cssi/SciSciGPT-SciSciNet huggingface dataset:
Drinking from the firehose of experience

Objective: Computational concepts from robotics and computer vision hold great promise to account for major aspects of the phenomenon of consciousness, including philosophically problematical aspects such as the vividness of qualia, the first-person character of conscious experience, and the property of intentionality. Methods: We present a dynamical systems model describing human or robotic agents and their interaction with the environment. In order to cope with the enormous information content of the sensory stream, this model includes trackers for selected coherent spatio-temporal portions of the sensory input stream, and a self-constructed plausible coherent narrative describing the recent history of the agent's sensorimotor interaction with the world. Results: We describe how an agent can autonomously learn its own intentionality by constructing computational models of hypothetical entities in the external world. These models explain regularities in the sensorimotor interaction, and serve as referents for the agent's symbolic knowledge representation. The high information content of the sensory stream allows the agent to continually evaluate these hypothesized models, refuting those that make poor predictions. The high information content of the sensory input stream also accounts for the vividness and uniqueness of subjective experience. We then evaluate our account against 11 features of consciousness ''that any philosophical-scientific theory should hope to explain'', according to the philosopher and prominent AI critic John Searle. Conclusion: The essential features of consciousness can, in principle, be implemented on a robot with sufficient computational power and a sufficiently rich sensorimotor system, embodied and embedded in its environment.
Inhibition of casein kinase 1-epsilon induces cancer-cell-selective, PERIOD2-dependent growth arrest.

Background Kinases are under extensive investigation as targets for drug development. Discovering novel kinases whose inhibition induces cancer-cell-selective lethality would be of value. Recent advances in RNA interference have enabled the realization of this goal.
Calibration of a self-aligning polarization analyzer

The self-aligning polarization analyzer evaluates the state of polarization of an incoming electromagnetic plane wave using (scalar) power measurements. Self-alignment is achieved utilizing three six-ports with relative orientations chosen to differ in a prescribed way. Suitable six-port circuits are defined, calibrated and optimized. The three six-ports are (simultaneously) calibrated at various angles of incidence.
Analysis of Retry Limit for Supporting VoIP in IEEE 802.11e EDCA WLANs

We present in this paper an analysis of retry limit for supporting VoIP in IEEE 802.11e EDCA WLANs. The proposed research considers packet delay as an important factor of QoS performance measure for providing time-bounded service, such as VoIP and video in WLANs which usually implement default parameters. We also present an analytical method based on a Markov chain model that allows us to derive theoretical bounds for retry limit analysis. Based on the Markov chain model that considers retry limit, we can analyze the performance of VoIP over EDCA mechanism. In addition, in order to resolve the bottleneck transmission in VoIP in the downlink of AP, we maintain that the best service can be achieved when the throughputs of uplink and downlink are the same. Such a cross performance point is studied with respect to different retry limit parameters. Finally, extensive simulations have been carried out to validate the analytical model as well as to find out the corresponding cross point. We demonstrate that an enhanced VoIP capacity can be achieved by selecting appropriate retry limit and contention window size parameters.
Fusion Activation through Attachment Protein Stalk Domains Indicates a Conserved Core Mechanism of Paramyxovirus Entry into Cells

ABSTRACT Paramyxoviruses are a large family of membrane-enveloped negative-stranded RNA viruses causing important diseases in humans and animals. Two viral integral membrane glycoproteins (fusion [F] and attachment [HN, H, or G]) mediate a concerted process of host receptor recognition, followed by the fusion of viral and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm. However, the sequence of events that closely links the timing of receptor recognition by HN, H, or G and the “triggering” interaction of the attachment protein with F is unclear. F activation results in F undergoing a series of irreversible conformational rearrangements to bring about membrane merger and virus entry. By extensive study of properties of multiple paramyxovirus HN proteins, we show that key features of F activation, including the F-activating regions of HN proteins, flexibility within this F-activating region, and changes in globular head-stalk interactions are highly conserved. These results, together with functionally active “headless” mumps and Newcastle disease virus HN proteins, provide insights into the F-triggering process. Based on these data and very recently published data for morbillivirus H and henipavirus G proteins, we extend our recently proposed “stalk exposure model” to other paramyxoviruses and propose an “induced fit” hypothesis for F-HN/H/G interactions as conserved core mechanisms of paramyxovirus-mediated membrane fusion. IMPORTANCE Paramyxoviruses are a large family of membrane-enveloped negative-stranded RNA viruses causing important diseases in humans and animals. Two viral integral membrane glycoproteins (fusion [F] and attachment [HN, H, or G]) mediate a concerted process of host receptor recognition, followed by the fusion of viral and cellular membranes. We describe here the molecular mechanism by which HN activates the F protein such that virus-cell fusion is controlled and occurs at the right time and the right place. We extend our recently proposed “stalk exposure model” first proposed for parainfluenza virus 5 to other paramyxoviruses and propose an “induced fit” hypothesis for F-HN/H/G interactions as conserved core mechanisms of paramyxovirus-mediated membrane fusion.
Shuttle mutagenesis: bacterial transposons for genetic manipulations in yeast.

