cssi/SciSciGPT-SciSciNet huggingface dataset:
Replication routing in DTNs: a resource allocation approach

Routing protocols for disruption-tolerant networks (DTNs) use a variety of mechanisms, including discovering the meeting probabilities among nodes, packet replication, and network coding. The primary focus of these mechanisms is to increase the likelihood of finding a path with limited information, and so these approaches have only an incidental effect on such routing metrics as maximum or average delivery delay. In this paper, we present rapid, an intentional DTN routing protocol that can optimize a specific routing metric such as the worst-case delivery delay or the fraction of packets that are delivered within a deadline. The key insight is to treat DTN routing as a resource allocation problem that translates the routing metric into per-packet utilities that determine how packets should be replicated in the system. We evaluate rapid rigorously through a prototype deployed over a vehicular DTN testbed of 40 buses and simulations based on real traces. To our knowledge, this is the first paper to report on a routing protocol deployed on a real outdoor DTN. Our results suggest that rapid significantly outperforms existing routing protocols for several metrics. We also show empirically that for small loads, RAPID is within 10% of the optimal performance.
Proton pump inhibitors induce changes in colonocyte gene expression that may affect Clostridium difficile infection

Background. Proton pump inhibitors seem to promote Clostridium difficile infection (CDI). Although the current literature suggests that this association is mediated through gastric acid suppression, there has been little investigation into whether a direct effect on expression of colonocyte genes may also have a role. The aim of this study was to investigate the effect of omeprazole on genome-wide gene expression in a human colonic cell line. Methods. T84 cell monolayers were treated with acid-activated omeprazole at 0, 1, 10, or 100 mmol/L for 48 hours. Cells were lysed and total RNA samples were reverse transcribed and used to generate biotinylated cRNA. Whole-genome transcript expression levels were then quantified using an Illumina HT-12 BeadChip microarray targeting 25,440 genes. Transcripts with a stringent minimum absolute fold change of 1.5 and an adjusted nominal P value <.05 (false discovery) were identified as being differentially expressed. Results. Significant changes in expression were observed for 322 colonocyte transcripts, including genes with potential implications for susceptibility to CDI. These genes include roles in cell junctions, toxin susceptibility, and bile acid metabolism and transport. Conclusion. Omeprazole treatment decreases the expression of genes that have important functions in colonocyteintegrity.SuchimpairmentincolonocytefunctionmaypromoteCDI.(Surgery2014;156:972-8.)
Laminar and Orientation-Dependent Characteristics of Spatial Nonlinearities: Implications for the Computational Architecture of Visual Cortex

A full understanding of the computations performed in primary visual cortex is an important yet elusive goal. Receptive field models consisting of cascades of linear filters and static nonlinearities may be adequate to account for responses to simple stimuli such as gratings and random checkerboards, but their predictions of responses to complex stimuli such as natural scenes are only approximately correct. It is unclear whether these discrepancies are limited to quantitative inaccuracies that reflect well-recognized mechanisms such as response normalization, gain controls, and cross-orientation suppression or, alternatively, imply additional qualitative features of the underlying computations. To address this question, we examined responses of V1 and V2 neurons in the monkey and area 17 neurons in the cat to two-dimensional Hermite functions (TDHs). TDHs are intermediate in complexity between traditional analytic stimuli and natural scenes and have mathematical properties that facilitate their use to test candidate models. By exploiting these properties, along with the laminar organization of V1, we identify qualitative aspects of neural computations beyond those anticipated from the above-cited model framework. Specifically, we find that V1 neurons receive signals from orientation-selective mechanisms that are highly nonlinear: they are sensitive to phase correlations, not just spatial frequency content. That is, the behavior of V1 neurons departs from that of linear-nonlinear cascades with standard modulatory mechanisms in a qualitative manner: even relatively simple stimuli evoke responses that imply complex spatial nonlinearities. The presence of these findings in the input layers suggests that these nonlinearities act in a feedback fashion.
Low prevalence of necrolytic acral erythema in patients with chronic hepatitis C virus infection

Background Chronic hepatitis C virus (HCV) infection is associated with necrolytic acral erythema (NAE). However, the prevalence of NAE among patients with HCV is unknown, and the clinical and histologic features have not been well defined. Objective We sought to determine the prevalence, overall clinical features, and cutaneous histopathological characteristics of patients with NAE. Methods A cross-sectional study was performed among patients with chronic HCV infection cared for at 3 Philadelphia hospitals. Patients completed a questionnaire and underwent a dermatologic examination. All undiagnosed skin lesions with clinical features of NAE as described in the literature underwent skin biopsy. Results Among 300 patients with chronic HCV infection (median age 55 years; 73% male; 70% HCV genotype 1), 5 of them (prevalence 1.7%; 95% confidence interval 0.5%-3.8%) had skin lesions consistent with NAE clinically, which were analyzed and confirmed with skin biopsy specimen. All 5 skin biopsy specimens demonstrated variable psoriasiform hyperplasia, mild papillomatosis, parakeratosis, and necrotic keratinocytes in the superficial epidermis. All 5 patients were older than 40 years, were African American men, were infected with HCV genotype 1, and had a high viral load (>200,000 IU/mL). Limitations Previous descriptions of NAE were used to guide the evaluation and need for a biopsy; however, other unknown clinical characteristics of the disease may exist. The senior author was the sole interpreter of the biopsy specimens. Only 300 of the 2500 eligible patients enrolled in the study. Conclusion The prevalence of NAE among patients with chronic HCV in this sample was very low. Further research is needed to determine the origin and appropriate therapies of NAE.
Functional Analysis of V3A and Related Areas in Human Visual Cortex

