cssi/SciSciGPT-SciSciNet huggingface dataset:
Bone remodeling of diaphysial surfaces under constant load: Theoretical predictions

Abstract Theoretical predictions of surface bone remodeling in the diaphysis of a long bone under a constant superposed compressive load are made. The bone is modeled as a hollow circular cylinder. The surface remodeling theory due to Cowin and Van Buskirk is employed. It is shown that there is a great variety of solutions to the problem. Both endosteal and periosteal surfaces can move in either direction, in or out, in the same or opposite direction. It is possible for the medullary canal to fill up completely and for the endosteal surface to vanish. The particular type of response that develops depends upon the magnitude of the applied compressive load and the values of the surface remodeling rate coefficients.
Recursive Sliding-Window LMMSE-Based Equalization in Wireless Mobile Coded OFDM

Orthogonal frequency division multiplexing (OFDM) system suffers extra performance degradation in fast fading channels due to intercarrier interference (ICI). Combining frequency domain equalization and bit-interleaved coded modulation (BICM), the iterative receiver is able to harvest both temporal and frequency diversity. Using the fact that ICI energy is clustered in adjacent subcarriers, frequency domain equalization is made localized. Conventional localized q-tap frequency domain equalizer still bears a formidable computational complexity of O(K2q), where K is the number of subcarriers. By further restricting the observation window size, sliding-window (SW) type of equalizer is proposed in the literature with complexity O(Kq3). This paper proposes a recursive SW LMMSE based equalizer which further reduces the computational complexity to O(Kq2) and more importantly without compromising performance.
T1BT* structural study of an anti-plasmodial peptide through NMR and molecular dynamics

T1BT* is a peptide construct containing the T1 and B epitopes located in the 5’ minor repeat and the 3’ major repeat of the central repeat region of the Plasmodium falciparum circumsporozoite protein (CSP), respectively, and the universal T* epitope located in the C-terminus of the same protein. This peptide construct, with B = (NANP)3, has been found to elicit antisporozoite antibodies and gamma-interferon-screening T-cell responses in inbred strains of mice and in outbred nonhuman primates. On the other hand, NMR and CD spectroscopies have identified the peptide B’ = (NPNA)3 as the structural unit of the major repeat in the CSP, rather than the more commonly quoted NANP. With the goal of assessing the structural impact of the NPNA cadence on a proven anti-plasmodial peptide, the solution structures of T1BT* and T1B’T* were determined in this work. NMR spectroscopy and molecular dynamics calculations were used to determine the solution structures of T1BT* and T1B’T*. These structures were compared to determine the main differences and similarities between them. Both peptides exhibit radically different structures, with the T1B’T* showing strong helical tendencies. NMR and CD data, in conjunction with molecular modelling, provide additional information about the topologies of T1BT* and T1B’T*. Knowing the peptide structures required to elicit the proper immunogenic response can help in the design of more effective, conformationally defined malaria vaccine candidates. If peptides derived from the CSP are required to have helical structures to interact efficiently with their corresponding antibodies, a vaccine based on the T1B’T* construct should show higher efficiency as a pre-erythrocyte vaccine that would prevent infection of hepatocytes by sporozoites.
Distance Education And Learning Styles: Some Interesting Results

The rush to offer web courses has left many questions as to what makes them effective and satisfactory. Important issues are: the perceived advantages of web-based courses; appropriate pedagogical tools (e.g., streaming media, PowerPoint presentations) to facilitate student-content interaction, media richness, and the influence of antecedent characteristics, such as gender, experience, motivation, and learning styles. Research here indicates support for media richness, web-based course advantages, some pedagogies, and minimal support for learning styles, at least Gardner’s multiple intelligences and Keirsey’s personality styles.
Foraging Ecology and Interactions between Herring Gulls and Great Black-backed Gulls in New England

Abstract Numbers of Great Black-backed Gulls (Larus marinus) and Herring Gulls (L. argentatus) along coastal New England have changed dramatically during the last century. In recent years, Great Black-backed Gulls have displaced Herring Gulls from optimal breeding sites, thus potentially contributing to the recent decline of the Herring Gull. Although the quality of foraging habitat is also a strong determinate of reproductive success, potential for competition and interactions between these two species in natural foraging habitats have been largely ignored. In this study, the diet and prey preference of the two species were compared. In addition, the spatial and temporal patterns in foraging activities were examined and interspecific interactions in the rocky intertidal zones were also described. Diet and prey preference of the two species greatly overlapped, with both species consuming a large percentage of marine invertebrates (30-60%), especially crabs. Foraging differed, and the Great Black-backed Gu...
6 The revival of group A streptococcal diseases, with a commentary on staphylococcal toxic shock syndrome