Publisher Summary This chapter describes the methods and application of the Tn3 shuttle mutagenesis system. Tn3-free vectors can be used for random insertions scattered throughout the genome and used to screen for specific phenotypes linked to the insertion mutations. In shuttle mutagenesis procedure, gene (YFG) is cloned into a Tn3-free vector. A vector containing YFG (pHSS-YFG) is transformed into a pLBl01-containing strain. The resulting strain contains the pHSS-YFG target molecule and the pLB101 transposase-produeing plasmid. The transformant is then mated with a strain containing the conjugal plasmid pOX38 into which a defective minitransposon has been previously placed (pOX38::m-Tn3). Plasmid pOX38 acts as adelivery vehicle for the transposon. Transconjugants contain cointegrates between pOX38::mini-Tn3 and pHSS-YFG. The cointegmte is then resolved by conjugation with an F- strain that expresses the Cre protein from phage P1. The Cre enzyme is able to catalyze a site-specific recombination/resolution event at loxP sites carried on the Tn3-derived minitransposons. The products formed from cointegrate resolution are the original pOX38::mini-Tn3 and the target plasmid with a minitransposon insertion.
Upgrading ethanol to 1-butanol with a homogeneous air-stable ruthenium catalyst

An amide-derived N,N,N-Ru(II) complex catalyzes the conversion of EtOH to 1-BuOH with high activity. Conversion to alcohol upgraded products exceeds 250 turnovers per hour (>50% conversion) with 0.1 mol% catalyst loading. In addition to high activity for ethanol upgrading, catalytic reactions can be set up under ambient conditions with no loss in activity.
Scurvy Related to the Use of a Homemade Tube Feeding Formula

A family was administering a homemade formula to empirically treat presumed food allergies in their tube feeding–dependent child. He presented with widespread bruising and tenderness, loose teeth, ...
Community Detection in General Stochastic Block models: Fundamental Limits and Efficient Algorithms for Recovery

New phase transition phenomena have recently been discovered for the stochastic block model, for the special case of two non-overlapping symmetric communities. This gives raise in particular to new algorithmic challenges driven by the thresholds. This paper investigates whether a general phenomenon takes place for multiple communities, without imposing symmetry. In the general stochastic block model SBM (n, p, W), n vertices are split into k communities of relative siz{pi} ia#x03B5;[k], and vertices in community i and j connect independently with probability {Wij}i,j a#x03B5;[k]. This paper investigates the partial and exact recovery of communities in the general SBM (in the constant and logarithmic degree regimes), and uses the generality of the results to tackle overlapping communities. The contributions of the paper are: (i) an explicit characterization of the recovery threshold in the general SBM in terms of a new f-divergence function D+, which generalizes the Hellinger and Chern off divergences, and which provides an operational meaning to a divergence function analog to the KL-divergence in the channel coding theorem, (ii) the development of an algorithm that recovers the communities all the way down to the optimal threshold and runs in quasi-linear time, showing that exact recovery has no information-theoretic to computational gap for multiple communities, (iii) the development of an efficient algorithm that detects communities in the constant degree regime with an explicit accuracy bound that can be made arbitrarily close to 1 when a prescribed signal-to-noise ratio (defined in term of the spectrum of diag(p)W tends to infinity.
Staff Support Groups in the Helping Professions: Principles, Practice, and Pitfalls by Hartley, P., & Kennard, D. (Eds.)

Hartley and Kennard begin by stating, “It makes intuitive sense that in health care, support is needed for carers … However, the very widespread awareness of this issue is, paradoxically, matched w...
Le Portugal De Salazar Et La Droite Extrême Française (1928-1945) (Portugal Under Salazar And The French Far-Right (1928-1945))

French Abstract: La chute de la monarchie et l’instauration de la Premiere Republique en 1910 inaugurent une periode de grande instabilite politique au Portugal. Deux ans apres le coup d’Etat de 1926, Antonio de Oliveira Salazar est appele au ministere des Finances. Son nouveau regime durera jusqu'en 1974. Nous analysons les echanges et influences mutuelles entre le regime conservateur de Salazar et la droite extreme francaise jusqu'en 1945. Salazar attire des admirateurs de diverses origines: conservateurs charmes par le dictateur et par un pays fige dans son passe glorieux, et modernistes intrigues para la politique de la jeunesse et le corporatisme. Durant ces annees se developpe le mythe Salazar, mythe du bon dictateur.English Abstract: The fall of the monarchy in 1910 and the advent of the First Republic open a period of great political instability in Portugal. Two years after the coup of 1926, Antonio de Oliveira Salazar becomes Minister of Finance. The regime he instaured would last until 1974. We analyze the exchanges and mutual influences between the conservative regime of Salazar and the French far-right until 1945. Salazar managed to attract admirers from various backgrounds: conservative visitors charmed by the dictatorship and by a country glorifying its past, and modern intellectuals intrigued by his policies for the youth and for unions. The myth of Salazar grows during those years, the myth of a good dictator.
Polymorphism and polyethism in the neotropical antCephalotes Atratus (L.)

