cssi/SciSciGPT-SciSciNet huggingface dataset:
A Model for the Origin of Life through Rearrangements among Prebiotic Phosphodiester Polymers

This model proposes that the origin of life on Earth occurred as a result of a process of alteration of the chemical composition of prebiotic macromolecules. The stability of organic compounds assembled into polymers generally exceeded the stability of the same compounds as free monomers. This difference in stability stimulated accumulation of prebiotic macromolecules. The prebiotic circulation of matter included constant formation and decomposition of polymers. Spontaneous chemical reactions between macromolecules with phosphodiester backbones resulted in a non-Darwinian selection for chemical stability, while formation of strong structures provided an advantage in the struggle for stability. Intermolecular structures between nucleotide-containing polymers were further stabilized by occasional acquisition of complementary nucleotides. Less stable macromolecules provided the source of nucleotides. This process resulted first in the enrichment of nucleotide content in prebiotic polymers, and subsequently in the accumulation of complementary oligonucleotides. Finally, the role of complementary copy molecules changed from the stabilization of the original templates to the de novo production of template-like molecules. I associate this stage with the origin of life in the form of cell-free molecular colonies. Original life acquired ready-to-use substrates from constantly forming prebiotic polymers. Metabolism started to develop when life began to consume more substrates than the prebiotic cycling produced. The developing utilization of non-polymeric compounds stimulated the formation of the first membrane-enveloped cells that held small soluble molecules. Cells “digested” the nucleotide-containing prebiotic macromolecules to nucleotide monomers and switched the mode of replication to the polymerization of nucleotide triphosphates.
Health care expenditures of self-employed farm households in the United States

For self-employed individuals and their families, purchases of health care services and health insurance policies have the potential to impact their health status, as well as the financial viability of their businesses. Most people in the United States receive health insurance coverage through employer-sponsored programs. Self-employed individuals and their households, such as farm households, may face a greater challenge in getting affordable health insurance. Using a large cross-sectional farm household level dataset, we estimate the impact of the source of health insurance on health care expenditures of farm households in the United States. Results suggest that farm households purchasing individual health insurance directly from vendors are likely to spend more on health care than those with other sources of health insurance. After controlling for a variety of personal and local area characteristics, having health insurance was negatively related to total health care expenditures. Age and income, not surprisingly, were also found to be significant in explaining health care expenditures.
36.1: Wide Field of View Compressive Light Field Display using a Multilayer Architecture and Tracked Viewers

In this paper, we discuss a simple extension to existing compressive multilayer light field displays that greatly extends their field of view and depth of field. Rather than optimizing these displays to create a moderately narrow field of view at the center of the display, we constrain optimization to create narrow view cones that are directed to the viewer's eyes, allowing the available display bandwidth to be utilized more efficiently. These narrow view cones follow the viewer, creating a wide apparent field of view. Imagery is also recalculated for the viewer's exact position, creating a greater depth of field. The view cones can be scaled to match the positional error and latency of the tracking system. Using more efficient optimization and commodity tracking hardware and software, we demonstrate a real-time, glasses-free 3D display that offers a 110times45 degree field of view.
Mechanistic evaluation of binary effects of magnesium stearate and talc as dissolution retardants at 85% drug loading in an experimental extended-release formulation

The feasibility of producing extended-release matrix tablets with high drug loadings (80-90% w/w) containing a binary combination of magnesium stearate (MS) and talc (T) at different levels as major dissolution retardants was investigated. Matrix tablets were prepared from a granulation containing theophylline, starch, hydroxypropylcellulose, and varying amounts of MS and T. Using a 32 factorial design, the effect of MS and T levels on the physical properties and drug release characteristics of the tablets was evaluated. Response surface analysis showed that the binary combination of MS and T at levels >3% adversely affected both tensile strength and friability. A parabolic relationship was observed for the increase in time required for the release of 50% of the theophylline (t50%) with increased MS levels. Moreover, as the proportion of MS and T was increased, the release profiles became more linear. A combination of 3% MS and T provided both near zero-order release kinetics as well as a coherent matrix structure. Based on model fitting, a release mechanism combining diffusion and matrix erosion/dissolution is proposed. It may be concluded that in the development of controlled-release systems, the binary combination of MS and T at levels exceeding those conventionally used for lubrication can be employed as an inexpensive, low bulk dissolution retardant for formulations with high drug loading.
Observations on the geometry of saddle node bifurcation and voltage collapse in electrical power systems

Saddle node bifurcation is a generic instability of parameterized differential equation models. The bifurcation geometry and some implications for the study of voltage collapse in electric power systems is described. The initial direction in state space of dynamic voltage collapse can be calculated from a right eigenvector of a static power system model. The normal vector to the bifurcation set in parameter space is a simple function of a left eigenvector and is expected to be useful in emergency control near bifurcation and in computing the minimum distance to bifurcation in parameter space. >
UTERINE ADENOMATA IN THE RABBIT : I. CLINICAL HISTORY, PATHOLOGY AND PRELIMINARY TRANSPLANTATION EXPERIMENTS.