Using functional magnetic resonance imaging (fMRI) and cortical unfolding techniques, we analyzed the retinotopy, motion sensitivity, and functional organization of human area V3A. These data were compared with data from additional human cortical visual areas, including V1, V2, V3/VP, V4v, and MT (V5). Human V3A has a retinotopy that is similar to that reported previously in macaque: (1) it has a distinctive, continuous map of the contralateral hemifield immediately anterior to area V3, including a unique retinotopic representation of the upper visual field in superior occipital cortex; (2) in some cases the V3A foveal representation is displaced from and superior to the confluent foveal representations of V1, V2, V3, and VP; and (3) inferred receptive fields are significantly larger in human V3A, compared with those in more posterior areas such as V1. However, in other aspects human V3A appears quite different from its macaque counterpart: human V3A is relatively motion-selective, whereas human V3 is less so. In macaque, the situation is qualitatively reversed: V3 is reported to be prominently motion-selective, whereas V3A is less so. As in human and macaque MT, the contrast sensitivity appears quite high in human areas V3 and V3A.
Detectability of certain dark-matter candidates.

We consider the possibility that the neutral-current neutrino detector recently proposed by Drukier and Stodolsky could be used to detect some possible candidates for the dark matter in galactic halos. This may be feasible if the galactic halos are made of particles with coherent weak interactions and masses 1--${10}^{6}$ GeV; particles with spin-dependent interactions of typical weak strength and masses 1--${10}^{2}$ GeV; or strongly interacting particles of masses 1--${10}^{13}$ GeV.
Microcellular processing of polylactide–hyperbranched polyester–nanoclay composites

The effects of addition of hyperbranched polyesters (HBPs) and nanoclay on the material properties of both solid and microcellular polylactide (PLA) produced via a conventional and microcellular injection-molding process, respectively, were investigated. The effects of two different types of HBPs (i.e., Boltorn H2004® and Boltorn H20®) at the same loading level (i.e., 12%), and the same type of HBP at different loading levels (i.e., Boltorn H2004® at 6 and 12%), as well as the simultaneous addition of 12% Boltorn H2004® and 2% Cloisite®30B nanoclay (i.e., HBP–nanoclay) on the thermal and mechanical properties (both static and dynamic), and the cell morphology of the microcellular components were noted. The addition of HBPs and/or HBP with nanoclay decreased the average cell size, and increased the cell density. The stress–strain plots of all the solid and microcellular PLA-H2004 blends showed considerable strain softening and cold drawing, indicating a ductile fracture mode. Among the two HBPs, samples with Boltorn H2004® showed higher strain-at-break and specific toughness compared to Boltorn H20®. Moreover, the sample with Boltorn H2004® and nanoclay exhibited the highest strain-at-break (626% for solid and 406% for microcellular) and specific toughness (405% for solid and 334% for microcellular). Finally, the specific toughness, strain-at-break, and specific strength of microcellular samples were found to be lower than their solid counterparts.
Managing corporate strategy to cope with change

It is hard to find a reasonably informed person today who is not aware that the rate of change all around us has become not only inconvenient, uncomfortable, disconcerting or confusing, but outright dangerous with respect to the future of whole countries, socio‐economic systems, and certainly some private corporations—if not private enterprise as such.
Turbulent heat and momentum transfer for gases in a circular tube at wall to bulk temperature ratios to seven

Abstract Measurements are reported for local friction and heat-transfer coefficients with constant heat flux in an electrically heated circular tube. Precooled nitrogen in turbulent flow was used to obtain local wall to bulk temperature ratios from 1·24 to 7·54. The Inconel test section had a 40 diameter hydrodynamic entry section and a 160 diameter heated section. The bulk inlet Reynolds numbers covered the range from 18 300 to 279 000. Correlations in terms of both the bulk and the modified wall Reynolds numbers are presented for the local friction factors; the local heat-transfer results are presented in terms of the wall to bulk temperature ratio with bulk properties and also directly on the modified wall Reynolds number. Both the friction and heat-transfer results are shown to be significantly affected by the influence of the variable properties. Entrance region effects for both the heat-transfer and friction coefficients are discussed.
Applications of numbered undirected graphs

Numbered undirected graphs are becoming an increasingly useful family of mathematical models for a broad range of applications. They have found usage in various coding theory problems, including the design of good radar-type codes, synch-set codes and convolutional codes with optimal autocorrelation properties. They facilitate the optimal nonstandard encodings of integers. They have also been applied to determining ambiguities in X-ray crystallographic analysis, to design of a communication network addressing system, to determination of optimal circuit layouts, and to problems in additive number theory. An attempt has been made to systematically present all of these diverse applications in a unifying framework and to indicate the existence of additional applications and to suggest directions for additional research.
The specification of a robust network