Cephalotes atratus, the “giant turtle ant” of the Neotropical tribe Cephalotini, exhibits an intermediate stage in the evolution of polymorphism. The allometric growth line is straight, but the distribution of worker sizes is bimodal. An ethogram of workers in laboratory nests showed pronounced differences in behavior according to age. Under natural conditions, individual foraging specializations based on worker size were also found. Compared to other advanced cephalotines, this species appears to be less strongly adapted for arboreal life. A model is presented for the evolution of polymorphism in ants.
Verplanck Colvin, Adirondack Surveyor: Response to Wilderness

Verplanck Colvin explored and wrote about the Adirondack region of upstate New York between the Civil War and the end of the nineteenth century. Surveyor, amateur scientist, conservationist, and indefatigable promoter of the Adirondacks, Colvin became the single most knowledgable and articulate spokesman on local issues. For roughly three decades he explored parts of the Adirondacks never before described; this was the same period in which the region was emerging as one of the nation's most popular vacation spots and in which lumbermen were making furious assaults on the wilderness. Colvin publicized the many threats facing the Adirondacks and actively advocated conservation. His annual reports, a rich and neglected contribution to American nature writing, glorified the wilderness experience and suggested a response to wilderness which built on but differed from that of the romantics who had preceded him.1
Practical Experience with Animal Models for Translational Research in MS and NMO (P5.309)

Background: Experimental Allergic Encephalomyelitis (EAE) animal models are very powerful tools for investigating candidate treatments for MS and NMO, but many technical pitfalls and misconceptions exist in the interpretation of these pre-clinical studies. Here, we summarize our recent experience with these models to highlight the strengths and weaknesses of these models and their translation to human disease. Methods: Female animals 6-8 weeks old are used. C57Bl6 mice are immunized by injecting, subcutaneously, with MOG35-55, Lewis rats with whole guinea pig MBP, and DA rats with rat MOG1-125 in adjuvant containing 4, 5, and 1mg/ml complete Freund’s adjuvant, respectively. Water must be sterile and housing, pathogen-free. Studies using genetically altered animals must have littermate controls for comparison (>13 backcrosses). Results & Conclusions: Lewis rat-MBP is a non-destructive model unless a destructive antibody is injected BEFORE peak disease. Focal destructive lesions in C57Bl6 MOG35-55 EAE are poorly linked to behavioral signs; as such, behavioral signs are a poor indicator of tissue preservation or repair. We are continuing to develop an automatable way to count axon profiles at the distal end of spinal tracts. The DA rat MOG model results in both denuded axons suitable for remyelination studies and destructive lesions, but only upon relapse. However, thus far, induction of this relapsing disease has been very sensitive to environmental interference in our hands. Translational Implications: (1) BBB breakdown is transient in these models and should not be relied upon for drug access to the CNS. (2) Do not use the Lewis rat-MBP or C57Bl-MOG35-55 model to study repair as these are primarily immunological tools (3) We propose that studies involving remyelinating drugs or cells should be performed in DA rats that are also immunosuppressed after relapse, to model patients who would be treated with disease modifying or immunomodulatory drugs while undergoing reparative treatment. Disclosure: Dr. Jones has nothing to disclose. Dr. Schwartz has nothing to disclose. Dr. Levy has received personal compensation for activities with Alexion, Guidepoint Global, and Genzyme. Dr. Levy has received research support from Acorda Therapeutics, Sanofi, Alexian, TG Therapeutics, and TerumoBCT.
Constitutional Interpretation as Structured Choice

Professor Davis challenges lawyers and judges to acknowledge the inevitability of choice in judicial decision-making, to make doctrinal choices explicit, and to structure choice in the development of doctrine to maximize transparency and reasoned debate.
The Politics of Strolling

The large gatherings of youths from impoverished urban peripheries in the shopping malls of Sao Paulo and Rio, known as rolezinhos (little strolls), in the first two months of 2014 and their disput...
Exergy based optimization of rocket system staging times

Exergy is defined as the useful work available to a system. Exergy efficiency is an overall system metric that integrates across disciplines where exergy is used as a "common currency. " The use of exergy efficiency gives an overall performance metric which accounts for interactions and couplings between systems. As a holistic metric designers can focus on modifying design variables to improve exergy efficiency. The process of modifying design variables is the focus of Multidisciplinary Design Optimization (MDO), which combines multidisciplinary analysis and optimization methods to form useful design frameworks for large, complex systems. The proposed paper will explore the utilization of MDO with exergy-based analysis in order to optimize the staging times of a rocket system.
Update on obesity treatment

Although the formula for weight control is a simple matter, namely ensure that calories consumed equals calories expended, its implementation is a source of great frustration for an estimated 85 million Americans. This results in an estimated 40 billion dollars spent each year in health and related treatment costs. This review outlines the epidemiology, health consequences, and treatment of obesity with an emphasis on newer developments in our understanding of the etiology of obesity and its treatment.
The Future of Sport Philosophy in Higher Education Kinesiology.