83 cases of an adenomatous tumor of the uterine mucosa have been observed in a colony of rabbits during the past 4 years The results of a clinical and pathological study of the tumor, together with a description of transplantation experiments are included in the present report. The clinical histories of tumor bearing animals are similar in all cases. Discovery of the tumor is preceded by a long period of reproductive disturbance, and its subsequent course is one of slow, continuous growth which has terminated in death with metastasis in all animals held under observation for longer than 1 year. Microscopically, the tumor shows an atypical alveolar structure, and its characteristics closely resemble those of an adenocarcinoma of the uterine fundus in women. Pathological changes similar to those observed in mice after treatment with estrogenic substances occur in the thyroid, suprarenal, pituitary and mammary glands. Intraocular transplantation of the tumor has been successful, and at the present time the growth has been carried through 6 generations by serial transfer.
CT Neuroangiography: A Glance at the Common Pitfalls and Their Prevention

OBJECTIVE. The author’s objective was to address several pitfalls and missteps of CT angiography (CTA) with pictorial examples and ways to overcome potential misinterpretations. CTA is increasingly used for the noninvasive evaluation of the carotid and intracranial vessels. Ease of data acquisition may belie the complexity of interpreting each individual vessel and understanding myriad postprocessing techniques, each with its strengths and weaknesses. CONCLUSION. Diagnostic yield and accuracy of CT angiography are enhanced by good data acquisition and by understanding and fully exploiting postprocessing techniques. ewer-generation MDCT scanners with submillimeter detectors and subsecond rotation capabilities have led to quantum leaps in the noninvasive evaluation of the cerebral vasculature. Some of the MDCTs have isotropic voxel capability that ensures the same resolution in every plane of reformations. CT angiography (CTA) has been shown to be equal if not better than conventional angiogram in the detection of cerebral aneurysms [1]. In a series of 41 aneurysms measuring equal to or less than 4 mm, sensitivity of CTA for the detection of cerebral aneurysms was higher than that of digital subtraction angiography, with equal specificity [2]. In another study, aneurysms that were overlooked at the initial interpretation of CTA were identified at a retrospective reading [3]. This underscores the importance of careful scrutiny of CTA and the need to be familiar with factors that can adversely affect the interpretation. Several pitfalls of CTA have been described, including diffiN
Calibration considerations for piezoresistive-based stress sensors

The authors present a study of the variation of the piezoresistive coefficients over several devices on the same die, the same wafer, and at different doping levels. The sensor test vehicles are fully documented, and a thorough error analysis on the method of applying a known uniaxial state of stress is presented. It is shown that individual stress-sensor calibration is required if the uncertainty in the absolute values of the measured stresses needs to be less than 15%. If the uncertainty only needs to be less than 50%, then one device per wafer can be calibrated or an equation relating the unstressed resistance values to the piezoresistance coefficients can be used. >
Ross River virus envelope glycans contribute to type I interferon production in myeloid dendritic cells.

Alphaviruses are mosquito-transmitted viruses that cause significant human disease, and understanding how these pathogens successfully transition from the mosquito vector to the vertebrate host is an important area of research. Previous studies demonstrated that mosquito and mammalian-cell-derived alphaviruses differentially induce type I interferons (alpha/beta interferon [IFN-α/β]) in myeloid dendritic cells (mDCs), where the mosquito cell-derived virus is a poor inducer of IFN-α/β compared to the mammalian-cell-derived virus. Furthermore, the reduced IFN-α/β induction by the mosquito cell-derived virus is attributed to differential N-linked glycosylation (29). To further evaluate the role of viral envelope glycans in regulating the IFN-α/β response, studies were performed to assess whether the mosquito cell-derived virus actively inhibits IFN-α/β induction or is simply a poor inducer of IFN-α/β. Coinfection studies using mammalian- and mosquito cell-derived Ross River virus (mam-RRV and mos-RRV, respectively) indicated that mos-RRV was unable to suppress IFN-α/β induction by mam-RRV in mDC cultures. Additionally, a panel of mutant viruses lacking either individual or multiple N-linked glycosylation sites was used to demonstrate that N-linked glycans were essential for high-level IFN-α/β induction by the mammalian-cell-derived virus. These results suggest that the failure of the mosquito cell-derived virus to induce IFN-α/β is due to a lack of complex carbohydrates on the virion rather than the active suppression of the DC antiviral response.
Healthcare information technology's relativity problems: a typology of how patients' physical reality, clinicians' mental models, and healthcare information technology differ

