bluuebunny/crossref_metadata_2025 huggingface dataset:
Piezoelectric oxide semiconductor field effect transistor touch sensing devices
Authors: Dahiya Ravinder S. , Metta Giorgio , Valle Maurizio , Adami Andrea , Lorenzelli Leandro
Published: July 2009

This work presents piezoelectric oxide semiconductor field effect transistor (POSFET) based touch sensing devices. These devices are fabricated by spin coating thin (∼2.5 μm) piezoelectric polymer film directly on to the gate area of metal oxide semiconductor (MOS) transistor. The polymer film is processed in situ and challenging issues such as in situ poling of piezoelectric polymer film, without damaging or altering the characteristics of underlying MOS devices, are successfully dealt with. The POSFET device represents an integral “sensotronic” unit comprising of transducer and the transistor—thereby sensing as well as conditioning (and processing) the touch signal at “same site.”
Highly reliable 500 mW laser diodes with epitaxially grown AlON coating for high-density optical storage
Authors: Kamikawa T. , Kawaguchi Y. , Vaccaro P. O. , Ito S. , Kawanishi H.
Published: July 2009

Highly reliable operation of 405 nm laser diodes for high-density optical storage was demonstrated. Introduction of epitaxially grown AlON layer between the front facet and normal coating layer was shown to be effective to suppress catastrophic optical damage at the laser facet. Stable operation in excess of 1000 h was confirmed at an output power of 500 mW in a pulsed-mode at a case temperature of 80 °C.
Enhanced surface acoustic wave biosensor performance via delay path modifications in mutually interacting multidirectional transducer configuration: A computational study
Authors: Singh Reetu , Sankaranarayanan Subramanian K. R. S. , Bhethanabotla Venkat R.
Published: July 2009

Multidirectional interdigital transducers (IDTs) combined with delay path modifications for surface acoustic wave (SAW) sensors in a Langasite substrate are shown to positively and significantly impact power consumption, device sensitivity, and biofouling elimination capability. Simulated devices have mutually interacting orthogonal IDTs and microcavities of square cross sections of side λ/2, and of different depths located in the middle of the delay path. A combined orthogonal IDT-polystyrene filled microcavities device (dimensions λ/2×λ/2×λ/2), with constructive wave interference and enhanced SAW entrapment in the delay region, is shown to be most efficient and reduces insertion loss by 23.6 dB, generates two orders of magnitude larger streaming forces, and exhibits velocity sensitivity 100% larger than that of a simulated standard SAW sensor with unidirectional IDTs along the (0, 22, 90) direction.
Langmuir–Blogett monolayer transistors of copper phthalocyanine
Authors: Wei Zhongming , Cao Yang , Ma Weizhu , Wang Chengliang , Xu Wei , Guo Xuefeng , Hu Wenping , Zhu Daoben
Published: July 2009

Bottom-contact monolayer thin-film transistors (MTFTs) were fabricated using copper phthalocyanine (CuPc) Langmuir–Blodgett monolayer as the active channel. The devices with tens of micrometers long channels showed typical p-type field-effect properties and obvious saturation regimes. Mobilities of these CuPc MTFTs were channel length dependent. The best performance obtained from the molecule-scaled CuPc MTFT with a channel length of 5 μm showed mobility even higher than that of the 50 nm thick vacuum-deposited films. These MTFTs may find potential applications in sensors and organic integrated circuits.
Increased sampling blurs morphological and molecular species limits: revision of the Hispaniolan endemic spider genus Tainonia (Araneae:Pholcidae)
Authors: Huber Bernhard A. , Astrin Jonas J.
Published: July 2009

The genus Tainonia comprises unusually large pholcids endemic to Hispaniola. Previously, only the type species had been formally described, represented in collections by no more than 12 adult specimens. However, the existence of more species has been hypothesised based on a few further individuals. The present paper is based on a sample of 205 mostly newly collected adult specimens from 18 localities in the Dominican Republic and four localities in Haiti. The increased sampling reveals a wide range of variation, including intermediate levels of divergence that often blur rather than clarify species limits. Therefore, although not all taxonomic questions can be settled here, morphological (including morphometric) and molecular (mitochondrial 16S, CO1) data strongly support two new species: one in La Visite National Park, Haiti (T. visite, sp. nov.) and another on Samaná Peninsula and parts of the eastern Dominican Republic (T. samana, sp. nov.). Species limits among the other populations are more difficult to support or reject. Specimens from Bayahibe (eastern Dominican Republic) and from La Ciénaga (Cordillera Central) are each assigned species status on the basis of consistent morphological differences (T. bayahibe, sp. nov., T. cienaga, sp. nov.), but no molecular data are available due to lack of specimens. All other specimens are provisionally assigned to a possibly paraphyletic T. serripes (Simon). There is considerable morphological variation within this widely distributed group of populations but this variation is rather continuous and molecular distances fill most of the range between morphologically unambiguous conspecifics and unambiguous heterospecifics.
Characteristics of tree hollows used by Australian birds and bats
Authors: Goldingay Ross L.
Published: July 2009