ABSTRACTMassengale’s Trends Toward the Future of Physical Education (1987) makes no reference to the existence of the philosophic inquiry of physical activity within higher education kinesiology programs—even though the sub-discipline had been formalized by academics in the early 1970s. In contrast, Massengale and Swanson’s The History of Exercise and Sport Science (1997) dedicated a chapter to sport philosophy’s development, including a prognosis of its future. Since then, there has been tremendous growth in the sub-discipline, including an increase in publication outlets, stand-alone monographs, and the creation of academic associations globally. Yet this growth has not necessarily secured sport philosophy’s place in higher education curriculum. In this article, we briefly review the history of philosophic inquiry into physical activity and review previous predictions of the sub-discipline’s future before offering our own prognostication of its future in higher education.
Parameter estimation in the Burgers equation using retrospective-cost model refinement

We apply retrospective cost model refinement to parameter estimation in a nonlinear partial differential equation. Specifically, for the scalar Burgers equation, we estimate the viscosity from measurements of flow velocity at a single grid point. We also consider the analogous problem for a modified Burgers equation as a proxy for a large eddy simulation to estimate a parameter that relates subgrid-scale stresses to the resolved strain rate.
Part I The Journey

The reader is taken on a journey alongside the author’s evolving relationship to the Moments project, an empirical study of the moments people remember from their lives. Moments are first introduced as a scholarly object of inquiry related to contemporary issues in the field of narrative identity. As the moments are collected and analyzed, however, a different relation to the moments emerges, a relation that explores the decontexted experience of moments, not as indicative of traumatic fragmentation, but as a normative phenomenon and a viable, although neglected, mode of healthy identity formation. Moments are viewed from their characteristic of having an inherent coherence in contrast to narrative meanings that are products of a construction process.
The viscosity of planetary tholeiitic melts: A configurational entropy model

Abstract The viscosity (η) of silicate melts is a fundamental physical property controlling mass transfer in magmatic systems. Viscosity can span many orders of magnitude, strongly depending on temperature and composition. Several models are available that describe this dependency for terrestrial melts quite well. Planetary basaltic lavas however are distinctly different in composition, being dominantly alkali-poor, iron-rich and/or highly magnesian. We measured the viscosity of 20 anhydrous tholeiitic melts, of which 15 represent known or estimated surface compositions of Mars, Mercury, the Moon, Io and Vesta, by concentric cylinder and parallel plate viscometry. The planetary basalts span a viscosity range of 2 orders of magnitude at liquidus temperatures and 4 orders of magnitude near the glass transition, and can be more or less viscous than terrestrial lavas. We find that current models under- and overestimate superliquidus viscosities by up to 2 orders of magnitude for these compositions, and deviate even more strongly from measured viscosities toward the glass transition. We used the Adam–Gibbs theory (A–G) to relate viscosity (η) to absolute temperature (T) and the configurational entropy of the system at that temperature (Sconf), which is in the form of log η = A e + B e / TS conf . Heat capacities (CP) for glasses and liquids of our investigated compositions were calculated via available literature models. We show that the A–G theory is applicable to model the viscosity of individual complex tholeiitic melts containing 10 or more major oxides as well or better than the commonly used empirical equations. We successfully modeled the global viscosity data set using a constant Ae of −3.34 ± 0.22 log units and 12 adjustable sub-parameters, which capture the compositional and temperature dependence on melt viscosity. Seven sub-parameters account for the compositional dependence of Be and 5 for Sconf. Our model reproduces the 496 measured viscosity data points with a 1σ root-mean-square deviation (rmsd) of 0.12 log units across 13 orders of measured melt viscosity. The model performed well in predicting the viscosity of lunar and martian melts not used in calibration, and should be used to calculate lava flow velocities and fluxes for anhydrous basaltic volcanism on other moons and planets.
RF-interconnect for future inter- and intra-ULSI communications

Future ULSI interconnect system demands extremely high data rate (up to 100Gbps/channel or 20Tbps/chip) as well as multi-I/O service, re-configurable and fault-tolerant computing/processing architecture and total compatibility with the mainstream silicon CMOS and MCM technologies. In this paper, we present a novel RF-interconnect system that promises to meet all of those system needs. The intended "active" RF-interconnect is based on principles of near-field capacitive coupling, low-loss microwave signal transmission and modern multiple-access algorithms (such as CDMA and FDMA) for shared transmission medium. We will address issues relevant to RF-interconnect system design and discuss its advantages in speed, signal integrity and channel reconfiguration. As a proof of concept, we have realized on-chip 2/spl times/2 CDMA-interconnect system and FDMA/CDMA combined RF-interconnects in 0.18/spl mu/m CMOS with complete functions of signal coupling, transmission and channel reconfiguration at the clock speed of f/sub clk/=2.8GHz and 5GHz RF carrier.
Latino Health Behavior: An Exploratory Analysis of Health Risk and Health Protective Factors in a Community Sample.

