bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicate transformers as power operations
Authors: Rewitzky I. , Brink C.
Published: February 2005

In predicate transformer semantics, a program is represented as a mapping from predicates to predicates. In relational semantics, a program is represented as an (input-output) binary relation over some state space. We show how each of these approaches can be obtained from the other by using the
power construction
.
An action-based formal model for concurrent real-time systems
Authors: Fidge C. J. , Wellings A. J.
Published: February 2005

Action systems are a formalism for representing concurrent behaviours, based on interleaved atomic actions. We show how this model can be used to represent time-consuming, pre-emptible actions with real-time constraints. A development procedure is described which captures the steps programmers typically undertake in the design of real-time multi-tasking systems.
A logic for reasoning about time and reliability
Authors: Hansson Hans , Jonsson Bengt
Published: February 2005

We present a logic for stating properties such as, “after a request for service there is at least a 98% probability that the service will be carried out within 2 seconds”. The logic extends the temporal logic CTL by Emerson, Clarke and Sistla with time and probabilities. Formulas are interpreted over discrete time Markov chains. We give algorithms for checking that a given Markov chain satisfies a formula in the logic. The algorithms require a polynomial number of arithmetic operations, in size of both the formula and the Markov chain. A simple example is included to illustrate the algorithms.
Refinement of a typed WAM extension by polymorphic order-sorted types
Authors: Beierle Christoph , Börger Egon
Published: February 2005

We refine the mathematical specification of a WAM extension to typeconstraint logic programming given in [BeB96]. We provide a full specification and correctness proof of the PROTOS Abstract Machine (PAM), an extension of the WAM by polymorphic order-sorted unification as required by the logic programming language PROTOS-L, by refining the abstract type constraints used in [BeB96] to the polymorphic order-sorted types of PROTOS-L. This allows us to develop a detailed and mathematically precise account of the PAM's compiled type constraint representation and solving facilities, and to extend the correctness theorem to compilation on the fully specified PAM.
Compositional minimisation of finite state systems using interface specifications
Authors: Graf Susanne , Steffen Bernhard , Lüttgen Gerald
Published: February 2005

We present a method for thecompositional constructionof theminimal transition systemthat represents the semantics of a given distributed system. Our aim is to control thestate explosioncaused by the interleavings of actions of communicating parallel components byreduction stepsthat exploitglobalcommunication constraints given in terms ofinterface specifications.Theeffectof the method, which is developed forbisimulation semanticshere, depends on the structure of the distributed system under consideration, and theaccuracyof the interface specifications. However, itscorrectnessis independent of the correctness of the interface specifications provided by the program designer.
Verifying a distributed list system: A case history
Authors: Krogdahl Stein , Lysne Olav
Published: February 2005

The background for this paper is twofold: One is the definition of a caching protocol for shared memory parallel computers called SCI, and the other is the usage of rewriting techniques in program verification. The paper concentrates on a linked list system, which is a central aspect of the caching protocol. We first describe an informal proof of this system, including a rather large invariant. Thereafter we show how the list system and the invariant can both be described in the formalism of rewriting logic, and we use this to carry through a significant part of the verification mechanically, using the OBJ3 interpreter.
Integration of parametric and “ad hoc” second order polymorphism in a calculus with subtyping
Authors: Castagna Giuseppe
Published: February 2005

In this paper we define an extension ofF≤[CUG92] to which we add functions that dispatch on different terms according to the type they receive as argument. In other words, we enrich the explicit parametric polymorphism ofF≤by an explicit “ad hoc” polymorphism (according the classification of [Str67]). We prove that the calculus we obtain, calledF≤&, enjoys the properties of Church-Rosser and Subject Reduction and that its proof system is coherent. We also define a significant subcalculus for which the subtyping is decidable. This extension has not only a logical interest but it is strongly motivated by the foundation of a broadly used programming style: object-oriented programming. The connections betweenF≤&and object-oriented languages are widely stressed, and the modelling byF≤&of some features of the object-oriented style is described, continuing the work of [CGL96].
Compositional verification of real-time systems with Explicit Clock Temporal Logic
Authors: Zhou Ping , Hooman Jozef , Kuiper Ruurd
Published: February 2005

To specify and verify real-time systems, we consider a real-time version of temporal logic called Explicit Clock Temporal Logic. Timing properties are specified by extending the classical framework of temporal logic with a special variable which explicitly refers to a global notion of time. Programs are written in an Occam-like real-time language with synchronous message passing. To show that a program satisfies a specification, we formulate a proof system which is proved to be sound and relatively complete. The proof system is compositional, which makes it possible to decompose the design of a large system into the design of subsystems. This is shown by the verification of a small part of an avionics system.
Brief report: The effects of condom insistence on the perceptions of adolescents in first time and repeated occasions of sexual intercourse
Authors: Turk Don R. , Hocking John E.
Published: February 2005