The authors describe the process used to specify a robust network using the Spec specification language, which is intended for giving black-box specifications of large software systems in the early stages of software design and in the software evolution process. The underlying computational model of Spec combines temporal events with message passing to support system descriptions. The authors illustrate the use of the Spec language to define the behavior of a robust distributed system with timing constraints. The robust network specified is a simplified bidirectional-ring network. >
Impact of Tillage Practices on Hessian Fly-Susceptible and Resistant Spring Wheat Cultivars

Abstract Hessian fly, Mayetiola destructor (Say), is a residue-borne pest of spring wheat that can become important in reduced tillage production systems. The relative abundance of Hessian fly was examined on spring wheat cultivars grown under conventional tillage (CT) and no-tillage (NT) practices in northern Idaho from 2000 to 2002. Six cultivars were tested: Hessian fly-susceptible ‘Penawawa’ and ‘Westbred 936’ and -resistant (H3 gene) ‘Wawawai’, ‘Jefferson’, ‘Hank’, and ‘Westbred 926.’ Hessian fly egg densities were not significantly different among treatments, indicating ovipositing females showed no preference for tillage treatment or cultivar. Mean number of Hessian fly puparia per plant was significantly greater in CT plots during the last sampling in 2000; however, in 2001, NT plots had significantly more puparia than CT plots. Tillage had no significant effect on mean Hessian fly per plant in 2002. Significantly more puparia were observed on susceptible compared with resistant cultivars in 2000 ...
On Integrating Machine Learning with Planning

Domain-independent classical planning is faced with serious difficulties. Many of these are traceable to some facet of the frame problem. Perfect knowledge of the planner’s world and operators is impossible for most domains. With anything less, small unmodeled errors can result in large discrepancies between the expected and observed worlds. Such discrepancies may interfere with the achievement of a goal. Reactivity provides an extreme response. It allows only sensor information after an action is taken to judge the action’s effects, and abandons projection altogether. There must be a vast space of possibilities between the extremes of classical planning and reactivity. This paper describes two called computable planning and permissive planning. Machine learning, in the form of Explanation-Based Learning, is used in computable planning to recognize deferrable goals, resulting in many of the benefits offered by reactivity but in a domain independent form. In permissive planning, machine learning techniques are used to refine plans through experience so that they become less sensitive to the necessarily approximate knowledge.
Influence of a WC/a-C:H tribological coating on micropitting wear of bearing steel

Abstract The focus of this work was to evaluate the use of a WC/a-C:H coating, specifically designed to withstand rolling contact fatigue, to mitigate micropitting damage on through-hardened AISI 52100 bearing steel. This was accomplished by conducting experiments with various combinations of coated discs and rollers using a three-disc-on-roller rolling contact fatigue machine. In addition to testing coated and uncoated contacts, discs and rollers with three hardness levels and different surface roughness values were also evaluated. Upon the completion of this work, it was observed that the onset of micropitting damage was affected by the hardness of the asperities on the mated roller and disc samples. It was also observed that the coated surface can cause abrasive wear damage on an uncoated surface if the coating is applied to a surface that has a roughness R q ≥0.5 μm. If the coating is applied to a smoother roller surface ( R q ≤0.26 μm), the coating is able to mitigate micropitting damage on the roller surface without causing high abrasive wear rates on the disc surfaces.
Price Include Tax: Protecting Consumers from Tax-Exclusive Pricing

This Note contributes to the debate regarding the behavioral effects of the salience of taxes on taxpayers by examining the impact of including the value of sales taxes in the displayed prices of goods. The Note concludes that consumers should make more beneficial decisions regarding consumption when the value of sales taxes is included in or with displayed prices.
Race and the Use of Local Initiatives in American Cities

This article examines the influence of constituent demographics on the frequency and success of local initiative contests. We find that local initiatives are more common and more successful in citi...
We Have to Talk: Results of an Interprofessional Clinical Simulation for Delivering Bad Health News in Palliative Care

Abstract Background Primary care providers, including nurse practitioners and social workers, are often the first point of contact in communicating difficult health news to their clients. Method This article reports an innovative interprofessional simulation created by faculty to pair graduate nurse practitioner and social work students to deliver bad health news in a simulated primary care setting. Results Students improved in their readiness to work together in delivering bad news and reported that they gained proficiency in completing this task. Conclusions This project promoted improved communication and interprofessional practice skills in graduate nursing and social work students.
Feasibility of Home-Based Computerized Working Memory Training With Children and Adolescents With Sickle Cell Disease.