Objective To model inconsistencies or distortions among three realities: patients' physical reality; clinicians' mental models of patients' conditions, laboratories, etc; representation of that reality in electronic health records (EHR). To serve as a potential tool for quality improvement of EHRs. Methods Using observations, literature, information technology (IT) logs, vendor and US Food and Drug Administration reports, we constructed scenarios/models of how patients' realities, clinicians' mental models, and EHRs can misalign to produce distortions in comprehension and treatment. We then categorized them according to an emergent typology derived from the cases themselves and refined the categories based on insights gained from the literature of interactive sociotechnical systems analysis, decision support science, and human computer interaction. Typical of grounded theory methods, the categories underwent repeated modifications. Results We constructed 45 scenarios of misalignment between patients' physical realities, clinicians' mental models, and EHRs. We then identified five general types of misrepresentation in these cases: IT data too narrowly focused; IT data too broadly focused; EHRs miss critical reality; data multiplicities–perhaps contradictory or confusing; distortions from data reflected back and forth across users, sensors, and others. The 45 scenarios are presented, organized by the five types. Conclusions With humans, there is a physical reality and actors' mental models of that reality. In healthcare, there is another player: the EHR/healthcare IT, which implicitly and explicitly reflects many mental models, facets of reality, and measures thereof that vary in reliability and consistency. EHRs are both microcosms and shapers of medical care. Our typology and scenarios are intended to be useful to healthcare IT designers and implementers in improving EHR systems and reducing the unintended negative consequences of their use.
Security analysis of and proposal for image-based authentication

Most human authentication systems have been text-based. Recent psychological studies show users' inability to recall random character sequences. Image-based authentication systems have shown promise in circumventing this problem. In addition, they are more intuitive and user-friendly. This paper presents and analyzes a user authentication technique using images that can be used in local as well as remote authentication. We also consider TEMPEST and other forms of attack.
Why Tests Appear to Prevent Forgetting: A Distribution-Based Bifurcation Model.

Retrieving information from memory produces more learning than does being presented with the same information, and the benefits of such retrieval appear to grow as the delay before a final recall test grows longer. Recall tests, however, measure the number of items that are above a recall threshold, not memory strength per se. According to the model proposed in this paper, tests without feedback produce bifurcated item distributions: Retrieved items become stronger, but non-retrieved items remain weak, resulting in a gap between the two classes of items. Restudying items, on the other hand, strengthens all items, though to a lesser degree than does retrieval. These differing outcomes can make tested items appear to be forgotten more slowly than are restudied items—even if all items are forgotten at the same rate—because the test-induced bifurcation leaves items either well above or well below threshold. We review prior evidence and present three new experiments designed to test the bifurcation interpretation.
Error compensation for sculptured surface productions by the application of control-surface strategy using predicted machining errors

In this paper, the principle and effectiveness of the control-surface strategy in machining-error compensation for end milling processes are studied. Using this strategy, two new approaches, namely the direct compensation approach and the sensitivity function approach, are proposed. When compared to existing approaches, there are two major improvements in the proposed approaches. First, machining errors caused by tool deflection are estimated from a developed surface generation model. This eliminates the time and costs required to design and conduct the actual machining experiments and dimensional inspections. Second, the effectiveness of the proposed approaches is improved either by increasing the number of times the strategy is been used or by selecting the appropriate shifted distance based on the estimated machining-error curve. The effectiveness of the proposed error-compensation approaches is verified from simulations and experimental results for a 2D sculptured surface. By using computer aided design tool, this surface generation model can be easily applied to the problems in which the designed surfaces are complex 3D sculptured by considering more complicated chip geometry model. These proposed approaches can also be integrated into an integrated framework for machining path planning in which prediction and compensation of dimensional errors take place in the process development phase rather than in the manufacturing phase of the production cycle.
Neoaortic Valve Function 10 to 18 Years After Arterial Switch Operation

Anatomical correction is a procedure of choice for transposition of the great arteries (TGA) in neonates. During surgery, the aorta and pulmonary artery are switched-the native pulmonary valve becomes the neoaortic valve. The fate of this valve remains uncertain. Many reports suggest that its ability to function worsens with time after surgery. Of 519 patients with TGA operated on between 1991 and 2008, 161 met inclusion criteria for this retrospective study and were followed 10 years or more to assess neoaortic valve regurgitation (NeoAR) occurrence and development and to estimate potential risk factors. The subjects were divided into 2 groups: group 1 (simple TGA) and group 2 (TGA + ventricle septal defect). Within the analyzed group, the frequency of significant regurgitation increased from 9% 1 year after the operation to 47% at the most recent follow-up. No severe regurgitation necessitating reoperation was observed. Analysis of potential risk factors revealed that pulmonary/aortic valve diameter discrepancy and nonfacing commissures were associated with increased risk of development of neoaortic insufficiency. NeoAR arises and develops over time after correction of the defect. No hemodynamic repercussions necessitating cardiac surgical interventions were observed. The majority of insufficiencies are detected between 2 and 6 years after surgery. The degree of incompetence is usually mild and increases during follow-up by about 0.5 or 1 degree. The risk factors for NeoAR appearance are pulmonary artery/aortic annulus discrepancy and nonfacing commissures.
Using Environmental Variables and Soil Processes to Forecast Denitrification Potential and Nitrous Oxide Fluxes in Coastal Plain Wetlands Across Different Land Uses

