cssi/SciSciGPT-SciSciNet huggingface dataset:
Evaluation of the HC-04 Cell Line as an In Vitro Model for Mechanistic Assessment of Changes in Hepatic Cytochrome P450 3A during Adenovirus Infection

HC-04 cells were evaluated as an in vitro model for mechanistic study of changes in the function of hepatic CYP3A during virus infection. Similar to in vivo observations, infection with a first generation recombinant adenovirus significantly inhibited CYP3A4 catalytic activity in an isoform-specific manner. Virus (MOI 100) significantly reduced expression of the retinoid X receptor (RXR) by 30% 96 hours after infection. Cytoplasmic concentrations of the pregnane X receptor (PXR) were reduced by 50%, whereas the amount of the constitutive androstane receptor (CAR) in the nuclear fraction doubled with respect to uninfected controls. Hepatocyte nuclear factor 4α (HNF-4α) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) were also reduced by ∼70% during infection. Virus suppressed CYP3A4 activity in the presence of the PXR agonist rifampicin and did not affect CYP3A4 activity in the presence of the CAR agonist CITCO [6-(4-chlorophenyl) imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime], suggesting that virus-induced modification of PXR may be responsible for observed changes in hepatic CYP3A4. The HC-04 cell line is easy to maintain, and CYP3A4 in these cells was responsive to known inducers and suppressors. Dexamethasone (200 μM) and phenobarbital (500 μM) increased activity by 230 and 124%, whereas ketoconazole (10 μM) and lipopolysaccharide (LPS) (10 μg/ml) reduced activity by 90 and 92%, respectively. This suggests that HC-04 cells can be a valuable tool for mechanistic study of drug metabolism during infection and for routine toxicological screening of novel compounds prior to use in the clinic.
The dynamics of a localized surfactant on a thin film

We investigate the flow induced by a localized insoluble surfactant on a thin film. This problem is intended to model the behaviour of the lung's thin-film lining after an aerosol droplet lands on its surface. The surfactant-induced surface-tension gradients drive convection (Marangoni convection) within the film, disrupting the film surface and causing the surfactant to spread. The surfactant may also spread on the film's surface by surface diffusion without inducing convection. Gravity provides a restoring force that decreases film disturbances.Lubrication theory is employed to derive equations that describe the evolution of the film thickness and surfactant concentration. A nonlinear surface-tension equation of state describes the relationship between the surfactant concentration and the surface tension. Solutions of the evolution equations are found numerically using the method of lines and analytically under limiting cases of small and large surface diffusivity. The results elucidate the behaviour of the thin-film/surfactant system.We find that surface-tension-induced convection creates film disturbances that increase the film thickness near the surfactant's leading edge, and thins the film in the central region. Surface diffusion causes more rapid spreading of the surfactant, and decreases the film disturbances. Gravity decreases the film disturbances by creating bi-directional flow in the form of a ring vortex. This behaviour may have implications for the delivery of medications or toxins by aerosol inhalation.
The role of the reticulo-endothelial system in hemorrhagic shock.

"Blockade" of the RES by thorotrast so lowered the tolerance of hemorrhagic shock in rabbits and dogs that a reversible degree of hemorrhagic shock became irreversible. This was true not only in normal rabbits, but in rabbits made resistant to hemorrhagic shock by producing resistance to endotoxins. Rabbits which had been pretreated with thorotrast and then subjected to hemorrhagic shock displayed at death the hemorrhagic lesions and the renal cortical necrosis characteristic of the Shwartzman reaction, in addition to the intramural hemorrhages in the gut which are characteristic of animals dying of hemorrhagic or of endotoxic shock. Elimination of the Shwartzman reaction by the prior administration of nitrogen mustard did not prevent the endotoxemia or the death in shock. Rabbits made more resistant to thorotrast than normal rabbits by prior repeated administration of this substance were also more resistant than normal rabbits to endotoxin, and survived an ordinarily lethal exposure to hemorrhagic shock. During the first few hours after its administration thorotrast induced excessive vulnerability not only to endotoxin and to hemorrhagic shock, but also to an additional small dose of thorotrast. Moreover, a non-absorbable antibiotic given by gavage shortly after thorotrast produced the same lesions as these other agents; i.e. endotoxic shock, the Shwartzman reaction, and death. These data indicate that the lesions induced by thorotrast are produced by endotoxins which the injured or blockaded RES cannot inactivate. The presence of endotoxins in the blood of these rabbits was indicated by the lethal effect of this blood in test recipients. The foregoing observations did not apply to rabbits with an intestinal flora free of coliform bacteria. Over 80 per cent of such rabbits were resistant to an ordinarily lethal exposure to hemorrhagic shock, and they escaped the damage caused by the usual doses of thorotrast. They did, however, develop endotoxic shock and die if given a large dose of thorotrast. These data were taken to indicate that coliform-free rabbits are not entirely free of endotoxins. (In the ordinary environment animals cannot avoid swallowing endotoxin and coliform bacteria.) The absence of the Shwartzman reaction in the coliform-free rabbits is taken to signify that this reaction requires the participation of the endotoxins derived from the intraintestinal bacteria. The absence of endotoxic shock in the coliform-free rabbits is taken to signify that the endotoxins of the coliform bacteria are involved in the shock and death of the coliform-bearing rabbits. Finally the prevention by dibenamine of both the Shwartzman reaction and endotoxic shock and death in rabbits with a normal flora demonstrates that adrenergic activity plays an indispensable role in both phenomena. The foregoing data provide strong support for the thesis that when the RES is severely disabled by any agent, endotoxins which normally and continuously enter the circulation from the gut will produce endotoxic shock and death.
Two-monopole systems and the formation of non-Abelian clouds