Background. Demographic and cultural factors have been found to affect health behaviors in Latinos in both positive and negative ways, but few studies have examined the impact of culture and adhere...
A compressive channel estimation technique robust to synchronization impairments

Initial access at millimeter wave frequencies is a challenging problem due to hardware non-idealities and low SNR measurements prior to beamforming. Prior work has exploited the observation that mmWave MIMO channels are sparse in the spatial angle domain and has used compressed sensing based algorithms for channel estimation. Most of them, however, ignore hardware impairments like carrier frequency offset and phase noise, and fail to perform well when such impairments are considered. In this paper, we develop a compressive channel estimation algorithm for narrowband mmWave systems, which is robust to such non idealities. We address this problem by constructing a tensor that models both the mmWave channel and CFO, and estimate the tensor while still exploiting the sparsity of the mmWave channel. Simulation results show that under the same settings, our method performs better than comparable algorithms that are robust to phase errors.
Bivalirudin versus heparin in patients undergoing percutaneous transcatheter aortic valve interventions: A systematic review and meta-analysis.

Background Bivalirudin may be an effective anticoagulation alternative to heparin as anticoagulant agent in percutaneous transcatheter aortic valve interventions (PAVI). We aimed to compare safety and efficacy of bivalirudin versus heparin as the procedural anticoagulant agent in patients undergoing PAVI. Methods We conducted an electronic database search of all published data. The primary efficacy endpoints were all-cause mortality, cardiovascular mortality, myocardial infarction, and stroke. Safety endpoints include major and life-threatening bleed according to VARC and BARC bleeding, blood transfusion, vascular complications, and acute kidney injury. Odds ratios (OR) and 95% confidence intervals (CI) computed using the Mantel-Haenszel method. Results Three studies (n = 1690 patients) were included, one randomized trial and two observational studies. There was a significant difference favoring bivalirudin over heparin for myocardial infarction (OR 0.41, 95%CI 0.20-0.87). There was no significant difference in all-cause mortality at 30 days (OR 0.97, 95%CI 0.62-1.52), cardiovascular mortality (OR 1.03, 95%CI 0.52-2.05), stroke (OR 1.23, 95%CI 0.62-2.46), vascular complications (OR 0.96, 95%CI 0.70-1.32), acute kidney injury (OR 1.03, 95%CI 0.53-2.00), blood transfusion (OR 0.67, 95% CI 0.45-1.01), major and life-threatening bleed (OR 0.74, 95%CI 0.37-1.49), and BARC bleeding (OR 0.52, 95%CI 0.23-1.18). Conclusions In patient undergoing aortic valve interventions, no difference was seen between the use of bivalirudin and heparin as the procedural anticoagulant agent, except for a significant lower myocardial infarction events when bivalirudin was used. Further large randomized trials are needed to confirm current results.
A Comparative Analysis of Domestic Violence Shelter Staff Perceptions Regarding Barriers to Services in Bosnia and Herzegovina and the United States.

Service provision for domestic violence (DV) survivors has been a long-standing staple of shelters in the United States. Although shelter services provide numerous benefits for survivors, barriers ...
Participatory mobile- and web-based tools for eliciting landscape knowledge and perspectives: introducing and evaluating the Wisconsin geotools project

Despite synergistic goals across a wide breadth of fields and modalities, coastal landscape conservation projects that engage the lay public and integrate narratives of place remain elusive. This paper addresses these needs by introducing and evaluating the Wisconsin Geotools, an integrated pair of mobile-and web-based applications that allow users to generate and share spatially defined multimedia observations — including photos, short textual descriptions (or journals), and audio and video clips — of their surrounding bioregional landscapes. We followed a participatory, user-centered design process to develop a mobile application that uses GPS capabilities to geolocate multimedia observations of landscapes and feed them into a web-based application, which displays content through the structure of an interactive story map. The applications were piloted with coastal community user groups in Green Bay (Lake Michigan), Wisconsin, USA. Over 800 observations were recorded by participants in our study area. Results from a user evaluation survey indicate the geotools effectively engaged participants in learning about and exploring their surrounding coastal landscapes. A spatial analysis revealed participants’ affinity for water-related features in landscapes. We close by suggesting a variety of ways in which these tools can support future projects and existing methodologies that are advancing transdisciplinary approaches to engaging the public in coastal conservation.
Predicting Code Hotspots in Open-Source Software from Object-Oriented Metrics Using Machine Learning

Software engineers are able to measure the quality of their code using a variety of metrics that can be derived directly from analyzing the source code. These internal quality metrics are valuable ...
The Past Will Not Stay Buried: Female Bodies and Colonial Crime in the Australian Ghost Stories of Mary Fortune

This chapter discusses the Gothic short stories of Mary Fortune, one of the pioneering writers of detective fiction in the nineteenth century. Over the course of several decades, Fortune contributed numerous stories to the Australian Journal under the pseudonym “Waif Wander.” This chapter builds on previous discussions of Fortune as a detective story writer to consider how she appropriated the Colonial Gothic through examinations of violent crimes against colonial Australian women. The chapter begins with a discussion of two early Fortune stories which feature the recurring character Mark Sinclair, a Hobart-based detective: “Mystery and Murder” (1866) and “The Illumined Grave” (1867). The chapter then moves to a discussion of “The Old Shaft” (1886). In each of these stories that appeared in the Australian Journal, the murdered women return as revenants set on bringing their killers to justice and “speaking” the trauma of their premature deaths. Through the portrayal of these female ghosts, Fortune critiques issues of physical and sexual violence against women, as well as the precarious nature of women’s safety within colonial Australia.
Abstract TP67: Safety of Intravenous Alteplase in Chronic Intracranial Hemorrhage: a Five Year Multicenter Study