The research reported here replicated Hocking et al. (Journal of Adolescence 22 (1999) 355) and further examined the effects of insisting on condom usage, by expanding the experimental conditions under which condom use occurs to include repeated sexual encounters in ongoing relationships. In Study 1, Hocking et al. (Journal of Adolescence 22 (1999) 355) results were replicated. In Study 2, using identical procedures, participants imagined engaging in sexual intercourse in which their partner of 3 months either insisted on the continued use of a condom or requested that no condom be used. Results for Study 2 were such that participants in the condom insistence conditions reported greater feelings of positivity about themselves, their partners, and the sexual experience, than participants whose partners did not insist on condom use during sex.
Isolation and structural characterization of epilancin 15X, a novel lantibiotic from a clinical strain of Staphylococcus epidermidis
Authors: Ekkelenkamp Miquel B. , Hanssen Micha , Danny Hsu Shang-Te , de Jong Ad , Milatovic Dana , Verhoef Jan , van Nuland Nico A.J.
Published: February 2005

The potential application of lantibiotics as food‐preserving agents and more recently as antibiotics has strongly increased the interest in these antibacterial peptides. Here, we report the elucidation of the primary and three‐dimensional structures of the novel lantibiotic epilancin 15X from Staphylococcus epidermidis using high‐resolution nuclear magnetic resonance spectroscopy and tandem mass spectrometry. The molecule contains ten post‐translationally modified amino acids, three lanthionine ring structures and a hydroxy‐propionyl N‐terminal moiety. The primary and tertiary structure and the distribution of positive charges are closely similar to the previously identified lantibiotic epilancin K7, most likely indicative of a common mode of action.
Identification of non‐specific lipid transfer protein‐1 as a calmodulin‐binding protein in Arabidopsis
Authors: Wang Zhe , Xie Wanqin , Chi Fang , Li Cuifeng
Published: February 2005

Although non‐specific lipid transfer proteins (nsLTPs) are widely present in plants, their functions and regulations have not been fully understood. In this report, Arabidopsis nsLTP1 was cloned and expressed to investigate its binding to calmodulin (CaM). Gel overlay assays revealed that recombinant nsLTP1 bound to CaM in a calcium‐independent manner. The association of nsLTP1 and CaM was corroborated using CaM–Sepharose beads to specifically isolate recombinant nsLTP1 from crude bacterial lysate. The CaM‐binding site was mapped in nsLTP1 to the region of 69–80 amino acids. This region is highly conserved among plant nsLTPs, implicating that nsLTPs are a new family of CaM‐binding proteins whose functions may be mediated by CaM signaling.
Direct interaction of coenzyme M with the active‐site Fe–S cluster of heterodisulfide reductase
Authors: Shokes Jacob E. , Duin Evert C. , Bauer Carsten , Jaun Bernhard , Hedderich Reiner , Koch Jürgen , Scott Robert A.
Published: February 2005

Heterodisulfide reductase (HDR) catalyzes the formation of coenzyme M (CoM–SH) and coenzyme B (CoB–SH) by the reversible reduction of the heterodisulfide, CoM–S–S–CoB. This reaction recycles the two thiol coenzymes involved in the final step of microbial methanogenesis. Electron paramagnetic resonance (EPR) and variable‐temperature magnetic circular dichroism spectroscopic experiments on oxidized HDR incubated with CoM–SH revealed a S
= 1/2 [4Fe–4S]3+ cluster, the EPR spectrum of which is broadened in the presence of CoM–33SH [Duin, E.C., Madadi‐Kahkesh, S., Hedderich, R., Clay, M.D. and Johnson, M.K. (2002) Heterodisulfide reductase from Methanothermobacter marburgensis contains an active‐site [4Fe–4S] cluster that is directly involved in mediating heterodisulfide reduction. FEBS Lett. 512, 263–268; Duin, E.C., Bauer, C., Jaun, B. and Hedderich, R. (2003) Coenzyme M binds to a [4Fe–4S] cluster in the active site of heterodisulfide reductase as deduced from EPR studies with the [33S]coenzyme M‐treated enzyme. FEBS Lett. 538, 81–84]. These results provide indirect evidence that the disulfide binds to the iron–sulfur cluster during reduction. We report here direct structural evidence for this interaction from Se X‐ray absorption spectroscopic investigation of HDR treated with the selenium analog of coenzyme M (CoM–SeH). Se K edge extended X‐ray absorption fine structure confirms a direct interaction of the Se in CoM–SeH‐treated HDR with an Fe atom of the Fe–S cluster at an Fe–Se distance of 2.4 Å.
A comparison of bottling alternatives in the pharmaceutical industry
Authors: Teunter Ruud H. , Flapper Simme Douwe P.
Published: February 2005

This paper presents the results of a case study in a batch production facility for biological vaccines with possibilities for rework. The problem considered is that of finding the best bottling alternative for produced batches when these have to undergo several lengthy quality tests related to the foregoing production processes. Produced batches can be bottled directly after production when the results of these test are completely unknown, after some positive (intermediate) test results are known, or after all test have been completed with positive results. When waiting in order to be bottled, a batch has to stay in the production tank. Alternatives that start the bottling process quickly after production have the advantages of a relatively low tank capacity requirement and of a relatively small flow time if all test results are positive. However, a produced batch can only be reworked as long as it has not been bottled. So fast bottling reduces the possibilities for rework and therefore reduces the production yield. We present performance measures for comparing the different alternatives and derive closed form expressions for them. We also present the results obtained for the considered case.
How long can left and right handed life forms coexist?
Authors: Brandenburg Axel , Multamäki Tuomas
Published: February 2005