Many hundreds of species of wildlife worldwide are dependent on tree hollows (cavities) for their survival. I reviewed the published literature for hollow-using Australian birds and microbats to document their tree-hollow requirements and to guide future research and management. Such information is vital to the conservation of these species. The hollow requirements of only 35 of 114 hollow-using bird species and 15 of 42 hollow-using microbat species were documented in some detail. This overall paucity of information limits the ability to manage for the future requirements of species. However, some generalisations can guide management until further studies are conducted. Most species used a variety of available tree species, and the extensive use of dead trees probably reflects the high likelihood of these trees containing hollows. Birds (other than large parrots) and bats chose hollow entrances of a size close to body width. Large parrots require large hollows, with a preference for large vertical spouts and trunk hollows. Few birds or bats demonstrated an absolute requirement for high (>10 m) tree hollows, with most (70%) using some hollows with entrances ≤5 m above ground. Temperature has been postulated to influence roost selection among microbats because it enables passive rewarming from torpor and there is some evidence from Australian bats to support this. Many studies suggest a future shortage of hollow-bearing trees. Currently, artificial hollows appear to be the most likely interim solution to address this. Knowledge of the natural hollow requirements of species can be used to refine artificial-hollow designs. An increase in research effort is needed to address the many gaps in knowledge that currently exist. Priorities for research include (1) many additional studies to document the characteristics of the hollow-bearing trees used by species of microbat, (2) the need to conduct long-term bioregional studies of hollow-bearing tree attrition to help identify where management responses are most needed and (3) investigating whether fire plays a significant role in the creation of tree hollows of a range of size classes and therefore may have a management use. Such information has broad relevance because it will provide ecological insight that can be applied to the management of hollow-using birds and bats elsewhere in the world.
The transmission rate of MCMV in house mice in pens: implications for virally vectored immunocontraception
Authors: Arthur A. D. , Krebs C. J. , Pech R. P. , Farroway L. N. , Singleton G. R.
Published: July 2009

Pest mammals have severe economic, environmental and social impacts throughout the world. Fertility control could reduce these impacts. Murine cytomegalovirus (MCMV) is being considered as an immunocontraceptive vector to control outbreaks of house mice (Mus domesticus) in Australian grain-growing regions. For successful control, a modified MCMV must transmit at a sufficient rate to keep populations of house mice below acceptable economic thresholds. We used disease models developed previously by using observations of free-ranging wild-mouse populations to assess the transmission rate of two laboratory strains of MCMV (N1 and G4) collected in a previous experiment. Mice contained in pens were deliberately infected with the N1 strain only, or with the N1 strain followed by the G4 strain. If we assume density-dependent transmission, which is the more likely mode of transmission, we found the N1 strain of MCMV transmitted at a rate ~1/300 of the rate of field strains, and hence too slowly for successful virally vectored immunocontraception (VVIC). If transmission was frequency-dependent, the rate of transmission was ~1/3 of the rate of field strains, and hence may allow successful VVIC. The G4 strain transmitted at least as slowly as the N1 strain, and possibly much more slowly; however, we could not determine whether this was an inherent property of the G4 strain or whether it was caused by competition with the N1 strain. Given the reliance of successful VVIC on rapid transmission, we recommend that future work in any VVIC system explicitly quantifies the transmission rate of recombinant viruses relative to field strains, both in the presence and absence of competing strains.
Cell fate decision mediated by p53 pulses
Authors: Zhang Xiao-Peng , Liu Feng , Cheng Zhang , Wang Wei
Published: July 2009

The tumor suppressor p53 plays a crucial role in cellular response to various stresses. Recent experiments have shown that p53 level exhibits a series of pulses after DNA damage caused by ionizing radiation (IR). However, how the p53 pulses govern cell survival and death remains unclear. Here, we develop an integrated model with four modules for the p53 network and explore the mechanism for cell fate decision based on the dynamics of the network. By numerical simulations, the following processes are characterized. First, DNA repair proteins bind to IR-induced double-strand breaks, forming complexes, which are then detected by ataxia telangiectasia mutated (ATM). Activated ATM initiates the p53 oscillator to produce pulses. Consequently, the target genes of p53 are selectively induced to control cell fate. We propose that p53 promotes the repair of minor DNA damage but suppresses the repair of severe damage. We demonstrate that cell fate is determined by the number of p53 pulses relying on the extent of DNA damage. At low damage levels, few p53 pulses evoke cell cycle arrest by inducing p21 and promote cell survival, whereas at high damage levels, sustained p53 pulses trigger apoptosis by inducing p53AIP1. We find that p53 can effectively maintain genomic integrity by regulating the efficiency and fidelity of DNA repair. We also show that stochasticity in the generation and repair of DNA damage leads to variability in cell fate. These findings are consistent with experimental observations and advance our understanding of the dynamics and functions of the p53 network.
Energetics of glutamate receptor ligand binding domain dimer assembly are modulated by allosteric ions
Authors: Chaudhry Charu , Plested Andrew J. R. , Schuck Peter , Mayer Mark L.
Published: July 2009