Background Children with sickle cell disease (SCD) are at increased risk for neurocognitive deficits, yet the literature describing interventions to ameliorate these problems and promote academic achievement is limited. We evaluated the feasibility and preliminary efficacy of a home-based computerized working memory (WM) training intervention (Cogmed) in children with SCD. Procedure Youth with SCD between the age of 7 and 16 years completed an initial neuropsychological assessment; those with WM deficits were loaned an iPad on which they accessed Cogmed at home. Participants were instructed to work on Cogmed 5 days each week for 5 weeks (25 training sessions). We examined Cogmed usage characteristics and change on WM assessment scores following the intervention. Results Of the 21 participants (M age = 11.38, SD = 2.78; Mdn age = 10.00, interquartile range [IQR] = 5.00; 52% female) screened, 60% exhibited WM deficits (n = 12) and received the intervention and 50% (n = 6) completed Cogmed. The mean number of sessions completed was 15.83 (SD = 7.73; Mdn = 17.00, IQR = 16.00); females were more likely to complete Cogmed, χ2(1) = 6.00, P = 0.01. Participants who reported lower SCD-related pain impact completed more sessions (r = 0.71, P = 0.01). Children who completed Cogmed exhibited improvements in verbal WM, visuospatial short-term memory, and visuospatial WM. Conclusions Initial findings suggest Cogmed is associated with WM improvement in youth with SCD; however, adherence was lower than expected. Home-based WM interventions may ameliorate SCD-related WM deficits but strategies are needed to address barriers to program completion.
Use of Clostridium botulinum toxin in gastrointestinal motility disorders in children

More than a century has elapsed since the identification of Clostridia neurotoxins as the cause of paralytic diseases. Clostridium botulinum is a heterogeneous group of Gram-positive, rod-shaped, spore-forming, obligate anaerobic bacteria that produce a potent neurotoxin. Eight different Clostridium botulinum neurotoxins have been described (A-H) and 5 of those cause disease in humans. These toxins cause paralysis by blocking the presynaptic release of acetylcholine at the neuromuscular junction. Advantage can be taken of this blockade to alleviate muscle spams due to excessive neural activity of central origin or to weaken a muscle for treatment purposes. In therapeutic applications, minute quantities of botulinum neurotoxin type A are injected directly into selected muscles. The Food and Drug Administration first approved botulinum toxin (BT) type A in 1989 for the treatment of strabismus and blepharospasm associated with dystonia in patients 12 years of age or older. Ever since, therapeutic applications of BT have expanded to other systems, including the gastrointestinal tract. Although only a single fatality has been reported to our knowledge with use of BT for gastroenterological conditions, there are significant complications ranging from minor pain, rash and allergic reactions to pneumothorax, bowel perforation and significant paralysis of tissues surrounding the injection (including vocal cord paralysis and dysphagia). This editorial describes the clinical experience and evidence for the use BT in gastrointestinal motility disorders in children.
Research in the Real World: Improving Adult Learners’ Web Search and Evaluation Skills through Motivational Design and Problem-Based Learning

How can we better engage adult learners during information literacy sessions? How do we increase students’ perception of the relevance and importance of information literacy skills for academic work and life in the real world? To explore these questions, the ARCS Model of Motivational Design and Problem-Based Learning were used to develop activities for a library instruction workshop. Community college students completed a pretest and posttest assessment to measure change in skill level, perceived confidence, and perceived relevance of the research workshop. Results show learners’ skill levels, perceived confidence, and perceived relevance increased significantly. Based on the results, suggestions are made for incorporating Motivational Design and Problem-Based Learning into information literacy sessions to increase student engagement.
What Philosophers Know: Turning the tables: Plantinga and the rise of philosophy of religion

For at least the first half of the twentieth century, there was no such thing as the philosophy of religion among analytic philosophers. Most analytic philosophers rejected religion as at best rationally gratuitous and at worst meaningless and, in any case, saw no need for serious, prolonged philosophical discussion of its ideas and status. This situation began to change around 1950, as witnessed by the still remarkable volume edited by Anthony Flew and Alasdair MacIntyre, which gathered papers by philosophers (a roughly equal mix of believers and non-believers), all working in the analytic tradition and sharing “a concern with theological questions, and a conviction that these call for serious and particular treatment” through philosophical analysis and argument. The editors noted that they would have liked to described the pieces they collected as essays in “the philosophy of religion,” but did not do so because “this expression has become, and seems likely for some time to remain, associated with Idealist attempts to present philosophical prolegomena to theistic theology” (viii). Their title spoke instead of “new essays in philosophical theology .” Although the volume represents a new opening to religious questions, it still presents religion as distinctly under siege from analytic philosophy. A dominant issue is whether religious language even meets the standards of meaningful discourse, and although there are several discussions of theistic proofs, no one defends their soundness. Even the essay by the Christian co-editor, Alasdair MacIntyre, attacks arguments from religious experience.
Lenin: The Revolutionary Party and Movement

A “Second International Workingmen’s Association” was established in 1889, six years after the death of Marx in 1883. The Second International became a powerful worldwide organization that included some of the largest political parties in western European countries. The Second International was distinguished from the First International in that its member parties were required to accept the orthodox principles of “scientific socialism” of Marxist revolutionary theory, as opposed to a heterogeneous mix of other socialist theories. Germany was seen as the leading country of the Second International in terms of both its political strength and its leading theoreticians of Marxist orthodoxy. Following the death of Frederick Engels in 1895, three of the leading German theoreticians were Karl Liebknecht, Karl Kautsky, and Rosa Luxemburg.
Interruptions: Estranging Empathy

