cssi/SciSciGPT-SciSciNet huggingface dataset:
Direct Measure of Rigid Body Accelerations for Wave Impact of a Planing Hull

Measurements of accelerations during wave impact of a planing hull are usually contaminated by nonhydrodynamic disturbances inherent in full-scale tests and by vibrations induced by the test model and towing carriage in towing tank tests. As a consequence, researchers have resorted to the use of electronic filters to extract rigid body hydrodynamic impact accelerations. This article first calculates the rigid body impact acceleration time histories of two-dimensional deadrise wedges impacting on a level water surface as a function of initial contact velocity, deadrise angle, and unit drop weight. It also calculates the spectral content of these time histories. It then demonstrates how the time histories, time to peak, and spectral content of these 2D wedges are distorted by the use of standard “one-way” electronic filters when processing the data. In a sense, this section of the article can be taken as a simple tutorial on the impact process. The Davidson Laboratory suggests and demonstrates the use of a rigid “free-running” model that is not rigidly connected to the towing carriage and is thus devoid of carriage-induced disturbances. This obviates the use of filters in processing the recorded data. Hence, the directly measured impact accelerations are thus rigid body hydrodynamic accelerations. These are compared with measurements made with the model rigidly attached to the carriage to demonstrate its effect on contaminating the recorded hydrodynamic signal. It is recommended that other towing tanks consider the use of this or other “free-model” test procedures to identify the possible contamination of the recorded acceleration time histories introduced by their carriage and model disturbances. It is also recommended that for those full-scale tests, where the “Standard G” method of data reduction has been applied, that a model be built and tested using the “free-model” test procedure suggested in this article. This will compare the derived rigid body accelerations with the true hydrodynamic impact accelerations as obtained in these free-model tests.
The Use of Physician Profiling and Prior Approval (Gatekeeping) in Utilization Management in the Clinical Laboratory

Physician profiling is a technique that can be used to identify variations in practice among physicians. These data have been employed to control costs, improve quality, and assess compliance with practice guidelines. Physician profiling is frequently criticized for producing unreliable or misleading data that fails to reflect the realities of actual clinical practice.
Travels through time

Time is what everybody agrees the time is," a researcher says a few pages into Why Time Flies: A Mostly Scientific Investigation. It sounds like something the Mad Hatter might have said in Alice's Adventures in Wonderland. But it's the truth. Time is such a fundamental part of modern life that sometimes we forget how it insinuates itself into everything that we do. In this, his second book, New Yorker staff writer Alan Burdick deftly counts the ways
Towards decision-making using individualized risk estimates for personalized medicine: A systematic review of genomic classifiers of solid tumors

Recent advances in the understanding of the genetic underpinnings of cancer offer the promise to customize cancer treatments to the individual through the use of genomic classifiers (GCs). At present, routine clinical utilization of GCs is uncommon and their current scope and status, in a broad sense, are unknown. As part of a registered review (PROSPERO 2014:CRD42014013371), we systematically reviewed the literature evaluating the utility of commercially available GCs by searching Ovid Medline (PubMed), EMBASE, the Cochrane Database of Systematic Reviews, and CINAHL on September 2, 2014. We excluded articles involving pediatric malignancies, non-solid or non-invasive cancers, hereditary risk of cancer, non-validated GCs, and GCs involving fewer than 3 biomarkers. A total of 3,625 studies were screened, but only 37 met the pre-specified inclusion criteria. Of these, 15 studies evaluated outcomes and clinical utility of GCs through clinical trials, and the remainder through the use of mathematical models. Most studies (29 of 37) were specific to hormone-receptor positive breast cancer, whereas only 4 studies evaluated GCs in non-breast cancer (prostate, colon, and lung cancers). GCs have spurred excitement across disciplines in recent decades. While there are several GCs that have been validated, the general quality of the data are weak. Further research, including prospective validation is needed, particularly in the non-breast cancer GCs.
Guaranteed Domains of Attraction for Multivariable Luré Systems Via Open Lyapunov Surfaces 1

Abstract In this paper we provide guaranteed stability regions for multivariable Lure systems, Specifically, using the Lure-Postnikov Lyapunov function a guaranteed subset of the domain of attraction for a feedback system whose forward path contains a dynamic linear time-invariant system and whose feedback path contains multiple sector-bounded time-invariant memoryless nonlinearities is constructed via open Lyapunov surfaces, It is shown that the use of open Lyapunov surfaces yields a considerable improvement over closed Lyapunov surfaces in estimating the domain of attraction of the zero solution of the nonlinear system
Moisture driven thermal conduction in polymer and polymer blends

