cssi/SciSciGPT-SciSciNet huggingface dataset:
Poster 011. Do ALS Providers Need Vital Signs to Assess and Manage Prehospital Patients

Purpose: Routine vital signs (VS) assessment is considered a fundamental component of patient assessment. This study was undertaken to determine if advanced life support EMS providers can manage patients without VS. Methods: Twenty-seven paramedics and 37 intermediates were presented with 20 randomized patient scenarios that did not include VS. They were asked to identify all interventions they would perform for each patient. Six weeks later, the same scenarios were presented in a new order, with VS, and the participants again identified the interventions they would perform. The frequency of specific interventions for each patient in the no-VS group was compared to the frequency in the VS group using chi-square or Fisher's Exact test. Results: There were two cases for which paramedics significantly changed their interventions when given VS. They were more likely to run IVs wide open in an unresponsive 86-year-old woman with an unobtainable blood pressure ( p = 0.024), and less likely to immobilize a 65-year-old man who had fallen the night before ( p = 0.001). There were three cases for which intermediates significantly changed their interventions when given VS. They were more likely to start two IVs for a 69-year-old with near syncope ( p = 0.020), less likely to run IVs wide open for a 32-year-old gunshot victim ( p = 0.016), and they, too, were less likely to immobilize the 65-year-old man who had fallen the night before ( p = 0.013). Conclusion: Vital signs do not significantly affect interventions for most prehospital patients, and may not be necessary.
Treatment of macular edema due to central retinal vein occlusion another score for repackaged bevacizumab

Central retinal or hemiretinal vein occlusion, due to a thrombus at an arteriovenous crossing within the optic nerve, is a common disease of the retinal vasculature, the blood supply to the inner layers of the retina that are closest to the vitreous cavity. Central retinal vein occlusion sometimes has been described as a “blood and thunder” appearance due to extensive flame-shaped hemorrhages throughout 2 (hemiretinal) or 4 quadrants of the retina and causes sudden vision loss in one eye when venous flow is acutely compromised. The vision loss at first may be due in part to blood that has extravasated into the retina, but as this blood clears, vision loss may be due to ischemia or infarction of the inner retina due to nonperfusion of retinal capillaries that feed into the occluded retinal veins, as well as complications of abnormal vascular endothelial growth factor (VEGF) produced by the damaged retina. These complications include the development of edema in the center of the retina, or macular edema, which, if left untreated, can cause substantial vision loss. In a pooled analysis using individual population-based data of fundus photographs from 11 studies (n = 49 869), the age- and sex-standardized prevalence was 0.08% (95% CI, 0.06%-0.10%) for central retinal vein occlusion, although the proportion of cases with macular edema, while generally considered to be common, was not reported
High-level intrinsic disorder explains the universality of CLIP binding to diverse MHC class II variants.

High-level intrinsic disorder explains the universality of CLIP binding to diverse MHC class II variants
Digital workflow in full-arch implant rehabilitation with segmented minimally veneered monolithic zirconia fixed dental prostheses: 2-year clinical follow-up.

Objective To illustrate a digital workflow in full-arch implant rehabilitation with minimally veneered monolithic zirconia and to report the outcomes including technical complications. Clinical considerations Three patients (5 edentulous arches) received full-arch fixed implant rehabilitation with monolithic zirconia and mild facial porcelain veneering involving a digital workflow. The incisal edges and occluding surface areas were milled out of monolithic zirconia to reduce the possibility of chipping. Porcelain veneering was applied on the facial aspect to improve the esthetic result. Outcomes and technical complications are reported after 2 years of clinical and radiographic follow-up. Conclusion Implant and prosthesis survival rates were 100% after a short-term follow-up of 2 years. Technical complications were encountered in one patient. They did not adversely affect prosthesis survival or patient satisfaction and were easily addressed. A digital workflow for the design and fabrication of full-arch monolithic zirconia implant fixed implant prostheses has benefits, but caution is necessary during CAD planning of the prosthesis to ensure a successful outcome. Long-term clinical studies are needed to corroborate the findings discussed in this report. Clinical significance This article presents an integrated digital workflow that was implemented for the implant-prosthodontic rehabilitation of three edentulous patients with monolithic zirconia prostheses. Monolithic zirconia has been successfully incorporated in implant prosthodontics in an effort to reduce the technical complications associated with bilayered ceramics. This workflow simplifies design and fabrication of the zirconia prostheses. However, caution should be taken during CAD planning of the prosthesis to make sure the zirconia cylinder is sufficiently thick at the interface with the titanium insert. Additionally, when cutback is planned for facial porcelain veneering, the functional occluding cusps and incisal edges should be fabricated in monolithic zirconia to avoid chipping.
Genomics and advances towards precision medicine for head and neck squamous cell carcinoma.

