propofol were significantly greater at the bottom than the top of the syringes in all groups. Conclusion Our data indicate that remifentanil solution and propofol emulsion are immiscible: remifentanil separates from propofol and rises to the top. Thus, concentrations of remifentanil and propofol delivered to patients from the same syringe during TIVA are not those expected and cannot be reliable. Remifentanil and propofol should be administered in separate syringes when used in combination for TIVA.
Second-line chemotherapy for non-small-cell lung cancer

Most of the experience with second-line chemotherapy for non-small-cell lung cancer (NSCLC) comes from small phase II trials, which have shown disappointing or inconsistent results. The notable exception has been docetaxel, which has been extensively studied as a second-line therapy for NSCLC. On the basis of consistent phase II activity, two large randomized phase III trials were conducted for patients with advanced NSCLC that had progressed either on or after first-line platinum-based therapy. In one trial, docetaxel, at either 100 or 75 mg/m2, was compared with a regimen of either vinorelbine or ifosfamide. In the second trial, docetaxel 75 to 100 mg/m2 was compared with best supportive care. Both trials showed significant improvement in survival, time to progression, and quality of life in the patients receiving docetaxel versus the control therapy. Based on these two large trials, it appears that the use of second-line therapy with single-agent docetaxel at a dose of 75 mg/m2 every 3 weeks is a reasonable practice in patients who maintain a good performance status.
The Influence of Older Adults’ Beliefs and Attitudes on Adopting Fall Prevention Behaviors

Among Americans aged 65 years and older, falls are the leading cause of injury death and disability, and finding effective methods to prevent older adult falls has become a public health priority. While research has identified effective interventions delivered in community and clinical settings, persuading older adults to adopt these interventions has been challenging. Older adults often do not acknowledge or recognize their fall risk. Many see falls as an inevitable consequence of aging. Health care providers can play an important role by identifying older adults who are likely to fall and providing clinical interventions to help reduce fall risks. Many older people respect the information and advice they receive from their providers. Health care practitioners can encourage patients to adopt effective fall prevention strategies by helping them understand and acknowledge their fall risk while emphasizing the positive benefits of fall prevention such as remaining independent. To help clinicians integrate f...
Apparent diffusion coefficient values may help predict which MRI-detected high-risk breast lesions will upgrade at surgical excision.

Purpose To investigate whether diffusion-weighted imaging (DWI) features could assist in determining which high-risk lesions identified on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and diagnosed on core needle biopsy (CNB) will upgrade to malignancy on surgical excision. Materials and methods This Institutional Review Board (IRB)-approved prospective study included participants with MRI-detected Breast Imaging Reporting and Data System (BI-RADS) 4 or 5 lesions with high-risk pathology on CNB who underwent surgical excision. Twenty-three high-risk lesions detected on 3T breast MRI in 20 women (average age = 54 ± 9 years) were evaluated, of which six lesions (26%) upgraded to malignancy at surgery. DCE, DWI characteristics, and clinical factors were compared between high-risk lesions that upgraded to malignancy on surgical excision and those that did not. Logistic regression modeling was performed to identify features that optimally predicted upgrade to malignancy, with performance described using area under the receiver operating characteristic curve (AUC). Results High-risk lesions that upgraded on excision demonstrated lower apparent diffusion coefficient (ADC) than those that did not (median, 1.08 × 10-3 mm2 /s vs.1.39 × 10-3 mm2 /s, P = 0.046), and a trend of greater maximum lesion size (median, 24 mm vs. 8 mm, P = 0.053). There were no significant differences in lesion type (mass vs. nonmass enhancement, P = 1.0) or kinetic features (P = 0.78 for peak initial enhancement; P = 1.0 for worst curve type) among the high-risk cohorts. A model incorporating maximum lesion size and ADC provided optimal performance to predict upgrade to malignancy (AUC = 0.89). Conclusion ADC and maximum lesion size on MRI show promise for predicting which MRI-detected high-risk lesions will upgrade to malignancy at surgical excision. Level of evidence 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1028-1036.
Experiencing Civil Unrest: Elder Voices on Ferguson

Ferguson, Missouri became the center of the nation's attention when an unarmed African American teenager was killed by a Caucasian police officer. Civic unrest continued for weeks. The aim of this study was to learn how older adults experienced the social unrest. Ten focus groups were conducted with 73 participants. Eight themes were identified. Issues related to safety were most commonly discussed. Participants reported a breakdown in intergenerational communications and expressed a desire for more exchange. Findings are being discussed with relevant organizations to increase the involvement of older adults in on-going community development efforts and to provide opportunities for intergenerational dialogue.
Scaling Expert Feedback: Two Case Studies