[1] We examined relationships between denitrification (DNF) and nitrous oxide (N2O) fluxes and potentially important chemical and physical predictors to build a predictive understanding of gaseous N losses from coastal plain wetlands. We collected soil, gas, and pore water samples from 48 sampling locations across a large (440 ha) restored wetland, an adjacent drained agricultural field, and nearby forested wetlands every two months over two years. In summer and fall 2007, we measured soil DNF potential (21.6–3560 mg N m−3 d−1) and N2O efflux (−4.36–8.81 mg N m−2 d−1), along with 17 predictor variables. We developed statistical models for the most comprehensive subset of the data set (fall 2007) and used another subset (summer 2007) for cross-validation. Soil pH and total soil nitrogen were the best predictors of DNF potential (Radj2 = 0.68). A regression using carbon dioxide flux and soil temperature together with soil extractable NH4+ and DNF potential explained 85% of the variation in fall N2O fluxes. The model for DNF performed reasonably well when cross-validated with summer data (R2 = 0.40), while the N2O model did not predict summer N2O fluxes (R2 < 0.1). Poor model performance was likely due to nonlinear responses to high temperatures and/or higher and more variable root respiration by plants during the growing season, leading to overprediction of N2O flux. Our results suggest that soil DNF potential may be modeled fairly effectively from a small number of soil parameters, that DNF potential is uncorrelated with N2O effluxes, and that successful estimation of wetland N2O effluxes will require finer-scale models that incorporate seasonal dynamics.
A depth-first search algorithm automatic initialization splitting of snakes

For object segmentation, the classical snake algorithms often require laborious human interaction; region growing methods are considerably dependent on the selected homogeneity criterion and initial seeds. In this paper we propose a new segmentation method for multi-object segmentation which is depth-first search algorithm based on GVF. The depth-first search process ends with a set of seeds scored and selected by considering local gradient direction information around each pixel. This step requires no human interaction; it enables our algorithm to segment objects which are separated from the background, while ignoring the internal structures of these objects. We have tested the proposed algorithm with several realistic images and obtained good results.
Age Differences in Imagery Abilities.

Age differences were examined in 4 aspects of visual mental imagery, namely, image generation, maintenance, scanning, and rotation. The results suggested that one or more distinct processes are used to carry out each aspect of imagery, and that this is true for 5-year-olds, 8-year-olds, 14-year-olds, and adults. There was no evidence that younger children have fewer processing components, which become differentiated into more specialized subsystems over age. In addition, the results suggested that younger children are relatively poor at scanning, rotating, and generating objects in images, but are relatively good at maintaining images.
Analysis and Design of Protein Based Nanodevices: Challenges and Opportunities in Mechanical Design

Nanomachines are devices that are in the size range of billionths of meters 10−9 m and therefore are built necessarily from individual atoms. These devices will have intrinsic mobilities that result in their geometry change and hence enable them to perform specific functions. Futuristic scholars and researchers believe that nanodevices will one day be used as “assemblers” in the construction of new materials and objects from inside out 1 ; They will be able to “self replicate;” They will be able to enter biological cells to cure disease; They will be able to facilitate space travel; They will be used to clean up the environment; They will be the building blocks of the electronic circuitry and computers 2 . While these claims may prompt profound philosophical and scientific debates for many years to come, they offer humanity with the potential to eliminate poverty, pollution and disease. In the foreseeable future, nanodevices and molecular machines are expected to lead to breakthroughs in technology and life sciences. Impacted industries include Semiconductors molecular electronics, nanophotonics, memory , Microsystems micro electro-mechanical systems—MEMS, communications, optical, fluidics, rf , energy fuel cells, biomimetics, membranes, carbon systems , materials compounds, powders, polymers, nanostructures , biotechnology delivery, lab-on-chip, proteomics, genomics and medical drug design, molecular medicine .
Optimal training of thresholded linear correlation classifiers

A closed-form solution for improved pattern recognition that reduces the training time to a single epoch (one presentation of each of the training patterns) is presented. It is shown that the corresponding hardware requirements are no greater than those for regular recognition under certain conditions. A simple example which shows that the generalization obtained with the closed-form method exceeds that obtained by a model that admits only diagonal transformations is discussed. >
Factors determining the distribution and adequacy of left ventricular myocardial blood flow.

