Computational Mechanics of Input-Output Processes: Structured transformations and the ϵ\epsilon-transducer

Computational mechanics quantifies structure in a stochastic process via its causal states, leading to the process's minimal, optimal predictor---the $\epsilon$-machine. We extend computational mechanics to communication channels between two processes, obtaining an analogous optimal model---the $\epsilon$-transducer---of the stochastic mapping between them. Here, we lay the foundation of a structural analysis of communication channels, treating joint processes and processes with input. The result is a principled structural analysis of mechanisms that support information flow between processes. It is the first in a series on the structural information theory of memoryful channels, channel composition, and allied conditional information measures.Comment: 30 pages, 19 figures; http://csc.ucdavis.edu/~cmg/compmech/pubs/et1.htm; Updated to conform to published version plus additional corrections and update

Allosteric modulation of zinc speciation by fatty acids

Background: Serum albumin is the major protein component of blood plasma and is responsible for the circulatory transport of a range of small molecules that include fatty acids, hormones, metal ions and drugs. Studies examining the ligand-binding properties of albumin make up a large proportion of the literature. However, many of these studies do not address the fact that albumin carries multiple ligands (including metal ions) simultaneously in vivo. Thus the binding of a particular ligand may influence both the affinity and dynamics of albumin interactions with another. Scope of review: Here we review the Zn2 + and fatty acid transport properties of albumin and highlight an important interplay that exists between them. Also the impact of this dynamic interaction upon the distribution of plasma Zn2 +, its effect upon cellular Zn2 + uptake and its importance in the diagnosis of myocardial ischemia are considered. Major conclusions: We previously identified the major binding site for Zn2 + on albumin. Furthermore, we revealed that Zn2 +-binding at this site and fatty acid-binding at the FA2 site are interdependent. This suggests that the binding of fatty acids to albumin may serve as an allosteric switch to modulate Zn2 +-binding to albumin in blood plasma. General significance: Fatty acid levels in the blood are dynamic and chronic elevation of plasma fatty acid levels is associated with some metabolic disorders such as cardiovascular disease and diabetes. Since the binding of Zn2 + to albumin is important for the control of circulatory/cellular Zn2 + dynamics, this relationship is likely to have important physiological and pathological implications. This article is part of a Special Issue entitled Serum Albumin

Prion infection in cells is abolished by a mutated manganese transporter but shows no relation to zinc

The cellular prion protein has been identified as a metalloprotein that binds copper. There have been some suggestions that prion protein also influences zinc and manganese homeostasis. In this study we used a series of cell lines to study the levels of zinc and manganese under different conditions. We overexpressed either the prion protein or known transporters for zinc and manganese to determine relations between the prion protein and both manganese and zinc homeostasis. Our observations supported neither a link between the prion protein and zinc metabolism nor any effect of altered zinc levels on prion protein expression or cellular infection with prions. In contrast we found that a gain of function mutant of a manganese transporter caused reduction of manganese levels in prion infected cells, loss of observable PrPSc in cells and resistance to prion infection. These studies strengthen the link between manganese and prion disease

A metalloproteomic analysis of interactions between plasma proteins and zinc: elevated fatty acid levels affect zinc distribution

Serum albumin is a highly abundant plasma protein associated with the transport of metal ions, pharmaceuticals, fatty acids and a variety of small molecules in the blood. Once thought of as a molecular ‘sponge’, mounting evidence suggests that the albumin-facilitated transport of chemically diverse entities is not independent. One such example is the transport of Zn2+ ions and non-esterified ‘free’ fatty acids (FFAs) by albumin, both of which bind at high affinity sites located in close proximity. Our previous research suggests that their transport in blood plasma is linked via an allosteric mechanism on serum albumin. In direct competition, albumin-bound FFAs significantly decrease the binding capacity of albumin for Zn2+, with one of the predicted consequences being a change in plasma/serum zinc speciation. Using liquid chromatography (LC), ICP-MS and fluorescence assays, our work provides a quantitative assessment of this phenomenon, and finds that in the presence of high FFA concentrations encountered in various physiological conditions, a significant proportion of albumin-bound Zn2+ is re-distributed amongst plasma/serum proteins. Using peptide mass fingerprinting and immunodetection, we identify candidate acceptor proteins for Zn2+ liberated from albumin. These include histidine-rich glycoprotein (HRG), a multifunctional protein associated with the regulation of blood coagulation, and members of the complement system involved in the innate immune response. Our findings highlight how FFA-mediated changes in extracellular metal speciation might contribute to the progression of certain pathological conditions

