Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression.

Several studies have proposed that brain glutamate signaling abnormalities and glial pathology have a role in the etiology of major depressive disorder (MDD). These conclusions were primarily drawn from post-mortem studies in which forebrain brain regions were examined. The locus coeruleus (LC) is the primary source of extensive noradrenergic innervation of the forebrain and as such exerts a powerful regulatory role over cognitive and affective functions, which are dysregulated in MDD. Furthermore, altered noradrenergic neurotransmission is associated with depressive symptoms and is thought to have a role in the pathophysiology of MDD. In the present study we used laser-capture microdissection (LCM) to selectively harvest LC tissue from post-mortem brains of MDD patients, patients with bipolar disorder (BPD) and from psychiatrically normal subjects. Using microarray technology we examined global patterns of gene expression. Differential mRNA expression of select candidate genes was then interrogated using quantitative real-time PCR (qPCR) and in situ hybridization (ISH). Our findings reveal multiple signaling pathway alterations in the LC of MDD but not BPD subjects. These include glutamate signaling genes, SLC1A2, SLC1A3 and GLUL, growth factor genes FGFR3 and TrkB, and several genes exclusively expressed in astroglia. Our data extend previous findings of altered glutamate, astroglial and growth factor functions in MDD for the first time to the brainstem. These findings indicate that such alterations: (1) are unique to MDD and distinguishable from BPD, and (2) affect multiple brain regions, suggesting a whole-brain dysregulation of such functions

Using schedulers to test probabilistic distributed systems

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s00165-012-0244-5. Copyright © 2012, British Computer Society.Formal methods are one of the most important approaches to increasing the confidence in the correctness of software systems. A formal specification can be used as an oracle in testing since one can determine whether an observed behaviour is allowed by the specification. This is an important feature of formal testing: behaviours of the system observed in testing are compared with the specification and ideally this comparison is automated. In this paper we study a formal testing framework to deal with systems that interact with their environment at physically distributed interfaces, called ports, and where choices between different possibilities are probabilistically quantified. Building on previous work, we introduce two families of schedulers to resolve nondeterministic choices among different actions of the system. The first type of schedulers, which we call global schedulers, resolves nondeterministic choices by representing the environment as a single global scheduler. The second type, which we call localised schedulers, models the environment as a set of schedulers with there being one scheduler for each port. We formally define the application of schedulers to systems and provide and study different implementation relations in this setting

Longest Common Extensions in Sublinear Space

The longest common extension problem (LCE problem) is to construct a data structure for an input string $T$ of length $n$ that supports LCE$(i,j)$ queries. Such a query returns the length of the longest common prefix of the suffixes starting at positions $i$ and $j$ in $T$. This classic problem has a well-known solution that uses $O(n)$ space and $O(1)$ query time. In this paper we show that for any trade-off parameter $1 \leq \tau \leq n$, the problem can be solved in $O(\frac{n}{\tau})$ space and $O(\tau)$ query time. This significantly improves the previously best known time-space trade-offs, and almost matches the best known time-space product lower bound.Comment: An extended abstract of this paper has been accepted to CPM 201

Performance of parental genotypes and inheritance of Angular Leaf Spot (Phaeosariopsis griseola) resistance in the common bean (Phaseolus vulgaris)

Two studies, one on performance of six common bean parental genotypes and another on inheritance of resistance to Phaeosariopsis griseola (Pg) in the common bean were carried out in Malawi. Common bean entries namely; Chimbamba, Nasaka, RC 15, CAL 143 and Mexico 54 were evaluated on station in the 2004/2005 growing season at Bunda, Dedza, Ng'onga and Ntchenachena sites. The second study started by generating F1s and then F2 and F3 seeds in greenhouse at Bunda College. CAL 143 and Mexico 54 were sources of Pg resistance genes while Chimbamba, Nasaka and RC 15 were susceptible recipient parents. Following green house trials, Pg resistance was evaluated on station in the samesites. CAL 143 was highest yielding but unstable across sites. RC 15 was stable and gave the highest yield at the dry-spell-stricken Ng’onga whereas Mexico 54 was superior at Ntchenachena but highly unstable across sites. Yield was strongly correlated to number of effective pods per plant in all genotypes. The inheritance study showed that resistance to Pg in the common bean is controlled by one gene using both CAL 143 and Mexico 54 as resistant parents.&#160