Publisher Summary This chapter presents the revival of group A streptococcal diseases, with a commentary on staphylococcal toxic shock syndrome. Staphylococcus aureus is a gram-positive bacterium that is the cause of numerous diseases in humans and animals, including food poisoning, endocarditis, sepsis, scalded-skin syndrome, furunculosis, and economically important mastitis in cows and sheep. The pathogen also is responsible for human toxic shock syndrome (TSS). The study of TSS has also provided new information on the critical role of bacterial superantigens in mediating human disease. TSST-1 is a member of the class of structurally related molecules, which are designated as “superantigens.” The evidence has implicated the introduction of superabsorbent materials in catemenial products, perhaps associated with decreased or decreasing levels of anti-TSST-1 antibody in human populations, as a major factor in the rapid increase in the disease frequency. Serological studies demonstrated that although most adults have preexisting antibody to TSST-1, most women who developed TSS associated with the menses have little or no detectable antibodies.
Charged V+A Currents in Left-Right Symmetric Gauge Models

Knowledge of weak interactions increased dramatically in 1956 and 1957. During those years parity non-conservation and the V-A hypothesis for charged weak currents were proposed.
The effects of loaded and unloaded high-velocity resistance training on functional fitness among community-dwelling older adults

BACKGROUND Physical function declines up to 4% per year after the age of 65. High-velocity training is important for maintaining muscular power and ultimately, physical function; however, whether performing high-velocity training without external resistance increases functional fitness among older adults remains unclear. OBJECTIVE The purpose of this investigation was to evaluate loaded and unloaded high-velocity training on lower body muscular power and functional fitness in older adults. SUBJECTS Fifty-seven community-dwelling older adults (n = 16 males, n = 41 females) participated in this study. Inclusion criteria comprised ≥65 years of age, ≥24 on the Mini-mental state examination and no falls within past year. METHODS Two groups completed a 20-week high-velocity training intervention. The non-weighted group (UNLOAD, n = 27) performed the protocol without external load while the intervention group (LOAD, n = 30) used external loads via exercise machines. Functional fitness was assessed using the Short Physical Performance Battery (SPPB), Senior Fitness Test (SFT), hand-grip and lower body power measures. RESULTS Multivariate ANOVA revealed that both groups had significant improvements for average (17.21%) and peak (9.26%) lower body power, along with the SFT arm curl (16.94%), chair stand (20.10%) and 8 ft. up-and-go (15.67%). Improvements were also noticed for SPPB 8 ft. walk (25.21%). However, improvements for all functional fitness measures were independent of training group. CONCLUSIONS Unloaded high-velocity training increased functional fitness and power the same as loaded training. The ability of high-velocity movements to elicit gains in functional fitness without external loads may help health professionals develop fitness programs when time/space is limiting factor.
Abstract T P218: Peripheral Organ Proteomics, a Novel Approach to Biomarker Discovery for Brain Disorders

Introduction: Brain disorders may produce changes in function of peripheral organs. The lack of omics characterization of peripheral organs hinders development of novel approaches for diagnosing/managing brain disorders. We have characterized proteomes of ischemic brain injury (Stapels et al., 2010, Science Signaling 3 (111):ra15). Here, we demonstrate: 1) Acute brain disorders induce systemic responses in peripheral proteomes; 2) Brain disorder-induced peripheral proteomic changes are specific to injury conditions. Renal proteomic responses to focal brain ischemia are examples. Methods Ischemia: suture occlusion (30 or 60 minutes: n=5, sham: n=4) of middle cerebral artery (MCAO) in mice. After 4 hours reperfusion, brain cortices and one kidney were removed at sacrifice. Proteins were extracted from individual tissues. Tryptic digests from animals of the same experimental group were pooled, and analyzed by quantitative mass spectrometry with triplicate replications. Proteins showing differences in abundance between sham and 30 minutes or 60 minutes brain ischemia were further analyzed by bioinformatics. Results and Conclusion: At 4 hours after 30 or 60 minutes MCAO, kidney proteome showed significant changes compared to that of sham controls: 72 and 56 proteins with increased abundance in the former and latter brain conditions, respectively. Interestingly, among up-regulated proteins, only 24 showed an overlap between the 30 and 60 minute brain ischemic conditions. Results of bioinformatic analyses of regulated kidney proteins indicated an association with cellular pathways or processes of cell adhesion, small molecule metabolism, protein folding, as well as immune response, for both brain ischemic conditions. Differential changes were also observed: an increase of amino acid metabolism and nucleoside catabolic processes were detected only in 60 but not 30 minutes brain ischemic conditions. Our previous work has shown that 30 minutes MCAO results in very limited cortical injury whereas 60 minutes MCAO leads to broad tissue infarction. Hence, our results present distinguishable kidney proteomic characteristics associated with different brain ischemic conditions.
Discharge of Tax Liabilities in Bankruptcy

Professors John R. Leavins and Darshan Wadhwa of the University of Houston-Downtown review the state of the law on how filing for bankruptcy protection affects tax liabilities.
Pediatric surgical extracorporeal membrane oxygenation - a case series

