132 research outputs found
A Study of the Servant Class in South Ayrshire, 1750-1914
The laws which have regulated the master-servant relationship in Scotland and the part played by the Church in giving moral guidance on such matters, provided the background to the way the master-servant relationships were conducted in South Ayrshire. The manner in which servants were engaged and discharged was examined, also the conditions under which they served. Wages, duties, accommodation, food and clothing were dealt with, followed by an attempt to account for the movement of the servant population into, out of, and within the area. Some attention was paid to the subject of servants' health and of the savings schemes available to them. The hazards and consequences of impoverishment were examined, together with the types of crime with which some of the servant class might have become involved. Finally, their opportunities for leisure activities and of acquiring literacy skills were studied
Probabilistic Synapses
Learning, especially rapid learning, is critical for survival. However,
learning is hard: a large number of synaptic weights must be set based on
noisy, often ambiguous, sensory information. In such a high-noise regime,
keeping track of probability distributions over weights - not just point
estimates - is the optimal strategy. Here we hypothesize that synapses take
that optimal strategy: they do not store just the mean weight; they also store
their degree of uncertainty - in essence, they put error bars on the weights.
They then use that uncertainty to adjust their learning rates, with higher
uncertainty resulting in higher learning rates. We also make a second,
independent, hypothesis: synapses communicate their uncertainty by linking it
to variability, with more uncertainty leading to more variability. More
concretely, the value of a synaptic weight at a given time is a sample from its
probability distribution. These two hypotheses cast synaptic plasticity as a
problem of Bayesian inference, and thus provide a normative view of learning.
They are consistent with known learning rules, offer an explanation for the
large variability in the size of post-synaptic potentials, and make several
falsifiable experimental predictions
Altered Glycosylated PrP Proteins Can Have Different Neuronal Trafficking in Brain but Do Not Acquire Scrapie-like Properties
N-Linked glycans have been shown to have an important role in the cell biology of a variety of cell surface glycoproteins, including PrP protein. It has been suggested that glycosylation of PrP can influence the susceptibility to transmissible spongiform encephalopathy and determine the characteristics of the many different strains observed in this particular type of disease. To understand the role of carbohydrates in influencing the PrP maturation, stability, and cell biology, we have produced and analyzed gene-targeted murine models expressing differentially glycosylated PrP. Transgenic mice carrying the PrP substitution threonine for asparagine 180 (G1) or threonine for asparagine 196 (G2) or both mutations combined (G3), which eliminate the first, second, and both glycosylation sites, respectively, have been generated by double replacement gene targeting. An in vivo analysis of altered PrP has been carried out in transgenic mouse brains, and our data show that the lack of glycans does not influence PrP maturation and stability. The presence of one chain of sugar is sufficient for the trafficking to the cell membrane, whereas the unglycosylated PrP localization is mainly intracellular. However, this altered cellular localization of PrP does not lead to any overt phenotype in the G3 transgenic mice. Most importantly, we found that, in vivo, unglycosylated PrP does not acquire the characteristics of the aberrant pathogenic form (PrPSc), as was previously reported using in vitro models
Updating the Phase Diagram of the Gross-Neveu Model in 2+1 Dimensions
The method of optimized perturbation theory (OPT) is used to study the phase
diagram of the massless Gross-Neveu model in 2+1 dimensions. In the temperature
and chemical potential plane, our results give strong support to the existence
of a tricritical point and line of first order phase transition, previously
only suspected to exist from extensive lattice Monte Carlo simulations. In
addition of presenting these results we discuss how the OPT can be implemented
in conjunction with the Landau expansion in order to determine all the relevant
critical quantities.Comment: 7 pages, 2 eps figures. Replaced with the version that matches the
published one (PLB
Co-dependence between trypanosome nuclear lamina components in nuclear stability and control of gene expression
The nuclear lamina is a filamentous structure subtending the nuclear envelope and required for chromatin organization, transcriptional regulation and maintaining nuclear structure. The trypanosomatid coiled-coil NUP-1 protein is a lamina component functionally analogous to lamins, the major lamina proteins of metazoa. There is little evidence for shared ancestry, suggesting the presence of a distinct lamina system in trypanosomes. To find additional trypanosomatid lamina components we identified NUP-1 interacting proteins by affinity capture and mass-spectrometry. Multiple components of the nuclear pore complex (NPC) and a second coiled-coil protein, which we termed NUP-2, were found. NUP-2 has a punctate distribution at the nuclear periphery throughout the cell cycle and is in close proximity to NUP-1, the NPCs and telomeric chromosomal regions. RNAi-mediated silencing of NUP-2 leads to severe proliferation defects, gross alterations to nuclear structure, chromosomal organization and nuclear envelope architecture. Further, transcription is altered at telomere-proximal variant surface glycoprotein (VSG) expression sites (ESs), suggesting a role in controlling ES expression, although NUP-2 silencing does not increase VSG switching. Transcriptome analysis suggests specific alterations to Pol I-dependent transcription. NUP-1 is mislocalized in NUP-2 knockdown cells and vice versa, implying that NUP-1 and NUP-2 form a co-dependent network and identifying NUP-2 as a second trypanosomatid nuclear lamina component
Cytoreductive Nephrectomy in the Tyrosine Kinase Inhibitor Era: A Question That May Never Be Answered.
Despite great interest, two randomised controlled trials (RCTs) of cytoreductive nephrectomy in the tyrosine kinase inhibitor setting in metastatic renal cell carcinoma have either closed early (SURTIME) or are recruiting very slowly (CARMENA) after 7 yr. Challenges in RCT delivery in uro-oncologic surgery are many. Multiple steps are needed to ensure strong recruitment to trials addressing important urologic cancer questions. Feasibility/pilot studies are key stepping stones towards successful delivery of surgical RCTs.CARMENA is sponsored by Assistance Publique-HĂ´pitaux de Paris (APHP). CARMENA-UK was funded by Cancer Research UK and administered by the CRUK Clinical Trials Unit, The Beatson West of Scotland Cancer Centre, Glasgow. SURTIME was sponsored by the European Organisation for Research and Treatment of Cancer (EORTC)
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