Like the Writer in the dialogue quoted above, most audience members attending the National Theatre of Scotland’s Black Watch have come, at least in part, to find out “what it was like” for members of the Scottish regiment during their deployments in Iraq in 2003 and 2004. This play, based on interviews with former members of the Black Watch, promises a kind of intimacy not available through more “impersonal” media accounts of the war. In other words, it promises an opportunity to empathize. But our curiosity, like the Writer’s in the epigraph, is rebuked. Black Watch is replete with cautionary reminders that what we are seeing is never the whole story and that our interest may be exploitative. Yet the play persists in attempting to communicate these soldiers’ experiences, first encouraging empathy, then interrupting it, and then encouraging it again. As audience members, we repeatedly confront our inability to know the very thing that we have come to the theatre to learn—what it was like for the soldiers on the ground. In the process, we are prompted to consider why we want to know these things and what it feels like to be on the receiving end of our empathetic curiosity.
Accelerating BigBench on Hadoop

Benchmarking Big Data systems is an open challenge. The existing Micro-Benchmarks (e.g. TeraSort) do not present an end-to-end scenario in real world. To solve this issue, a new towards industry standard benchmark for Big Data Analytics called BigBench has been proposed. And with BigBench, we’ve been keeping our collaboration with Apache Open Source Community to work on performance tuning and optimization for Hadoop ecosystem. In this paper, we share our contributions to BigBench, and present our tuning and optimization experience along with the benchmark results.
Structural Requirements of HDAC Inhibitors: SAHA Analogues Modified at the C2 Position Display HDAC6/8 Selectivity

Histone deacetylase (HDAC) proteins are epigenetic regulators that deacetylate protein substrates, leading to subsequent changes in cell function. HDAC proteins are implicated in cancers, and several HDAC inhibitors have been approved by the FDA as anticancer drugs, including SAHA (suberoylanilide hydroxamic acid; Vorinostat and Zolinza). Unfortunately, SAHA inhibits most HDAC isoforms, which limits its use as a pharmacological tool and may lead to side effects in the clinic. In this work SAHA analogues substituted at the C2 position were synthesized and screened for HDAC isoform selectivity in vitro and in cells. The most potent and selective compound, C2-n-hexyl SAHA, displayed submicromolar potency with 49- to 300-fold selectivity for HDAC6 and HDAC8 compared to HDAC1, -2, and -3. Docking studies provided a structural rationale for selectivity. Modification of the nonselective inhibitor SAHA generated HDAC6/HDAC8 dual selective inhibitors, which can be useful lead compounds toward developing pharmacolo...
Transdiagnostic Dimensional Assessment of Psychopathology in Later Life

The purpose of this review is to present a transdiagnostic dimensional approach to evidence-based assessment designed to facilitate applications of neuroscientific advances to phenotypic psychopathology in later life. Standardized assessment forms were developed to obtain collateral- and self-ratings of a broad spectrum of behavioral, emotional, social, and thought problems, as well as strengths. Factor analyses of ratings of American elders yielded seven syndromes, while judgments by international panels of expert clinicians yielded six DSM-oriented scales. Gender-specific norms for ages 60–75 and >75 years enable users to view individuals’ scale scores in relation to scores for population samples of peers. Cross-informant comparisons are designed to reveal important discrepancies and consistencies between collateral- and self-ratings. Significant associations are found between the dimensional measures and psychiatric disorders. Multicultural research supports the generalizability of the statistically derived syndromes. Indigenous researchers are obtaining data for testing syndromes and comparing problems and strengths across many societies. Standardized transdiagnostic dimensional assessments can be used in multiple societies to construct multicultural norms based on collateral- and self-ratings and can foster international collaboration to advance clinical services, neuroscientific research, and training.
Comparative test beam studies of precision timing calorimeter technologies

Current and future high energy physics particle colliders are capable to provide instantaneous luminosities of 1034 cm−2 s−1 and above. The high center of mass energy, the large number of simultaneous collision of beam particles in the experiments and the very high repetition rates of the collision events pose huge challenges. They result in extremely high particle fluxes, causing very high occupancies in the particle physics detectors operating at these machines. To reconstruct the physics events, the detectors have to make as much information as possible available on the final state particles. We discuss different detector concepts which can provide time measurements for charged particles and photons with a precision in the range of a few 10 ps. We present in detail measurements utilizing Lutetiumyttrium oxyorthosilicate (LYSO) based calorimeter prototype. With an improved understanding of the signal creation, light propagation and detection characteristics we achieve a precision of down to 30 ps for electrons with energies of 30 GeV. Further we present beam test measurements with a multichannel plate based detectors and studies using semi-conductor based detectors. We discuss possible implementations based on these different technologies in a large scale particle physics detector for the high luminosity LHC (HL-LHC).
Blockade of NMDA receptors blocks the acquisition of cocaine conditioned approach in rats

