Structural and Symbolic Parallels Within the Adventures of Huckleberry Finn and the Catcher in the Rye

The Adventures of Huckleberry Finn and The Catcher in the Rye are both quest narratives in which the youthful protagonist begins his story trapped within a paradigm that oppresses him and -in order to escape- dies a symbolic death, descending to the underworld to learn a sacred truth that will be revealed at novel\u27s end. The structure and symbolism are quite similar and follow the archetypal hero\u27s journey, which I closely examine. In my thesis, I seek to prove that by descending to the hell of the Antebellum South and the conformist/materialistic world of post-war America, both Huck and Holden ultimately help to exorcise the demons of their respective war-torn societies. In my research, I discovered that most critics had not taken this comprehensive spiritual approach in analyzing Huck and Holden\u27s quest, and I concluded that their journey through the underworld, and the sacred knowledge that they discovered there, helped in a small way change America hersel

Structural and Symbolic Parallels Within the Adventures of Huckleberry Finn and the Catcher in the Rye

The Adventures of Huckleberry Finn and The Catcher in the Rye are both quest narratives in which the youthful protagonist begins his story trapped within a paradigm that oppresses him and -in order to escape- dies a symbolic death, descending to the underworld to learn a sacred truth that will be revealed at novel\u27s end. The structure and symbolism are quite similar and follow the archetypal hero\u27s journey, which I closely examine. In my thesis, I seek to prove that by descending to the hell of the Antebellum South and the conformist/materialistic world of post-war America, both Huck and Holden ultimately help to exorcise the demons of their respective war-torn societies. In my research, I discovered that most critics had not taken this comprehensive spiritual approach in analyzing Huck and Holden\u27s quest, and I concluded that their journey through the underworld, and the sacred knowledge that they discovered there, helped in a small way change America hersel

Stac Proteins Suppress Ca2+-Dependent Inactivation of Neuronal L-type Ca2+ Channels

Stac protein (named for its SH3-and cysteine-rich domains) was first identified in brain 20 years ago and is currently known to have three isoforms. Stac2, Stac1, and Stac3 transcripts are found at high, modest, and very low levels, respectively, in the cerebellum and forebrain, but their neuronal functions have been little investigated. Here, we tested the effects of Stac proteins on neuronal, high-voltage-activated Ca2+ channels. Overexpression of the three Stac isoforms eliminated Ca2+-dependent inactivation (CDI) ofL-type current in rat neonatal hippocampal neurons (sex unknown), but not CDI of non-L-type current. Using heterologous expression in tsA201 cells (together with β and α2-δ1 auxiliary subunits), we found that CDI for CaV1.2 and CaV1.3 (the predominant, neuronalL-type Ca2+ channels) was suppressed by all three Stac isoforms, whereas CDI for the P/Q channel, CaV2.1, was not. For CaV1.2, the inhibition of CDI by the Stac proteins appeared to involve their direct interaction with the channel’s C terminus. Within the Stac proteins, a weakly conserved segment containing ~100 residues and linking the structurally conserved PKC C1 and SH3_1 domains was sufficient to fully suppress CDI. The presence of CDI forL-type current in control neonatal neurons raised the possibility that endogenous Stac levels are low in these neurons and Western blotting indicated that the expression of Stac2 was substantially increased in adult forebrain and cerebellum compared with neonate. Together, our results indicate that one likely function of neuronal Stac proteins is to tune Ca2+ entry via neuronal L-type channels. © 2018 the authors

Increasing pattern recognition accuracy for chemical sensing by evolutionary based drift compensation

Artificial olfaction systems, which mimic human olfaction by using arrays of gas chemical sensors combined with pattern recognition methods, represent a potentially low-cost tool in many areas of industry such as perfumery, food and drink production, clinical diagnosis, health and safety, environmental monitoring and process control. However, successful applications of these systems are still largely limited to specialized laboratories. Sensor drift, i.e., the lack of a sensor's stability over time, still limits real in dustrial setups. This paper presents and discusses an evolutionary based adaptive drift-correction method designed to work with state-of-the-art classification systems. The proposed approach exploits a cutting-edge evolutionary strategy to iteratively tweak the coefficients of a linear transformation which can transparently correct raw sensors' measures thus mitigating the negative effects of the drift. The method learns the optimal correction strategy without the use of models or other hypotheses on the behavior of the physical chemical sensors

Correlation of Aqueous, Vitreous, and Serum Protein Levels in Patients With Retinal Diseases.