We study the energy density of two distinct fundamental monopoles in SU~3! and Sp~4! theories with an arbitrary mass ratio. Several special limits of the general result are checked and verified. Based on the analytic expression of energy density the coefficient of the internal part of the moduli space metric is computed, which gives it a nice ‘‘mechanical’’ interpretation. We then investigate the interaction energy density for both cases. By analyzing the contour of the zero interaction energy density we propose a detailed picture of what happens when one gets close to the massless limit. The study of the interaction energy density also sheds light on the formation of the non-Abelian cloud. @S0556-2821~98!04822-X#
PicXAA-Web: a web-based platform for non-progressive maximum expected accuracy alignment of multiple biological sequences

In this article, we introduce PicXAA-Web, a web-based platform for accurate probabilistic alignment of multiple biological sequences. The core of PicXAA-Web consists of PicXAA, a multiple protein/DNA sequence alignment algorithm, and PicXAA-R, an extension of PicXAA for structural alignment of RNA sequences. Both PicXAA and PicXAA-R are probabilistic non-progressive alignment algorithms that aim to find the optimal alignment of multiple biological sequences by maximizing the expected accuracy. PicXAA and PicXAA-R greedily build up the alignment from sequence regions with high local similarity, thereby yielding an accurate global alignment that effectively captures local similarities among sequences. PicXAA-Web integrates these two algorithms in a user-friendly web platform for accurate alignment and analysis of multiple protein, DNA and RNA sequences. PicXAA-Web can be freely accessed at http://gsp.tamu.edu/picxaa/.
Structural, catalytic and stabilizing consequences of aromatic cluster variants in human carbonic anhydrase II

The presence of aromatic clusters has been found to be an integral feature of many proteins isolated from thermophilic microorganisms. Residues found in aromatic cluster interact via π-π or C-H⋯π bonds between the phenyl rings, which are among the weakest interactions involved in protein stability. The lone aromatic cluster in human carbonic anhydrase II (HCA II) is centered on F226 with the surrounding aromatics F66, F95 and W97 located 12 A posterior the active site; a location which could facilitate proper protein folding and active site construction. The role of F226 in the structure, catalytic activity and thermostability of HCA II was investigated via site-directed mutagenesis of three variants (F226I/L/W) into this position. The measured catalytic rates of the F226 variants via (18)O-mass spectrometry were identical to the native enzyme, but differential scanning calorimetry studies revealed a 3-4 K decrease in their denaturing temperature. X-ray crystallographic analysis suggests that the structural basis of this destabilization is via disruption and/or removal of weak C-H⋯π interactions between F226 to F66, F95 and W97. This study emphasizes the importance of the delicate arrangement of these weak interactions among aromatic clusters in overall protein stability.
Localization of MglA, an essential gliding motility protein in Myxococcus xanthus.

MglA, a 22-kDa protein related to monomeric GTPases, is required for the normal operation of the A (Adventurous) and S (Social) motility and for multicellular development of Myxococcus xanthus. To determine how MglA controls A- and S-motility, MglA was assayed biochemically and its cellular location was determined. His-tagged MglA hydrolyzed GTP slowly in vitro at a rate nearly identical to that of Ras showing that MglA has GTPase activity. Immunofluorescence microscopy of fixed cells from liquid showed that MglA was associated with helical track similar to the MreB spiral that spanned the length of the cell. The distribution pattern of MglA depended on the type of surface from which cells were harvested. In cells gliding on 1.5% (w/v) agar, the helical pattern gave way to punctate clusters of MglA-Yfp at the poles and along the long axis (lateral clusters). The lateral clusters emerged near the leading pole as the cell advanced coincident with a decrease in the intensity of the MglA-Yfp cluster at the leading pole. Newly formed lateral clusters remained fixed with regard to the substratum as the cell moved forward, similar to focal adhesion complexes described for AglZ, a protein partner of MglA. Lateral clusters did not form in cells gliding in methylcellulose, a polymer that stimulates S-motility at low cell density; rather MglA-Yfp was diffuse in the cytoplasm and more concentrated at the poles. The results suggest that conditions that favor S-motility prevent the formation of lateral clusters of MglA, which are associated with A-motility functions. © 2010 Wiley-Liss, Inc.
Notch Signaling Inhibits Axon Regeneration