Introduction: Although, the recently updated tPA label removed a history of intracranial hemorrhage (ICH) as a contraindication, there is very limited data on the safety of intravenous thrombolysis in chronic ICH. The purpose of this study is to evaluate the safety of intravenous tPA among patient with chronic ICH. Methods: We analyzed consecutive patients who received intravenous tPA for stroke symptoms at three tertiary stroke centers in a five-year period. Patients without imaging confirmation of the old hemorrhage were excluded from the study. Outcome measures in our study were occurrences of symptomatic ICH and were defined according to European Cooperative Acute Stroke Study (ECASS)-III criteria combined with clinical deterioration of ≥4 points on NIHSS or death. Results: Out of 1212 post tPA patients evaluated in this study, seven patients (age 72 ± 11, four men, median NIHSS 5, IQR [2-8], volume ICH 1-21 cm3) had a history and neuroimaging findings consistent with an old ICH. Patients with old ICH did not differ in terms of rates of symptomatic ICH (0%, 95%CI (0-32%) by the adjusted Wald method versus 3.6%, p=0.61) and in-hospital mortality (0% versus 6.0%, p=0.5) when compared with the rest of patients. There was no significance difference between two groups in terms of age and admission NIHSS. Out of seven patients, five patients had ICH in basal ganglia and two patients had ICH in pre-ventricular white matter region. Discussion: Our study indicates that administration of intravenous tPA is safe among patients with a history of chronic ICH. More studies are needed to define chronic in such a setting.
Pharmacological and molecular dynamics analyses of differences in inhibitor binding to human and nematode PDE4: Implications for management of parasitic nematodes.

Novel chemical controls are needed that selectively target human, animal, and plant parasitic nematodes with reduced adverse effects on the host or the environment. We hypothesize that the phosphodiesterase (PDE) enzyme family represents a potential target for development of novel nematicides and anthelmintics. To test this, we identified six PDE families present in the nematode phylum that are orthologous to six of the eleven human PDE families. We characterized the binding interactions of family-selective PDE inhibitors with human and C. elegans PDE4 in conjunction with molecular dynamics (MD) simulations to evaluate differences in binding interactions of these inhibitors within the PDE4 catalytic domain. We observed that roflumilast (human PDE4-selective inhibitor) and zardaverine (selective for human PDE3 and PDE4) were 159- and 77-fold less potent, respectively, in inhibiting C. elegans PDE4. The pan-specific PDE inhibitor isobutyl methyl xanthine (IBMX) had similar affinity for nematode and human PDE4. Of 32 residues within 5 A of the ligand binding site, five revealed significant differences in non-bonded interaction energies (van der Waals and electrostatic interaction energies) that could account for the differential binding affinities of roflumilast and zardaverine. One site (Phe506 in the human PDE4D3 amino acid sequence corresponding to Tyr253 in C. elegans PDE4) is predicted to alter the binding conformation of roflumilast and zardaverine (but not IBMX) into a less energetically favorable state for the nematode enzyme. The pharmacological differences in sensitivity to PDE4 inhibitors in conjunction with differences in the amino acids comprising the inhibitor binding sites of human and C. elegans PDE4 catalytic domains together support the feasibility of designing the next generation of anthelmintics/nematicides that could selectively bind to nematode PDEs.
VALIDATION OF ELECTRONIC HEALTH RECORD-BASED ASCERTAINMENT OF OBSESSIVE COMPULSIVE DISORDER CASES AND CONTROLS

