Molecular mechanisms underlying a cellular analog of operant reward learning.

Operant conditioning is a ubiquitous but mechanistically poorly understood form of associative learning in which an animal learns the consequences of its behavior. Using a single-cell analog of operant conditioning in neuron B51 of Aplysia, we examined second-messenger pathways engaged by activity and reward and how they may provide a biochemical association underlying operant learning. Conditioning was blocked by Rp-cAMP, a peptide inhibitor of PKA, a PKC inhibitor, and by expressing a dominant-negative isoform of Ca2+-dependent PKC (apl-I). Thus, both PKA and PKC were necessary for operant conditioning. Injection of cAMP into B51 mimicked the effects of operant conditioning. Activation of PKC also mimicked conditioning but was dependent on both cAMP and PKA, suggesting that PKC acted at some point upstream of PKA activation. Our results demonstrate how these molecules can interact to mediate operant conditioning in an individual neuron important for the expression of the conditioned behavior.

Ach, analog, digital - Quanten! Blitzkurs für alle Feinde des Digitalen und Technologieverächter

Die Natur integriert digitale und analoge Systeme umstandslos, man muss nur auf die Welt der Quantenmechanik schauen. Warum also diese Dauerproduktion gesellschaftlicher und kultureller Endzeitszenarien? Warum die Dauerbeschwörung der digitalen Bedrohung? Warum lassen wir uns nicht einfach auf das ein, was unsere physikalische Existenz grundlegend determiniert — die Koexistenz.

First intercomparison study on the analysis of oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) and nitrogen heterocyclic polycyclic aromatic compounds (N-PACs) in contaminated soil

Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) and nitrogen heterocyclic polycyclic aromatic compounds (N-PACs) are toxic, highly leachable and often abundant at sites that are also contaminated with PAHs. However, due to lack of regulations and standardized methods for their analysis, they are seldom included in monitoring and risk-assessment programs. This intercomparison study constitutes an important step in the harmonization of the analytical methods currently used, and may also be considered a first step towards the certification of reference materials for these compounds. The results showed that the participants were able to determine oxy-PAHs with accuracy similar to PAHs, with average determined mass fractions agreeing well with the known levels in a spiked soil and acceptable inter- and intra-laboratory precisions for all soils analyzed. For the N-PACs, the results were less satisfactory, and have to be improved by using analytical methods more specifically optimized for these compounds.

Virus-like particle-mediated intracellular delivery of mRNA cap analog with in vivo activity against hepatocellular carcinoma.

UNLABELLED Adenovirus dodecahedron (Dd), a nanoparticulate proteinaceous biodegradable virus-like particle (VLP), was used as a vector for delivery of an oncogene inhibitor to hepatocellular carcinoma (HCC) rat orthotopic model. Initiation factor eIF4E is an oncogene with elevated expression in human cancers. Cell-impermeant eIF4E inhibitor, cap structure analog (cap) and anti-cancer antibiotic doxorubicin (Dox) were delivered as Dd conjugates. Dd-cap and Dd-dox inhibited cancer cell culture proliferation up to 50 and 84%, respectively, while with free Dox similar results could be obtained only at a 5 times higher concentration. In animal HCC model the combination treatment of Dd-cap/Dd-dox caused 40% inhibition of tumor growth. Importantly, the level of two pro-oncogenes, eIF4E and c-myc, was significantly diminished in tumor sections of treated rats. Attachment to Dd, a virus-like particle, permitted the first demonstration of cap analog intracellular delivery and resulted in improved doxorubicin delivery leading to statistically significant inhibition of HCC tumor growth. FROM THE CLINICAL EDITOR Adenovirus dodecahedron, a nanoparticulate proteinaceous biodegradable virus-like particle was used in this study as a vector for the concomitant delivery of cap structure analog and doxorubicine to hepatocellular carcinoma in a rat model, resulting in significant inhibition of tumor growth.