Objective To provide a review of emerging knowledge from genomics and related basic science, preclinical, and clinical precision medicine studies in head and neck squamous cell carcinoma (HNSCC). Data Sources The Cancer Genome Atlas Network (TCGA) publications, PubMed-based literature review, and ClinicalTrials.gov. Review Methods TCGA publications, PubMed, and ClinicalTrials.gov were queried for genomics and related basic science, preclinical, and developmental clinical precision medicine studies in HNSCC. Results TCGA reported comprehensive genomic analyses of 279 HNSCC, defining the landscape and frequency of chromosomal copy number alterations, mutations, and expressed genes that contribute to pathogenesis, prognosis, and resistance to therapy. This provides a road map for basic science and preclinical studies to identify key pathways in cancer and cells of the tumor microenvironment affected by these alterations, and candidate targets for new small molecule and biologic therapies. Conclusion Recurrent chromosomal abnormalities, mutations, and expression of genes affecting HNSCC subsets are associated with differences in prognosis, and define molecules, pathways, and deregulated immune responses as candidates for therapy. Activity of molecularly targeted agents appears to be enhanced by rational combinations of these agents and standard therapies targeting the complex alterations that affect multiple pathways and mechanisms in HNSCC. Level of Evidence N/A
Manipulation of structure and properties of two-dimensional systems employing the pseudo Jahn-Teller effect

Abstract In a semi-review paper, the achievements in using the pseudo Jahn-Teller effect (PJTE) to manipulate the puckering or buckling of the planar configuration of two-dimensional (2D) or quasi 2D structures are demonstrated using a series of molecular and extended systems as examples. First the PJTE is briefly outlined as the only source of instability and distortions of high-symmetry configurations of polyatomic systems in nondegenerate states, which includes all the other forces driving out-of-plan distortions as particular cases. Then it is shown how the main features and parameters of the PJTE in molecular systems are revealed using ab initio calculations of their electronic structure and energy profiles along the distortion mode in the ground and low-lying excited states. The latter are most vulnerable to external perturbations that can suppress the PJTE instability and restore the planar configuration of 2D system, thus changing also the other related properties, notably energy gaps and charge mobility. Described in this review methods of targeted external influence that suppresses the PJTE includes coordination to other atoms or atomic groups, oxidation, reduction, and chemical substitutions. Applications are demonstrated on a series of molecular and extended 2D systems including silicene, phosphorene, germanene, and graphitic carbon nitride, as well as carbon and silicon tetra-, penta-, and hexa-cyclic compounds, and more complicated tricyclic and polycyclic systems like dithiine containing dithianon, thiantrene, and anthracene.
Models with unequal transition rates favor marine origins of Cyanobacteria and photosynthetic eukaryotes.

Using a broadly sampled, time-calibrated phylogeny of Cyanobacteria and photosynthetic eukaryotes, Sanchez-Baracaldo et al. (1) report that the most-recent common ancestor (MRCA) of Archaeplastida likely inhabited a low-salinity (freshwater) habitat, providing an advance on a longstanding debate about the ecological context for the origin of plastids (2). The freshwater ancestry for Cyanobacteria and Archaeplastida was based on reconstructions that assumed equal transition rates among marine, brackish, and freshwater habitats (1), which likely oversimplified the 2.5-billion-year history of these groups. We relaxed the assumption of a single transition rate by fitting a model with additional parameters for independent transition rates among marine, brackish, and freshwater habitats. This model provided a … [↵][1]1To whom correspondence should be addressed. Email: tnakov{at}uark.edu. [1]: #xref-corresp-1-1
The Case for Functional Pedagogical Skills in School Psychology Training: An Empirical Investigation

In the last twenty years, the field of school psychology has changed much of its focus in service provision, from a reactive and individually-oriented intervention model to a proactive and systems-based prevention model. In the last decade, the field has also transformed its positions regarding the ways in which skills of future school psychologists should be assessed: current standards regarding adequate preparation require the demonstration of skills in a competency-based framework. One key competency, described in training standards as prevalent in all aspects of service provision, is consultation. This competency requires the consultant to be able to instruct adults, but teaching is not named specifically as a skill within the standards. The chapter begins with a brief review of relevant historical trends and an overview of consultative practice within the discipline of school psychology. The most recent standards for preparing future school psychologists are considered in light of a definition of teaching, to demonstrate that teaching is a tacitly assumed skill within many domains of practice. A review of relevant literature frames the present study, which qualitatively investigates nine school psychology professors’ training priorities and practices relative to training students how to teach. Finally, implications of findings and recommendations for further inquiry are discussed.
Pricing of digital resources: an interview with Simon Tanner

Abstract In this interview, Simon Tanner, senior consultant with Higher Education Digitization Services at the University of Hertfordshire in the United Kingdom, discusses the economics and market issues related to pricing of digital resources. Serials Review 2003; 29:121–126.
Common metabolic disorder (inborn errors of metabolism) concerns in primary care practice.