Many neurons have limited capacity to regenerate their axons after injury. Neurons in the mammalian central nervous system do not regenerate, and even neurons in the peripheral nervous system often fail to regenerate to their former targets. This failure is likely due in part to pathways that actively restrict regeneration; however, only a few factors that limit regeneration are known. Here, using single-neuron analysis of regeneration in vivo, we show that Notch/lin-12 signaling inhibits the regeneration of mature C. elegans neurons. Notch signaling suppresses regeneration by acting autonomously in the injured cell to prevent growth cone formation. The metalloprotease and gamma-secretase cleavage events that lead to Notch activation during development are also required for its activity in regeneration. Furthermore, blocking Notch activation immediately after injury improves regeneration. Our results define a postdevelopmental role for the Notch pathway as a repressor of axon regeneration in vivo.
The role of estrogens in normal and abnormal development of the prostate gland.

Abstract: Estrogens play a physiologic role during prostate development with regard to programming stromal cells and directing early morphogenic events. However, if estrogenic exposures are abnormally high during the critical developmental period, permanent alterations in prostate branching morphogenesis and cellular differentiation will result, a process referred to as neonatal imprinting or developmental estrogenization. These perturbations are associated with an increased incidence of prostatic lesions with aging, which include hyperplasia, inflammation, and dysplasia. To understand how early estrogenic exposures can permanently alter the prostate and predispose it to neoplasia, we examined the effects of estrogens on prostatic steroid receptors and key developmental genes. Transient and permanent alterations in prostatic AR, ERα, ERβ, and RARs are observed. We propose that estrogen-induced alterations in these critical transcription factors play a fundamental role in initiating prostatic growth and differentiation defects by shifting the prostate from an androgen-dominated gland to one whose development is regulated by estrogens and retinoids. This in turn leads to specific disruptions in the expression patterns of key prostatic developmental genes that normally dictate morphogenesis and differentiation. Specifically, we find transient reductions in Nkx3.1 and permanent reductions in Hoxb-13, which lead to differentiation defects particularly within the ventral lobe. Prolonged developmental expression of Bmp-4 contributes to hypomorphic growth throughout the prostatic complex. Reduced expression of Fgf10 and Shh and their cognate receptors in the dorsolateral lobes leads to branching defects in those specific regions in response to neonatal estrogens. We hypothesize that these molecular changes initiated early in life predispose the prostate to the neoplastic state upon aging.
Compressive behavior of articular cartilage is not completely explained by proteoglycan osmotic pressure

It has been hypothesized that applied mechanical or osmotic loads which decrease cartilage volume by 5% or more are sufficient to relieve all collagen tensile forces, and that further changes in the applied load are completely supported by changes in proteoglycan osmotic pressure. In this view, cartilage should behave mechanically like a concentrated solution of proteoglycans. We tested this hypothesis by measuring the equilibrium axial and radial stresses in bovine articular cartilage during uniaxial confined compression. If the hypothesis is correct, the observed changes in the radial and axial stresses in confined compression should be equal for compression greater than 5%. However, the observed change in axial stress was always substantially greater than the change in radial stress over the range of strains (5-26%) and saline concentrations (0.05-0.15 M) tested. This indicates that the mechanical behavior of cartilage in confined compression cannot solely be explained by changes in proteoglycan osmotic pressure even for strains as large as 26%. A linear isotropic model was found to describe the observed equilibrium behavior adequately. In addition, the inferred shear modulus was found to be independent of saline concentration and similar to measurements by others of the flow-independent shear modulus. Our results have implications regarding the relative contribution of the proteoglycans and collagen to the mechanical properties of the tissue in compression, and suggest that tensile forces in the collagen network may play an important role in determining tissue behavior in confined compression even for relatively large volume changes.
Ordination Methods and the Evaluation of Ediacaran Communities

Analysis of paleocommunity data poses a challenge because of its multivariate nature, containing counts of many species in many samples. Comparison of the abundance of a single species among all samples provides only incomplete information, whereas attempting to consider every species is impractical. Ordination methods are analytical techniques that reduce the original multivariate dataset to a few important components by creating new synthetic variables designed to explain the maximum amount of original data variability. The ultimate goal is to order the samples along ecologically or environmentally meaningful gradients in order to interpret differences in community structure. This chapter describes three of the most widely-used ordination methods, principal components analysis (PCA), detrended correspondence analysis (DCA), and non-metric multidimensional scaling (NMDS), explaining the methodology of each and outlining their strengths and weaknesses for analysis of paleoecological data. The techniques are illustrated using Ediacaran paleocommunity data from Mistaken Point, Newfoundland. PCA relies on assumptions that are inappropriate for ecological data, such as the requirement that species abundances change in a linear fashion along the environmental gradient, and is not well suited for community ordination. In contrast, DCA and NMDS both perform well with ecological data; DCA incorporates a more ecologically-realistic measure of distance between samples but some of the detrending methods have been criticized, whereas NMDS only assumes a monotonic relationship between compositional similarity and gradient distance. The two methods also have complementary strengths, with DCA typically better at extracting the primary gradient and NMDS better at resolving the overall pattern.
High order discontinuous Galerkin method for simulating miscible flooding in porous media