Objective. To review demographic and procedural factors and their association with weaning rate and survival from extracorporeal membrane oxygenation (ECMO) in pediatric patients undergoing repair of cardiac malformations. Methods. The hospital records of children requiring ECMO during cardiac operation due to failure to wean from cardio-pulmonary by pass (CPB) were retrospectively reviewed, and an analysis of variables affecting survival was performed. Results. Thirty-five pediatric patients between January 1, 2000 and December 31, 2006 required ECMO for cardiopulmonary support during cardiac operations. ECMO survival was 54.3% and was comparable across all age groups. The lowest pH during ECMO treatment was the only predictor of mortality (P = 0.006). No other patient, surgical or anesthetic, factor was associated with either weaning from ECMO or hospital survival. Conclusions. No clear risk factor could be identified for survival from ECMO in our pediatric patients who underwent cardiac surgery and failed weaning from cardiopulmonary bypass.
Particle Image Velocimetry Measurements in a High-Swirl Engine Used for Evaluation of Computational Fluid Dynamics Calculations

Two-dimensional in-cylinder velocity distributions measured with Particle Image Velocimetry were compared with computed results from Computational Fluid Dynamics codes. A high-swirl, two-valve, four-stroke transparent-combustion-chamber research engine was used. Comparisons were made of mean-flow velocity distributions, swirl-ratio evolution during the intake and compression strokes, and turbulence distributions at top-dead-center compression. This comparison with the measured flows led to more accurate calculations by identifying code improvements including swirl in the residual gas, modeling of the gas exchange during the valve overlap, and improved numerical accuracy. 14 refs., 14 figs.
Health locus of control and biofeedback training.

To draw conclusions about the effects of biofeedback training on health locus of control or any other psychological response, an attention placebo condition should be included.
Volcanic Activity in Katmai National Monument, In Early August, 1965

From August 3 until August 5, 1965, a heavy concentration of dust and some sulphurous fumes were noted in the Valley of 10, 000 Smokes and the Brooks River area of Katmai National Monument, Alaska. Visual and seismic observations during July and August indicated that although there was no major volcanic eruption, there was a slight increase of seismic activity in late July near Mt. Trident and in early August near Mt. Martin. Observations of volcanic activity, however, in the Katmai region during 1965, were inadequate to relate volcanic and seismic events. While an aeolian origin for the observed dust and fumes can not be ruled out, some type of volcanic activity seems likely.
Comparison of amoxicillin and ampicillin in the treatment of urinary tract infections.

In a double-blind study of uncomplicated cystitis, amoxicillin appeared (by bacteriologic criteria) to be similar to ampicillin in efficacy. Because of superior gastrointestinal absorption of amoxicillin and resulting prolonged high concentrations in urine, these results were obtained with a reduction in the dosage of amoxicillin to one-third that of ampicillin and an increase in the interval between doses of both antibiotics to 8 hr. The data require confirmation with a larger patient population.
Active resonator using comb-shaped defected ground structure with negative resistance

A design for a new active resonator with gain using a comb-shaped defected ground structure (DGS) with a negative resistance is presented. The negative resistance is realized using a single transistor coupled between two separated parts of the DGS. This negative resistance is realized on a separate circuit-board layer that is attached to the DGS. It is used to compensate for the insertion loss of the resonator. An HFSS-ADS co-simulation is used to combine the electromagnetic structure as well as all parasitic effects along with the behavior of the active circuitry. The design consists of a single resonating element with a center frequency of 2.93 GHz, 3-dB bandwidth of 137 MHz, simulated noise figure of 4.9 dB, and 3.48 dB of gain. The results from the simulation are presented along with the measured response. A good agreement is observed between the results.
Permeability Parameters of Pulp Fibers from Filtration Resistance Data and Their Application to Pulp Dewatering

The drainage resistance of pulp fibers can be characterized by means of a specific surface area and the specific volume. These parameters can be used to determine the impact not only of processing the pulp fibers but also to compare and distinguish between different pulp mixes. We determined the specific surface area and specific volume of hardwood kraft pulp fibers by measuring the rate of filtrate flow under different applied pressures by a modified filtration apparatus. The specific surface area and specific volume can be used as parameters for monitoring fiber changes due to source and variation, determination of polymer dosage (retention, drainage aids, and flocculation control), and so on. The specific surface area serves as an indicator of the flocculation state of the pulp suspension, while the specific volume indicates the hydration of the fibers. Two mathematical models to describe dewatering of fibrous suspensions under varying pressure were applied. The first is based on conventional cake filt...
Study on numerical simulation of the dual-mode scramjet combustor

On the basis of 3-D viscous, turbulent and reactive Navier-Stokes numerical equation, the finite-rate chemistry/eddy-dissipation model for modeling the turbulent combusion is established. The fluid dynamic mechanisms of the dual-mode scramjet combustor using hydrogen as the fuel is studied. The effects of the ratio of the air to fuel, fuel injection angle and flight Mach number on the dual-scramjet working mode are analyzed, and the function of the isolator is analyzed too.
Disinfection By-Product Exposures and the Risk of Specific Cardiac Birth Defects.