The activity of many ligand-gated ion channels and cell surface receptors is modulated by small molecules and ions, but an understanding of the underlying molecular mechanisms is scarce. For kainate, but not AMPA subtype glutamate receptors, the binding of Na
+
and Cl
−
ions to discrete, electrostatically coupled sites in the extracellular ligand binding domain (LBD) dimer assembly regulates the rate of entry into the desensitized state, which occurs when the dimer interface ruptures and the channel closes. Studies on glutamate receptors have defined the LBD dimer assembly as a key functional unit that controls activation and desensitization. Here we use analytical ultracentrifugation to probe the energetic effects of allosteric ions on kainate receptor dimer stability in solution, using a GluR6 mutant that desensitizes slowly. Our results show that sodium and chloride ions modulate kainate receptor dimer affinity as much as 50-fold, and that removal of either Cl
−
or Na
+
disrupts the dimer. The applicability of a similar allosteric mechanism for modulation of delta2 glutamate receptors by Ca
2+
was also tested. Our results indicate that ions can contribute substantial free energy to active state stabilization in both these receptors, and provide quantitative measurements of the energetic consequences of allosteric ion binding to a ligand-gated ion channel.
The Insulin-like Growth Factor (IGF)-I E-Peptides Modulate Cell Entry of the Mature IGF-I Protein
Authors: Pfeffer Lindsay A. , Brisson Becky K. , Lei Hanqin , Barton Elisabeth R.
Published: July 2009

Insulin-like growth factor (IGF)-I is a critical protein for cell development and growth. Alternative splicing of the igf1 gene gives rise to multiple isoforms. In rodents, proIGF-IA and proIGF-IB have different carboxy-terminal extensions called the E-peptides (EA and EB) and upon further posttranslational processing, produce the identical mature IGF-I protein. Rodent EB has been reported to have mitogenic and motogenic effects independent of IGF-I. However, effects of EA or EB on mature IGF-I, or whether proIGF-IA and proIGF-IB have different properties, have not been addressed. To determine whether the presence of EA or EB affected the distribution and stability of mature IGF-I protein, transient transfections of cDNAs encoding murine IGF-IA, IGF-IB, and mature IGF-I were performed in C2C12 cells, a skeletal muscle cell line. IGF-I secretion was measured by enzyme-linked immunosorbent assay of the media, and did not differ between expression of proIGF-IA, proIGF-IB, or mature IGF-I expression. Next, epitope-tagged constructs were transfected to determine cellular distribution of IGF-I, EA, and EB in the cells throughout the culture. IGF-I was detected in significantly fewer nontransfected cells in cultures transfected with mature IGF-I compared with transfection of proIGF-IA or proIGF-IB. These results demonstrate that EA and EB are not required for IGF-I secretion but that they increase cell entry of IGF-I from the media. This study provides evidence that the EA and EB may modulate IGF-I in addition to having independent activity.
Basolateral Internalization of GPI-anchored Proteins Occurs via a Clathrin-independent Flotillin-dependent Pathway in Polarized Hepatic Cells
Authors: Aït-Slimane Tounsia , Galmes Romain , Trugnan Germain , Maurice Michèle
Published: July 2009

In polarized hepatocytes, the predominant route for apical resident proteins to reach the apical bile canalicular membrane is transcytosis. Apical proteins are first sorted to the basolateral membrane from which they are internalized and transported to the opposite surface. We have noted previously that transmembrane proteins and GPI-anchored proteins reach the apical bile canaliculi at very different rates. Here, we investigated whether these differences may be explained by the use of distinct endocytic mechanisms. We show that endocytosis of both classes of proteins at the basolateral membrane of polarized hepatic cells is dynamin dependent. However, internalization of transmembrane proteins is clathrin mediated, whereas endocytosis of GPI-anchored proteins does not require clathrin. Further analysis of basolateral endocytosis of GPI-anchored proteins showed that caveolin, as well as the small GTPase cdc42 were dispensable. Alternatively, internalized GPI-anchored proteins colocalized with flotillin-2–positive vesicles, and down-expression of flotillin-2 inhibited endocytosis of GPI-anchored proteins. These results show that basolateral endocytosis of GPI-anchored proteins in hepatic cells occurs via a clathrin-independent flotillin-dependent pathway. The use of distinct endocytic pathways may explain, at least in part, the different rates of transcytosis between transmembrane and GPI-anchored proteins.
ZO-1 Stabilizes the Tight Junction Solute Barrier through Coupling to the Perijunctional Cytoskeleton
Authors: Van Itallie Christina M. , Fanning Alan S. , Bridges Arlene , Anderson James M.
Published: July 2009

ZO-1 binds numerous transmembrane and cytoplasmic proteins and is required for assembly of both adherens and tight junctions, but its role in defining barrier properties of an established tight junction is unknown. We depleted ZO-1 in MDCK cells using siRNA methods and observed specific defects in the barrier for large solutes, even though flux through the small claudin pores was unaffected. This permeability increase was accompanied by morphological alterations and reorganization of apical actin and myosin. The permeability defect, and to a lesser extent morphological changes, could be rescued by reexpression of either full-length ZO-1 or an N-terminal construct containing the PDZ, SH3, and GUK domains. ZO-2 knockdown did not replicate either the permeability or morphological phenotypes seen in the ZO-1 knockdown, suggesting that ZO-1 and -2 are not functionally redundant for these functions. Wild-type and knockdown MDCK cells had differing physiological and morphological responses to pharmacologic interventions targeting myosin activity. Use of the ROCK inhibitor Y27632 or myosin inhibitor blebbistatin increased TER in wild-type cells, whereas ZO-1 knockdown monolayers were either unaffected or changed in the opposite direction; paracellular flux and myosin localization were also differentially affected. These studies are the first direct evidence that ZO-1 limits solute permeability in established tight junctions, perhaps by forming a stabilizing link between the barrier and perijunctional actomyosin.
Supervised prediction of drug–target interactions using bipartite local models
Authors: Bleakley Kevin , Yamanishi Yoshihiro
Published: July 2009

Motivation:  In silico prediction of drug–target interactions from heterogeneous biological data is critical in the search for drugs for known diseases. This problem is currently being attacked from many different points of view, a strong indication of its current importance. Precisely, being able to predict new drug–target interactions with both high precision and accuracy is the holy grail, a fundamental requirement for in silico methods to be useful in a biological setting. This, however, remains extremely challenging due to, amongst other things, the rarity of known drug–target interactions.