Inborn errors of metabolism (IEMs) are rare genetic or inherited disorders resulting from an enzyme defect in biochemical and metabolic pathways affecting proteins, fats, carbohydrates metabolism or impaired organelle function presenting as complicated medical conditions involving several human organ systems. They involve great complexity of the underlying pathophysiology, biochemical workup, and molecular analysis, and have complicated therapeutic options for management. Age of presentation can vary from infancy to adolescence with the more severe forms appearing in early childhood accompanied by significant morbidity and mortality. The understanding of these complex disorders requires special in-depth training, American Board of Medical Genetics and Genomics (ABMGG) certification and experience. Most primary care physicians (PCPs) are reluctant to deal with IEM due to unfamiliarity and rarity of such conditions compounded by prompt progression to crisis situations along with paucity of time involved in dealing with such complex disorders. While there are biochemical geneticists aka metabolic specialists’ expertise available, mostly in larger academic medical centers, with expertise to deal with these rare complex issues, their initial clinical presentation in most newborns, children, adolescents or adults including asymptomatic positive newborn screen (NBS), occur in the out-patient PCP settings. Therefore, it is important that PCPs’ comfort to recognize early signs and symptoms is important to initiate appropriate diagnostic and therapeutic interventions, and be able to make appropriate referrals. The following article reviews common IEM clinical presentations for a robust diagnostic differential and discuss evaluation and management approaches of patients with known or suspected IEM.
Considering “Sameness” of Monographic Holdings in Shared Print Retention Decisions

In addition to the pressure of operating in a steady state of insufficient funding, academic libraries face incessant pressure to use space differently. As a result, libraries are aggressively withdrawing materials to relieve cramped shelves and reduce overall collection footprints. Selection for withdrawal may be based on various factors, but of concern is the withdrawal of materials for which copies are currently held in shared print repositories. Recent publications point to the need for thoughtful and strategic evaluation of shared print for quality and completeness, plus the evaluation of copies considered for withdrawal to ensure the perseverance of our print heritage. This study focuses on the comparison of forty-seven monographic titles cataloged as identical items that show broadly varying differences in editions, printings, condition, and preservation and repair. Survey data collected includes information about bibliographic accuracy, printing and binding variances, completeness, physical damage, chemical deterioration, provenance, and presence in the HathiTrust. The results show wide variability in the accuracy of cataloging records, historical use, physical condition of the materials, and the ability for those materials to be successfully digitized in the future. These results are illustrative of the strong potential for variation in “identical” bibliographic holdings among the broader academic library community.
The Limitations of "Boilerplate" Language in Informed Consent: Single IRB Review of Multisite Genetic Research in Military Personnel.

Informed consent forms have commonly included standardized language, often referred to as “boilerplate” language, that has been vetted by institutional officials. The implicit goal is to ensure tha...
On the Noncommutative and Nonassociative Geometry of Octonionic Spacetime, Modified Dispersion Relations and Grand Unification

The Octonionic Geometry (Gravity) developed long ago by Oliveira and Marques is extended to Noncommutative and Nonassociative Spacetime coordinates associated with octonionic-valued coordinates and momenta. The octonionic metric Gμν already encompasses the ordinary spacetime metric gμν, in addition to the Maxwell U(1) and SU(2) Yang-Mills fields such that implements the Kaluza-Klein Grand Unification program without introducing extra spacetime dimensions. The color group SU(3) is a subgroup of the exceptional G2 group which is the automorphism group of the octonion algebra. It is shown that the flux of the SU(2) Yang-Mills field strength Fμν through the area momentum Σμν in the internal isospin space yields corrections O(1/M2Planck) to the energy-momentum dispersion relations without violating Lorentz invariance as it occurs with Hopf algebraic deformations of the Poincare algebra. The known Octonionic realizations of the Clifford Cl(8),Cl(4) algebras should permit the construction of octonionic string actions that should have a correspondence with ordinary string actions for strings moving in a curved Clifford-space target background associated with a Cl(3, 1) algebra.
Archaeal ribosomal proteins possess nuclear localization signal-type motifs: implications for the origin of the cell nucleus

Abstract Eukaryotic cells are divided into the nucleus and the cytosol, and, to enter the nucleus, proteins typically possess short signal sequences, known as nuclear localization signals (NLSs). Although NLSs have long been considered as features unique to eukaryotic proteins, we show here that similar or identical protein segments are present in ribosomal proteins from the Archaea. Specifically, the ribosomal proteins uL3, uL15, uL18, and uS12 possess NLS-type motifs that are conserved across all major branches of the Archaea, including the most ancient groups Microarchaeota and Diapherotrites, pointing to the ancient origin of NLS-type motifs in the Archaea. Furthermore, by using fluorescence microscopy, we show that the archaeal NLS-type motifs can functionally substitute eukaryotic NLSs and direct the transport of ribosomal proteins into the nuclei of human cells. Collectively, these findings illustrate that the origin of NLSs preceded the origin of the cell nucleus, suggesting that the initial function of NLSs was not related to intracellular trafficking. Overall, our study reveals rare evolutionary intermediates among archaeal cells that can help elucidate the sequence of events that led to the origin of the eukaryotic cell.
The clinical and biologic impact of PPP6C mutations in melanoma.

9067 Background: PP6C binds to regulatory units to affect a number of important pathways including cell proliferation and DNA repair. Recently two independent groups reported for the first time the...
Automatic Generation of Flexible-Monomer Intermolecular Potential Energy Surfaces.