Desiccation of phyllosilicate-bearing samples as analog for desiccation cracks on Mars: Experimental setup and initial results

The surface of Mars is host to many regions displaying polygonal crack patterns that have been identified as potential desiccation cracks. These regions are mostly within Noachian-aged terrains and are closely associated with phyllosilicate occurrences and smectites in particular. We have built a laboratory setup that allows us to carry out desiccation experiments on Mars-analog materials in an effort to constrain the physical and chemical properties of sediments that display polygonal cracks. The setup is complemented by a pre-existing simulation chamber that enables the investigation of the spectral and photometric properties of analog materials in Mars-like conditions. The initial experiments that have been carried out show that (1) crack patterns are visible in smectite-bearing materials in varying concentrations down to similar to 10% smectite by weight, (2) chlorides, and potentially other salts, delay the onset of cracking and may even block it from occurring entirely, and (3) the polygonal patterns, while being indicative of the presence of phyllosilicates, cannot be used to differentiate between various phyllosilicate-bearing deposits. However, their size-scale and morphology yields important information regarding their thickness and the hydrological conditions at the time of formation. Furthermore, the complementary spectral measurements for some of the analog samples shows that crack patterns may develop in materials with such low concentrations of smectites that would not be expected to be identified using remote-sensing instruments. This may explain the presence of polygonal patterns on Mars in sediments that lack spectral confirmation of phyllosilicates. (C) 2015 Elsevier Ltd. All rights reserved.

Breast cancer risk and heterocyclic amines and effect modification by NAT gene polymorphisms

Breast cancer is the most common cancer in women in the United States and is a leading cause of cancer-related deaths (1). Recently, dietary heterocyclic amines (HCAs) have been proposed to be a risk factor for breast cancer (2). This study uses the data collected for a case-control study conducted at the M.D. Anderson Cancer Center to assess the association between breast cancer risk and HCAs {2-amino-1-methyl-6-phenylimidazole [4,5-b] pyridine (PhIP), 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo [4,5-f] quinoxaline (DiMeIQx) and mutagenicity of HCAs} and to examine if this association is modified by genetic polymorphisms of N-acetyl transferases (NAT1/NAT2). The NAT1/2 genotype was determined using Taqman technology. HCAs were estimated by using a meat preparation questionnaire on meat type, cooking method, and doneness, combined with a quantitative HCA database. Three hundred and fifty patients with breast cancer attending the Diagnostic Radiology Clinic at M. D. Anderson Cancer Center and fulfilling the eligibility criteria were compared to three hundred and fifty patients attending the same clinic for benign breast lesions to answer these questions. Logistic regression models were used to control for known risk factors and showed no statistically significant association between breast cancer versus benign breast cancer lesions and dietary intake of heterocyclic amines. There was no clear difference in their effect after subgroup analyses in different acetylator strata of NAT1/2 and no statistical interactions were found between NAT1/2 genotypes and HCAs, suggesting no effect modification by NAT1/2 acetylator status. These results suggest the need for further research to analyze if these null associations were because of the benign breast lesions sharing the risk factors with breast cancer or any other factors which haven't been explored yet.^

Analog mitigation of out of band strong interferers in wide band acquisition for multiband HF transmissions

It is clear that in the near future much broader transmissions in the HF band will replace part of the current narrow band links. Our personal view is that a real wide band signal is infeasible in this environment because the usage is typically very intensive and may suffer interferences from all over the world. Therefore, we envision that dynamic multiband transmissions may provide better satisfactory performance. From the very beginning, we observed that real links with our broadband transceiver suffered interferences out of our multiband but within the acquisition bandwidth that degrade the expected performance. Therefore, we concluded that a mitigation structure is required that operates on severely saturated signals as the interference may be of much higher power. In this paper we address a procedure based on Higher Order Crossings (HOC) statistics that are able to extract most of the signal structure in the case where the amplitude is severely distorted and allows the estimation of the interference carrier frequency to command a variable notch filter that mitigates its effect in the analog domain.