Aesthetics vs. Ethics in the Plays of Oscar Wilde

Oscar Wilde is renowned for the sharp wit of his pithy aphorisms, which are evident throughout his writing. In particular, his dramatic oeuvre demonstrates the enduring qualities of his skill as a playwright. However, one of his most enduring legacy comes from one of his critical writings: the effective separation between aesthetics and ethics. In "The Critic as Artist", one of the essays published in Intentions, in 1891, Wilde draws a distinction between Aesthetics and Ethics, arguing that they belong to different spheres. Wilde’s essay was of seminal importance in altering the way in which works of art were analysed: to this day, morality and utility are no longer considered valid criteria with which to judge the artistic qualities of any creative work. The aim of this article is to discuss Wilde’s plays in the light of his aesthetic criticism, focusing primarily on the separation between aesthetics and ethics, demonstrating that the very aesthetic principles Wilde helped to establish and disseminate are also present in the texts of his plays, since the first tragedy, Vera, or The Nihilists (1882) to his last play, The Importance of Being Earnest (1895)

Regulating the Energy Flow in a Cyanobacterial Light Harvesting Antenna Complex

Photosynthetic organisms harvest light energy, utilizing the absorption and energy transfer properties of protein-bound chromophores. Controlling the harvesting efficiency is critical for the optimal function of the photosynthetic apparatus. Here, we show that cyanobacterial light-harvesting antenna may be able to regulate the flow of energy in order to switch reversibly from efficient energy conversion to photo-protective quenching via a structural change. We isolated cyanobacterial light harvesting proteins, phycocyanin and allophycocyanin, and measured their optical properties in solution and in an aggregated-desiccated state. The results indicate that energy band structures are changed, generating a switch between two modes of operation: exciton transfer and quenching; achieved without dedicated carotenoid quenchers. This flexibility can contribute greatly to the large dynamic range of cyanobacterial light harvesting systems.Comment: Published at J. Phys. Chem.

Clinical Characteristics and Treatment-Related Biomarkers Associated with Response to High-Dose Interleukin-2 in Metastatic Melanoma and Renal Cell Carcinoma: Retrospective Analysis of an Academic Community Hospital\u27s Experience.

Background Immunotherapy in the treatment of metastatic melanoma and renal cell carcinoma can produce durable therapeutic responses, which may improve survival. We aimed to identify clinical characteristics and biomarkers associated with response to high-dose interleukin-2 therapy (IL-2) in patients with metastatic melanoma and renal cell carcinoma treated at an academic community hospital. Patients/Methods We retrospectively analyzed clinical variables and biomarkers of 50 consecutive metastatic melanoma or renal cell carcinoma patients treated at our institution with IL-2 during 2004 – 2012. We evaluated clinical characteristics: metastatic sites of disease, prior therapies, number of IL-2 doses per cycle, response duration, autoimmune phenomena, and peak fever, as well as laboratory biomarkers: baseline LDH, platelet nadir, and baseline and highest absolute lymphocyte count (ALC). Survival outcomes were calculated using Kaplan-Meier curves. Results Variables differing between responders (clinical benefit group) and non-responders (no clinical benefit group) in metastatic melanoma included platelet nadir during treatment (p = 0.015), autoimmune phenomena (p = 0.049), and in renal cell carcinoma, platelet nadir (p = 0.026). There were no significant differences between number of doses of IL-2 received per cycle and response in either cancer subtype. Clinical benefit occurred in 25% of patients (9/36) when IL-2 was given as first-line therapy. Median overall survival for the clinical benefit group from the initiation of IL-2 to death or last follow-up was 61 months versus 17 months for the no clinical benefit group (p \u3c 0.001) for metastatic melanoma. In renal cell carcinoma overall survival for clinical benefit patients was 48 months versus 17 months. No treatment-related deaths occurred. Conclusions High-dose IL-2 can be safely administered by an experienced team in a non–intensive care oncology unit. The clinical benefit group developed autoimmune phenomena (melanoma patients), lower platelet nadir, and on average, received the same number of IL-2 doses as the no clinical benefit group, suggesting a response relationship to the patient’s baseline immune status. Further investigation of immune predictors of response may be useful to select appropriate patients for this therapy. Keywords: Interleukin-2, Metastatic melanoma, Metastatic renal cell carcinoma, IL-2, Biomarkers, Safety, Respons