Abstract Though lots of work is available in thermally conductive filler-polymer composite, clear understanding of the heat conduction mechanism in neat polymers or polymer blends is a subject of great investigation especially for the promotion and development of new thermal management technologies. This study shows an interesting tale of intermolecular interaction in governing thermal conduction in polymers and how the quality of “thermal connections” through intermolecular interactions like hydrogen bonding can effectively drive heat propagation in polymers. Here by engineering intermolecular interaction through hydrogen bonding in polymer chains, a significant enhancement in thermal conductivity was achieved and corresponding decrement was observed by breaking those interactions. Thermal conductivity of free standing PVA films with different molecular weights and its blends with PEG and PVP was investigated. Effect of the absorption of vapor molecules of water, ethanol, methanol and ethylene diamine on polymer film's thermal conductivity was studied. Penetration of water molecule in films was found to drastically alter inter-molecular interaction contributing to remarkable 200% increment in thermal conductivity. Thermal conduction of polymer blends with varied intermolecular interactions was further explored. Neat PVA films with lower molecular weight had higher thermal conductivity due to less dense and hindered polymer chains and ease of interaction to form continuous thermal network. This study unveils some of the important yet fascinating drivers of thermal conductivity in polymers & polymer blends which can pave the way for development and fabrication of polymer based materials for thermal management applications.
Increased glycine-amidated hyocholic acid correlates to improved early weight loss after sleeve gastrectomy

Bile acids (BAs) are post-prandial hormones that play an important role in glucose and lipid homeostasis as well as energy expenditure. Total and glycine-amidated BAs increase after sleeve gastrectomy (SG) and correlate to improved metabolic disease. No specific bile acid subtype has been shown conclusively to mediate the weight loss effect. Therefore, the objective of this study was to prospectively evaluate the comprehensive changes in meal-stimulated BAs after SG and determine if a specific change in the BA profile correlates to the early weight loss response. Patients were prospectively enrolled at the University of Nebraska Medical Center who were undergoing a SG for treatment of morbid obesity. Primary and secondary plasma bile acids and their amidated (glycine, G-, or taurine, T-) subtypes were measured at fasting, 30 and 60 min after a liquid meal performed pre-op, and at 6 and 12 weeks post-op. Area under the curve (AUC) was calculated for the hour meal test for each bile acid subtype. BAs that were significantly increased post-op were correlated to body mass index (BMI) loss. Total BA AUC was significantly increased at 6 (p < 0.01) and 12 weeks post-op (p < 0.01) compared to pre-operative values. The increase in total BA AUC was due to a statistically significant increase in G-BAs. Nine different BA AUC subtypes were significantly increased at both 6 and 12 weeks post-op. Increased total and G-chenodeoxycholic acid AUC was significantly correlated to the 6 week BMI loss (p = 0.03). Increased G-hyocholic acid was significantly correlated to increased weight loss at both 6 (p = 0.05) and 12 weeks (p = 0.006). SG induced an early and persistent post-prandial surge in multiple bile acid subtypes. Increased G-hyocholic consistently correlated with greater early BMI loss. This study provides evidence for a role of BAs in the surgical weight loss response after SG.
New Dimensions of Intersection Control with Connected and Automated Vehicles

Connected and automated vehicle (CAV) technologies are believed to offer tremendous benefits to the urban transportation system. Intersection control will also experience a transition process from the state-of-the-practice paradigm to a fully CAV deployed environment, and new dimensions will be added to the control framework. In this paper, we envision that the transition process mainly contains three major stages, namely, the detector-free signal operation, the generalized spatiotemporal intersection control, and the infrastructure adaptation. Several key challenges are discussed.
Magnesium Catalyzed Polymerization of End Functionalized Poly(propylene maleate) and Poly(propylene fumarate) for 3D Printing of Bioactive Scaffolds

The ring-opening copolymerization of maleic anhydride and propylene oxide, using a functionalized primary alcohol initiator and magnesium 2,6-di-tert-butyl phenoxide as a catalyst, was investigated in order to produce high end-group fidelity poly(propylene maleate). Subsequent isomerization of the material into 3D printable poly(propylene fumarate) was utilized to produce thin films and scaffolds possessing groups that can be modified with bioactive groups postpolymerization and postprinting. The surface concentration of these modifiable groups was determined to be 30.0 ± 3.3 pmol·cm–2, and copper-mediated azide–alkyne cycloaddition was used to attach a small molecule dye and cell adhesive GRGDS peptides to the surface as a model system. The films were then studied for cytotoxicity and found to have high cell viability before and after surface modification.
Assessing the Impact of Life Changes

This chapter reviews the literature on life changes, particularly as they relate to health, disease, and recovery from illness. One of the areas of greatest current activity concerns the quantitative assessment of these changes, which are often referred to as stressful life events. We shall review this topic and provide a theoretical perspective for future research.
Targeting ovarian cancer and endothelium with an allosteric PTP4A3 phosphatase inhibitor.