Results: We propose a novel supervised inference method to predict unknown drug–target interactions, represented as a bipartite graph. We use this method, known as bipartite local models to first predict target proteins of a given drug, then to predict drugs targeting a given protein. This gives two independent predictions for each putative drug–target interaction, which we show can be combined to give a definitive prediction for each interaction. We demonstrate the excellent performance of the proposed method in the prediction of four classes of drug–target interaction networks involving enzymes, ion channels, G protein-coupled receptors (GPCRs) and nuclear receptors in human. This enables us to suggest a number of new potential drug–target interactions.

Availability: An implementation of the proposed algorithm is available upon request from the authors. Datasets and all prediction results are available at http://cbio.ensmp.fr/~yyamanishi/bipartitelocal/.

Contact:  kevbleakley@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
DiProGB: the dinucleotide properties genome browser
Authors: Friedel Maik , Nikolajewa Swetlana , Sühnel Jürgen , Wilhelm Thomas
Published: July 2009

Motivation: DiProGB is an easy to use new genome browser that encodes the primary nucleotide sequence by thermodynamical and geometrical dinucleotide properties. The nucleotide sequence is thus converted into a sequence graph. This visualization, supported by different graph manipulation options, facilitates genome analyses, because the human brain can process visual information better than textual information. Also, DiProGB can identify genomic regions where certain physical properties are more conserved than the nucleotide sequence itself. Most of the DiProGB tools can be applied to both, the primary nucleotide sequence and the sequence graph. They include motif and repeat searches as well as statistical analyses. DiProGB adds a new dimension to the common genome analysis approaches by taking into account the physical properties of DNA and RNA.

Availability and Implementation: Source code and binaries are freely available for download at http://diprogb.fli-leibniz.de, implemented in C++ and supported on MS Windows and Linux (using e.g. WineHQ).

Contact:  maikfr@fli-leibniz.de; thomas.wilhelm@bbsrc.ac.uk
Intensity of Extremely Low-frequency Electromagnetic Fields Produced in Operating Rooms during Surgery at the Standing Position of Anesthesiologists
Authors: Roh Jang Ho , Kim Deok Won , Lee Sung Jin , Kim Ji Young , Na Sung Won , Choi Seung Ho , Kim Ki Jun
Published: July 2009

Background

Numerous electronic devices have been introduced into operating rooms. Although little is known about the relationship between exposure to electromagnetic fields and health hazards, several studies have demonstrated causal relationships between electromagnetic fields exposure and various symptoms, cancers, and other diseases.

Methods

This study was approved by the Institutional Review Board. The intensity of extremely low-frequency electromagnetic fields was measured during surgery with the extremely low-frequency electromagnetic field strength measurement system at the standing position of anesthesiologists in 18 operating rooms and analyzed with EMDEX analysis and graphical program (EMCALC 95; ENERTECH, Campbell, CA).

Results

The average measurement duration per operating room per day was 7.41 +/- 0.70 h (mean +/- SD). The average sample number of measurements was 888.11 +/- 82.75 per operating room. The average magnetic field was 5.83 +/- 5.23 milliGuass (mG) (range, 0.10-33.80 mG), with 70% of these levels 2 mG or greater.

Conclusions

The authors' results indicate that anesthesiologists in operating rooms are exposed to extremely low-frequency electromagnetic field levels that exceed magnetic field intensity of 2 mG recommended by the Swedish Board for Technical Accreditation for production by computer monitors and detected 30 cm from them. It currently is not clear if this exposure has health effects on anesthesiologists and other operating room personnel.
Anesthetic-induced Preconditioning Delays Opening of Mitochondrial Permeability Transition Pore via Protein Kinase C-ϵ–mediated Pathway
Authors: Pravdic Danijel , Sedlic Filip , Mio Yasushi , Vladic Nikolina , Bienengraeber Martin , Bosnjak Zeljko J.
Published: July 2009

Background

Cardioprotection by volatile anesthetic-induced preconditioning (APC) involves activation of protein kinase C (PKC). This study investigated the importance of APC-activated PKC in delaying mitochondrial permeability transition pore (mPTP) opening.

Methods

Rat ventricular myocytes were exposed to isoflurane in the presence or absence of nonselective PKC inhibitor chelerythrine or isoform-specific inhibitors of PKC-delta (rottlerin) and PKC-epsilon (myristoylated PKC-epsilon V1-2 peptide), and the mPTP opening time was measured by using confocal microscopy. Ca-induced mPTP opening was measured in mitochondria isolated from rats exposed to isoflurane in the presence and absence of chelerythrine or in mitochondria directly treated with isoflurane after isolation. Translocation of PKC-epsilon was assessed in APC and control cardiomyocytes by Western blotting.