We present a high-order method for miscible displacement simulation in porous media. The method is based on discontinuous Galerkin discretization with weighted average stabilization technique and flux reconstruction post processing. The mathematical model is decoupled and solved sequentially. We apply domain decomposition and algebraic multigrid preconditioner for the linear system resulting from the high-order discretization. The accuracy and robustness of the method are demonstrated in the convergence study with analytical solutions and heterogeneous porous media, respectively. We also investigate the effect of grid orientation and anisotropic permeability using high-order discontinuous Galerkin method in contrast with cell-centered finite volume method. The study of the parallel implementation shows the scalability and efficiency of the method on parallel architecture. We also verify the simulation result on highly heterogeneous permeability field from the SPE10 model.
A pilot study examining the effects of faculty incivility on nursing program satisfaction

Uncivil behavior in the classroom threatens the teaching-learning process. Research to date has focused on nursing student incivility in academia with little research examining the faculty role associated with incivility. Due to the lack of research examining faculty incivility toward nursing students, additional research in this area is indicated. The purpose of this study was to examine the effects of faculty incivility on nursing students' satisfaction with their Bachelor of Science Nursing (BSN) nursing program in a rural Southeastern state. Quantitative data was collected via surveys. Research questions included: (1) What percentage of senior nursing students report experiencing faculty incivility? (2) What is the relationship between faculty incivility and nursing students' ratings of program satisfaction? (3) In what educational settings does perceived incivility toward nursing students occur? (4) How do nursing students respond to perceived faculty incivility? The results of this survey revealed that 35.3% of students had at least one nursing instructor that put them down or was condescending toward them during their educational experience. Furthermore, 20.7% reported that two or more faculty put them down or were condescending toward them. Collectively, the pilot study revealed that over half of the participants reported faculty behaving in a way that was perceived as uncivil. Incivility in the nursing profession has been an on-going problem. The high number (over half) of participating students reporting that they perceived that at least one nursing instructor had put them down or was condescending toward them during their educational experience raises additional concerns for the level of civility in nursing programs and the role modeling that is presented to students. It is imperative that nursing faculty and students interact professionally and establish effective communication patterns.
The mTOR Pathway and Its Inhibitors

The mammalian target of rapamycin (mTOR) plays a central role in the regulation of cell growth and proliferation by controlling translation in response to nutrients, energy levels, and growth factors. A number of proteins both upstream and downstream in the mTOR signaling pathway have been found to be modified in multiple cancers. As a result, significant interest has been generated in developing small-molecule inhibitors directed against mTOR. Over 30 yr ago a naturally occurring macrolide antibiotic, rapamycin, was isolated that subsequently was identified as a specific inhibitor of mTOR. Rapamycin has played a critical role as a chemical probe for defining the role of mTOR and served as a template for developing compounds with improved therapeutic properties. This chapter will describe our current understanding of the cellular functions of mTOR, modifications of the mTOR pathway currently identified in various types of cancer, the status of clinical trials using rapamycin analogs targeting mTOR, and future possibilities for novel small-molecule inhibitors of mTOR.
Do Cues about Harm to the Elderly and African Americans Reduce Support for Voter ID Laws

The scant research on public opinion toward voter ID laws suggests that opinions on the topic can be influenced by valenced issue frames emphasizing how the laws might harm eligible voters. We advance this line of research by examining the effects of frames that include cues about harm to specific groups of eligible voters, namely “the elderly” and “African Americans.” We hypothesize that exposure to such frames will reduce support for voter ID laws, especially among in-group members. Analyzing data from a question wording experiment embedded in a state public opinion poll, we replicate the finding that a frame emphasizing the harmful effects of the laws on eligible voters reduces support for voter ID laws. We also find that emphasizing harm to African Americans in particular further reduced support, whereas emphasizing harm to the elderly did not produce any additional effect. The strength of the framing effects varied across respondent characteristics, including racial-ethnic minority status, education, and ideology. These results reinforce the practical importance of framing in contemporary political discourse, as well as the interplay between group identity, group cues, and public opinion about voter ID laws.
Severity Levels of Inconsistent Code

Inconsistent code detection is a variant of static analysis that detects statements that never occur on feasible executions. This includes code whose execution ultimately must lead to an error, faulty error handling code, and unreachable code. Inconsistent code can be detected locally, fully automatically, and with a very low false positive rate. However, not all instances of inconsistent code are worth reporting. For example, debug code might be rendered unreachable on purpose and reporting it will be perceived as false positive.
Structural Equation Models in Experimental Research