// Kelley E. McQueeney 1 , Joseph M. Salamoun 2 , James C. Burnett 2 , Nektarios Barabutis 3 , Paula Pekic 1 , Sophie L. Lewandowski 1 , Danielle C. Llaneza 4 , Robert Cornelison 4 , Yunpeng Bai 5 , Zhong-Yin Zhang 5 , John D. Catravas 3 , Charles N. Landen 4 , Peter Wipf 2 , John S. Lazo 1 and Elizabeth R. Sharlow 1 1 Department of Pharmacology, University of Virginia, Charlottesville, VA, USA 2 Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA 3 Frank Reidy Center for Bioelectrics, Old Dominion University, Norfolk, VA, USA 4 Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, VA, USA 5 Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA Correspondence to: Elizabeth R. Sharlow, email: // John S. Lazo, email: // Keywords : phosphatase, ovarian cancer, endothelium, inhibitor Received : October 05, 2017 Accepted : November 25, 2017 Published : December 30, 2017 Abstract Overexpression of protein tyrosine phosphatase PTP4A oncoproteins is common in many human cancers and is associated with poor patient prognosis and survival. We observed elevated levels of PTP4A3 phosphatase in 79% of human ovarian tumor samples, with significant overexpression in tumor endothelium and pericytes. Furthermore, PTP4A phosphatases appear to regulate several key malignant processes, such as invasion, migration, and angiogenesis, suggesting a pivotal regulatory role in cancer and endothelial signaling pathways. While phosphatases are attractive therapeutic targets, they have been poorly investigated because of a lack of potent and selective chemical probes. In this study, we disclose that a potent, selective, reversible, and noncompetitive PTP4A inhibitor, JMS-053, markedly enhanced microvascular barrier function after exposure of endothelial cells to vascular endothelial growth factor or lipopolysaccharide. JMS-053 also blocked the concomitant increase in RhoA activation and loss of Rac1. In human ovarian cancer cells, JMS-053 impeded migration, disrupted spheroid growth, and decreased RhoA activity. Importantly, JMS-053 displayed anticancer activity in a murine xenograft model of drug resistant human ovarian cancer. These data demonstrate that PTP4A phosphatases can be targeted in both endothelial and ovarian cancer cells, and confirm that RhoA signaling cascades are regulated by the PTP4A family.
Pseudomonas aeruginosa protease IV produces corneal damage and contributes to bacterial virulence.

PURPOSE A Pseudomonas mutant deficient in protease IV has significantly reduced virulence in experimental keratitis. In the present study, the corneal toxicity of purified protease IV and its ability to augment the virulence of protease-IV-deficient bacteria were analyzed. METHODS The toxicity of purified protease IV was determined by intrastromally injecting the exoenzyme (20-200 ng) into the cornea. The effects of protease IV on the corneal virulence of the protease-IV-deficient strain, PA103-29::Tn9, were determined by injecting eyes with 1000 CFU of log phase bacteria plus either 200 ng active purified protease IV or 200 ng heat-inactivated protease IV. Changes in ocular disease, determined by slit-lamp examination, were measured at 3, 16, 22, and 27 hours after infection. Colony-forming units per cornea were quantified at 27 hours after infection. RESULTS Purified protease IV at doses from 50 to 200 ng induced epithelial defects within 3 hours of injection. Injection of 20 ng active protease IV or heat-inactivated protease IV (200 ng) had no effect on ocular tissue. Corneal virulence of the protease-IV-deficient strain was augmented by intrastromal injection with purified protease IV but not with heat-inactivated protease IV (P < or = 0.0001). Neither active nor heat-inactivated protease IV altered the growth of bacteria in the cornea (6 log units; P = 0.81). CONCLUSIONS The important role of protease IV in corneal virulence was demonstrated by direct toxicity and by its ability to significantly augment the virulence of protease-IV-deficient Pseudomonas.
Effect of γ-Radiation on Isothermal Crystallization of Polypropylene

Polypropylene (PP), is a very important polymeric material used in biomedical, and medical applications. A major drawback of PP is the development of the brittleness upon sterilization by y-radiation. The chemical aspects of the mechanism of degradation of PP have been extensively studied. Radicals and ions are created in the polymer matrix upon sterilization. Most of the radicals, and ions formed are trapped. These radicals, and ions promote the cross linking or chain scission. Polypropylene undergoes both cross linking and chain scission simultaneously. With increasing dose rate, the rate of destruction effected by the radiation increases, resulting in smaller molecular fragments, and partially cross linked structure. The isothermal crystallization behavior of polypropylene was analyzed before, and after exposing it to 2.5 Mrads of ϒ-radiation. Isothermal kinetics shows an average Avrarmi exponent of 3 for both irradiated, and the virgin polypropylene. For both polypropylenes the relation between the In(- In(l-v t )) vs. In(t) was not linear, where v 1 , is the extent of conversion at the time “t”. The effect of the isothermal crystallization temperature on the crystallization process of irradiated polypropylene was different from that of the virgin polypropylenes.
Possible Structure of Weak Interaction

There has been a great deal of theoretical activity attempting to endow the weak interaction with additional structure, beyond the “standard” four quarks coupled via left-handed currents. In particular, within this past year the question of right-handed currents received much attention.
Power Generation and Human Health