Results

In cardiomyocytes, APC prolonged time necessary to induce mPTP opening (261 +/- 26 s APC vs. 216 +/- 27 s control; P < 0.05), and chelerythrine abolished this delay to 213 +/- 22 s. The effect of isoflurane was also abolished when PKC-epsilon inhibitor was applied (210 +/- 22 s) but not in the presence of PKC-delta inhibitor (269 +/- 31 s). Western blotting revealed translocation of PKC-epsilon toward mitochondria in APC cells. The Ca concentration required for mPTP opening was significantly higher in mitochondria from APC rats (45 +/- 8 microM x mg control vs. 64 +/- 8 microM x mg APC), and APC effect was reversed with chelerythrine. In contrast, isoflurane did not protect directly treated mitochondria.

Conclusion

APC induces delay of mPTP opening through PKC-epsilon mediated inhibition of mPTP opening, but not through PKC-delta. These results point to the connection between cytosolic and mitochondrial components of cardioprotection by isoflurane.
End-tidal Sevoflurane and Halothane Concentrations during Simulated Airway Occlusion in Healthy Humans
Authors: Talbot Nick P. , Farmery Andrew D. , Dorrington Keith L.
Published: July 2009

Background

In a patient whose airway is likely to become obstructed upon loss of consciousness, anesthesia may be induced using an inhaled vapor. If the airway occludes during such an inhalational induction, the speed of patient awakening is related to the rate at which anesthetic gas redistributes away from lung and brain to other body compartments. To determine whether redistribution occurs more rapidly with a more blood-soluble or a less blood-soluble agent, the authors used subanesthetic concentrations of halothane and sevoflurane to simulate inhalational induction and airway obstruction in eight healthy human volunteers.

Methods

Inhalational induction was simulated using stepwise increases in inspired halothane or sevoflurane concentration, sufficient to reach an end-tidal concentration of approximately 0.1 minimal alveolar concentration. Airway occlusion was then simulated by initiating a 90-s period of rebreathing from a 1-l bag. During rebreathing, end-tidal halothane or sevoflurane concentration was measured continuously by mass spectrometry, and a time constant for the decline in concentration was calculated using a monoexponential model.

Results

At the onset of rebreathing, end-tidal concentrations of halothane and sevoflurane were 0.10 +/- 0.03 and 0.11 +/- 0.03 minimal alveolar concentration, respectively (mean +/- SD; P > 0.1, Student t test). During rebreathing, the time constants for the decline in end-tidal halothane and sevoflurane concentration were 22 +/- 9 and 62 +/- 16 s, respectively (P < 0.0001).

Conclusions

During simulated airway occlusion in healthy volunteers, the end-tidal concentration of halothane falls more rapidly than that of sevoflurane. Halothane may therefore lead to more rapid awakening, compared with sevoflurane, should the airway obstruct during an inhalational induction of anesthesia.
Analysis of Memory Formation during General Anesthesia (Propofol/Remifentanil) for Elective Surgery Using the Process-dissociation Procedure
Authors: Hadzidiakos Daniel A. , Horn Nadja , Degener Roland , Buchner Axel , Rehberg Benno
Published: July 2009

Background

There have been reports of memory formation during general anesthesia. The process-dissociation procedure has been used to determine if these are controlled (explicit/conscious) or automatic (implicit/unconscious) memories. This study used the process-dissociation procedure with the original measurement model and one which corrected for guessing to determine if more accurate results were obtained in this setting.

Methods

A total of 160 patients scheduled for elective surgery were enrolled. Memory for words presented during propofol and remifentanil general anesthesia was tested postoperatively by using a word-stem completion task in a process-dissociation procedure. To assign possible memory effects to different levels of anesthetic depth, the authors measured depth of anesthesia using the BIS XP monitor (Aspect Medical Systems, Norwood, MA).

Results

Word-stem completion performance showed no evidence of memory for intraoperatively presented words. Nevertheless, an evaluation of these data using the original measurement model for process-dissociation data suggested an evidence of controlled (C = 0.05; 95% confidence interval [CI] 0.02-0.08) and automatic (A = 0.11; 95% CI 0.09-0.12) memory processes (P < 0.01). However, when the data were evaluated with an extended measurement model taking base rates into account adequately, no evidence for controlled (C = 0.00; 95% CI -0.04 to 0.04) or automatic (A = 0.00; 95% CI -0.02 to 0.02) memory processes was obtained. The authors report and discuss parallel findings for published data sets that were generated by using the process-dissociation procedure.

Conclusion

Patients had no memories for auditory information presented during propofol/remifentanil anesthesia after midazolam premedication. The use of the process-dissociation procedure with the original measurement model erroneously detected memories, whereas the extended model, corrected for guessing, correctly revealed no memory.
Axotomy Depletes Intracellular Calcium Stores in Primary Sensory Neurons
Authors: Rigaud Marcel , Gemes Geza , Weyker Paul D. , Cruikshank James M. , Kawano Takashi , Wu Hsiang-En , Hogan Quinn H.
Published: July 2009

Background

The cellular mechanisms of neuropathic pain are inadequately understood. Previous investigations have revealed disrupted Ca signaling in primary sensory neurons after injury. The authors examined the effect of injury on intracellular Ca stores of the endoplasmic reticulum, which critically regulate the Ca signal and neuronal function.

Methods

Intracellular Ca levels were measured with Fura-2 or mag-Fura-2 microfluorometry in axotomized fifth lumbar (L5) dorsal root ganglion neurons and adjacent L4 neurons isolated from hyperalgesic rats after L5 spinal nerve ligation, compared to neurons from control animals.