Left ventricular subendocardial necrosis and fibrosis occurs in patients whose coronary arteries are normal (1–3). In the absence of coronary artery obstruction, these changes are likely due to a discrepancy between cardiac oxygen demands and myocardial oxygen supply.
Explaining Party Polarization Given Voters with Convergent Preferences: A Marketing Model of Branding

Over the past few electoral cycles, the two major American political parties have both pursued strategies of polarization. At the same time, opinion polls have shown the American electorate to be generally centrist in its policy preferences. Under the current economic models of voter behavior, these two developments present a paradox. More precisely, the current economic models of voter behavior, as exemplified by Anthony Downs, would predict both parties to adopt policy positions directed towards the distributional center of the electorate, and not toward the outskirts of the distribution as observed. While this paradox might simply be interpreted as a failure of the economic model to describe voter behavior, denying the relevance of that model — in which thoughtful decisions are presumed to be based on preferences — would seem imprudent. Alternatively, there is an economic model of behavior that would resolve this paradox. In particular, we might consider the marketing model of branding, in which a producer creates a brand based on its opposition to another brand and identifies features disliked by consumers to repel those consumers from the opposing brand. In a duopoly, such repelled consumers have no other option than to fall to the opposing brand. This paper presents such a model as it might be applied to the two major American political parties.
Abstract A11: Crosstalk between mTORC1 and estrogen receptor in breast cancer

Approximately two thirds of all breast cancer cases are estrogen receptor (ER) positive, which underscores the dependence of cancer cells on estrogen for growth and survival. However, resistance to endocrine therapy develops in most cases. mTORC1 (the mechanistic target of rapamycin complex 1) is a critical node of estrogen signaling in the cell, however the mechanism of estrogen activation of mTORC1 is not well understood. We have previously demonstrated that mTORC1 promotes growth factor-mediated ER activation by phosphorylating ERα on Ser167. This phosphorylation, which is mediated by the mTORC1 effector kinase S6K1, is important for ERα dimerization, DNA binding and transcriptional activity, is associated with endocrine resistance and correlates with therapy response. Moreover, ERα promotes expression of S6K1, generating a feed-forward positive activation loop. Our current efforts are focused on fully understanding the nature and mechanism of the relationship between mTORC1 and estrogen pathways. Our data indicate that mTOR, raptor and ER form a complex whereby ER directly interacts with raptor. Moreover, this interaction is stimulated by estrogen as seen by co-immunoprecipitation analysis. We additionally found that ER and raptor co-localize to the nucleus upon estrogen stimulation, where they interact as detected by both immunofluorescence and cellular fractionation experiments. Our current efforts are focused on understanding the role of this interaction and the mechanism of estrogen mediated localization of raptor to the nucleus. We are also investigating the role of raptor and estrogen receptor interaction in endocrine therapy treatment and resistance. Citation Format: Anya Alayev, Rachel S. Salamon, Marina K. Holz. Crosstalk between mTORC1 and estrogen receptor in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A11.
A hybrid grid finite difference method for acoustic wave propagation in tilted orthorhombic media

I propose a hybrid grid method for the pseudo-acoustic tilted orthorhombic wave equation, in which I use the centered finite difference method for the nonmixed second derivatives and employ the staggered grid finite difference method in a rotated coordinate system for the mixed derivatives. Compared to the standard grid finite difference implementation where all the spatial derivatives are evaluated using the centered finite difference operators, this hybrid grid method can offer a more efficient numerical solution without damaging any P-wave event.
Design for the Interval between Upper Fixing Plate and Front Windscreen

It is easy to see big interval between upper fixing plate and front windscreen of mini ears after the installation of the upper fixing plate or after exposure under high temperature.This article therefore works to find out the major factors. Without changing the sheet metal and increasing the cost,the upper fixing plate is improved by analyzing the installation of rapid forming components and molding process via moldilow software.The modified components,after cold-hot alternative test in the lad and exposure to high temperature and installation,have solved the problem.
Robotics across the curriculum

We describe a comprehensive program using educational robotics as a hands-on, constructionist learning environment, integrated into teaching across the undergraduate computer science curriculum. Five courses are described in detail. For the three courses which have been offered multiple times, evaluations were conducted to assess students’ attitudes towards the robotics-based curriculum. These results are presented here. Lessons learned are shared, and new directions for the future are highlighted.
Substance use among adolescent sexual minority athletes: A secondary analysis of the youth risk behavior survey.

Abstract Aims While a robust literature exists regarding substance use patterns among adolescent athletes, no studies have examined substance use among adolescent sexual minority athletes; a subpopulation of adolescents that may experience greater rates of substance use due to their marginalized status within the context of sport. Methods This study uses data from the Youth Risk Behavior Survey (2009–2013). Adolescents (N = 26,940) from four states were included in the analyses that assessed past 30-day cigarette use, alcohol use, binge drinking and marijuana use among sexual minority athletes, heterosexual athletes, heterosexual non-athletes, and sexual minority non-athletes. Results Approximately 4% of the sample included athletes who identified as a sexual minority (3.7% males and 5.3% females). While the bivariate analyses found that sexual minority athletes had higher past 30-day prevalence rates of substance use when compared to heterosexual athletes and non-athletes, these rates were similar to sexual minority non-athletes. Moreover, when demographic characteristics and history of substance use were included in the multivariate analytic models, many of these differences were no longer statistically significant. These results were generally consistent for both males and females. Conclusions The results of the study suggest that the context of sport may not be an additional site for stress among adolescent athletes who identify as a sexual minority, and subsequently may have little impact on substance use behaviors. However, participating in sport may not serve as a protective context for adolescent sexual minorities given that substance use behaviors may be learned and reinforced.
Analytical Period- m Motions in a Parametric, Quadratic Nonlinear Oscillator