A method is developed for automatic generation of nonreactive intermolecular two-body potential energy surfaces (PESs) including intramonomer degrees of freedom. This method, called flex-autoPES, i...
Prescription Pain Reliever Use and Misuse among Cannabis Users Aged 50+ Years.

Objectives: To examine rates and correlates of dual cannabis and prescription pain reliever (PPNR) use and misuse among U.S. individuals aged 50+ who reported past-year cannabis use.Methods: Using ...
Reciprocity and informal institutions in international market entry

Abstract This article first identifies two gaps in the literature: (1) the need to expand international market entry research beyond contractual modes of “make, buy, and ally;” and (2) the need to address the imbalance in the institution-based view that has paid inadequate attention to informal institutions. To help close the two gaps, we identify reciprocity—the mutually contingent exchange of gratifications that is supported by informal institutions—to be a non-contractual mode of international market entry. We focus on how informal institutions provide some of the conditions, motivations, and precipitating circumstances behind the use of reciprocity.
A Speech Emotion Recognition Solution-based on Support Vector Machine for Children with Autism Spectrum Disorder to Help Identify Human Emotions

Children who fall into the autism spectrum have difficulty communicating with others. In this work, a speech emotion recognition model has been developed to help children with Autism Spectrum Disorder (ASD) identify emotions in social interactions. The model is created using the Python programming language to develop a machine learning model based on the Support Vector Machine (SVM). SVM has proven to yield high accuracies when classifying inputs in speech processing. Individual audio databases are specifically designed to train models for the emotion recognition task. One such speech corpus is the Ryerson Audio-Visual Database of Emotional Speech and Song (RAVDESS), which is used to train the model in this work. Acoustic feature extraction will be part of the pre-processing step utilizing Python libraries. The libROSA library is used in this work. The first 26 Mel-frequency Cepstral Coefficients (MFCCs) and the zero-crossing rate (ZCR) are extracted and used as the acoustic features to train the machine learning model. The final SVM model provided a test accuracy of 77%. This model also performed well when significant background noise was introduced to the RAVDESS audio recordings, for which it yielded a test accuracy of 64%.
Conservation management practices reduce non-point source pollution from grazed pastures

Abstract Producers in Northwest Arkansas and globally need alternative management practices to ensure long-term sustainable and economical use of poultry litter, which is an abundant source of valuable carbon (C), nitrogen (N) and phosphorus (P). Project objectives were to measure the efficacy of conservation management practices (i.e., pasture aeration and subsurface litter incorporation) to reduce nutrient runoff compared to poultry litter surface applications from small watersheds under rainfed and grazed conditions. Watersheds (0.23 ha each) were assigned a treatment [pasture aeration, subsurface litter incorporation, or surface application of litter (positive control)] on a Leadvale (fine-silty, siliceous, thermic Typic Fragiudult) silt loam. Poultry litter was applied annually to each watershed from 2007-2012. Over the 4-yr study period, runoff loads of NO3–N, total nitrogen (TN), soluble reactive phosphorus (SRP), and total phosphorus (TP) varied per conservation practice (P ≤ 0.05). Specifically, average annual loads of NO3–N, TN, SRP, and TP loads were reduced 49, 42, 28, and 35% following pasture aeration and by 78, 72, 55, and 59% from subsurface applying poultry litter, relative to surface applications, respectively. Greatest annual N loads and runoff corresponded with surface poultry litter applications, followed by pasture aeration, with subsurface incorporation of poultry litter resulting in lowest (P ≤ 0.05) TN and NO3–N loads. Overall, subsurface incorporation of poultry litter and pasture aeration are two promising conservation practices for reducing non-point source pollution in watersheds with nutrient imbalances. Further work needs to be done on factors influencing the efficacy of these conservation practices under rainfed conditions, as well as the economic feasibility of these conservation agricultural practices.
Ribosome states signal RNA quality control

Eukaryotic cells integrate multiple quality control (QC) responses during protein synthesis in the cytoplasm. These QC responses are signaled by slow or stalled elongating ribosomes. Depending on the nature of the delay, the signal may lead to translational repression, messenger RNA decay, ribosome rescue, and/or nascent protein degradation. Here, we discuss how the structure and composition of an elongating ribosome in a troubled state determine the downstream quality control pathway(s) that ensue. We highlight the intersecting pathways involved in RNA decay and the crosstalk that occurs between RNA decay and ribosome rescue.
Urban resilience: Analyzing the policies of U.S. cities.

