Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.     

Quantitative Proteomic Approach Reveals Altered Metabolic Pathways in Response to the Inhibition of Lysine Deacetylases in A549 Cells under Normoxia and Hypoxia

Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies.     

Value of information in remanufacturing complex products

Remanufacturing facilities usually face a trade-off between limited information about remanufacturing yields and potentially long supplier lead times. To improve production performance, these firms may attempt to acquire more timely and accurate information about remanufacturing yields or alternatively, to reduce the lead times of purchased parts. We develop four decision-making models to evaluate the impact of yield information and supplier lead time on manufacturing costs. We identify the operating conditions under which these capabilities are valuable, along with their relative impact on facility performance. Each model is formulated as an infinite horizon, stochastic dynamic program (Markov decision process). Our results indicate that the yield information is generally quite valuable, while investments in supplier responsiveness provide trivial returns to products with few parts. However, as product complexity increases with large number of target parts, the value of short lead times increases.     

Gorillas (Gorilla gorilla) and Orangutans (Pongo pygmaeus) Encode Relevant Problem Features in a Tool-Using Task.

Two important elements in problem solving are the abilities to encode relevant task features and to combine multiple actions to achieve the goal. The authors investigated these 2 elements in a task in which gorillas (Gorilla gorilla) and orangutans (Pongo pygmaeus) had to use a tool to retrieve an out-of-reach reward. Subjects were able to select tools of an appropriate length to reach the reward even when the position of the reward and tools were not simultaneously visible. When presented with tools that were too short to retrieve the reward, subjects were more likely to refuse to use them than when tools were the appropriate length. Subjects were proficient at using tools in sequence to retrieve the reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synthesis and Properties of Photoisomerizable Derivatives of Isosorbide and Their Use in Cholesteric Filters

This paper describes the synthesis of photoisomerizable derivatives of isosorbide. These derivatives contain a stilbene or cinnamate moiety and can therefore be used as photoisomerizable chiral compounds in cholesteric liquid‐crystalline mixtures. The reflection wavelength of cholesteric layers made from these mixtures is increased by UV irradiation due to the fact that the Z‐isomers of these derivatives exhibit a lower helical twisting power than the corresponding E‐isomers. The cinnamate derivatives are very suitable for use in cholesteric color filters that find application in liquid‐crystal displays.     

Biofiltration of toluene in the absence and the presence of ethyl acetate under continuous and intermittent loading

BACKGROUND: Two peat biofilters were used for the removal of toluene from air for one year. One biofilter was fed with pure toluene and the other received 1:1 (by weight) ethyl acetate:toluene mixture. RESULTS: The biofilters were operated under continuous loading: the toluene inlet load (IL) at which 80% removal occurred was 116 g m^?3 h^?1 at 57 s gas residence time. Maximum elimination capacity of 360 g m^?3 h^?1 was obtained at an IL of 745 g m^?3 h^?1. The elimination of toluene was inhibited by the presence of ethyl acetate. Intermittent loading, with pollutants supplied for 16 h/day, 5 days/week, did not significantly affect the removal efficiency (RE). Biomass was fully activated in 2 h after night closures, but 6 h were required to recover RE after weekend closures. Live cell density remained relatively constant over the operational period, while the dead cell fraction increased. Finally, a 15 day starvation period was applied and operation then re‐started. Performance was restored with similar re‐acclimatization period to that after weekend closures, and a reduction in dead cell fraction was observed. CONCLUSION: This study demonstrates the capacity of the system to handle intermittent loading conditions that are common in industrial practices, including long‐term starvation. Copyright © 2008 Society of Chemical Industry     

A high-frequency nonquasi-static analytical model including gate leakage effects for on-chip decoupling capacitors

This paper presents a compact model for on-chip decoupling capacitors (decaps) including gate-oxide leakage. The model makes use of only four parameters, namely, channel resistance, gate-oxide capacitance, and two parameters to quantify gate-oxide leakage, to predict the static and dynamic response of decaps. Quality indices have been defined to enable development of decap design guidelines and evaluation of performance of such capacitors. The model shows how the gate leakage and longer channel lengths severely affect the performance of on-chip decaps for both low and high frequencies. The model also shows that lumped models of decaps at high frequencies fail and have to be substituted by a distributed model. Application of the model uncovers tradeoffs for thin- and thick-oxide capacitors in an available 90-nm CMOS technology. For a general-purpose technology, a reference capacitance value has been realized using decaps with a discrete width and length. Our model predicts that thick-oxide n-channel (p-channel) capacitors require /spl sim/3.37x (/spl sim/3.31x) more silicon area and /spl sim/1.70x (/spl sim/1.17x) degraded time response as compared to their thin-oxide versions. The time response is even more degraded (/spl prop/L/sup 2/) when longer channel decaps are used. This paper contributes by defining performance benchmarks for decaps.     

Immunoglobulin A levels in southern elephant seal (Mirounga leonina) milk during the suckling period

Immunoglobulin A (IgA) levels in milk samples from southern elephant seals at King George Island, Antarctica are reported. IgA levels were determined throughout the suckling period (approximately 23 days). The IgA concentration in southern elephant seal milk was lower than in other mammals and, unlike most mammalian milk, was not high during early lactation. There was not a definite pattern in IgA levels, which fluctuated within narrow limits throughout the suckling period (mean +/- SD, 30.81 +/- 6.38 mg IgA/100 g milk). If IgG was present, its level was too low to be detected by the method used. This is the first evidence in Southern elephant seal of the possibility of transmission of passive immunity after birth involving secretion of IgA in the milk.