Analytical solutions of period-m motions in a parametric quadratic nonlinear oscillator are obtained through the finite Fourier series, and the corresponding stability and bifurcation analysis for periodic motions are discussed. The bifurcation trees of periodic motions to chaos in a parametric oscillator with quadratic nonlinearity are presented. Numerical illustration shows good agreement between the analytical and numerical results.
Increased mortality of incident rheumatoid arthritis (RA) versus matched non-RA control subjects: a community-based long-term prospective cohort study.

This is a copy of an article published in Clinical and Experimental Rheumatology. © 2015 Clinical and Experimental Rheumatology Publications.
N-Heterocyclic Carbene and Chiral Brønsted Acid Cooperative Catalysis for a Highly Enantioselective [4+2] Annulation

A chiral NHC/Bronsted acid cooperative catalysis system has been developed for the asymmetric annulation of functionalized benzaldehydes and activated ketones, through dearomative generation of dienolate, to give 3-aryl-3-(perfluoroalkyl)isochroman-1-ones.
Ceftazidime/Avibactam: Who Says You Can’t Teach an Old Drug New Tricks?

Purpose: Gram-negative resistance continues to rise with treatment options becoming more limited. Ceftazidime/avibactam was recently approved in the United States and Europe, which combines an established third-generation cephalosporin with a new, unique, non-β-lactam β-lactamase inhibitor. This review conducts a thorough examination of structure, pharmacology, spectrum of activity, pharmacokinetics/pharmacodynamics, in vitro and clinical efficacy and safety/tolerability of ceftazidime/avibactam, as well as detailed future directions for the agent. Methods: Pubmed and clinicaltrials.gov searches, as well as abstracts from the 2015 Interscience Conference on Antimicrobial Agents and Chemotherapy/International Society of Chemotherapy (ICAAC/ICC) and ID Week meetings and the 2016 American Society of Microbiology Microbe meeting, were conducted from January 2004 – September 2016. Relevant search terms included ceftazidime, ceftazidime/avibactam, avibactam, NXL104 and AVE1330A. The US package insert for ceftazidime/avibactam (02/2015) and European public assessment report (06/2016) were also reviewed. Results: In vitro susceptibility for ceftazidime/avibactam displayed potent activity against many Enterobacteriaceae including extended-spectrum-β-lactamase (ESBL) and carbapenemase-producing strains, as well as Pseudomonas aeruginosa . Phase II clinical trials utilized for approval demonstrated comparable safety and efficacy to imipenem/cilistatin for treatment of complicated urinary tract infections (70.4% vs. 71.4%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (91.2% vs 93.4%). Phase III data displayed non-inferior efficacy of ceftazidime/avibactam compared to doripenem for complicated urinary tract infections (70.2% vs 66.2%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (82.5% vs 84.9%), as well as comparable safety. Ceftazidime/avibactam was well-tolerated but does require renal adjustments. Additionally, 3 case series and a single case report have demonstrated the potential for ceftazidime/avibactam against multidrug resistant organisms for compassionate use or failure after previous therapy. Conclusion: By adding avibactam to ceftazidime, clinicians’ antimicrobial armamentarium is expanded, potentially increasing the ability to combat multi-drug resistant gram-negative pathogens, particularly ESBL and carbapenemase-producing organisms, as well as Pseudomonas aeruginosa . This article is open to POST-PUBLICATION REVIEW . Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
JAK inhibitors in dermatology: The promise of a new drug class

New molecularly targeted therapeutics are changing dermatologic therapy. Janus kinase–signal transducer and activator of transcription (JAK-STAT) is an intracellular signaling pathway upon which many different proinflammatory signaling pathways converge. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on JAK-STAT signaling, and inhibition of this pathway using JAK inhibitors might be a useful therapeutic strategy for these diseases. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. The use of JAK inhibitors in dermatology is reviewed here.
ASIA, WEST | Phoenicia