Emissions from power generation are associated with adverse health and ecological effects. Fossil fuel-based power plants (such as coal, oil, and to a lesser extent, natural gas) are associated with emissions of particulate matter (PM), nitrogen oxides (NOx), sulfur dioxide (SO2), and a variety of organic contaminants such as mercury and volatile organic compounds (VOCs). Exposure to emissions from power plants has been associated with a variety of respiratory symptoms, typically based on short-term (e.g., from 5–10 min to 24 h) increases in ambient concentrations. In addition, exposure to constituents from emissions generated by fossil fuels has been associated with increases in premature mortality, particularly in the elderly, and a variety of respiratory and cardiovascular illnesses. Fossil fuels, particularly coal-fired power plants, are responsible for generating the majority of emissions to which humans are exposed.
Malignant Brain Tumors

Malignant brain tumors, also called brain cancer, are the second leading cause of cancer deaths among children and young adults. The causes of brain tumors are currently unknown. They are likely to grow rapidly and invade the nearby normal brain. Cancer cells can break away and spread to other parts within the brain and spinal cord. It is very important for patients and their families to be familiar with this disease and have clear expectations. It is also important for them to know that there a treatment options, including surgery, chemotherapy, and radiotherapy. After reading this book chapter, patients should be more familiar with the incidence, clinical presentations, diagnosis, treatment, and prognosis of a malignant brain tumor. It is also important for patients and families to know that every patient has a different clinical course and life expectancy.
Hepatic Flavin-containing Monooxygenase and Aldehyde Oxidase Activities in Male Domestic Pigs at Different Ages.

BACKGROUND Age has a significant impact on activities of hepatic metabolizing enzymes in humans and animals. Flavin-containing Monooxygenase (FMO) and Aldehyde Oxidase (AO) are two important hepatic enzymes. Understanding of the impact of age on these two enzymes is still limited in pigs. OBJECTIVE The aim of this work was to assess hepatic FMO and AO activities of male domestic pigs at five different ages of 1 day, 2, 5, 10 and 20 weeks. METHODS Porcine liver microsomes and cytosol were prepared from the livers of male domestic pigs at ages of 1 day, 2, 5, 10 and 20 weeks. FMO activity was assessed using N-oxidation of benzydamine in porcine liver microsomes and AO activity was evaluated using oxidation of O6-benzylguanine in the porcine liver cytosol. RESULTS Porcine hepatic FMO activity was substantial at the age of 1 day, rapidly increased in 2 weeks, and remained high afterwards. Porcine hepatic AO activity was minimal at the age of 1 day and gradually increased to the maximum in 5 weeks and remained relatively constant to the age of 20 weeks. Porcine hepatic FMO activity is higher than other species, including humans. Age-dependent FMO developmental pattern in porcine liver is different from porcine hepatic CYP450 and human hepatic FMO. Porcine hepatic AO activity is much lower than humans although their developmental patterns are similar. CONCLUSION Age impact on hepatic activities of both FMO and AO is obvious in domestic male pigs although age patterns of both enzymes are different.
Children with Autism Spectrum Disorder, Developmental Coordination Disorder, and typical development differ in characteristics of dynamic postural control: A preliminary study.

Abstract Background Autism Spectrum Disorder (ASD) and Developmental Coordination Disorder (DCD) are developmental disorders with distinct definitions and symptoms. However, both conditions share difficulties with motor skills, including impairments in postural control. While studies have explored postural sway variables in children with DCD and ASD as compared to typical development (TD), few have used kinematic data to assess the magnitude of differences between these two neurodevelopmental conditions. There are few sensitive and specific measures available to assess balance impairment severity in these populations. Research question Do individuals with ASD, DCD, and TD differ in dynamic postural control? Methods We quantified postural control differences between ASD, DCD, and TD during a dynamic balance task. 10 ASD, 10 DCD, and 8 TD agematched children completed a dynamic postural control task in a virtual environment. They leaned to shift their center of pressure (CoP) to match a user-controlled object to an oscillating target (0.1 Hz–0.8 Hz). Results The DCD group had higher CoP accelerations compared to ASD or TD. While the DCD and TD groups did not differ in their medial-lateral velocity, the ASD group had low medial-lateral velocity and acceleration as compared to DCD and TD. ASD group velocity and acceleration did not differ from that of the TD group in the anterior-posterior direction. Higher accelerations in the DCD group reflected non-fluid movements; by contrast, the ASD group had slower, more fluid movements. Results may reflect differences in how children with ASD and DCD plan, execute, and modify motor actions. Significance This study demonstrates the potential utility of CoP acceleration and velocity as a sensitive and specific means of differentiating between ASD, DCD, and TD. Results indicating group differences between ASD and DCD in velocity and acceleration profiles represent an important step toward understanding how these populations modify motor plans during dynamic tasks.
The AtmosphereOpen image in new window

The atmosphere is divided into layers by temperature inversions. An ‘inversion’ is where light, warm air overlies denser cold air, preventing convection.
Age-related mortality in abusive head trauma