A general model is derived and illustrated for the analysis of field and laboratory experimental data. The model explicitly provides for the determination of the magnitude and significance of exper...
Intentions to Purchase Related to Consumer Characteristics

An earlier article by the same author in the JOURNAL OF MARKETING studied fulfillment of intentions to buy, or not to buy, as a function of income, liquid assets, personal debt, attitudes about one...
The utility of post ablation PET/CT as a marker for local disease progression and pain

Purpose: This study measured the F-18 FDG and C-11 Choline activity on PET/CT scans before and after percutaneous ablation of bone tumors comparing these values to local tumor recurrence and pain/functional status in the ablated region. Materials: Using our institutional tumor ablation database, patients with PET/CT scans acquired before and after bone tumor ablation procedures performed between January 1, 2002 and September 1, 2015 were identified. F-18 FDG and C-11 Choline PET/CTs were evaluated for preand post-ablation maximum SUV with readers blinded to clinical information except for the location of the targeted bone metastasis. For SUV determination, a region of interest (ROI) incorporating the lesion was manually placed by the radiologist. The SUVmax was subtracted from blood pool (right atria), and a ratio comparing SUVmax before and after ablation (SUVmax post-ablation/SUVmax pre-ablation) was calculated. Clinical information, including patient demographics, pain level and function, and oncologic outcome, was obtained from the electronic medical record. Local tumor recurrence was defined as any growth on CT, MRI, or by tissue sample. Results: This study identified 96 patients with a mean age of 58.3 years (SD 15.4 years, range 26-83) at time of bone ablation with a PET positive bone lesion prior to ablation and at least one PET/CT post ablation. Eight-one of the patients were followed with F-18 FDG PET and 15 with C-11 Choline PET. Patients with no evidence of local tumor recurrence and overall better functionality/decreased pain had a lower SUVmax ratio, mean 0.37±0.0.780, relative to patients who had evidence of local recurrence and worsening pain, mean 2.04± 1.68 (p o0.04). There was no correlation between SUV and interval between ablation procedure and post-ablation PET/CT (mean 516.5 days, range 15-2081) with an R value of 0.0179. Conclusions: Patients with no evidence of locally recurrent disease and decreased pain had significantly lower SUVmax ratios than with evidence of recurrence independent of duration of follow up. This suggests that any increase in PET radiotracer uptake within the ablation bed is concerning for recurrence regardless of the imaging time interval post ablation.
Radio-anatomic measurements and statistical generation of a safe surgical corridor to enter the ventricular trigone while avoiding injury to the optic radiations.

Objective To find a safe operative corridor to the ventricular trigone avoiding injury to the optic radiations (ORs). Methods In 24 adult hemispheres, dimensions of the atrium, height of the OR, and the cortex-to-atrium distance were measured. Superior parietal lobule (SPL), parieto-occipital sulcus (POS), and middle temporal gyrus (MTG) traced approaches were used to measure maximum safe angles to enter the atrium without traversing the OR. A statistical algorithm was generated using these measurements to predict the height of the OR and safe angles from measurements from MR imaging of five test hemispheres. Statistically calculated angles were compared with measured angles from dissection. Results Mean length and height of atrium, height of OR, and cortico-atrium distances were 2.07 cm, 3.36 cm, 2.53 cm, and 4.11 cm, respectively. The height of the atrium influenced the height of the OR significantly ( p 4.5 cm (> 95th percentile) and Conclusion The height of the normal atrium was 2.58 cm (height of atrium to height of OR ratio was 1:0.76). An operative corridor to the atrium without damaging the OR can be calculated from MR imaging of the brain.
Drug susceptibility analysis of 122 Klebsiella pneumoniae strains isolated from children

AIM To investigate the resistance of 122 Klebsiella pneumoniae clinical strains isolated from children in 2007.METHODS According to National Committee for Clinical Laboratary Standards(2005),the clinical isolates were identified and their antimicrobial susceptibility was tested by VITEK-32 automatic identification microbiological analysis system.RESULTS One hundred and twenty-two Klebsiella pneumoniae isolated including 62 extended-spectrum β-lactamases producing strains(ESBLs) were identified.The incidence of Klebsiella pneumoniae producing ESBLs was 50.82%.All the ESBLs-producing strains were susceptible to imipenem and cefoxitin.They showed variant resistances to most other antibiotics.CONCLUSION It is important to determine the ESBLs-producing strains and select antibiotics on the basis of the results of susceptibility test.Imipenem and cefoxitin are the effective antibiotics to infections caused by Klebsiella pneumoniae ESBLs producing strains.
Determination of arsenic in bag tea samples of health food by hydride generator atomic fluorescence spectrometry