Results

Endoplasmic reticulum Ca stores released by the ryanodine-receptor agonist caffeine decreased by 46% in axotomized small neurons. This effect persisted in Ca-free bath solution, which removes the contribution of store-operated membrane Ca channels, and after blockade of the mitochondrial, sarco-endoplasmic Ca-ATPase and the plasma membrane Ca ATPase pathways. Ca released by the sarco-endoplasmic Ca-ATPase blocker thapsigargin and by the Ca-ionophore ionomycin was also diminished by 25% and 41%, respectively. In contrast to control neurons, Ca stores in axotomized neurons were not expanded by neuronal activation by K depolarization, and the proportionate rate of refilling by sarco-endoplasmic Ca-ATPase was normal. Luminal Ca concentration was also reduced by 38% in axotomized neurons in permeabilized neurons. The adjacent neurons of the L4 dorsal root ganglia showed modest and inconsistent changes after L5 spinal nerve ligation.

Conclusions

Painful nerve injury leads to diminished releasable endoplasmic reticulum Ca stores and a reduced luminal Ca concentration. Depletion of Ca stores may contribute to the pathogenesis of neuropathic pain.
Helicobacter pylori Infection Is Associated With Low Serum Ferritin Levels in Israeli Arab Children—A Seroepidemiologic Study
Authors: Muhsen Khitam , Barak Mira , Shifnaidel Luba , Nir Avishag , Bassal Ravit , Cohen Dani
Published: July 2009

We examined the association between Helicobacter pylori seropositivity and low ferritin levels in sera of 509 Israeli Arab children aged 1 to 19 years. Serum ferritin levels were measured using the immunoturbidity assay. ELISA was used to detect serum IgG antibodies to H pylori and IgG antibodies to H pylori CagA+ strains. Low ferritin level was found between 14.5% and 8.6% of the H pylori seropositive and seronegative participants, respectively (P = 0.035). A trend for a higher frequency of low ferritin was detected among H pylori‐CagA seropositive children. Multivariate analysis showed an increased frequency of low ferritin only among children younger than or equal to 5 years: adjusted OR 4.62 (95% CI 1.53–13.99) P = 0.007.
Technical Limitations in Detection of Gastroesophageal Reflux in Neonates
Authors: Di Fiore Juliann M , Arko Marina , Churbock Kim , Hibbs Anna Maria , Martin Richard J
Published: July 2009

Objective:

Characterize the incidence and possible etiologies of acid reflux events detected by pH and not identified by multiple intraluminal impedance (MII) monitoring.

Materials and Methods:

Acid reflux events detected by pH but not identified by MII (pH‐only) were documented in 80 preterm and 39 term infants. Reasons for failure of MII to detect these events were classified as failure to meet MII scoring criteria, presence of an air bolus, technical artifact, and no change in impedance. Events with no change in impedance were stratified to low impedance throughout the study (possible esophageal inflammation), transient decrease in pre‐event impedance (presence of refluxate), occurrence <30 seconds of a preceding event, and no explanation.

Results:

A total of 2572 events were detected by pH, with 59% of events not identified by MII. A higher incidence of pH‐only events occurred in preterm versus term infants (54 ± 27% versus 42 ± 23%, P = .025, respectively). Thirteen percent of pH‐only events were missed due to MII scoring criteria, 12% due to technical artifact, 11% due to an air bolus, and 64% had no change in impedance. Of the 978 events with no change in impedance, 154 were associated with low impedance throughout the study, 430 with a transient decrease in pre‐event impedance, and 175 were preceded by a reflux episode within 30 seconds.

Conclusions:

There was a high incidence of acid reflux events detected by pH but not identified by MII. This occurred more often in the least mature infants, and we speculate that delayed esophageal fluid clearance is the major underlying mechanism.
Association Between Genotypes and Phenotypes in Coeliac Disease
Authors: Gudjónsdóttir Audur H , Nilsson Staffan , Naluai Åsa Torinsson , Ek Johan , Amundsen Silja S , Wahlström Jan , Ascher Henry
Published: July 2009

Background:

Coeliac disease (CD) is a genetically driven immunological intolerance to dietary gluten with a wide range of clinical presentations. The aim of this study was to investigate the heritability of the phenotype in CD and the influence on the phenotype of different genes associated with the disease.

Patients and Methods:

One hundred and seven families with at least 2 siblings with CD were collected. The patients were grouped in symptom grades on the basis of the clinical presentation, the age at diagnosis, and sex. Stratification analyses of the human leucocyte antigen‐DQA1 and human leucocyte antigen‐DQB1 genotypes, the CTLA4 +49A/G polymorphism, the CTLA4 haplotype MH30*G:−1147*T:+49*A:CT60*G:CT61*A, and the 5q31‐33 loci were done.

Results:

The heritability of the phenotype was estimated to be 0.45. Significant association and linkage was found between the clinical presentation and the CTLA4 +49A/G polymorphism but not for the other genotypes. No correlation was found between genotypes and age at diagnosis or sex.

Conclusions:

Our results indicate that the heritability is determiner of the phenotype in CD. The CTLA4 +49A/G polymorphism is correlated to the clinical presentation: the AA genotype is associated with clinically silent disease.
Partial External Biliary Diversion in Children With Progressive Familial Intrahepatic Cholestasis and Alagille Disease
Authors: Yang Huiqi , Porte Robert J , Verkade Henkjan J , De Langen Zacharias J , Hulscher Jan BF
Published: July 2009

Background:

Partial external biliary diversion (PEBD) is a promising treatment for children with progressive familial intrahepatic cholestasis (PFIC) and Alagille disease. Little is known about long‐term outcomes.