Timed Implementation Relations for the Distributed Test Architecture

In order to test systems that have physically distributed interfaces, called ports, we might use a distributed approach in which there is a separate tester at each port. If the testers do not synchronise during testing then we cannot always determine the relative order of events observed at different ports and this leads to new notions of correctness that have been described using corresponding implementation relations. We study the situation in which each tester has a local clock and timestamps its observations. If we know nothing about how the local clocks relate then this does not affect the implementation relation while if the local clocks agree exactly then we can reconstruct the sequence of observations made. In practice, however, we are likely to be between these extremes: the local clocks will not agree exactly but we have some information regarding how they can differ. We start by assuming that a local tester interacts synchronously with the corresponding port of the system under test and then extend this to the case where communications can be asynchronous, considering both the first-in-first-out (FIFO) case and the non-FIFO case. The new implementation relations are stronger than implementation relations for distributed testing that do not use timestamps but still reflect the distributed nature of observations. This paper explores these alternatives and derives corresponding implementation relations

Quasiperiodicity and non-computability in tilings

We study tilings of the plane that combine strong properties of different nature: combinatorial and algorithmic. We prove existence of a tile set that accepts only quasiperiodic and non-recursive tilings. Our construction is based on the fixed point construction; we improve this general technique and make it enforce the property of local regularity of tilings needed for quasiperiodicity. We prove also a stronger result: any effectively closed set can be recursively transformed into a tile set so that the Turing degrees of the resulted tilings consists exactly of the upper cone based on the Turing degrees of the later.Comment: v3: the version accepted to MFCS 201

The Weak Gravity Conjecture and the Viscosity Bound with Six-Derivative Corrections

The weak gravity conjecture and the shear viscosity to entropy density bound place constraints on low energy effective field theories that may help to distinguish which theories can be UV completed. Recently, there have been suggestions of a possible correlation between the two constraints. In some interesting cases, the behavior was precisely such that the conjectures were mutually exclusive. Motivated by these works, we study the mass to charge and shear viscosity to entropy density ratios for charged AdS5 black branes, which are holographically dual to four-dimensional CFTs at finite temperature. We study a family of four-derivative and six-derivative perturbative corrections to these backgrounds. We identify the region in parameter space where the two constraints are satisfied and in particular find that the inclusion of the next-to-leading perturbative correction introduces wider possibilities for the satisfaction of both constraints.Comment: 24 pages, 6 figures, v2: published version, refs added, minor clarificatio

Using genetic algorithms to generate test sequences for complex timed systems

The generation of test data for state based specifications is a computationally expensive process. This problem is magnified if we consider that time con- straints have to be taken into account to govern the transitions of the studied system. The main goal of this paper is to introduce a complete methodology, sup- ported by tools, that addresses this issue by represent- ing the test data generation problem as an optimisa- tion problem. We use heuristics to generate test cases. In order to assess the suitability of our approach we consider two different case studies: a communication protocol and the scientific application BIPS3D. We give details concerning how the test case generation problem can be presented as a search problem and automated. Genetic algorithms (GAs) and random search are used to generate test data and evaluate the approach. GAs outperform random search and seem to scale well as the problem size increases. It is worth to mention that we use a very simple fitness function that can be eas- ily adapted to be used with other evolutionary search techniques

Peer assessment of outpatient consultation letters – feasibility and satisfaction

<p>Abstract</p> <p>Background</p> <p>Written correspondence is one of the most important forms of communication between health care providers, yet there is little feedback provided to specialists. The objective of this study was to determine the feasibility and satisfaction of a peer assessment program on consultation letters and to determine inter-rater reliability between family physicians and specialists.</p> <p>Methods</p> <p>A rating scale of nine 5-point Likert scale items including specific content, style items, education value of the letter and an overall rating was developed from a previous validated tool.</p> <p>Nine Internal Medicine specialists/subspecialists from two tertiary care centres submitted 10 letters with patient and physician identifiers removed. Two Internal Medicine specialists, and 2 family physicians from the other centre rated each letter (to protect writer anonymity). A satisfaction survey was sent to each writer and rater after collation of the results. A follow-up survey was sent 6–8 months later.</p> <p>Results</p> <p>There was a high degree of satisfaction with the process and feedback. The rating scale information was felt to be useful and appropriate for evaluating the quality of consultation letters by 6/7 writers. 5/7 seven writers felt that the feedback they received resulted in immediate changes to their letters. Six months later, 6/9 writers indicated they had maintained changes in their letters.</p> <p>Raters rank ordered letters similarly (Cronbach's alpha 0.57–0.84) but mean scores were highly variant. At site 1 there were significant differences in scoring brevity (p < 0.01) between family physician and specialist raters; whereas, at site 2 there were differences in scoring of history (p < 0.01), physical examination (p < 0.01) and educational value (p < 0.01) of the letter.</p> <p>Conclusion</p> <p>Most participants found peer assessment of letters feasible and beneficial and longstanding changes occurred in some individuals. Family physicians and specialists appear to have different expectations on some items. Further studies on reliability and validity, with a larger sample, are required before high stakes professional assessments include consultation letters.</p