Conditioned stimuli (CSs) exert motivational effects on both adaptive and pathological reward-related behaviors, including drug taking and seeking. We developed a paradigm that allows us to investigate the neuropharmacology by which previously neutral stimuli acquire the capacity to function as CSs and elicit (intravenous) cocaine conditioned approach and used this paradigm to test the role of NMDA receptor stimulation in the acquisition of cocaine conditioned approach. Rats were injected systemically with the NMDA receptor antagonist, MK-801, before the start of 4 consecutive conditioning sessions, each of which consisted of 20 randomly presented light/tone (CS) presentations paired with cocaine infusion contingent upon nose pokes. Rats later were subjected to a CS-only test. To test the role of NMDA receptor stimulation in the already established conditioned approach, rats were injected with MK-801 prior to the CS-only test that occurred after 18 CS-cocaine conditioning sessions. Blockade of NMDA receptors significantly impaired the acquisition of cocaine-conditioned approach as indicated by the emission of significantly fewer nose pokes and significantly longer latencies to nose poke during CS presentations. When MK-801 treatment was applied after the acquisition of conditioned approach responding it had no effect on these measures. These results suggest that NMDA receptor stimulation plays an important role in the acquisition of reward-related conditioned responses driven by intravenous cocaine-associated CSs.
Risk Factors for the Development of Premature Cardiovascular Disease

Coronary artery disease is the major cause of death and disability in the United States and in other industrial countries. During the last twenty years smoking, high plasma cholesterol, and hypertension have been identified as major risk factors for the development of premature cardiovascular disease.1,2 Major insights into the mechanisms involved in the development of vascular disease associated with hypercholesterolemia have occurred due to detailed analyses of plasma lipids, the characterization of plasma lipoproteins, and the identification of changes in the plasma lipoproteins which predispose to vascular disease. Recently research has also focused on the role of receptors and apolipoproteins, the protein moeity of plasma lipoproteins, in lipid and lipoprotein metabolism in normal subjects and patients with dyslipoproteinemia and atherosclerosis. Specific defects in apolipoproteins and receptors are now known to result in the development of dyslipoproteinemias characterized by atherosclerosis. The present review will summarize our current knowledge on the plasma lipoproteins, apolipoproteins, and the risk factors associated with the development of premature atherosclerosis.
Rolling Bearing Fault Diagnosis Based on an Improved Denoising Method Using the Complete Ensemble Empirical Mode Decomposition and the Optimized Thresholding Operation

Vibration signals are widely used in monitoring and diagnosing of rolling bearing faults. These signals are usually noisy and masked by other sources, which may therefore result in loss of information about the faults. This paper proposes an improved denoising method in order to enhance the sensitivity of kurtosis and the envelope spectrum for early detection of rolling bearing faults. The proposed method is based on a complete ensemble empirical mode decomposition with an adaptive noise (CEEMDAN) associated with an optimized thresholding operation. First, the CEEMDAN is applied to the vibration signals to obtain a series of functions called the intrinsic mode functions (IMFs). Second, an approach based on the energy content of each mode and the white noise characteristic is proposed to determine the trip point in order to select the relevant modes. By comparing the average energy of all the unselected IMFs with the energy of each selected IMFs, the singular IMFs are selected. Third, an optimized thresholding operation is applied to the singular IMFs. Finally, the kurtosis and the envelope spectrum are used to test the effectiveness of the proposed method. Different experimental data of the Case Western Reserve University Bearing Data Center are used to validate the effectiveness of the proposed method. The obtained experimental results illustrate well the merits of the proposed method for the diagnosis and detection of rolling bearing faults compared to those of the conventional method.
Can a transgenic chestnut restore a forest icon

American chestnut trees once dominated forests in eastern North America. But in the early 1900s, a deadly fungal infection appeared on trees and spread rapidly. The so-called chestnut blight—an accidental import from Asia—essentially erased the trees from forests. Now, researchers have created a genetically modified (GM) chestnut that resists the blight. And in the coming weeks, they plan to formally ask U.S. regulators to allow their transgenic trees to breed with nonengineered relatives and grow wild in forests. If the regulators approve the request, it would be precedent setting—the first use of a GM tree to try to restore a native species in North America. But three agencies are expected to review the proposal, and it could take years to reach a decision.
The Use of Modeling to Facilitate Decision-Making in Safety Pharmacology Assessments

Abstract Safety pharmacology is a translation-rich discipline because many of the endpoints of interest are measured in both animals and man. Many of these endpoints are readily measured noninvasively. Easy access to time series of endpoint measures is a key criterion enabling pharmacokinetic and pharmacodynamic (PKPD) modeling. The assays are generally conducted similarly across the pharmaceutical industry and these same assays are also conducted for most compounds progressing to clinical development. This creates an opportunity for efficiency in building models—the modeling platform can be used over and over again. The first question, however, should be “why model”? The answer has two key components that relate to the types of models, which will be described below. Firstly, quantification of concentration–response relationships is crucial in understanding exposure multiples. Exposure multiples are a key tool used by every safety scientist in placing experimental data into context with human safety. Secondly, the main purpose of nonclinical and especially preclinical safety studies is in making predictions about human safety and toxicity. Prediction is difficult and is reliant on the sensitivity and specificity of any decision-making tool used. Models integrate information in ways that enhance sensitivity and specificity relative to the individual assays. Overall, a model can offer quantitative information and predictive capabilities to address the two key reasons outlined. Thus, safety pharmacology offers the motive and means to use PKPD modeling to address key drug safety topics.
Use of Script Concordance Activity With the Think-Aloud Approach to Foster Clinical Reasoning in Nursing Students.