BACKGROUND Abusive head trauma (AHT) peaks during early infancy and decreases in toddler years. Infants and toddlers experience different injuries, possibly impacting the risk of mortality. We aimed to evaluate the association of age with mortality. METHODS We conducted a retrospective study of AHT hospitalizations in 2000, 2003, 2006, 2009, and 2012 from the Kid's Inpatient Claims Database. An accidental head trauma cohort was included to hypothesize that the association between age and mortality is unique to abuse. A nested multivariable logistic regression was used to perform the analysis. RESULTS Children aged 2 years to 4 years experienced higher mortality than those younger than 2 years (22% vs. 10%, p < 0.0001; adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2). The presence of subarachnoid hemorrhage (OR, 1.9; 95% CI, 1.3-2.9), cerebral edema (OR, 4.0; 95% CI, 2.9-5.4), and retinal hemorrhage (OR, 1.9; 95% CI, 1.5-2.5) were associated with an increase risk in mortality. Children younger than 2 years experienced more fractures and hemorrhage (subdural, subarachnoid, retinal) while children aged 2 years to 4 years encountered more internal injuries and cerebral edema.In children with accidental head trauma, those aged 2 years to 4 years have a lower mortality compared with those younger than 2 years (OR, 0.4; 95% CI, 0.3-0.6). Among children younger than 2 years, AHT and accidental trauma had comparable risk of mortality (OR, 0.9; 95% CI, 0.6-1.3). However, among those aged 22 years to 4 years, AHT had a higher risk of mortality than accidental trauma (OR, 3.3; 95% CI, 2.1-5.1). CONCLUSION There is a considerable risk of mortality associated with age at diagnosis in children with AHT.Children younger than 2 years and those aged 2 years to 4 years present with different types of injuries. The high risk of mortality in the children aged 2 years to 4 years is unique to AHT. Efforts should be made to increase awareness about the risk of mortality and identify factors that can aide in a timely accurate diagnosis. LEVEL OF EVIDENCE Prognostic and epidemiological study, level III.
A review of sensor technology development at NASA's Goddard Space Flight Center for earth science

It is critically important for the existence of life on Earth to understand and reliably predict how our planet is changing on a long-term basis. Over the past few decades, NASA, and other space agencies, have developed technologies and methodologies to measure Earth science parameters on a global scale with high spatial and temporal resolutions. NASA’s Goddard Space Flight Center (GSFC) has significantly contributed to this cause. In this report, we plan to review the microwave, millimeter wave and optical sensors technology developed, validated, and patented at GSFC for Earth monitoring and analyzing data to create more accurate predictive models. Since its foundation, GSFC has been in the business of launching many spacecraft to explore Earth and the solar system. A number of novel technologies developed at GSFC have been embedded into sensor instruments on these exploring missions. This report will explore some of these innovations, many of which have been patented. GSFC is interested in licensing these patented technologies to U.S. industries and participating in collaborating discussions with global entities.
Neurophysiological and Interpersonal Correlates of Emotional Face Processing in Alcohol Use Disorder.

BACKGROUND A growing literature suggests deficient emotional facial expression (EFE) processing among recently abstinent individuals with alcohol use disorders (AUDs). Further investigation is needed to clarify valence-related discrepancies and elucidate neural and psychosocial correlates. We examined neurobehavioral indices of EFE processing and interpersonal problems in treatment seekers with AUDs and healthy community controls (CCs). METHODS Thirty-four individuals with AUDs and 39 CCs completed an emotion judgment task (EJT), requiring discrimination between happy, angry, and sad EFEs. A second task requiring discrimination of male and female faces with neutral expressions served as the control task (i.e., sex judgment task, SJT). Neurophysiological (i.e., N170 and P3) and behavioral measures were analyzed using generalized linear mixed models (GLMM). Interpersonal problems were assessed with the Inventory of Interpersonal Problems-64 (IIP-64). The relationship of IIP-64 and EJT performance was investigated via within-group correlations. RESULTS Analysis of the SJT revealed no group differences in behavioral measures, N170 amplitude, or P3 latency. P3 amplitudes, however, were significantly lower in the AUD group. For the EJT, initial observations of group differences in P3 amplitude were accounted for by differences in the control task. Behavioral analyses indicated that the AUD group was significantly less accurate than the CC group. Hypothesis-driven analyses using GLMM-estimated group differences indicated that anger processing was affected to a greater degree than were other emotions. Significant EJT/IIP-64 correlations were observed for anger processing within the AUD group and were confined to IIP-64 subscales with relatively high ratings on the affiliation dimension. CONCLUSIONS Findings provide partial support for an emotion-specific processing deficit in persons with AUDs. Anger processing was more robustly affected than other emotions and was associated with interpersonal problems characterized by being overly needy, nonassertive, and overly accommodating. Results extend prior reports and reinforce the need for comprehensive study of emotion processing and its real-world implications.
A Reconfigurable Architecture for a VLSI Implementation of Artificial Neural Networks

In this paper, a VLSI design of a Basic Neural Unit (BNU) for artificial neural networks (ANNs) is proposed. The BNU is used as a basic processing element in constructing an ANN. An important issue to address in the design of BNU is to reduce the interconnection complexity of ANNs. When the size of an ANN grows, the number of synaptic weights connected to each neuron increases rapidly. From the hardware implementation point of view, an expandable and reconfigurable architecture design for ANNs is in demand. A new approach has been used in designing a BNU. This BNU design is the foundation of a reconfigurable architecture for constructing an ANN with a very strong expandability.
An Organotypic Mammary Duct Model Capturing Distinct Events of DCIS Progression