Background:Epidemiological studies suggest that women exposed to disinfection by-products (DBPs) have an increased risk of delivering babies with cardiovascular defects (CVDs).Objective:We examined...
Movement coherence and mobilization

If people are getting the same ask from everybody, they obviously have to take you seriously. If you have ten different groups asking for ten different things, nothing happens. Mark Milano, ACT UP activist, 2012 In this chapter, we provide a theoretically informed account of why movement coherence around a common “ask” – global treatment access based on lower drug prices – was a necessary albeit insufficient condition contributing to the AIDS treatment campaign's overall or relative success. The chapter elucidates the importance and mechanisms of influence of movement coherence contrasted with other less successful campaigns, namely, those addressing climate change and maternal mortality. We also examine within-case variation in the AIDS advocacy movement, including differences between treatment and prevention, the effects of splintering among national level AIDS advocates in the United States, and changes in unity over time in support for the global treatment agenda. Using interviews, archival material, and other narratives, we provide a historically contingent account of how the movement cohered around global access to treatment. The main contribution of this chapter is thus conceptual, clarifying why movements that lack coherence or unity tend to fail. While a number of other important foundational pieces have told the chronological history of treatment advocacy (Sawyer 2002; Behrman 2004; d'Adesky 2004; ’t Hoen 2009; Geffen 2010), these pieces by their nature are more descriptive than analytical, making it difficult to identify generalizable aspects of the campaign's organization. Even more theoretically inclined accounts (such as Smith and Siplon 2006; Grebe 2008; 2011; Messac 2008; Gartner 2009a) tend to use existing scholarship instrumentally (such as McAdam, McCarthy, and Zald 1996; Zald 1996; Keck and Sikkink 1998) rather than make their own theoretical contributions or systematically test their arguments.
Data Citation in Neuroimaging: Proposed Best Practices for Data Identification and Attribution

Data sharing and reuse, while widely accepted as good ideas, have been slow to catch on in any concrete and consistent way. One major hurdle within the scientific community has been the lack of widely accepted standards for citing that data, making it difficult to track usage and measure impact. Within the neuroimaging community, there is a need for a way to not only clearly identify and cite datasets, but also to derive new aggregate sets from multiple sources, while clearly maintaining lines of attribution. This work presents a functional prototype of a system to integrate Digital Object Identifiers (DOI) and a standardized metadata schema into a XNAT-based repository workflow, allowing for identification of data at both the project and image level. These item and source level identifiers allow any newly defined combination of images, from any number of projects, to be tagged with a new group-level DOI that automatically inherits the individual attributes and provenance information of its constituent parts. This system enables the tracking of data reuse, down to the level of individual images. The implementation of this type of data identification system would impact researchers and data creators, data hosting facilities, and data publishers, but the benefit of having widely accepted standards for data identification and attribution would go far towards making data citation practical and advantageous.
Abstract 122: Activation of Nuclear Factor Erythroid 2-related Factor 2 (Nrf2) Enhances Cyclooxygenase 2 Expression via Promoter Antioxidant Response Element in Preglomerular Vascular Smooth Muscle Cells (PGVSMCs)

Nrf2 is a key cytoprotective transcription factor driving many antioxidant and anti-inflammatory genes expression via binding to antioxidant response elements (AREs) in promoters of targeting genes. However, it was reported that Nrf2 also increased expression of pro-inflammatory and pro-oxidative genes IL-6 and NOX4 through the same mechanism. We detected 2 putative ARE consensus sequences within 1500 nucleotides (nts) located in the genomic region upstream of the transcription start site in rat cyclooxygenase 2 (COX2) gene. Therefore, we hypothesized that activation of Nrf2-dependent AREs upregulates COX2 expression in rat PGVSMCs. Incubation of the cells for 24 hours with Nrf2 activator, tert-butylhydroquinone (tBHQ), did not significantly alter Nrf2 expression but dose-dependently increased COX2 gene and protein in a dose response manner (5-20μM). Twenty μM of tBHQ treatment enhanced expression of COX2 gene and protein by 10.7±2.2 and 9.2±3.4 fold (both p<0.01, N=3), COX2 activity (from COX2-based product of fluorescent resorufin) by 229.9±28.8% (p<0.005, N=6) but reactive oxygen species (ROS) generated in the cells (from oxidized dihydroethidium-based fluorescent intensity) were reduced by 35.1±10.2% (p<0.01, N=4). tBHQ also significantly promoted Nrf2 nuclear translocation by 86±7.4% (p<0.05, N=3) and potentiated Nrf2 activity by 387.5±19.2% (p<0.005, N=4) determined with cell fraction immunoblotting and Nrf2-ARE binding-based enzyme-linked immunosorbent assay. Nrf2 expression was dramatically knocked down with markedly decreased COX2 expression and activity in the cells transfected with Nrf2 specific siRNA and treated with tBHQ compared to those transfected with the scramble control siRNA and treated with tBHQ. Chromatin immunoprecipitation (CHIP)-based PCR analysis revealed an enhanced recruitment of Nrf2 to the endogenous COX2 promoter spanning the ARE (-417 to -426 nts) after 24 hour-tBHQ treatment but knockdown of Nrf2 gene with siRNA significantly diminished the tBHQ-mediated role, suggesting that there is a functional ARE located in COX2 promoter. In conclusion, these results show a novel role of Nrf2 in inducing COX2 expression through binding to promoter ARE in the absence of increased ROS in rat PGVSMCs.
A Responsive Hydrogel as a Means of Preventing Calcification in Urological Prostheses