Reaction-diffusion equations based on a polymerization model are solved to simulate the spreading of hypothetic left and right-handed life forms on the Earth's surface. The equations exhibit front-like behavior as is familiar from the theory of the spreading of epidemics. It is shown that the relevant time scale for achieving global homochirality is not, however, the time scale of front propagation, but the much longer global diffusion time. The process can be sped up by turbulence and large scale flows. It is speculated that, if the deep layers of the early ocean were sufficiently quiescent, there may have been the possibility of competing early life forms with opposite handedness.
Microbial colonization in impact-generated hydrothermal sulphate deposits, Haughton impact structure, and implications for sulphates on Mars
Authors: Parnell J. , Lee P. , Cockell C.S. , Osinski G.R.
Published: February 2005

Hydrothermal gypsum deposits in the Haughton impact structure, Devon Island, Canada, contain microbial communities in an endolithic habitat within individual gypsum crystals. Cyanobacterial colonies occur as masses along cleavage planes, up to 5 cm from crystal margins. The crystals are transparent, so allow transmission of light for photosynthesis, while affording protection from dehydration and wind. The colonies appear to have modified their mineral host to provide additional space as they expanded. The colonies are black due to UV-screening pigments. The relative ease with which microbial colonization may be detected and identified in impact-generated sulphate deposits at Haughton suggests that analogous settings on other planets might merit future searches for biosignatures. The proven occurrence of sulphates on the Martian surface suggests that sulphate minerals should be a priority target in the search for life on Mars.
The CD4 molecule on CD8+T lymphocytes directly enhances the immune response to viral and cellular antigens
Authors: Kitchen Scott G. , Whitmire Jason K. , Jones Nicole R. , Galic Zoran , Kitchen Christina M. R. , Ahmed Rafi , Zack Jerome A.
Published: February 2005

CD8+T lymphocytes play a major role in cellular-mediated immune responses to foreign antigen. We have previously demonstrated that costimulation of purified human CD8+T cells inducesde novoexpression of the CD4 molecule and that ligation of CD4 on this cell type modulates CD8+T cell activityin vitro. Herein, we investigate how the CD4 molecule expressed on murine CD8+T cells contributes to CD8+cell responsesin vivoby employing adoptive transfer of CD8 cells from CD4 knockout mice into severe combined immunodeficient (SCID) recipients. Transfer of these cells into syngeneic SCID mice resulted in a decreased immune response to infection by lymphocytic choriomeningitis virus. These decreased responses occurred even in the presence of CD4+T cells, indicating that this was truly a CD8-cell defect. Similarly, transfer of CD8+T cells incapable of expressing CD4 into allogeneic SCID mice resulted in a decreased response to alloantigens compared with that of normal CD8+T cells. Therefore, CD4 expression on CD8 T lymphocytes modulates cytotoxic T lymphocyte function and is criticalin vivofor optimal cell-mediated immunity to viral and alloantigens.
Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination
Authors: Lee Young-Ho , Coonrod Scott A. , Kraus W. Lee , Jelinek Mary Anne , Stallcup Michael R.
Published: February 2005

Nuclear receptors activate transcription by recruiting multiple coactivators to the promoters of specific target genes. The functional synergy of the p160 coactivators [steroid receptor coactivator-1, glucocorticoid receptor interacting protein (GRIP1), or the activator for thyroid hormone and retinoid receptors], the histone acetyltransferases cAMP response element binding protein binding protein (CBP) and p300 and the histone methyltransferase coactivator-associated arginine methyltransferase (CARM1) depends on the methyltransferase activity of CARM1. CARM1 methylates histone H3 and other factors including the N-terminal region of p300. Here, we report that CARM1 also methylates Arg-2142 within the C-terminal GRIP1 binding domain (GBD) of p300. In the GBD, both Arg-2088 and Arg-2142 are important for binding GRIP1. Methylation of Arg-2142 inhibits the bimolecular interaction of GRIP1 to p300
in vitro
and
in vivo
. This methylation mark of p300 GBD is removed by peptidyl deiminase 4, thereby enhancing the p300–GRIP1 interaction. These methylation and demethylimination events also alter the conformation and activity of the coactivator complex and regulate estrogen receptor-mediated transcription, and they thus represent unique mechanisms for regulating coactivator complex assembly, conformation, and function.
The basic helix–loop–helix
olig3
establishes the neural plate boundary of the trunk and is necessary for development of the dorsal spinal cord
Authors: Filippi Alida , Tiso Natascia , Deflorian Gianluca , Zecchin Elisabetta , Bortolussi Marino , Argenton Francesco
Published: February 2005