ABSTRACT Ductal carcinoma in situ (DCIS) is a pre-cancerous stage breast cancer, where abnormal cells are contained within the duct, but have not invaded into the surrounding tissue. However, only 30-40% of DCIS cases are likely to progress into an invasive ductal carcinoma (IDC), while the remainder are innocuous. Since little is known about what contributes to the transition from DCIS to IDC, clinicians and patients tend to opt for treatment, leading to concerns of overdiagnosis and overtreatment. In vitro models are currently being used to probe how DCIS transitions into IDC, but many models do not take into consideration the macroscopic tissue architecture and the biomechanical properties of the microenvironment. Here, we developed an organotypic mammary duct model by molding a channel within a collagen matrix and lining it with a basement membrane. By adjusting the concentration of collagen, we effectively modulated the stiffness and morphological properties of the matrix and examined how an assortment of breast cells responded to changing density and stiffness of the matrix. We first validated the model using two established, phenotypically divergent breast cancer cell lines by demonstrating the ability of the cells to either invade (MDA-MB-231) or cluster (MCF7). We then examined how cells of the isogenic MCF10 series—spanning the range from healthy to aggressive—behaved within our model and observed distinct characteristics of breast cancer progression such as hyperplasia and invasion, in response to collagen concentration. Our results show that the model can recapitulate different stages of breast cancer progression and that the MCF10 series is adaptable to physiologically relevant in vitro studies, demonstrating the potential of both the model and cell lines to elucidate key factors that may contribute to understanding the transition from DCIS to IDC. IMPACT STATEMENT The success of early preventative measures for breast cancer has left patients susceptible to overdiagnosis and overtreatment. Limited knowledge of factors driving an invasive transition has inspired the development of in vitro models that accurately capture this phenomenon. However, current models tend to neglect the macroscopic architecture and biomechanical properties of the mammary duct. Here, we introduce an organotypic model that recapitulates the cylindrical geometry of the tissue and the altered stroma seen in tumor microenvironments. Our model was able to capture distinct features associated with breast cancer progression, demonstrating its potential to uncover novel insights into disease progression.
Boundary pressure projection for partitioned solution of fluid-structure interaction with incompressible Dirichlet fluid domains

Abstract Partitioned solutions to fluid-structure interaction problems often employ a Dirichlet-Neumann decomposition, where the fluid equations are solved subject to Dirichlet boundary conditions on velocity from the structure, and the structure equations are solved subject to forces from the fluid. In some scenarios, such as an elastic balloon filling with air, an incompressible fluid domain may have pure Dirichlet boundary conditions, leading to two related issues which have been described as the incompressibility dilemma. First, the Dirichlet boundary conditions must satisfy the incompressibility constraint for a solution to exist. However, the structure solver is unaware of this constraint and may supply the fluid solver with incompatible velocities. Second, the constant fluid pressure mode lies in the null space of the fluid pressure solver, but must be determined to apply to the structure. Previously proposed solutions to the incompressibility dilemma have included modifying the fluid solver, the structure solver, or the Dirichlet-Neumann coupling interface between them. In this paper, we present a boundary pressure projection method which alleviates the incompatibility while maintaining the Dirichlet-Neumann structure of the decomposition and without modification of the fluid or solid solvers. Our method takes incompatible velocities from the structure solver and projects them to be compatible while in the process computing the constant pressure modes for the Dirichlet regions. The compatible velocities are then used as Dirichlet boundary conditions for the fluid while the constant pressure modes are added to the fluid-solver-computed pressures to be applied to the structure. The intermediate computation performed in the boundary pressure projection method is small, with the number of unknowns equal to the number of Dirichlet regions. We show that the boundary pressure projection method can be used to solve a variety of scenarios including inflation of an elastic balloon and the action of a hydraulic press. We also demonstrate the method on multiple coupled Dirichlet regions. The method offers a simple approach to overcome the incompressibility dilemma using a small intermediate computation that requires no additional knowledge of the black box fluid and solid solvers.
Impacts of a large invasive mammal on water quality in riparian ecosystems

Wild pigs (Sus scrofa) are a highly invasive species in many regions of the world and can act as ecosystem engineers in areas where they are established. In riparian ecosystems, wild pigs may affect water quality parameters and introduce fecal bacteria, although previous studies have reported conflicting results. We propose four conditions that we believe are needed for an accurate assessment of wild pig impacts on water quality and address each one in our study. Water samples were collected between May 2018 and June 2019 in riparian watersheds on a privately owned property in Alabama that was densely populated by wild pigs (treatment) and in watersheds at a nearby national forest without an established population. Samples were analyzed for concentrations of water quality parameters, such as anions and cations, dissolved oxygen, total suspended solids, N, dissolved organic C, and Escherichia coli and other fecal coliforms. An additional 38 samples were analyzed using quantitative polymerase chain reaction for swine fecal bacteroidetes. At treatment watersheds, specific conductivity and concentrations of organic N and C, SO42- , and Ca2+ were between 2 and 11 times that of reference watersheds. Escherichia coli values at treatment watersheds were 40 times reference watershed values. DNA from swine fecal bacteroidetes was detected in 70% of treatment samples and 0% of reference samples. Wild pigs are a threat to water quality in riparian areas, and our results indicate that it may be important to control populations upstream of major drinking water sources and recreational areas.
Phase II trial of the PARP inhibitor, niraparib, in BRCA1-Associated Protein 1 (BAP1) and other DNA damage response (DDR) pathway deficient neoplasms including cholangiocarcinoma.