Hydrogel prostheses made of poly(2-hydroxyethyl methacrylate), pHEMA, have demonstrated resistance to calcification in the urinary tract(1–3). Implantation studies in non-urinary locations suggest that the methacrylic acid, MAA, content in these gels plays a critical role in their calcification resistance(4,5) and hence may be important for urine compatibility. It is well known that the equilibrium water content and other properties of the gel change significantly according to MAA content(6). Our work, presented here and elsewhere(7,8), shows that gels fabricated with small amounts of MAA and with low crosslinker content demonstrate a reversible shrink/swell behavior. The swollen volume or water content of these gels is highly dependent on electrolyte, pH, or urea contents of the test solutions. In response to a small change in the local environment the shrink/swell behavior may cause volume changes as large as seven hundred percent (largest swollen volume/smallest swollen value) and can occur quite rapidly for thin geometries. The responsive shrink/swell behavior occurs within the normal range of urine composition.
What drives attitude towards telemedicine among families of pediatric patients? A survey

Telemedicine has been recognized as a way to improve accessibility, quality, and efficiency of care. In view of the introduction of new telemedicine services, we conducted a survey through a self-administered questionnaire among families of children attending the Bambino Gesu Children’s Hospital IRCCS, a tertiary care children’s hospital located in Rome, Italy. We investigated sociodemographic data, clinical information, technological profile, attitude towards telemedicine, perceived advantages of telemedicine, fears regarding telemedicine, willingness to use a smartphone app providing telemedicine services and willingness to use a televisit service. Through logistic regression, we explored the effect of sociodemographic and clinical variables and technological profile on willingness of using a telemedicine app and a televisit service. We enrolled a total of 751 families. Most patients had a high technological profile, 81% had at least one account on a social network. Whatsapp was the most popular messaging service (76%). Seventy-two percent of patients would use an app for telemedicine services and 65% would perform a televisit. Owning a tablet was associated with both outcome variables - respectively: OR 2.216, 95% CI 1.358–3.616 (app) and OR 2.117, 95% CI 1.415–3.168 (televisit). Kind of hospitalization, diagnosis of a chronic disease, disease severity and distance from the health care center were not associated with the outcome variables. Families of pediatric patients with different clinical problems are keen to embark in telemedicine programs, independently from severity of disease or chronicity, and of distance from the hospital.
GLOBAL LIFE WORLD

The essay is designed to disclose one aspect of modern Western civilization that has become the ground for what is known as “globalization.” The argument is presented that this civilization is premised on formal systems that are not derivable either from physical or from empirical grounds. Such systems are constructs and their connection with the environment is technical and productive. Thus the selection among the systems to be applied depends on social valuations with respect to their usefulness. The current global systems of internet communication have no physical presence; they are purely “signitive” in the sense that they have no specific space-time location, although can be embodied at any time and any place. Such systems provide an invisible net that can be utilized to access and communicate messages about all events around the globe. The argument that such communication although very fast, takes some time, since the logic of this communication is signitive, a net of meanings that by themselves, as a matter of course define even space and time. It can be stated without a contradiction that the invisible signitive world is a variant of traditional metaphysics, such as Plato’s understanding of mathematics, or the world of ideas.
Medio Oriente en el pasado y futuro de la ciencia social.

Suele atribuirse el nacimiento de los estudios de area a un proyecto politico-militar estadounidense en el marco de la Guerra Fria. Sin embargo, su surgimiento data del periodo de entreguerras y fue promovido no solo por razones politicas sino tambien por la aspiracion occidental de crear una ciencia universal. Asi, las ciencias sociales construyeron los objetos que les dieron forma a partir determinado modo de diferenciacion de lo local y de lo global. Los estudios de area, por su parte, contribuyeron a delimitar los territorios locales cuyos rasgos expresarian formas mas o menos imperfectas de lo universal. Este capitulo reconstruye este proceso poniendo el foco en los estudios de area de Medio Oriente.
FACTA the matter: Recent cases involving payment card receipts illustrate flaws in "Bounty" enforcement regime

This article discusses flaws in the "bounty" enforcement regime within FACTA and its application to payment card receipt disclosures in recent cases.
INSTITUTIONAL CAPACITY AND POLITICAL CHALLENGE: THE CATHOLIC CHURCH IN LATIN AMERICA

With increased competition from the Protestant denominations, the Catholic Church finds itself precariously placed in Latin America in recent years. In light of the steady decline in the number of Catholics and Catholic priests in the region, many have predicted the Church’s gradual irrelevance in politics. But as this study argues, that is not exactly the case. Although the growth in Protestant populations continues unabated in Latin America, the Catholic Church has increased its involvement in educational and social welfare activities. This seems to be a long-terms strategy, and is particularly true in countries where it faces the most intense competition from other religions.
Abstract IA23: Overcoming drug resistance and tumor heterogeneity in gastrointestinal cancers