Traditionally, education relies on a linear relationship between enrollment and staff; rising enrollment dictates increases to staff with some expertise (such as teaching assistants, TAs) for evaluation. This relationship is expensive, so learning at scale has largely deemphasized expert evaluation and feedback. Two organizations, though, have used different models to scale up class size online while retaining this expert evaluation and feedback. In this paper, we analyze the methods these two organizations have used to increase enrollment while preserving scalability and feedback. We observe an academic program has scaled feedback with traditional TAs by relying on unique characteristics of its student body, while a commercial program has done so with a novel, network-based model. These successes show the potential of learning from experts at scale.
A novel proteolytic event controls Hedgehog intracellular sorting and distribution to receptive fields

The patterning activity of a morphogen depends on secretion and dispersal mechanisms that shape its distribution to the cells of a receptive field. In the case of the protein Hedgehog (Hh), these mechanisms of secretion and transmission remain unclear. In the developing Drosophila visual system, Hh is partitioned for release at opposite poles of photoreceptor neurons. Release into the retina regulates the progression of eye development; axon transport and release at axon termini trigger the development of postsynaptic neurons in the brain. Here we show that this binary targeting decision is controlled by a C-terminal proteolysis. Hh with an intact C-terminus undergoes axonal transport, whereas a C-terminal proteolysis enables Hh to remain in the retina, creating a balance between eye and brain development. Thus, we define a novel mechanism for the apical/basal targeting of this developmentally important protein and posit that similar post-translational regulation could underlie the polarity of related ligands.
Ferrari: The 2015 Initial Public Offering

This case examines the October 2015 initial public offering pricing decision for legendary Italian sports car company Ferrari by Fiat Chrysler management. Students are invited to model the value of Ferrari in light of Ferrari CEO Sergio Marchionne's interest in expanding production despite the company's long standing tradition of severely limiting production strategy to maintain an exclusive brand image. The case is designed to showcase corporate valuation using discounted cash flow and peer-company market multiples for a company that exists in two sectors: automotive and luxury goods. Excerpt UVA-F-1775 Rev. Apr. 14, 2017 Ferrari: The 2015 Initial Public Offering The Ferrari is a dream—people dream of owning this special vehicle, and for most people it will remain a dream apart from those lucky few. -Enzo Ferrari, Founder, Ferrari . . .
Evolutionary Systems Biology integration of multi-level CTMC interaction models of biochemistry and cancer cell growth using Evolvix.

While biochemistry evidently affects the growth rate of cells, many biochemists routinely ignore population variation, just like population geneticists usually ignore causal details of biochemistry that underpin a change in growth rate caused by a mutation. A true EvoSysBio integration requires an explicit mechanism for how molecular reaction rates affect the reproduction rates that determine the fitness of an organism. Here we simulate a very simple and completely explicit Continuous-Time Markov Chain (CTMC) model of cancer cells whose growth rate is affected by the biochemical equilibrium between two molecular complexes. Approximately 70% of breast cancers are of a type that overexpress Estrogen Receptor-alpha (ERα). Cell growth in this type of cancer is inhibited by hormonal therapies that antagonize ERα function as a transcription factor. ERα is encoded by the ESR1 gene, which itself is a target of ERα mediated transcription. When activated by estrogen, ERα binds to the ESR1 promoter, repressing new synthesis of ERα protein. Estrogen binding also induces pathways that lead to degradation of ERα protein. This negative feedback loop is finely tuned to natural levels of estrogen and results in natural levels of growth. In breast cancer, the system is thrown off its natural course such that increased levels of ERα induce levels of cell growth that can lead to cancer. Thus, both genetic changes to the ESR1 promoter, ERα protein degradation, and biochemical changes in estrogen metabolism can effectively cause changes in cell growth rates, which can be seen as the ‘fitness’ of a cancer cell. Predicting cancer cell growth in this system raises a conceptual multi-level simulation problem, because the molecular aspects of this model need to compute the biochemistry in a way that influences growth rates at the cellular level, without resetting growth at each cell division. We present progress towards addressing this simulation challenge in pure mass-action models, which we implemented using the Evolvix model description language. We found that such models can be constructed in more than one way. We explored some candidate model properties that could aid efforts to develop abstractions for more efficiently simulating the common multi-level modeling problems behind many important biological questions. These efforts are ongoing and aim to find efficient ways of encoding and exploring such models in silico. In particular, we are investigating how architecting a new compiler for a general-purpose programming language for biology could improve the efficiency of analyzing the dynamic multi-level simulation scenarios that characterize many questions in EvoSysBio. Progress can be followed at http://evolvix.org.
A Virtual Animated Commentator Architecture for Cybersecurity Competitions