Background Obsessive-Compulsive Disorder (OCD) is a common, disabling psychiatric disorder characterized by intrusive thoughts, images, or impulses that typically cause anxiety or distress (obsessions), and by repetitive mental acts or behaviors that one feels compelled to do (compulsions). Initial Genome-Wide Association Studies (GWAS) for OCD were underpowered to identify individual risk variants but clearly indicated that OCD is a heritable complex genetic trait and that increased sample size will yield significant loci. The use of existing Electronic Medical Records (EMR) in the US and other countries represents another rapid and cost-efﬁcient strategy to increase ascertainment for OCD genomic studies. Methods BioVU is a repository of over 250,000 DNA samples extracted from discarded blood collected during routine clinical testing at Vanderbilt University Medical Center. The DNA samples obtained are linked to a de-identified Electronic Medical Record (EMR) datamart called the Synthetic Derivative containing clinical information extracted from over 2.2 million individuals in a searchable form covering the past 20 years. We thus undertook the task of building a diagnostic algorithm for OCD which could be applied to the EMR. To do this, we utilized ICD 9 and 10 codes (300.3 and F42.⁎) along with Natural Language Processing (NLP) to detect context-aware diagnostic keywords (e.g., Obsessive-compulsive, etc.), treatment keywords (e.g., cognitive-behavioral, etc.), and medications (e.g., fluoxetine, etc.) commonly prescribed for the treatment of OCD. Contextual information from 50 cases identified by the algorithm was then abstracted by trained non-expert reviewers and abstracted charts were reviewed by two domain experts to determine the Positive Predictive Value (PPV) of the algorithm. Results Our algorithm identified 7,547 OCD cases in the EMR and PPV was high (> 92%) across the two reviewers with high interrater reliability when all algorithm elements including ICD codes, diagnostic keywords, and treatment keywords were present in case charts. We then analyzed the PPV amongst the different ways in which the cases met criteria. Of these 7,547 potential cases, 1,528 have DNA available within the BioVU biobank. We are in the process of genotyping all of these OCD cases, along with matched controls, on the Illumina MEGA array, in preparation for GWAS. Results will be meta-analyzed with those from the PGC TS/OCD Working Group. Discussion We have designed and validated a phenotype algorithm for the ascertainment of OCD cases from electronic medical records. This algorithm can be deployed in any EMR and we will make it freely available in a forthcoming publication.
Catabolism and excretion of fibrinopeptide-A.

Mean urinary excretion of fibrinopeptide-A (FPA) in 51 normal individuals ranging in age from 7 to 92 yr was 1.67 ± .1 (SE) μg/24 hr with no significant differences related to age or sex, though children tended to excrete less FPA. Calculation suggests that FPA urinary excretion represents 0.2%–0.5% of total FPA released from fibrinogen/24 hr. Urinary FPA eluted from gel permeation columns in the same position as 12BI-FPA. 126I-FPA (human) was cleared from dog plasma with a half-life of 3.9 min, and 0.5% of the total dose could be accounted for in the urine over a 3-hr period. FPA assay in paired plasma and 24-hr urine samples from 15 normal individuals, 16 patients with malignancy, 3 patients with other disease, and 5 patients with severe burns (several samples from each) demonstrated significant correlation between plasma FPA concentration and 24-hr urinary FPA excretion (p
Structures That Protect Coastal Populations, Assets, and GDPs: Sea Dikes, Breakwaters, Seawalls

In 2018, about one billion people of the Earth’s 7.6 billion lived in marine coastal zones. The people, their property, and the infrastructure that supports them, and a city or national per capita GDP are at risk at multiple levels. These include coastal erosion, high and spring tides that cause lowland flooding, weather-related events (storm surges, flooding, wind, crop loss, unprotected anchorage, stabilization of navigation channels, and rarely, killer tsunamis). These coastal zones now, and more so in the future, are likely to be at high risk because of global warming-driven sea level rise. Human activity inshore can increase the level of risk from the above cited sources, such as flooding by abetting subsidence because of overuse of coastal aquifers for a water supply. Dikes, breakwaters, sea walls, and related structures are designed to thwart for some time (50 years?) damaging, destructive forces that assault coastal regions worldwide. They are costly to build and maintain but in short and long terms present economic benefits that preserve much, much more in capital investment.
Inability to Achieve Adequate Left Ventricular Unloading Predicts Hospitalization or Death after Invasive Optimization in LVAD Patients

Background A left heart catheterization optimization protocol was recently developed at our institution and several physiologic indices, including LV end diastolic pressure (LVEDP) and trans-aortic gradient (TAG), previously only available in computational or animal models, were evaluated in patients supported on LVAD therapy. We sought to evaluate the prognostic significance of these markers. Hypothesis Inability to achieve adequate ventricular unloading will result in worse heart failure hospitalization-free survival. Methods All patients undergoing combined left and right heart catheterization protocol at our institution between 2015 and 2018 were evaluated. Patients whose left ventricles were inaccessible or who underwent non-standard protocols were excluded. Comprehensive clinical data were obtained. Primary endpoints included a composite outcome of hospitalization or death and overall survival. Results Thirty one patients were analyzed from the cohort. Optimization resulted in normalization of hemodynamic parameters on average (RA 11 mmHg, PA 25 mmHg, PCWP 13 mmHg, LVEDP 12 mmHg, cardiac index 2.53 L/min/m2), which was significantly improved from baseline for all variables [p ≤ 0.05]). On univariate modeling, only LVEDP was associated with the primary endpoint (HR 1.2 per 1 mmHg increase, CI[1.1-1.3], p Conclusions Left ventricular offloading as measured by left ventricular end-diastolic pressure was a significant marker of poor outcomes over time. Further research should focus on pathophysiology corresponding to poor unloading.
Transition state theory for enzyme kinetics

This article is an essay that discusses the concepts underlying the application of modern transition state theory to reactions in enzymes. Issues covered include the potential of mean force, the quantization of vibrations, the free energy of activation, and transmission coefficients to account for nonequilibrium effect, recrossing, and tunneling.
Letter from Interim Director, Doctorate in Educational Leadership

A letter from Dr. Rose Borunda, the interim director of the Doctorate in Educational Leadership program at California State University, Sacramento
Ammonia Predicts Hepatic Involvement and Pulmonary Hypertension in Patients With Hereditary Hemorrhagic Telangiectasia.