PURPOSE To further establish aqueous humor (AH) as a clinically suitable source of protein biomarkers in retinal diseases by evaluating the correlation of a large panel of proteins between AH, vitreous humor (VH), and serum (SE). METHODS We enrolled 60 subjects (eyes) with various non-infectious retinal diseases. AH, VH, and SE proteins were analyzed using the Olink Target 96 platform (1196 protein assays in total). We compared these three matrices in terms of quantification overlap, principal component analysis, and correlation. RESULTS In the AH, VH, and SE samples, 841, 917, and 1133 proteins, respectively, were consistently quantified above the limit of detection in more than 30% of patients. AH and VH shared 812 of these proteins. AH and VH samples overlapped along principal component 1, but SE samples were distinct. We identified 490 proteins with significant (false discovery rate [FDR]-adjusted P 0.5) between AH and VH, compared to only 33 and 40 proteins for VH and SE and for AH and SE, respectively. CONCLUSIONS Due to a close correlation between protein concentrations in the AH and VH and a clear difference from the SE, AH has the potential to serve as a substitute for VH and may hold significance in identifying protein biomarkers and novel targets related to retinal diseases. TRANSLATIONAL RELEVANCE This study further supports AH as a clinically suitable source of protein biomarkers in retinal diseases. In addition, the identified AH and VH correlations can inform the selection of protein biomarker candidates in future translational research

Investigation of Mitochondrial Dysfunction by Sequential Microplate-Based Respiration Measurements from Intact and Permeabilized Neurons

Mitochondrial dysfunction is a component of many neurodegenerative conditions. Measurement of oxygen consumption from intact neurons enables evaluation of mitochondrial bioenergetics under conditions that are more physiologically realistic compared to isolated mitochondria. However, mechanistic analysis of mitochondrial function in cells is complicated by changing energy demands and lack of substrate control. Here we describe a technique for sequentially measuring respiration from intact and saponin-permeabilized cortical neurons on single microplates. This technique allows control of substrates to individual electron transport chain complexes following permeabilization, as well as side-by-side comparisons to intact cells. To illustrate the utility of the technique, we demonstrate that inhibition of respiration by the drug KB-R7943 in intact neurons is relieved by delivery of the complex II substrate succinate, but not by complex I substrates, via acute saponin permeabilization. In contrast, methyl succinate, a putative cell permeable complex II substrate, failed to rescue respiration in intact neurons and was a poor complex II substrate in permeabilized cells. Sequential measurements of intact and permeabilized cell respiration should be particularly useful for evaluating indirect mitochondrial toxicity due to drugs or cellular signaling events which cannot be readily studied using isolated mitochondria

Constraining Antimatter Domains in the Early Universe with Big Bang Nucleosynthesis

We consider the effect of a small-scale matter-antimatter domain structure on big bang nucleosynthesis and place upper limits on the amount of antimatter in the early universe. For small domains, which annihilate before nucleosynthesis, this limit comes from underproduction of He-4. For larger domains, the limit comes from He-3 overproduction. Most of the He-3 from antiproton-helium annihilation is annihilated also. The main source of He-3 is photodisintegration of He-4 by the electromagnetic cascades initiated by the annihilation.Comment: 4 pages, 2 figures, revtex, (slightly shortened