Cybersecurity competitions are exciting for the game participants; however, the excitement and educational value do not necessarily transfer to audiences because audiences may not be experts in the field. To improve the audiences’ comprehension and engagement levels at these events, we have proposed a virtual commentator architecture for cybersecurity competitions. Based on the architecture, we have developed a virtual animated agent that serves as a commentator in cybersecurity competition. This virtual commentator can interact with audiences with facial expressions and the corresponding hand gestures. The commentator can provide several types of feedback including causal, congratulatory, deleterious, assistive, background, and motivational responses. In addition, when producing speech, the lips, tongue, and jaw provide visual cues that complement auditory cues. The virtual commentator is flexible enough to be employed in the Collegiate Cyber Defense Competitions environment. Our preliminary results demonstrate the architecture can generate phonemes with timestamps and behavioral tags. These timestamps and tags provide solid building blocks for implementing desired responsive behaviors.
RMSEA, CFI, and TLI in structural equation modeling with ordered categorical data: The story they tell depends on the estimation methods

In structural equation modeling, application of the root mean square error of approximation (RMSEA), comparative fit index (CFI), and Tucker–Lewis index (TLI) highly relies on the conventional cutoff values developed under normal-theory maximum likelihood (ML) with continuous data. For ordered categorical data, unweighted least squares (ULS) and diagonally weighted least squares (DWLS) based on polychoric correlation matrices have been recommended in previous studies. Although no clear suggestions exist regarding the application of these fit indices when analyzing ordered categorical variables, practitioners are still tempted to adopt the conventional cutoff rules. The purpose of our research was to answer the question: Given a population polychoric correlation matrix and a hypothesized model, if ML results in a specific RMSEA value (e.g., .08), what is the RMSEA value when ULS or DWLS is applied? CFI and TLI were investigated in the same fashion. Both simulated and empirical polychoric correlation matrices with various degrees of model misspecification were employed to address the above question. The results showed that DWLS and ULS lead to smaller RMSEA and larger CFI and TLI values than does ML for all manipulated conditions, regardless of whether or not the indices are scaled. Applying the conventional cutoffs to DWLS and ULS, therefore, has a pronounced tendency not to discover model–data misfit. Discussions regarding the use of RMSEA, CFI, and TLI for ordered categorical data are given.
Female Bodies Adrift: Violation of the Female Bodies in Becoming a Subject in the Western Media

This article focuses on how the violation of female bodies in the case of mass harassment of women is rendered intelligible by the Western media and the refugees. Violation of female bodies is approached as a site for politicizing possibilities of becoming a subject in the Western media. Informed by Deleuzian notion of “becoming” and the subjectivation of the refugees, I argue that the understanding of “violation” is a central component in contributing to possibilities of becoming affirmed as a subject in the Western media. Empirical material subjected to critical text analysis includes a key text form the Finnish daily newspaper Helsingin Sanomat and refugee interviews. The analysis suggests that the repression of irreducible conceptions of “violation,” and the subsequent erasure of the uncertainty of a “self” in the process of becoming, yields to offering possibilities of becoming primarily in Western terms and the affirmation of Western ideological certainty in understanding mass harassment of European women by the refugees.
Iatrogenic and Traumatic Ureteral Injury

Ureteral injuries result from either iatrogenic or external trauma. Iatrogenic ureteral injuries far outnumber traumatic injuries. Ureteroscopy currently accounts for the majority of iatrogenic ureteral injuries. However, most of these injuries are minor and managed with JJ stent. Open pelvic surgery, particularly gynecological procedures, account for the majority of open surgical injuries to the ureter. It is estimated that ureteral injuries occur in 0.5-1% of pelvic surgery. Other abdominal surgical procedures that can result in ureteral injury include colectomy, appendectomy, aorto-iliac bypass, and urological surgeries such as ureteral reimplantation and ureterolithotomy. Many ureteral injuries can be repaired endoscopically with a combination of internal ureteral stenting and percutaneous nephrostomy tube drainage. The rest are amenable to a variety of open surgical techniques depending on the level of injury. Ureteral injuries as a result of external trauma are uncommon, are mostly the result of penetrating gunshot wounds, and are almost always associated with multiple organ injuries.
Management of Ventricular Arrhythmias: An Historical Perspective