Comparison of intraoperative frozen section analysis for sentinel lymph node biopsy during breast cancer surgery for invasive lobular carcinoma and invasive ductal carcinoma

<p>Abstract</p> <p>Background</p> <p>Sentinel lymph node (SLN) biopsy is the standard of care for the surgical assessment of the axilla during breast cancer surgery. However, the diagnostic accuracy of intraoperative frozen section analysis for confirming metastatic involvement of SLNs in cases of invasive lobular carcinoma (ILC) versus that of invasive ductal carcinoma (IDC) has generated controversy secondary to a frequently low-grade cytologic appearance and an often discohesive pattern displayed by metastatic lymph nodes in ILC. In the current report, we present a comparison of intraoperative frozen section analysis for confirming the presence of metastatic disease within SLNs during breast cancer surgery for ILC and IDC.</p> <p>Methods</p> <p>We evaluated the results of 131 consecutive cases of ILC from 1997 to 2008 and 133 cases of IDC (selected by a random sequence generator program) from amongst 1163 consecutive cases of IDC from the same time period. All cases had at least one SLN that had both intraoperative frozen section analysis and confirmatory permanent section analysis performed.</p> <p>Results</p> <p>No statistically significant difference was found in the sensitivity (67% vs. 75%, P = 0.385), specificity (100% vs. 100%), accuracy (86% vs. 92%, P = 0.172), false negative rate (33% vs. 25%, P = 0.385), negative predictive value (81% vs. 89%, P = 0.158), and positive predictive value (100% vs. 100%) for frozen section analysis for confirming the presence of metastatic disease within SLNs during breast cancer surgery for ILC and IDC.</p> <p>Conclusion</p> <p>Since there was no statistically significant difference in sensitivity, specificity, accuracy, false negative rate, negative predictive value, and positive predictive value between frozen section analysis of SLNs for patients with ILC and IDC, the clinical accuracy of confirming metastatic involvement of SLNs on frozen section analysis for ILC should not be considered inferior to the clinical accuracy for IDC. Therefore, frozen section analysis of all SLNs during breast cancer surgery in patients with ILC should remain the standard of care in order to reduce the risk of the need of a later, separate axillary lymph node dissection.</p

Design and test of field programmable gate arrays in space applications

Field Programmable Gate Arrays (FPGAU's) offer substantial benefits in terms of flexibility and design integration. In addition to qualifying this device for space applications by establishing its reliability and evaluating its sensitivity to radiation, screening the programmed devices with Automatic Test Equipment (ATE) and functional burn-in presents an interesting challenge. This paper presents a review of the design, qualification, and screening cycle employed for FPGA designs in a space program, and demonstrates the need for close interaction between design and test engineers

Teleportation-based number state manipulation with number sum measurement

We examine various manipulations of photon number states which can be implemented by teleportation technique with number sum measurement. The preparations of the Einstein-Podolsky-Rosen resources as well as the number sum measurement resulting in projection to certain Bell state may be done conditionally with linear optical elements, i.e., beam splitters, phase shifters and zero-one-photon detectors. Squeezed vacuum states are used as primary entanglement resource, while single-photon sources are not required.Comment: 9 pages, 4 figures, Misprints are corrected. 3 figures for number sum measurement are added. Discussion on manipulations are expanded. Calculations for success probabilities are added. Fig.4 is adde

