Rapid bidirectional reorganization of cortical microcircuits.

Mature neocortex adapts to altered sensory input by changing neural activity in cortical circuits. The underlying cellular mechanisms remain unclear. We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to show reorganization in somatosensory cortex elicited by altered whisker sensory input. We found that there was rapid expansion followed by retraction of whisker cortical maps. The cellular basis for the reorganization in primary somatosensory cortex was investigated with paired electrophysiological recordings in the periphery of the expanded whisker representation. During map expansion, the chance of finding a monosynaptic connection between pairs of pyramidal neurons increased 3-fold. Despite the rapid increase in local excitatory connectivity, the average strength and synaptic dynamics did not change, which suggests that new excitatory connections rapidly acquire the properties of established excitatory connections. During map retraction, entire excitatory connections between pyramidal neurons were lost. In contrast, connectivity between pyramidal neurons and fast spiking interneurons was unchanged. Hence, the changes in local excitatory connectivity did not occur in all circuits involving pyramidal neurons. Our data show that pyramidal neurons are recruited to and eliminated from local excitatory networks over days. These findings suggest that the local excitatory connectome is dynamic in mature neocortex

Catalytic transfer hydrogenolysis of organosolv lignin using B-containing FeNi alloyed catalysts

© 2017 Elsevier B.V. In this work, FeB, NiB, and FeNiB nanomaterials were examined as catalysts for catalytic transfer hydrogenolysis (CTH) using supercritical ethanol (sc-EtOH) as the hydrogen donor and reaction solvent. The earth-abundant alloys were synthesized using simple aqueous chemical reductions and characterized using ICP-OES, XRD, and STEM-EDS. Using acetophenone to model the desired catalytic reactivity, FeNiB was identified as having superior reactivity (74% conversion) and selectivity for complete deoxygenation to ethylbenzene (84%) when compared to the monometallic materials. Given its high reactivity and selectivity for deoxygenation over ring saturation, FeNiB was screened as a lignin valorization catalyst. FeNiB mediates deoxygenation of aliphatic hydroxyl and carbonyls in organosolv lignin via CTH in sc-EtOH. A combination of gel permeation chromatography, GC/MS, and NMR spectroscopy was used to demonstrate the production of a slate of monomeric phenols with intact deoxygenated aliphatic side chains. In total, these results highlight the utility of CTH for the valorization of biorefinery-relevant lignin using an inexpensive, earth-abundant catalyst material and a green solvent system that can be directly derived from the polysaccharide fraction of lignocellulosic biomass

The Replication Argument for Incompatibilism

In this paper, I articulate an argument for incompatibilism about moral responsibility and determinism. My argument comes in the form of an extended story, modeled loosely on Peter van Inwagen’s “rollback argument” scenario. I thus call it “the replication argument.” As I aim to bring out, though the argument is inspired by so-called “manipulation” and “original design” arguments, the argument is not a version of either such argument—and plausibly has advantages over both. The result, I believe, is a more convincing incompatibilist argument than those we have considered previously

Elementary processes governing the evolution of road networks

Urbanisation is a fundamental phenomenon whose quantitative characterisation is still inadequate. We report here the empirical analysis of a unique data set regarding almost 200 years of evolution of the road network in a large area located north of Milan (Italy). We find that urbanisation is characterised by the homogenisation of cell shapes, and by the stability throughout time of high-centrality roads which constitute the backbone of the urban structure, confirming the importance of historical paths. We show quantitatively that the growth of the network is governed by two elementary processes: (i) `densification', corresponding to an increase in the local density of roads around existing urban centres and (ii) `exploration', whereby new roads trigger the spatial evolution of the urbanisation front. The empirical identification of such simple elementary mechanisms suggests the existence of general, simple properties of urbanisation and opens new directions for its modelling and quantitative description.Comment: 10 pages, 6 figure

An inventory of supraglacial lakes and channels across the West Antarctic Ice Sheet

Quantifying the extent and distribution of supraglacial hydrology, i.e. lakes and streams, is important for understanding the mass balance of the Antarctic ice sheet and its consequent contribution to global sea-level rise. The existence of meltwater on the ice surface has the potential to affect ice shelf stability and grounded ice flow through hydrofracturing and the associated delivery of meltwater to the bed. In this study, we systematically map all observable supraglacial lakes and streams in West Antarctica by applying a semi-automated Dual-NDWI (normalised difference water index) approach to >2000 images acquired by the Sentinel-2 and Landsat-8 satellites during January 2017. We use a K-means clustering method to partition water into lakes and streams, which is important for understanding the dynamics and inter-connectivity of the hydrological system. When compared to a manually delineated reference dataset on three Antarctic test sites, our approach achieves average values for sensitivity (85.3 % and 77.6 %), specificity (99.1 % and 99.7 %) and accuracy (98.7 % and 98.3 %) for Sentinel-2 and Landsat-8 acquisitions, respectively. We identified 10 478 supraglacial features (10 223 lakes and 255 channels) on the West Antarctic Ice Sheet (WAIS) and Antarctic Peninsula (AP), with a combined area of 119.4 km2 (114.7 km2 lakes, 4.7 km2 channels). We found 27.3 % of feature area on grounded ice and 54.9 % on floating ice shelves. In total, 17.8 % of feature area crossed the grounding line. A recent expansion in satellite data provision made new continental-scale inventories such as these, the first produced for WAIS and AP, possible. The inventories provide a baseline for future studies and a benchmark to monitor the development of Antarctica's surface hydrology in a warming world and thus enhance our capability to predict the collapse of ice shelves in the future. The dataset is available at https://doi.org/10.5281/zenodo.5642755 (Corr et al., 2021)

Determination of an optimal dosing regimen for aspirin chemoprevention of 1,2-dimethylhydrazine-induced colon tumours in rats

In order to establish an optimal timing and duration of aspirin treatment in the chemoprevention of 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats, colon tumours were induced using an established protocol and aspirin was given in the diet at 500 p.p.m. during various stages of colon carcinogenesis. Results indicate that only aspirin treatment throughout the entire carcinogenic period significantly reduced tumour incidence and volume whereas intermittent aspirin dosing increased tumour number and/or volume, suggesting that aspirin must be used for an extended period in order to gain any chemopreventive benefit. © 1999 Cancer Research Campaig

A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

Molecular characterization of commensal Escherichia coli adapted to different compartments of the porcine gastrointestinal tract

The role of Escherichia coli as a pathogen has been the focus of considerable study, while much less is known about it as a commensal and how it adapts to and colonizes different environmental niches within the mammalian gut. In this study, we characterize Escherichia coli organisms (n=146) isolated from different regions of the intestinal tracts of eight pigs (dueodenum, ileum, colon, and feces). The isolates were typed using the method of random amplified polymorphic DNA (RAPD) and screened for the presence of bacteriocin genes and plasmid replicon types. Molecular analysis of variance using the RAPD data showed that E. coli isolates are nonrandomly distributed among different gut regions, and that gut region accounted for 25% (