Normalized Affymetrix expression data are biased by G-quadruplex formation

Probes with runs of four or more guanines (G-stacks) in their sequences can exhibit a level of hybridization that is unrelated to the expression levels of the mRNA that they are intended to measure. This is most likely caused by the formation of G-quadruplexes, where inter-probe guanines form Hoogsteen hydrogen bonds, which probes with G-stacks are capable of forming. We demonstrate that for a specific microarray data set using the Human HG-U133A Affymetrix GeneChip and RMA normalization there is significant bias in the expression levels, the fold change and the correlations between expression levels. These effects grow more pronounced as the number of G-stack probes in a probe set increases. Approximately 14 of the probe sets are directly affected. The analysis was repeated for a number of other normalization pipelines and two, FARMS and PLIER, minimized the bias to some extent. We estimate that ∼15 of the data sets deposited in the GEO database are susceptible to the effect. The inclusion of G-stack probes in the affected data sets can bias key parameters used in the selection and clustering of genes. The elimination of these probes from any analysis in such affected data sets outweighs the increase of noise in the signal. © 2011 The Author(s)

Integrating monitor alarms with laboratory test results to enhance patient deterioration prediction

AbstractPatient monitors in modern hospitals have become ubiquitous but they generate an excessive number of false alarms causing alarm fatigue. Our previous work showed that combinations of frequently co-occurring monitor alarms, called SuperAlarm patterns, were capable of predicting in-hospital code blue events at a lower alarm frequency. In the present study, we extend the conceptual domain of a SuperAlarm to incorporate laboratory test results along with monitor alarms so as to build an integrated data set to mine SuperAlarm patterns. We propose two approaches to integrate monitor alarms with laboratory test results and use a maximal frequent itemsets mining algorithm to find SuperAlarm patterns. Under an acceptable false positive rate FPRmax, optimal parameters including the minimum support threshold and the length of time window for the algorithm to find the combinations of monitor alarms and laboratory test results are determined based on a 10-fold cross-validation set. SuperAlarm candidates are generated under these optimal parameters. The final SuperAlarm patterns are obtained by further removing the candidates with false positive rate>FPRmax. The performance of SuperAlarm patterns are assessed using an independent test data set. First, we calculate the sensitivity with respect to prediction window and the sensitivity with respect to lead time. Second, we calculate the false SuperAlarm ratio (ratio of the hourly number of SuperAlarm triggers for control patients to that of the monitor alarms, or that of regular monitor alarms plus laboratory test results if the SuperAlarm patterns contain laboratory test results) and the work-up to detection ratio, WDR (ratio of the number of patients triggering any SuperAlarm patterns to that of code blue patients triggering any SuperAlarm patterns). The experiment results demonstrate that when varying FPRmax between 0.02 and 0.15, the SuperAlarm patterns composed of monitor alarms along with the last two laboratory test results are triggered at least once for [56.7–93.3%] of code blue patients within an 1-h prediction window before code blue events and for [43.3–90.0%] of code blue patients at least 1-h ahead of code blue events. However, the hourly number of these SuperAlarm patterns occurring in control patients is only [2.0–14.8%] of that of regular monitor alarms with WDR varying between 2.1 and 6.5 in a 12-h window. For a given FPRmax threshold, the SuperAlarm set generated from the integrated data set has higher sensitivity and lower WDR than the SuperAlarm set generated from the regular monitor alarm data set. In addition, the McNemar’s test also shows that the performance of the SuperAlarm set from the integrated data set is significantly different from that of the SuperAlarm set from the regular monitor alarm data set. We therefore conclude that the SuperAlarm patterns generated from the integrated data set are better at predicting code blue events

Release of infectious hepatitis C virus from huh7 cells occurs via a trans-golgi network-to-endosome pathway independent of very-low-density lipoprotein secretion

© 2016 Mankouri et al. The release of infectious hepatitis C virus (HCV) particles from infected cells remains poorly characterized. We previously demonstrated that virus release is dependent on the endosomal sorting complex required for transport (ESCRT). Here, we show a critical role of trans-Golgi network (TGN)-endosome trafficking during the assembly, but principally the secretion, of infectious virus. This was demonstrated by both small interfering RNA (siRNA)-mediated silencing of TGN-associated adaptor proteins and a panel of dominant negative (DN) Rab GTPases involved in TGN-endosome trafficking steps. Importantly, interfering with factors critical for HCV release did not have a concomitant effect on secretion of triglycerides, ApoB, or ApoE, indicating that particles are likely released from Huh7 cells via pathways distinct from that of very-low-density lipoprotein (VLDL). Finally, we show that HCV NS2 perturbs TGN architecture, redistributing TGN membranes to closely associate with HCV core protein residing on lipid droplets. These findings support the notion that HCV hijacks TGN-endosome trafficking to facilitate particle assembly and release. Moreover, although essential for assembly and infectivity, the trafficking of mature virions is seemingly independent of host lipoproteins