Background Script concordance testing and the think-aloud (TA) approach uses clinical scenarios to evaluate clinical reasoning (CR). Problem Teaching strategies to both facilitate and evaluate CR are lacking. Adaptation of script concordance testing and the TA approach may be a useful teaching/learning strategy for CR. Approach Script concordance activity with the TA approach (SCA-TA method) was created and implemented in a nursing course to facilitate and evaluate CR. Evaluation Survey data provided valuable information of students' perception about the SCA-TA method as a teaching strategy. Conclusions The SCA-TA method holds promise to foster CR. Ongoing research to predict progression of CR is needed.
Relapse Rates in Patients Receiving Azithromycin for the Treatment of Bronchiolitis Obliterans after Allogeneic Hematopoietic Stem Cell Transplant

Introduction The FDA issued a warning on the increased risk of hematologic relapse based on the ALLOZITHRO trial, recommending azithromycin not be used long-term in patients that have undergone allogenic hematopoietic stem cell transplant (HSCT). In the ALLOZITHRO trial, azithromycin was started at the time of the conditioning regimen for prophylaxis of bronchiolitis obliterans (BO); however, at our site and many others across the country, azithromycin is initiated after BO. Objective The goal of this study was to evaluate if azithromycin used in treatment of BO is associated with an increase in the rate of relapse. Methods IRB approval was obtained prior to review of the electronic medical record and the Mayo Clinic HSCT database. Adult patients who received an allogeneic HSCT from January 2008 – August 2018 for a malignant disease and received ≥ 2 weeks of azithromycin were included in this study. Patients were excluded if they received Results Of 466 adult patients who received an allogenic HSCT at Mayo Clinic Hospital-Rochester for malignant disease, 185 patients received azithromycin. Of 185 patients who received azithromycin, 87 were excluded: declined research participation (n = 7), received Conclusion The use of azithromycin as treatment for BO was not associated with a high incidence of disease relapse in this study. Further research is needed to confirm our findings.
Increased skeletal intermuscular fat is associated with reduced exercise capacity in cancer survivors: a cross-sectional study.

Cancer survivors experience on average a 20% reduction in peak exercise capacity (VO2 peak) post-cancer treatment. Intermuscular fat (IMF) is a strong predictor of reduced exercise capacity in heart failure (HF) patients; however it is unknown whether increased IMF is related to reduced VO2 peak in cancer survivors. Twenty eight individuals: 14 cancer survivors > 12-months post-cancer treatment and 14 individuals without cancer were matched on age, gender, and body mass index (BMI). Participants underwent magnetic resonance imaging (MRI) assessments of IMF within the paraspinal muscles, VO2 peak and exercise-associated measures of left ventricular ejection fraction (LVEF). Blinded analyses were performed. Associations between the ratio of IMF to skeletal muscle (SM) were estimated using Pearson’s partial correlation coefficients. Individuals with cancer and non-cancer comparators were of similar age (54 ± 17 versus 54 ± 15 years; p = 1.0), gender (5 men and 9 women, both groups), and BMI (27 ± 4 versus 26 ± 4; p = 0.57). Peak VO2 was 22% lower in cancer survivors versus non-cancer comparators (26.9 vs 34.3 ml/kg/min; p = 0.005), and was correlated with IMF:SM in both cancer survivors and non-cancer individuals after accounting for exercise-associated LVEF, resting LVEF, BMI, other body fat depots, and cardiovascular disease (CVD) co-morbidities (p < 0.001 to 0.08 for all adjusted correlations). Among cancer survivors that previously received anthracyclines, increased intermuscular fat is associated with reduced VO2 peak even after accounting for exercise-associated cardiac function. This suggests IMF is important in the development of exercise intolerance, an outcome experienced by a large number of cancer survivors.
TNF-α and autotaxin-LPA signaling is linked in hepatitis associated hepatocellular carcinoma