TPS354Background: BRCA1-Associated Protein 1 (BAP1) is a critical regulator of the cell cycle, cellular differentiation, cell death, and DNA damage response. It also acts as a tumor suppressor. Pre...
A First Generation Fusion Reactor Using the D-3He Cycle

With the goal of reducing the radiation damage and radioactive waste that will occur in a tokamak reactor using the deuterium-tritium cycle, this paper proposes a new magnetic scheme capable of con...
Child Labour and the Global Economy: Abolition or Acceptance?

This article traces the evolution of international attitudes toward child labour, and outlines its relationship to the global economy. It examines the way in which international treaties promulgated by the International Labor Organization (ilo) have conceived of child labour over time. At the national level, the most extreme pro-child labour position may be found in recent Bolivian legislation that recognizes work performed by children as young as ten years old. Much has been written on the problem of conflicting global values on child labour, but all agree that exploitative forms should be eliminated. The author updates her earlier recommendation that the World Trade Organization should place conditions on participation in the global economy by requiring its member states to honour core ilo standards. Eliminating exploitative child labour could thus be linked indirectly to the global economy, by requiring the elimination of children’s work detrimental to the child’s full development.
Characterization of a variable bit-rate receiver for applications in WDM/WDMA systems

A receiver optimized for a range of bit rates is desirable for full protocol transparent operations in WDM and WDMA systems. In order for a receiver to be optimally configured for a range of bit rates, the transimpedance of the preamplifier needs to be tunable. Here, we report the characteristics of a receiver whose performance can be optimized for bit rates ranging from 300 to 1,500 Mbps. The receiver is part of an eight-channel receiver array. The other seven receivers use passive feedback resistors in the transimpedance amplifiers.
Hawaii Cyclonic Eddies and Blue Marlin Catches: The Case Study of the 1995 Hawaiian International Billfish Tournament

The combination of prevailing northeasterly tradewinds and island topography results in the formation of vigorous, westward propagating cyclonic eddies in the lee of the Hawaiian Islands on time scales of 50–70 days. These mesoscale (∼102 km) features are nowhere more conspicuous or spin up more frequently than in the Alenuihaha Channel between the Island of Maui and the Big Island of Hawaii. Cyclonic eddies in subtropical waters such as those around Hawaii vertically displace the underlying nutricline into the overlying, nutrient-depleted euphotic zone creating localized biologically enhanced patches. Insight into how these eddies may directly influence pelagic fish distribution is provided by examination of recreational fish catch data coinciding with the presence of eddies on the fishing grounds. We highlight the 1995 Hawaii International Billfish Tournament in which a cyclonic eddy dominated the ocean conditions during the weeklong event and the fish catch distribution differed significantly from the average historical tournament catch patterns. On the tournament fishing grounds, well-mixed surface layers and strong current flows induced by the eddy's presence characterized the inshore waters where the highest catches of the prized Pacific blue marlin (Makaira mazara) occurred, suggesting possible direct (e.g., physiological limitations) or indirect (e.g., prey availability) biological responses of blue marlin to the prevailing environment.
The Right Remedy

Antitrust law respects economic logic by establishing two goals for remedy, restoration of competition harmed by the anticompetitive acts and prevention of further anticompetitive acts. Microsoft has a pattern of anticompetitive acts, interfering with the commercialization of competitive technologies brought by the Internet in the 1990s and committed to repeating the pattern by preventing valuable innovation in the new century. Microsoft is strategically quite predictable; it will always resort to anticompetitive means if - as has been so often the case since the mid 1990s - it cannot win a technology race on the merits. On the other hand, Microsoft is tactically quite resourceful; its violations of the antitrust law are wide-ranging and varied. Such a widespread, lawless and harmful ongoing pattern calls for a remedy that accomplishes both goals. Standard antitrust analysis would lead to the obvious, traditional remedy: ending the Windows monopoly, either by breaking up the company into multiple sellers of Windows or by licensing Windows technology widely. Both goals for remedy can be accomplished in this case without that traditional step. First, divestiture of the company into an applications and an operating system company restores competitive conditions very like those destroyed by the anticompetitive acts. Absent the anticompetitive acts, Microsoft would have lost the browser war, and other firms would have commercialized useful technologies no w controlled by Microsoft. Divided technical leadership, which could be accomplished by having an independent browser company in the late 1990s or an applications company now, lowers barriers to entry and competition in many markets. It was exactly this route to an increase in competition that Microsoft avoided by its anticompetitive acts. Second, ending Microsoft's unique position in the industry offers innovative new technologies the choice of two mass-market distribution partners, either AppsCo or OSCo. The divestiture will do much to reduce the motive to violate and also to reduce the effectiveness of future anticompetitive acts. It restores conditions for competitive innovation at a moment in technology history when having a single firm set the direction of innovation in PC and end-user oriented internet markets is most unwise.
Civil Religion and National Politics in a Neoliberal Era