Behavioral economic approaches to reduce college student drinking

Abstract There is a need for novel, theory-based approaches to reduce heavy drinking on college campuses. Behavioral economics has guided basic laboratory research on drug administration for over 30 years and has recently been applied to human substance use in naturalistic and clinical settings. This paper provides an introduction to behavioral economics, reviews applications of behavioral economics to college student drinking, and describes prevention and intervention strategies that are consistent with behavioral economic theory. Behavioral economic theory predicts that college students&apos; decisions about drinking are related to the relative availability and price of alcohol, the relative availability and price of substance-free alternative activities, and the extent to which reinforcement from delayed substance-free outcomes is devalued relative to the immediate reinforcement associated with drinking. Measures of problem severity are based on resource allocation towards alcohol and the relative value of alcohol compared to other reinforcers. Policy and individual level prevention approaches that are consistent with behavioral economic theory are discussed, including strategies for increasing the behavioral and monetary price of alcohol, increasing engagement in rewarding alternatives to substance use, and counteracting student drinkers&apos; tendency to overvalue immediate relative to delayed rewards

High-salinity growth conditions promote tat-independent secretion of tat substrates in Bacillus subtilis

The Gram-positive bacterium Bacillus subtilis contains two Tat translocases, which can facilitate transport of folded proteins across the plasma membrane. Previous research has shown that Tat-dependent protein secretion in B. subtilis is a highly selective process and that heterologous proteins, such as the green fluorescent protein (GFP), are poor Tat substrates in this organism. Nevertheless, when expressed in Escherichia coli, both B. subtilis Tat translocases facilitated exclusively Tat-dependent export of folded GFP when the twin-arginine (RR) signal peptides of the E. coli AmiA, DmsA, or MdoD proteins were attached. Therefore, the present studies were aimed at determining whether the same RR signal peptide-GFP precursors would also be exported Tat dependently in B. subtilis. In addition, we investigated the secretion of GFP fused to the full-length YwbN protein, a strict Tat substrate in B. subtilis. Several investigated GFP fusion proteins were indeed secreted in B. subtilis, but this secretion was shown to be completely Tat independent. At high-salinity growth conditions, the Tat-independent secretion of GFP as directed by the RR signal peptides from the E. coli AmiA, DmsA, or MdoD proteins was significantly enhanced, and this effect was strongest in strains lacking the TatAy-TatCy translocase. This implies that high environmental salinity has a negative influence on the avoidance of Tat-independent secretion of AmiA-GFP, DmsA-GFP, and MdoD-GFP. We conclude that as-yet-unidentified control mechanisms reject the investigated GFP fusion proteins for translocation by the B. subtilis Tat machinery and, at the same time, set limits to their Tat-independent secretion, presumably via the Sec pathway

Learning from monitoring networks: Few-large vs. many-small plots and multi-scale analysis

In order to learn about broad scale ecological patterns, data from large-scale surveys must allow us to either estimate the correlations between the environment and an outcome and/or accurately predict ecological patterns. An important part of data collection is the sampling effort used to collect observations, which we decompose into two quantities: the number of observations or plots (n) and the per-observation/plot effort (E; e.g., area per plot). If we want to understand the relationships between predictors and a response variable, then lower model parameter uncertainty is desirable. If the goal is to predict a response variable, then lower prediction error is preferable. We aim to learn if and when aggregating data can help attain these goals. We find that a small sample size coupled with large observation effort coupled (few large) can yield better predictions when compared to a large number of observations with low observation effort (many small). We also show that the combination of the two values (n and E), rather than one alone, has an impact on parameter uncertainty. In an application to Forest Inventory and Analysis (FIA) data, we model the tree density of selected species at various amounts of aggregation using linear regression in order to compare the findings from simulated data to real data. The application supports the theoretical findings that increasing observational effort through aggregation can lead to improved predictions, conditional on the thoughtful aggregation of the observational plots. In particular, aggregations over extremely large and variable covariate space may lead to poor prediction and high parameter uncertainty. Analyses of large-range data can improve with aggregation, with implications for both model evaluation and sampling design: testing model prediction accuracy without an underlying knowledge of the datasets and the scale at which predictor variables operate can obscure meaningful results