A cybernetic approach to prediction with an outline of an adaptive optical computer

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Since the pioneering work of Kolmogoroff and Wiener the use of computing devices to solve problems concerned with - the prediction of future states of a time series has stimulated a large amount of research. Despite all this, however the results have been disappointing. If significant progress were to be made in this field it would lead not only to the possibility of forecasting economic events, the weather, earthquakes, epidemics, and so on, but also -to the possibility of simulating these system. Approaches involving the programming of a computer to carry out this task run into the difficulty of defining the variables involved in a precise enough manner, whereas using the computer -to investigate all the past events of that time series requires a large processing time and an enormous memory store. This thesis examines an approach to this problem which involves the use of a device for processing information in a parallel manner. The system envisaged consists of a holographic recognition device controlled by a digital computer -a combination of analogue and digital techniques. The principle of this device is that developed by Gabor and others, and allows the system to learn to predict the future of a time series. The system learns to predict the future of a time series by using a past length of time series as a training set. Using this training set it attempts to predict the next values of the time series, which can then be compared with the actual time series. The system, then, attempts to optimize its prediction by minimizing the error between the predicted and actual values

Formation and spreading of Red Sea Outflow Water in the Red Sea

Author Posting. © American Geophysical Union, 2015. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 120 (2015): 6542–6563, doi:10.1002/2015JC010751.Hydrographic data, chlorofluorocarbon-12 (CFC-12) and sulfur hexafluoride (SF6) measurements collected in March 2010 and September–October 2011 in the Red Sea, as well as an idealized numerical experiment are used to study the formation and spreading of Red Sea Outflow Water (RSOW) in the Red Sea. Analysis of inert tracers, potential vorticity distributions, and model results confirm that RSOW is formed through mixed-layer deepening caused by sea surface buoyancy loss in winter in the northern Red Sea and reveal more details on RSOW spreading rates, pathways, and vertical structure. The southward spreading of RSOW after its formation is identified as a layer with minimum potential vorticity and maximum CFC-12 and SF6. Ventilation ages of seawater within the RSOW layer, calculated from the partial pressure of SF6 (pSF6), range from 2 years in the northern Red Sea to 15 years at 17°N. The distribution of the tracer ages is in agreement with the model circulation field which shows a rapid transport of RSOW from its formation region to the southern Red Sea where there are longer circulation pathways and hence longer residence time due to basin wide eddies. The mean residence time of RSOW within the Red Sea estimated from the pSF6 age is 4.7 years. This time scale is very close to the mean transit time (4.8 years) for particles from the RSOW formation region to reach the exit at the Strait of Bab el Mandeb in the numerical experiment.King Abdullah University of Science and Technology (KAUST) Grant Numbers: USA 00002, KSA 00011, KSA 00011/02; National Science Foundation; WHOI Academic Program Office Grant Number: OCE09270172016-03-2

Pifithrin-alpha inhibits p53 signaling after interaction of the tumor suppressor protein with hsp90 and its nuclear translocation

Pifithrin-alpha (PFTalpha) was originally thought to be a specific inhibitor of signaling by the tumor suppressor protein p53. However, the laboratory that discovered pifithrin recently reported that the compound also inhibits heat shock and glucocorticoid receptor (GR) signaling, and they suggested that PFTalpha targets a factor common to all three signal transduction pathways, such as the hsp90/hsp70-based chaperone machinery (Komarova, E. A., Neznanov, N., Komarov, P. G., Chernov, M. V., Wang, K., and Gudkov, A. V. (2003) J. Biol. Chem. 278, 15465-15468). Because it is important for the mechanistic study of this machinery to identify unique inhibitors of chaperone action, we have examined the effect of PFTalpha on transcriptional activation, the hsp90 heterocomplex assembly, and hsp90-dependent nuclear translocation for both p53 and the GR. At concentrations where PFTalpha blocks p53-mediated induction of p21/Waf-1 in human embryonic kidney cells, we observed no inhibition of GR-mediated induction of a chloramphenicol acetyl transferase reporter in LMCAT cells. PFTalpha did, however, cause a left shift in the dexamethasone dose response curve by increasing intracellular dexamethasone concentration, apparently by competing for dexamethasone efflux from the cell. The assembly of p53 or GR heterocomplexes with hsp90 and immunophilins was not affected by PFTalpha either in vivo or in vitro and did not affect the nuclear translocation of either transcription factor. Thus, we conclude that PFTalpha does not inhibit GR-mediated induction or the function of the chaperone machinery, and, as originally thought, it may specifically inhibit p53 signaling by acting at a stage after p53 translocation to the nucleus.Fil: Murphy, Patrick J.. University of Michigan; Estados UnidosFil: Galigniana, Mario Daniel. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Morishima, Yoshihiro. University of Michigan; Estados UnidosFil: Harrell, Jennifer M.. University of Michigan; Estados UnidosFil: Kwok, Roland P.. University of Michigan; Estados UnidosFil: Ljungman, Mats. University of Michigan; Estados UnidosFil: Pratt, William B.. University of Michigan; Estados Unido