Effect of Cyclooxygenase(COX)-1 and COX-2 inhibition on furosemide-induced renal responses and isoform immunolocalization in the healthy cat kidney

BACKGROUND: The role of cyclooxygenase(COX)-1 and COX-2 in the saluretic and renin-angiotensin responses to loop diuretics in the cat is unknown. We propose in vivo characterisation of isoform roles in a furosemide model by administering non-steroidal anti-inflammatory drugs (NSAIDs) with differing selectivity profiles: robenacoxib (COX-2 selective) and ketoprofen (COX-1 selective). RESULTS: In this four period crossover study, we compared the effect of four treatments: placebo, robenacoxib once or twice daily and ketoprofen once daily concomitantly with furosemide in seven healthy cats. For each period, urine and blood samples were collected at baseline and within 48 h of treatment starting. Plasma renin activity (PRA), plasma and urinary aldosterone concentrations, glomerular filtration rate (GFR) and 24 h urinary volumes, electrolytes and eicosanoids (PGE(2), 6-keto-PGF1(α,) TxB(2)), renal injury biomarker excretions [N-acetyl-beta-D-glucosaminidase (NAG) and Gamma-Glutamyltransferase] were measured. Urine volume (24 h) and urinary sodium, chloride and calcium excretions increased from baseline with all treatments. Plasma creatinine increased with all treatments except placebo, whereas GFR was significantly decreased from baseline only with ketoprofen. PRA increased significantly with placebo and once daily robenacoxib and the increase was significantly higher with placebo compared to ketoprofen (10.5 ± 4.4 vs 4.9 ± 5.0 ng ml(−1) h(−1)). Urinary aldosterone excretion increased with all treatments but this increase was inhibited by 75 % with ketoprofen and 65 % with once daily robenacoxib compared to placebo. Urinary PGE(2) excretion decreased with all treatments and excretion was significantly lower with ketoprofen compared to placebo. Urinary TxB(2) excretion was significantly increased from baseline only with placebo. NAG increased from baseline with all treatments. Immunohistochemistry on post-mortem renal specimens, obtained from a different group of cats that died naturally of non-renal causes, suggested constitutive COX-1 and COX-2 co-localization in many renal structures including the macula densa (MD). CONCLUSIONS: These data suggest that both COX-1 and COX-2 could generate the signal from the MD to the renin secreting cells in cats exposed to furosemide. Co-localization of COX isoenzymes in MD cells supports the functional data reported here. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0598-z) contains supplementary material, which is available to authorized users

Simple model of adsorption on external surface of carbon nanotubes: a new analytical approach basing on molecular simulation data

Nitrogen adsorption on carbon nanotubes is wide- ly studied because nitrogen adsorption isotherm measurement is a standard method applied for porosity characterization. A further reason is that carbon nanotubes are potential adsorbents for separation of nitrogen from oxygen in air. The study presented here describes the results of GCMC simulations of nitrogen (three site model) adsorption on single and multi walled closed nanotubes. The results obtained are described by a new adsorption isotherm model proposed in this study. The model can be treated as the tube analogue of the GAB isotherm taking into account the lateral adsorbate-adsorbate interactions. We show that the model describes the simulated data satisfactorily. Next this new approach is applied for a description of experimental data measured on different commercially available (and characterized using HRTEM) carbon nanotubes. We show that generally a quite good fit is observed and therefore it is suggested that the observed mechanism of adsorption in the studied materials is mainly determined by adsorption on tubes separated at large distances, so the tubes behave almost independently

Fast, scalable, Bayesian spike identification for multi-electrode arrays

We present an algorithm to identify individual neural spikes observed on high-density multi-electrode arrays (MEAs). Our method can distinguish large numbers of distinct neural units, even when spikes overlap, and accounts for intrinsic variability of spikes from each unit. As MEAs grow larger, it is important to find spike-identification methods that are scalable, that is, the computational cost of spike fitting should scale well with the number of units observed. Our algorithm accomplishes this goal, and is fast, because it exploits the spatial locality of each unit and the basic biophysics of extracellular signal propagation. Human intervention is minimized and streamlined via a graphical interface. We illustrate our method on data from a mammalian retina preparation and document its performance on simulated data consisting of spikes added to experimentally measured background noise. The algorithm is highly accurate

The Phase Diagram of Fluid Random Surfaces with Extrinsic Curvature

We present the results of a large-scale simulation of a Dynamically Triangulated Random Surface with extrinsic curvature embedded in three-dimensional flat space. We measure a variety of local observables and use a finite size scaling analysis to characterize as much as possible the regime of crossover from crumpled to smooth surfaces.Comment: 29 pages. There are also 19 figures available from the authors but not included here - sorr