Personalized cancer medicine approaches, inhibiting kinases in tumors driven by defined genomic alterations, have demonstrated striking efficacy in many cancer types. However, the development of drug resistance is a major limitation to the efficacy of targeted therapies in oncology. Identifying and understanding the molecular mechanisms driving resistance may foster opportunities to develop therapeutic strategies to overcome resistance. For example, in the ~10% of colorectal cancer patients whose tumors harbor BRAF V600 mutations, we have found that feedback reactivation of MAPK signaling, often mediated by EGFR, underlies the relative insensitivity of these cancers to RAF inhibitors. The development of targeted therapy combination strategies to block feedback reactivation of MAPK signaling has led to marked improvements in response rates for these patients from ~5% to >30% over the past few years. However, in patients who respond to these targeted combinations, the rapid development of acquired resistance still limits clinical benefit. Acquired resistance in BRAF mutant colorectal cancer and in other molecularly-defined tumor types can be marked by the development of extensive molecular heterogeneity due to the selection of sub-clonal tumor cell populations, capable of growing under drug pressures, which poses significant diagnostic and therapeutic challenges. We will present data demonstrating how a single-lesion biopsy at disease progression to diagnose the mechanism of acquired resistance can vastly underrepresent the molecular heterogeneity of resistant tumor clones in an individual patient, and may fail to detect the existence of distinct but important resistance mechanisms that can drive mixed or lesion-specific responses and treatment failure to subsequent targeted therapy. By contrast, liquid biopsy approaches analyzing circulating tumor DNA have the potential to detect the presence of simultaneous resistance mechanisms residing in separate metastases in a single patient and to monitor the effects of subsequent therapies on specific sub-clonal tumor cell populations. These findings highlight the critical role of tumor heterogeneity in driving therapeutic resistance and how convergent targeted therapy strategies blocking common signaling nodes capable of overcoming multiple resistance mechanisms may be needed. Citation Format: Ryan B. Corcoran. Overcoming drug resistance and tumor heterogeneity in gastrointestinal cancers [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr IA23.
Investigative Knowledge Discovery for Combating Illicit Activities

Developing scalable, semi-automatic approaches to derive insights from a domain-specific Web corpus is a longstanding research problem in the knowledge discovery community. The problem is particularly challenging in illicit fields, such as human trafficking, where traditional assumptions concerning information representation are frequently violated. In this article, we describe an end-to-end investigative knowledge discovery system for illicit Web domains. We built and evaluated a prototype, involving separate components for information extraction, semantic modeling and query execution, on a real-world human trafficking Web corpus containing 1.3 million pages, with promising results.
Brief Report: Cancer Immunotherapy in Patients With Preexisting Rheumatic Disease: The Mayo Clinic Experience

Objective To determine the risk of rheumatic disease flare and adverse effects in patients with preexisting rheumatic disease who were receiving immune checkpoint inhibitor (ICI) therapy. Methods A retrospective medical record review was performed to identify all patients who received ICI therapy at Mayo Clinic in Rochester, Minnesota between 2011 and 2016 (~700 patients). Those with a preexisting rheumatic disease were identified using specific diagnostic codes. Results Sixteen patients were identified (81% female, median age 68.5 years). The most common rheumatic diseases were rheumatoid arthritis (n = 5), polymyalgia rheumatica (n = 5), Sjogren's syndrome (n = 2), and systemic lupus erythematosus (n = 2). Seven patients were receiving immunosuppressive therapy or glucocorticoids for their rheumatic disease at the time of initiation of the ICI. The primary malignancies were melanoma (n = 10), pulmonary (n = 4), or hematologic (n = 2). In most cases, ICIs were offered only after failure of several other therapies. Immune-related adverse effects (IRAEs) occurred in 6 patients, and all were treated successfully with glucocorticoids and discontinuation of the ICI therapy. There were no significant differences in time from cancer diagnosis to immunotherapy, duration of immunotherapy, age, or sex between the patients with and those without IRAEs. Conclusion To our knowledge, this represents the largest single-center cohort of patients with rheumatic diseases who were exposed to modern cancer immunotherapy. Only a minority of these patients experienced a flare of their preexisting rheumatic disease or any other IRAE.
Patent foramen ovale closure vs. medical therapy for cryptogenic stroke: a meta-analysis of randomized controlled trials