olig
genes encode a previously unrecognized group of vertebrate-specific basic helix–loop–helix transcription factors. As shown in mice, chickens, and zebrafish, two members of this group,
olig1
and
olig2
, are involved in the differentiation of motoneurons and oligodendrocytes, but nothing is known about the role of the third member,
olig3
. Here, we show that
olig3
plays an essential role in the establishment of the neural crest–lateral neural plate boundary. In zebrafish embryos, morpholino-induced
olig3
inactivation dramatically increases the number of neural crest cells, but lateral neural plate fates (interneurons and astrocytes) are missing. Zebrafish
swirl
mutants that have impaired bone morphogenetic protein signaling and lack neural crest cells display an expanded
olig3
expression domain. Moreover,
olig3
is up-regulated in
mindbomb
mutants lacking the neural crest because of an impaired
notch
signaling, and
olig3
repression in such mutants rescues the neural crest. In addition,
olig3
regulates
ngn1
and
deltaA
expression in interneuron precursors. Our results indicate that
olig3
has an essential proneural activity in the dorsal spinal cord and cooperates with the Delta/Notch regulatory loop to establish the boundary between the neural crest and the lateral neural plate. Thus, a proper regulation of the
olig
gene family is essential for the formation of three cell types (oligodendrocytes, astrocytes, and neural crest) that are unique to vertebrates.
Reciprocal evolution of the cerebellum and neocortex in fossil humans
Authors: Weaver Anne H.
Published: February 2005

Human brain evolution involved both neurological reorganization and an increase in overall brain volume relative to body mass. It is generally difficult to draw functional inferences about the timing and nature of brain reorganization, given that superficial brain morphology recorded on fossil endocasts is functionally ambiguous. However, the cerebellum, housed in the clearly delineated posterior cranial fossa, is functionally and ontologically discrete. The cerebellum is reciprocally connected to each of 14 neocortical regions important to human cognitive evolution. Cerebellar volume varies significantly relative to overall brain volume among mammalian orders, as well as within the primate order. There is also significant diachronic variation among fossil human taxa. In the australopithecines and early members of the genusHomo, the cerebral hemispheres were large in proportion to the cerebellum, compared with other hominoids. This trend continued in Middle and Late Pleistocene humans, including Neandertals and Cro-Magnon 1, who have the largest cerebral hemispheres relative to cerebellum volume of any primates, including earlier and Holocene humans. In recent humans, however, the pattern is reversed; the cerebellum is larger with respect to the rest of the brain (and, conversely, the cerebral hemispheres are smaller with respect to the cerebellum) than in Late Pleistocene humans. The cerebellum and cerebral hemispheres appear to have evolved reciprocally. Cerebellar development in Holocene humans may have provided greater computational efficiency for coping with an increasingly complex cultural and conceptual environment.
Calling emergency medical services during drug overdose: an examination of individual, social and setting correlates
Authors: Tobin Karin E. , Davey Melissa A. , Latkin Carl A.
Published: February 2005

Aims  The purpose of this study was to examine individual, social and setting correlates of calling the emergency number, 911, during an overdose.

Design  Cross‐sectional survey.

Methods  A sample of 397 current or former drug users in Baltimore, MD, USA who reported having ever witnessed an overdose.

Findings  Participants reported calling an ambulance in 23% of the overdose cases. Results from multivariate logistic regression indicate that having ever overdosed and having four or more bystanders present independently decreased the likelihood of calling 911. Having ever witnessed a fatal overdose and having any female bystanders present increased the likelihood of calling 911. There was a significant interaction between fear of arrest and prior exposure to the police. Setting of the overdose (public versus private) was not associated with calling 911 after controlling for other factors.

Conclusions  These findings suggest that in addition to personal characteristics of witnesses, social factors influence calling 911. Intervention at the social level may be a viable means to increase bystander helping behaviors.
Tests of causal linkages between cannabis use and psychotic symptoms
Authors: Fergusson David M. , Horwood L. John , Ridder Elizabeth M.
Published: February 2005

Aim  To examine possible causal linkages between cannabis use and psychosis using data gathered over the course of a 25‐year longitudinal study.

Design  A 25‐year longitudinal study of the health, development and adjustment of a birth cohort of 1265 New Zealand children (635 males, 630 females).

Setting  The Christchurch Health and Development Study, a general community sample.

Participants  A total of 1055 participants from the Christchurch Health and Development Study (CHDS) cohort for whom data on cannabis use and psychotic symptoms were available on at least one occasion from 18, 21 and 25 years.

Measurements  As part of this study, data were gathered on frequency of cannabis use and psychotic symptoms at ages 18, 21 and 25 years.

Findings  Regression models adjusting for observed and non‐observed confounding suggested that daily users of cannabis had rates of psychotic symptoms that were between 1.6 and 1.8 times higher (P < 0.001) than non‐users of cannabis. Structural equation modelling suggested that these associations reflected the effects of cannabis use on symptom levels rather than the effects of symptom levels on cannabis use.

