Mass spectrometry-based thermal shift assay for protein-ligand binding analysis.

Described here is a mass spectrometry-based screening assay for the detection of protein-ligand binding interactions in multicomponent protein mixtures. The assay utilizes an oxidation labeling protocol that involves using hydrogen peroxide to selectively oxidize methionine residues in proteins in order to probe the solvent accessibility of these residues as a function of temperature. The extent to which methionine residues in a protein are oxidized after specified reaction times at a range of temperatures is determined in a MALDI analysis of the intact proteins and/or an LC-MS analysis of tryptic peptide fragments generated after the oxidation reaction is quenched. Ultimately, the mass spectral data is used to construct thermal denaturation curves for the detected proteins. In this proof-of-principle work, the protocol is applied to a four-protein model mixture comprised of ubiquitin, ribonuclease A (RNaseA), cyclophilin A (CypA), and bovine carbonic anhydrase II (BCAII). The new protocol's ability to detect protein-ligand binding interactions by comparing thermal denaturation data obtained in the absence and in the presence of ligand is demonstrated using cyclosporin A (CsA) as a test ligand. The known binding interaction between CsA and CypA was detected using both the MALDI- and LC-MS-based readouts described here.

Neural mechanisms of context effects on face recognition: automatic binding and context shift decrements.

Although people do not normally try to remember associations between faces and physical contexts, these associations are established automatically, as indicated by the difficulty of recognizing familiar faces in different contexts ("butcher-on-the-bus" phenomenon). The present fMRI study investigated the automatic binding of faces and scenes. In the face-face (F-F) condition, faces were presented alone during both encoding and retrieval, whereas in the face/scene-face (FS-F) condition, they were presented overlaid on scenes during encoding but alone during retrieval (context change). Although participants were instructed to focus only on the faces during both encoding and retrieval, recognition performance was worse in the FS-F than in the F-F condition ("context shift decrement" [CSD]), confirming automatic face-scene binding during encoding. This binding was mediated by the hippocampus as indicated by greater subsequent memory effects (remembered > forgotten) in this region for the FS-F than the F-F condition. Scene memory was mediated by right parahippocampal cortex, which was reactivated during successful retrieval when the faces were associated with a scene during encoding (FS-F condition). Analyses using the CSD as a regressor yielded a clear hemispheric asymmetry in medial temporal lobe activity during encoding: Left hippocampal and parahippocampal activity was associated with a smaller CSD, indicating more flexible memory representations immune to context changes, whereas right hippocampal/rhinal activity was associated with a larger CSD, indicating less flexible representations sensitive to context change. Taken together, the results clarify the neural mechanisms of context effects on face recognition.

Iterative inversion of experimental data in weighted spaces

We present iterative algorithms for solving linear inverse problems with discrete data and compare their performances with the method of singular function expansion, in view of applications in optical imaging and particle sizing.

The Use of Singular Systems and other Inversion Methods in Weighted L2- spaces

info:eu-repo/semantics/published

Minimizing total weighted completion time in a proportionate flow shop

We study the special case of the m machine flow shop problem in which the processing time of each operation of job j is equal to pj; this variant of the flow shop problem is known as the proportionate flow shop problem. We show that for any number of machines and for any regular performance criterion we can restrict our search for an optimal schedule to permutation schedules. Moreover, we show that the problem of minimizing total weighted completion time is solvable in O(n2) time. © 1998 John Wiley & Sons, Ltd.

A fully polynomial approximation scheme for the single machine weighted total tardiness problem with a common due date

We develop a fully polynomial-time approximation scheme (FPTAS) for minimizing the weighted total tardiness on a single machine, provided that all due dates are equal. The FPTAS is obtained by converting an especially designed pseudopolynomial dynamic programming algorithm.

Probabilistic approach in weighted Markov branching processes

This note provides a new probabilistic approach in discussing the weighted Markov branching process (WMBP) which is a natural generalisation of the ordinary Markov branching process. Using this approach, some important characteristics regarding the hitting times of such processes can be easily obtained. In particular, the closed forms for the mean extinction time and conditional mean extinction time are presented. The explosion behaviour of the process is investigated and the mean explosion time is derived. The mean global holding time and the mean total survival time are also obtained. The close link between these newly developed processes and the well-known compound Poisson processes is investigated. It is revealed that any weighted Markov branching process (WMBP) is a random time change of a compound Poisson process.

Two simple constant ratio approximation algorithms for minimizing the total weighted completion time on a single machine with a fixed non-availability interval

In this note, we consider the scheduling problem of minimizing the sum of the weighted completion times on a single machine with one non-availability interval on the machine under the non-resumable scenario. Together with a recent 2-approximation algorithm designed by Kacem [I. Kacem, Approximation algorithm for the weighted flow-time minimization on a single machine with a fixed non-availability interval, Computers & Industrial Engineering 54 (2008) 401–410], this paper is the first successful attempt to develop a constant ratio approximation algorithm for this problem. We present two approaches to designing such an algorithm. Our best algorithm guarantees a worst-case performance ratio of 2+ε. © 2008 Elsevier B.V. All rights reserved.