Aims The efficacy of patent foramen ovale (PFO) closure for cryptogenic stroke has been controversial. We undertook a meta-analysis of randomized controlled trials (RCTs) comparing device closure with medical therapy to prevent recurrent stroke for patients with PFO. Methods and results We systematically identified all RCTs comparing device closure to medical therapy for cryptogenic stroke in patients with PFO. The primary efficacy endpoint was recurrent stroke, analysed on an intention-to-treat basis. The primary safety endpoint was new onset atrial fibrillation (AF). Five studies (3440 patients) were included. In all, 1829 patients were randomized to device closure and 1611 to medical therapy. Across all patients, PFO closure was superior to medical therapy for prevention of stroke [hazard ratio (HR) 0.32, 95% confidence interval (95% CI) 0.13-0.82; P = 0.018, I2 = 73.4%]. The risk of AF was significantly increased with device closure [risk ratio (RR) 4.68, 95% CI 2.19-10.00, P<0.001, heterogeneity I2 = 27.5%)]. In patients with large shunts, PFO closure was associated with a significant reduction in stroke (HR 0.33, 95% CI 0.16-0.72; P = 0.005), whilst there was no significant reduction in stroke in patients with a small shunt (HR 0.90, 95% CI 0.50-1.60; P = 0.712). There was no effect from the presence or absence of an atrial septal aneurysm on outcomes (P = 0.994). Conclusion In selected patients with cryptogenic stroke, PFO closure is superior to medical therapy for the prevention of further stroke: this is particularly true for patients with moderate-to-large shunts. Guidelines should be updated to reflect this.
Mindfulness and Self-Compassion Based Interventions for Substance Use Disorders: A Literature Review

This literature review examines eight peer reviewed studies reporting on the efficacy of mindfulness-based and self-compassion-based interventions for adults diagnosed with substance use disorders. Prevalence of substance use disorders is provided, and relevant definitions are discussed. The syndrome model of addiction is advanced as an etiological explanation, and the search methodology described. Results of this literature review support mindfulness training as an effective intervention for substance use disorders. Only one study supporting self-compassion as an effective intervention for substance use disorders was reviewed so it is not possible at this time to make a judgment regarding the efficacy of that intervention. Limitations of this body of literature include attrition, unmatched treatment conditions, and lack of fidelity measures. Recommendations include more self-compassion research, more use of fidelity scales in intervention research, and greater use of mindfulness-based interventions in substance use disorder treatment.
AABB Cell Therapy Standards

AABB standards have played a vital role in assisting blood bank centers and transfusion services to achieve regulatory compliance. These standards have subsequently expanded to cover the field of cellular therapies. This chapter will provide a brief history of blood banking and transfusion practices and the events leading up to the need to regulate these activities. It will also explore how the quality management system approach to regulatory compliance has been applied to the development of the AABB cell therapy standards and accreditation program.
Negative Growth Regulation of Oncogene-Transformed Mammary Epithelial Cells by Tumor Inhibitors

Deregulated expression of Ras and myc oncogenes confers neoplastic transformation in non-tumorigenic mammary epithelial cells. Down-regulation of perturbed biomarkers prior to tumorigenesis may provide a means of effective chemoprevention. In vitro experiments were designed to i) identify specific molecular, endocrine and cellular biomarkers as quantitative end points for preneoplastic transformation, and ii) utilize these end points to evaluate chemopreventive efficacy of selected naturally-occurring and synthetic tumor inhibitors. Stable Ras and myc transfectants exhibited persistent expression of oncogene specific mRNA transcripts, altered estradiol biotransformation and enhanced anchorage-independent growth in vitro prior to tumorigenesis in vivo. Treatment of the transfectants with omega-3-fatty acid, indole-3-carbinol and tamoxifen individually suppressed the perturbed molecular, endocrine and cellular biomarkers in vitro. Thus, suppressed oncogen expression and altered estrogen metabolism may be important determinants for antiproliferative mechanisms in mammary tumor inhibition, providing useful end points for chemopreventive intervention of preneoplasia.
ParLearning 2018 Invited Talk 3

Generalized linear models, such as logistic regression and support vector machines, remain some of the most widely-used techniques in the machine learning field. Their enduring popularity can be attributed to their desirable theoretical properties, effective training algorithms, and relative ease of interpretability. In this talk we will introduce Snap Machine Learning: a new library for fast training of such models, that is designed to enable new real-time and large-scale applications. The library was designed from the ground up with performance in mind. It exploits parallelism at three different levels: across multiple machines in a network, across heterogeneous compute nodes within a machine (e.g. CPU and GPU), as well as the massive parallelism offered by modern GPUs. In this talk we will review this new architecture and give examples of how the library can be used via the various APIs that are provided (e.g. Python, Apache Spark, MPI). Finally, we will present benchmarking results using the publicly available Terabyte Click Logs dataset (from Criteo Labs) and show that Snap Machine Learning can train a logistic regression classifier in 1.53 minutes, 46x faster than any of the results that have been previously reported using the same dataset.
Emerging investigators series: revisiting greenhouse gas mitigation from conventional activated sludge and anaerobic-based wastewater treatment systems