5394 Autotaxin (ATX), known as nucleotide pyrophosphatase-phosphodiesterase-2 (ENPP2), is a secreted lysophospholipase D that hydrolyzes lysophosphatidylcholine into lysophosphatidic acid (LPA). An LPA rich microenvironment can promote inflammatory process, wound healing, and tumor progression. We have previously shown that ATX is a potential biomarker of hepatocellular carcinoma (HCC) risk in patients with hepatitis. However, the regulation and functions of ATX in hepatocellular carcinogenesis have not been studied. Known mechanisms associated with inflammation induced cancers included an increased expression of tumor necrosis factor-alpha (TNF-α), which can trigger a cascade of other cytokines that cooperate in recruiting inflammatory cells and promoting the development of cancer in chronic active hepatitis. The objective of this study was to investigate the ATX-LPA signaling pathway in HCC and identify a potential link between TNF-α and ATX-LPA signaling. Initially, we examined the expression of ATX and LPA receptors in human hepatocyte cell lines: normal (CL48), hepatitis associated HCC (Hep3B) and HCC in the background of normal liver (HepG2). Migration assay was used to determine whether ATX functions as a chemoattractant for human hepatocytes. The effect of ATX on the expression of LPA receptors and downstream target genes such as uPA, MMP9 and VEGF was evaluated. The roles of inflammatory cytokines (TNF-α and TGF-β) on the expression of ATX were studied. The expression of ATX between normal and hepatoma cell lines is significantly different. Quantitative real-time RT-PCR (Q-PCR) showed the endogenous expression of ATX is negligible in CL-48 and 42-fold higher in Hep3B than HepG2. Immunoblot analysis confirmed ATX is differentially expressed. LPA receptors (LPA1, LPA2 and LPA3) are overexpressed in Hep3B compared to HepG2 and CL-48. Migration assays show ATX secreted by Hep3B cells promote the migration of Hep3B and HepG2 cells, while has little effect on CL-48 cells. Treatment with 220ng/ml ATX for 20hrs increases the mRNA expression of LPA2, uPA, MMP9 and VEGF to 1.8-, 1.6-, 2-, and 1.8-fold respectively. Both Q-PCR and immunoblot results show TNF-α (10ng/ml) promotes ATX expression only in Hep3B cells (3.2 fold for mRNA expression), while TGF-β (5ng/ml) does not affect ATX expression in these three cell lines. In conclusion: The overexpression of ATX and LPA receptors along with the induced LPA2 expression by ATX in Hep3B cells indicate ATX-LPA signaling is actively involved in human hepatitis associated HCC. The ATX-LPA signaling is linked to the invasiveness and angiogenesis of liver cancer. Pro-inflammatory cytokine TNF-α promotes ATX expression only in hepatitis associated HCC. The connection between TNF-α and ATX-LPA signaling appears to be unique to human hepatitis associated cancer.
The Special Medical Physics Consult Process for Reirradiation Patients.

Abstract Purpose To present a systematic approach to the reirradiation special medical physics consult (ReRT-SMPC) process. Materials and Methods An in-house reirradiation committee of physicians and physicists was formed to develop a streamlined and well-documented approach to ReRT-SMPCs. Dosimetric goals and considerations for tissue repair were generated by the committee with input from the literature, clinical trial guidelines, and physician experience. Procedural workflow was also defined. Results The total number of ReRT-SMPCs performed in our department in 2018 was 401, corresponding to 369 unique patients and 16% of the total number of patients receiving external beam radiation in our department that year. This constituted a large increase over the 183 ReRT-SMPCs performed in 2017. We have found that a standardized ReRT-SMPC workflow helps to safeguard patients, documents the clinical decision-making process for medical and legal purposes, and facilitates the peer-review process. The data being collected from each consult along with toxicity and outcomes data can be used to help inform future re-treatment guidelines. Conclusions As the number of patients returning for additional courses of radiation continues to increase, a uniform method for the ReRT-SMPC workflow and analysis is a powerful tool for ensuring patient safety, understanding and predicting treatment toxicity, and refining reirradiation dosimetric limits.
Anatomic shoulder parameters and their relationship to the presence of degenerative rotator cuff tears and glenohumeral osteoarthritis: a systematic review and meta-analysis.

Background Scapular anatomy, as measured by the acromial index (AI), critical shoulder angle (CSA), lateral acromial angle (LAA), and glenoid inclination (GI), has emerged as a possible contributor to the development of degenerative shoulder conditions such as rotator cuff tears and glenohumeral osteoarthritis. The purpose of this study was to investigate the published literature on influences of scapular morphology on the development of degenerative shoulder conditions. Methods A systematic review of the Embase and PubMed databases was performed to identify published studies on the potential influence of scapular bony morphology on the development of degenerative rotator cuff tears and glenohumeral osteoarthritis. The studies were reviewed by 2 authors. The findings were summarized for various anatomic parameters. A meta-analysis was completed for parameters reported in more than 5 related publications. Results A total of 660 unique titles and 55 potentially relevant abstracts were reviewed with 30 published articles identified for inclusion. The AI, CSA, LAA, and GI were the most commonly reported bony measurements. Increased CSA and AI correlated with rotator cuff tears, whereas lower CSA appeared to be related to the presence of glenohumeral osteoarthritis. Decreased LAA correlated with degenerative rotator cuff tears. Five articles reported on the GI with mixed results on shoulder pathology. Discussion Degenerative rotator cuff tears appear to be significantly associated with the AI, CSA, and LAA. There does not appear to be a significant relationship between the included shoulder parameters and the development of osteoarthritis.