The treatment of ventricular arrhythmias has undergone vibrant change in the last 40 years, evolving from a largely intellectual exercise to an evidence-based, guideline-supported set of patient care strategies. This progress have been fueled by basic and clinical science and by the initial application of randomized clinical trials to the study of electrophysiology. Along the way, several strongly held beliefs were reconsidered, most notably the use of programmed stimulation or serial Holter montoring to guide pharmacologic therapy for ventricular tachycardia. Although antiarrhythmic drugs are still considered useful in reducing the frequency of recurrent VT episodes, our loss of confidence in guided drug therapy led to the development of device, surgical ablation, and catheter ablation therapies, which form the mainstay of treatment today.
Complications of diabetes

Microvascular complications are specific for diabetes and are almost certainly related to hyperglycemia (see Figure 5.1). Hyperglycemia leads to multiple biochemical changes, some of which are listed in Figure 5.2, that cause tissue damage [1, 2]. These lead to changes in various organs as summarized in Figure 5.1. Most of these changes can be prevented by good glycemic control which prevents the development of the complications and slows their progression [3].
Guest Editorial IEEE BIBM 2017 Special Issue

Bioinformatics and biomedicine research is fundamental to our understanding of complex biological systems, impacting the science and technology of fields ranging from agricultural and environmental sciences to pharmaceutical and medical sciences. This type of research requires close collaboration among multidisciplinary teams of researchers in computer science, statistics, physics, engineering, life sciences and medical sciences, and their interfaces. The IEEE International Conference on Bioinformatics and Biomedicine aims to provide an open and interactive forum to catalyze the cross-fertilization of ideas from these disciplines and to bridge our knowledge gaps.
Abstract B09: Evaluating transcription factor networks as targets for the treatment of small cell lung cancer

Achaete-scute homolog 1 (ASCL1) is a transcription factor that is highly expressed in most small cell lung cancer (SCLC) tumors and cell lines and is critical for their proliferation. Inhibiting ASCL1 transcriptional activity may thus be a valid therapeutic strategy for SCLC. However, transcription factors (TFs) have been historically difficult to target. Given that TFs belong to complex regulatory networks, we propose to identify and target multiple components within an ASCL1-transcriptional network rather than ASCL1 alone. We have previously detected ASCL1-bound genomic regions associated with the active chromatin epigenetic mark, H3K27Ac in SCLC cells. Here we report the identification of an ASCL1-containing transcriptional network in SCLC cells and evaluate its targeting by the transcriptional inhibitor, mithramycin. We conducted chromatin immunoprecipitation (ChIP) by immunoprecipitating the H3K27Ac chromatin mark from NCI-H2107 and NCI-H69 SCLCs (5X107 cells) nuclear lysates with10 μg H3K27Ac antibodies (Abcam-Ab4729), and sequenced ChIP libraries on an Illumina High-Seq2000. Further characterization using siRNA transfections, immunoblotting and MTS-cell proliferation assays were conducted following standard procedures. We found 82 overlapping TF genes, including lineage-specific TF genes for ASCL1, Forkhead box protein A2 (FOXA2), and nuclear factor 1 B-type (NFIB), associated with the active chromatin epigenetic marks H3K27Ac in SCLC cell lines. This suggests that ASCL1, FOXA2, and NFIB may belong to the same transcriptional network. siRNA-mediated knockdown of ASCL1 leads to decreased FOXA2 levels, but it has no effect on NFIB levels, implicating ASCL1 as a transcriptional regulator of FOXA2 but not NFIB. Mithramycin stops cell proliferation and reduces ASCL1, FOXA2 but not NFIB protein levels. In conclusion, our studies identify the beginning of a transcriptional network necessary for SCLC proliferation in which ASCL1 regulates FOXA2. Targeting multiple TFs within a network with mithramycin can stop cell proliferation and as such suggests a therapeutic strategy for SCLC. Because of the importance of NFIB in mediating metastatic behavior of SCLC, these data indicate that approaches other than targeting ASCL1 and use of mithramycin will be needed to target NFIB. Citation Format: Karine Pozo, Rahul K. Kollipara, John D. Minna, Adi F. Gazdar, Jane E. Johnson. Evaluating transcription factor networks as targets for the treatment of small cell lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B09.