Recent literature on carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) emissions from wastewater treatment plants (WWTPs) has highlighted the poor consensus in total greenhouse gas (GHG) estimation (ranging from 0.243 to 2.4 kg CO2e per m3). In the present study, the major components of GHG emission variability in both conventional activated sludge (CAS) and mainstream anaerobic WWTPs are systematically investigated as a basis for delineating a roadmap to their future control and minimization. Through analysis of N2O generation pathways, it was determined that additional research via isotope labelling is necessary to elucidate distinct generation mechanisms in CAS WWTPs (e.g., nitrifier denitrification and hydroxylamine denitrification) and better predict N2O contributions to total GHGs. Conversely, mainstream anaerobic processes, although a potentially more sustainable alternative to conventional aerobic treatment, introduce effluent dissolved CH4 as a potentially significant GHG contributor. Sweep gas and vacuum driven membrane contactors are promising dissolved methane management strategies. However, further optimization of gas-to-liquid ratios and transmembrane pressures, respectively, are vital to balancing treatment efficiency with energy neutral/positive operation. Overall, a thorough elucidation of N2O generation pathways in CAS WWTPs and the development of effective dissolved CH4 management strategies for mainstream anaerobic processes will define their respective future roles in reducing wastewater-associated GHG emissions.
The Frontier Crimes Regulation in Colonial India: Local Critiques and Persistent Effects

AbstractIn their pursuit of self-serving goals, sometimes governments create and use various instruments as the means to relatively short-term ends. Such instruments, however, can be tenacious, and...
A Network Optimization Framework for the Analysis and Control of Traffic Dynamics and Intersection Signaling

This paper proposes a simplified version of classical models for urban transportation networks, and studies the problem of controlling intersections with the goal of optimizing network-wide congestion. Differently from traditional approaches to control traffic signaling, our simplified framework allows a more tractable analysis of the network dynamics and, yet, accurately captures the behavior of traffic flows along roads and in proximity of intersections in regimes of free flow. We cast an optimization problem to describe the goal of optimally controlling automated intersections, and relate congestion objectives with the problem of optimizing a metric of controllability of the associated dynamical system. We characterize the system performance in relation to (sub)optimal configurations, and identify conditions that guarantee network stability. Lastly, we assess the benefits of the proposed modeling and optimization framework through a microscopic simulator.
VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY IN EARLY ADULTHOOD AND SUBCLINICAL ATHEROSCLEROSIS AND ARTERIAL WALL THICKNESS BY MIDDLE AGE: THE CORONARY ARTERY RISK DEVELOPMENT IN YOUNG ADULTS (CARDIA) STUDY

Visit-to-Visit BP variability is a risk measure that is independently associated with the risk of cardiovascular disease (CVD). The mechanisms that link visit-to-visit BP variability to CVD are however incompletely studied. We examined the association between visit-to-visit BP variability in early
Visible light cure packages for improved drying kinetics in alkyd coatings

Abstract A solventborne linseed oil alkyd was formulated with two different free radical photo-initiators and a photosensitizer to enhance autoxidative crosslinking. Irgacure 784 and Irgacure 819 significantly decreased the dry-to-touch and through-cure times of alkyd systems at ambient conditions using indoor lighting. Real-time Fourier transform infrared spectroscopy, and solid state 13 C NMR were used to monitor the curing process and two mechanisms are proposed to explain the increase in crosslinking. Films were evaluated for tensile, viscoelastic, and thermal properties, indicating an increase in crosslink density. Coating performance was evaluated, significantly increasing film hardness, while maintaining appearance. However, the adhesion and chemical resistance decreased. Visible-light curable alkyds offer excellent appearance and fast curing rates, without the use of cobalt driers.
Progression of hearing loss and cochlear implantation in large vestibular aqueduct syndrome.

Abstract Objectives Large vestibular aqueduct syndrome (LVAS) is a congenital inner ear malformation that commonly results in progressive sensorineural hearing loss (SNHL) and cochlear implantation (CI). Though LVAS accounts for approximately 15% of pediatric SNHL, little is known regarding the rate and severity of SNHL in these patients. We sought to characterize the timing of SNHL progression to CI in patients with LVAS. Methods We performed a retrospective chart review at our institution from 2000 to 2018 using ICD-10 “large vestibular aqueduct syndrome,” and through identifying patients with CI who had LVAS. Demographic, surgical, and audiometric data were collected. Theoretical CI candidacy was approximated using a pure tone average (PTA) HL threshold of 70 dB. Results Of 103 patients, 96 had bilateral LVAS, and 7 had unilateral LVAS. Forty-one patients had bilateral implants, 52 had unilateral implants, and 10 were not implanted. The mean age at first implant was 8.62 years old [95%CI = 6.75,10.49], the mean age at second implant was 12.24 years old [95%CI = 8.33,16.15], and the mean time between implants was 4.37 years [95%CI = 3.02,5.73]. LVAS patients reached HL threshold of 70 dB at a mean age of 5.16 years old (SD = 3.04) for the “worse ear” and 9.08 years old (SD = 4.96) for the “better ear.” Conclusions LVAS patients are a heterogenous population of patients, in which some may undergo progression of HL and some may not. Further, there may be a discrepancy in the timing between patients’ theoretical CI candidacy and when they undergo CI. In order to optimize timing of CI, individual monitoring and close observation of LVAS patients is recommended.