Conclusions  The results of the present study add to a growing body of evidence suggesting that regular cannabis use may increase risks of psychosis. The present study suggests that: (a) the association between cannabis use and psychotic symptoms is unlikely to be due to confounding factors; and (b) the direction of causality is from cannabis use to psychotic symptoms.
Genetics of individual differences in bitter taste perception: lessons from the PTC gene
Authors: Kim UK , Drayna D
Published: February 2005

The ability or inability to taste the compound phenylthiocarbamide (PTC) is a classic inherited trait in humans and has been the subject of genetic and anthropological studies for over 70 years. This trait has also been shown to correlate with a number of dietary preferences and thus may have important implications for human health. The recent identification of the gene that underlies this phenotype has produced several surprising findings. This gene is a member of the T2R family of bitter taste receptor genes. It exists in seven different allelic forms, although only two of these, designated the major taster and major non‐taster forms, exist at high frequency outside sub‐Saharan Africa. The non‐taster allele resides on a small chromosomal region identical by descent, indicating that non‐tasters are descended from an ancient founder individual, and consistent with an origin of the non‐taster allele preceding the emergence of modern humans out of Africa. The two major forms differ from each other at three amino acid positions, and both alleles have been maintained at high frequency by balancing natural selection, suggesting that the non‐taster allele serves some function. We hypothesize that this function is to serve as a receptor for another, as yet unidentified toxic bitter substance. At least some of the remaining five haplotypes appear to confer intermediate sensitivity to PTC, suggesting future detailed studies of the relationships between receptor structure and taste function.
Identification of germline BRCA1 and BRCA2 genetic alterations in Greek breast cancer moderate‐risk and low‐risk individuals – correlation with clinicopathological data
Authors: Kataki A , Gomatos IP , Pararas N , Armakolas A , Panousopoulos D , Karantzikos G , Voros D , Zografos G , Markopoulos C , Leandros E , Konstadoulakis MM
Published: February 2005

The current study was designed to evaluate the prevalence of BRCA1 and BRCA2 germline mutations in Greek moderate‐ and low‐risk individuals with respect to clinicopathological phenotype and clinical outcome of breast cancer. Ninety‐four consecutive individuals were prospectively recruited from two University Breast Cancer Clinics (Hippokrateion Hospitan and Laikon Hospital) between 1989 and 1999 and were categorized as moderate‐risk and low‐risk individuals for carrying BRCA1/2 germline mutations. To identify the underlying mutations, protein‐truncation test and single‐strand conformation polymorphism methods were used, followed by direct sequencing. Three novel BRCA1 missense mutations, one novel BRCA1 intronic deletion, three novel (previously reported) BRCA2 truncating mutations, and one novel BRCA2 missense mutation were identified in the moderate‐risk group of individuals studied. The BRCA1/2 missense mutations as well as the single intronic variant identified were designated as unclassified genetic variants. Two BRCA1 unclassified genetic variants (missense mutations) were detected in two of the three (66.7%) male breast cancer patients analyzed, while the third one was identified in a sporadic (low‐risk) breast cancer patient. Clinicopathological characteristics of breast carcinomas originating from BRCA1/2 heterozygotes were consistent with those already reported and not different from those observed in BRCA1/2 mutation (–) breast cancer patients. Furthermore, BRCA1/2 mutation carriers presented an excellent 4.5‐year overall survival (100%). Our results reveal the unique characteristics of BRCA1/2 mutation status, genotype–phenotype correlations, and prognosis, in moderate‐ and low‐risk individuals of Greek ancestry. Breast cancer due to mutations in BRCA1 and BRCA2 genes appears to be a heterogeneous syndrome in the Greek population.
Elastic fiber abnormalities in hypermobility type Ehlers–Danlos syndrome patients with tenascin‐X mutations
Authors: Zweers MC , Dean WB , Van Kuppevelt TH , Bristow J , Schalkwijk J
Published: February 2005

Ehlers–Danlos syndrome (EDS) is a heterogeneous group of connective tissue disorders with characteristic skin and joint involvement. The concept that EDS is a disease of fibrillar collagen was challenged by the identification of a clinically distinct, recessive type of EDS caused by deficiency of the extracellular matrix protein tenascin‐X (TNX). Interestingly, haploinsufficiency of TNX is associated with the dominantly inherited hypermobility type of EDS. In this study, we examined whether missense mutations in the TNX gene can account for some of the cases of hypermobility type EDS. Furthermore, we studied whether missense mutations or heterozygosity for truncating mutations in the TNX gene lead to alterations in the dermal connective tissue. Sequence analysis revealed three missense mutations in TNX in hypermobility type EDS patients, which were not present in 192 control alleles. Morphometric analysis of skin biopsies of these patients showed altered elastic fibers in one of them, suggesting that this missense mutation is disease causing. Light microscopic and ultrastructural changes of the elastic fibers were observed in TNX‐haploinsufficient hypermobility type EDS patients, which were not found in hypermobility type EDS patients in whom TNX mutations were excluded. Our results indicate that the observed alterations in elastic fibers are specific for hypermobility type EDS patients with mutations of TNX.
The I1307K APC mutation in a high‐risk clinic setting: a follow‐up study
Authors: Regev M , Barzilai S‐Eisenberg , Figer A , Zidan J , Fidder HH , Friedman E
Published: February 2005