Abstract Resilience has become an important concept in urban governance, yet, the policies that cities actually adopt and implement to build resilience remain largely unknown. The lack of empirical studies on resilience policies hinders our ability to develop theory, ask new questions, and test hypotheses. The goal of this paper is to quantify and compare policies and programs of the 101 largest cities in the U.S. that tangibly affect resilience. We develop a set of resilience policies and then search government websites for evidence of adoption of those policies. To explore patterns of policy adoption, we conduct factor analysis and correlation. We find that resilience does not coalesce around any particular sets of programs. Instead, resilience is a flexible concept, modified to address local context. Substantive groupings of policies do not explain policy adoption. Different dimensions such as funding and level of needed commitment may better explain empirical patterns of policy adoption. Across cities, greater attention must be dedicated to addressing drivers of social vulnerability and climate change impacts. By examining what cities are doing and whether there are underlying patterns to the policies they pursue, we tackle basic empirical questions of how to make sense of the evolving resilience landscape.
Multiorgan Infarctions in a Young Adult with COVID-19: Autopsy Findings

Coronavirus disease 2019 (COVID-19) may cause a hypercoagulability state and thrombotic complications. Multiorgan infarctions in young patients are very rare. Here we report a 35-year-old male patient with COVID-19 complicated by multiorgan infarctions. The patient had a past medical history of uncontrolled insulin-dependent diabetes mellitus and was admitted to the intensive care unit with progressive hypoxia in the setting of SARS-CoV-2 infection. The patient received prophylactic anticoagulant during the entire hospital course. During the hospitalization, the patient developed hypoxic respiratory arrest, diffuse anoxic brain injury and brain herniation. Postmortem examination demonstrated multiple infarctions and thromboses involving the heart, bilateral lungs, kidneys, and spleen. In conclusion, multiple organ infarctions may occur in young patients with COVID-19 despite prophylactic anticoagulation therapy.
Disease modification is not all - we need symptomatic therapies for Alzheimer disease.

A new study found methylphenidate to be effective in treating apathy in individuals with Alzheimer disease. At a time when the recent aducanumab approval is focusing attention on the promise of disease-modifying therapies, the new findings highlight the importance of developing better symptomatic treatment options for individuals with psychiatric disorders of Alzheimer disease.
Alleviating the Negative Effect of Up and Downvoting on Help Seeking in MOOC Discussion Forums

Through the lens of Expectancy Value Theory, we examine the effect of help giver badges, information about helper expertise, and up- and downvoting on help seeking in a MOOC discussion forum. Results show that badges alleviated the negative impact on help seeking introduced by up- and downvoting.
Simplified quantification of dopamine transporters in humans using [99mTc]TRODAT-1 and single-photon emission tomography.

Quantification of dopamine transporters (DAT) using [99mTc]TRODAT-1 and single-photon emission tomography (SPET) requires full kinetic modeling of the data, using complex and invasive arterial blood sampling to provide an input function to the model. We have shown previously that a simpler reference tissue model provides accurate quantitative results, using a reference region devoid of DAT as the input to the model and thereby obviating the need for blood sampling. We now extend this work into humans, and develop further simplifications to make the imaging protocol much more practical as a routine procedure. Fourteen healthy subjects (age 29.8±8.4 years, range 18.7–45.5 years) underwent dynamic SPET for 6 h following injection of 752±28 MBq [99mTc]TRODAT-1. The kinetic data were analyzed using nonlinear regression analysis (NLRA) and Logan-Patlak graphical analysis. In addition, simple average ratios of striatal-to-background counts were obtained for three 1-h periods (3–4 h, 4–5 h, 5–6 h), and compared against the kinetic models. All methods gave an index of specific binding, proportional to the binding potential, known as the distribution volume ratio (DVR). The reference tissue NLRA gave mean values of k 3=0.013±0.003 min–1, k 4=0.011±0.002 min–1, and DVR=2.29±0.17. Graphical analysis gave a value of DVR=2.28±0.16, and the three ratio values of DVR were: 3–4 h, 2.18±0.15; 4–5 h, 2.34±0.13; and 5–6 h, 2.46±0.19. Graphical analysis was highly correlated with NLRA (R 2=0.91, slope=0.90±0.08). The ratio methods correlated well with NLRA (3–4 h, R 2=0.71, slope=0.73±0.13; 4–5 h, R 2=0.86, slope=0.73±0.09; 5–6 h, R 2=0.80, slope=1.00±0.15), and also with graphical analysis (3–4 h, R 2=0.65, slope=0.74±0.16; 4–5 h, R 2=0.85, slope=0.78±0.09; 5–6 h, R 2=0.88, slope=1.11±0.12). The optimum equilibrium time point for obtaining a simple ratio was approximately 4.5–5.5 h. In conclusion, the simple ratio techniques for obtaining a quantitative measure of specific binding correlated well with the reference tissue kinetic models, using both NLRA and graphical analysis. The optimum time for obtaining a ratio appeared to be in the range 4.5–5.5 h. Earlier time points, while still relatively accurate, had a lower sensitivity and may not be optimized for measuring small changes in DAT concentrations.
Sphingosine 1-phosphate as an intracellular messenger and extracellular mediator in immunity.