Geographically, the Phoenicians present a challenge to define. According to the ancient classical authors, they occupied the entire Levantine coast between the Suez and the Gulf of Alexandretta. In actuality, however, their heartland was considerably smaller, consisting of a narrow coastal strip between the Lebanon mountains and the Mediterranean sea stretching from northern Palestine to southern Syria – a slightly extended version of modern-day Lebanon. This dichotomy suggests that the term ‘Phoenician’ in antiquity was broadly applied to any Semitic sea-trader, regardless of origins. Such ambiguity may indeed reflect historical reality. Unlike their Syrian, Palestinian, or Mesopotamian neighbors, the Phoenicians were a confederation of traders rather than a country defined by territorial boundaries. Their empire was less a stretch of land than a patchwork of widely scattered merchant communities. Maritime trade, not territory, defined their sphere. In this geographic survey, the parameters of this Phoenician maritime confederation will be reviewed, as it encompassed regions around the Mediterranean basin and beyond, into the coastal Atlantic regions of Europe and West Africa. The areas to be covered are the Levantie continental homeland with its major port cities (Tyre, Sidon, Byblos, and Arvad), the island of Cyprus, the Aegean (including Rhodes and Crete), the North African littoral (from Egypt west to Morocco), the central Mediterranean (Sicily, Malta, Sardinia, and western Italy), and the Far West (southern Spain and the Balearics, and Atlantic coastal Africa). In surveying these regions, emphasis will be placed on the commercial objectives of Phoenician trade and colonization, which was largely driven by the pursuit of valued raw materials, especially ores and precious metals.
Interlaboratory validation of a real-time PCR 24-hour rapid method for detection of Salmonella in foods.

The efficacy of a 24-h Salmonella real-time, or quantitative, PCR (qPCR) detection method was assessed through a collaborative effort involving eight Federal and state laboratories. Eleven foods including mashed potatoes, soft cheese, chili powder, chocolate, eggs, sprouts, apple juice, fish, shrimp, ground beef, and ground chicken were tested. For each food, seven blind samples were distributed to each participant for testing. These included six samples equivalently inoculated with 1 to 5 CFU/25 g of various serotypes of Salmonella (Gaminara, Weltevreden, Heidelberg, Senftenberg, Enteritidis, Newport, Typhimurium, and Kentucky for each food) and 10 to 50 CFU/25 g of the competitor Enterobacter cloacae. The seventh sample was inoculated with 10 to 50 CFU/25 g of the competitor, E. cloacae, only. These samples were tested for Salmonella by using four methods in parallel: (i) 24-h qPCR method detecting Salmonella from modified buffered peptone water enrichment medium; (ii) 48-h qPCR method detecting Salmone...
CRISPR-Mediated Base Editing Enables Efficient Disruption of Eukaryotic Genes through Induction of STOP Codons

Standard CRISPR-mediated gene disruption strategies rely on Cas9-induced DNA double-strand breaks (DSBs). Here, we show that CRISPR-dependent base editing efficiently inactivates genes by precisely converting four codons (CAA, CAG, CGA, and TGG) into STOP codons without DSB formation. To facilitate gene inactivation by induction of STOP codons (iSTOP), we provide access to a database of over 3.4 million single guide RNAs (sgRNAs) for iSTOP (sgSTOPs) targeting 97%-99% of genes in eight eukaryotic species, and we describe a restriction fragment length polymorphism (RFLP) assay that allows the rapid detection of iSTOP-mediated editing in cell populations and clones. To simplify the selection of sgSTOPs, our resource includes annotations for off-target propensity, percentage of isoforms targeted, prediction of nonsense-mediated decay, and restriction enzymes for RFLP analysis. Additionally, our database includes sgSTOPs that could be employed to precisely model over 32,000 cancer-associated nonsense mutations. Altogether, this work provides a comprehensive resource for DSB-free gene disruption by iSTOP.
Mental Illness and Immigration

The immigration experience can be difficult at best. Immigrants are exposed to a variety of noxious situations in the country of arrival. Also, in their place of origin, immigrants may have been subject to traumatic experiences, as in the case of Latin American and Southeast Asian refugees to the United States. Even the best of journeys can be trying for some. But an extended voyage with many transit points and many unpleasant experiences, as with nonlegal immigrants from Mexico, can put many at risk for psychiatric disturbances in the short and long run. One must consider, as well, that immigrants are often the more vulnerable members of their respective countries of origin.
Organizational Readiness Tools for Global Health Intervention: A Review

The ability of non-governmental organizations, government agencies, and corporations to deliver and support the availability and use of interventions for improved global public health depends on their readiness to do so. Yet readiness has proven to be a rather fluid concept in global public health, perhaps due to its multidimensional nature and because scholars and practitioners have applied the concept at different levels such as the individual, organization, and community. This review concerns 30 publically available tools created for the purpose of organizational readiness assessment in order to carry out global public health objectives. Results suggest that these tools assess organizational capacity in the absence of measuring organizational motivation, thus overlooking a key aspect of organizational readiness. Moreover, the tools reviewed are mostly untested by their developers to establish whether the tools do, in fact, measure capacity. These results suggest opportunities for implementation science researchers.
Evaluation of as-installed properties of transformer bushings