While the I1307K APC mutation clearly confers an increased lifetime risk for colorectal cancer, there is a paucity of data on the natural history of colonic neoplasia in symptomatic and asymptomatic mutation carriers. In this study, 51 Jewish I1307K APC mutation carriers were identified in a high‐risk familial cancer clinic over a 4‐year period, of whom 29 (56.8%) (four males and 25 females) were successfully telephone interviewed for 0.5–5 years (mean 2.4 ± 1.4) after initial genetic testing. Of these 29 cases, one individual was diagnosed with colon cancer at the age of 45 years, five had adenomatous polyps (mean number of polyps = 1.8), 11 had breast cancer (mean age at diagnosis 49.5 ± 10.5 years), and 12 were asymptomatic, at the time of the testing. During the follow‐up period, new colonic polyps were diagnosed in three mutation carriers, two with previously diagnosed colon cancer and polyps and only one of the asymptomatic mutation carriers, and two additional previously affected patients had new cancer diagnoses: gastric cancer and melanoma. From this descriptive study, it seems that the short‐term risk for colonic polyps in I1307K APC mutation is low, primarily affecting patients with previously diagnosed colon tumors.
Beauty is in the eye of the examiner: reaching agreement about physical signs and their value
Authors: Joshua A. M. , Celermajer D. S. , Stockler M. R.
Published: February 2005

Abstract

Despite advances in other areas, evidence‐based medicine is yet to make substantial inroads on the standard medical physical examination. We have reviewed the evidence about the accuracy and reliability of the physical examination and common clinical signs. The physical examination includes many signs of marginal accuracy and reproducibility. These may not be appreciated by clinicians and could adversely affect decisions about treatment and investigations or the teaching and examination of students and doctors‐in‐training. We provide a selected summary of the reliability and accuracy as well as important messages of key findings in the physical examination. (Intern Med J 2005; 35: 178–187)
Functional characterization of rat ρ2 subunits expressed in HEK 293 cells
Authors: Alakuijala Anniina , TalviOja Katri , Pasternack Arja , Pasternack Michael
Published: February 2005

GABAC receptors are thought to be homo‐ or heteropentamers composed of ρ1, ρ2 and ρ3 subunits. Previous work on rat ρ2 subunits expressed in Xenopus oocytes has suggested that they do not form functional homo‐oligomeric GABAC receptors, but do combine with ρ1 or ρ3 subunits to form hetero‐oligomers. These findings are difficult to interpret because both human and mouse ρ2 subunits do form functional homo‐oligomeric receptors. Also, many regions of the rat brain express solely ρ2 subunit transcripts which, according to presently available evidence, would not result in expression of functional GABAC receptors. We show here that homomeric rat ρ2 receptors can be expressed in HEK 293 cells. Homo‐oligomeric rat ρ2 receptors expressed in mammalian cells matured slowly and displayed small but detectable GABA‐induced currents with slow kinetics. Rat ρ2 receptors also had a decreased sensitivity to picrotoxin and a marked sensitivity to the GABAC receptor agonist cis‐aminocrotonic acid. Our results demonstrate for the first time the expression of functional homomeric rat ρ2 receptors, and suggest that ρ2 subunits may contribute to brain function, including in areas not expressing other ρ subunits.
The removal of extracellular calcium: a novel mechanism underlying the recruitment of N‐methyl‐d‐aspartate (NMDA) receptors in neurotoxicity
Authors: Xin Wen‐Kuan , Zhao Xiao‐Han , Xu Jindong , Lei Gang , Kwan Chun L. , Zhu Kang‐Min , Cho Jae‐Sung , Duff Missy , Ellen Richard P. , McCulloch Christopher A. G. , Yu Xian‐Min
Published: February 2005

The involvement of NMDA‐type glutamate receptor in neuronal injury established in experimental stroke and neurotrauma models has been recently challenged by failures in treatment of stroke/neurotrauma patients with NMDA receptor antagonists. NMDA receptor activity is known to be essential for mediating a multitude of physiological functions. However, how NMDA receptors are recruited to cause neuronal injury remains unclear. Here we report that the time period during which initial NMDA receptor up‐regulation occurs is critical for the recruitment of NMDA receptors causing neuronal injury during extracellular calcium (Ca2+) reperfusion in cultured hippocampal neurons, and represents the key period for neuronal protection by NMDA receptor antagonists. Furthermore, we identified that via intracellular sodium (Na+), extracellular Ca2+ depletion induces the up‐regulation of NMDA receptor gating. Taken together, our study provides direct experimental evidence suggesting that determination of when and how NMDA receptors are recruited to cause neurotoxicity is essential for guiding treatment via antagonism of NMDA receptor functions.
A TASK‐like pH‐ and amine‐sensitive ‘leak’ K+ conductance regulates neonatal rat facial motoneuron excitability in vitro
Authors: Larkman Philip M. , Perkins Emma M.
Published: February 2005