UNLABELLED The omnific mediator system composed of sphingosine 1-phosphate (S1P) and its five G-protein-coupled receptors, designated S1P(1)-S1P(5), affects diverse cellular functions in the nervous, endocrine, cardiovascular and immune systems. The many activities of the S1P-S1P(1) axis, which predominates in the cardiovascular and immune systems, have previously been classified according to their relationship with the distinct functional roles of each type of cell or according to their most frequently used signalling pathways. In the immune system, cell surface S1P(1) receptors transduce the rapid, transient effects of extracellular S1P on T- and B-lymphocyte trafficking in the lymphoid system, lymphocyte migration in non-immune tissues and cytokine generation. After immune stimulation of T- and B-lymphocytes, S1P(1) receptors translocate from the cell surface to endosomal and nuclear compartments. The present hypothesis is that nuclear S1P(1) receptors represent distinct signalling complexes that, through a series of transcriptional events, transduce the sustained effects of intracellular S1P on survival and proliferation of T-lymphocytes. It is postulated that similar types of sustained signalling from nuclear S1P receptors in other types of cells affect proliferation, survival and specific effector functional activities. Effective pharmacological approaches to intracellular, as well as cell surface, S1P-S1P receptor axes will thus require the bioaccessibility of agonists and antagonists to the nuclear domain of relevant target cells. CONCLUSION Most investigations of the effects of the S1P-S1P(1) axis in immunity have focused primarily on rapid, transient alterations in lymphocyte migration and trafficking, and on mast cell migration and secretion of chemical mediators. The discovery of functional S1P(1)-G protein signalling complexes in the nuclear membranes of activated lymphocytes, that are coupled to the transduction of prolonged inhibition of proliferative responses by intracellular S1P, adds a new dimension to the role of the S1P-S1P(1) axis in immunity. Recruitment of this novel, potentially immunosuppressive, function of S1P(1) may be beneficial in some autoimmune diseases and will require application of cell membrane-permeant S1P(1)-specific drugs.
Riemann–Finsler geometry and Lorentz-violating kinematics

Effective field theories with explicit Lorentz violation are intimately linked to Riemann–Finsler geometry. The quadratic single-fermion restriction of the Standard-Model Extension provides a rich source of pseudo-Riemann–Finsler spacetimes and Riemann–Finsler spaces. An example is presented that is constructed from a 1-form coefficient and has Finsler structure complementary to the Randers structure.
Contribution of extrasynaptic N-methyl-D-aspartate and adenosine A1 receptors in the generation of dendritic glutamate-mediated plateau potentials

Thin basal dendrites can strongly influence neuronal output via generation of dendritic spikes. It was recently postulated that glial processes actively support dendritic spikes by either ceasing glutamate uptake or by actively releasing glutamate and adenosine triphosphate (ATP). We used calcium imaging to study the role of NR2C/D-containing N-methyl-d-aspartate (NMDA) receptors and adenosine A1 receptors in the generation of dendritic NMDA spikes and plateau potentials in basal dendrites of layer 5 pyramidal neurons in the mouse prefrontal cortex. We found that NR2C/D glutamate receptor subunits contribute to the amplitude of synaptically evoked NMDA spikes. Dendritic calcium signals associated with glutamate-evoked dendritic plateau potentials were significantly shortened upon application of the NR2C/D receptor antagonist PPDA, suggesting that NR2C/D receptors prolong the duration of calcium influx during dendritic spiking. In contrast to NR2C/D receptors, adenosine A1 receptors act to abbreviate dendritic and somatic signals via the activation of dendritic K(+) current. This current is characterized as a slow-activating outward-rectifying voltage- and adenosine-gated current, insensitive to 4-aminopyridine but sensitive to TEA. Our data support the hypothesis that the release of glutamate and ATP from neurons or glia contribute to initiation, maintenance and termination of local dendritic glutamate-mediated regenerative potentials.
Trade Secret Law and Information Development Incentives

Trade secrets differ from other forms of intellectual property in many subtle ways that affect incentives to invest in information development. These differences relate not only to the types of information protected, but also to the requirements one must meet to protect that type of information. The various divergences and intersections of trade secret laws with other intellectual property laws lead to differences in the amount and types of investments companies make in developing information. This chapter explores five types of differential incentives associated with trade secret law: - Trade secret law v. no trade secret law- Trade secret law v. patent law- Trade secret law v. copyright law- Trade secret law v. trademark law- Trade secret law v. right to privacyTrade secret law provides little incentive to innovate as compared to a world without trade secret law for two possible reasons. First, the law provides little incentive because companies will create secret information even in the absence of the legal protection - trade secret law provides little protection that self-help protection does not. Second, the value of shared information means that nominal secrets would otherwise be shared, such that trade secret laws are routinely disregarded in investment decisions. This chapter explores each of these alternate theories, as well as limits and exceptions to each.Trade secret law does, however, provide some incentives to innovate vis a vis other types of intellectual property, although the incentives are not always obvious, intuitive, or necessarily great. This chapter considers how trade secret law differs from other types of intellectual property laws, and uses those distinctions to show that trade secret law will have some effect on incentives to innovate when compared to other forms of protection.
Effect of phosphodiesterase antagonists on glucocorticoid mediated growth inhibition in murine skin cell lines