Objective:To establish a method of hydride generator atomic fluorescence spectrometry(HG-AFS) to determine arsenic in bag tea samples of 20 kinds of health food.Methods: After microwave or wet digestion,the contents of arsenic in twenty bag tea samples were determined by HG-AFS.Results: Linear range for the determination of arsenic was 0 μg/L~80 μg/L.The linear correlative coefficient for arsenic was 0.9994.The quality of the results was proved by the recovery experiments(ranging from 92.4% to 109.6%).The relative standard deviation was 2.5%(n=11) for arsenic in bag tea samples.The contents of arsenic in bag tea were in the range of 0.10 mg/kg~0.80 mg/kg.Conclusion: The findings indicate that the proposed method is simple,fast and accurate,which can meet the demand for determining arsenic in bag tea samples of health food.
CCD emulator design for LSST camera

As part of the LSST project, a comprehensive CCD emulator that operates three CCDs simultaneously has been developed for testing multichannel readout electronics. Based on an Altera Cyclone V FPGA for timing and control, the emulator generates 48 channels of simulated video waveform in response to appropriate sequencing of parallel and serial clocks. Two 256Mb serial memory chips are adopted for storage of arbitrary grayscale images. The arbitrary image or fixed pattern image can be generated from the emulator in triple as three real CCDs perform, for qualifying and testing the LSST 3-stripe Science Raft Electronics Board (REB) simultaneously. Using the method of comparator threshold scanning, all 24 parallel clocks and 24 serial clocks from the REB are qualified for sequence, duration and level before the video signal is generated. In addition, 66 channels of input bias and voltages are sampled through the multi-channel ADC to verify that correct values are applied to the CCD. In addition, either a Gigabit Ethernet connector or USB bus can be used to control and read back from the emulator board. A user-friendly PC software package has been developed for controlling and communicating with the emulator.
New lipid therapies: PCSK9 inhibitors

Abstract Pharmacologic therapy reduces cardiovascular risk in a variety of primary and secondary prevention clinical situations in addition to lifestyle modifications. Low density lipoprotein cholesterol (LDL-C) is a key mediator of atherogenesis. Most cholesterol guidelines propose specific LDL-C while recently the ACC/AHA recommends statin therapy without a specific LDL-C target. Proprotein convertase subtilisin kexin 9 (PCSK9) is a serine protease that leads to LDL receptor degradation. The decreased availability of LDL receptors results in decreased clearance and an increase of circulating LDL-C particles. Monoclonal antibodies that inhibit PCSK9 (PCSK9 abs) reduce LDL-C levels and may be especially helpful in familial hypercholesterolemia and statin-intolerant patients. PCSK9 inhibition is an exciting and promising new therapy for protection against macrovascular events.
Adaptive Evolution of the Genetic Code

All known genetic codes use 4 bases and 20 amino acids, but many other bases and amino acids have been synthesized and/or found in organisms. The coding relation ships between particular trinucleotides and amino acids can and have evolved, as shown by variants in both mitochondrial and nuclear lineages. Here we review the evidence that vari-ous aspects of the genetic code, including its composition, its degeneracy and the assignments of particular codons to particular amino acids are in some sense optimal, chosen over alterna-tives by natural selection. We also examine several specific proposals about how the code evolved prior to its fixation in the last common ancestor of extant life. Although the pattern of codon assignments appears nearly optimal, other claims for adaptive features are more speculative and many interesting questions remain unresolved.
Fault Evaluator: A tool for experimental investigation of effectiveness in software testing

The specifications for many software systems, including safety-critical control systems, are often described using complex logical expressions. It is important to find effective methods to test implementations of such expressions. Analyzing the effectiveness of the testing of logical expressions manually is a tedious and error prone endeavor, thus requiring special software tools for this purpose. This paper presents Fault Evaluator, which is a new tool for experimental investigation of testing logical expressions in software. The goal of this tool is to evaluate logical expressions with various test sets that have been created according to a specific testing method and to estimate the effectiveness of the testing method for detecting specific faulty variations of the original expressions. The main functions of the tool are the generation of complete sets of faults in logical expressions for several specific types of faults; gaining expected (Oracle) values of logical expressions; testing faulty expressions and detecting whether a test set reveals a specific fault; and evaluating the effectiveness of a testing approach.
Abstract P258: Gender, Race, Age and Insurance Status in Patients Treated with tPA

BACKGROUND AND PURPOSE: At a large Stroke Certified Hospital serving a diverse population we analyzed Tissue Plasminogen Activator treatment (tPA) administration for ischemic stroke patients. tPA treatment is time dependent and we wanted to determine whether insurance type, race, age and/or gender affected the time frame of tPA treatment. METHODS: We used data from our Stroke database which covered patients treated at Fairfax INOVA hospital from February 2004 to April 2010. A total of 144 patients were treated within this time for ischemic stroke. Of these 144 patients, 99 were White, 19 were Asian, 16 were Black, and 10 belonged to other races. In order to avoid computational and estimation problems associated with small cell sizes, all non-White races were combined into a single category (n = 45). We used time between last known well and treatment as our dependent variable. Our predictors were demographic controls including age, gender, and sex and other dummy variables and an ANOVA model was run to produce the results. RESULTS: The factorial ANOVA results are presented in Table 1. As the p values indicate, no significant group differences were observed for race, gender, age or insurance type. CONCLUSIONS: We found that ischemic stroke patients receiving tPA treatment did so in a timely manner and factors such as insurance type, race, gender or age had no significant effect on the likelihood of receiving treatment. There appeared to be no disparity based on the variables examined in our sample. In the future we recommend this study be replicated with a larger sample size. ![Graphic][1] [1]: /embed/inline-graphic-1.gif
Pharmacokinetic Drug Interactions with Panax ginseng