Civil religion, or the connection of the nation-state, its history, destiny, and people, to understandings of transcendence or divinity, is in crisis both as a theoretical concept and as a politico-cultural phenomenon. The crisis has been brought about by the weakened capacity of the nation-state to generate collective identity and a version of ‘charismatic’ authority. We argue that this has resulted in a shift from the widely accepted conceptualization of civil religion as a unifying force in societies to a more exclusionary force that Williams (2103) calls “tribal civil religion” That, in its own way, undermines the nation-state. In this paper, we examine the history and various understandings of the concept of civil religion, develop an argument that the assault on the nation-state has meant the rise of increasingly exclusive and exclusionist expressions of civil religion, and present possible suggestions for sites where ‘unitive’ civil religion may still be found.
Chemotherapy in the Setting of Severe Liver Dysfunction in Patients with Metastatic Colorectal Cancer.

The liver is the dominant site of metastases for patients with metastatic colorectal cancer (mCRC). Depending on the timing of diagnosis and the biology of the disease, it is not uncommon for these patients to present with visceral crisis in the form of severe liver dysfunction. Treatment of these individuals is, however, difficult and challenging. The decision to consider chemotherapy in these dire circumstances entails consideration of numerous factors. If we were to focus on just the metabolism of the different drugs and biologic agents available to treat mCRC, both 5-fluorouracil and oxaliplatin alone or in combination with a monoclonal antibody are reasonable choices. Specifically, FOLFOX is a feasible and safe option in patients with mCRC with severe liver dysfunction. Choice of the biologic agent to add to the doublet chemotherapy could be individualized based on the RAS status and the clinical scenario. Based on the divergent experience of treating 2 cases and other prior reports, a summary of recommendations with a model in the form of a “therapeutic triad” is presented. The paper highlights the therapeutic challenges in patients with mCRC and severe liver dysfunction. The choice of chemotherapeutic agents and reports of other cases/series is also presented.
A Slowness Matching Eulerian Method for Multivalued Solutions of Eikonal Equations

Traveltime, or geodesic distance, is locally the solution of the eikonal equation of geometric optics. However traveltime between sufficiently distant points is generically multivalued. Finite difference eikonal solvers approximate only the viscosity solution, which is the smallest value of the (multivalued) traveltime (“first arrival time”). The slowness matching method stitches together local single-valued eikonal solutions, approximated by a finite difference eikonal solver, to approximate all values of the traveltime. In some applications, it is reasonable to assume that geodesics (rays) have a consistent orientation, so that the eikonal equation may be viewed as an evolution equation in one of the spatial directions. This paraxial assumption simplifies both the efficient computation of local traveltime fields and their combination into global multivalued traveltime fields via the slowness matching algorithm. The cost of slowness matching is on the same order as that of a finite difference solver used to compute the viscosity solution, when traveltimes from many point sources are required as is typical in seismic applications. Adaptive gridding near the source point and a formally third order scheme for the paraxial eikonal combine to give second order convergence of the traveltime branches.
MEASUREMENT OF THE RADIATIVE LIFETIME OF THE 1S2S 3S1 LEVEL IN HELIUMLIKE MAGNESIUM

We apply a recently developed electron-beam ion trap technique to measure the lifetime of the 1s2s${\mathrm{}}^{3}$${\mathit{S}}_{1}$ level in heliumlike magnesium. The technique employs a fast-switching electron beam to produce and excite electrostatically trapped ions. The radiative lifetime is determined by observing the fluorescent decay of the 1s2s${\mathrm{}}^{3}$${\mathit{S}}_{1}$ level after the beam energy is switched below the threshold for electron-impact excitation. A value of 13.61\ifmmode\pm\else\textpm\fi{}0.49 \ensuremath{\mu}s has been measured for the 1s2s${\mathrm{}}^{3}$${\mathit{S}}_{1}$ level in heliumlike magnesium, in good agreement with theoretical predictions.
Localization in virtual acoustic displays

This paper discusses the development of a particular spatial display medium, the virtual acoustic display. Although the technology can stand alone, it is envisioned ultimately to be a component of a larger multisensory environment and will no doubt find its greatest utility in that context. A general philosophy of the project has been that the development of advanced computer interfaces should be driven first by an understanding of human perceptual requirements, and secondarily by technological capabilities or constraints. In expanding on this view, the paper addresses why virtual acoustic displays are useful, characterizes the abilities of such displays, reviews some recent approaches to their implementation and application, describes the research project at NASA Ames in some detail, and finally outlines some critical research issues for the future.