A ‘leak’ potassium (K+) conductance (gKLeak) modulated by amine neurotransmitters is a major determinant of neonatal rat facial motoneuron excitability. Although the molecular identity of gKLeak is unknown, TASK‐1 and TASK‐3 channel mRNA is found in facial motoneurons. External pH, across the physiological range (pH 6–8), and noradrenaline (NA) modulated a conductance that displayed a relatively linear current/voltage relationship and reversed at the K+ equilibrium potential, consistent with inhibition of gKLeak. The pH‐sensitive current (IpH), was maximal around pH 8, fully inhibited near pH 6 and was described by a modified Hill equation with a pK of 7.1. The NA‐induced current (INA) was occluded at pH 6 and enhanced at pH 7.7. The TASK‐1 selective inhibitor anandamide (10 µm), its stable analogue methanandamide (10 µm), the TASK‐3 selective inhibitor ruthenium red (10 µm) and Zn2+ (100–300 µm) all failed to alter facial motoneuron membrane current or block INA or IpH. Isoflurane, a volatile anaesthetic that enhances heteromeric TASK‐1/TASK‐3 currents, increased gKLeak. Ba2+, Cs+ and Rb+ blocked INA and IpH voltage‐dependently with maximal block at hyperpolarized potentials. 4‐Aminopyridine (4‐AP, 4 mm) voltage‐independently blocked INA and IpH. In summary, gKLeak displays some of the properties of a TASK‐like conductance. The linearity of gKLeak and an independence of activation on external [K+] suggests against pH‐sensitive inwardly rectifying K+ channels. Our results argue against principal contributions to gKLeak by homomeric TASK‐1 or TASK‐3 channels, while the potentiation by isoflurane supports a predominant role for heterodimeric TASK‐1/TASK‐3 channels.
Functional links between motor and language systems
Authors: Pulvermüller Friedemann , Hauk Olaf , Nikulin Vadim V. , Ilmoniemi Risto J.
Published: February 2005

Transcranial magnetic stimulation (TMS) was applied to motor areas in the left language‐dominant hemisphere while right‐handed human subjects made lexical decisions on words related to actions. Response times to words referring to leg actions (e.g. kick) were compared with those to words referring to movements involving the arms and hands (e.g. pick). TMS of hand and leg areas influenced the processing of arm and leg words differentially, as documented by a significant interaction of the factors Stimulation site and Word category. Arm area TMS led to faster arm than leg word responses and the reverse effect, faster lexical decisions on leg than arm words, was present when TMS was applied to leg areas. TMS‐related differences between word categories were not seen in control conditions, when TMS was applied to hand and leg areas in the right hemisphere and during sham stimulation. Our results show that the left hemispheric cortical systems for language and action are linked to each other in a category‐specific manner and that activation in motor and premotor areas can influence the processing of specific kinds of words semantically related to arm or leg actions. By demonstrating specific functional links between action and language systems during lexical processing, these results call into question modular theories of language and motor functions and provide evidence that the two systems interact in the processing of meaningful information about language and action.
Environmental specialists: their prevalence and their influence on community‐similarity analyses
Authors: Pither Jason , Aarssen Lonnie W.
Published: February 2005

Recent research suggests that environmental or habitat specialization among plants may be less common than previously thought. These findings need to be reconciled with interpretations of community‐level similarity analyses that emphasize a strong role for specialization. Here we examine specialization within a taxonomic group that, owing to their widespread use as environmental indicators, should provide ample supportive evidence of specialization: freshwater sediment diatoms. Using an ideal, 239‐lake survey data set that reliably represents the environmental conditions among c. 9500 north‐eastern US lakes (encompassing a c. 405 000 km2 region), we show that only 29 and 14% of 401 species (those occurring in at least two lakes) exhibited narrower pH and total phosphorus niche breadths, respectively, than expected from the random occupation of lakes. These rates increase slightly using more stringent species‐inclusion criteria. Highly significant correlations between compositional and environmental resemblance matrices are shown to reflect a balance between a strong signal generated by the minority specialists, and noise generated by the majority generalists.
Limiting similarity and functional diversity along environmental gradients
Authors: Schwilk Dylan W. , Ackerly David D.
Published: February 2005

Recent developments in community models emphasize the importance of incorporating stochastic processes (e.g. ecological drift) in models of niche‐structured community assembly. We constructed a finite, spatially explicit, lottery model to simulate the distribution of species in a one‐dimensional landscape with an underlying gradient in environmental conditions. Our framework combines the potential for ecological drift with environmentally‐mediated competition for space in a heterogeneous environment. We examined the influence of niche breadth, dispersal distances, community size (total number of individuals) and the breadth of the environmental gradient on levels of species and functional trait diversity (i.e. differences in niche optima). Three novel results emerge from this model: (1) niche differences between adjacent species (e.g. limiting similarity) increase in smaller communities, because of the interaction of competitive effects and finite population sizes; (2) immigration from a regional species pool, stochasticity and niche‐assembly generate a bimodal distribution of species residence times (‘transient’ and ‘resident’) under a heterogeneous environment; and (3) the magnitude of environmental heterogeneity has a U‐shaped effect on diversity, because of shifts in species richness of resident vs. transient species. These predictions illustrate the potential importance of stochastic (although not necessarily neutral) processes in community assembly.
Parasites hinder monarch butterfly flight: implications for disease spread in migratory hosts
Authors: Bradley Catherine A. , Altizer Sonia
Published: February 2005

Monarch butterflies (Danaus plexippus) are parasitized by the protozoanOphryocystis elektroscirrhathroughout their geographical range. Monarchs inhabiting seasonally fluctuating environments migrate annually, and parasite prevalence is lower among migratory relative to non‐migratory populations. One explanation for this pattern is that long‐distance migration weeds out infected animals, thus reducing parasite prevalence and transmission between generations. In this study we experimentally infected monarchs from a migratory population and recorded their long‐distance flight performance using a tethered flight mill. Results showed that parasitized butterflies exhibited shorter flight distances, slower flight speeds, and lost proportionately more body mass per km flown. Differences between parasitized and unparasitized monarchs were generally not explained by individual variation in wing size, shape, or wing loading, suggesting that poorer flight performance among parasitized hosts was not directly caused by morphological constraints. Effects of parasite infection on powered flight support a role for long‐distance migration in dramatically reducing parasite prevalence in this and other host–pathogen systems.
Proposing a framework to assess Internet usage in university education: an empirical investigation from a student's perspective
Authors: Cheung Waiman , Huang Wayne
Published: February 2005

University administrators are continuously investing in Information Technology (IT) to support learning and help deal with educational budget cuts. Instructors are increasingly making their teaching materials available on the Internet. While administrators and instructors would like to make the Internet an effective educational tool, they need to understand what their students’ attitudes towards using it are. Since the use of the Internet in university education is still in its early stages, many issues regarding its use have not been fully addressed. This study was conducted to provide a better understanding of how the Internet is used in university learning from a student's perspective. Our research framework is based on the Theory of Reasoned Action, Technology Acceptance Model, and IT Diffusion Process Model. We use a survey conducted among university students to explore these issues. Research findings provide some useful insights for university administrators and educators.
An investigation into students’ use of a computer‐based social learning space: lessons for facilitating collaborative approaches to learning
Authors: Brett Paul , Nagra Jas
Published: February 2005

Provision of computers in universities for self‐study is taken for granted and is seen as a “must have” educational resource, yet it is very expensive to fund. Students report that they use the Internet as their first stop in approaching research tasks. Learning theorists posit the important role of social interaction in contributing to learning. The use of collaborative methodologies such as group work also illustrate the importance, and perceived beneficial role of, learning with others. However, in general, student access to computers for self‐study in UK Higher Education is provided through large rooms furnished with serried ranks of computers, which do not allow or encourage computer‐based collaborative working. This study addresses this mismatch between approaches to learning and the way universities make computers available to learners. The University of Wolverhampton provides a social learning space with 24 computers on four fishbone‐shaped tables, in a room without any restrictions on talking, eating, or drinking. It was provided so as to encourage learners to work collaboratively and to be able to integrate the use of a computer whilst doing so. This paper reports the initial findings of a study into its use, through questionnaires, observational data, and interviews. Has the provision of a computer‐based collaborative learning space positively affected approaches to computer‐based self‐study? The results of this study inform how best Higher Education institutions might provide computer access to learners so as to encourage collaborative working and positively affect student approaches to their learning.
Morphing images: a potential tool for teaching word recognition to children with severe learning difficulties
Authors: Sheehy Kieron
Published: February 2005

Children with severe learning difficulties who fail to begin word recognition can learn to recognise pictures and symbols relatively easily. However, finding an effective means of using pictures to teach word recognition has proved problematic. This research explores the use of morphing software to support the transition from picture to word recognition. Morphing software was used to teach word recognition to a group of eight children who were previously unable to recognise words. At the end of 16 teaching sessions, in a related design, the morphing technique was more effective than a word‐alone approach ( p < 0.05, one‐tailed). These results support the use of techniques such as symbol accentuation (Miller & Miller, 1971) and challenge the concept that the use of pictorial information is inherently detrimental to learning in this context, in comparison to the repeated presentation of words alone. The recent advent of accessible morphing software removes previous barriers to this type of approach. The investigation highlights several useful avenues for future research, in particular, the use of mnemonic elements within morphing teaching methods.
Computers and 2D geometric learning of Turkish fourth and fifth graders
Authors: Olkun Sinan , Altun Arif , Smith Glenn
Published: February 2005

This research investigated the possible impacts of computers on Turkish fourth‐grade students’ geometry scores and further geometric learning. The study used a pretest–intervention–posttest experimental design. Results showed that students who did not have computers at home initially had lower geometry scores. However, these differences were minimised with an appropriate intervention containing computer‐based Tangram puzzles. This suggests that at schools, it seems more effective to integrate mathematical content and technology in a manner that enables students to do playful mathematical discoveries.
The Organizational Innovation Laboratory
Authors: Lewis Michael , Moultrie James
Published: February 2005

Organizational ‘innovation laboratories’, dedicated facilities for encouraging creative behaviours and supporting innovative projects, have received scant academic attention despite their increasing popularity with a range of different practitioners. This paper develops an initial theoretical explanation of the phenomenon, based upon notions of organizational learning and dynamic capabilities. This framework is then used as the basis for analysing the structure, infrastructure, benefits and dis‐benefits of three UK‐based laboratory facilities (mass service, government department, academic institution). Preliminary conclusions suggest that the ‘innovation laboratory’ can offer real benefits for organizations: reinforcing corporate commitment to innovation and creativity by providing a physical manifestation of dynamic capability and double‐loop learning concepts. Although the physical design of the space is central to its functionality – emphasizing dislocation from day‐to‐day activity, eliminating hierarchy, encouraging participation – direct facilitation remains critical to successful operation. There are also dis‐benefits associated with what can be substantial financial investments and there is some evidence that such facilities can have a relatively short useful lifespan. Given the limited nature of the empirical base, the paper concludes with some specific suggestions for further work.