Black Hole Entropy and Finite Geometry

It is shown that the $E_{6(6)}$ symmetric entropy formula describing black holes and black strings in D=5 is intimately tied to the geometry of the generalized quadrangle GQ$(2,4)$ with automorphism group the Weyl group $W(E_6)$. The 27 charges correspond to the points and the 45 terms in the entropy formula to the lines of GQ$(2,4)$. Different truncations with $15, 11$ and 9 charges are represented by three distinguished subconfigurations of GQ$(2,4)$, well-known to finite geometers; these are the "doily" (i. e. GQ$(2,2)$) with 15, the "perp-set" of a point with 11, and the "grid" (i. e. GQ$(2,1)$) with 9 points, respectively. In order to obtain the correct signs for the terms in the entropy formula, we use a non- commutative labelling for the points of GQ$(2,4)$. For the 40 different possible truncations with 9 charges this labelling yields 120 Mermin squares -- objects well-known from studies concerning Bell-Kochen-Specker-like theorems. These results are connected to our previous ones obtained for the $E_{7(7)}$ symmetric entropy formula in D=4 by observing that the structure of GQ$(2,4)$ is linked to a particular kind of geometric hyperplane of the split Cayley hexagon of order two, featuring 27 points located on 9 pairwise disjoint lines (a distance-3-spread). We conjecture that the different possibilities of describing the D=5 entropy formula using Jordan algebras, qubits and/or qutrits correspond to employing different coordinates for an underlying non-commutative geometric structure based on GQ$(2,4)$.Comment: 17 pages, 3 figures, v2 a new paragraph added, typos correcte

Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial

BACKGROUND: Dravet syndrome is a rare, treatment-resistant developmental epileptic encephalopathy characterised by multiple types of frequent, disabling seizures. Fenfluramine has been reported to have antiseizure activity in observational studies of photosensitive epilepsy and Dravet syndrome. The aim of the present study was to assess the efficacy and safety of fenfluramine in patients with Dravet syndrome. METHODS: In this randomised, double-blind, placebo-controlled clinical trial, we enrolled children and young adults with Dravet syndrome. After a 6-week observation period to establish baseline monthly convulsive seizure frequency (MCSF; convulsive seizures were defined as hemiclonic, tonic, clonic, tonic-atonic, generalised tonic-clonic, and focal with clearly observable motor signs), patients were randomly assigned through an interactive web response system in a 1:1:1 ratio to placebo, fenfluramine 0·2 mg/kg per day, or fenfluramine 0·7 mg/kg per day, added to existing antiepileptic agents for 14 weeks. The primary outcome was the change in mean monthly frequency of convulsive seizures during the treatment period compared with baseline in the 0·7 mg/kg per day group versus placebo; 0·2 mg/kg per day versus placebo was assessed as a key secondary outcome. Analysis was by modified intention to treat. Safety analyses included all participants who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov with two identical protocols NCT02682927 and NCT02826863. FINDINGS: Between Jan 15, 2016, and Aug 14, 2017, we assessed 173 patients, of whom 119 patients (mean age 9·0 years, 64 [54%] male) were randomly assigned to receive either fenfluramine 0·2 mg/kg per day (39), fenfluramine 0·7 mg/kg per day (40) or placebo (40). During treatment, the median reduction in seizure frequency was 74·9% in the fenfluramine 0·7 mg/kg group (from median 20·7 seizures per 28 days to 4·7 seizures per 28 days), 42·3% in the fenfluramine 0·2 mg/kg group (from median 17·5 seizures per 28 days to 12·6 per 28 days), and 19·2% in the placebo group (from median 27·3 per 28 days to 22·0 per 28 days). The study met its primary efficacy endpoint, with fenfluramine 0·7 mg/kg per day showing a 62·3% greater reduction in mean MCSF compared with placebo (95% CI 47·7-72·8, p<0·0001); fenfluramine 0·2 mg/kg per day showed a 32·4% reduction in mean MCSF compared with placebo (95% CI 6·2-52·3, p=0·0209). The most common adverse events (occurring in at least 10% of patients and more frequently in the fenfluramine groups) were decreased appetite, diarrhoea, fatigue, lethargy, somnolence, and decreased weight. Echocardiographic examinations revealed valve function within the normal physiological range in all patients during the trial and no signs of pulmonary arterial hypertension. INTERPRETATION: In Dravet syndrome, fenfluramine provided significantly greater reduction in convulsive seizure frequency compared with placebo and was generally well tolerated, with no observed valvular heart disease or pulmonary arterial hypertension. Fenfluramine could be an important new treatment option for patients with Dravet syndrome. FUNDING: Zogenix