Abstract The effects of two cyclic nucleotide phosphodiesterase type 4 (PDE4) inhibitors on proliferation of cell lines representing different stages of mouse skin tumorigenesis were studied. Skin papillomas and carcinomas become resistant to the growth inhibition by glucocorticoids. Their control of cellular functions is mediated by a well-known transcription factor, glucocorticoid receptor. The primary aim of the present study was to determine whether the PDE4 inhibitors, that raise intracellular cAMP levels, can increase the sensitivity of mouse skin papillomas and carcinomas to the glucocorticoids. We sought to establish the effect of cAMP signaling on the glucocorticoid receptor function using well-known model representing non-tumorigenic keratinocyte cell line (3PC), papilloma (MT1/2) and squamous cell carcinoma cell line (Ca3/7). These cells were treated with the glucocorticoid fluocinolone acetonide (FA) alone or in concert with PDE4 inhibitors – rolipram or YM976. Results of our study revealed that both PDE4 inhibitors may increase the sensitivity of transformed cell lines to the growth inhibitory effect of FA. In the transformed cell lines, changes in the viability of cells were accompanied by an increase in mRNA level of two negative regulators of the cell cycle – p21 and p27 proteins. Co-treatment with PDE4 inhibitors and FA caused inhibition of an endogenous glucocorticoid-responsive gene (MT-1) expression. Thus, the PDE4 inhibitors exerted a differential effect on non-transformed and transformed keratinocytes and on glucocorticoid receptor signal transduction. These findings warrant further studies to clarify the mechanism by which PDE4 inhibitors modulate glucocorticoid receptor signal transduction in transformed cells.
Climate-driven synchrony across tree, bivalve, and rockfish growth-increment chronologies of the northeast Pacific

Interrelationships are analyzed among growth-increment chronologies of yelloweye rockfish Sebastes ruberrimus, splitnose rockfish Sebastes diploproa, and the bivalve species Pacific geoduck Panopea abrupta in the northeast Pacific. The chronologies are annually resolved, multi- decadal in length, and range in location from central California through northern British Columbia. In a principal components analysis, the first component explained 52% of the variance in the dataset and separated chronologies from the northern half of the study area from those in the southern half. The northern chronologies significantly and positively correlate with seasonally averaged records of the Multivariate ENSO Index (MEI) and the Pacific Decadal Oscillation (PDO), while the southern chronologies negatively correlate with the same variables, especially during the winter and spring. Such an inverse growth regime is consistent with primary and secondary productivity patterns in the northeast Pacific. The second principal component accounted for 23% of the variance in the dataset and captured a growth pattern associated with climatic variability in the spring and summer months. Both principal components derived from the marine chronologies relate to tree-ring chronologies in western North America, due to shared sensitivities to climatic variability. Interrelationships among these chronologies underscore the synchronous and pervasive impacts of climate on very diverse taxa and ecosystems in western North America.
Teaching Trauma Care in India: An Educational Pilot Study From Bangalore

Background Trauma has become a major cause of death and disability in developing countries. In India, most trauma patients receive initial care at general practitioner-staffed hospitals. We hypothesize that general practitioners (GPs) could improve their knowledge of trauma care after attending an educational course. Methods A 2-day trauma course was conducted at a teaching hospital (170 bed) in Bangalore, India. Referral GPs, local surgeons and residents in training attended. A pre-course test was given to assess baseline trauma knowledge. The core didactic sessions included: resuscitation/recognition of shock states, airway prioritization, and evaluation/initial management of head, cardiothoracic, abdominal, pelvic/genitourinary, and thermal injuries. A post-course test was used to assess trauma knowledge obtained from the course. Paired t tests were performed on the test scores and demographic data were stratified by specialty and training status. Results Of the 44 participants, 32 (72%) met study inclusion criteria: MBBS degree and course completion. The study population was 62.5% male with 47% surgeons and 53% GPs. Residents were 71.8% of the entire group. Overall, the pre- and post- course scores improved from 70.7% ±11.2 to 87.5% ±8.9, P = 0.000 (95%CI 12.1, 21.2). There was an increase of mean scores: 21.4% (SD ±13.7) for GPs and 11.3% (SD ±8.5) for surgeons ( P = 0.02). Conclusion Although GPs had significantly lower pre-course scores than surgeons, at the end of the course, GPs performed as well as surgeons. These findings suggest allocation of limited educational resources for trauma care in India may be best used by GPs.
There is grandeur in this view of Newton: Charles Darwin, Isaac Newton and Victorian conceptions of scientific virtue

For Victorian men of science, the scientific revolution of the seventeenth century represented a moral awakening. Great theoretical triumphs of inductive science flowed directly from a philosophical spirit that embraced the virtues of self-discipline, courage, patience and humility. Isaac Newton exemplified this union of moral and intellectual excellence. This, at least, was the story crafted by scientific leaders like David Brewster, Thomas Chalmers, John Herschel, Adam Sedgwick and William Whewell. Not everyone accepted this reading of history. Evangelicals who decried the 'materialism' of mainstream science assigned a different meaning to Newton's legacy on behalf of their 'scriptural' alternative. High-church critics of science like John Henry Newman, on the other hand, denied that Newton's secular achievements carried any moral significance at all. These debates over Newtonian standards of philosophical behavior had a decisive influence on Charles Darwin as he developed his theory of evolution by natural selection.
Reduced Ileal Taurocholate Absorption with Total Parenteral Nutrition