Patients and Methods:

A retrospective chart review of all patients undergoing PEBD in the University Medical Centre of Groningen (UMCG).

Results:

Between 2000 and 2005, PEBD was performed on 14 children with severe pruritus (PFIC 11, mean age 5.3 ± 4.4 years; Alagille 3, mean age 7.4 ± 4.2 years). Stature was <−2 standard deviation score (SDS) in 50%. Median preoperative serum bile salt concentration was 318 μmol/L (range 23–527 μmol/L). Twenty‐nine percent had severe liver fibrosis and 71% had mild or moderate fibrosis. Median follow‐up was 3.1 years (range 2.0–5.7 years). One patient (7%) underwent a liver transplantation at 3.2 years post‐PEBD. Two years postoperatively, 50% were without pruritus and 21% had mild pruritus. In 29%, pruritus had not diminished; 3 of them had severe fibrosis preoperatively. In patients with mild or moderate fibrosis, PEBD decreased serum bile salts (105 μmol/L [range 8–269 μmol/L] 2 years postoperatively). Bile salts did not decrease in the patients with severe fibrosis. Two years after PEBD, 27% had a stature below −2 SDS.

Conclusions:

At median follow‐up of 3.1 years after PEBD, pruritus has been relieved in 75%. Bile salts level and growth are improved in most patients. Longer follow‐up is needed to determine whether PEBD can postpone or avoid the demand for liver transplantation.
Autoimmune Hepatitis
Authors: Mieli‐Vergani Giorgina , Heller Solange , Jara Paloma , Vergani Diego , Chang Mei‐Hwei , Fujisawa Tomoo , González‐Peralta Regino P , Kelly Deirdre , Mohan Neelam , Shah Uzma , Murray Karen F
Published: July 2009

Autoimmune hepatitis is characterized by inflammatory liver histology, circulating nonorgan‐specific autoantibodies, and increased levels of immunoglobulin G, in the absence of a known etiology. Two types of juvenile autoimmune hepatitis (AIH) are recognized according to seropositivity for smooth muscle and/or anti‐nuclear antibody (AIH type 1) or liver kidney microsomal antibody (AIH type 2). There is a female predominance in both. AIH type 2 presents more acutely, at a younger age and commonly with immunoglobulin A deficiency, whereas duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long‐term prognosis are similar in the 2 groups. Immunosuppressive treatment with steroids and azathioprine, which should be instituted promptly to avoid progression to cirrhosis, induces remission in 80% of cases. Relapses are common, often due to nonadherence. Drugs effective in refractory cases include cyclosporine and mycophenolate mofetil. Long‐term treatment is usually required, with only some 20% of AIH type 1 patients able to discontinue therapy successfully. In childhood, sclerosing cholangitis with strong autoimmune features, including interface hepatitis and serological features identical to AIH type 1, is as prevalent as AIH, but it affects boys and girls equally. Differential diagnosis relies on cholangiographic studies. In autoimmune sclerosing cholangitis liver parenchymal damage responds satisfactorily to immunosuppressive treatment, whereas bile duct disease tends to progress. In this article we review the state of the art of diagnosis, monitoring, and treatment for children with AIH.
Accessory male investment can undermine the evolutionary stability of simultaneous hermaphroditism
Authors: Michiels Nico K. , Crowley Philip H. , Anthes Nils
Published: July 2009

Sex allocation (SA) models are traditionally based on the implicit assumption that hermaphroditism must meet criteria that make it stable against transition to dioecy. This, however, puts serious constraints on the adaptive values that SA can attain. A transition to gonochorism may, however, be impossible in many systems and therefore realized SA in hermaphrodites may not be limited by conditions that guarantee stability against dioecy. We here relax these conditions and explore how sexual selection on male accessory investments (e.g. a penis) that offer a paternity benefit affects the evolutionary stable strategy SA in outcrossing, simultaneous hermaphrodites. Across much of the parameter space, our model predicts male allocations well above 50 per cent. These predictions can help to explain apparently ‘maladaptive’ hermaphrodite systems.
Sexual conflict, sex allocation and the genetic system
Authors: Shuker David M. , Moynihan Anna M. , Ross Laura
Published: July 2009

Decisions over what sex ratio to produce can have far-reaching evolutionary consequences, for both offspring and parents. However, the extent to which males and females come into evolutionary conflict over aspects of sex allocation depends on the genetic system: when genes are passed to the next generation unequally by the two sexes (as in haplodiploidy, for example), this biased transmission can facilitate a range of conflicts not seen in diploids. However, much less attention has been paid to these forms of sexual conflict, not least because it has not always been clear how the conflicts could be realized. Here we consider how biased gene transmission, as expressed in different genetic systems, enhances the opportunity for sex ratio conflict and give empirical examples that confirm that males and females have the opportunity to influence sex ratios.
Strategic (adaptive) hypothermia in bull dromedary camels during rut; could it increase reproductive success?
Authors: Grigg Gordon , Beard Lyn , Dörges Birgit , Heucke Jürgen , Coventry Jocelyn , Coppock Alex , Blomberg Simon
Published: July 2009