Point Mutations in the 90-kDa Heat Shock Protein Binding Region of the Glucocorticoid Receptor Affect the Functional Characteristics of the Receptor a

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72162/1/j.1749-6632.1995.tb31403.x.pd

DNA-binding and non-DNA-binding forms of the transformed glucocorticoid receptor

In this work we have probed the mechanism responsible for two non-DNA-binding states of the mouse glucocorticoid receptor. In the first case, transformed receptors were treated with hydrogen peroxide. It is known that oxidizing agents promote the formation of disulfide bonds in the glucocorticoid receptor, but it has not been determined what domains are involved in any disulfide bond formation that leads to inactivation of DNA-binding activity. We show here that hydrogen peroxide inhibits DNA-binding by the 15-kDa tryptic fragment containing the DNA-binding fingers with the same concentration dependency as it inhibits DNA-binding by the uncleaved receptor. This suggests that all of the effect of peroxide is on sulfhydryl groups within the zinc fingers. After dissociation (transformation) of cytosolic heteromeric glucocorticoid receptor complexes, only a portion (40-60%) of the dissociated receptors can bind to DNA-cellulose. We show that the 15-kDA tryptic fragment derived from the portion of transformed receptors that do not bind to DNA is itself competent at DNA-binding.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30198/1/0000586.pd

The hsp56 immunophilin component of steroid receptor heterocomplexes: Could this be the elusive nuclear localization signal-binding protein?

In many cells, the glucocorticoid receptor undergoes rapid steroid-mediated translocation from the cytoplasm to the nucleus, and this receptor is an excellent model for studying the mechanism of targeted protein movement through the cytoplasm. For such unidirectional movement to occur, the receptor must attach to a retrograde movement system in a manner that involves the nuclear localization signal. It is improbable that such attachment occurs via a direct protein-protein interaction between the receptor and the movement system; rather, one or more linker proteins are likely to be involved. As with other steroid receptors, the glucocorticoid receptor is associated with several other proteins in a heterocomplex. Two of these receptor-associated proteins are the heat shock proteins hsp90 and hsp56, and a third heat shock protein, hsp70, is required for assembly of the receptor heterocomplex. The hormone binding domain of the steroid receptors determines the interaction with both hsp90 and hsp70. Hsp56 is known to bind to hsp90, but its potential site, or sites, of interaction with the receptor are undefined. Hsp56 has recently been cloned and demonstrated to be an immunophilin of the FK506/rapamycin binding class. The immunophilins have peptidyl-prolyl isomerase activity but their cellular functions are unknown. Herein, we review the literature on the hsp56 immunophilin component of the receptor heterocomplex and present a rationale for hsp56 being the protein that determines the direction of receptor movement via a direct protein-protein interaction with the nuclear localization signal.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30603/1/0000240.pd

Spin-Diffusion Lengths in Metals and Alloys, and Spin-Flipping at Metal/Metal Interfaces: an Experimentalist's Critical Review

In magnetoresistive (MR) studies of magnetic multilayers composed of combinations of ferromagnetic (F) and non-magnetic (N) metals, the magnetic moment (or related 'spin') of each conduction electron plays a crucial role, supplementary to that of its charge. While initial analyses of MR in such multilayers assumed that the direction of the spin of each electron stayed fixed as the electron transited the multilayer, we now know that this is true only in a certain limit. Generally, the spins 'flip' in a distance characteristic of the metal, its purity, and the temperature. They can also flip at F/N or N1/N2 interfaces. In this review we describe how to measure the lengths over which electron moments flip in pure metals and alloys, and the probability of spin-flipping at metallic interfaces. Spin-flipping within metals is described by a spin-diffusion length,l^M(sf), where the metal M = F or N. Spin-diffusion lengths are the characteristic lengths in the current-perpendicular-to-plane (CPP) and lateral non-local (LNL) geometries that we focus upon in this review. In certain simple cases, l^N(sf) sets the distance over which the CPP-MR and LNL-MR decrease as the N-layer thickness (CPP-MR) or N-film length (LNL) increases, and l^F(sf) does the same for increase of the CPP-MR with increasing F-layer thickness. Spin-flipping at M1/M2 interfaces can be described by a parameter, delta(M1/M2), which determines the spin-flipping probability, P = 1 - exp(-delta). Increasing delta(M1/M2) usually decreases the MR. We list measured values of these parameters and discuss the limitations on their determinations.Comment: Invited Review, to appear in J. Phys. Cond. Matter. 50 pages, 18 figures. The new version contains additional material and revisions to improve clarit

Bostonia: The Boston University Alumni Magazine. Volume 10

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs