bluuebunny/crossref_metadata_2025 huggingface dataset:
Open Field or Enclosure? Peasants, Planters’ Agents and Lawyers in Jamaica, 1866–1875
Authors: Stevenson Simon
Published: October 2008

The fencing of boundaries so as to confine or exclude cattle was a major preoccupation in the most densely populated parishes of Jamaica in the mid nineteenth century. Part-time labourers (who constituted a new semi-peasantry) were being settled on the fringes of the old estates in increasing numbers, having been granted licenses or pretended leases for land on which they grew their crops. The same ‘attorneys’ who managed the older declining plantations where such squatting was arranged also tended to be introducing cattle in place of sugar and they wished to shift the costs of fencing onto their small ‘peasant’ occupiers. However, English law, which imposed an obligation to fence in cattle, initially assisted the peasantry. The attorneys therefore looked to New World models that would require those growing crops to fence out animals. This article examines actions in court and the agitation in more detail so as to suggest that fencing was a major source of inter-racial friction in the period before and after the Morant Bay rebellion, but with the outcome strongly favouring a late-century resurgence in the plantation economy.
Sonographische Befunde bei materno-fetalen Infektionen
Authors: Vökt Cora Alexandra , Visca Eva , Tercanli Sevgi
Published: October 2008

Mindestens 5% aller Frauen erkranken an einer symptomatischen, viralen Infektion während der Schwangerschaft. Weit mehr Schwangere durchleben eine akute Infektion, welche subklinisch oder gänzlich asymptomatisch verläuft und somit in der Regel unentdeckt bleibt [1]. Eine transplazentare Transmission mit konsekutiver fetaler Infektion ist kein seltenes Ereignis und kann schwerwiegende Folgen für die Schwangerschaft und die Gesundheit des Kindes haben. Die bedeutendsten diesbezüglichen materno-fetalen Infektionen werden unter dem Akronym TORCH (Toxoplasmose, Others, Röteln, Cytomegalie, Herpes) subsummiert. Bei begründetem Verdacht auf eine potentiell embryopathische oder fetopathische Infektion kann mittels eines positiven Polymerase Chain Reaction (PCR)-Befundes im Fruchtwasser die fetale Infektion bewiesen werden, jedoch nicht die Frage oder das Ausmaß einer intrauterinen Schädigung beantwortet werden. Denn Infektion heißt nicht zwangsläufig Erkrankung. Die meisten betroffenen Feten erscheinen sonographisch unauffällig, allerdings können Auffälligkeiten auch erst im Verlauf auftreten; regelmäßige Ultraschallverlaufskontrollen sind notwendig. Können charakteristische Ultraschallbefunde, wie Wachstumsrestriktion, Aszites, Hydrops, Ventrikulomegalie, intrakranielle Kalzifikationen, Hydrozephalus, hyperechogener Darm, Plazentomegalie und abnorme Fruchtwassermenge in der Hochrisikopatientin gefunden werden, so haben diese eine hohe prädiktive Aussagekraft für eine manifeste fetale Infektion und können auch von prognostischer Bedeutung sein. Gewisse sonographische Befunde sind regelrecht pathognomonisch für spezielle Infektionen. So ist eine Ventrikulomegalie in Kombination mit intrakraniellen und hepatischen Kalzifikationen typisch für eine Zytomegalievirusinfektion, eine kombinierte Augen- und Herzfehlbildung für ein kongenitales Rötelnsyndrom und Extremitätenfehlbildungen mit Gelenkskontrakturen in Verbindung mit zerebralen Auffälligkeiten für eine Varizella-Zoster bedingte Schädigung. Auch bei sonographischen fetalen Auffälligkeiten im Niedrigrisikokollektiv sollte deshalb differentialdiagnostisch an eine fetale Infektion gedacht werden, insbesondere wenn mehrere Organe betroffen sind, eine fetale Wachstumsrestriktion besteht und/oder eine auffällig dicke Plazenta und abnorme Fruchtwassermenge zur Darstellung kommen.
FGF signalling modulates transcriptional repression by Xenopus groucho‐related‐4
Authors: Burks Patrick J. , Isaacs Harry V. , Pownall Mary E.
Published: November 2008

Background information. Developmental cell signals co‐operate in the processes of cell specification and tissue patterning during embryogenesis. Interactions between the FGF (fibroblast growth factor) and Wnt signalling pathways have been demonstrated in a number of developmental processes, including mesoderm formation in amphibian embryos. However, the mechanism underlying the interactions between these key signalling pathways remains unclear.

Results. In the present study, we find that the ability of TLE4/Xgrg4 (transducin‐like enhancer of split 4/Xenopus groucho‐related gene 4) to inhibit a transcriptional target of canonical Wnt signalling is reduced in the presence of FGF and that this is partially dependent on a consensus site for MAPK (mitogen‐activated protein kinase) phosphorylation in TLE4/Xgrg4.

Conclusions. These data suggest to us a novel molecular mechanism where FGF and Wnt signalling pathways interact at the level of the co‐repressor TLE4/Xgrg4: the weakening of TLE4/Xgrg4 repression by FGF signalling, combined with the stabilization of β‐catenin by Wnt signals, enhances expression of Wnt target genes.
Tryptophan degradation in multiple trauma patients: survivors compared with non-survivors
Authors: Ploder Martin , Spittler Andreas , Schroecksnadel Katharina , Neurauter Gabriele , Pelinka Linda E. , Roth Erich , Fuchs Dietmar
Published: November 2008

Immune dysfunction in trauma patients is associated with immune system activation and inflammation. The cytokine-inducible enzyme IDO (indoleamine 2,3-dioxygenase) initiates the degradation of the essential aromatic amino acid tryptophan via the kynurenine pathway and could contribute to deficient immune responsiveness. Activated IDO is indicated by an increased kyn/trp (kynurenine/tryptophan) ratio. The aim of the present study was to investigate whether tryptophan degradation is associated with outcome in patients post-trauma. Tryptophan and kynurenine concentrations were measured by HPLC in serum specimens of 15 patients post-trauma during 12–14 days of follow-up. Up to five samples within this observation period from each patient were included in this analysis, and a total a 69 samples were available. For further comparisons, concentrations of the immune activation marker neopterin were measured. Compared with healthy controls, the average kyn/trp ratio and kynurenine concentrations were increased in patients, whereas tryptophan concentrations were decreased. During follow-up, increased kyn/trp ratio and kynurenine concentrations (all P<0.001) were observed, whereas the changes in tryptophan concentrations were not significant. Non-survivors had higher kyn/trp ratios and kynurenine concentrations compared with survivors. The kyn/trp ratio correlated with neopterin concentrations (rs=0.590, P<0.001). In conclusion, these results imply that increased tryptophan degradation in patients is due to activated IDO, which most probably is a consequence of a host defence response. These findings support a possible role for IDO in the development of immunodeficiency and death in patients.
Modulation of Frontal Lobe Speech Areas Associated With the Production and Perception of Speech Movements
Authors: Fridriksson Julius , Moser Dana , Ryalls Jack , Bonilha Leonardo , Rorden Chris , Baylis Gordon
Published: November 2008

Purpose

It is unclear whether the production and perception of speech movements are subserved by the same brain networks. The purpose of this study was to investigate neural recruitment in cortical areas commonly associated with speech production during the production and visual perception of speech.

Method

This study utilized functional magnetic resonance imaging (fMRI) to assess brain function while participants either imitated or observed speech movements.

Results

A common neural network was recruited by both tasks. The greatest frontal lobe activity in Broca’s area was triggered not only when producing speech but also when watching speech movements. Relatively less activity was observed in the left anterior insula during both tasks.

Conclusion

These results support the emerging view that cortical areas involved in the execution of speech movements are also recruited in the perception of the same movements in other speakers.
Identifying Prosodic Contrasts in Utterances Produced by 4-, 7-, and 11-Year-Old Children
Authors: Patel Rupal , Brayton Julie T.
Published: November 2008

Purpose

Acquisition of prosodic control appears to evolve across development with younger children relying on durational cues and older children utilizing a broader spectrum of cues including fundamental frequency, intensity, and duration. This study aimed to determine whether unfamiliar listeners could identify prosodic contrasts produced by 4-, 7-, and 11-year-olds despite differences in acoustic cues used by each age group.

Method

Thirty-six adult monolingual speakers of American English participated as listeners. A previous study yielded speech recordings from 12 children (2 male, 2 female from each age group) producing 2 linguistic contrasts, question–statement and contrastive stress, which served as listening stimuli.

Results

In both tasks, listener accuracy ranged from 39.7% to 100% with significant differences between 4-year-olds and both older age groups. Listeners had difficulty deciphering the 4-year-olds' questions compared with statements and were more accurate in identifying contrastive stress placed on sentence-initial words compared with sentence-final words across all age groups.

Conclusion

Although listeners identified prosodic contrasts produced by all 3 age groups, accuracy was significantly higher for 7- and 11-year-old productions. Findings are consistent with production studies that suggest relative stabilization of prosodic control between ages 4 and 7. Parallels between prosodic and segmental acquisition are discussed.
Voice Onset Time Characteristics of Esophageal, Tracheoesophageal, and Laryngeal Speech of Cantonese
Authors: Ng Manwa L. , Wong Juliana
Published: November 2008

Purpose

To investigate the ability of standard esophageal (SE) and tracheoesophageal (TE) speakers of Cantonese to differentiate between aspirated and unaspirated stops produced at 3 places of articulation were investigated.

Method

Six Cantonese stops, /p, t, k, p
h
, t
h
, k
h
/, followed by the vowel /a/ produced by 10 SE, TE, and normal laryngeal (NL) speakers were examined through perceptual tasks and voice onset time (VOT) analysis.

Results

Perceptual experiments showed lower accuracy of identification of stops produced by SE and TE than by NL speakers, with mostly misidentification of aspirated stops as their unaspirated counterparts. Acoustic analysis revealed that aspirated stops produced by NL, SE, and TE speakers were associated with significantly longer VOT values than their unaspirated counterparts. Unaspirated velar stops showed significantly longer VOT than bilabial and alveolar stops in NL and SE speech. SE and TE speakers were still able to use VOT to signal aspiration contrast, but TE was unable to differentiate among different places of articulation.
Effects of Loud and Amplified Speech on Sentence and Word Intelligibility in Parkinson Disease
Authors: Neel Amy T.
Published: November 2008

Purpose

In the two experiments in this study, the author examined the effects of increased vocal effort (loud speech) and amplification on sentence and word intelligibility in speakers with Parkinson disease (PD).

Methods

Five talkers with PD produced sentences and words at habitual levels of effort and using loud speech techniques. Amplified sets of sentences and words were created by increasing the intensity of habitual stimuli to the level of loud stimuli. Listeners rated the intelligibility of the 3 sets of sentences on a 1–7 scale and transcribed the 3 sets of words.

Results

Both loud speech and amplification significantly improved intelligibility for sentences and words. Loud speech resulted in greater intelligibility improvement than amplification.

Conclusions

By comparing loud and amplified scores, about one third to one half of intelligibility improvement with loud speech could be attributed to increases in audibility or signal-to-noise ratio. Thus, factors other than increased intensity must be partly responsible for the loud speech benefit. Changes in articulation appear to play a relatively small role: Initial /h/ was the only consonant to consistently show improvement with loud speech. Phonatory changes such as improvements in F
0
and spectral tilt may account for improved speech intelligibility using loud speech techniques.
Fabrication of organic solar array for applications in microelectromechanical systems
Authors: Lewis Jason , Zhang Jian , Jiang Xiaomei
Published: November 2008

We have developed an innovative way to fabricate organic solar arrays for application in dc power supplies for electrostatic microelectromechanical systems devices. A solar array with 20 miniature cells interconnected in series was fabricated and characterized. Photolithography was used to isolate the individual cells and output contacts of the array, whereas the thermal-vacuum deposition is employed to make the series connections of the array. With 1mm2 for single cell and a total device area of 2.2cm2, the organic solar array based on bulk heterojunction structure of π-conjugated polymers and C60 derivative [6,6]-phenyl C61 butyric acid methyl ester produced an open-circuit voltage of 7.8V and a short-circuit current of 55μA under simulated air mass (AM) 1.5 illumination with an intensity of 132mW/cm2. The procedure described here has the full potential for use in future fabrication of microarray with the size as small as 0.01mm2.
Electronic structure of organic diradicals: Evaluation of the performance of coupled-cluster methods
Authors: Li Xiangzhu , Paldus Josef
Published: November 2008

The performance of (i) the reduced multireference (RMR) coupled-cluster (CC) method with singles and doubles (RMR CCSD) that employs a modest-size MR CISD wave function as an external source for the most important (primary) triples and quadruples in order to account for the nondynamic correlation effects in the presence of quasidegeneracy, (ii) the RMR CCSD(T) method that adds a perturbative correction for the remaining (secondary) triples to the RMR CCSD energy, and (iii) the recently developed partially linearized MR CCSD method, which determines primary triples and quadruples using a subset of linear CC equations projected onto the corresponding higher-than-doubly excited configurations, are tested by considering the singlet-triplet splitting for several diradicals, ranging from a prototypical methylene radical to trimethylenemethane, and benzyne and pyridynium cation isomers. Both RHF and multiconfigurational self-consistent field molecular orbitals are employed. The equilibrium geometries for the lowest-lying singlet and triplet states are determined using both the density functional theory (DFT) and various CC approaches, and a comparison with both the experiment and other theoretical results, wherever available, is made. The RMR CCSD(T) results provide the most satisfactory description in all cases. The dependence of the MR diradical character on a spatial separation of radical centers, as well as the artifactual DFT geometry in the case of benzyne and pyridynium meta-isomers, is also pointed out.
Study of electrical properties of silica glasses, intended for FED spacers, under electron irradiation
Authors: Fakhfakh S. , Jbara O. , Belhaj M. , Rondot S. , Mouze D. , Fakhfakh Z.
Published: November 2008

The charge properties, under electron irradiation, of three types of glasses are studied by employing scanning electron microscope (SEM) associated with the technique called the electrostatic influence method. The experimental conditions are closed to those of typical field emission display (FED) operation. To determine the amount of trapped charges during and after electron irradiation, a special arrangement adapted to the SEM was used. This arrangement allows displacement and leakage currents to be simultaneously measured. The secondary electron emission yield during electron irradiation is also deduced. The trapping ability of each glass is analyzed taking into account the regulation mechanisms involved under electron irradiation. Finally useful indications permitting an adequate selection of glasses that may be used as FED spacers are deduced.
In situ viscometry by optical trapping interferometry
Authors: Guzmán Camilo , Flyvbjerg Henrik , Köszali Roland , Ecoffet Carole , Forró László , Jeney Sylvia
Published: November 2008

We demonstrate quantitative in situ viscosity measurements by tracking the thermal fluctuations of an optically trapped microsphere subjected to a small oscillatory flow. The measured power spectral density of the sphere’s positions displays a characteristic peak at the driving frequency of the flow, which is simply proportional to the viscosity, when measured in units of the thermal power spectral density at the same frequency. Measurements are validated on different water-glycerol mixtures, as well as in a glycerol gradient, where no a priori knowledge of the solution is used to determine the glycerol concentration.
Computational Study of CO Reactivity with Nb3X Heteronuclear Clusters
Authors: Addicoat Matthew A. , Metha Gregory F.
Published: November 2008

Density functional calculations were performed to determine the equilibrium structures, ionization potentials, and electron affinities of Nb3X clusters (X = Na, Al, Sc, Sr, Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag, Cd). Pseudo-tetrahedral geometries were preferred for all Nb3X clusters except Nb3Cd. The equilibrium structures and binding energies of the associatively and dissociatively bound products of the Nb3X + CO reaction were calculated at the same level of theory. All clusters were found to thermodynamically dissociate CO. Only Nb3Al and Nb3Cd reduced the enthalpy of dissociation relative to Nb4, whereas all other heteroatoms increased it.
Nucleophilic Attack on the Carbon - Nitrogen Double Bond Leading to Tetrahedral Intermediates with Conformationally Restricted Stereochemistry
Authors: Johnson James E. , Lu Lei , Li Yi , Hou Mei , Rowe Jeffrey E.
Published: November 2008

Methoxide ion substitution on 4-chloro-1H-2,3-benzoxazine 4 has been investigated. The rates of cyclization have been measured for (Z)- and (E)-O-(2-hydroxyethyl)benzohydroximoyl halides (PhC(X)=NOCH2CH2OH; X = Cl or Br) using potassium t-butoxide to generate alkoxide ions from the alcohols. The element effect for the Z and E isomers are kZBr/kZCl = 3.08 and kEBr/kECl = 2.38. The Z-to-E rate ratios are 0.25 (chlorides) and 0.33 (bromides). These reactions are proceeding by rate-determining nucleophilic attack by the alkoxide ion on the carbon–nitrogen double bond (AN# + DN). The restricted stereochemistry of the tetrahedral intermediates suggests that the E-hydroximoyl bromide and chloride may be undergoing unassisted ionization to form a zwitterionic intermediate that leads to product. Alternatively, the chair conformation of the tetrahedral intermediate may be undergoing a ring flip to a boat conformation in which there are antiperiplanar electron pairs that assist in the ionization of the bromide or chloride ion.
A microbial factory for lactate-based polyesters using a lactate-polymerizing enzyme
Authors: Taguchi Seiichi , Yamada Miwa , Matsumoto Ken'ichiro , Tajima Kenji , Satoh Yasuharu , Munekata Masanobu , Ohno Katsuhiro , Kohda Katsunori , Shimamura Takashi , Kambe Hiromi , Obata Shusei
Published: November 2008

Polylactate (PLA) is synthesized as a representative bio-based polyester by the chemo-bio process on the basis of metal catalyst-mediated chemical polymerization of lactate (LA) supplied by microbial fermentation. To establish the one-step microbial process for synthesis of LA-based polyesters, we explored whether polyhydroxyalkanoate (PHA) synthase would exhibit polymerizing activity toward a LA-coenzyme A (CoA), based on the fact that PHA monomeric constituents, especially 3-hydroxybutyrate (3HB), are structurally analogous to LA. An engineered PHA synthase was discovered as a candidate by a two-phase
in vitro
polymerization system previously developed. An LA-CoA producing
Escherichia coli
strain with a CoA transferase gene was constructed, and the generation of LA-CoA was demonstrated by capillary electrophoresis/MS analysis. Next, when the engineered PHA synthase gene was introduced into the resultant recombinant strain, we confirmed the one-step biosynthesis of the LA-incorporated copolyester, P(6 mol% LA-
co
-94 mol% 3HB), with a number-average molecular weight of 1.9 × 10
5
, as revealed by gel permeation chromatography, gas chromatography/MS, and NMR.
Universality of citation distributions: Toward an objective measure of scientific impact
Authors: Radicchi Filippo , Fortunato Santo , Castellano Claudio
Published: November 2008

We study the distributions of citations received by a single publication within several disciplines, spanning broad areas of science. We show that the probability that an article is cited
c
times has large variations between different disciplines, but all distributions are rescaled on a universal curve when the relative indicator

c
f

=
c
/
c
0
is considered, where
c
0
is the average number of citations per article for the discipline. In addition we show that the same universal behavior occurs when citation distributions of articles published in the same field, but in different years, are compared. These findings provide a strong validation of

c
f

as an unbiased indicator for citation performance across disciplines and years. Based on this indicator, we introduce a generalization of the h index suitable for comparing scientists working in different fields.
Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA–PEG nanoparticles
Authors: Dhar Shanta , Gu Frank X. , Langer Robert , Farokhzad Omid C. , Lippard Stephen J.
Published: November 2008

Cisplatin is used to treat a variety of tumors, but dose limiting toxicities or intrinsic and acquired resistance limit its application in many types of cancer including prostate. We report a unique strategy to deliver cisplatin to prostate cancer cells by constructing Pt(IV)-encapsulated prostate-specific membrane antigen (PSMA) targeted nanoparticles (NPs) of poly(D,L-lactic-
co
-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-functionalized controlled release polymers. By using PLGA-
b
-PEG nanoparticles with PSMA targeting aptamers (Apt) on the surface as a vehicle for the platinum(IV) compound
c,t,c
-[Pt(NH
3
)
2
(O
2
CCH
2
CH
2
CH
2
CH
2
CH
3
)
2
Cl
2
] (
1
), a lethal dose of cisplatin was delivered specifically to prostate cancer cells. PSMA aptamer targeted delivery of Pt(IV) cargos to PSMA
+
LNCaP prostate cancer cells by endocytosis of the nanoparticle vehicles was demonstrated using fluorescence microscopy by colocalization of green fluorescent labeled cholesterol-encapsulated NPs and early endosome marker EEA-1. The choice of linear hexyl chains in 1 was the result of a systematic study to optimize encapsulation and controlled release from the polymer without compromising either feature. Release of cisplatin from the polymeric nanoparticles after reduction of 1 and formation of cisplatin 1,2-intrastrand d(GpG) cross-links on nuclear DNA was confirmed by using a monoclonal antibody for the adduct. A comparison between the cytotoxic activities of Pt(IV)-encapsulated PLGA-
b
-PEG NPs with the PSMA aptamer on the surface (Pt-NP-Apt), cisplatin, and the nontargeted Pt(IV)-encapsulated NPs (Pt-NP) against human prostate PSMA-overexpressing LNCaP and PSMA
-
PC3 cancer cells revealed significant differences. The effectiveness of PSMA targeted Pt-NP-Apt nanoparticles against the PSMA
+
LNCaP cells is approximately an order of magnitude greater than that of free cisplatin.
PConPy—a Python module for generating 2D protein maps
Authors: Ho Hui Kian , Kuiper Michael J. , Kotagiri Ramamohanarao
Published: November 2008

Summary: PConPy is an open-source Python module for generating protein contact maps, distance maps and hydrogen bond plots. These maps can be generated in a number of publication-quality vector and raster image formats. Contact maps can be annotated with secondary structure and hydrogen bond assignments. PConPy offers a more flexible choice of contact definition parameters than existing toolkits, most notably a greater choice of inter-residue distance metrics. PConPy can be used as a stand-alone application or imported into existing source code. A web-interface to PConPy is also available for use.

Availability: The PConPy web-interface and source code can be accessed from its website at http://www.csse.unimelb.edu.au/~hohkhkh1/pconpy/.

Contact:  hohkhkh1@csse.unimelb.edu.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
Stochastic modelling of genotypic drug-resistance for human immunodeficiency virus towards long-term combination therapy optimization
Authors: Prosperi Mattia C. F. , D'Autilia Roberto , Incardona Francesca , De Luca Andrea , Zazzi Maurizio , Ulivi Giovanni
Published: November 2008

Motivation: Several mathematical models have been investigated for the description of viral dynamics in the human body: HIV-1 infection is a particular and interesting scenario, because the virus attacks cells of the immune system that have a role in the antibody production and its high mutation rate permits to escape both the immune response and, in some cases, the drug pressure. The viral genetic evolution is intrinsically a stochastic process, eventually driven by the drug pressure, dependent on the drug combinations and concentration: in this article the viral genotypic drug resistance onset is the main focus addressed. The theoretical basis is the modelling of HIV-1 population dynamics as a predator–prey system of differential equations with a time-dependent therapy efficacy term, while the viral genome mutation evolution follows a Poisson distribution. The instant probabilities of drug resistance are estimated by means of functions trained from in vitro phenotypes, with a roulette-wheel-based mechanisms of resistant selection. Simulations have been designed for treatments made of one and two drugs as well as for combination antiretroviral therapies. The effect of limited adherence to therapy was also analyzed. Sequential treatment change episodes were also exploited with the aim to evaluate optimal synoptic treatment scenarios.

Results: The stochastic predator–prey modelling usefully predicted long-term virologic outcomes of evolved HIV-1 strains for selected antiretroviral therapy combinations. For a set of widely used combination therapies, results were consistent with findings reported in literature and with estimates coming from analysis on a large retrospective data base (EuResist).

Contact:  prosperi@dia.uniroma3.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
Model-based analysis of non-specific binding for background correction of high-density oligonucleotide microarrays
Authors: Furusawa Chikara , Ono Naoaki , Suzuki Shingo , Agata Tomoharu , Shimizu Hiroshi , Yomo Tetsuya
Published: November 2008

Motivation: High-density DNA microarrays provide us with useful tools for analyzing DNA and RNA comprehensively. However, the background signal caused by the non-specific binding (NSB) between probe and target makes it difficult to obtain accurate measurements. To remove the background signal, there is a set of background probes on Affymetrix Exon arrays to represent the amount of non-specific signals, and an accurate estimation of non-specific signals using these background probes is desirable for improvement of microarray analyses.

Results: We developed a thermodynamic model of NSB on short nucleotide microarrays in which the NSBs are modeled by duplex formation of probes and multiple hypothetical targets. We fitted the observed signal intensities of the background probes with those expected by the model to obtain the model parameters. As a result, we found that the presented model can improve the accuracy of prediction of non-specific signals in comparison with previously proposed methods. This result will provide a useful method to correct for the background signal in oligonucleotide microarray analysis.

Availability: The software is implemented in the R language and can be downloaded from our website (http://www-shimizu.ist.osaka-u.ac.jp/shimizu_lab/MSNS/).

Contact:  furusawa@ist.osaka-u.ac.jp

Supplementary information:  Supplementary data are available at Bioinformatics online.
Excess acoustic absorption attributable to the biological modification of seawater viscosity
Authors: Rhodes Christopher J.
Published: November 2008

Rhodes, C. J. 2008. Excess acoustic absorption attributable to the biological modification of seawater viscosity. – ICES Journal of Marine Science, 65: 1747–1750. There is increasing evidence that a ubiquitous species of oceanic phytoplankton (Phaeocystis globosa) can significantly modify the rheological properties of seawater. The effect is seasonal and, during spring when the species multiplies rapidly, one can observe large increases in the viscosity of the seawater they inhabit. One of the principal determinants of acoustic absorption in a fluid is viscosity, so in addition to the well-understood modulations attributable to temperature- and salinity-dependent molecular relaxation, there may be an additional absorption component resulting from the presence of phytoplankton. Using data from recent measurements of biologically induced excess viscosity during blooms of P. globosa, the additional acoustic absorption attributable to the presence of this organism is estimated. This suggests that a novel, biologically induced acoustic-absorption mechanism may be observable in seawater for frequencies >100 kHz. The implications for a variety of at-sea acoustic-measurement activities are noted.
Diagnosis and Management of Irritable Bowel Syndrome in General Practice
Authors: Everitt Hazel
Published: November 2008

Irritable bowel syndrome (IBS) is one of the commonest causes of gastrointestinal (GI) consultations in primary and secondary care—it accounts for approximately 3% of all GP consultations. IBS has a prevalence of between 10% and 20%; however, most people (75%) never consult a GP. It is a relapsing and remitting condition and those who do present to general practice have a wide range of symptoms including abdominal pain, bloating, change in bowel habit, fatigue, nausea, backache and bladder symptoms. IBS symptoms can be distressing, leading to time off work, reduced social functioning and a reduced quality of life. This article will outline the key aspects of diagnosing and managing IBS in general practice including highlighting the new NICE guidelines for the diagnosis and management of IBS in adults (published February 2008).
Practice Based Commissioning
Authors: Davies Richard
Published: November 2008

Through a number of different mechanisms, practice-based commissioning (PBC) was intended to improve patient care. Firstly, it was meant to increase clinician involvement in the commissioning of new services for patients. Secondly, PBC made it easier for GPs to develop new services themselves. Thirdly, through the greater familiarity of local budgets and Payment by Results (PBR), GPs were meant to feel financially accountable for their referral decisions.
Inflammatory Bowel Disease
Authors: Simon Chantal
Published: November 2008

Ulcerative colitis (UC) and Crohn's disease are collectively termed inflammatory bowel disease (IBD). Both UC and Crohn's disease are chronic, relapsing-remitting diseases characterized by acute, non-infectious inflammation of the gut. Diarrhoeal diseases likely to be IBD have been described for centuries. King Alfred (849–899 AD) suffered from an illness which caused pain on eating, discomfort, and much embarrassment. This affliction plagued the King from the age of 20, without remission. At the time the illness was thought to be due to witchcraft or a punishment for the King's infidelities. In retrospect, however, the illness was probably IBD. Despite this, UC was not formally described until 1859, and Burrill B. Crohn did not describe the disease later named after him until 1932.
Can Practice-Based Commissioning Improve the Provision of Pulmonary Rehabilitation in the Community? Plan for a New Service
Authors: Diggines Edward
Published: November 2008

The aim of this project was to see if and how practice-based commissioning (PBC) can be used to set up a pulmonary rehabilitation (PR) service for my practice and the neighbouring practices within our PBC consortium.
Testosterone Deficiency — The Male Menopause?
Authors: Simon Chantal
Published: November 2008

Testosterone deficiency in older men as a result of testicular failure is commonly termed the ‘andropause’ or ‘male menopause’. This is a misleading term as it implies a sudden and complete cessation of male sex hormone production and resulting loss of fertility. In reality, the process is more of a gradual decline with reduction, and not cessation, of testosterone production. As a result, other terms have also been used to describe the same phenomenon. These include ‘symptomatic late onset hypogonadism’, ‘androgen deficiency (or decline) of the ageing male’, or ‘partial androgen deficiency in ageing males’.
Crammer's Corner
Authors: Riley Ben
Published: November 2008

This issue of Crammer's Corner considers how to approach learning those topics encountered in general practice that do not appear to have a RCGP curriculum statement of their own and how to tackle those topics that appear more than once in the curriculum.
Prostate Cancer
Authors: Bolland Will
Published: November 2008

Prostate cancer is the most common cancer in men—it accounts for approximately 23% of all new male cancer diagnoses and is responsible for 13% of cancer deaths in men, second only to lung cancer (24%). Approximately, 34 986 new cases are diagnosed each year and 10 000 men die from prostate cancer every year in England and Wales. It is predicted to overtake lung cancer as a cause of death in the future. Worldwide it is the sixth most common cancer. The incidence varies widely by ethnic group around the world. The lifetime risk of being diagnosed with prostate cancer in the UK is 1 in 14 men (though many more will die with undiagnosed prostate cancer). It is estimated that 15–30% of men over 50 will have histological evidence of prostate cancer. At 80 years, approximately two-thirds will have detectable prostate cancer. Despite this high prevalence only one in four will die from the disease, hence the phrase ‘Men are more likely to die with prostate cancer than from it’.
Who Should Be Referred for Endoscopy?
Authors: Ayling Lesley
Published: November 2008

Dyspepsia is a very common condition affecting 40% of the adult population of the UK in any given year. Many of these will self-treat with over-the-counter (OTC) preparations including antacids and alginates. Only 2% of the population will present dyspepsia symptoms to their GP. Prescribed drugs and endoscopies cost the health service £600 million a year. A further £100 million is spent on OTC treatment for dyspepsia.
Benign Prostatic Hypertrophy
Authors: Bolland Will
Published: November 2008

The prevalence of symptomatic benign prostatic hypertrophy (BPH) in Europe varies from 14% for men in their fourth decade to more than 40% in their sixth. Assuming an overall prevalence of symptomatic BPH of 30%, in the UK, would mean that approximately 4 million men aged more than 40 years suffer from the condition.
Methods derived from nonlinear dynamics for analysing heart rate variability
Authors: Voss Andreas , Schulz Steffen , Schroeder Rico , Baumert Mathias , Caminal Pere
Published: November 2008

Methods from nonlinear dynamics (NLD) have shown new insights into heart rate (HR) variability changes under various physiological and pathological conditions, providing additional prognostic information and complementing traditional time- and frequency-domain analyses. In this review, some of the most prominent indices of nonlinear and fractal dynamics are summarized and their algorithmic implementations and applications in clinical trials are discussed. Several of those indices have been proven to be of diagnostic relevance or have contributed to risk stratification. In particular, techniques based on mono- and multifractal analyses and symbolic dynamics have been successfully applied to clinical studies. Further advances in HR variability analysis are expected through multidimensional and multivariate assessments. Today, the question is no longer about whether or not methods from NLD should be applied; however, it is relevant to ask which of the methods should be selected and under which basic and standardized conditions should they be applied.
A provisional transport mechanism for a chloride channel-type Cl
−
/H
+
exchanger
Authors: Miller Christopher , Nguitragool Wang
Published: November 2008

Chloride channel (CLC)-type Cl
−
/H
+
exchangers are widespread throughout the biological world, and one of these, CLC-ec1 from
Escherichia coli
, has been extensively studied. The structure of this protein is known, and several of its mechanistic hot spots have been identified, but a mechanism for Cl
−
/H
+
exchange has not previously been offered. We herein confirm by direct measurements of Cl
−
and H
+
fluxes a Cl
−
-to-H
+
exchange stoichiometry of 2, and summarize experimental facts pertinent to the exchange mechanism. While the mechanism must involve a conformational cycle of alternating exposure of substrate-binding sites to the two sides of the membrane, CLC transporters do not adhere to a familiar ping-pong scheme in which the two ions bind in a mutually exclusive fashion. Instead, Cl
−
and H
+
occupy the ion-binding region simultaneously. A conformational cycle is proposed that accounts for the exchange stoichiometry, several key mutants and the tendency of the protein to become uncoupled and allow ‘slippage’ of Cl
−
.
KCNJ11
knockout morula re-engineered by stem cell diploid aggregation
Authors: Nelson Timothy J , Martinez-Fernandez Almudena , Terzic Andre
Published: November 2008

KCNJ11
-encoded Kir6.2 assembles with ATP-binding cassette sulphonylurea receptors to generate ATP-sensitive K
+
(K
ATP
) channel complexes. Expressed in tissues with dynamic metabolic flux, these evolutionarily conserved yet structurally and functionally unique heteromultimers serve as high-fidelity rheostats that adjust membrane potential-dependent cell functions to match energetic demand. Genetic defects in channel subunits disrupt the cellular homeostatic response to environmental stress, compromising organ tolerance in the adult. As maladaptation characterizes malignant K
ATP
channelopathies, establishment of platforms to examine progression of K
ATP
channel-dependent adaptive behaviour is warranted. Chimeras provide a powerful tool to assay the contribution of genetic variance to stress intolerance during prenatal or post-natal development. Here,
KCNJ11
K
ATP
channel gene knockout↔wild-type chimeras were engineered through diploid aggregation. Integration of wild-type embryonic stem cells into zona pellucida-denuded morula derived from knockout embryos achieved varying degrees of incorporation of stress-tolerant tissue within the K
ATP
channel-deficient background. Despite the stress-vulnerable phenotype of the knockout,
ex vivo
derived mosaic blastocysts tolerated intrauterine transfer and implantation, followed by full-term embryonic development in pseudopregnant surrogates to produce live chimeric offspring. The development of adult chimerism from the knockout↔wild-type mosaic embryo offers thereby a new paradigm to probe the ecogenetic control of the K
ATP
channel-dependent stress response.
The molecular logic of sodium-coupled neurotransmitter transporters
Authors: Gouaux Eric
Published: November 2008

Synaptic transmission at chemical synapses requires the removal of neurotransmitter from extracellular spaces. At synapses in the central nervous system, this is accomplished by sodium-coupled transport proteins, integral membrane proteins that thermodynamically couple the uptake of neurotransmitter to the uptake of sodium and, in some cases, the uptake and export of additional ions. Recent X-ray crystallographic studies have revealed the architecture of the two major families of neurotransmitter transporters and, together with additional biochemical and biophysical studies, have provided insights into mechanisms of ion coupling, substrate uptake, and inhibition of transport.
Neural mechanisms of recovery following early visual deprivation
Authors: Mitchell Donald E , Sengpiel Frank
Published: November 2008

Natural patterned early visual input is essential for the normal development of the central visual pathways and the visual capacities they sustain. Without visual input, the functional development of the visual system stalls not far from the state at birth, and if input is distorted or biased the visual system develops in an abnormal fashion resulting in specific visual deficits. Monocular deprivation, an extreme form of biased exposure, results in large anatomical and physiological changes in terms of territory innervated by the two eyes in primary visual cortex (V1) and to a loss of vision in the deprived eye reminiscent of that in human deprivation amblyopia. We review work that points to a special role for binocular visual input in the development of V1 and vision. Our unique approach has been to provide animals with mixed visual input each day, which consists of episodes of normal and biased (monocular) exposures. Short periods of concordant binocular input, if continuous, can offset much longer episodes of monocular deprivation to allow normal development of V1 and prevent amblyopia. Studies of animal models of patching therapy for amblyopia reveal that the benefits are both heightened and prolonged by daily episodes of binocular exposure.
Bidirectional synaptic mechanisms of ocular dominance plasticity in visual cortex
Authors: Smith Gordon B , Heynen Arnold J , Bear Mark F
Published: November 2008

As in other mammals with binocular vision, monocular lid suture in mice induces bidirectional plasticity: rapid weakening of responses evoked through the deprived eye followed by delayed strengthening of responses through the open eye. It has been proposed that these bidirectional changes occur through three distinct processes: first, deprived-eye responses rapidly weaken through homosynaptic long-term depression (LTD); second, as the period of deprivation progresses, the modification threshold determining the boundary between synaptic depression and synaptic potentiation becomes lower, favouring potentiation; and third, facilitated by the decreased modification threshold, open-eye responses are strengthened via homosynaptic long-term potentiation (LTP). Of these processes, deprived-eye depression has received the greatest attention, and although several alternative hypotheses are also supported by current research, evidence suggests that α-amino-3- hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor endocytosis through LTD is a key mechanism. The change in modification threshold appears to occur partly through changes in
N
-methyl-
d
-aspartate (NMDA) receptor subunit composition, with decreases in the ratio of NR2A to NR2B facilitating potentiation. Although limited research has directly addressed the question of open-eye potentiation, several studies suggest that LTP could account for observed changes
in vivo
. This review will discuss evidence supporting this three-stage model, along with outstanding issues in the field.
Interactions of alkali cations with glutamate transporters
Authors: Holley David C , Kavanaugh Michael P
Published: November 2008

The transport of glutamate is coupled to the co-transport of three Na
+
ions and the countertransport of one K
+
ion. In addition to this carrier-type exchange behaviour, glutamate transporters also behave as chloride channels. The chloride channel activity is strongly influenced by the cations that are involved in coupled flux, making glutamate transporters representative of the ambiguous interface between carriers and channels. In this paper, we review the interaction of alkali cations with glutamate transporters in terms of these diverse functions. We also present a model derived from electrostatic mapping of the predicted cation-binding sites in the X-ray crystal structure of the
Pyrococcus horikoshii
transporter Glt
Ph
and in its human glutamate transporter homologue EAAT3. Two predicted Na
+
-binding sites were found to overlap precisely with the Tl
+
densities observed in the aspartate-bound complex. A novel third site predicted to favourably bind Na
+
(but not Tl
+
) is formed by interaction with the substrate and the occluding HP2 loop. A fourth predicted site in the apo state exhibits selectivity for K
+
over both Na
+
and Tl
+
. Notably, this K
+
site partially overlaps the glutamate-binding site, and their binding is mutually exclusive. These results are consistent with kinetic and structural data and suggest a plausible mechanism for the flux coupling of glutamate with Na
+
and K
+
ions.
A review of the generalization of auditory learning
Authors: Wright Beverly A , Zhang Yuxuan
Published: November 2008

The ability to detect and discriminate attributes of sounds improves with practice. Determining how such auditory learning generalizes to stimuli and tasks that are not encountered during training can guide the development of training regimens used to improve hearing abilities in particular populations as well as provide insight into the neural mechanisms mediating auditory performance. Here we review the newly emerging literature on the generalization of auditory learning, focusing on behavioural investigations of generalization on basic auditory tasks in human listeners. The review reveals a variety of generalization patterns across different trained tasks that can not be summarized with a simple rule, and a diversity of views about the definition, evaluation and interpretation of generalization.
Perceptual learning and sensomotor flexibility: cortical plasticity under attentional control?
Authors: Fahle Manfred
Published: November 2008

Recent research reveals long-lasting cortical plasticity of early sensory cortices even in adults. Sensory signals could be modified under top-down control if necessary quite early in order to optimize their signal-to-noise ratio, leading to ‘low level’ or ‘early’ perceptual learning (PL). For easy tasks, such elaborate top-down influences are usually not required, and learning is restricted to late selection of the appropriate signals on higher cortical levels, which seems easier and faster to achieve. But to reach the absolute limits of sensory performance, PL seems to optimize the entire chain of sensory processing. Hence, improvement for these extreme perceptual abilities is quite specific for a number of stimulus parameters, such as the position in the visual field and sometimes even the trained eye, reflecting the specificity of receptive fields in early sensory cortices. Early PL may be just one example—even if a very extensive one—of the mechanisms of neuronal plasticity and sensomotor flexibility that are constantly updating our sensomotor representations as a result of experience. As an illustration, this review contains some new experimental results on PL and sensory flexibility in the context of adaptation to multifocal intraocular lenses.