Ghost and self: Jung's paradigm shift and a response to Zinkin

Zinkin's lucid challenge to Jung makes perfect sense. Indeed, it is the implications of this `making sense' that this paper addresses. For Zinkin's characterization of the `self' takes it as a `concept' requiring coherence; a variety of abstract non-contextual knowledge that itself has a mythical heritage. Moreover, Zinkin's refinement of Jung seeks to make his work fit for the scientific paradigm of modernity. In turn, modernity's paradigm owes much to Newton's notion of knowledge via reductionism. Here knowledge or investigation is divided up into the smallest possible units with the aim of eventually putting it all together into `one' picture of scientific truth. Unfortunately, `reductionism' does not do justice to the resonant possibilities of Jung's writing. These look forward to a new scientific paradigm of the twenty-first century, of the interactive `field', emergence and complexity theory. The paper works paradoxically by discovering Zinkin's `intersubjective self' after all, in two undervalued narratives by Jung, his doctoral thesis and a short late ghost story. However, in the ambivalences and radical fictional experimentation of these fascinating texts can be discerned an-Other self, one both created and found. [From the Publisher]

When the shift hits the critical fan: a Foucauldian analysis

In the past 15 years in the UK, the state has acquired powers, which mark a qualitative shift in its relationship to higher education. Since the introduction and implementation of the Further and Higher Education Act 1992, the Teaching and Higher Education Act 1998 and the Higher Education Act 2004, a whole raft of changes have occurred which include the following: Widening participation; the development of interdisciplinary, experiential and workplace-based learning focused on a theory-practice dialogue; quality assurance; and new funding models which encompass public and private partnerships. The transformation of higher education can be placed in the context of New Labour’s overall strategies for overarching reform of public services, as set out in the Prime Minister’s Strategy Unit’s discussion paper The UK Government’s Approach to Public Service Reform (2006). An optimistic view of changes to higher education is that they simultaneously obey democratic and economic imperatives. There is an avowed commitment through the widening participation agenda to social inclusion and citizenship, and to providing the changing skills base necessary for the global economy. A more cynical view is that, when put under critical scrutiny, as well as being emancipatory, in some senses these changes can be seen to mobilise regulatory and disciplinary practices. This paper reflects on what kinds of teaching and learning are promoted by the new relationship between the state and the university. It argues that, whilst governmental directives for innovations and transformations in teaching and learning allegedly empower students and put their interests at the centre, reforms can also be seen to consist of supervisory and controlling mechanisms with regard both to our own practices as teachers and the knowledge/ learning we provide for the students.

A regime shift in the North Sea circa 1988 linked to changes in the North Sea horse mackerel fishery

After 1987, Phytoplankton Colour (a visual estimate of chlorophyll) measured on samples taken by the continuous plankton recorder (CPR) in the North Sea increased substantially, both in level and seasonal extent, compared to earlier years since 1946. Many species of phytoplankton and zooplankton showed marked changes in abundance at about the same time. These events coincided with a large increase in catches of the western stock of the horse mackerel (Trachurus trachurus L.) in the northern North Sea reflecting a northerly expansion of the stock along the shelf edge from the Bay of Biscay to the North Sea after 1987. Using a 3D hydrodynamic model, with input from measured wind parameters, monthly transport of oceanic water into the North Sea has been calculated for the period 1976–1994, integrated for a section from Orkney to Shetland to Norway. A substantial increase in oceanic inflow occurred in the winter months, December to March, from 1988. Higher sea surface temperatures were also measured after 1987 especially in spring and summer months. These biological and physical events may be a response to observed changes in pressure distribution over the North Atlantic. From 1988 onwards, the North Atlantic Oscillation (NAO) index, the pressure difference between Iceland and the Azores, increased to the highest positive level observed in this century. Positive NAO anomalies are associated with stronger and more southerly tracks of the westerly winds and higher temperatures in western Europe. These changing wind distributions may have led to an increase in the northerly advection of water along the western edge of the European shelf and may have assisted the migration of the horse mackerel. This study is possibly a unique demonstration of a correlation between three different trophic levels of a marine ecosystem and hydrographic and atmospheric events at decadal and regional scales. The results emphasise the importance of maintaining into the future long term programmes such as the CPR.

The Mediterranean Sea Regime Shift at the End of the 1980s, and Intriguing Parallelisms with Other European Basins

Regime shifts are abrupt changes encompassing a multitude of physical properties and ecosystem variables, which lead to new regime conditions. Recent investigations focus on the changes in ecosystem diversity and functioning associated to such shifts. Of particular interest, because of the implication on climate drivers, are shifts that occur synchronously in separated basins. In this work we analyze and review long-term records of Mediterranean ecological and hydro-climate variables and find that all point to a synchronous change in the late 1980s. A quantitative synthesis of the literature (including observed oceanic data, models and satellite analyses) shows that these years mark a major change in Mediterranean hydrographic properties, surface circulation, and deep water convection (the Eastern Mediterranean Transient). We provide novel analyses that link local, regional and basin scale hydrological properties with two major indicators of large scale climate, the North Atlantic Oscillation index and the Northern Hemisphere Temperature index, suggesting that the Mediterranean shift is part of a large scale change in the Northern Hemisphere. We provide a simplified scheme of the different effects of climate vs. temperature on pelagic ecosystems.