Panax ginseng is widely used as an adaptogen throughout the world. The major active constituents of P. ginseng are ginsenosides. Most naturally occurring ginsenosides are deglycosylated by colonic bacteria to intestinal metabolites. Ginsenosides along with these metabolites are widely accepted as being responsible for the pharmacologic activity and drug interaction potential of ginseng. Numerous preclinical studies have assessed the influence of various ginseng components on cytochrome P450 (CYP), glucuronidation, and drug transport activity. Results from these investigations have been largely inconclusive due to the use of different ginseng products and variations in methodology between studies. Drug interaction studies in humans have been conflicting and have largely yielded negative results or results that suggest only a weak interaction. One study using a midazolam probe found weak CYP3A induction and another using a fexofenadine probe found weak P-gp inhibition. Despite several case reports indicating a drug interaction between warfarin and P. ginseng, pharmacokinetic studies involving these agents in combination have failed to find significant pharmacokinetic or pharmacodynamic interactions. To this end, drug interactions involving P. ginseng appear to be rare; however, close clinical monitoring is still suggested for patients taking warfarin or CYP3A or P-gp substrates with narrow therapeutic indices.
Molecular Testing for Polyomaviruses

Polyomaviruses are genomically small, nonenveloped DNA viruses that are ubiquitous among humans. Primary infection is still poorly understood, since patients are either asymptomatic or disease is subclinical. The most important polyomaviruses in human medicine are the BK and JC viruses. Symptomatic infections caused by the BK and JC polyomaviruses present exclusively in immunocompromised patients. Both of these viruses replicate in the urothelium of urinary tract, but have been detected in other sites of latency. The principle diseases caused by the BK virus are nephropathy in patients that have undergone renal transplantation and hemorrhagic cystitis in patients undergoing hematopoietic stem cell transplantation. Although the JC virus replicates in the lower urinary tract, the most important disease caused by this virus is progressive multifocal leukoencephalopathy, which occurs predominantly in patient with a T-cell immunodeficiency syndrome. The diagnosis and/or monitoring of patients with these diseases relies heavily on quantitative PCR, and occasionally other diagnostic methods. A variety of other polyomaviruses have been described which will be discussed briefly. Among these, the Merkel cell polyomavirus is the most important, which is a cause of Merkel cell carcinoma.
Digital Citizenship: You Can't Go Home Again.

In the July/August 2011 edition of TechTrends, a group of AECT members and academic professionals explored the state of digital citizenship for students in K-12 through an article entitled: Digital Citizenship in K-12: It Takes a Village. Identified was a significant need for digital citizenship awareness by parents, educators, and students through a series of interviews, exploration of resources, reports, and surveys. In this current article, the purpose is to provide an updated perspective of the state of digital citizenship in the K-12 academic and professional environments as gathered from re-administering the 2010 survey and interviewing experts quoted in the 2010 article. Results showed the need for teaching digital citizenship at an earlier age, improved digital citizenship awareness by both educators and administrators, and a continued focus on the misuse and abuse of technology.
Reply to Whiteman et al.: In-Deed wise to get some sensible sun exposure.

Whiteman, Olsen and Green noted the Felton study (1) was short term and limited by the number of biopsies. What this study demonstrated was that even for only 6 weeks of repeated exposures to sensible suberythemal doses of simulated solar ultraviolet radiation (UVR), there was a marked increase in the skin's defense mechanisms to overcome the damaging effects caused by the DNA absorbing the UVR. Whiteman et al. acknowledge that within 24 hours after the final exposure the levels of photo damage were significantly lower. This article is protected by copyright. All rights reserved.
Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients.

Abstract Background Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). However, data on the long-term effect on CAV progression and clinical outcomes are lacking. Objectives The aim of this study was to test the long-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT. Methods A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascular ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies. Results The progression in plaque volume (2.8 ± 2.3 mm3/mm vs. 0.46 ± 1.8 mm3/mm; p 2 years) after HT. Conclusions Early conversion to SRL is associated with attenuated CAV progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI use.
Current challenges for cancer vaccine adjuvant development

Introduction: Although much progress has been made in the last decade(s) toward development of effective cancer vaccines, there are still important obstacles to therapeutic successes. New generatio...
Construction and transformation of probability densities

We present a simple unified approach for the transformation of probability densities. The approach relates any two probability densities by an operator transformation using the standard differentiation operator. We obtain a generalization of the Gram-Charlier and Edgeworth series. We further generalize the approach by showing that the differentiation operator can be replaced by an arbitrary Hermitian operator. As a further special case we obtain the operator transformation that scales the mean and standard deviation of a probability density. Furthermore, we show how the unusual formalism of quantum mechanics for constructing densities can be related to standard probability theory. We do so by generalising the theorem of Khinchin regarding characteristic functions.
Estimation of Direct Healthcare Costs of Fungal Diseases in the United States.