In this study of body temperatures (
T
b
) in free ranging dromedary camels, we found that bulls in rut start the days cooler. Daily minima during rut averaged 0.6°C lower than at other times (95% CI 0.27–0.94°C) and daily maxima averaged 0.45°C higher (95% CI −0.01 to –0.91°C), increasing the daily
T
b
cycle. Knut Schmidt-Nielsen described a similar pattern in captive dromedaries deprived of water in hot conditions, which he interpreted as a strategy to conserve water. Our observations were made in winter and with water freely available. Dromedaries can apparently employ heterothermy for more than just water conservation. In the strenuous daily contests between rival bulls in rut, a lower
T
b
early in the day should extend the time for which a contestant can challenge or defend before heat stress becomes a problem. Calculations show that lowering
T
b
by even 0.6°C extends that time by more than 30 min, and many daily minima during rut were lower than that. Because the eventual winner of contests gains or retains a herd of females, we speculate that cooler
T
b
at the start of daily contests confers an advantage which translates directly into increased reproductive success.
A distinct infection cost associated with trans-generational priming of antibacterial immunity in bumble-bees
Authors: Sadd Ben M. , Schmid-Hempel Paul
Published: July 2009

The adaptive value of facultative maternal adjustment of offspring immunity, or trans-generational immune-priming, will depend on the ecological background. In particular, where there is a mismatch between the immune adjustment and offspring environment, the immunological link between mothers and offspring may be disadvantageous owing to the presence of associated costs. Costs to an individual of responding to an immune challenge are extensively documented. However, in addition to parents, the relevant costs for trans-generational immune-priming also pertain to offspring, but as yet it is unknown what costs offspring will bear. In bumble-bees, higher antibacterial activity has been shown as a trans-generational effect when mothers receive a bacterial-based immune challenge prior to colony founding. Here we show that while naive offspring from immune-challenged mothers do not show evidence for a direct energy-related survival cost, they do show increased susceptibility to a parasite distinctly unrelated to the maternal challenge. The presence of costs associated with trans-generational immune-priming will shape the evolution of this trait depending on the ecological setting.
Ecology, evolution and genetics join together on Canada's east coast
Authors: Starzomski Brian M. , Brown Carissa D.
Published: July 2009

The 4th regular meeting of the Canadian Society of Ecology and Evolution was held in conjunction with the 52nd Annual Conference of the Genetics Society of Canada at Dalhousie University, Halifax, from 14 to 17 May 2009.
Constrained solution scattering modelling of human antibodies and complement proteins reveals novel biological insights
Authors: Perkins Stephen J. , Okemefuna Azubuike I. , Nan Ruodan , Li Keying , Bonner Alexandra
Published: July 2009

X-ray and neutron-scattering techniques characterize proteins in solution and complement high-resolution structural studies. They are useful when either a large protein cannot be crystallized, in which case scattering yields a solution structure, or a crystal structure has been determined and requires validation in solution. These solution structures are determined by the application of constrained modelling methods based on known subunit structures. First, an appropriate starting model is generated. Next, its conformation is randomized to generate thousands of models for trial-and-error fits. Comparison with the experimental data identifies a small family of best-fit models. Finally, their significance for biological function is assessed. We illustrate this in application to structure determinations for secretory immunoglobulin A, the most prevalent antibody in the human body and a first line of defence in mucosal immunity. We also discuss the applications to the large multi-domain proteins of the complement system, most notably its major regulator factor H, which is important in age-related macular degeneration and renal diseases. We discuss the importance of complementary data from analytical ultracentrifugation, and structural studies of protein–protein complexes. We conclude that constrained scattering modelling makes useful contributions to our understanding of antibody and complement structure and function.
On determinism and well-posedness in multiple time dimensions
Authors: Craig Walter , Weinstein Steven
Published: July 2009

We study the initial value problem for the wave equation and the ultrahyperbolic equation for data posed on initial hypersurfaces surface of arbitrary space–time signature. We show that, under a non-local constraint, the initial value problem posed on codimension-one hypersurfaces—the Cauchy problem—has global unique solutions in the Sobolev spaces
H

m

. Thus, it is well-posed. However, we show that the initial value problem on higher codimension hypersurfaces is ill-posed due to failure of uniqueness, at least when specifying a finite number of derivatives of the data. This failure is in contrast to a uniqueness result for data given in an arbitrary
neighbourhood
of such initial hypersurfaces, which Courant deduces from Asgeirsson’s mean value theorem. We give a generalization of Courant’s theorem that extends to a broader class of equations. The proofs use Fourier synthesis and the Holmgren–John uniqueness theorem.
Aromatic adsorption on metals via first-principles density functional theory
Authors: Jenkins S. J.
Published: July 2009

We review first-principles calculations relevant to the adsorption of aromatic molecules on metal surfaces. Benzene has been intensively studied on a variety of substrates, providing an opportunity to comment upon trends from one metal to another. Meanwhile, calculations elucidating the adsorption of polycyclic aromatic molecules are more sparse, but nevertheless yield important insights into the role of non-covalent interactions. Heterocyclic and substituted aromatic compounds introduce the complicating possibility of electronic and steric effects, whose relative importance can thus far only be gauged on a case-by-case basis. Finally, the coadsorption and/or reaction of aromatic molecules is discussed, highlighting an area where the predictive power of theory is likely to prove decisive in the future.