INTRODUCTION Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) is common and can be associated with severe clinical consequences, including portal hypertension, cardiac failure, and encephalopathy. However, there are no reliable clinical predictors of hepatic involvement and its associated complications, limiting appropriate identification of these patients. In this work, we define the utility of serum ammonia and liver biochemical tests (LFTs) in predicting hepatic HHT involvement and its complications. METHODS We performed a retrospective study examining a well-characterized cohort of patients with HHT. Clinical characteristics, laboratory tests, liver imaging, transthoracic echocardiography assessment of right ventricular systolic pressure (RVSP), and history of other HHT-related outcomes were assessed. Patients were followed for the development of encephalopathy. RESULTS Of 45 patients with definite HHT, 18 (40%) had elevated ammonia levels. An elevated ammonia associated with the presence of hepatic arteriovenous malformations (AVMs) on imaging (P 35 mm Hg), providing an 80% sensitivity and 71% specificity for predicting the presence of pulmonary hypertension. In contrast, there was no association with an elevated serum ammonia and encephalopathy over a total of 859 months of follow-up. DISCUSSION Elevated ammonia in a cohort of patients with HHT was associated with the presence of hepatic AVMs and elevated RVSP, but no other complications of HHT, including encephalopathy.
SAFETY OF MAGNETIC RESONANCE IMAGING (MRI) IN PATIENTS WITH A PACEMAKER OR DEFIBRILLATOR WITH EPICARDIAL AND/OR ABANDONED LEADS

Abandoned and epicardial leads from cardiovascular implantable electronic devices (CIED) remains a contraindication to magnetic resonance imaging (MRI) studies due to previous in vitro data showing lead heating and a theoretical concern for device malfunction. We postulated that a MRI in patients
A Physics-Motivated DNN for X-Ray CT Scatter Correction

The scattering of photons by the imaged object in X-ray computed tomography (CT) produces degradations of the reconstructions in the form of streaks, cupping, shading artifacts and decreased contrast. We describe a new physics-motivated deep-learning-based method to estimate scatter and correct for it in the acquired projection measurements. The method incorporates both an initial reconstruction and the scatter-corrupted measurements using a specific deep neural network architecture and a cost function tailored to the problem. Numerical experiments show significant improvement over a recent projection-based deep neural network method.
JAK/STAT pathway inhibition sensitizes CD8 T cells to dexamethasone-induced apoptosis in hyperinflammation

Cytokine storm syndromes (CSS) are severe hyperinflammatory conditions characterized by excessive immune system activation leading to organ damage and death. Hemophagocytic lymphohistiocytosis (HLH), a disease often associated with inherited defects in cell-mediated cytotoxicity, serves as a prototypical CSS for which the 5-year survival is only 60%. Frontline therapy for HLH consists of the glucocorticoid dexamethasone (DEX) and the chemotherapeutic agent etoposide. Many patients, however, are refractory to this treatment or relapse after an initial response. Notably, many cytokines that are elevated in HLH activate the JAK/STAT pathway, and the JAK1/2 inhibitor ruxolitinib (RUX) has shown efficacy in murine HLH models and humans with refractory disease. We recently reported that cytokine-induced JAK/STAT signaling mediates DEX resistance in T cell acute lymphoblastic leukemia (T-ALL) cells, and that this could be effectively reversed by RUX. On the basis of these findings, we hypothesized that cytokine-mediated JAK/STAT signaling might similarly contribute to DEX resistance in HLH, and that RUX treatment would overcome this phenomenon. Using ex vivo assays, a murine model of HLH, and primary patient samples, we demonstrate that the hypercytokinemia of HLH reduces the apoptotic potential of CD8 T cells leading to relative DEX resistance. Upon exposure to RUX, this apoptotic potential is restored, thereby sensitizing CD8 T cells to DEX-induced apoptosis in vitro and significantly reducing tissue immunopathology and HLH disease manifestations in vivo. Our findings provide rationale for combining DEX and RUX to enhance the lymphotoxic effects of DEX and thus improve the outcomes for patients with HLH and related CSS.
Zips: Experimental Lines of Flight

By applying a few of the concepts and transformative tools presenting in many of Deleuze?s texts, Barnett Newman?s paintings receive a much-needed re-interpretation. In many of Newman?s paintings, the fields of colors and the pulsating zips that sear through these vast landscapes can be seen as intensive sensations pushing away from philosophical and artistic domains that cling to images of thought rooted in recognition and binarism. The function of such a Deleuzian reading of Barnett Newman is to evoke the potentiality for destabilization so that one is able to create new sensations, new ways of conceiving of painting and life that are never able to be captured by a single system of signification. Rather than the desire to imitate, represent, or capture, Newman is able to mark an intensive threshold of becoming. Beneath a representational regime is a plane of imperceptible forces that traverse the face of the painting and extend beyond the canvas infinitely in every direction.