Total parenteral nutrition is associated with decreased primary bile acid output. This may result from reduced synthesis or decreased absorption of primary bile acids in the enterohepatic circulation. Ileal atrophy occurs with total parenteral nutrition, and we postulated that absorption of primary bile acids is reduced. Ileal absorption of taurocholate was investigated in miniswine on total parenteral nutrition and this was compared to orally fed animals. Following cholecystectomy and bile duct cannulation, 20 cm, of lieum was perfused with taurocholate. Since miniswine have no significant endogenous taurocholate secretion, the measured taurocholate output reflected ileal absorption. To examine uptake and secretion of taurocholate by the liver, pigs on total parenteral nutrition and controls were infused with intravenous taurocholate (0.5 to 2.5 μmole/kg/min), and bile acid output was determined. Baseline bile acid output was decreased in animals on total parenteral nutrition, yet the response to intravenous taurocholate was similar to controls. When taurocholate was perfused in the ileum, taurocholate output was markedly different. Taurocholate output (pmole/cm ileum/min) at the taurocholate perfusate concentrations of 3 and 20 mM was, respectively, 65 ± 14 and 183 ± 63 for controls and 18 ± 3 and 63 ± 17 for miniswine on total parenteral nutrition. The latter group's output was significantly lower, at P < 0.05. Both groups of pigs had equal increases in bile acid output with intravenous infusion of taurocholate, suggesting normal hepatic uptake and secretion. Ileal perfusion with taurocholate, however, resulted in decreased taurocholate output with total parenteral nutrition due to decreased ileal absorption of bile acids. This may contribute to the reduction in primary bile acid secretion that occurs with total parenteral nutrition.
Ischemic versus pharmacologic hepatic preconditioning

Background: Hepatic ischemiaereperfusion injury has a significant impact on liver resection and transplantation. Many strategies have been developed to reduce the effects of ischemiaereperfusion injury, including pharmacologic and ischemic preconditioning; however, studies comparing these two methods are lacking. Material and methods: Anexperimentalstudywasperformedinaswinemodel.Eighteenswine
Preferential glial cell attachment to microcontact printed surfaces

Microcontact printing is introduced as a method for fabricating test surfaces for attachment of cells to chemically patterned silicon surfaces. Tests with astroglial cells indicate that cells attach to microcontact printed surfaces similarly to surfaces produced by traditional photolithographic methods. Astroglial cells attach selectively to 50 μm wide bars of N1[3-(Trimethoxysilyl)propyl]diethylenetriamine (DETA) self-assembled monolayers (SAMs) on surfaces prepared using variable width spaces generated from microcontact printing with octadecyltrichlorosilane (OTS) as the ink. Our results demonstrate that microcontact printing provides an effective and rapid method for routine production of patterned self-assembled monolayers that can be used for directing cell attachment and studying cell morphology.
Low-temperature dehydrogenation reaction–separation membranes using zeolite 13X polyethylacrylate

Abstract We prepared blend and pseudo-interpenetrating network (PIPN) membranes containing zeolite 13X with the dehydrogenation catalyst (Ti or Ni) and polyethylacrylate (PEA). Membranes were tested by a single cell reactor using the dehydrogenation reaction of cyclohexane to benzene at low temperatures (323–360 K). Proton nuclear magnetic resonance (NMR) was used to analyze the composition of the throughput and the feed in our experiments. Using 2 wt% of Ti or Ni on 40 wt% of zeolite with 60 wt% PEA the conversion ratio of benzene to cyclohexane was about 4–8%. The feed did not contain measurable amounts of benzene, hence the separation was complete. Scanning electron microscopy (SEM) results showed that the blend membrane developed cracks considerably earlier than the PIPN membrane. We also find the pseudo-first-order rate constant and its activation energy for the dehydrogenation reaction in the membrane by using a phenomenological diffusion–reaction model. The latter values are consistent with surface diffusion control of the kinetics.
Negative Correlation of Distributions of Streptococcus cristatus and Porphyromonas gingivalis in Subgingival Plaque

Porphyromonas gingivalis is one of the major causative agents of adult periodontitis. One of the features of this periodontal pathogen is its ability to attach to a variety of oral bacterial surfaces and to colonize subgingival dental plaque. We have shown that Streptococcus cristatus CC5A inhibits expression of fimA, a gene encoding the major protein subunit of long fimbriae in P. gingivalis; as a result, S. cristatus interrupts formation of P. gingivalis biofilms. Here we further demonstrate that the inhibitory activity of S. cristatus affects multiple strains of P. gingivalis and that optimal inhibitory activity correlates with levels of arginine deiminase expression in S. cristatus. More strikingly, the impact of S. cristatus on P. gingivalis colonization was revealed by comparing levels of P. gingivalis and S. cristatus in subgingival dental plaque. Spearman correlation analysis indicated a negative correlation between the distributions of S. cristatus and P. gingivalis (r = -0.57; P < 0.05). These data suggest that some early colonizers of dental plaque, such as S. cristatus, may be beneficial to the host by antagonizing the colonization and accumulation of periodontal pathogens such as P. gingivalis.