Background Fungal diseases range from relatively-minor superficial and mucosal infections to severe, life-threatening systemic infections. Delayed diagnosis and treatment can lead to poor patient outcomes and high medical costs. The overall burden of fungal diseases in the United States is challenging to quantify, because they are likely substantially underdiagnosed. Methods To estimate the total, national, direct medical costs associated with fungal diseases from a healthcare payer perspective, we used insurance claims data from the Truven Health MarketScan 2014 Research Databases, combined with hospital discharge data from the 2014 Healthcare Cost and Utilization Project National Inpatient Sample and outpatient visit data from the 2005-2014 National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. All costs were adjusted to 2017 dollars. Results We estimate that fungal diseases cost more than $7.2 billion in 2017, including $4.5 billion from 75055 hospitalizations and $2.6 billion from 8993230 outpatient visits. Hospitalizations for Candida infections (n = 26735, total cost $1.4 billion) and Aspergillus infections (n = 14820, total cost $1.2 billion) accounted for the highest total hospitalization costs of any disease. Over half of outpatient visits were for dermatophyte infections (4981444 visits, total cost $802 million), and 3639037 visits occurred for non-invasive candidiasis (total cost $1.6 billion). Conclusions Fungal diseases impose a considerable economic burden on the healthcare system. Our results likely underestimate their true costs, because they are underdiagnosed. More comprehensive estimates of the public health impact of these diseases are needed to improve their recognition, prevention, diagnosis, and treatment.
Airbrushing and surface modification for fabricating flexible electronics on polydimethylsiloxane

Polydimethylsiloxane (PDMS) is known to be more flexible and stretchable than other commonly used substrates for flexible electronics, including thermoplastic polyurethane (TPU) and polyethylene terephthalate (PET). However, commercially available inks for printing flexible electronics are not formulated for PDMS, resulting in very poor adhesion of printed electronic components on PDMS. To address this limitation, we have developed a surface-modification method that enables inks to adhere firmly onto PDMS. Using the ASTM protocols (tape-pull test and pencil-hardness test), we confirmed that the surface modification method significantly improved the adhesion and abrasion resistance of conductive components fabricated on PDMS. In addition, we investigated using an airbrush as a low-cost alternative for fabricating flexible electronics. We compared airbrushing with screen printing, the common fabrication method used for flexible electronics. We found that the change in resistance of resistors airbrushed on both surface-modified PDMS and TPU was slightly less after 30–100 cycles of stretching than the same resistors screen-printed on the same substrates, indicating that airbrushing is able to fabricate electronic components of similar quality, if not better, when compared with screen printing. To further illustrate the effect of the surface modification method and airbrushing, we fabricated a patch antenna by airbrushing inks on surface-modified PDMS and pristine PDMS. The measurement results of the antenna on surface-modified PDMS showed a close agreement with the simulation result, giving a resonant frequency at 2.4 GHz.
Counterculture: 1960s and Beyond

The article on counterculture begins with an exploration of the counterculture of the 1960s. The definition of the term ‘counterculture’ is examined and refined. The legacy of the counterculture of the 1960s is analyzed in light of subsequent social and cultural changes. The English revolution of the mid-seventeenth century is explored as an historical instance of a counterculture. The article concludes with a discussion of the relationship between social movements and countercultures.
Molecular Imaging of Renal Malignancy: A Review

Renal cell carcinoma (RCC) is a common malignancy that is often detected incidentally in patients undergoing cross-sectional imaging of the abdomen for workup of pain or other symptoms. Due to overlap in imaging findings of RCC and benign tumors, biopsy may be necessary to confirm the diagnosis. Biopsies are occasionally non-diagnostic, however, and in small lesions or patients with comorbidities may not be technically feasible. Molecular imaging techniques can characterize tumors as being more likely malignant or benign and obviate the need for invasive testing, as well as providing accurate whole-body staging in patients with known RCC. PET/CT with 18F-FDG and other radionuclides can identify primary renal masses with higher malignant potential and also allows for sensitive detection of metastatic RCC. SPECT/CT imaging with 99mTc-sestamibi can provide useful information to support the diagnosis of benign oncocytic neoplasms over more aggressive RCC subtypes. Investigational molecular imaging techniques such as immunoPET and hyperpolarized 13C MRI have also shown promise in renal mass characterization. This review article aims to outline the various molecular imaging modalities available in the evaluation of primary renal tumors and in whole-body staging of metastatic RCC.