Abstract High voltage transformers are essential parts of the electrical distribution grid. Severe failure of entire grids can occur during earthquakes, when transformer bushings fail due to structural dynamic mismatch to the seismic demands. Proper consideration of the fundamental frequency of vibration, which depends on the flexibility of the cover plate of the transformer to which they are connected, is therefore crucial for determining the seismic response of bushings. A simplified method is developed in this work for the evaluation of the “as-installed” fundamental frequency of transformer bushings. Such bushings are modeled as cantilever beams with distributed mass and elasticity, and an additional rotational spring is introduced at the base, to account for the flexibility of the cover plate of the transformer. A simple yet efficient expression is derived for the as-installed frequency, based on the Southwell-Dunkerley method. The solutions require the knowledge of the bending rigidity of the bushing and the (out-of-plane) rotational stiffness of the cover plate. The evaluation of both these quantities is presented. While analytical solutions for the (out-of-plane) rotational stiffness of circular plates are well known, solutions for rectangular plates have not yet been addressed. A semi-empirical-numerical solution is suggested, based on finite element models and analytical expressions derived by force-fitting the “circular plate solution” to the numerical analyses. The results yielded by the proposed method are compared with experiments on real bushings.
Head and Neck: Thyroid

Thyroid nodules are a frequent finding in the general population, with palpable nodules found in 4–7 % of adults and subclinical nodules identified in up to 70 % of adults, although the vast majority (90–95 %) of these nodules are benign. Since its introduction in the early 1950s, fine-needle aspiration (FNA) of the thyroid has proven to be an integral and reliable method of evaluating patients presenting with a thyroid mass. The addition of thyroid FNA to clinical evaluation of a thyroid nodule has dramatically increased the triage efficiency: not only determining which nodules are at greatest risk of malignancy and should undergo surgery but also indicating which nodules are benign, thus sparing the patient unnecessary surgery. As such, thyroid FNA acts as both a diagnostic test and a screening test.
Magnus force on skyrmions in ferromagnets and quantum Hall systems.

The topological solitons, or ``skyrmions,'' in a planar ferromagnet experience a Magnus force proportional to the product of their velocity and the surrounding magnetization. It has been suggested that the charged quasiparticles near filling factor \ensuremath{\nu}=1 in the GaAs quantum Hall effect are skyrmions. If so, we might expect this spin-induced Magnus force to act on the quasiparticles in addition to the Lorentz force they experience because of their charge. We show that this is not the case, and that the Magnus and Lorentz forces are merely different descriptions of the same physical effect. \textcopyright{} 1996 The American Physical Society.
Modulating Pain in the Periphery: Gene-based Therapies to Enhance Peripheral Opioid Analgesia Bonica Lecture, ASRA 2010

This article provides a brief overview of earlier work of our group on the peripheral signaling of pain, summarizes more recent studies on the role of opioids in chronic neuropathic pain, and speculates on the future of gene-based therapies as novel strategies to enhance the peripheral modulation of pain. Neurophysiologic and psychophysical studies have revealed features of primary afferent activity from somatic tissue that led to improved understanding of the physiology and pathophysiology of pain signaling by nociceptive and nonnociceptive fibers. The demonstration of peripheral opioid mechanisms in neuropathic pain suggests a potential role for these receptors in the modulation of pain at its initiation site. Our work has focused on characterizing this peripheral opioid analgesia in chronic neuropathic pain such that it can be exploited to develop novel and potent peripheral analgesics for its treatment. Ongoing research on virus-mediated gene transfer strategies to enhance peripheral opioid analgesia is presented.
Structure-Function Relationships of NAD-Dependent Dehydrogenases

High resolution structural studies of four NAD-dependent dehydrogenases and five NADP-dependent enzymes have now been completed (Table 1). In many cases, extensive results are also available for complexes of these enzymes with substrates, inhibitors, coenzymes, and coenzyme analogs. I shall review here the wealth of information obtained from these studies and show the stimulus derived in some quite unexpected topics.
Differential Bee Attraction Among Crape Myrtle Cultivars (Lagerstroemia spp.: Myrtales: Lythraceae)

Lagerstroemia is a genus of plants comprised of deciduous shrubs or small trees native to China southward into Southeast Asia. There is a wide range among cultivars of tolerance to key pests and diseases, such as powdery mildew, Erysiphe australiana (McAlpine), flea beetle, Altica spp., crape myrtle aphid, Tinocallis kahawaluokalani Kirkaldy (Hemiptera: Aphididae), and Japanese beetle, Popillia japonica Newman (Coleoptera: Scarabaeidae). We found variation in bee visitation to 40 cultivars evaluated in a 2-yr study in north Georgia. The cultivars 'Seminole' and 'Victor' were the two most often visited by all bees, including honey bees, carpenter bees, and several small bee species. 'Apalachee', however, was the cultivar most frequently visited by bumblebees. Plant height and flower color also influenced frequency of bee visitation. Dark pink, dark purple, and white were the flower colors most frequently visited among the nine color categories evaluated. Pollinator visitation should be a consideration in cultivar choice along with pest susceptibility and horticultural attributes.